David C. Christiani, M.D.

Specialty: Pulmonary and Occupational Medicine

Massachusetts General Hospital

50 Staniford Street
Boston, MA 02114


The following is a list of recent publications for which this Partners Asthma Center physician has been cited as an author in PubMed databases. Study abstracts have been provided for your convenience.

Zhou, W., G. Liu, et al. (2003). "Polymorphisms in the DNA repair genes XRCC1 and ERCC2, smoking, and lung cancer risk." Cancer Epidemiol Biomarkers Prev 12(4): 359-65.

XRCC1 (X-ray cross-complementing group 1) and ERCC2 (excision repair cross-complementing group 2) are two major DNA repair proteins. Polymorphisms of these two genes have been associated with altered DNA repair capacity and cancer risk. We have described statistically significant interactions between the ERCC2 polymorphisms (Asp312Asn and Lys751Gln) and smoking in lung cancer risk. In this case-control study of 1091 Caucasian lung cancer patients and 1240 controls, we explored the gene-environment interactions between the XRCC1 Arg399Gln polymorphism, alone or in combination with the two ERCC2 polymorphisms, and cumulative smoking exposure in the development of lung cancer. The results were analyzed using logistic regression models, adjusting for relevant covariates. Overall, the adjusted odds ratio (OR) of XRCC1 Arg399Gln polymorphism (Gln/Gln versus Arg/Arg) was 1.3 [95% confidence interval (CI), 1.0-1.8]. Stratified analyses revealed that the ORs decreased as pack-years increased. For nonsmokers, the adjusted OR was 2.4 (95% CI, 1.2-5.0), whereas for heavy smokers (>/=55 pack-years), the OR decreased to 0.5 (95% CI, 0.3-1.0). When the three polymorphisms were evaluated together, the adjusted ORs of the extreme genotype combinations of variant alleles (individuals with 5 or 6 variant alleles) versus wild genotype (individuals with 0 variant alleles) were 5.2 (95% CI, 1.7-16.6) for nonsmokers and 0.3 (95% CI, 0.1-0.8) for heavy smokers, respectively. Similar gene-smoking interaction associations were found when pack-years of smoking (or smoking duration and smoking intensity) was fitted as a continuous variable. In conclusion, cumulative cigarette smoking plays an important role in altering the direction and magnitude of the associations between the XRCC1 and ERCC2 polymorphisms and lung cancer risk.

Wang, X. R., L. D. Pan, et al. (2003). "A longitudinal observation of early pulmonary responses to cotton dust." Occup Environ Med 60(2): 115-21.

AIMS: To examine early adverse pulmonary effects of exposure to cotton dust, and to identify potential risk factors, including atopy for pulmonary responses to cotton dust. METHODS: Spirometry, methacholine challenge testing, and questionnaire; performed among 101 non-smoking newly hired textile workers at baseline (prior to starting work), and at 3, 12, and 18 months after starting work. Concentrations of airborne cotton dust in various work areas were measured at each follow up survey using vertical elutriators. RESULTS: The incidence of non-specific respiratory symptoms was 8% at three months, then diminished afterwards. Substantial acute cross shift drops in FEV(1) at each follow up survey, and longitudinal declines in FVC and FEV(1) after 12 months of exposure were observed. Airway responsiveness to methacholine increased with follow up time, and was more pronounced among atopics. Increasing airway responsiveness was strongly correlated with cross shift drops in FEV(1). In addition, one or more respiratory symptoms at three months was significantly, and pre-existing atopy marginally significantly, associated with cross shift drops in FEV(1) after adjusting for other covariates and confounders. CONCLUSION: Results suggest that non-specific respiratory symptoms, decreasing lung function, and increasing airway responsiveness are early pulmonary responses to cotton dust. In addition, the occurrence of respiratory symptoms and increasing airway responsiveness, as well as atopy, may be important predictors for acute changes in lung function among cotton textile workers.

Wang, X. R., L. D. Pan, et al. (2003). "Lung function, airway reactivity, and atopy in newly hired female cotton textile workers." Arch Environ Health 58(1): 6-13.

To assess changes in lung function and airway reactivity resulting from exposure to cotton dust, and the role of atopic status in these changes, the authors observed a group of 225 newly hired Chinese textile workers for 1 yr. All workers were female, lifelong nonsmokers, and none of them had been exposed previously to cotton or other occupational dust. Atopic status was determined at baseline. Spirometry, response to methacholine challenge, and total serum immunoglobulin E level were examined at baseline and again after subjects began work in the cotton mills. Obvious cross-shift drops in forced expiratory volume in 1 sec (FEV1.0), and declines in forced vital capacity and FEV1.0 over 1 yr, were observed. Atopic workers had a significantly greater acute drop in FEV1.0 than did nonatopic workers. Both atopic and nonatopic workers had slightly increased airway reactivity at 1 yr, compared with baseline values. The results suggest that exposure to cotton dust is responsible for acute and longitudinal declines in lung function, as well as for slightly increased airway reactivity. Atopy may interact with cotton dust to accentuate the acute lung function response.

Tsai, H. T., M. T. Wu, et al. (2003). "Exposure to environmental tobacco smoke and urinary 1-hydroxypyrene levels in preschool children." Kaohsiung J Med Sci 19(3): 97-104.

Environmental tobacco smoke (ETS) contains relatively high concentrations of polycyclic aromatic hydrocarbons (PAHs). Urinary 1-hydroxypyrene (1-OHP), a metabolite of pyrene, is a good indicator of PAH exposure in occupational studies. In this study, we investigated the relationship between urinary 1-OHP concentration and ETS exposure in preschool children. Forty preschool children, aged 24-76 months, were studied during November and December, 1999. Two spot-urine specimens (one in the morning immediately after the subject woke up and the other at night before the subject went to bed) were collected 1 day after completion of a questionnaire, in order to determine 1-OHP concentrations by fluorescent spectrophotometry. Overall, urinary 1-OHP concentrations were relatively low but detectable (morning: median, 0.021 microg/g creatinine; range, 0.002-1.019 microg/g creatinine; night: median, 0.015 microg/g creatinine; range, 0.002-1.328 microg/g creatinine). Multiple linear regression analyses revealed that the total number of cigarettes smoked by the children's fathers during the 3 days prior to collection of the urine specimens was significantly associated with their urinary 1-OHP concentrations, after adjusting for other confounders. Each cigarette smoked by a child's father resulted in an average 9.6% increase in 1-OHP concentration in the morning urine specimen (95% confidence interval = 1.8-18.1%; p = 0.02). We did not find a significant increase in the 1-OHP concentration in night urine specimens (p = 0.19). Although the sample size was small, these findings indicate that urinary 1-OHP may be a suitable biomarker of ETS carcinogen exposure in children.

Su, L., G. Liu, et al. (2003). "No association between the p21 codon 31 serine-arginine polymorphism and lung cancer risk." Cancer Epidemiol Biomarkers Prev 12(2): 174-5.

Su, L., Y. Sai, et al. (2003). "P53 (codon 72) and P21 (codon 31) polymorphisms alter in vivo mRNA expression of p21." Lung Cancer 40(3): 259-66.

p21 (Waf1/Cip1) is a downstream target of p53. We evaluated the association between p21 polymorphism (codon 31), p53 polymorphism (codon 72) and their corresponding in vivo mRNA expression. In this study, p21 and p53 genetic polymorphisms (using standard PCR-RFLP techniques) and p21 and p53 gene expressions (using a radiolabelled ribonuclease protection assay (RPA) technique) were evaluated in the peripheral leukocytes of 84 individuals (63 with lung cancer). Log-transformed values of mRNA expression by RPA, which approximated a normal distribution, were analyzed. p53 genotypes did not correlate with p53 mRNA log-expression (P>0.05 for all comparisons), but the Pro allele variants of p53 were associated with a significant decrease in mRNA log-expression of its downstream target, p21. The variant Arg allele of p21 was also associated with a significant decrease in p21 mRNA log-expression. When individuals with at least one variant allele of both p53 and p21 (double-variants) were compared with all other genotype groups, these double-variants had significantly lower log-expression of p21 (P<0.005 by both t-tests (crude) and linear regression analyses (adjusted)). This is translated into an approximate 48% reduction in the geometric mean of the mRNA expression of the double-variants, when compared with all other groups. Results were consistent in both patients with lung cancer (n=63) and in normal controls (n=21). In conclusion, the presence of a p53 Pro allele and/or p21 Arg allele is associated with lower downstream target gene expression of p21.

Sorensen, G., A. M. Stoddard, et al. (2003). "A comprehensive worksite cancer prevention intervention: behavior change results from a randomized controlled trial (United States)." J Public Health Policy 24(1): 5-25.

OBJECTIVE: Workplace cancer prevention initiatives have been least successful with blue-collar workers. This study assesses whether an intervention integrating health promotion with occupational health and safety results in significant and meaningful increases in smoking cessation and consumption of fruits and vegetables, compared to a standard health promotion intervention, for workers overall and for blue-collar workers in particular. METHODS: A randomized controlled design was used, with 15 manufacturing worksites assigned to a health promotion (HP) or a health promotion plus occupational health and safety intervention (HP/OHS), and compared from baseline (1997) to final (1999). The response rates to the survey were 80% at baseline (n = 9019) and 65% at final (n = 7327). Both groups targeted smoking and diet; the HP/OHS condition additionally incorporated reduction of occupational exposures. RESULTS: Smoking quit rates among blue-collar workers in the HP/OHS condition more than doubled relative to those in the HP condition (OR = 2.13, p = 0.04), and were comparable to quit rates of white-collar workers. No statistically significant differences between groups were found for mean changes in fruits and vegetables. CONCLUSIONS: Integration of occupational health and safety and health promotion may be an essential means of enhancing the effectiveness of worksite tobacco control initiatives with blue-collar workers.

Miller, D. P., I. De Vivo, et al. (2003). "Association between self-reported environmental tobacco smoke exposure and lung cancer: modification by GSTP1 polymorphism." Int J Cancer 104(6): 758-63.

Environmental Tobacco Smoke (ETS) exposure has been associated with lung cancer risk. ETS is composed of emissions from cigarette smoke and contains a higher concentration of tobacco smoke carcinogens than mainstream smoke. Polymorphisms in genes that metabolize tobacco smoke carcinogens have been studied as effect modifiers of the association between active smoking and lung cancer risk. GSTP1 is a polymorphic gene that encodes for GST pi, a detoxification enzyme and has a high expression in the lung. We investigated the association between ETS and lung cancer risk and the modification of this association by the GSTP1 polymorphism. Using a case-control design, individuals were genotyped for GSTP1 using PCR-RFLP techniques. All analyses were carried out using multiple logistic regression. The association between ETS exposure and lung cancer risk was evaluated in different strata based on smoking habits to evaluate the consistency of results. The effect of the GSTP1 polymorphisms on lung cancer risk was evaluated by considering the joint effect of having both an ETS exposure and the GSTP1 GG genotype compared to the absence of ETS exposure and the GSTP1 AA genotype as a reference group as well as doing stratified analysis by genotype. ETS exposure was associated consistently with higher lung cancer risk in all the strata considered. The adjusted odds ratios (AOR) evaluating the association between ETS and lung cancer risk for the different strata were: nonsmokers (Cases/Controls 66/413; AOR = 1.38; 95% CI = 0.78-2.43), ex-smokers (Cases/Controls 560/527; AOR = 1.66; 95% CI = 1.22-2.25), current smokers (Cases/Controls 415/219; AOR = 1.56; 95% CI = 1.00-2.41). The AORs for ex-smokers and light smoking subgroups were: ex-smokers who quit for 19 years or more (Cases/Controls 144/244; AOR = 2.64; 95% CI = 1.55-4.50), ex-smokers who quit for 10-19 years (Cases/Controls 141/128; AOR = 1.16; 95% CI = 0.66-2.04), ex-smokers who quit for 10 years or less (Cases/Controls 247/122; AOR = 1.45; 95% CI = 0.83-2.55) and participants who had <15 packyears and nonsmokers combined (Cases/Controls 143/640; AOR = 1.52; 95% CI = 1.02-2.28). Among those with the GSTP1 GG genotype the ETS-lung cancer risk association was greater than those with the GSTP1 AA genotype: nonsmokers (GSTP1 GG AOR = 7.84; 95% CI = 0.80-76.68; GSTP1 AA AOR = 1.15; 95% CI = 0.46-2.90), ex-smokers (GSTP1 GG AOR = 2.32; 95% CI = 0.90-5.96; GSTP1 AA AOR = 2.15; 95% CI = 1.34-3.44), current smokers (GSTP1 GG AOR = 1.75; 95% CI = 0.42-7.32; GSTP1 AA AOR = 1.32; 95% CI = 0.67-2.58) and participants who had <15 packyears and nonsmokers (GSTP1 GG AOR = 1.93; 95% CI = 0.54-6.97; GSTP1 AA AOR = 1.58; 95% CI = 0.83-3.01). We found that ETS exposure is associated with higher lung cancer risk. Furthermore, the presence of the GSTP1 GG genotype appears to enhance the magnitude of the association between ETS exposure and lung cancer. Larger studies will be needed to confirm these preliminary findings.

Lee, B. W., L. London, et al. (2003). "Association between human paraoxonase gene polymorphism and chronic symptoms in pesticide-exposed workers." J Occup Environ Med 45(2): 118-22.

Pesticides, such as parathion, are metabolized by cytochrome p-450 system to paraoxon, which is a potent cholinesterase inhibitor. Paraoxonase (PON) catalyzes the hydrolysis of these toxic metabolites and protects against pesticide toxicity. A glutamine/arginine (Gln/Arg) polymorphism at amino acid position 192 of PON has been described. The Arg/Arg genotype is associated with higher serum paraoxonase activity compared to Gln/Gln. The Arg/Gln genotype is associated with intermediate serum PON activity. The potential association between PON genotype and symptoms of chronic pesticide toxicity was examined among 100 farm workers. As part of a cross-sectional study of pesticide toxicity among mixed-race farm workers in the Western Cape. South Africa, 100 farm workers were genotyped for polymorphism of the paraoxonase gene at amino acid position 192. Subjects with two or more of the following symptoms were considered to have evidence of chronic toxicity: abdominal pain, nausea, rhinorrhea, dizziness, headache, somnolence, fatigue, gait disturbance, limb numbness, paresthesias, limb pain, or limb weakness. In multivariable logistic regression analysis, the independent predictors of chronic toxicity were previous history of head trauma resulting in loss of consciousness (OR 2.8, 95% CI = 1.7-6.7), having worked as a pesticide applicator (OR 5.4, 95% CI = 3.2-8.9), and having one of the two "slow metabolism" (Gln/Gln or Gln/Arg) genotypes (OR 2.9, 95% CI = 1.7-6.9). Furthermore, the prevalence of chronic toxicity increased in a stepwise fashion from 15% among pesticide nonapplicators with a "fast metabolism" (Arg/Arg) genotype, to 42.9% among pesticide nonapplicators with "slow metabolism" (Gln/Gln or Gln/Arg) genotypes, to 58.8% among pesticide applicators with "fast metabolism" genotype, and 75.0% among pesticide applicators with "slow metabolism" genotypes (P = 0.001). Age, number of years on the job, smoking history, alcohol history, education level, plasma or red blood cell cholinesterase level, or previous history of acute organophosphate poisoning were not statistically significant predictors of chronic toxicity. The PON genotype is an important determinant of a farmworker's susceptibility to chronic pesticide poisoning.

Lee, D. H., M. H. Ha, et al. (2003). "Gamma-glutamyltransferase and diabetes-a 4 year follow-up study." Diabetologia 46(3): 359-64.

AIMS/HYPOTHESIS. Gamma-glutamyltransferase (GGT) is located on the external surface of most cells and mediates the uptake of gluthathione, an important component of intracellular antioxidant defenses. An increase in GGT concentration has been regarded as a marker of alcohol consumption or liver disease. However, more subtle gradations in GGT could be informative because its expression is enhanced by oxidative stress and it could be released by several conditions inducing cellular stress. Recently, serum GGT concentrations have been associated with many cardiovascular disease risk factors or components of the insulin resistance syndrome. We did a prospective study with the hypothesis that serum GGT is a predictor of incident diabetes. METHODS. A total of 4,088 healthy men working in a steel manufacturing company were examined in 1994 and 1998. Diabetes was defined as a serum fasting glucose concentration of more than 126 mg/dl or the use of diabetes medication. RESULTS. There was a strong dose-response relation between serum GGT concentrations at baseline and the incidence of diabetes. In contrast to the 31% of men with GGT concentrations under 9 U/l, adjusted relative risks for incidence of diabetes for GGT concentrations 10-19, 20-29, 30-39, 40-49, and over 50 U/l were 8.0, 13.3, 12.6, 19.6 and 25.8, respectively. The associations of age and BMI with incident diabetes became stronger the higher the value of baseline serum GGT concentration. CONCLUSION/INTERPRETATION. This study suggests that an increase in GGT concentration within its physiological range is a sensitive and early biomarker for the development of diabetes.

LaMontagne, A. D., R. A. Youngstrom, et al. (2003). "An exposure prevention rating method for intervention needs assessment and effectiveness evaluation." Appl Occup Environ Hyg 18(7): 523-34.

This article describes a new method for (1) systematically prioritizing needs for intervention on hazardous substance exposures in manufacturing work sites, and (2) evaluating intervention effectiveness. We developed a checklist containing six unique sets of yes/no variables organized in a 2 x 3 matrix of exposure potential versus protection (two columns) at the levels of materials, processes, and human interface (three rows). The three levels correspond to a simplified hierarchy of controls. Each of the six sets of indicator variables was reduced to a high/moderate/low rating. Ratings from the matrix were then combined to generate a single overall exposure prevention rating for each area. Reflecting the hierarchy of controls, material factors were weighted highest, followed by process, and then human interface. The checklist was filled out by an industrial hygienist while conducting a walk-through inspection (N = 131 manufacturing processes/areas in 17 large work sites). One area or process per manufacturing department was assessed and rated. Based on the resulting Exposure Prevention ratings, we concluded that exposures were well controlled in the majority of areas assessed (64% with rating of 1 or 2 on a 6-point scale), that there is some room for improvement in 26 percent of areas (rating of 3 or 4), and that roughly 10 percent of the areas assessed are urgently in need of intervention (rated as 5 or 6). A second hygienist independently assessed a subset of areas to evaluate inter-rater reliability. The reliability of the overall exposure prevention ratings was excellent (weighted kappa = 0.84). The rating scheme has good discriminatory power and reliability and shows promise as a broadly applicable and inexpensive tool for intervention needs assessment and effectiveness evaluation. Validation studies are needed as a next step. This assessment method complements quantitative exposure assessment with an upstream prevention focus.

Kodavanti, U. P., C. F. Moyer, et al. (2003). "Inhaled environmental combustion particles cause myocardial injury in the Wistar Kyoto rat." Toxicol Sci 71(2): 237-45.

Epidemiologists have associated particulate matter (PM) air pollution with cardiovascular morbidity and premature mortality worldwide. However, experimental evidence demonstrating causality and pathogenesis of particulate matter (PM)-induced cardiovascular damage has been insufficient. We hypothesized that protracted, repeated inhalation by rats of oil combustion-derived, fugitive emission PM (EPM), similar in metal composition to selected sources of urban air PM, causes exposure duration- and dose-dependent myocardial injury in susceptible rat strains. Zinc was the only primary water-leachable/bioavailable element of this EPM. Male Sprague-Dawley (SD), Wistar Kyoto (WKY), and spontaneously hypertensive (SH) rats were exposed nose-only to EPM (2, 5, or 10 mg/m(3), 6 h/day for 4 consecutive days or 10 mg/m(3), 6 h/day, 1 day/week for 4 or 16 consecutive weeks). Two days following the last EPM exposure, cardiac and pulmonary tissues were examined histologically. The results showed that particle-laden alveolar macrophages were the only pulmonary lesions observed in all three rat strains. However, WKY rats exposed to EPM (10 mg/m(3) 6 h/day, 1 day/week for 16 weeks) demonstrated cardiac lesions with inflammation and degeneration. To further characterize the nature of EPM-associated lesions, more rigorous histopathological and histochemical techniques were employed for WKY and SD rats. We examined the hearts for myocardial degeneration, inflammation, fibrosis, calcium deposits, apoptosis, and the presence of mast cells. Decreased numbers of granulated mast cells, and multifocal myocardial degeneration, chronic-active inflammation, and fibrosis were present in 5 of 6 WKY rats exposed to EPM for 16 weeks. None of these lesions were present in WKY exposed to clean air. EPM-related cardiac lesions were indistinguishable from air-exposed controls in SD and SH rats. This study demonstrates that long-term inhalation exposures to environmentally relevant PM containing bioavailable zinc can cause myocardial injury in sensitive rats. These findings provide supportive evidence for the epidemiological associations of cardiovascular morbidity and ambient PM.

Kim, J. Y., M. P. Wand, et al. (2003). "Association of expired nitric oxide with occupational particulate exposure." Environ Health Perspect 111(5): 676-80.

Particulate air pollution has been associated with adverse respiratory health effects. This study assessed the utility of expired nitric oxide to detect acute airway responses to metal-containing fine particulates. Using a repeated-measures study design, we investigated the association between the fractional concentration of expired nitric oxide (F(E)NO) and exposure to particulate matter with an aerodynamic mass median diameter of less than or equal to 2.5 micro m (PM(2.5)) in boilermakers exposed to residual oil fly ash and metal fumes. Subjects were monitored for 5 days during boiler repair overhauls in 1999 (n = 20) or 2000 (n = 14). The Wilcoxon median baseline F(E)NO was 10.6 ppb [95% confidence interval (CI): 9.1, 12.7] in 1999 and 7.4 ppb (95% CI: 6.7, 8.0) in 2000. The Wilcoxon median PM(2.5) 8-hr time-weighted average was 0.56 mg/m(3) (95% CI: 0.37, 0.93) in 1999 and 0.86 mg/m(3) (95% CI: 0.65, 1.07) in 2000. F(E)NO levels during the work week were significantly lower than baseline F(E)NO in 1999 (p < 0.001). A significant inverse exposure-response relationship between log-transformed F(E)NO and the previous workday's PM(2.5) concentration was found in 1999, after adjusting for smoking status, age, and sampling year. With each 1 mg/m(3) incremental increase in PM(2.5) exposure, log F(E)NO decreased by 0.24 (95% CI: -0.38, -0.10) in 1999. The lack of an exposure-response relationship between PM(2.5) exposure and F(E)NO in 2000 could be attributable to exposure misclassification resulting from the use of respirators. In conclusion, occupational exposure to metal-containing fine particulates was associated with significant decreases in F(E)NO in a survey of workers with limited respirator usage.

Huang, C. I., D. Neuberg, et al. (2003). "Expression of bcl-2 protein is associated with shorter survival in nonsmall cell lung carcinoma." Cancer 98(1): 135-43.

BACKGROUND: The aim of this study was to assess the relationship between the expression of the 27-kilodalton (kD) bcl-2 protein and survival among nonsmall cell lung carcinoma (NSCLC) patients. METHODS: Paired tissue samples of histologically confirmed tumor and uninvolved lung of 91 randomly selected NSCLC patients were used in this study. The expression of 27-kD bcl-2 proteins in uninvolved lung and tumor tissue specimens was analyzed using Western blot analysis. Overall survival was estimated using the Kaplan-Meier method. The relation between patient survival and expression of the 27-kD bcl-2 protein in uninvolved lung, tumor, and in uninvolved lung and/or tumor tissue specimens was assessed using log-rank tests and Cox proportional hazards multiple regression. RESULTS: The 27-kD bcl-2 protein was expressed in 54% of the uninvolved lung tissue specimens, in 53% of the tumor tissue specimens, and in 70% of the uninvolved lung and/or tumor tissue specimens. When NSCLC patient survival was considered with respect to the expression of the 27-kD bcl-2 protein, a statistically significant shorter survival was observed for patients whose tissue samples expressed the 27-kD bcl-2 protein in the uninvolved lung and in the uninvolved lung and/or tumor (log-rank test, P = 0.008 and P = 0.001, respectively). Cox proportional hazards multiple regression models also showed statistically significant associations between shorter survival and positive 27-kD protein expression in the uninvolved lung (hazard ratio of 2.27; P = 0.05) and in the uninvolved lung and/or tumor (hazard ratio of 5.58, P = 0.008) after controlling for tumor size, stage, the type of surgery received, smoking status, age, and cell type. CONCLUSIONS: In the current study, patients with nonsmall cell lung carcinoma with positive expression of the 27-kD protein bcl-2, either in the uninvolved lung or in uninvolved lung and/or tumor, were found to have significantly poorer postresection survival.

Ha, E. H., J. T. Lee, et al. (2003). "Infant susceptibility of mortality to air pollution in Seoul, South Korea." Pediatrics 111(2): 284-90.

OBJECTIVE: Susceptibility of target populations to air pollution is an important issue, because air pollution policies and standards should be based on the susceptibilities of those at particular risk. To evaluate which age group is more susceptible to the adverse health effects of air pollution, we compared the effects of air pollution on mortality among postneonates, those aged 2 to 64 years, and those over 65 years of age. DESIGN: Daily counts of total and respiratory death along with daily levels of meteorological variables and air pollutants were analyzed using generalized additive Poisson regression. The relative risks (RR) of mortality for interquartile changes of the levels of particulate matter <10 micro m (PM(10)) were calculated on the same day. RESULTS: For postneonates, the RR of total mortality for an interquartile change (42.9 micro g/m(3)) in PM(10) (RR: 1.142; 95% confidence interval [CI]: 1.096-1.190) was greatest among age groups. Next were the elderly over 65 years of age (RR: 1.023; 95% CI: 1.022-1.024). Regarding respiratory mortality, RR for an interquartile change of PM(10) in postneonates (RR: 2.018; 95% CI: 1.784-2.283) was also greater than those in the other groups. CONCLUSIONS: These results agree with the hypothesis that infants are most susceptible to PM(10) in terms of mortality, particularly respiratory mortality.

Duty, S. M., N. P. Singh, et al. (2003). "The relationship between environmental exposures to phthalates and DNA damage in human sperm using the neutral comet assay." Environ Health Perspect 111(9): 1164-9.

Phthalates are industrial chemicals widely used in many commercial applications. The general population is exposed to phthalates through consumer products as well as through diet and medical treatments. To determine whether environmental levels of phthalates are associated with altered DNA integrity in human sperm, we selected a population without identified sources of exposure to phthalates. One hundred sixty-eight subjects recruited from the Massachusetts General Hospital Andrology Laboratory provided a semen and a urine sample. Eight phthalate metabolites were measured in urine by using high-performance liquid chromatography and tandem mass spectrometry; data were corrected for urine dilution by adjusting for specific gravity. The neutral single-cell microgel electrophoresis assay (comet assay) was used to measure DNA integrity in sperm. VisComet image analysis software was used to measure comet extent, a measure of total comet length (micrometers); percent DNA in tail (tail%), a measure of the proportion of total DNA present in the comet tail; and tail distributed moment (TDM), an integrated measure of length and intensity (micrometers). For an interquartile range increase in specific gravity-adjusted monoethyl phthalate (MEP) level, the comet extent increased significantly by 3.6 micro m [95% confidence interval (95% CI), 0.74-6.47]; the TDM also increased 1.2 micro m (95% CI, -0.05 to 2.38) but was of borderline significance. Monobutyl, monobenzyl, monomethyl, and mono-2-ethylhexyl phthalates were not significantly associated with comet assay parameters. In conclusion, this study represents the first human data to demonstrate that urinary MEP, at environmental levels, is associated with increased DNA damage in sperm.

Duty, S. M., M. J. Silva, et al. (2003). "Phthalate exposure and human semen parameters." Epidemiology 14(3): 269-77.

BACKGROUND: There is scientific and public concern about commonly used chemicals, including phthalates, that are associated with reproductive toxicity in laboratory animals and are hormonally active. People are exposed to phthalates through diet, consumer products and medical devices. The present study explored whether environmental levels of phthalates are associated with altered semen quality in humans. METHODS: We recruited 168 men who were part of subfertile couples and who presented to the Massachusetts General Hospital andrology laboratory for semen analysis between January 2000 and April 2001. Semen parameters were dichotomized based on 1999 World Health Organization reference values for sperm concentration (< 20 million/ml) and motility (< 50% motile), as well as Tygerberg Strict criteria for morphology (< 4% normal). The comparison group was men for whom these semen parameters were all above the reference values. In urine, eight phthalate metabolites were measured with high-performance liquid chromatography and tandem mass spectrometry. Specific gravity-adjusted phthalate metabolite levels were categorized into tertiles. RESULTS: There was a dose-response relation between tertiles of mono-butyl phthalate and sperm motility (odds ratio per tertile = 1.0, 1.8, 3.0; P-value for trend = 0.02) and sperm concentration (1.0, 1.4, 3.3; P-value for trend = 0.07). In addition, there was a dose-response relation between tertiles of mono-benzyl phthalate and sperm concentration (1.0, 1.4, 5.5; P-value for trend = 0.02). CONCLUSIONS: There were dose-response relations for monobutyl phthalate and monobenzyl phthalate with one or more semen parameters, and suggestive evidence for monomethyl phthalate with sperm morphology. The lack of a relation for other phthalates may indicate a difference in spermatotoxicity among phthalates.

Christiani, D. C. and X. R. Wang (2003). "Respiratory effects of long-term exposure to cotton dust." Curr Opin Pulm Med 9(2): 151-5.

Traditionally, the concept of cotton dust-related disease focused on acute airway responses. A possible connection of long-term exposure to cotton dust with chronic obstructive airway disease was not addressed until the past two decades. This review summarizes the latest findings relevant to this topic that were observed from longitudinal cohort studies and discusses the relation between acute airway responses and chronic losses of lung function.

Chen, Y. C., L. Xu, et al. (2003). "Genetic polymorphism in p53 codon 72 and skin cancer in southwestern Taiwan." J Environ Sci Health Part A Tox Hazard Subst Environ Eng 38(1): 201-11.

The Pro/Pro polymorphism of p53 codon 72 has been reported to be related to bladder and lung cancer, but its relationship with skin cancer is unclear. We assessed the hypothesis that there is a relationship between the p53 codon 72, Pro/Pro polymorphism, cumulative arsenic exposure, and the risk of skin cancer in a hospital-based case-control study in southwestern Taiwan. From 1996 to 1999, 93 newly-diagnosed skin cancer patients at the National Cheng-Kung University (NCKU) Hospital and 71 community controls matched on residence were recruited in southwestern Taiwan. The genotype of p53 codon 72 (Arg/Arg, Arg/Pro, or Pro/Pro) was determined for all subjects by polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP). A questionnaire was administered to each subject for collection of demographic information, personal habits, disease history, diet information, and other relevant questions. The Pro/Pro (homozygous) genotype was more frequent in skin cancer patients (cases, 20%; controls, 12%; P = 0.37). Subjects with the susceptible genotype Pro/Pro and heterozygous (intermediate) genotype Pro/Arg had 2.18 and 0.99 times risk of skin cancer than the wild type Arg/Arg (95% confidence interval, 0.74-4.38; 95% confidence interval, 0.44-2.21), respectively. Compared with subjects with 18.5 < BMI < 23, subjects with BMI > 18.5 had 5.78 times risk of skin cancer (95% confidence interval, 1.06 to 31.36) after adjusting for other risk factors. There was no interaction between BMI and genotype, but the sample size was small. The risk of skin cancer did not significantly vary by tumor cell-type. The risk of skin cancer is increased in individuals with the Pro/Pro genotype. Larger, confirmatory studies are needed to clarify the role of constitutional polymorphisms in p53 and skin cancer risk.

Chen, Y. C., Y. L. Guo, et al. (2003). "Arsenic methylation and skin cancer risk in southwestern Taiwan." J Occup Environ Med 45(3): 241-8.

Arsenic is a known carcinogen, but data are especially lacking on the health effects of low-level exposure, and on the health significance of methylation ability. We conducted a case-control study (76 cases and 224 controls from 1996 to 1999) in southwestern Taiwan to explore the association among primary and secondary arsenic methylation index (PMI and SMI, respectively), cumulative arsenic exposure (CAE), and the risk of skin cancer. As compared with the controls, the skin cancer group reported more sun exposure (P = 0.02) and had a lower BMI (P = 0.03), as well as lower education level (P = 0.01). Skin cancer patients and controls were similar with regard to age, gender, smoking and alcohol consumption. Given a low SMI (< or = 5), CAE > 15 mg/L-year was associated with an increased risk of skin cancer (OR, 7.48; 95% CI, 1.65-33.99) compared to a CAE < or = 2 mg/L-year. Given the same level of PMI, SMI, and CAE, men had a higher risk of skin cancer (OR, 4.04; 95% CI, 1.46-11.22) when compared to women. Subjects with low SMI and high CAE have a substantially increased risk of skin cancer. Males in all strata of arsenic exposure and methylation ability had a higher risk of skin cancer than women.

Chen, Y. C., H. J. Su, et al. (2003). "Arsenic methylation and bladder cancer risk in Taiwan." Cancer Causes Control 14(4): 303-10.

OBJECTIVE: The mechanism of arsenic detoxification in humans remains unclear. Data are especially lacking for low-level arsenic exposure. We hypothesize that arsenic methylation ability, defined as the ratios of monomethylarsonic acid (MMA(V))/inorganic arsenic (primary arsenic methylation index, PMI) and dimethylarsinic acid (DMA(V))/ MMA(V) (secondary arsenic methylation index, SMI), may modify the association between cumulative arsenic exposure (CAE, mg/L-year) and the risk of bladder cancer. In this study we investigated the relationship among arsenic methylation ability, CAE, and the risk of bladder cancer in a hospital-based case-control study in southwestern Taiwan. METHODS: From January 1996 to December 1999 we identified 49 patients with newly diagnosed cases of bladder cancer at the National Cheng-Kung University (NCKU) Medical Center; controls consisted of 224 fracture and cataract patients selected from the same medical center. The levels of four urinary arsenic species: arsenite (As(III)), arsenate (As(V)), MMA(V), and DMA(V)) were determined in all subjects by using the high-performance liquid chromatography hydride-generation atomic absorption spectrometry (HPLC-HGAAS). CAE was estimated by using published data collected in a survey from 1974 to 1976. RESULTS: Compared to a CAE < or = 2 mg/L-year, CAE > 12 mg/L-year was associated with an increased risk of bladder cancer (multivariate odds ratio (OR) 4.23, 95% confidence interval (CI) 1.12-16.01), in the setting of a low SMI (< or = 4.8). Compared to women, smoking men (OR 6.23, 95% CI 1.88-20.62) and non-smoking men (OR 3.25, 95% CI 0.95-11.06) had higher risks of bladder cancer. Given the same level of PMI, smoking men (OR 9.80, 95% CI 2.40-40.10) and non-smoking men (OR 4.45, 95% CI 1.00-19.84) had a higher risk of bladder cancer when compared to women. With the same level of SMI, both smoking men (OR 6.28, 95% CI 1.76-22.39) and non-smoking men (OR 3.31, 95% CI 0.84-12.97) had a higher risk of bladder cancer when compared to women. CONCLUSIONS: Subjects with low SMI have a substantially increased risk of bladder cancer, especially when combined with high CAE levels.

Chen, J. C., W. R. Chang, et al. (2003). "Predictors of whole-body vibration levels among urban taxi drivers." Ergonomics 46(11): 1075-90.

To identify a set of important WBV predictors that could be used to develop a statistical instrument for exposure assessment in a large epidemiologic study, a total of 432 WBV measures were taken from a sample of 247 male drivers in Taipei City, Taiwan. In accordance with the ISO 2631-1 (1997) methods, we measured the frequency-weighted vertical acceleration (z-axis) over drivers' seat surface, under conditions representing different types of rides (vacant vs. short vs. long) assigned to random destinations. Mixed effect models were used to analyse the WBV data including repeated measures. For this group of urban taxi drivers regularly exposed to WBV of low intensity (mean = 0.31 ms( - 2), ranging from 0.17 to 0.55 ms( - 2) r.m.s.), our analyses indicated that average driving speed was the primary predictor (p < 0.0001). As average driving speed increased, measured vertical acceleration increased in a quadratic-linear manner (p < 0.0001). Other WBV predictors, after adjusting for the effects of other covariates, included automobile manufacturer (p = 0.02), engine size (p = 0.04), body weight (p = 0.002), age (p = 0.02), use of seat cushion (p = 0.03), and traffic period (p = 0.02). Our study suggests that a similar statistical approach could be employed in future studies to improve the quality and efficiency of WBV exposure assessment in professional drivers.

Agalliu, I., E. A. Eisen, et al. (2003). "Truncating the dose range for methacholine challenge tests: three occupational studies." J Occup Environ Med 45(8): 841-7.

The methacholine challenge test protocol was assessed in the reanalysis of three occupational studies. We evaluated the impact of truncating the range of methacholine on responsiveness, as defined by slope and PC(20.) In original analysis, reactivity was similar for apprentices and auto body shop workers, whereas boilermakers were more responsive. Truncating high concentrations did not change the classification of subjects with PC(20) <8 or 16 in any population. However, when responsiveness was measured by slope, the mean responsiveness increased, from -7.9 to -15.3 for apprentices and -7.2 to -10.0 for auto-body shop workers. Results support the American Thoracic Society's recommended maximum of 16 mg/mL and provide evidence that extending the dose range beyond that does not increase sensitivity, whereas stopping before 16 may exaggerate response. Furthermore, to ensure validity, neither slope nor PC(20) should be extrapolated beyond data.

Zhou, W., G. Liu, et al. (2002). "Genetic polymorphisms in N-acetyltransferase-2 and microsomal epoxide hydrolase, cumulative cigarette smoking, and lung cancer." Cancer Epidemiol Biomarkers Prev 11(1): 15-21.

N-acetyltrasferase-2 (NAT2) and microsomal epoxide hydrolase (mEH) are polymorphic genes that metabolize different tobacco carcinogens. Smaller studies found inconsistent relationships between NAT2 or mEH polymorphisms and lung cancer risk. To determine whether there is gene-environment interaction between NAT2 polymorphisms, alone or in combination with mEH polymorphisms, and cumulative smoking exposure in the development of lung cancer, we conducted a case control study of 1115 Caucasian lung cancer patients and 1250 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between NAT2 genotype and lung cancer risk; the adjusted odds ratio (OR) of the rapid versus slow acetylator genotypes was 0.96 [95% confidence interval (CI), 0.79-1.16]. However, gene-environment interaction analyses revealed that the adjusted ORs increased significantly as pack-years increased. For nonsmokers, the fitted OR was 0.66 (95% CI, 0.44-0.99), whereas for heavy smokers (80 pack-years), the OR increased to 1.22 (95% CI, 0.89-1.67). When comparing the extreme genotype combinations of the NAT2 rapid acetylator, higher mEH activity genotype to the NAT2 slow acetylator, and very low mEH activity genotype, the corresponding ORs at 0 and 80 pack-years were 0.30 (95% CI, 0.14-0.62) and 2.19 (95% CI, 1.26-3.81), respectively. Results were similar with ORs derived from stratified models. In conclusion, NAT2 rapid acetylator genotypes are protective against lung cancer in nonsmokers but are risk factors in heavy smokers. The joint effects of NAT2 and mEH polymorphisms are consistent with an independent, additive effect of these two genes, modified by smoking history.

Zhou, W., G. Liu, et al. (2002). "Gene-environment interaction for the ERCC2 polymorphisms and cumulative cigarette smoking exposure in lung cancer." Cancer Res 62(5): 1377-81.

Excision repair cross-complementing group 2 (ERCC2), a major DNA repair protein, is involved in nucleotide excision repair and basal transcription. The ERCC2 polymorphisms have been associated with altered DNA repair capacity. We investigated two ERCC2 polymorphisms, Asp312Asn and Lys751Gln, in 1092 Caucasian lung cancer patients and 1240 spouse and friend controls. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. The overall adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.47 (95% CI, 1.1-2.0) for the Asp312Asn polymorphism (Asn/Asn versus Asp/Asp) and 1.06 (95% CI, 0.8-1.4) for the Lys751Gln polymorphism (Gln/Gln versus Lys/Lys). Gene-smoking interaction analyses revealed that the adjusted ORs for each of the two polymorphisms decreased significantly as pack-years increased. When comparing individuals with Asn/Asn + Gln/Gln versus individuals with Asp/Asp + Lys/Lys, the fitted ORs (95% CIs) were 2.56 (95% CI, 1.3-5.0) in nonsmokers and 0.69 (95% CI, 0.4-1.2) in heavy smokers (80 pack-years; P < 0.01 for the interaction term). Consistent and robust results were found when models incorporated different definitions of cumulative cigarette smoking. A stronger gene-smoking interaction was observed for the Asp312Asn polymorphism than for the Lys751Gln polymorphism. In conclusion, cumulative cigarette smoking modifies the associations between ERCC2 polymorphisms and lung cancer risk.

Zhou, W., Y. Liang, et al. (2002). "Utility of the WHO neurobehavioral core test battery in Chinese workers-a meta-analysis." Environ Res 88(2): 94-102.

We performed a meta-analysis to determine the most sensitive subtests of the WHO Neurobehavioral Core Test Battery (NCTB) when administered to Chinese workers. Extensive Chinese Biological Medical Database and MEDLINE searches, review of cited references, and discussion with other investigators were undertaken. Data were extracted from 39 eligible studies; the summary effects (effect sizes) were calculated using a fixed-effect model. Various exposure agents showed different sensitivities to the seven subtests of NCTB. For mercury-exposure, the Benton Visual Retention was the most sensitive subtest, with an effect size (95% CI) of 6.0 (4.4-7.6). For lead-exposure, the most sensitive subtests were the Pursuit Aiming II and Profile of Mood States, with effect sizes (95% CI) of 11.3 (8.3-14.3) and 10.6 (7.5-13.7), respectively. For organic solvents-exposure, Digit Span, Pursuit Aiming II, and Digit Symbol were the most sensitive subtests, with effect sizes (95- CI) of 4.7 (3.3-6.1), 4.6 (3.1-6.1), and 4.1 (2.7-5.5), respectively.

Zhai, R., G. Liu, et al. (2002). "Genetic polymorphisms of MnSOD, GSTM1, GSTT1, and OGG1 in coal workers' pneumoconiosis." J Occup Environ Med 44(4): 372-7.

Little is known about the genetic susceptibility to coal workers' pneumoconiosis (CWP). We investigated the association between genetic polymorphisms of MnSOD, GSTM1, GSTT1, or OGG1 and susceptibility to CWP. The study population was composed of 259 Chinese retired coal miners who had similar dust exposure histories. Of these, there were 99 cases with International Labor Organization chest radiologic criteria for CWP and 160 controls (with no radiologic criteria for CWP). Individual dust exposure variables were estimated from work histories, and smoking information was obtained from interviews. Polymerase chain reaction-based techniques evaluated the genotypes of all study subjects. There were no differences in genotype frequency of MnSOD, GSTM1, GSTT1, and OGG1 between miners with CWP and miners without CWP, by logistic regression analysis. Cumulative dust exposures, but not genetic polymorphisms, were associated significantly with the presence of CWP. This study illustrates the complexity of factors that may contribute to the development of CWP.

Xu, L. L., G. Liu, et al. (2002). "Counterpoint: the myeloperoxidase -463G-->a polymorphism does not decrease lung cancer susceptibility in Caucasians." Cancer Epidemiol Biomarkers Prev 11(12): 1555-9.

The myeloperoxidase (MPO) G-to-A substitution polymorphism in the promoter region of the MPO gene has been associated with a 40-70% reduction in lung cancer risk in several studies, although a recent nested case-control study disputes these findings. MPO is involved in the activation of a number of procarcinogens, including benzo(a)pyrene. The variant A allele has been shown to reduce MPO mRNA expression, thus potentially decreasing carcinogen activation. To confirm results from smaller studies, we evaluated this MPO polymorphism in 988 incident Caucasian lung cancer cases and 1128 controls. Logistic regression evaluated the association between MPO genotype and lung cancer risk, adjusting for age, gender, smoking status, time since quitting smoking, and pack-years of smoking. In the controls, the A allele frequency was 21%, and genotype distribution was in the Hardy-Weinberg equilibrium. Compared with the wild-type G/G genotype, the adjusted odds ratios for the A/A and A/G genotypes were 1.15 (95% confidence interval 0.7-1.9, P > 0.2) and 1.03 (95% confidence interval 0.8-1.3, P > 0.20), respectively. A similar lack of association was seen in analyses stratified by smoking status, median age, a number of smoking variables, disease stage, tumor grade, and histological subtype. These findings are in contrast with earlier studies suggesting a protective effect of carrying the variant A allele.

Wu, M. T., C. D. Simpson, et al. (2002). "Relationship of exposure to coke-oven emissions and urinary metabolites of benzo(a)pyrene and pyrene in coke-oven workers." Cancer Epidemiol Biomarkers Prev 11(3): 311-4.

Coke-oven workers are occupationally exposed to a high concentration of polycyclic aromatic hydrocarbons (PAH). r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo(a)pyrene (trans-anti-BaP-tetraol) and 1-hydroxypyrene (1-OHP) are urinary metabolites of benzo(a)pyrene and pyrene, respectively. In this study, we investigated the relationship among individual air exposure to benzene soluble fraction (BSF) of total particulates, as a surrogate marker of ambient PAH exposures, and urinary trans-anti-BaP-tetraol and 1-OHP concentrations in coke-oven workers at a steel plant in Taiwan. Fifty-seven subjects, including 41 male workers who work in one coke-oven plant and 16 men (referents) from an administrative area, were studied. The mean trans-anti-BaP-tetraol and 1-OHP concentrations (mean +/- SD) were 0.4 +/- 0.3 nmol/mol creatinine and 9.7 +/- 21.6 micromol/mol creatinine, respectively, in coke-oven workers. These levels were significantly higher than those in referents (0.03 +/- 0.03 nmol/mole creatinine, P < 0.001 and 0.4 +/- 0.2 micromol/mol creatinine, P < 0.01, respectively). Urinary trans-anti-BaP-tetraol concentrations were significantly and positively correlated with individual average BSF and urinary 1-OHP concentrations. That is, the higher the urinary trans-anti-BaP-tetraol concentrations, the more ambient BSF exposure and urinary 1-OHP concentrations (Spearman correlation coefficients r = 0.68 and 0.70, respectively; P < 0.0001; n = 57). These findings suggest that urinary 1-OHP and trans-anti-BaP-tetraol might be considered as potential biomarkers for the assessment of uptake of known PAH carcinogens in the air.

Wang, X. R., L. D. Pan, et al. (2002). "Follow-up study of respiratory health of newly-hired female cotton textile workers." Am J Ind Med 41(2): 111-8.

BACKGROUND: Numerous studies have investigated adverse effects of exposure to cotton dust on respiratory health, but very limited longitudinal data are available with regard to the early pulmonary response to cotton dust. Moreover, the adverse effects of occupational exposure to cotton dust have been difficult to separate from the confounding effects of smoking. This setting provided a unique opportunity to evaluate early respiratory effects in newly hired and non-smoking female textile workers. METHODS: To identify early pulmonary responses to cotton dust exposure and associated gram-negative bacterial endotoxin, respiratory symptoms and pulmonary function in 225 newly-hired textile workers were assessed at work initiation, and at three and twelve months later. RESULTS: All the workers were females and nonsmokers, with an average age of 18 years. Symptom incidence at three months was 3.6% for usual cough with phlegm, and 6.7% for usual dry cough. Lung function changes were detectable at one year: FEV1 declined by 70 ml and FVC by 124 ml over the year, and workers reporting respiratory symptoms at three months showed a significantly greater cross-shift drop in FEV1 (- 2.3%) than those without the symptoms (- 0.7%). CONCLUSIONS: These results suggest that the occurrence of respiratory symptoms represents the earliest response to cotton dust exposure, followed by lung function changes. Early respiratory symptoms may be a risk factor for subsequent loss of pulmonary function in cotton textile workers.

Soteriades, E. S., S. N. Kales, et al. (2002). "Lipid profile of firefighters over time: opportunities for prevention." J Occup Environ Med 44(9): 840-6.

Heart disease is the primary cause of on-duty deaths in firefighters, but little is known about their lipid profile. We evaluated the lipid profile in relation to other cardiovascular disease risk factors in 321 firefighters at a baseline examination. Prospective comparisons were performed for 285 firefighters, who were enrolled in a statewide medical surveillance program, and had complete follow-up data for 4 years. The average cholesterol level in firefighters declined from 224 mg/dL at baseline (1996-1997) to 214 mg/dL at the follow-up examination (P < 0.0001). Conversely, both obesity (body mass index > or = 30; 34% versus 40%, P = 0.008) and triglycerides (> or = 200 mg/dL; 27% versus 35%, P = 0.047) increased over time. The proportion of firefighters taking lipid-lowering medications increased from 3% at baseline to 12% at follow-up (P < 0.0001). Cholesterol levels declined significantly, and treatment rates for elevated cholesterol increased over time. Despite repeated examinations, a considerable number of firefighters had persistently elevated cholesterol, and only a minority were receiving adequate treatment.

Sorensen, G., A. M. Stoddard, et al. (2002). "A comprehensive worksite cancer prevention intervention: behavior change results from a randomized controlled trial (United States)." Cancer Causes Control 13(6): 493-502.

OBJECTIVE: Workplace cancer prevention initiatives have been least successful with blue-collar workers. This study assess whether an intervention integrating health promotion with occupational health and safety results in significant and meaningful increases in smoking cessation and consumption of fruits and vegetables, compared to a standard health promotion intervention, for workers overall and for blue-collar workers in particular. METHODS: A randomized controlled design was used, with 15 manufacturing worksites assigned to a health promotion (HP) or a health promotion plus occupational health and safety intervention (HP/OHS), and compared from baseline (1997) to final (1999). The response rates to the survey were 80% at baseline (n = 9019) and 65% at final (n = 7327). Both groups targeted smoking and diet; the HP/OHS condition additionally incorporated reduction of occupational exposures. RESULTS: Smoking quit rates among blue-collar workers in the HP/OHS condition more than doubled relative to those in the HP condition (OR = 2.13, p = 0.04), and were comparable to quit rates of white-collar workers. No statistically significant differences between groups were found for mean changes in fruits and vegetables. CONCLUSIONS: Integration of occupational health and safety and health promotion may be an essential means of enhancing the effectiveness of worksite tobacco control initiatives with blue-collar workers.

Mukherjee, S., E. Rodrigues, et al. (2002). "1-hydroxypyrene as a biomarker of occupational exposure to polycyclic aromatic hydrocarbons (PAH) in boilermakers." J Occup Environ Med 44(12): 1119-25.

A repeated measures short-term prospective study was performed in boilermakers to determine occupational polycyclic aromatic hydrocarbon (PAH) exposure using the biomarker, 1-hydroxypyrene (1-OHP). Two work sites were studied; an apprentice school (metal fume exposure) and a boiler overhaul (residual oil fly ash [ROFA] and metal fume exposure). Pre- and postshift urine samples (n = 241; 41 male subjects) were analyzed for cotinine and 1-OHP. Descriptive statistics and generalized estimating equations were calculated. At the apprentice school cross-shift 1-OHP levels did not significantly differ. At the overhaul 1-OHP levels increased during the week in smokers and nonsmokers; in nonsmokers the 1-OHP level increased significantly postshift compared to preshift. In conclusion this study suggests that boilermakers exposed to occupational particulates are exposed to PAH. The urinary 1-OHP level may be a useful biomarker of PAH exposure in boilermakers exposed to ROFA, particularly in nonsmokers.

Miller, D. P., G. Liu, et al. (2002). "Combinations of the variant genotypes of GSTP1, GSTM1, and p53 are associated with an increased lung cancer risk." Cancer Res 62(10): 2819-23.

GSTP1 and GSTM1 are genes involved in Phase II metabolism, whereas p53 is a tumor suppressor gene. Individually, functional polymorphisms of these genes have been studied as risk factors for lung cancer. Small sample sizes have hindered the detection of possible increases in risk associated with having two or more "at risk" polymorphisms of these three genes. In a large Caucasian population, we examined the association of combined variant genotypes [or double-variants (DVs)] of these three genes and lung cancer risk, compared with their corresponding "double-wild-type" genotypes. Because these DVs may promote lung carcinogenesis at an earlier age, a subgroup of individuals aged 55 years or younger was examined separately. Using a case-control design, individuals were genotyped for GSTM1, GSTP1, and p53 codon 72 using PCR-RFLP techniques. All of the analyses used multiple logistic regression. Indicator variables were created to evaluate the risk for individuals with the following DVs: GSTP1 GG + GSTM1-null and GSTP1 GG + p53 Arg/Pro or Pro/Pro. A total of 1694 cases and controls were evaluated. In the whole population, those with the double variants have a higher risk of lung cancer when compared with those with the double-wild-type genotypes, supporting our original hypothesis. Individuals with the GSTP1 and GSTM1, DV (P1-M1 DV) had a marginally significant higher risk of lung cancer compared with their double-wild-type counterparts [adjusted odds ratio (AOR), 1.60; 95% confidence interval (CI), 0.95-2.70]. A significantly higher risk was found for the GSTP1, p53 DV (P1-p53 DV; AOR, 1.99; 95% CI, 1.12-3.53). Among individuals aged 55 or younger, these risks were even higher: for the P1-M1 DV the AOR was 4.03 (95% CI, 1.47-11.1); for the P1-p53 DV the AOR was 5.10 (95% CI, 1.42-18.30). Specific DVs of GSTM1, GSTP1, and p53 codon 72 are associated with a higher lung cancer risk. This susceptibility is highest among younger individuals.

Magari, S. R., J. Schwartz, et al. (2002). "The association between personal measurements of environmental exposure to particulates and heart rate variability." Epidemiology 13(3): 305-10.

BACKGROUND: Epidemiologic evidence indicates that airborne particulates are associated with mortality risk, predominately from heart disease. This may occur through changes in the cardiac autonomic nervous system, witnessed by changes in heart rate variability. METHODS: This short-term longitudinal study used continuous personal particulate matter measurements to examine the effects of exposure to particulate matter less than 2.5 microm in diameter (PM2.5) on heart rate and rate variability in 20 relatively young, healthy male workers. Continuous exposure and cardiac monitoring were performed on each subject on a nonwork day. The 5-minute standard deviation of the normal-to-normal interval was used as the main measure of heart rate variability. RESULTS: Mixed-effects regression models estimate an average 1.4% (95% confidence limits = -2.1, -0.6) decrease in the 5-minute standard deviation of the normal-to-normal interval for each 100 microg/m3 increase in the 3-hour PM2.5 moving average, and small increases in heart rate, after adjustment for potential confounding factors. Predicted effects of exposure were greatest using the 3-hour averaging interval for PM2.5 and decreased in magnitude using shorter and longer intervals. CONCLUSIONS: These results reveal an association between cardiac autonomic function and environmental PM2.5 exposure. These observed associations may result from decreased vagal or increased sympathetic tone.

Magari, S. R., J. Schwartz, et al. (2002). "The association of particulate air metal concentrations with heart rate variability." Environ Health Perspect 110(9): 875-80.

Numerous studies show an association between particulate air pollution and adverse health effects. Particulate matter is a complex mixture of elemental carbon, ammonium, sulfates, nitrates, organic components, and metals. The mechanisms of action of particulate matter less than or equal to 2.5 micro m in mean aerodynamic diameter (PM(2.5)), as well as the constituents responsible for the observed cardiopulmonary health effects, have not been identified. In this study we focused on the association between the metallic component of PM(2.5) and cardiac autonomic function based on standard heart rate variability (HRV) measures in an epidemiologic study of boilermakers. Thirty-nine male boilermakers were monitored throughout a work shift. Each subject wore an ambulatory electrocardiogram (Holter) monitor and a personal monitor to measure PM(2.5). We used mixed-effects models to regress heart rate and SDNN index (standard deviation of the normal-to-normal) on PM(2.5) and six metals (vanadium, nickel, chromium, lead, copper, and manganese). There were statistically significant mean increases in the SDNN index of 11.30 msec and 3.98 msec for every 1 micro g/m(3) increase in the lead and vanadium concentrations, respectively, after adjusting for mean heart rate, age, and smoking status. Small changes in mean heart rate were seen with all exposure metrics. The results of this study suggest an association between exposure to airborne metals and significant alterations in cardiac autonomic function. These results extend our understanding of the adverse health effects of the metals component of ambient PM(2.5).

Kodavanti, U. P., M. C. Schladweiler, et al. (2002). "Pulmonary and systemic effects of zinc-containing emission particles in three rat strains: multiple exposure scenarios." Toxicol Sci 70(1): 73-85.

As a common component of ambient particulate matter (PM), zinc has been proposed to play a role in PM-induced adverse health effects. Although occupational exposures to high levels of zinc-fume have been associated with metal-fume fever accompanied by pulmonary inflammation and injury, the effects of PM-associated zinc are unclear. We hypothesized that an oil combustion emission PM (EPM) containing bioavailable zinc would induce pulmonary injury and systemic hematological changes attributable to the leachable zinc following acute as well as longer-term exposures in a rat strain-specific manner. In order to initially characterize the pulmonary response to EPM, male Sprague-Dawley (SD) rats were intratracheally (IT) instilled with 0.0, 0.8, 3.3, or 8.3 mg/kg EPM in saline. To further determine if the pulmonary injury was associated with the EPM leachable zinc, subsequent studies included IT instillation of SD rats with either saline, whole EPM suspension, the saline leachable fraction of EPM, the particulate fraction of EPM (all at 8.3 mg/kg, soluble Zn = 14.5 microg/mg EPM), or ZnSO(4) (0.0, 33.0, or 66.0 microg/kg Zn). Finally, to ascertain the cumulative impact of inhaled EPM in the causation of acute pulmonary and systemic effects as well as long-term fibrotic responses, we exposed three rat strains of differential susceptibility to PM. Male SD, normotensive Wistar-Kyoto (WKY), and spontaneously hypertensive (SH) rats (90 days old) were exposed nose-only to either filtered air or EPM: 2, 5, or 10 mg/m(3) (6 h/day x 4 days/week x 1 week); or 10 mg/m(3) (6 h/day x 1 day/week for 1, 4, or 16 weeks) and assessed at 2 days postexposure. IT exposures to whole EPM suspensions were associated with a dose-dependent increase in protein/albumin permeability and neutrophilic inflammation. Pulmonary protein/albumin leakage and neutrophilic inflammation caused by the leachable fraction of EPM and ZnSO(4) were comparable to the effect of whole suspension. However, protein/albumin leakage was not associated with the particulate fraction, although significant neutrophilic inflammation did occur following instillation. With EPM nose-only inhalation, acute exposures (10 mg/m(3) only) for 4 days resulted in small increases in bronchoalveolar lavage fluid (BALF) protein and n-acetyl glucosaminidase activities (approximately 50% above control). Surprisingly, unlike IT exposures, no neutrophilic influx was detectable in BALF from any of the inhalation groups. The only major effect of acute and long-term EPM inhalation was a dose- and time-dependent increase in alveolar macrophages (AM) regardless of the rat strain. Histological evidence also showed dose- and time-dependent accumulations of particle-loaded AM. Particles were also evident in interstitial spaces, and in the lung-associated lymph nodes following the inhalation exposures (SH > WKY = SD). There were strain-related differences in peripheral white blood cell counts and plasma fibrinogen with no major EPM inhalation effect. The present study demonstrated the critical differences in pulmonary responsiveness to EPM between IT and inhalation exposures, probably attributable to the dose of bioavailable zinc. EPM IT exposures, but not acute and long-term inhalation of up to 10 mg/m(3), caused neutrophilic inflammation. Inhalation exposures may result in particle accumulation and macrophage recruitment with potential strain differences in EPM clearance.

Kodavanti, U. P., M. C. Schladweiler, et al. (2002). "Temporal association between pulmonary and systemic effects of particulate matter in healthy and cardiovascular compromised rats." J Toxicol Environ Health A 65(20): 1545-69.

Exposure to particulate matter (PM) has been associated with increased morbidity and mortality among individuals with cardiovascular disease. It is hypothesized that systemic alterations occur concurrent to pulmonary injury/inflammation, and contribute to cardiac events in compromised hosts. We explored this hypothesis using a rat model for human hypertension and cardiovascular disease (spontaneously hypertensive, SH), and normotensive Wistar Kyoto (WKY) rats. SH and WKY rats (12-13 wk old) were exposed either intratracheally (IT; 0.0, 1.0, or 5.0 mg/kg in saline) or nose-only (15 mg/m(3) x 6 h/d x 3 d/wk x 1, 2 or 4 wk) to combustion source residual oil fly ash (ROFA) with low metal content, and examined 1, 2 or 4 d later. Bronchoalveolar lavage fluid (BALF) albumin and neutrophils increased (SH approximately equal WKY) at d 1 following ROFA IT. With inhalation exposure, both strains experienced progressive histological lung damage and increases in BALF albumin and neutrophils during 1 to 4 wk (SH > WKY). Acute lung injury from ROFA IT was temporally associated with increases in plasma fibrinogen in both strains, but only the SH rats responded to the acute 1-wk ROFA inhalation. Longer term (2 or 4 wk) ROFA caused progressive lung injury (SH > WKY), but did not sustain the increase in fibrinogen. BALF glutathione increased in a temporal fashion similar to fibrinogen; however, only WKY rats demonstrated this response. There was a small but consistent decrease in blood lymphocytes and an increase in blood neutrophils in SH rats exposed to ROFA acutely. In conclusion, acute PM exposure can provoke an acute systemic thrombogenic response associated with pulmonary injury/inflammation and oxidative stress in cardiovascular compromised rats. This evidence is consistent with greater cardiovascular events during acute PM episodes in compromised humans.

Kales, S. N., E. S. Soteriades, et al. (2002). "Firefighters' blood pressure and employment status on hazardous materials teams in Massachusetts: a prospective study." J Occup Environ Med 44(7): 669-76.

We evaluated the association between hypertension and changes in employment status in 334 hazardous materials firefighters. Firefighters were categorized by blood pressure (BP) at baseline (1996 or 1997) and subsequent follow-up examinations (1997, 1998, and 1999). They were followed up for a maximum of 4 years for possible adverse outcomes (death, placement on "injured-on-duty" status, termination of duty, resignation, retirement, or incident cardiovascular disease). In several analytic models, we found that firefighters with stage II hypertension (BP > or = 160/100 mm Hg) were consistently 2 to 3 times more likely to experience an adverse outcome compared with those with normal BP. Cox proportional-hazards regression was used to adjust for age, body mass index, smoking, cholesterol, and antihypertensive medication. In these models, the hazard ratio for stage II hypertension was 3.2 (95% confidence interval [CI], 1.50 to 7.04, P = 0.003) and for untreated stage II hypertension, it was 4.6 (95% CI, 2.08 to 10.11, P = 0.0002). Firefighters with a BP > or = 160/100 mm Hg should receive further evaluation and demonstrate improved BP control before being determined fit for duty.

Hu, Y. A., T. J. Smith, et al. (2002). "Comparison of self-assessment of solvent exposure with measurement and professional assessment for female petrochemical workers in China." Am J Ind Med 41(6): 483-9.

OBJECTIVE: The primary objective of this paper is to examine the validity of self-assessment of solvent exposure by comparing it with professional assessment and actual measurements. METHODS: Self-assessment of exposures to benzene, toluene, styrene, and xylene was obtained from 132 female workers. The exposures were also estimated by an occupational hygienist and by actual measurement. Self-assessment, professional assessment, and measurement were then compared with each other. RESULTS: Fair to good agreement was found between self-assessment, professional assessment, and measurement for benzene, styrene, and xylene. The agreement between self-assessment and measurement was poor for toluene, whereas the agreement between self-assessment and professional assessment was good. The latter was caused by a biased professional assessment. CONCLUSIONS: Workers' self-assessment and professional assessment provided useful information for benzene, styrene, and xylene exposure, but not for toluene exposure. False agreement can be obtained when professional assessment was used as reference in validity study.

Hong, Y. C., J. T. Lee, et al. (2002). "Effects of air pollutants on acute stroke mortality." Environ Health Perspect 110(2): 187-91.

The relationship between stroke and air pollution has not been adequately studied. We conducted a time-series study to examine the evidence of an association between air pollutants and stroke over 4 years (January 1995-December 1998) in Seoul, Korea. We used a generalized additive model to regress daily stroke death counts for each pollutant, controlling for seasonal and long-term trends and meteorologic influences, such as temperature, relative humidity, and barometric pressure. We observed an estimated increase of 1.5% [95% confidence interval (CI), 1.3-1.8%] and 2.9% (95% CI, 0.3-5.5%) in stroke mortality for each interquartile range increase in particulate matter < 10 microm aerodynamic diameter (PM(10)) and ozone concentrations in the same day. Stroke mortality also increased 3.1% (95% CI, 1.1-5.1%) for nitrogen dioxide, 2.9% (95% CI, 0.8-5.0%) for sulfur dioxide, and 4.1% (95% CI, 1.1-7.2%) for carbon monoxide in a 2-day lag for each interquartile range increase in single-pollutant models. When we examined the associations among PM(10) levels stratified by the level of gaseous pollutants and vice versa, we found that these pollutants are interactive with respect to their effects on the risk of stroke mortality. We also observed that the effects of PM(10) on stroke mortality differ significantly in subgroups by age and sex. We conclude that PM(10) and gaseous pollutants are significant risk factors for acute stroke death and that the elderly and women are more susceptible to the effect of particulate pollutants.

Hong, Y. C., K. H. Lee, et al. (2002). "Genetic susceptibility of term pregnant women to oxidative damage." Toxicol Lett 129(3): 255-62.

Genetic polymorphisms involved in the activation and detoxification of exogenous chemicals and in the production and scavenging of reactive oxygen species may modulate the levels of oxidative injury biomarker. We investigated 81 pregnant women in Inchon, Korea. In addition to a questionnaire survey, urinary concentrations of 8-hydroxydeoxyguanosine (8-OH-dG) and malondialdehyde (MDA) were measured as oxidative injury biomarkers. Cytochrome P-450(CYP)1A1, CYP2E1, glutathione S-transferase (GST)M1 and GSTT1 polymorphisms and myeloperoxidase (MPO) and manganese superoxide dismutase (MnSOD) polymorphisms were evaluated to determine the effect of genetic modification on urinary 8-OH-dG and MDA. The concentrations of urinary 8-OH-dG were significantly elevated in the presence of the MnSOD variant genotype (P=0.04) and in the case of GSTM1 null status (P=0.02) by multivariate regression. The concentrations of urinary MDA were not affected significantly by the genetic polymorphisms. This result shows that oxidative stress injury is modified by some heritable polymorphisms, including GSTM1 and MnSOD.

Hauser, R., L. Altshul, et al. (2002). "Environmental organochlorines and semen quality: results of a pilot study." Environ Health Perspect 110(3): 229-33.

There have been numerous studies that suggest that sperm concentrations (sperm counts) are declining in men. However, other studies suggest that sperm counts are not declining or may be increasing in some areas. Although there is disagreement on whether there is a downward temporal trend in sperm counts, the studies provide evidence that sperm counts vary by geographic location. It has been hypothesized that the geographic variation in sperm concentrations may be due to environmental exposures, lifestyle factors, or some unknown causes. To determine whether contemporary ambient levels of polychlorinated biphenyls (PCBs) and p,p-DDE are associated with altered semen quantity and quality, we selected a study population without specific exposure to PCBs or p,p-DDE. The present study presents the results from a pilot study on the relationship between serum PCBs and p,p-DDE and semen quality in 29 subjects recruited from the Massachusetts General Hospital Andrology Laboratory. Of the 29 subjects, 3 had sperm concentrations < 20 million/mL, 7 had < 50% motile sperm, 9 had < 4% normal morphology, and 6 were below normal in more than one semen parameter. The 18 subjects with normal spermatozoa concentration, motility, and morphology were used as comparison subjects. The mean (SE) concentration of the sum of PCBs and p,p-DDE was 242 ng/g lipids (34.0) and 354 ng/g lipids (120), respectively, for men with below normal motility as compared to 202 ng/g lipids (16.6) and 240 ng/g lipids (31.1), respectively, for the comparison subjects. The data showed general trends that were suggestive of an association between PCBs and p,p-DDE and abnormal motility, as well as with sperm concentration and morphology. A full-scale study is currently in progress.

Hauser, R., E. A. Eisen, et al. (2002). "Spirometric abnormalities associated with chronic bronchitis, asthma, and airway hyperresponsiveness among boilermaker construction workers." Chest 121(6): 2052-60.

STUDY OBJECTIVES: In a 2-year longitudinal study of boilermaker construction workers, we found a significant association between working at oil-fired, coal-fired, and gas-fired industries during the past year and reduced lung function. In the present study, we investigated whether chronic bronchitis, asthma, or baseline methacholine airway responsiveness can explain the heterogeneity in lung function response to boilermaker work. DESIGN: This study is part of an ongoing prospective cohort study of boilermakers. Exposure was assessed with a work history questionnaire. Spirometry was performed annually to assess lung function. A generalized estimating equation approach was used to account for the repeated-measures design. SETTING: Boilermaker union members. PARTICIPANTS: One hundred eighteen boilermakers participated in the study. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Self-reported history of chronic bronchitis and asthma were associated with a larger FEV1 reduction in response to workplace exposure at coal-fired and gas-fired industries. Although we found a high prevalence (39%) of airway hyperresponsiveness (provocative concentration of methacholine causing a 20% fall in FEV1 of < 8 mg/mL) among boilermakers, we did not find a consistent pattern of effect modification by airway responsiveness. CONCLUSIONS: Although chronic bronchitis and asthma were associated with a greater loss in lung function in response to hours worked as a boilermaker, and therefore they acted as effect modifiers of the exposure-lung function relationship, airway hyperresponsiveness did not. However, the high prevalence of airway hyperresponsiveness found in the cohort may be a primary consequence of long-term workplace exposure among boilermakers.

Ha, E., S. I. Cho, et al. (2002). "Does standing at work during pregnancy result in reduced infant birth weight?" J Occup Environ Med 44(9): 815-21.

The purpose of this study was to investigate the association between infant birth weight and standing at work during pregnancy. A total of 1222 pregnant women employed in a large petrochemical corporation in Beijing, China, were enrolled in the study, after receiving permission from the government to have a child. The subjects were followed up from that time through their entire pregnancy, for a total of up to 12 months. All subjects delivered at the company staff hospital between 1996 and 1998. Various work-related physical activities during pregnancy were assessed using a structured questionnaire, and generalized additive models (GAMs) were performed to examine their association with birth weight. Of the assessed activities, only standing was significantly associated with birth weight. After adjusting for potential confounders, maternal standing hours per day at work was found to be significantly associated with reduced birth weight (-17.7 g, P = 0.03).

Ha, E., S. I. Cho, et al. (2002). "Parental exposure to organic solvents and reduced birth weight." Arch Environ Health 57(3): 207-14.

The authors investigated the association of birth weight with maternal and paternal exposure to organic solvents in 1,222 couples employed in a large petrochemical corporation in Beijing, China, during the period between 1994 and 1998. A trained interviewer assessed parental exposures to organic solvents. The authors used generalized additive models to examine the association between birth weight and parental exposure to organic solvents. After the authors adjusted for potential confounders, maternal exposure to solvents was significantly associated with reduced birth weight (-81.7 gm, 95% confidence interval = -106.3, -3.1), and reduced birth weights of female babies and of younger mothers' babies were statistically significant. Maternal exposure to organic solvents was associated with reduced birth weight in this population, but paternal exposure to organic solvents was not similarly associated.

Christiani, D. C., X. Tan, et al. (2002). "Occupational health in China." Occup Med 17(3): 355-70, iii.

China has been experiencing rapid industrialization and economic growth, resulting in a transformed industrial structure and expansion of the labor force. Occupational health and safety services, nonexistent before 1949, have made remarkable advances over the past decades. However, these services face greater challenges, consisting of both traditional and new occupational health problems. Poorly regulated work environments often lacking health services in recently developed and thriving small-scale industries and joint venture enterprises have created increasing risks for occupational diseases and work-related injuries. A special strategy based on cooperation among and contributions from the legal, administrative, social, economic, and scientific communities is critical to achieving the ultimate goal of control and prevention of these occupational health problems.

Cho, S. I., M. B. Goldman, et al. (2002). "Reliability of serial urine HCG as a biomarker to detect early pregnancy loss." Hum Reprod 17(4): 1060-6.

BACKGROUND: To examine the reliability of HCG as a biomarker for early pregnancy loss, five experienced researchers independently assessed data from 153 menstrual cycles, determining whether each cycle represented 'no conception,' a 'continuing conception' or a 'conception lost.' METHODS: Urine samples were analysed by immunoradiometric assay using a combination of capture antibodies for the intact heterodimer (B109) and for an epitope common to the beta subunit and the beta core fragment (B204). For each cycle, HCG data were presented as graphs of daily assay results. Summary statistics for HCG assays from 46 women who had undergone bilateral tubal ligation represented baseline values. RESULTS: Pairwise agreement among the assessors for any of the three options ranged from 78-89%. At least three experts agreed for 147 cycles (96%), accounting for 28 conception losses and 19 continuing conceptions. The multi-rater kappa was 0.62 for the conception lost category and 0.68 for continuing conceptions, indicating substantial agreement. CONCLUSION: The main sources of disagreement involved deciding whether there was sufficient information for assessment, interpreting cycle parameters such as cycle length or bleeding event, and interpreting a distinct HCG rise pattern that does not exceed the baseline value obtained from the sterilized women.

Chen, Y. C., C. J. Amarasiriwardena, et al. (2002). "Stability of arsenic species and insoluble arsenic in human urine." Cancer Epidemiol Biomarkers Prev 11(11): 1427-33.

Urinary arsenic species are important short-term biomarkers that have been used in epidemiological studies. However, the stability of soluble arsenic species and the amount of arsenic lost during sample pretreatment remain unclear. The objective of this study is to evaluate the stability of soluble arsenic species in urine and aqueous standards, as well as to assess the amount of insoluble and soluble arsenic lost during pretreatment (centrifugation and filtration, respectively). High-performance liquid chromatogram inductively coupled plasma mass spectrometry was used to speciate arsenic species [Arsenite [As(III)], arsenate [As(V)], monomethylarsonic acid [MMA(V)], monomethylarsonous acid [MMA(III)], dimethylarsinic acid [DMA(V)], and arsenobetaine [AsB]] in aqueous standards and in urine samples. The arsenic levels in both freshly collected urine samples (pH = 5.5-7.0) and National Institute of Standards and Technology Standard Reference Material 2670 toxic elements in frozen-dried urine (pH 4.4) remained constant up to 6 months when stored at -20 degrees C. In an aqueous solution mixed with 10 micro g/liter of As(III), As(V), MMA, and DMA standards, and stored at 4 degrees C, As(III) and As(V) were stable only up to 4 weeks, and MMA and DMA remained stable up to 4.5 months. The same phenomenon was observed for 100 micro g/liter mixed aqueous standards. There was no significant loss of arsenic species in urine (<5%) when passed through a 0.45- micro m filter. The amounts of insoluble arsenic in urine lost during centrifuge ranged from 1/2 to 1/17 of soluble arsenic. These findings indicated that the urinary matrix plays an important role in stabilizing arsenic species. Also, the loss of insoluble arsenic in urine during centrifuging results in underestimation of arsenic exposure, and may explain the lack of an association between arsenic exposure and the risk of health outcomes reported in some epidemiological studies.

Bracken, M. B., K. Belanger, et al. (2002). "Genetic and perinatal risk factors for asthma onset and severity: a review and theoretical analysis." Epidemiol Rev 24(2): 176-89.

Zhou, W., D. Yuan, et al. (2001). "Health effects of occupational exposures to vehicle emissions in Shanghai." Int J Occup Environ Health 7(1): 23-30.

The authors investigated the health effects of occupational exposures to vehicle emissions in 745 bus drivers, conductors, and taxi drivers, compared with 532 unexposed controls, in Shanghai. Logistic regression and general linear models were used to examine the relationship between exposure and respiratory illness. Results showed that the prevalences of some respiratory symptoms and chronic respiratory diseases were significantly higher (p < 0.05) in the exposed group than in the controls. The adjusted odds ratios for throat pain, phlegm, chronic rhinitis, and chronic pharyngitis were 1.95 (95% CI 1.55-2.46), 3.90 (95% CI 2.61-5.81), 1.96 (95% CI 1.11-3.46), and 4.19 (95% CI 2.49-7.06), respectively. Also, there were exposure time response relationships for the prevalences of phlegm and chronic respiratory disease. Pulmonary function and blood lead levels were not significantly correlated with exposure status. The results suggest that occupational exposure to vehicle emissions may induce detectable adverse health effects.

Zhou, W., S. W. Thurston, et al. (2001). "The interaction between microsomal epoxide hydrolase polymorphisms and cumulative cigarette smoking in different histological subtypes of lung cancer." Cancer Epidemiol Biomarkers Prev 10(5): 461-6.

Microsomal epoxide hydrolase (mEH) is involved in the metabolism of environmental and tobacco carcinogens. Smaller studies found inconsistent results in the relationship between mEH polymorphisms and lung cancer risk. We investigated the two polymorphisms of mEH in 974 Caucasian lung cancer patients and 1142 controls using PCR-RFLP techniques. The results were analyzed using generalized additive models and logistic regression, adjusting for relevant covariates. There was no overall relationship between mEH genotypes and lung cancer risk. The adjusted odds ratio (OR) of the very low activity genotype versus that of other genotypes combined was 1.00 [95% confidence interval (CI), 0.74-1.34]. However, gene-environment interaction analyses revealed that the ORs decreased as cumulative smoking (defined as square root of pack-years) increased. When pack-years = 0, the OR was 1.89 (95% CI, 1.08-3.28). When pack-years = 28.5, the OR was 1.00 (95% CI, 0.76-1.32), and when pack-years = 80, the OR decreased to 0.65 (95% CI, 0.42-1.00). When cases were stratified according to histological subtypes, the interaction between mEH genotype and cumulative smoking was statistically significant (P < 0.01) for the 222 squamous cell carcinoma cases, whereas it was not significant (P = 0.18) for the 432 adenocarcinoma cases. In conclusion, cumulative cigarette smoking plays a pivotal role in the association between mEH polymorphisms and lung cancer risk, altering the direction of risk (in the case of the very low activity genotype) from a risk factor in nonsmokers to a relatively protective factor in heavy smokers.

Zhai, R., G. Liu, et al. (2001). "The G to C polymorphism at -174 of the interleukin-6 gene is rare in a Southern Chinese population." Pharmacogenetics 11(8): 699-701.

Interleukin-6 is thought to be involved in the pathogenesis of coal workers' pneumoconiosis. Recently, a functional G to C polymorphism at position -174 of the promoter of the IL-6 gene has been described. We examined the -174 polymorphisms in 259 retired Chinese men from Guangxi province (all retired coal miners). Only one GC heterozygous and no CC homozygous variants were found. Our results suggest that the frequency of the C allele in this Chinese population is lower than in Caucasian and east Indian populations.

Xu, L. L., J. C. Wain, et al. (2001). "The NAD(P)H:quinone oxidoreductase 1 gene polymorphism and lung cancer: differential susceptibility based on smoking behavior." Cancer Epidemiol Biomarkers Prev 10(4): 303-9.

We conducted a hospital-based case-control study of 814 lung cancer patients and 1123 controls to examine the association of the NAD(P)H: quinone oxidoreductase 1 (NQO1) gene polymorphism with lung cancer susceptibility. Using PCR-RFLP genotyping assay techniques, we analyzed DNA samples to detect the variant forms of the NQO1 gene in exon 6 on chromosome 16q. We examined the relationship between lung cancer odds and NQO1 genotypes after adjusting for age, gender, and smoking behavior using generalized additive modeling. We found no overall association between NQO1 genotypes and lung cancer susceptibility, regardless of age, gender, family history of cancer, or histological cell type. However, our data demonstrated that in both former and current smokers, there was an association between NQO1 genotypes and lung cancer susceptibility that was dependent upon cigarette smoking duration and smoking intensity. For both current and former smokers, smoking intensity was more important in predicting cancer risk than smoking duration for all of the genotypes. Among former smokers, individuals with the T/T genotype were predicted to have a greater cancer risk than those with the C/C genotype for smoking durations up to 37 years. The predicted cancer risk for former smokers with the C/T versus T/T genotype depended on both smoking intensity and smoking duration. Our results support the concept that differential susceptibility to lung cancer is a function of both an inheritable trait in NQO1 metabolism and individual smoking characteristics.

Wang, X. R., E. Yano, et al. (2001). "Pulmonary function in long-term asbestos workers in China." J Occup Environ Med 43(7): 623-9.

The relationship of pulmonary function to exposure to asbestos and radiographic abnormalities has been controversial, especially when smoking is present as a confounder. The aim of the study was to provide further understanding on the radiographic-physiologic associations in nonsmoking and smoking asbestos workers. Radiographic asbestosis, pleural lesion, and pulmonary function were studied in 269 Chinese asbestos workers, with average exposure years of 23 for male workers and 18 for female workers. Their functional data were compared with those of 274 controls without exposure to dust. Although most of the male workers were smokers, none of the female workers smoked. In comparison with controls, asbestos workers had significantly lower lung volume and diffusing capacity, irrespective of gender. Female workers and smoking male workers had lower measurements of forced expiratory volume in 1 second and instantaneous forced expiratory flow at 50% and 25% of forced vital capacity. After adjustment for relevant covariates, asbestos exposure, asbestosis, and pleural abnormalities were associated with decreased parameters of pulmonary function, including lung volume, diffusing capacity, and airway flow. These data indicate that asbestos-related functional defects manifested by lung restriction and mild airway obstruction correlate with exposure to asbestos and with parenchymal and pleural abnormalities, independent of smoking.

Wang, L. I., D. P. Miller, et al. (2001). "Manganese superoxide dismutase alanine-to-valine polymorphism at codon 16 and lung cancer risk." J Natl Cancer Inst 93(23): 1818-21.

Schaeffner, E. S., D. P. Miller, et al. (2001). "Use of an asbestos exposure score and the presence of pleural and parenchymal abnormalities in a lung cancer case series." Int J Occup Environ Health 7(1): 14-8.

To assess whether there was an association between asbestos exposure and abnormalities on chest x-rays or CT scans, chest radiographs and CT scans of 103 asbestos-exposed patients with known lung cancer were reviewed for pleural or parenchymal abnormalities. Asbestos exposure was assessed using an asbestos exposure index that integrated time and intensity of reported exposure via a weighting scheme. Chest CT scans were clearly more sensitive in detecting pleural or parenchymal abnormalities than were standard PA chest x-rays. Furthermore, there was a significant correlation between higher asbestos exposure index scores and abnormalities on CT scans. Multivariable logistic regression models were used to investigate the relationship between the asbestos exposure index score and pleural or parenchymal abnormalities after adjusting for gender, pack-years of smoking, and cell type. None of these variables was associated with abnormalities on chest x-rays or CT scans. An asbestos exposure score > 10 was associated with pleural or parenchymal abnormalities (OR = 4.93; 95%CI 1.05-23.12). The results suggest that assessment of asbestos exposures by means of an algorithm-based index can classify the exposures accurately for epidemiologic studies.

Perry, M. J., D. C. Christiani, et al. (2001). "Urinalysis of atrazine exposure in farm pesticide applicators." Toxicol Ind Health 16(7-8): 285-90.

This study compared three relatively common laboratory methods for the detection of atrazine (a triazine herbicide commonly used in US agriculture), and related metabolites in urine. Ninety-nine samples collected from atrazine applicators within 8 h post application were analyzed. Thirty-seven percent of applicators showed detectable levels (minimum = 1.0 ng/ml) of deethylatrazine (an atrazine metabolite typically found in environmental samples) in their urine, based on gas chromatography-mass spectrometry (GC-MS) analysis (mean = 14.2 ng/ml). Fifty applicator samples were tested using an enzyme-linked immunosorbent assay (ELISA) designed for the mercapturate metabolic product. Most of these samples (80%) had detectable levels of the mercapturate product. A triazine in water ELISA was also used to test several diluted urine samples from atrazine applicators, and all samples were positive for triazines. Mediocre agreements between the three methods indicated that each detected distinct atrazine exposure products. The results indicate that single field applications of atrazine result in measurable pesticide doses to applicators and that the choice of field assay should depend on the exposure product to be evaluated.

Magari, S. R., R. Hauser, et al. (2001). "Association of heart rate variability with occupational and environmental exposure to particulate air pollution." Circulation 104(9): 986-91.

BACKGROUND: Airborne particulate matter has been linked to excess morbidity and mortality. Recent attention has focused on the effects of particulate exposure on cardiac autonomic control. Inhaled particulates may affect the autonomic nervous system either directly, by eliciting a sympathetic stress response, or indirectly, through inflammatory cytokines produced in the lungs and released into the circulation. METHODS AND RESULTS: This longitudinal study examined the association of particulates </=2.5 microm in diameter (PM(2.5)) with heart rate variability (HRV) in an occupational cohort (N=40). Continuous monitoring of exposure and HR was performed during and away from work. PM(2.5) levels were higher than ambient levels typically reported in Boston, 0.167+/-3.205 mg/m(3) (geometric mean+/-geometric SD). We found a 2.66% decrease (95% CI, -3.75% to -1.58%) in the 5-minute SD of normal RR intervals (SDNN) for every 1 mg/m(3) increase in the 4-hour moving PM(2.5) average and a 1.02% increase (95% CI, 0.59% to 1.46%) in HR after adjusting for potential confounding factors. The decrease in SDNN became larger as the averaging interval increased. CONCLUSIONS: Workers experienced altered cardiac autonomic control after exposure to occupational and environmental PM(2.5). There appears to be either a long-acting (several hours) and a short-acting (several minutes) component to the mechanism of action that may be related to the production of cytokines and the sympathetic stress response, respectively, or a cumulative effect that begins shortly after exposure begins. The clinical significance of these effects in a healthy working population is unclear.

Liu, G., D. P. Miller, et al. (2001). "Differential association of the codon 72 p53 and GSTM1 polymorphisms on histological subtype of non-small cell lung carcinoma." Cancer Res 61(24): 8718-22.

Traditionally, non-small cell lung cancer (NSCLC) has been evaluated as a unique entity in genotyping studies. However, recent biological data suggest that different NSCLC subtypes, specifically adenocarcinomas (AC) and squamous cell carcinomas (SCC), differentially alter cancer behavior. Several studies have associated a p53 polymorphism at codon 72 with NSCLC susceptibility. This study investigated whether different p53 genotypes altered the overall risk of developing AC versus SCC. Polymorphisms in metabolizing enzymes, together with prolonged exposure to tobacco carcinogens, can result in accumulation of DNA damage; these effects may potentiate the effects of subtle differences in p53 function. Thus, interactions between polymorphisms of p53 and either GSTM1 or GSTT1 were also evaluated. We analyzed 1168 incident lung cancer cases and 1256 control subjects using multiple logistic regression. Histological data were available for 1144 cases (98%): 585 with AC, 284 with SCC, and 275 with other histological subtypes (large cell, small cell, mixed, and other). An increase in the NSCLC risk posed by the p53 Pro allele (versus Arg/Arg) was seen in AC compared with controls [adjusted odds ratio (OR), 1.36; 95% confidence interval (CI), 1.1-1.7] but not in SCC (adjusted OR, 1.04; 95% CI, 0.8-1.4). Among AC and SCC cancer patients, individuals with the GSTM1-null genotype had an OR of 1.80 (95% CI, 1.1-2.8; case-only analysis) of having AC versus SCC if they also carried a p53 Pro allele. We conclude that different genotype combinations of p53 and GSTM1 increase the risk of developing specific histological subtypes of NSCLC.

Lee, D. H., M. H. Ha, et al. (2001). "Body weight, alcohol consumption and liver enzyme activity--a 4-year follow-up study." Int J Epidemiol 30(4): 766-70.

BACKGROUND: This prospective study was performed in order to investigate the effect of baseline body mass index (BMI), BMI changes, baseline alcohol consumption, and changes in alcohol consumption on liver enzyme activity. METHODS: This study population consisted of 6846 male workers in a steel manufacturing company who had undergone health examinations in 1994 and 1998. RESULTS: The risk for elevated both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values over the four years increased with the baseline BMI and BMI changes, but not with alcohol consumption. Compared with the subject BMI < 20, the adjusted odds ratios (OR) for those with baseline BMI 20-21.9, 22-24.9, 25- were 1.2, 1.6, 1.7 in AST and 1.4, 2.4, 2.8 in ALT, respectively. Compared with subjects who either lost or maintained their weight, the adjusted OR for men with slight, moderate, and heavy weight gain were 1.7, 2.6, 6.8 in AST and 2.4, 3.9, 11.3 in ALT, respectively. However gamma-glutamyl transferase (GGT) was associated with BMI changes and baseline alcohol consumption, not with baseline BMI and changes in alcohol consumption. Compared with subjects who lost or maintained weight, the adjusted OR for men with slight, moderate, and heavy weight gain were 2.4, 4.4 and 8.5, respectively. In comparison with non-drinkers, the adjusted OR for light, moderate and heavy drinkers were 1.8, 2.1 and 5.8, respectively. CONCLUSION: These data suggest that body weight, rather than alcohol consumption, may be the major factor in determining the serum level of liver enzymes. Even when body weight was not generally considered to be overweight, slight to moderate gains in weight were associated with increases in serum liver enzymes.

Lara-Marquez, M. L., M. J. Moan, et al. (2001). "Atopic asthma: differential activation phenotypes among memory T helper cells." Clin Exp Allergy 31(8): 1232-41.

BACKGROUND: T cells have been implicated in the pathogenesis of atopic asthma. We have previously shown that memory T helper cells (CD4+CD45RO+) are preferentially activated relative to naive T helper cells (CD4+CD45RA+) after bronchial allergen challenge. However, specific T helper subpopulations that are activated in atopy and/or asthma remain undefined. OBJECTIVE: To determine the T helper subpopulations and activation phenotypes relevant to acute and stable asthma that may be common with or distinct from atopy. METHODS: Two groups of atopic asthmatics (ten acute and nine stable asthmatics) and two non-asthmatic groups (14 non-asthmatic atopics and eight normal non-atopic controls) were analysed. Ten acute asthmatics were assessed in the emergency room during an acute episode (FEV1 43.6% +/- 18.4). Nine stable asthmatics were assessed during a symptom-free period (FEV1 85% +/- 6). Using multiple colour flow cytometry we analysed T cell subpopulations and the expression of IL-2-receptor (IL-2R) and MHC-class II antigens (MHC II) on naive and memory T helper cells in the peripheral blood of asthmatic and non-asthmatic groups. RESULTS: Atopic asthmatics (acute and stable) had an increased percentage of memory T helper cells expressing IL-2R compared with normal non-atopics (mean SD 16.1 +/- 6%, 12.4 +/- 2% and 7.7 +/- 1.8%, P < 0.05) but not compared with non-asthmatic atopics (10 +/- 3.5%). Naive T helper cells had low expression of IL-2R and MHC II in all four groups. MHC II antigen expression was increased in memory T helper cells of asthmatics (acute and stable) compared with normal non-atopics (13.9 +/- 7.5, 10.6 +/- 5 and 4.9 +/- 2.5, P < 0.05) but not compared with non-asthmatic atopics (7.92 4). A novel finding was that IL-2R and the MHC II molecules were mainly expressed in non-overlapping populations and coexpression was found predominantly on memory T helper cells. Asthmatics (acute and stable) had higher proportion of double positive memory T helper cells (IL-2R+MHC II+) compared with both non-asthmatic groups (P < 0.05). CONCLUSIONS: We demonstrate a differential expression of IL-2R+ and MCH II+ on CD45RO+ T helper cells that would suggest that there are three subsets of activated memory T helper cells in asthmatics. Two non-overlapping IL-2R+ or MHC II+ CD45RO+ T helper cells and a third subpopulation of activated cells that coexpress IL-2R and MHC II (double positives). This latter subpopulation is significantly higher in asthmatics (acute or stable) compared with both non-asthmatic groups, suggesting a specific T helper activation phenotype distinct to atopic asthmatics as compared with atopic non-asthmatics.

Kim, D. H., H. H. Nelson, et al. (2001). "p16(INK4a) and histology-specific methylation of CpG islands by exposure to tobacco smoke in non-small cell lung cancer." Cancer Res 61(8): 3419-24.

The p16(INK4a) protein inhibits cyclin-dependent kinase 4, a key regulator of progression through the G(1) phase of the cell cycle. Methylation of CpG islands in the promoter region is an important avenue for inactivation of p16. The mechanism of methylation of the p16 promoter region, however, has not been elucidated. Recent reports investigating p16 methylation in non-small cell lung cancer (NSCLC) suggest that carcinogens in tobacco smoke induce the DNA methylation process. We investigated the association between methylation of the p16 promoter region and exposure to tobacco smoke in 185 primary NSCLCS: We also studied the relationship of p16 methylation with mutation of the K-ras and p53 genes, as well as with methylation at the DAP-kinase and p14(ARF) loci. Finally, we evaluated the prognostic significance of p16 methylation in NSCLC. The prevalence of p16 methylation was greater in squamous cell carcinoma (41%) compared with adenocarcinoma (22%; P = 0.03; Fisher's exact test). Methylation of p16 was significantly associated with pack-years smoked (P = 0.007; Wilcoxon rank sum test), duration of smoking (P = 0.0009; Wilcoxon rank sum test), and negatively with the time since quitting smoking (P = 0.03; Wilcoxon rank sum test). No methylation of the nearby p14(ARF) locus was detected, and methylation of the DAP-kinase locus was not associated with either p16 methylation or with exposure to tobacco smoke. In patients with stage 1 adenocarcinoma, p16 methylation was an independent risk factor predicting significantly shorter postsurgery survival (P = 0.03), controlling for the significant effects of other factors, including K-ras mutation. These findings suggest that methylation of CpG islands in tobacco-associated cancers occurs in a gene- and tissue-specific manner and is induced directly or indirectly by exposure to tobacco smoke in NSCLC.

Kim, D. H., H. H. Nelson, et al. (2001). "Promoter methylation of DAP-kinase: association with advanced stage in non-small cell lung cancer." Oncogene 20(14): 1765-70.

Death associated protein (DAP)-kinase is a 16 kDa calmodulin-dependent serine/threonine kinase that carries a death domain at its C-terminus. DAP-kinase functions as a positive mediator of apoptosis that is induced by interferon-gamma. Recent studies suggest that DAP-kinase is involved in tumor metastasis and that it can be inactivated by methylation of CpG islands in the promoter region of the gene in some human tumors. However, little is known about the factors that are associated with the occurrence of DAP-kinase promoter methylation. We investigated both the possible associations of tobacco carcinogen and asbestos exposure with DAP-kinase promoter methylation, and the demographic and clinical factors associated with DAP-kinase promoter methylation in non-small cell lung cancer (NSCLC). One hundred and eighty-five patients diagnosed with NSCLC undergoing surgical resection from June, 1992 through December, 1996 at Massachusetts General Hospital participated in this study. Methylation-Specific PCR (MSP), performed using fresh-frozen tissue, was used to determine the methylation status of the promoter region of the DAP-kinase gene. Forty-seven (25%) of 185 tumors showed DAP-kinase promoter methylation. There was a significant association between methylation and an advanced pathologic stage (P=0.003, Fisher's exact test). Methylation of the DAP-kinase promoter was also associated with an increase in tumor size (P=0.009, Fisher's exact test) and lymph node involvement (P=0.04). No association was found between promoter methylation of DAP-kinase and k-ras or p53 mutation. In addition there was no association with a history of exposure to tobacco or asbestos. Controlling for age, sex, and histology, the odds ratios describing the association of DAP-kinase hypermethylation with stage were 2.70 (1.13--6.45), 3.11 (1.37--7.08) and 7.77 (1.21--50.03) in stages II, III and IV, respectively. Stage I cases with DAP-kinase promoter methylation had worse overall survival, but with the small sample size and limited follow-up this did not reach statistical significance. Our findings suggest that methylation of the promoter region of the DAP-kinase gene is not associated with exposure to tobacco or asbestos. However, they strongly suggest that DAP-kinase may be important in the progression of non-small cell lung cancer from early to late stage disease.

Kales, S. N., G. N. Polyhronopoulos, et al. (2001). "Prospective study of hepatic, renal, and haematological surveillance in hazardous materials firefighters." Occup Environ Med 58(2): 87-94.

OBJECTIVES: To evaluate possible health effects related to work with hazardous materials as measured by end organ effect markers in a large cohort over about 2 years, and in a subcohort over 5 years. METHODS: Hepatic, renal, and haematological variables were analysed from 1996-98 in hazardous materials firefighters including 288 hazardous materials technicians (81%) and 68 support workers (19%). The same end organ effect markers in a subcohort of the technicians were also analysed (n=35) from 1993-98. Support workers were considered as controls because they are also firefighters, but had a low potential exposure to hazardous materials. RESULTS: During the study period, no serious injuries or exposures were reported. For the end organ effect markers studied, no significant differences were found between technicians and support workers at either year 1 or year 3. After adjustment for a change in laboratory, no significant longitudinal changes were found within groups for any of the markers except for creatinine which decreased for both technicians (p<0.001) and controls (p<0.01). CONCLUSIONS: Health effects related to work are infrequent among hazardous materials technicians. Haematological, hepatic, and renal testing is not required on an annual basis and has limited use in detecting health effects in hazardous materials technicians.

Kales, S. N., R. L. Freyman, et al. (2001). "Firefighters' hearing: a comparison with population databases from the International Standards Organization." J Occup Environ Med 43(7): 650-6.

We investigated firefighters' hearing relative to general population data to adjust for age-expected hearing loss. For five groups of male firefighters with increasing mean ages, we compared their hearing thresholds at the 50th and 90th percentiles with normative and age- and sex-matched hearing data from the International Standards Organization (databases A and B). At the 50th percentile, from a mean age of 28 to a mean age of 53 years, relative to databases A and B, the firefighters lost an excess of 19 to 23 dB, 20 to 23 dB, and 16 to 19 dB at 3000, 4000, and 6000 Hz, respectively. At the 90th percentile, from a mean age of 28 to a mean age of 53 years, relative to databases A and B, the firefighters lost an excess of 12 to 20 dB, 38 to 44 dB, 41 to 45 dB, and 22 to 28 dB at 2000, 3000, 4000, and 6000 Hz, respectively. The results are consistent with accelerated hearing loss in excess of age-expected loss among the firefighters, especially at or above the 90th percentile.

Kales, S. N., P. J. Mendoza, et al. (2001). "Spirometric surveillance in hazardous materials firefighters: does hazardous materials duty affect lung function?" J Occup Environ Med 43(12): 1114-20.

We analyzed spirometry results for 351 male hazardous materials firefighters from 1996 to 1999 who underwent one or more annual medical surveillance/fitness for duty examinations: 276 (79%) technicians and 75 (21%) support members. Support members had a very limited potential for hazardous materials exposure and served as referents. In cross-sectional comparisons, the technicians' average forced vital capacity and forced expiratory volume in 1 second were either statistically better or not significantly different from that of the support members at all four examinations. Longitudinally, no statistically significant differences were seen for forced vital capacity. The mean percent of predicted forced expiratory volume in 1 second decreased by 3% for technicians (P = 0.029), support controls (P = 0.433), and the total cohort (P = 0.014). Although respiratory irritants are the most common type of exposure in hazardous materials releases, the results suggest that hazardous materials technicians do not lose pulmonary function at a more accelerated rate than support team firefighters.

Hong, Y. C., H. Kim, et al. (2001). "Maternal genetic effects on neonatal susceptibility to oxidative damage from environmental tobacco smoke." J Natl Cancer Inst 93(8): 645-7.

Hirao, T., H. H. Nelson, et al. (2001). "Tobacco smoke-induced DNA damage and an early age of smoking initiation induce chromosome loss at 3p21 in lung cancer." Cancer Res 61(2): 612-5.

The short arm of chromosome 3 is thought to harbor a novel oncogenic locus that is important in the genesis of lung cancer. The region at 3p21 is believed to contain a distinct locus that is sensitive to loss from the action of tobacco smoke carcinogens and has been reported to be specifically targeted for deletion in lung cancer. To investigate whether 3p21 alteration in lung cancer is associated with carcinogen exposure, PCR-based analysis was performed to detect loss of heterozygosity (LOH) on chromosome 3 at 3p21 in non-small cell lung carcinoma (NSCLC). We also measured instability at the BAT-26 locus, because the mismatch DNA repair gene, hMLH1, is found at 3p21. LOH at 3p21 was analyzed for association with the clinical features of NSCLC, p53 mutation status, polynuclear aromatic hydrocarbon-DNA adduct levels (measured using 32P-postlabeling) and carcinogen exposure information including cigarette smoking and asbestos exposure. Of 219 lung cancers, 150 cases (68.5%) were informative at the D3S1478 locus, and 44.2% of squamous cell carcinoma cases and 30.2% of adenocarcinoma cases showed 3p21 LOH. None of the cancers showed BAT-26 instability. The prevalence of 3p21 LOH was higher in both current and former smokers compared with never smokers and was higher in p53 mutated cases. Among squamous cell carcinoma cases, there was a strong association of increased 3p21 LOH with increasing polynuclear aromatic hydrocarbon-DNA adducts levels (P = 0.03), as well as an increased prevalence LOH with earlier age of smoking initiation (P = 0.02). Our results confirm that 3p21 LOH is strongly associated with measures of biologically effective dose of exposure to tobacco carcinogens. Our results also suggest that alterations of hMLH1 are not related to any of the reported associations, because there was no evidence of microsatellite instability. Finally, LOH in 3p21 may be an early molecular event in NSCLC, because it is significantly associated with a tendency to start smoking at a young age.

Hauser, R., E. A. Eisen, et al. (2001). "A prospective study of lung function among boilermaker construction workers exposed to combustion particulates." Am J Ind Med 39(5): 454-62.

BACKGROUND: Given the evidence of both acute cross-shift and short-term decrements in lung function in boilermaker construction workers following occupational exposure to combustion particulates, we sought to determine whether exposure is associated with an annual loss in lung function. METHODS: As part of an ongoing investigation, we conducted a 2-year longitudinal study of lung function among 118 boilermakers. Exposure was assessed with a work history questionnaire. Spirometry measurements were performed annually. RESULTS: We found an association between annual FEV(1) and hours worked at a gas-fired plant during the previous year, beta = - 9.8 mls/100 hours worked (95% CI: - 16.0, - 3.5) after adjustment for age, baseline FEV(1) and cigarette smoking status. The adjusted association between FEV(1) and "ever" worked at a gas-fired plant was - 99.7 mls (95% CI: - 154.8, - 44.5). There was also evidence of a negative association between FEV(1) and "ever" worked and hours worked at oil and coal-fired plants. CONCLUSIONS: These data suggest an association between annual lung function loss and working at gas, coal and oil-fired plants. Further follow-up of this cohort of boilermakers is in progress.

Hauser, R., J. J. Godleski, et al. (2001). "Ultrafine particles in human lung macrophages." Arch Environ Health 56(2): 150-6.

As knowledge about size dependency of particle toxicity continues to grow, attention has been focused on ultrafine particles (i.e., < 0.1 microm in diameter). In recent studies with rats, investigators learned that ultrafine particles likely have greater pulmonary toxicity than larger particles, and it is possible that exposure to, and accumulation of, these particles in the human lung may be associated with adverse respiratory health effects. As part of an ongoing study, the authors performed bronchoalveolar lavage in 14 healthy current nonsmokers to investigate the extent to which ultrafine particles were present in lung macrophages. In addition, 10 of the 14 subjects performed pulmonary function tests. Eleven of the 14 subjects were utility workers, and 3 were nonmaintenance employees of a university. The authors used a Zeiss CEM902 electron microscope to study macrophages isolated from bronchoalveolar lavage fluid. Morphometric quantification revealed ultrafine particles in lung macrophages of all 14 volunteers; the average number of ultrafine particles/microm3 cytoplasm per cell (UFavg) ranged from 34 to 231 (mean = 95, standard deviation = 54). Regression analysis showed that the UFavg was associated inversely with percent predicted forced expiratory volume in 1 second (FEV1.0) (beta = -1.2 percent predicted FEV1.0/10 ultrafine particles x microm3 cytoplasm per cell [standard error = 0.45, p = .031). The demonstration of ultrafine particles in all 14 subjects, independent of occupational exposure, suggests that there is environmental exposure to ultrafine particles. The negative association between the number of ultrafine particles and ventilatory function demonstrates a need for further investigation into the pulmonary health effects of ultrafine particles.

Ha, E. H., Y. C. Hong, et al. (2001). "Is air pollution a risk factor for low birth weight in Seoul?" Epidemiology 12(6): 643-8.

Environmental factors contributing to reduced birth weight are of great concern because of the well-known relation of birth weight to infant mortality and adverse effects in later life. We examined the associations between air pollution exposures during pregnancy and low birth weight among all full-term births (gestational age 37-44 weeks) for a 2-year period (January 1996 through December 1997) in Seoul, South Korea. We evaluated these associations with a generalized additive logistic regression adjusting for gestational age, maternal age, parental educational level, parity, and infant sex. We used smoothing plots with generalized additive models to analyze the exposure-response relation for each air pollutant. The adjusted relative risk of low birth weight was 1.08 [95% confidence interval (CI) = 1.04-1.12] for each interquartile increase for carbon monoxide concentrations during the first trimester of pregnancy. The relative risks were 1.07 (95% CI = 1.03-1.11) for nitrogen dioxide, 1.06 (95% CI = 1.02-1.10) for sulfur dioxide, and 1.04 (95% CI = 1.00-1.08) for total suspended particles also for interquartile increase in exposure. Carbon monoxide, nitrogen dioxide, sulfur dioxide, and total suspended particle concentrations in the first trimester of pregnancy period are risk factors for low birth weight.

Christiani, D. C., X. R. Wang, et al. (2001). "Longitudinal changes in pulmonary function and respiratory symptoms in cotton textile workers. A 15-yr follow-up study." Am J Respir Crit Care Med 163(4): 847-53.

To evaluate the chronic effects of exposure to cotton dust, a 15-yr follow-up study in cotton textile workers was performed in Shanghai, China from 1981 to 1996. Testing occurred four times during the 15-yr period. The achieved follow-up rates were 76-88% of the original 447 cotton textile workers, and 70-85% of the original 472 silk textile workers (as a control group). Identical questionnaires, equipment, and methods were used throughout the study. The prevalence of byssinosis increased over time in cotton workers, with 15.3% at the last survey versus 7.6% at the baseline, whereas no byssinosis was found in silk workers. More workers in the cotton group consistently reported symptoms than in the silk group, although symptom reporting varied considerably from survey to survey. Cotton workers had small, but significantly greater, adjusted annual declines in FEV(1) and FVC than did the silk workers. Years worked in cotton mills, high level of exposure to endotoxin, and across-shift drops in FEV(1) were found to be significant determinants for longitudinal change in FEV(1), after controlling for appropriate confounders. Furthermore, there were statistically significant associations between excessive loss of FEV(1) and byssinosis, chest tightness at work, and chronic bronchitis in cotton workers. Workers who consistently (three or four of the surveys) reported byssinosis or chest tightness at work had a significantly greater 15-yr loss of FEV(1). We conclude that long-term exposure to cotton dust is associated with chronic or permanent obstructive impairments. Consistent reporting of respiratory symptoms, including byssinosis and chest tightness at work, is of value to predict the magnitude and severity of chronic impairments in textile workers.

Christiani, D. C., R. R. Sharp, et al. (2001). "Applying genomic technologies in environmental health research: challenges and opportunities." J Occup Environ Med 43(6): 526-33.

Recent discoveries in molecular biology and genetics have made it possible for environmental health researchers to examine how genetic characteristics affect response to environmental exposures. Understanding such gene-environment interactions offers exciting possibilities for the prevention and control of environmentally induced diseases. Despite these potential benefits, the collection and analysis of genetic information in environmental health research presents many of the same ethical, legal, and social (ELSI) challenges found in other types of genetic research. In this article, we describe a number of ELSI challenges in environmental genomic research and the opportunities and responsibilities that accompany this research.

Cho, S. I., A. I. Damokosh, et al. (2001). "Effects of exposure to organic solvents on menstrual cycle length." J Occup Environ Med 43(6): 567-75.

To investigate the association between organic solvent exposure and menstrual disturbance, we conducted a cross-sectional study among 1408 petrochemical workers in China. Based on an industrial hygiene evaluation, we classified the workshops according to the presence or absence of organic solvents (benzene, styrene, toluene, or xylene). We used logistic regression to estimate odds ratios and 95% confidence intervals for prolonged menstrual cycle length (oligomenorrhea: average cycle length > 35 days during the previous year) associated with the exposure. After adjustment for confounders, each additional year of work in an exposed workshop was associated with a 7% increase in oligomenorrhea (odds ratio, 1.07; 95% confidence interval, 1.00 to 1.14). Compared with no exposure, 3 or more years of exposure was associated with a 53% increase in oligomenorrhea (odds ratio, 1.53; 95% confidence interval, 1.00 to 2.34). We concluded that exposure to organic solvents is associated with a trend toward increased frequency of oligomenorrhea.

Chen, C., X. Wang, et al. (2001). "Tofu consumption and blood lead levels in young Chinese adults." Am J Epidemiol 153(12): 1206-12.

Tofu is a commonly consumed food in China. Tofu may interfere with lead absorption and retention because of its high calcium content. In this observational study, the authors examined whether dietary tofu intake was associated with blood lead levels among young adults in Shenyang, China. The analyses included 605 men and 550 women who completed baseline questionnaires and had blood lead measurements taken in 1996-1998 as part of a prospective cohort study on reproductive health. Mean blood lead levels were 13.2 microg/dl in men and 10.1 microg/dl in women. Blood lead levels were negatively associated with tofu intake in both genders. A linear trend test showed a 3.7% (0.5-microg/dl) decrease in blood lead level with each higher category of tofu intake (p = 0.003). The highest tofu intake group (> or =750 g/week) had blood lead levels 11.3% lower (95% confidence interval: 4.1, 18.0) than those of the lowest tofu intake group (<250 g/week). In all regression models, data were adjusted for gender, age, height, body mass index, district, cigarette smoking, alcohol drinking, education, occupation, use of vitamin supplements, season, and dietary intake of meat, fish, vegetables, eggs, and milk. In conclusion, the authors found a significant inverse dose-response relation between tofu consumption and blood lead levels in this Chinese population.

Xia, Z. L., T. K. Courtney, et al. (2000). "Fatal occupational injuries in a new development area in the People's Republic of China." J Occup Environ Med 42(9): 917-22.

Fatal occupational injuries in a new development region in Shanghai in east China are described. All occupational deaths in the East Pujiang New Area during the period 1991 through 1997 were abstracted from multiple, overlapping source documents. There were 426 deaths and a crude mortality rate of 9.1 per 100,000 workers. The death rate was highest in 1995 (14.6%), when expansion in the area was most rapid. The construction sector accounted for 55% of the deaths, followed by manufacturing (23%) and transport, storage, and telecommunications (11%). Falls, collisions, struck by/against incidents, and electrocutions accounted for 80% of all deaths. Falls led all other causes of deaths (33%) and were particularly prevalent in the construction industry (46% of all deaths in construction). The development of ongoing, comprehensive injury surveillance systems in the People's Republic of China will be essential to target and evaluate injury prevention activities in the future.

Xia, Z., G. S. Sorock, et al. (2000). "Fatal occupational injuries in the construction industry of a new development area in east China, 1991 to 1997." Aihaj 61(5): 733-7.

Two hundred thirty-five work-related deaths occurred in the construction industry in a new economic development area in eastern China between 1991 and 1997. These fatalities represented 55% of all occupational deaths. The average annual mortality rate was 51.5 per 100,000 construction workers. Falls were the leading cause of death (46.4%). Falls, collisions, struck by/against something, electrocutions, and excavation cave-ins were the main fatality antecedents, accounting for nearly 93.6% of all fatalities. The most common antecedents for incidents with multiple fatalities were falls, crane-related events, poisoning, and fire. These categories of antecedents were similar to those encountered in the construction industry in the United States. These data suggest that organizations need to focus on these event types when planning their prevention activities. Moreover, improved surveillance systems including computerized databases with narrative descriptions of injury events, antecedent factors, and person-time at-risk data are needed to target interventions more precisely.

Wu, M. T., B. Demple, et al. (2000). "Individual variability in the zinc inducibility of metallothionein-IIA mRNA in human lymphocytes." J Toxicol Environ Health A 61(7): 553-67.

The metallothionein-III gene (MT-IIA) is a major member of the human MT gene family. Metallothioneins (MTs) are low-molecular-weight, cysteine-rich proteins that bind and detoxify heavy metals. At least two different MT-IIA polymorphisms have been identified in humans, one or both of which may affect susceptibility to metal toxicity. The purpose of this study was to investigate whether these different genotypes affect the inducibility of MT-IIA mRNA in human lymphocytes treated with zinc (Zn), the major known inducer of MT-IIA in vitro. Fresh lymphocytes obtained from 16 healthy volunteers, aged 23-38 yr, were genotyped for the MT-IIA gene and tested for expression. A 43.5-bp HindIII-Taql fragment of the MT-IIA promoter was used to probe for the two known polymorphisms (a 7.8-kb vs. a 5.3-kb fragmnent, and a 1.7-kb vs. a 1.6-kb fragment). The allele frequencies of the 16 subjects were 14%, for 5.3-kb allele and 19% for 1.6-kb allele. In Northern blotting experiments, MT-II mRNA levels were induced over a wide range of Zn concentrations during 2-h exposures; specifcally, levels increased by 9- to 115-fold with exposure to 100 microM ZnCl, and by 16- to 311-fold with exposure to 200 microM ZnCl2. However, no significant differences in MT-IIA inducibility were found between the 7.8/5.3-kb allele pair (n = 4) and the 7.8/7.8-kb allele pair (n = 12) or between the 1.7/1.6-kb allele pair (n = 5) and the 1.7/1.7-kb allele pair (n = 11). Thus. MT-IIA is strongly inducible by Zn in human lymphocytes, but individual variations exceed those that can be attributed to the known promoter-region polymorphisms.

Woodin, M. A., Y. Liu, et al. (2000). "Acute respiratory symptoms in workers exposed to vanadium-rich fuel-oil ash." Am J Ind Med 37(4): 353-63.

BACKGROUND: Occupational exposure to fuel-oil ash, with its high vanadium content, may cause respiratory illness. It is unclear, however, what early acute health effects may occur on the pathway from normal to compromised respiratory function. METHODS: Using a repeated measures design, we studied prospectively 18 boilermakers overhauling an oil-fired boiler and 11 utility worker controls. Subjects completed a respiratory symptom diary five times per day by using a 0-3 scale where 0=symptom not present, 1=mild symptom, 2=moderate symptom, and 3=severe symptom. Daily symptom severity was calculated by using the highest reported score each day for upper and lower respiratory symptoms. Daily symptom frequency was calculated by summing all upper or lower airway symptom reports, then dividing by number of reporting times. Respiratory symptom frequency and severity were analyzed for dose-response relationships with estimated vanadium and PM(10) doses to the lung and upper airway by using robust regression. RESULTS: During the overhaul, 72% of boilermakers reported lower airway symptoms, and 67% reported upper airway symptoms. These percentages were 27 and 36 for controls. Boilermakers had more frequent and more severe upper and lower respiratory symptoms compared to utility workers, and this difference was greatest during interior boiler work. A statistically significant dose-response pattern for frequency and severity of both upper and lower respiratory symptoms was seen with vanadium and PM(10) in the three lower exposure quartiles. However, there was a reversal in the dose-response trend in the highest exposure quartile, reflecting a possible healthy worker effect. CONCLUSIONS: Boilermakers experience more frequent and more severe respiratory symptoms than utility workers. This is most statistically significant during boiler work and is associated with increasing dose estimates of lung and nasal vanadium and PM(10).

Wang, X., D. Chen, et al. (2000). "Genetic susceptibility to benzene and shortened gestation: evidence of gene-environment interaction." Am J Epidemiol 152(8): 693-700.

This study investigated whether the association between low level benzene exposure and shortened gestation is modified by two susceptibility genes, CYP1A1 and GSTT1. This report includes 542 (302 nonexposed, 240 benzene-exposed) nonsmoking and nondrinking mothers of singleton live births at Beijing Yanshan Petrochemical Corporation between June 1995 and June 1997. Epidemiologic and clinical data and blood samples were obtained from mothers. Multiple linear regression models were used to estimate the associations of benzene exposure and genetic susceptibility with gestational age, adjusting for maternal age, education, parity, stress, passive smoking, prepregnancy weight and height, and infant's sex. Without consideration of genotype, benzene exposure was associated with a decrease in mean gestational age of 0.29 (standard error (SE), 0.12) week. When stratified by the maternal CYP1A1 genotype, the estimated decrease was 0.54 (SE, 0.12) week for the AA group, which was significantly greater (p = 0.003) than that for the Aa/aa group, which showed no decrease in gestational age. When both CYP1A1 and GSTT1 were considered, the greatest decrease was found among exposed mothers with the CYP1A1 AA-GSTT1 absent group (0.79 (SE, 0.25) week) and the CYP1A1 AA-GSTT1 present group (0.50 (SE, 0.22) week). Among the nonexposed, genetic susceptibility alone did not confer a significant adverse effect. This study provides evidence of gene-environment interaction and supports further assessment of the role of genetic susceptibility in the evaluation of reproductive toxins.

Wang, X. R. and D. C. Christiani (2000). "Respiratory symptoms and functional status in workers exposed to silica, asbestos, and coal mine dusts." J Occup Environ Med 42(11): 1076-84.

This study aims to provide further understanding of physiologic and symptomatic changes and radiographic abnormalities due to exposure to silica, asbestos, and coal dusts. Questionnaires and pulmonary function tests were given to 220 silica, 277 asbestos, and 511 coal workers from three different industries in China. Posteroanterior chest radiographs were classified as stages 0, I, II, and III according to degree of parenchymal fibrosis. Significantly poorer pulmonary function and a higher prevalence of dyspnea and chronic cough were observed in workers with pneumoconiosis than those without, irrespective of dust type. Workers with stages II and III silicosis had worse pulmonary function and more common symptoms relative to workers with equivalent coal workers' pneumoconiosis or asbestosis. After adjusting for relevant confounders, reductions in the spirometric parameters and single breath diffusing capacity for carbon monoxide (DLCO) and the occurrence of respiratory symptoms were associated with increasing stage of silicosis, whereas lower DLCO and the occurrence of symptoms were associated with increasing stage of asbestosis and coal workers' pneumoconiosis. The study suggests that despite the differences in degree and pattern due to exposure to different fibrogenic dusts, respiratory impairments of all of the workers are associated with the presence and progression of parenchymal fibrosis and smoking.

Thurston, S. W., L. Ryan, et al. (2000). "Petrochemical exposure and menstrual disturbances." Am J Ind Med 38(5): 555-64.

BACKGROUND: An exploratory, cross-sectional retrospective study was conducted to examine the effects of benzene exposure on menstrual problems. METHODS: The study was based on a survey administered to over 3,000 women who worked in a large petrochemical company in Beijing, China. An abnormal menstrual cycle length (AMCL), defined as an average menstrual cycle length of greater than 35 days or less than 21 days, is the major outcome of interest. RESULTS: After 7 years of benzene exposure, the adjusted odds ratio of having AMCL for each additional 5 years of exposure was 1.71 (95% CI 1.27-2.31). Feeling stressed at work was also an important predictor. CONCLUSIONS: This study suggests a significant association of benzene exposure and perceived stress with menstrual disturbance. A prospective study is needed to confirm this finding.

Simpson, C. D., M. T. Wu, et al. (2000). "Determination of r-7,t-8,9,c-10-tetrahydroxy-7,8,9, 10-tetrahydrobenzo[a]pyrene in human urine by gas chromatography/negative ion chemical ionization/mass spectrometry." Chem Res Toxicol 13(4): 271-80.

r-7,t-8,9,c-10-Tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (trans-anti-BaP-tetraol) is the major hydrolysis product of r-7, t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE), the principal ultimate carcinogen of the environmental pollutant benzo[a]pyrene (BaP). As part of a program to establish activation/detoxification profiles of urinary metabolites of BaP in humans, we developed a method for quantifying trans-anti-BaP-tetraol. Urine was collected from three groups of individuals exposed to BaP: psoriasis patients treated with a coal tar-containing ointment, steel workers, and smokers. [(2)H(12)]-trans-anti-BaP-tetraol was added to the urine as an internal standard. The urine was treated with beta-glucuronidase and sulfatase, and then the BaP-tetraols were enriched by reverse-phase and phenylboronic acid solid-phase extraction. The resulting fraction was treated with sodium hydride and methylmethane sulfonate to convert BaP-tetraols to the corresponding tetramethyl ethers (BaP-TME). The mixture was purified by normal-phase HPLC and analyzed by gas chromatography/negative ion chemical ionization/mass spectrometry with selected ion monitoring. [(13)CH(3)](4)-trans-anti-BaP-TME was used as an external standard. Ions at m/z 376, 380, and 388 were monitored for quantitation of trans-anti-BaP-TME, [(13)CH(3)](4)-trans-anti-BaP-TME, and [(2)H(12)]-trans-anti-BaP-TME, respectively. The instrumental detection limit was approximately 1 fmol of trans-anti-BaP-TME. trans-anti-BaP-tetraol (as trans-anti-BaP-TME) was detected in 20 of 20 individuals receiving coal tar therapy (mean, 16 fmol/mL of urine), 13 of 13 exposed steel workers (mean, 4.1 fmol/mL of urine), and nine of 21 cigarette smokers (mean, 0.5 fmol/mL of urine). The means in these groups were significantly different (P < 0.0001). The urine of steel workers was also analyzed for cis-anti-BaP-tetraol and cys-syn-BaP-tetraol, but neither was found. The results of this study provide a quantitative method for determination of parts per trillion levels of trans-anti-BaP-tetraol in human urine. Ultimately, this method can be employed as part of a phenotyping approach for assessing BaP metabolites in human urine.

Padungtod, C., D. A. Savitz, et al. (2000). "Occupational pesticide exposure and semen quality among Chinese workers." J Occup Environ Med 42(10): 982-92.

This study investigated the association between occupational pesticide exposure and semen quality among Chinese workers. Male workers, 32 who were exposed to organophosphate pesticides and 43 who were not exposed were recruited from two nearby factories and interviewed. Following a work shift, semen and urine samples were collected for pesticide metabolite analysis. Semen samples were analyzed for sperm concentration, percentage of motility, and percentage of normal structure. Within the exposed group, the mean end-of-shift urinary p-nitrophenol levels were 0.22 and 0.15 mg/L for the high- and low-exposure subgroups, respectively. Linear regression analysis of individual semen parameters revealed a significant reduction of sperm concentration (35.9 x 10(6) vs 62.8 x 10(6), p < 0.01) and percentage of motility (47% vs 57%, p = 0.03) but not percentage of sperm with normal structure (57% vs 61%, p = 0.13). Multivariate modeling showed a significant overall shift in the mean semen parameter. Occupational exposure to ethylparathion and methamidophos seems to have a moderately adverse effect on semen quality.

Mahmud, M. A., B. S. Webster, et al. (2000). "Clinical management and the duration of disability for work-related low back pain." J Occup Environ Med 42(12): 1178-87.

Clinical practice guidelines recommend a conservative approach to management of acute low back pain (LBP). The present study sought to determine whether health care utilization and the physician's initial management of work-related LBP were associated with disability duration. Clinical management information was obtained for 98 randomly selected, workers' compensation claimants with acute, uncomplicated, disabling work-related LBP. Length of disability was based on indemnity (wage replacement) payments. Disability was significantly associated with increased utilization of specialty referrals (P = 0.013) and provider visits (P < 0.001), use of magnetic resonance imaging (P = 0.003), and use of opioids for more than 7 days (P = 0.013). Effects of early diagnostic imaging (first 30 days of care) on length of disability were observed (P = 0.001). Patients whose treatment course did not involve extended opioid use and early diagnostic testing were 3.78 times more likely (95% confidence interval, 1.6 to 8.9) to have gone off disability status by the end of the study. The nature of the association between these initial clinical management aspects and LBP disability duration merits further exploration.

Lee, J. T., H. Kim, et al. (2000). "Air pollution and daily mortality in seven major cities of Korea, 1991-1997." Environ Res 84(3): 247-54.

The relationship between ambient air pollution and daily mortality in seven major cities of Korea for the period 1991-1997 was examined. These cities account for half of the Korean population (about 22 million). The observed concentrations of sulfur dioxide (SO(2), mean=23.3 ppb), ozone (O(3), mean=23.7 ppb), and total suspended particulates (TSP, mean=77.9 microg/m(3)) during the study period were at levels below Korea's current ambient air quality standards. Generalized additive models were applied to allow for the highly flexible fitting of seasonal and long-term time trends in air pollution as well as nonlinear associations with weather variables, such as air temperature and relative humidity. In city-specific analyses, an increase of 50 ppb of SO(2) corresponded to 1-12% more deaths, given constant weather conditions. The risk of all-cause mortality was estimated to increase by 0.5-4%, with an increase in the 2-day moving average of TSP levels equal to 100 microg/m(3). In multipollutant models with pooled data, we found that the estimated risk of death by SO(2) was notably unaffected by adding the other two pollutants (TSP and O(3)) to the model and was statistically significant in various regression models. The rate ratio (RR) for SO(2) remained elevated, indicating an excess mortality of 3% 50 ppb (RR=1.03; 95% CI, 1.01-1.05). TSP's effect on mortality maintained its significance with O(3), but not with SO(2). This implies that there may be collinearity problems where TSP and SO(2) are included in the same model or that TSP may function less than SO(2) as a surrogate for fine particles in the ambient air of Korea. In conclusion, increased mortality was associated with air pollution at SO(2) levels below the current recommendation for air quality. Further research is needed to clarify the relationship between SO(2) and fine particles in Korea.

Kales, S. N. and D. C. Christiani (2000). "Cardiovascular fitness in firefighters." J Occup Environ Med 42(5): 467-8.

Fassa, A. G., L. A. Facchini, et al. (2000). "Child labor and health: problems and perspectives." Int J Occup Environ Health 6(1): 55-62.

Child labor remains a widespread problem. Although it can have positive effects, in some situations it has negative effects on health and development of the children. Although mainly a problem in developing countries, it is also possible to find child workers, some working in hazardous activities, in developed countries. The authors describe the child labor profiles in developed and developing countries, the principal occupations of children, and their concomitant hazards. They summarize the epidemiologic evidence for a greater impact of some occupational exposures on the health of children as compared with adults, and the theoretical concerns about the impact of child labor on health, and suggest policies that can be used to combat harmful child labor.

Fan, R., M. T. Wu, et al. (2000). "The p53 codon 72 polymorphism and lung cancer risk." Cancer Epidemiol Biomarkers Prev 9(10): 1037-42.

The p53 tumor suppressor gene frequently is mutated in many forms of human carcinomas. A common polymorphism occurs at codon 72 of exon 4, with two alleles encoding either arginine (CGC) or proline (CCC). This p53 polymorphism reportedly is associated with lung cancer susceptibility. However, not all investigations have been consistent, and this hypothesized association remains controversial. We tested the hypothesis that the Pro/Pro genotype is associated with increased lung cancer risk in a large case-control study of lung cancer that included 482 cases and 510 controls from the Massachusetts General Hospital in Boston, Massachusetts. DNA from peripheral blood samples was examined by PCR-RFLP. Pro/Pro homozygotes were found more frequently in adenocarcinomas (cases, 16.4%; controls, 12.0%; P = 0.03). The prevalence of the Pro/Pro homozygous genotype increased in frequency with increasing pack-years of smoking. The combined susceptible genotype homozygous Pro/Pro and heterozygous Arg/Pro was associated with a 1.45-fold higher risk of adenocarcinoma compared with Arg/Arg genotype (95% confidence interval = 1.01-2.06; P = 0.04) after adjustment for relevant variables. Lung adenocarcinoma risk increased with the presence of one or both variant alleles across smoking strata. In addition, at each level of smoking (except nonsmoker and light smoker), the risk associated with smoking was higher for the population with the combined variant (Arg/Pro + Pro/Pro) genotype. The risk for the combined genotype was associated with tobacco exposure status. In conclusion, the codon 72 germ-line polymorphism (Arg/Pro) of the common tumor suppressor gene p53 contributes to heritable susceptibility for smoke-induced lung adenocarcinoma. The modifications by p53 polymorphism and pack-years resulted in an increased risk of the susceptible genotype to lung adenocarcinoma. The p53 gene may modulate the response to environment carcinogens and thereby affect the risk of developing lung adenocarcinoma.

Duell, E. J., J. K. Wiencke, et al. (2000). "Polymorphisms in the DNA repair genes XRCC1 and ERCC2 and biomarkers of DNA damage in human blood mononuclear cells." Carcinogenesis 21(5): 965-71.

Polymorphisms in several DNA repair genes have recently been identified, but little is known about their phenotypic significance. To determine whether variation in DNA repair genes is related to host DNA damage, we studied the association between polymorphisms in XRCC1 (codon 399) and ERCC2 (codon 751) and two markers of DNA damage, sister chromatid exchange (SCE) frequencies (n = 76) and polyphenol DNA adducts (n = 61). SCE frequencies were determined using a modified fluorescence-Giemsa method and polyphenol DNA adducts were determined using a P1-enhanced (32)P-post-labeling procedure. XRCC1 and ERCC2 genotypes were identified using PCR-RFLP. Mean SCE frequencies among current smokers who were homozygous carriers of the 399Gln allele in XRCC1 were greater than those in 399Arg/Arg current smokers. We also observed a possible gene-dosage effect for XRCC1 399Gln and detectable DNA adducts, and significantly more adducts among older subjects who were carriers of the 399Gln allele than in younger subjects with the 399Arg/Arg genotype. The polymorphism in ERCC2 was unrelated to SCE frequency or DNA adduct level. Our results suggest that carriers of the polymorphic XRCC1 399Gln allele may be at greater risk for tobacco- and age-related DNA damage.

Christiani, D. C. (2000). "Smoking and the molecular epidemiology of lung cancer." Clin Chest Med 21(1): 87-93, viii.

Lung carcinogenesis in humans requires exposure to environmental agents, including the inhalation of tobacco smoke, radioactive compounds, asbestos, heavy metals, and petrochemicals. Tobacco smoking is the risk factor with the highest attributable lung cancer risk worldwide. This article discusses occupational carcinogen exposure and exposure from tobacco use, and the lung-cancer risk associated with these types of exposure.

Christiani, D. C., S. H. Chang, et al. (2000). "Urinary excretion of hippuric acid after consumption of nonalcoholic beverages." Int J Occup Environ Health 6(3): 238-42.

To investigate the types and quantities of beverages that increase urinary hippuric acid (HA) excretion, the authors recruited 137 healthy medical students and divided them into quintiles according to consumption of benzoic acid (BA) in beverages. Using chromatography, urinary HA before and 1.5 hours and 3 hours after consumption of various beverages and BA consumption in the beverages were measured. The mean age of the group was 24.2 years; 21 were female. The range of BA in 13 beverages was 0-1.02 mg/mL. The geometric means of urinary HA before consuming them in five groups were 0.276, 0.270, 0.207, 0.262, and 0.316 g/L, respectively (p = 0. 567); 1.5 hours after consuming the beverages, they were 0.210, 0. 603, 1.026, 1.066, and 1.688 g/L, respectively, and significantly increased after adjustment for urinary HA before ingestion (p < 0. 001). Three hours after ingestion, the geometric means were 0.160, 0. 232, 0.306, 0.287, and 0.337 g/L, respectively (p < 0.001). The authors estimate that beverages that contain more than 100 mg BA could increase urinary HA excretion significantly, up to 1.12 g/L without toluene exposure. Checking dietary and beverage-intake histories is essential in the interpretation of urinary HA concentrations in population studies.

Chong, I. W., M. M. Shi, et al. (2000). "Regulation of chemokine mRNA expression in a rat model of vanadium-induced pulmonary inflammation." Inflammation 24(6): 505-17.

Environmental and occupational exposure to vanadium dusts results in toxic effects mainly confined to the respiratory system. Using a rat model of acute lung inflammation induced by intratracheal instillation of sodium metavanadate (NaVO3) at the dose of 200 microg V/kg, we investigated the relationship between the cytologic characterization of pulmonary inflammation and the expression of chemokine mRNA. Significant polymorphonuclear leukocyte (PMN) influx (P < 0.01) into the lung was noted 4 h after NaVO3 instillation, whereas alveolar macrophages (AMs) in bronchoalveolar lavage (BAL) cells appeared to decrease significantly. In contrast, neither PMNs nor AMs changed substantially 1 h after NaVO3 instillation. By Northern analysis, macrophage inflammatory protein (MIP)-2 mRNA in BAL cells increased markedly 1 h after NaVO3 instillation and reduced a little bit at 4 h, whereas MIP-1alpha mRNA in BAL cells was expressed relatively high 1 h after NaVO3 instillation, although a basal expression was detected in control group, and returned rapidly nearly to control level at 4 h. Since MIP-2 is a potent PMN chemoattractant and MIP-1alpha is a potent macrophage/monocyte chemoattractant has been well known. The facts that PMN influx was preceded by increased MIP-2 mRNA expression, suggesting that MIP-2 is involved in the development of NaVO3-induced pulmonary inflammation, whereas increased MIP-1alpha mRNA expression was followed by decreased AMs in BAL cells, suggesting AMs might be activated by MIP-1alpha, adherent to the lining surface of the airways and then resistant to be washed out. To delineate the mechanisms of transcriptional activation, we recently cloned the 5'-flanking region of the MIP-2 gene. The promotor region contains consensus binding sites for transcription factor nuclear factor kappaB (NF-kappaB) and activator protein-1 (AP-1). Using electrophoretic mobility shift assay, increased nuclear NF-kappaB, not AP-1, binding activity was detected 1 h after NaVO3 instillation, which correlated with the induction of MIP-2 mRNA. p65 (Rel A) and p50 protein appears to be involved in MIP-2 NF-kappaB binding. Taken together, our studies suggest that MIP-2 is an important mediator of NaVO3-induced pulmonary inflammation in the rat model. In addition, elevated MIP-2 mRNA levels are accompanied by increased NF-kappaB binding activity in BAL cells, suggesting possible MIP-2 transcriptional regulation through NF-kappaB.

Chen, D., S. I. Cho, et al. (2000). "Exposure to benzene, occupational stress, and reduced birth weight." Occup Environ Med 57(10): 661-7.

OBJECTIVES: The association between birth weight and exposure to benzene, work stress, and other occupational and environmental hazards was investigated. METHODS: In a large petrochemical industry, 792 pregnant workers were enrolled and followed up through delivery between May 1996 and December 1998. Exposure to benzene and other solvents was assessed by an industrial hygienist based on each woman's job title and workplace information. Other occupational and environmental exposures and personal information, including perceived work stress, exposure to noise, physical exertion at work, and passive smoking, were obtained by an interview questionnaire. Univariate and multivariate regression models were used to examine the individual and combined associations of occupational and environmental exposures with birth weight, with adjustment for major confounders including gestational age. RESULTS: In the univariate model, birth weight was negatively associated with exposure to benzene (-58 g (95% confidence interval (95% CI), -115 to -2)) and with work stress (-84 g (95% CI, -158 to -10)). In the multivariate model, there was a significant interaction between exposure to benzene and work stress relative to reduced birth weight, after adjustment for other environmental and occupational exposures and personal variables. Adjusted mean birth weight was 3445 g (95% CI 3401 to 3489) among those with neither exposure, 3430 g for those with exposure to benzene only, 3426 g for those with work stress only, and 3262 g (95% CI 3156 to 3369) for those with both exposures. In other words, there was 183 g (95% CI 65 to 301) reduction in birth weight among those with both exposure to benzene and work stress compared with those with neither exposure. Other work or environmental factors could not explain these findings. CONCLUSIONS: Low level exposure to benzene and work stress interact to reduce birth weight in this population.

Xia, Z. L., S. X. Jin, et al. (1999). "Analysis of 541 cases of occupational acute chemical injuries in a large petrochemical company in China." Int J Occup Environ Health 5(4): 262-6.

The authors carried out a descriptive analysis of acute chemical intoxication in a large petrochemical corporation with 38,000 employees, located in a suburban district of Shanghai, China, to determine the chemicals involved and the primary causes of the incidents. Between 1977 and 1997, 350 cases of acute chemical-intoxication were recorded, resulting in a total of 541 workers with symptoms. Of these, 483 were male and 58, female, with over half the victims under 30 years old. Two hundred and seventy-five cases were serious enough to necessitate hospital admission. There were 266 cases of chemical irritation or inhalation responses (49.2%), 215 cases of mild chemical poisoning (39.7%), 31 cases of moderate poisoning (5.7%), and 29 cases resulting in critical injury (5.4%), including eight deaths (1.5%). The main causes of injury reported by patients were lack of training about safety (63%) and equipment failure (23%). The chemicals involved were asphyxiating gases (302 cases; 55.8%), irritating gases (111 cases; 20.5%), and other toxins. Intervention strategies for the prevention of acute chemical exposures were suggested to the corporation.

Wu, M. T., C. K. Ho, et al. (1999). "Modulating influence of cytochrome P-450 MspI polymorphism on serum liver function profiles in coke oven workers." Occup Environ Med 56(3): 159-63.

OBJECTIVES: It was reported previously that topside oven workers with heavy exposure to coke oven emissions had increased serum activities of hepatic aminotransferase in one coke oven plant. This study was conducted to investigate the modifying effect of CYP1A1 MspI polymorphism on liver function profiles in coke oven workers. METHODS: 88 coke oven workers from a large steel company in Taiwan were studied in 1995-6. Exposure was categorised by work area: topside oven workers and sideoven workers. Liver function profiles including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), r-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL) were examined in the morning after personal exposure measurements. The MspI polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). RESULTS: Five of 23 (22%) topside oven workers and seven of 65 (11%) sideoven workers had the CYP1A1 MspI homozygous variant genotype. With sideoven workers with the combined wild type and heterozygous variant as the reference group in multiple regression models, it was found that topside oven workers with the combined traits had mean AST and ALT activities that were 21% and 46% higher (95% confidence interval (95% CI) 4% to 42% and 12% to 91%, respectively) than the reference group after adjusting for appropriate confounders. Also, topside oven workers with the homozygous variant trait had mean AST, ALT, and GGT activities that were 59%, 68%, and 157% higher (95% CI 21% to 109%, 6% to 168%, and 39% to 374%, respectively) than the reference group. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/l or ALT > 39 IU/l) was more common in the topside oven workers with the homozygous variant than in the sideoven workers with the other combined genotypes (adjusted odds ratio 9.9, 95% CI 1.2 to 82.3) after adjusting for appropriate confounders. CONCLUSIONS: The CYP1A1 MspI polymorphism may modify the biotransformation of coke oven emissions, which results in hepatocellular damage in coke oven workers.

Woodin, M. A., Y. Liu, et al. (1999). "Pulmonary function in workers exposed to low levels of fuel-oil ash." J Occup Environ Med 41(11): 973-80.

Previously, we reported significant lung function changes after exposure to fuel-oil ash during a boiler overhaul in which median PM10 and vanadium concentrations were 2.9 mg/m3 and 11.9 micrograms/m3, respectively. In this study, we examined prospectively 18 boilermakers involved in the short-term, partial overhaul of a large, oil-fired boiler where occupational exposures to PM10 and metals were relatively low. Vanadium and PM10 exposure levels were measured before and during boiler work. For PM10, median exposure before and during boiler work was 0.5 and 0.6 mg/m3, respectively. For vanadium, median exposure before and during boiler work was 1.0 and 12.7 micrograms/m3, respectively, comparable with the results of our previous study. Spirometric (PFT) testing was done three times: first day on the job (PFT1), end of overhaul (PFT2), and 2 weeks post-overhaul (PFT3). Spirometry results were analyzed using repeated measures analysis of variance. No significant differences were found. Boilermakers working on a short-term overhaul of an oil-fired boiler exhibited no significant change in any lung function parameter comparing pre-, during, and 2 weeks post-exposure. The comparatively low levels of exposure to PM10 and vanadium observed during boiler work, the short duration of the overhaul, and the healthy worker effect are possible explanations for these results.

Wiencke, J. K., S. W. Thurston, et al. (1999). "Early age at smoking initiation and tobacco carcinogen DNA damage in the lung." J Natl Cancer Inst 91(7): 614-9.

BACKGROUND: DNA adducts formed as a consequence of exposure to tobacco smoke may be involved in carcinogenesis, and their presence may indicate a high risk of lung cancer. To determine whether DNA adducts can be used as a "dosimeter" for cancer risk, we measured the adduct levels in nontumorous lung tissue and blood mononuclear cells from patients with lung cancer, and we collected data from the patients on their history of smoking. METHODS: We used the 32P-postlabeling assay to measure aromatic hydrophobic DNA adducts in nontumorous lung tissue from 143 patients and in blood mononuclear cells from 54 of these patients. From the smoking histories, we identified exposure variables associated with increased DNA adduct levels by use of multivariate analyses with negative binomial regression models. RESULTS/ CONCLUSIONS: We found statistically significant interactions for variables of current and former smoking and for other smoking variables (e.g., pack-years [number of packs smoked per day x years of smoking] or years smoked), indicating that the impact of smoking variables on DNA adduct levels may be different in current and former smokers. Consequently, our analyses indicate that models for current and former smokers should be considered separately. In current smokers, recent smoking intensity (cigarettes smoked per day) was the most important variable. In former smokers, age at smoking initiation was inversely associated with DNA adduct levels. A highly statistically significant correlation (r=.77 [Spearman's correlation]; two sided P<.001) was observed between DNA adduct levels in blood mononuclear cells and lung tissue. IMPLICATIONS: Our results in former smokers suggest that smoking during adolescence may produce physiologic changes that lead to increased DNA adduct persistence or that young smokers may be markedly susceptible to DNA adduct formation and have higher adduct burdens after they quit smoking than those who started smoking later in life.

Wang, X., D. C. Christiani, et al. (1999). "Carcinogen exposure, p53 alteration, and K-ras mutation in synchronous multiple primary lung carcinoma." Cancer 85(8): 1734-9.

BACKGROUND: Synchronous multiple primary lung tumors (SMPLT) have been estimated to occur in 1% of lung carcinoma patients. Criteria for SMPLT diagnosis include different cancer histologies, location in different lobes of the lung, or genetic discordance. Patients with SMPLT have a poor clinical prognosis with decreased 5-year disease survival, despite diagnosis at an early stage. Field cancerization (the induction of somatic mutation in large clones of epithelial cells after carcinogen exposure) has been proposed to be an integral process involved in the development of SMPLT. Host factors also may contribute to the development of SMPLT. METHODS: The authors investigated the occurrence of p53 and K-ras alterations in tumors from SMPLT patients and also studied the association between carcinogen exposure and polymorphic metabolic traits in SMPLT patients, comparing these patients with individuals with one primarily lung tumor. RESULTS: In a case-control study of lung carcinoma susceptibility, 6 patients were identified whose 33 multiple tumors met the criteria of SMPLT. The incidence was 3.6% (16 of 451 patients), which was higher than many previously published series. Among the multiple tumors, 73% (24 of 33 tumors) were adenocarcinomas. Patients with SMPLT smoked more (73.0 pack-years vs. 56.2 pack-years; P = 0.07) and longer (45.8 years vs. 37.0 years; P < 0.03) than patients with only 1 tumor. For those patients who stopped smoking, patients with SMPLT had stopped smoking more recently than those with a single primary tumor (3.4 years vs. 7.3 years; P = 0.08). A total of 39% of SMPLT tumors (13 of 33 tumors) had detectable p53 alterations; 36% had genetic changes in p53 measured by polymerase chain reaction-single strand conformation polymorphism, and 33% showed positive immunostaining for p53 protein. This was comparable to the occurrence of p53 mutations and immunostaining in single tumor cases (30%). Age, gender, family history of cancer, and the prevalence of polymorphic metabolic traits previously associated with lung carcinoma susceptibility did not differ among SMPLT patients compared with patients with a single tumor. CONCLUSIONS: The patients with SMPLT had significantly more tobacco exposure, and their tumors apparently had independently arising p53 and K-ras mutations, suggesting that field cancerization may be important in lung carcinogenesis.

Tacci, J. A., B. S. Webster, et al. (1999). "Clinical practices in the management of new-onset, uncomplicated, low back workers' compensation disability claims." J Occup Environ Med 41(5): 397-404.

Recent consensus guidelines delineate what appears to be the most successful and cost-effective management of low back pain (LBP), and some recent studies have suggested that better outcomes occur with the least aggressive forms of medical intervention. The purpose of this study was to describe how practitioners manage new-onset, uncomplicated low back workers' compensation (WC) disability cases. A sample of cases was randomly selected from a large insurance carrier's national data source. An effort was made to select only uncomplicated cases, which would be expected to have relatively minimal need for medical intervention. There was an apparent overuse of diagnostic and treatment modalities. Diagnostic imaging was overutilized, not only in terms of the number of studies done (65% had plain films, 22% had magnetic resonance imaging scans) but also in the time frame in which they were performed (38% had plain films on the first clinic visit). Ninety percent received at least one medication, and 38% received more than one prescription for opioid analgesics. Expensive non-steroidal anti-inflammatory drugs were prescribed more often than acetaminophen (61% versus 6%, respectively). Sixty-two percent received physical therapy that often included modalities with as yet unproven efficacy. Overutilization of either diagnostic or treatment procedures increases the likelihood of iatrogenic complications, is not cost-effective, and may adversely impact clinical and occupational outcomes.

Perry, M. J. and D. C. Christiani (1999). "Herbicide and insecticide exposures among dairy farm pesticide applicators." Am J Public Health 89(7): 1118-9.

Padungtod, C., T. J. Hassold, et al. (1999). "Sperm aneuploidy among Chinese pesticide factory workers: scoring by the FISH method." Am J Ind Med 36(2): 230-8.

BACKGROUND: A study of the prevalence of sperm aneuploidy among pesticide factory workers was conducted in Anhui, China. METHODS: We recruited 75 men: 32 subjects from a large pesticide-manufacturing plant and 43 subjects from a nearby textile factory free of pesticide exposure. Each subject met the following criteria: age of 20-40 years; continuous work in the plant for 3 months prior to the study, no congenital anomalies or acquired disease of the external genitalia and no history of recent febrile illness or mumps. Within one hour after collection from each subject, semen was evaluated in terms of several parameters and smear slides were prepared. RESULTS: Exposure assessment revealed that workers in the pesticide plant were exposed to ethyl parathion or methamidophos, each of which is a potent organophosphate pesticide, at a median level of 0.02 mg/m3 (8-hour time weighted average as measured by personal pump) while workers in the control plant had no such occupational exposure. Twenty-nine semen slides (13 from the exposed group and 16 from the unexposed group) were randomly chosen for aneuploidy scoring by the three-color fluorescence in situ hybridization (FISH) method with scorers being unaware of exposure status. Median semen parameters were as follows for exposed (and unexposed) men: abstinence period, 3 days (4 days); sperm concentration, 52.8x10(6)/ml (53.1x10(6)/ml); proportion of sperm with normal motility, 50.5% (61.3%); and proportion of sperm with normal morphology, 59% (61.5%). The specific chromosome abnormalities of interest were disomy for chromosome 18 and the three different types of sex chromosome disomy (i.e. XX, XY, YY disomy). The crude proportion of all aneuploidy combined was 0.30% and 0.19% for sperm from exposed and unexposed men, respectively. Poisson regression with overdispersion adjustment yielded significantly different crude risks of aneuploidy - 3.03 and 1.94 per 1,000 sperm from exposed and unexposed men, respectively - giving a rate ratio of 1.56 (95% CI, 1.06-2.31). The regression coefficients remained statistically significant after adjustment for inter-technician variability giving a rate ratio of 1.51 (95% CI, 1. 04-2.20). CONCLUSIONS: We conclude that occupational exposure to organophosphate pesticides moderately increases the prevalence of sperm aneuploidy.

Padungtod, C., T. Niu, et al. (1999). "Paraoxonase polymorphism and its effect on male reproductive outcomes among Chinese pesticide factory workers." Am J Ind Med 36(3): 379-87.

BACKGROUND: Serum paraoxonase has been associated with the metabolism of organophosphate pesticides in humans. Molecular analysis of the human paraoxonase gene (PON1) has revealed that Arg192 homozygotes have a greater detoxifying capability than Gln192 homozygotes. We examined the effects of PON1 genotypes on male reproductive outcomes and its interaction with exposure to organophosphate pesticides. METHODS: We studied 60 Chinese pesticide-factory workers and 89 textile-factory workers who were unexposed to pesticides. The respective allele frequencies of Arg192 and Gln192 were 0.62 and 0.38. Pesticide exposure among 36 exposed subjects and 12 unexposed subjects, regardless of gender, was assessed by personal measurement of pesticide residues over an entire 8-hr shift and measurement of urinary p-nitrophenol level over a 24-hr period. We analyzed semen and hormone data collected from male subjects. RESULTS: When the three PON1 genotypes were analyzed separately, a gene dose effect was not detected. We used the unexposed Arg192 homo/heterozygotes as the reference group, and re-analyzed the data. Exposed Arg192 homo/heterozygotes had significantly lower sperm count (chi 2 = 9.01, P < 0.01) and lower percentage of sperm with normal morphology (chi 2 = 4.18, P < 0.05) than the reference group. Both unexposed Gln192 homozygotes (chi 2 = 4.90, P < 0.05) and exposed Arg192 homo/heterozygotes (chi 2 = 10.00, P < 0.01) showed significantly lower sperm concentrations than the reference group. In addition, exposed Arg192 homo/heterozygotes had significantly higher serum LH levels (chi 2 = 7.94, P < 0.01) than the reference group. CONCLUSIONS: Because of a small sample size, our findings are highly preliminary. Nevertheless, it calls for further investigation of the interaction between the PON1 genotype and organophosphate pesticide exposure on male reproductive outcomes.

Nelson, H. H., D. C. Christiani, et al. (1999). "k-ras mutation and occupational asbestos exposure in lung adenocarcinoma: asbestos-related cancer without asbestosis." Cancer Res 59(18): 4570-3.

Environmental carcinogen exposure is requisite for the development of nearly all lung cancer, and it is well known that asbestos exposure interacts synergistically with tobacco smoke to induce lung cancer. However, the precise molecular lesions induced by asbestos are unknown. Furthermore, it is also unknown whether asbestos carcinogenesis proceeds in a fashion independent of or dependent upon the induction of fibrosis in workers with high asbestos exposures. Previous studies have suggested that asbestos is associated with the presence of a k-ras mutation in adenocarcinoma of the lung. We aimed to test whether occupational asbestos exposure was associated with k-ras codon 12 mutations in lung adenocarcinoma tumors and to determine whether this was conditional on the presence of asbestosis. All newly diagnosed, resectable lung cancer patients receiving treatment at the Massachusetts General Hospital between November 1992 and December 1996 were eligible to participate. Because k-ras mutation is very strongly associated with adenocarcinoma, and men were more likely to be occupationally exposed to asbestos, the study was restricted to males with this histological diagnosis. There were 84 male patients with available questionnaire-derived work history data and paraffin-embedded tumor tissue for determination of k-ras mutation status. Chest radiographic evaluation was done for all of the patients who reported occupational exposure to asbestos. The prevalence of k-ras mutation was higher among those with a history of occupational asbestos exposure (crude odds ratio, 4.8; 95% confidence interval, 1.5-15.4) compared to those without asbestos exposure, and this association remained after adjustment for age and pack-years smoked (adjusted odds ratio, 6.9; 95% confidence interval, 1.7-28.6). An index score that weights both the dates of exposure and the estimated intensity of exposure indicated that those with k-ras mutations had significantly greater asbestos exposures than those without mutations (P < 0.01). Analysis of the descriptive components of exposure indicated that the duration of exposure was not associated with k-ras mutation, but that the time since initial exposure was significantly associated with mutation status. The association of k-ras mutation and reported asbestos exposure was not dependent on the presence of radiographic evidence of asbestos-related disease. These data suggest that asbestos exposure increases the likelihood of mutation at k-ras codon 12 and that this process occurs independently of the induction of interstitial fibrosis.

Nelson, H. H., D. C. Christiani, et al. (1999). "Implications and prognostic value of K-ras mutation for early-stage lung cancer in women." J Natl Cancer Inst 91(23): 2032-8.

BACKGROUND: Because there is no clear consensus as to the predictive value of K-ras gene mutation for survival in patients with lung cancer, we examined the occurrence of K-ras mutations in a large, prospective case series of non-small-cell lung cancer (NSCLC). Our goals were to define the patient characteristics associated with K-ras mutation and to determine whether mutation of this gene might be a biomarker of patient prognosis. METHODS: Consecutive, newly diagnosed patients with lung cancer treated with potentially curative resection over a 4-year period were recruited for study. The mutation status of K-ras codon 12 in each patient's tumor DNA was determined by means of polymerase chain reaction-restriction fragment length polymorphism analysis of archived pathology specimens. Analyses were restricted to adenocarcinoma. RESULTS: There was a statistically significant association between female sex and K-ras mutation after adjustment for carcinogen exposures (odds ratio = 3.3; 95% confidence interval [CI] = 1.3-7.9); mutations were found only in smokers. Comparison of Kaplan-Meier curves indicated a strong association between K-ras mutation and decreased patient survival (two-sided P =.009); analysis stratified by pathologic staging groups revealed that this association was statistically significant only for stage I tumors (two-sided P =.002). Cox proportional hazards modeling indicated that K-ras codon 12 mutation was a statistically significant predictor of patient survival, after adjustment for the effects of age, sex, and stage (risk ratio = 1.8; 95% CI = 1.1-3.1). CONCLUSIONS: After adjustment for environmental exposures, non-small-cell lung tumors in women appear to be more likely than those in men to harbor K-ras mutations, suggesting a possible role of estrogen exposure in either the initiation or the selection of K-ras mutant clones in adenocarcinoma. In addition, our data suggest that K-ras codon 12 mutation is a marker of aggressive NSCLC, as evidenced by its association with decreased patient survival, particularly for early-stage disease.

Moy, E. V., H. Hu, et al. (1999). "A retired shipyard worker with rapidly progressive pulmonary interstitial fibrosis." Environ Health Perspect 107(4): 321-7.

We present a case of progressive interstitial fibrosis in a retired shipyard worker who was exposed to asbestos during the postwar era of the late 1940s and 1950s, when asbestos exposures in the workplace were not regulated. Forty years later, at 63 years of age, the patient presented with restrictive lung disease. The patient was diagnosed with asbestos-related pleural disease and parenchymal asbestosis. He remained stable for the next 7 years, but then he began to manifest rapid clinical progression, which raised the possibility of an unusual variant of asbestosis, a concomitant interstitial process, or an unrelated disease. Lung biopsy was not undertaken because of the patient's low pulmonary reserve and limited treatment options. An empiric trial of oral steroids was initiated, but his pulmonary status continued to deteriorate and he died of pulmonary failure at 72 years of age. Many diseases result in pulmonary interstitial fibrosis. Ideally, open lung biopsy should be performed, but this procedure inevitably causes complications in many patients with end-stage restrictive lung disease. Furthermore, while the presence of asbestos bodies in tissue sections is a sensitive and specific marker of asbestos exposure, neither this finding nor any other charge is a marker indicative of asbestosis or the severity of asbestosis. With the enactment of the Asbestos Standard in the United States, asbestos exposures have been decreasing in this country. However, industries that produce asbestos products and wastes continue to expand in developing countries. Prevention of asbestos-related lung disease should be a global endeavor, and asbestos exposures should be regulated in both developed and developing countries.

Kales, S. N., G. N. Polyhronopoulos, et al. (1999). "Correlates of body mass index in hazardous materials firefighters." J Occup Environ Med 41(7): 589-95.

We analyzed results from the medical examinations of 340 hazardous materials (HAZMAT) firefighters and observed the relationships between selected parameters and body mass index (BMI). Heights and weights were available for 98% of the subjects (333 of 340). The mean BMI was 28.9 +/- 4.1 kg/m2. Eighty-seven percent (290 of 333) of subjects were overweight (BMI > or = 25) and 34% (113 of 333) were obese (BMI > or = 30). Two percent (7 of 333) were morbidly obese (BMI > or = 39). For comparison purposes, we divided subjects into low (BMI < 27), medium (BMI 27 to < 30), and high (BMI > or = 30) BMI groups. The results demonstrated adverse associations between increasing BMI and resting blood pressures, forced vital capacity, alanine aminotransferase, aspartate aminotransferase, serum cholesterol, and overall morbidity scores. The high prevalence of overweight and obesity and the associated adverse health effects support the development and implementation of fitness-promotion programs for firefighters.

Kales, S. N., J. M. Aldrich, et al. (1999). "Correlates of fitness for duty in hazardous materials firefighters." Am J Ind Med 36(6): 618-29.

BACKGROUND AND METHODS: From a statewide medical examination program, we identified firefighters who were deemed unfit for duty by attending physicians (ATTENDING FAIL, n=9) and those who would have been disqualified by the application of selected numerical criteria from the 1997 National Fire Protection Association (NFPA) guidelines (NFPA FAIL, n=27) and criteria from a Medical Workshop (WORK FAIL, n=16). The subjects who were unfit for duty or failed numerical criteria were compared with those who were fit for duty and passed all objective criteria (FIT group, n=302). All subjects were given an overall morbidity rating by a board certified internist. Comparisons on two surrogate measures of fitness, VO(2) max predicted and predicted coronary heart disease (CHD) risk, were also performed. RESULTS: We found a significant tendency towards worse results (e.g. higher blood pressure or lower spirometric function) among the three FAIL groups compared with the FIT group. The FAIL groups shared only a small overlap, however, with the firefighters with the highest morbidity ratings, lowest predicted VO(2) max, and highest CHD risks. Increasing morbidity was associated with higher age, lower spirometric function, lower predicted VO(2) max, increasing cholesterol, greater BMI, and higher predicted 10 year CHD risk. CONCLUSIONS: Although the presence of a single serious or poorly controlled condition may render an individual unfit for safe performance as a firefighter, examination of our cohort suggests that multiple risk factor models or overall clinical assessments are superior means of identifying firefighters with poor health status and increased CHD risk.

Hong, Y. C., J. H. Leem, et al. (1999). "PM(10) exposure, gaseous pollutants, and daily mortality in Inchon, South Korea." Environ Health Perspect 107(11): 873-8.

To evaluate the relative importance of various measures of particulate and gaseous air pollution as predictors of daily mortality in Inchon, South Korea, the association between total daily mortality and air pollution was investigated for a 20-month period (January 1995 through August 1996). Poisson regression was used to regress daily death counts on each air pollutant, controlling for time trends, season, and meteorologic influences such as temperature and relative humidity. Regression coefficients of a 5-day moving average of particulate matter less than or = to 10 microm in aerodynamic diameter (PM(10)) on total mortality were positively significant when considered separately and simultaneously with other pollutants in the model. PM(10) remained significant when the models were confined to cardiovascular or respiratory mortality. Sulfur dioxide (SO(2)) and carbon monoxide (CO) were significantly related to respiratory mortality in the single-pollutant model. Ozone exposure was not statistically significant with regard to mortality in the above models, and graphic analysis showed that the relationship was nonlinear. A combined index of PM(10), nitrogen dioxide, SO(2), and CO seemed to better explain the exposure-response relationship with total mortality than an individual air pollutant. Pollutants should be considered together in the risk assessment of air pollution, as opposed to measuring the risk of individual pollutants.

Ho, C. K., W. C. Lo, et al. (1999). "Suspected nasopharyngeal carcinoma in three workers with long-term exposure to sulphuric acid vapour." Occup Environ Med 56(6): 426-8.

Sulphuric acid vapour has been suspected of being an industrial carcinogen. In this study, a cluster is presented of three patients with nasopharyngeal carcinoma (NPC) who worked in the same building of a telecommunications conveyance station in southern Taiwan with long term exposure to sulphuric acid vapour concentrations as high as 0.18 mg/m3. All three workers were diagnosed with NPC within a 5 month period between September 1992, and March 1993. Compared with 19 other healthy workers from the same building, these three workers with NPC had worked significantly longer in this building than had the others (mean (SD) (years): 12.7 (0.6) v 7.4 (4.4); p = 0.01). With an in situ nucleic acid hybridisation and immunostaining method for colocalised Epstein-Barr virus (EBV) and secretory component (SC) protein among biopsy specimens of these three patients with NPCs, it was found that some tumour cells did not contain EBV and SC protein staining signals. These results indicate that EBV infection is not the only risk factor for NPC and long term exposure to relatively low concentrations of sulphuric acid vapour may be associated with the development of NPC.

Dalvie, M. A., N. White, et al. (1999). "Long-term respiratory health effects of the herbicide, paraquat, among workers in the Western Cape." Occup Environ Med 56(6): 391-6.

OBJECTIVE: To evaluate the possible effects of paraquat spraying among workers on deciduous fruit farms in the Western Cape, South Africa. Paraquat is a commonly used herbicide world wide and is a well documented cause of pulmonary fibrosis in studies of laboratory animals and in humans after exposure to a high dose (usually accidental or as parasuicide). The respiratory effects of long term, low dose exposure to paraquat have not been fully evaluated. METHODS: A cross sectional study of 126 workers. Administered questionnaires generated information on exposure, respiratory symptoms, and potential confounding variables. Spirometry and gas transfer were measured and chest radiographs performed. Oxygen desaturation on exercise testing was by oximetry during a modified stage one exercise test. RESULTS: No association was found between long term exposure to paraquat and reported symptoms, spirometry (forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), FEV1/FVC) and gas transfer (TLCO and KCO) or chest radiography. Multivariate analysis showed a significant relation between measures of long term exposure to paraquat and arterial oxygen desaturation during exercise independent of short term exposure. CONCLUSION: Previous studies have not shown a significant relation between measures of exposure to paraquat and standard tests of lung function. Arterial oxygen desaturation during exercise represents a more sensitive test. The findings indicate that working with paraquat under usual field conditions is associated with abnormal exercise physiology in a dose dependent fashion independent of recent exposure and acute poisoning events.

Christiani, D. C., T. T. Ye, et al. (1999). "Cotton dust and endotoxin exposure and long-term decline in lung function: results of a longitudinal study." Am J Ind Med 35(4): 321-31.

BACKGROUND: To evaluate the relationship between long-term exposure to cotton dust and Gram-negative bacterial endotoxin on lung function, we conducted an 11-year follow-up study of cotton textile workers in Shanghai, China. METHODS: Workers at a nearby silk-thread manufacturing mill were used as a referent population. Ninety percent of the original cohort of 445 cotton and 467 silk textile workers--both active and retired--were identified for testing in the 11th year. Questionnaires and spirometric testing were performed, as well as cotton dust and endotoxin sampling at three points over the 11-year follow-up period: at baseline, at Year 5, and at Year 11. After excluding deaths and subjects on sick-leave, 84% of the original cohort had complete health and environmental data. RESULTS: The data were reanalyzed using generalized estimating equations feedback model which allow for subject transfer over time between work areas, various exposure levels to dust and endotoxin, and FEV1. Cotton workers had a larger loss of FEV1 during the first 5 years of study (-40 mls/yr) as compared with the second 6 years of follow-up (-18 mls/yr). During the same periods, the average decline among silk workers was slightly higher in the first period, but was more consistent (-30 mls/yr vs. -27 mls/yr), and these differences could not be explained by worker selection or dropout. When cumulative exposure to dust and endotoxin were estimated and used in a multivariate model (GEE) for FEV1 loss, cumulative dust, but not endotoxin, was associated with 11-year loss in FEV1 after adjustments for confounders. There was evidence of feedback between dust-exposure levels and FEV1, indicating the existence of a healthy-worker survivor effect. After accounting for a healthy-worker survivor effect, we found a significant relationship between dust exposure and FEV1 decline. CONCLUSIONS: Our results suggest that cotton dust is more strongly associated with chronic airflow limitation than associated endotoxins. Further work is needed to clarify potential reversibility after cessation of exposure, and the relative contributions of dust, endotoxin, and tobacco to chronic respiratory impairment in cotton and other vegetable-exposed workers.

Cho, S. I., Q. Li, et al. (1999). "Drinking water source and spontaneous abortion: A cross-sectional study in a rural Chinese population." Int J Occup Environ Health 5(3): 164-9.

The authors examined the association between the risk of spontaneous abortion and the type of drinking water source in a rural Chinese population. Information about pregnancy outcomes and various exposures was collected by means of a detailed interview questionnaire. 2,876 pregnancies occurring in 1989-1993 among 2,201 nonsmoking and non-alcohol-drinking women were analyzed by logistic regression. Generalized estimating equations were used to adjust for correlations between multiple pregnancies in the same woman. The use of pond water as a drinking water source was associated with a higher risk of spontaneous abortion than the use of well or river water (odds ratio, 1.63; 95% confidence interval, 1.11 to 2.39), adjusting for potential confounders. More studies are needed to identify the agents responsible for the observed association. The results of this study emphasize the importance of monitoring potential drinking-water contamination in communities.

Chen, M. L., I. F. Mao, et al. (1999). "Assessment of coke oven emissions exposure among coking workers." Am Ind Hyg Assoc J 60(1): 105-10.

Coking workers are regularly exposed to coke oven emissions, which consist primarily of polycyclic aromatic hydrocarbons and volatile organic compounds. This study measured the workers' exposure to the benzene soluble fraction of total particulates (BSF). The study population consisted of 88 coking workers as an exposure group and 59 referents. Personal breathing-zone samples of BSF and total particulates were taken from all study subjects for 3 consecutive days. The highest BSF concentrations were found among the topside oven workers (geometric mean; range) (microgram/m3): lidman (515; 72-18, 181), tar chaser (432; 51-4334), and larry car operator (185; 55-649). The lowest was 7 micrograms/m3 in the referents. Among the samples at the topside oven 84% exceeded the Occupational Safety and Health Administration standard (150 micrograms/m3 BSF). The percentage of BSF in total particulates varied across job classifications, ranging from 0.3% in wharfmen to 24% in tar chasers. Area sampling indicated that the BSF concentration at the topside area was sixtyfold higher than that at the administrative area, which was approximately 2 km from the coke oven plant.

Chen, K. L., C. J. Amarasiriwardena, et al. (1999). "Determination of total arsenic concentrations in nails by inductively coupled plasma mass spectrometry." Biol Trace Elem Res 67(2): 109-25.

The analysis of trace elements in biological samples will extend our understanding of the impact that environmental exposure to these elements has on human health. Measuring arsenic content in nails has proven useful in studies evaluating the chronic body burden of arsenic. In this study, we developed methodology with inductively coupled plasma-mass spectrometry (ICP-MS) for the determination of total arsenic in nails. We assessed the utility of the washing procedures for removing surface contamination. Four types of preanalysis treatments (water bath, sonication, water bath plus sonication, and control) after sample decomposition by nitric acid were compared to evaluate the digestion efficiencies. In addition, we studied the stability of the solution over 1 wk and the effect of acidity on the arsenic signal. Arsenic content in the digested solution was analyzed by using Ar-N2 plasma with Te as the internal standard. The results suggest that washing once with 1% Triton X-100 for 20 min for cleaning nail samples prior to ICP-MS analysis is satisfactory. Repeated measurement analysis of variance revealed that there was no significant difference among the various sample preparation techniques. Moreover, the measurements were reproducible within 1 wk, and acidity seemed to have no substantial influence on the arsenic signal. A limit of detection (on the basis of three times the standard deviation of the blank measurement) of 7 ng As/g toenail was achieved with this system, and arsenic recoveries from reference materials (human hair and nails) were in good agreement (95-106% recovery) with the certified/reference values of the standard reference materials. ICP-MS offers high accuracy and precision, as well as high-throughput capacity in the analysis of total arsenic in nail samples.

Chatzis, C., G. Danaka, et al. (1999). "Lung cancer and occupational risk factors in Greece." J Occup Environ Med 41(1): 29-35.

This study estimated the proportion of lung cancer in Greece that was attributable to occupational exposure. Two hundred eighty-two patients with lung cancer and 494 controls were interviewed about their socioeconomic characteristics, sex, age, and occupational, smoking, and residential histories. Each subject was classified as exposed or unexposed to known occupational lung carcinogens. Because of the small number of females exposed, only males were included in the multivariate analyses. When the occupationally exposed subjects were compared with the unexposed subjects and an adjustment for smoking was made, the relative risk for lung cancer was 2.9 (95% confidence interval, 1.95-4.31). If 5% to 10% of the Greek population were occupationally exposed, the attributable risk would be 9.9% to 16.6%, respectively. Occupational exposures conferred an additional risk that was approximately threefold that of smoking alone. Risks increased in a dose-response fashion with increasing cigarette consumption.

Cernadas, M., G. T. De Sanctis, et al. (1999). "CD23 and allergic pulmonary inflammation: potential role as an inhibitor." Am J Respir Cell Mol Biol 20(1): 1-8.

CD23, a receptor for immunoglobulin E, is expressed at increased levels in asthmatic and atopic individuals and has been associated with disorders characterized by chronic inflammation. Using an established murine model, we employed several complementary strategies to investigate the role of CD23 in allergic pulmonary inflammation and airway hyperresponsiveness (AHR). Specifically, these approaches included the modulation of CD23 function in vivo by administration of anti-CD23 monoclonal antibody (mAb) or Fab fragments to wild-type mice and the analysis of CD23-deficient mice. Administration of anti-CD23 mAb, but not anti-CD23 Fab fragments, produced attenuation of pulmonary inflammation, AHR, and CD8(+) T-cell activation. On the basis of a model that the anti-CD23 mAb transduces, whereas the Fab fragment inhibits, CD23 signaling, these results suggest that CD23 negatively regulates pulmonary inflammation and AHR. This hypothesis is supported by our observation that CD23-deficient mice developed increased inflammation and AHR after sensitization and challenge with allergen. Together, these results indicate that CD23 negatively regulates pulmonary inflammation and airway hyperreactivity.

Ye, T. T., J. X. Huang, et al. (1998). "Respiratory symptoms and pulmonary function among Chinese rice-granary workers." Int J Occup Environ Health 4(3): 155-9.

The authors conducted a cross-sectional study of 474 rice-granary workers and 235 non-granary worker controls in a rural area near Shanghai, the People's Republic of China. Responses to a respiratory-symptom questionnaire and pre- and post-shift spirometry were obtained for all subjects. Area sampling was performed for total and vertically elutriated (</= 15 micrometer) dust levels. Total dust levels were high, ranging from 6.6 mg/m(3) to 59.8 mg/m(3), with vertical elutriated dust concentrations ranging from 2.0 to 10. 4 mg/m(3). The granary workers reported significantly more respiratory symptoms, including chronic cough, sputum production, chronic bronchitis, grain fever (ODTS), and nasal and skin irritation. Grain dust and tobacco smoking were more than additive for the prevalence of chronic cough and chronic bronchitis. After adjusting for confounders, the granary workers had lower mean FEV&inf1;/FVC values both pre- and post-shift, indicating an association between chronic grain-dust exposure and chronic airway obstruction. The results suggest that exposure to rice dust can induce pulmonary responses similar to those observed with exposures to other types of grains.

Xu, X., J. K. Wiencke, et al. (1998). "Benzene exposure, glutathione S-transferase theta homozygous deletion, and sister chromatid exchanges." Am J Ind Med 33(2): 157-63.

Recent studies have shown a strong positive correlation between chromosomal aberrations and future cancer risk. Sister chromatid exchange (SCE) has been widely applied in monitoring early biological effects to assess human genetic risk of cancer at the population level. We studied 45 Chinese workers (23 in the painting workshop of a glass factory with occupational exposure to benzene, and 22 fitters and planers in the punching and planing machine workshops of a nearby shipyard without such an exposure) to examine the association between occupational exposure to benzene and SCE frequency in peripheral blood lymphocytes. We also sought to investigate whether the glutathione S-transferase class theta gene (GSTT1) affects individual susceptibility to cytogenetic damage induced by in vivo exposure to benzene or in vitro exposure to diepoxybutane. The time-weighted average concentrations of benzene were 0.71 ppm in the exposed group and 0.03 ppm in the non-exposed group. Controlling for age, gender and educational level, cigarette smoking was significantly associated with increased SCE frequencies (P < 0.05), while GSTT1 genotype was significantly associated with DEB-induced SCEs (P < 0.01). There was no relationship between benzene exposure and baseline or DEB-induced SCEs. After stratification by smoking status, the GSTT1 deletion was a significant predictor of DEB-induced SCEs for both smokers (P < 0.05) and nonsmokers (P < 0.01). A significant benzene-GSTT1 interaction was found in nonsmokers (P < 0.05). Our study suggests that GSTT1 is an important determinant of heterogeneity in individual susceptibility to chromosomal damage associated with exposure to benzene.

Wu, M. T., D. Wypij, et al. (1998). "Temporal changes in urinary 1-hydroxypyrene concentrations in coke-oven workers." Cancer Epidemiol Biomarkers Prev 7(2): 169-73.

Coke-oven workers are exposed to high concentrations of coke-oven emissions, which are comprised mainly of polycyclic aromatic hydrocarbons. We conducted a pilot study to determine the time changes in urinary 1-hydroxypyrene (1-OHP) concentrations, as a metabolite of pyrene, in coke-oven workers after exposure to a benzene-soluble fraction (BSF) of total particulates. Thirteen subjects, including 2 men (referents) from an administrative area, 6 workers who work at the sideoven, and 5 who work on the top of the oven in one coke-oven plant were studied. After 1.5 to 2 days off, subjects were monitored individually for breathing zone air BSF over 3 consecutive days in August 1995. Seven spot urine samples, including preshift and postshift urine over 3 days and preshift urine on a fourth-day morning, were collected to determine 1-OHP concentrations by fluorescent spectrophotometry. The mean ambient BSF concentrations in the sideoven and topside oven workers ranged from 18 to 159 microg/m3 and from 251 to 1362 microg/ m3, respectively, whereas the BSF concentrations in the referents were low but detectable (11 and 29 microg/m3). Urinary 1-OHP concentrations increased during the work period, from 10+/-3 and 41+/-9 microg/g creatinine (mean+/-SE) on the preshift first day to 57+/-26 and 334+/-63 microg/g creatinine on the postshift third day in the sideoven and topside oven workers, respectively. However, the urinary 1-OHP concentrations were relatively flat in the two referents. The across-shift change in urinary 1-OHP defined as postshift 1-OHP on the third day minus preshift 1-OHP on the first day was highly associated with individual mean occupational exposure to air BSF (r = 0.80, P = 0.001). Repeated-measures regression analyses revealed that daily postshift 1-OHP concentrations were marginally associated with daily air BSF. A 10-fold increase of daily air BSF resulted in a 1.67-fold increase of daily postshift 1-OHP levels (95% confidence interval = 0.99-2.83; P = 0.07). After adjusting for daily preshift 1-OHP concentrations, we found that a 10-fold increase of daily air BSF resulted in a 1.90-fold increase of daily postshift 1-OHP levels (95% confidence interval = 1.10-3.28; P = 0.03). Although the sample size is small in this study, these results indicate that daily postshift 1-OHP levels in urine are determined mainly by current occupational exposure to coke-oven emissions.

Wu, M. T. and D. C. Christiani (1998). "Elevated serum hepatic aminotransferase in coking workers after exposure to coke oven emissions." J Occup Environ Med 40(4): 303-5.

Wu, M. T., B. J. Pan, et al. (1998). "Association between cancer mortality and residence near petrochemical industries in Taiwan." J Toxicol Environ Health A 53(8): 665-7.

Wu, M. T., S. L. Huang, et al. (1998). "Cytochrome P450 1A1 MspI polymorphism and urinary 1-hydroxypyrene concentrations in coke-oven workers." Cancer Epidemiol Biomarkers Prev 7(9): 823-9.

Coke-oven workers are regularly exposed to a high concentration of the benzene-soluble fraction (BSF) of total particulates, which are comprised mainly of polycyclic aromatic hydrocarbons (PAHs). A metabolite of pyrene, 1-hydroxpyrene (1-OHP), is readily measured in the urine of exposed individuals. Epidemiological studies have shown that P4501A1 (CYP1A1) genotypes are associated with PAH-related lung cancer risk. The purpose of this study was to investigate whether CYP1A1 MspI genotypes modulate the relationship of individual occupational exposure to air BSF to urinary 1-OHP concentrations among coke-oven workers. We monitored individual breathing zone air BSF over 3 consecutive days in 80 coke-oven workers in Taiwan from August 1995 to February 1996. Exposure was also dichotomized by work area (topside oven workers and sideoven workers). Preshift urine on the morning of day 1 and postshift urine on the afternoon of day 3 were measured by fluorescent spectrophotometry, and blood samples were analyzed to determine the relative distributions of CYP1A1 MspI polymorphisms. The frequency of the MspI homozygous variant genotypes of CYP1A1 was 15%. Multiple linear regression showed significant effects of individual occupational exposure to air BSF and preshift 1-OHP on postshift urinary 1-OHP concentrations (P = 0.002 and P < 0.001, respectively). After adjusting for preshift 1-OHP concentrations and air BSF, subjects with the homozygous variant genotype have a 2-fold higher postshift 1-OHP levels than the combined wild-type and heterozygous (P = 0.04). In addition, a positive trend was found in postshift 1-OHP and across-shift change of 1-OHP (postshift 1-OHP - preshift 1-OHP) in decreasing order, as follows: topside oven workers with the homozygous variant trait, topside oven workers with the heterozygous variant trait, sideoven workers with the homozygous variant trait, and sideoven workers with the heterozygous trait (P < 0.001). We conclude that CYP1A1 MspI variant genotype can modify the metabolism of PAHs in coke-oven workers.

Wu, M. T., I. F. Mao, et al. (1998). "Urinary 1-hydroxypyrene concentrations in coke oven workers." Occup Environ Med 55(7): 461-7.

OBJECTIVES: To investigate the relation of individual occupational exposure to total particulates benzene soluble fraction (BSF) of ambient air with urinary 1-hydroxypyrene (1-OHP) concentrations among coke oven workers in Taiwan. METHODS: 80 coke oven workers and 50 referents were monitored individually for the BSF of breathing zone air over three consecutive days. Exposures were categorised as high, medium, or low among coke oven workers based on exposure situations. The high exposure group (n = 18) worked over the oven. The medium and low exposure groups (n = 41 and n = 21) worked at the side of the oven for > 4 hours and < 4 hours a day, respectively. Urine was collected before the shift on the morning of day 1 and after the shift on the afternoon of day 3 to find the change of 1-OHP concentrations across the shift. RESULTS: The median (range) changes of urinary 1-OHP concentrations across the shift for various exposure situations (microgram/g creatinine) were as follows: high 182 (7 to 3168); medium 9 (-8 to 511); low 7 (-6 to 28); and referents 0.2 (-2 to 72). This change of urinary 1-OHP was highly associated with individual occupational exposure to the BSF in air (r = 0.74 and 0.64, p < 0.001). The regression model showed significant effects of individual exposures to the BSF and alcohol consumption on urinary postshift 1-OHP after adjusting for preshift 1-OHP in the total population (n = 130). More exposure to the BSF led to higher postshift 1-OHP (p < 0.001); current drinkers of > 120 g/week had lower urinary postshift 1-OHP than never and former drinkers (p = 0.01). A 10-fold increase in the average BSF in air resulted in about a 2.5-fold increase in postshift 1-OHP among the 80 coke oven workers. CONCLUSION: Urinary 1-OHP concentrations can be used as a good biomarker to assess individual exposure to the BSF in air. Alcohol drinking may modify the toxicokinetic pathway of the BSF; the effects of alcohol should be investigated further in occupational studies.

Woodin, M. A., R. Hauser, et al. (1998). "Molecular markers of acute upper airway inflammation in workers exposed to fuel-oil ash." Am J Respir Crit Care Med 158(1): 182-7.

Biomarkers in nasal lavage (NL) fluid may be useful in determining the presence and severity of upper airway inflammation. We studied 18 boilermakers overhauling a large, oil-fired boiler and 11 utility workers who served as controls for 6 wk. NL was performed before (NL1), during (NL2), and after (NL3) the overhaul. We measured nasal fluid levels of interleukins 6 (IL-6) and 8 (IL-8), eosinophilic cationic protein (ECP), and myeloperoxidase (MPO) as markers of response to fuel-oil ash exposure. In boilermakers, MPO was elevated during boiler work versus preboiler work (mean = 33.8 versus 22.7 ng/ml, p < 0.05), and at the 2-wk postexposure lavage (NL3) it had declined to 24.2 ng/ml (p = 0.08). Mean IL-8 levels increased in boilermakers between NL1 and NL2 (mean = 83.8 versus 134.8 pg/ml, p < 0.05), then decreased at NL3 (mean = 134.8 versus 89.0 pg/ml, p < 0.05). Nasal fluid vanadium increased in boilermakers between NL1 and NL2 (median < 1.0 versus 4.7 ppb, respectively, p < 0.05), then decreased at NL3 (median, 4.7 versus < 1.0 ppb, respectively, p < 0. 05). Levels of IL-6 and ECP did not change significantly during the study. Utility workers showed no significant change in any marker during the study period. Particulate matter < 10 micro(m) (PM10) levels were higher for boilermakers than for utility workers before boiler work (geometric mean (GM) = 0.40 versus 0.10 mg/m3, p < 0.05). This difference was more significant during boiler work (GM = 0.47 versus 0.13 mg/m3, p < 0.001). Ozone levels were low during the study. These data suggest that exposure to fuel-oil ash results in acute upper airway inflammation, potentially mediated by increased IL-8 levels and the recruitment and activation of polymorphonuclear leukocytes. These changes were associated with significantly increased PM10 levels and concentrations of upper airway vanadium.

Wang, X., B. Wang, et al. (1998). "Blood pressure at age 3-24 years in a rural community in Anhui, China." Ann Epidemiol 8(8): 504-12.

PURPOSE: This community-based study in Anhui, China examined the sex-specific pattern of blood pressure (BP) and its major determinants between age 3 and 24 years. METHODS: BP, height, weight, and related covariates were obtained from all eligible subjects by consistent methods. A generalized additive model was used to explore independent relations between BP and covariates. The sample for analyses included a total of 14,277 subjects (7244 males and 7033 females). RESULTS: Systolic blood pressure (SBP) increased linearly with age to an apparent plateau around the age of 15 years in girls and 20 years in boys. Diastolic blood pressure (DBP) essentially paralleled SBP. Until the age of 10, both SBP and DBP were similar in boys and girls; thereafter, values for boys surpassed those for girls with an average difference of 9 mmHg and 4 mmHg for SBP and DBP, respectively, at 20 years of age. This sex difference appeared to persist into early adulthood. The independent relation between BP and each of the three major determinants (age, height, and weight) was nonlinear over the age range studied. Sex-specific regression models with linear terms for age, height and weight were developed for each of four age groups (3-9, 10-14, 15-19, 20-24 years). The 5th, 10th, 90th, and 95th percentiles based on the percentage of predicted values can serve as the cutoffs for low, normal-low, normal-high, and high BP. The predicted values were derived from the above regression models that take into account an individual's sex, age, height, and weight. CONCLUSIONS: This analysis provided important basis for classification of hypertension status and subsequent investigation of environmental risk factors in this population.

Tacci, J. A., B. S. Webster, et al. (1998). "Healthcare utilization and referral patterns in the initial management of new-onset, uncomplicated, low back workers' compensation disability claims." J Occup Environ Med 40(11): 958-63.

Most episodes of low back pain are considered non-specific in nature, with the vast majority resolving within 2 weeks and almost all resolving within 6 weeks regardless of the medical intervention. Recently published clinical guidelines have clearly delineated a limited set of circumstances that would indicate the need for specialist referral. The purpose of this study was to describe the healthcare utilization and physician referral patterns for new-onset, uncomplicated, low back workers' compensation disability cases randomly selected from a large insurance carrier data source. The provision of care in urgent care centers and emergency departments for both initial and main sources of care occurred more frequently than was probably indicated. For this selected group of uncomplicated low back pain cases, specialist care was provided more commonly than would be expected or indicated (36% of the sample was seen by a surgeon, while only 2% received surgery). In addition, referral to specialists (other than occupational medicine specialists) was often made sooner than would be expected or indicated, with a median of 13 days for such referrals. Such overutilization of resources can reasonably be expected to increase overall medical costs.

Su, H. J., Y. L. Guo, et al. (1998). "The NAT2* slow acetylator genotype is associated with bladder cancer in Taiwanese, but not in the Black Foot Disease endemic area population." Pharmacogenetics 8(2): 187-90.

Padungtod, C., B. L. Lasley, et al. (1998). "Reproductive hormone profile among pesticide factory workers." J Occup Environ Med 40(12): 1038-47.

Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone levels, as well as urinary levels of FSH, LH, and E1C, a metabolite of testosterone, were measured to investigate the adverse reproductive effects of organophosphate pesticides among Chinese factory workers who were occupationally exposed to ethylparathion and methamidophos. Thirty-four exposed workers were randomly chosen and recruited from a large pesticide factory, and 44 unexposed workers were selected from a nearby textile factory. A quantitative pesticide exposure assessment was performed among a subset of the exposed and unexposed workers. Information on potential confounders was collected in an interview. A single blood sample was collected at the end of a work shift, when each subject also donated a semen sample. Three first-voided urine samples were collected from each worker on 3 consecutive days. Urinary p-nitrophenol level at 1 hour after the work shift correlated with serum (r = 0.71, P < 0.01) and urinary (r = 0.51, P = 0.04) FSH levels. Stratifying by the subjects' exposure status, we found a significant negative correlation among the exposed group between urinary FSH level and sperm count (r = -0.61, P < 0.01) and between urinary FSH level and sperm concentration (r = -0.53, P = 0.03). Pesticide exposure alone was significantly associated with serum LH level (beta [coefficient of exposure effect] = 0.79; 95% confidence interval [CI] = 0.42, 1.16) but not with serum FSH or testosterone or with any urinary hormone levels. With adjustment for age, rotating shift work, current cigarette smoking, and current alcohol consumption, exposure significantly increased the serum LH level by 1.1 mIU/mL (95% CI = 0.34, 1.82). Meanwhile, the serum FSH level was slightly elevated (beta [coefficient of exposure effect] = 1.38; 95% CI = -0.09, 2.85) and the serum testosterone level was decreased (beta = -55.13; 95% CI = -147.24, 37) with increased pesticide exposure. Age and rotating shift work appeared to act as confounders. We conclude that organophosphate pesticides have a small effect on male reproductive hormones, suggestive of a secondary hormonal disturbance after testicular damage.

Nelson, H. H., J. K. Wiencke, et al. (1998). "Chromosome 3p14 alterations in lung cancer: evidence that FHIT exon deletion is a target of tobacco carcinogens and asbestos." Cancer Res 58(9): 1804-7.

Alterations in the FHIT gene region have been previously associated with smoking status and the occurrence of lung tumors. In the current study, we examined the nature of the mutations that occur at FHIT and the types of carcinogen exposures that are associated with FHIT alterations. We screened 40 primary lung tumors for the presence of point mutations within the coding exons of FHIT using PCR-single-strand conformational polymorphism. Tumors were also analyzed for allelic loss using microsatellite markers located in or near FHIT. No tumors contained point mutations within the coding region of the FHIT gene. However, several samples failed to generate a PCR product, suggesting that regions of the gene are homozygously deleted. Samples were reanalyzed for exon loss using PCR; 13 of 30 tumors failed to generate a PCR product, and 20 of 30 tumors were missing at least one FHIT exon or had loss (loss of heterozygosity or deletion) of one microsatellite marker, suggesting that regions of the gene are homozygously deleted. These data indicate that the FHIT gene has a novel pattern of mutational inactivation not seen previously with other tumor suppressor genes, most likely influenced by the proximity of the FRA3B region. There were no associations of age, sex, p53, or k-ras mutation and FHIT exon deletion. However, there was an association of smoking duration and asbestos exposure with FHIT exon loss, indicating that carcinogenic exposures may be causal in the generation of alterations in the FHIT region.

Lee, B. W., J. C. Wain, et al. (1998). "Association of cigarette smoking and asbestos exposure with location and histology of lung cancer." Am J Respir Crit Care Med 157(3 Pt 1): 748-55.

Prior studies have suggested that lung cancers that arise in association with cigarette smoking favor an upper-lobe location while those associated with asbestos exposure favor a lower-lobe location. An excess of adenocarcinomas has also been reported among cases not exposed to cigarette smoke as well as among those exposed to asbestos. However, these studies typically have not adjusted adequately for potential confounders such as the patient's age, sex, race, or family history of cancer. To better examine the effects of cigarette smoking and asbestos exposure on location and histology of lung cancer, we analyzed data from a large case-control study that included 456 patients with stage I or II lung cancer. Patients with upper-lobe tumors tended to have had more exposure to tobacco as assessed by pack-years smoked (54.7 versus 46.2, p = 0.07) and less time since quitting smoking (3.0 versus 5.5 yr, p = 0.05). In contrast to some prior reports, asbestos exposure was also associated with an upper-lobe location of tumor. Among those with upper-lobe tumors, 14.6% had a history of significant asbestos exposure compared with 5.4% of those with lower-lobe tumors (p < 0.01). The relationship between asbestos exposure and upper-lobe location of tumor was also statistically significant whether stratified by smoking or analyzed by multivariable logistic regression modeling. Adenocarcinomas were more likely among those with less exposure to cigarette smoke based on fewer pack-years smoked (41.5 versus 61.8, p = 0.0001) and more time since quitting smoking (5.0 versus 3.0 yr, p = 0.02). The proportion of patients with significant exposure to asbestos was lower among those with adenocarcinomas but was not statistically significant (9.5 versus 15.3%, p = 0.09). In multivariable logistic regression analysis, longer time since smoking exposure remained a significant predictor of adenocarcinomas (p < 0.02), but history of asbestos exposure did not predict tumor histology. Thus, in patients with lung cancer, both cigarette smoking and asbestos exposure histories favor an upper-lobe location of tumor. Longer time since smoking exposure favors adenocarcinomas, but the history of asbestos exposure does not appear to influence the tumor histology.

Lee, B. W., J. C. Wain, et al. (1998). "Association between diet and lung cancer location." Am J Respir Crit Care Med 158(4): 1197-203.

Lung cancers occur more commonly in the upper lobes than in the lower lobes, but its pathophysiologic basis is not well understood. Because numerous studies have reported a consistent inverse relationship between lung cancer risk and intake of certain vegetables and fruits, we hypothesized that the balance between diet-derived protective substances delivered via the circulation and cigarette-derived carcinogenic substances delivered via the airways would be less favorable in the upper lobes compared with the lower lobes, hence accounting for the upper lobe predominance of tumors among smokers. Thus, we examined the association between diet and tumor location in 328 patients with lung cancer. The ratio of upper to lower lobe tumors was 2.5:1.0. In univariate analysis, age, height, weight, sex, race, family history of cancer, education level, tumor histology, calories consumed per day, and intake of animal fat did not differ significantly between patients with upper versus lower lobe tumors. Predictors of tumor location in univariate analysis were family history of lung cancer; smoking history; history of asbestos exposure; and intakes of yellow-orange vegetables, alpha-carotene, beta-carotene, and vitamins A, C, and E. In multivariable logistic regression analysis, the independent predictors of upper lobe tumor location were family history of lung cancer (p = 0.03), history of asbestos exposure (p = 0.02), less intake of yellow-orange vegetables (p < 0.04), and less intake of vitamin E (p = 0.05). Our results show a strong inverse association between upper lobe location of lung cancer and intake of yellow-orange vegetables and vitamin E.

Lara-Marquez, M. L., A. Deykin, et al. (1998). "Analysis of T-cell activation after bronchial allergen challenge in patients with atopic asthma." J Allergy Clin Immunol 101(5): 699-708.

BACKGROUND: T helper cells are a heterogeneous group of cells that have phenotypic and functional differences. Activated T helper cells have been found in peripheral blood after allergen challenge of subjects with atopic asthma, but the phenotypes of specific T helper subpopulation involved remains to be identified. OBJECTIVE: To characterize the T cell activation markers that may be regulated by allergens, we analyzed peripheral blood lymphocytes obtained before and after allergen challenge from subjects with atopic asthma. METHODS: We analyzed the distribution of the cell surface activation markers, interleukin 2 receptor (IL-2R) and major histocompatibility complex class II antigens (MHC II) among T helper subpopulations classified as naive (CD45RA) or memory (CD45RO) phenotypes. Nine adult subjects with atopic asthma underwent bronchoprovacative allergen inhalation and isocapnic cold air hyperventilation (ISH) challenge followed by serial spirometry. Peripheral blood mononuclear cells (PBMC) were isolated at baseline and 2 and 24 hours after challenge. Four-color flow cytometry was used to analyze the expression and distribution in vivo of IL-2R and MHC II activation markers on naive and memory T cell subsets after challenge. RESULTS: At 2 and 24 hours after allergen challenge, there was a significant increase in the CD45RO+IL-2R+ T helper cells compared with baseline (mean +/- SE, baseline, 12.5% +/- 1% versus 2 hours, 18.1% +/- 1% and 24 hours, 17.8% +/- 2%, p < 0.025). MHC II expression was not significantly increased after challenge on naive and memory T helper cells and coexpression of IL-2R and MHC II was only found in a small proportion of CD45RO+ T helper cells (2.7% +/- 1%). No changes of IL-2R or MHC II expression on T helper subsets were observed after ISH challenge in the same patients. We also found that 31% to 46% of T helper cells coexpress CD45RA and CD45RO simultaneously, and upregulation of IL-2-R and MHC II expression occurs only on those T helper cells that express CD45RO. CONCLUSIONS: We have found that T helper cells express both CD45RA and CD45RO isoforms, which suggests the existence of a transitional phenotype among naive and memory T helper cells in peripheral blood. In subjects with atopic asthma, our in vivo analysis characterizes two populations of activated memory T helper cells based on the expression of IL-2R or MHC II surface molecules after allergen challenge.

Kodavanti, U. P., R. Hauser, et al. (1998). "Pulmonary responses to oil fly ash particles in the rat differ by virtue of their specific soluble metals." Toxicol Sci 43(2): 204-12.

Occupational exposure to residual oil fly ash (ROFA) particulate has been associated with adverse respiratory health effects in humans. We hypothesized that ROFA collected at different sites within an oil burning power plant, by virtue of its differing metal and sulfate composition, will induce differential lung injury. Ten ROFA samples collected at various sites within a power plant were analyzed for water- and 1.0 M HCl-leachable arsenic (As), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), manganese (Mn), nickel (Ni), lead (Pb), vanadium (V), zinc (Zn), and sulfur by inductively coupled plasma-atomic emission spectroscopy. All ROFA samples contained variable amounts of leachable (water-extractable) and 1.0 M HCl-extractable Fe, V, and/or Ni. All other metals, except Zn (ROFA No. 1 contained 3.43 and No. 3, 6.35 micrograms/mg Zn), were present in negligible quantities (< 1.0 microgram/mg) in the water extract. In vivo pulmonary injury from exposure to whole saline suspensions of these ROFA was evaluated. Male, SD rats (60 days old) were intratracheally instilled with either saline or saline suspension of whole ROFA (< 3.0 mass median aerodynamic diameter) at three concentrations (0.833, 3.33, or 8.33 mg/kg). After 24 h, lungs were lavaged and bronchoalveolar lavage fluid (BALF) was analyzed for cellular influx and protein content as well as lactate dehydrogenase (LDH) and N-acetyl glucosaminidase (NAG) activity and total hemoglobin as indicators of lung injury. ROFA-induced increases in BALF protein and LDH, but not neutrophilic inflammation, were associated with its water-leachable total metal, Ni, Fe, and sulfate content. However, the neutrophilic response following ROFA exposure was positively correlated with its water-leachable V content. Modest lung injury was observed with the ROFA samples which contained the smallest amounts of water-leachable metals. The ability of ROFA to induce oxidative burst in alveolar macrophage (AM) was determined in vitro using a chemiluminescence (CL) assay. AM CL signals in vitro were greatest with ROFA containing primarily soluble V and were less with ROFA containing Ni plus V. In summary, ROFA-induced in vivo acute pulmonary inflammation appears to be associated with its water-leachable V content; however, protein leakage appears to be associated with its water-leachable Ni content. ROFA-induced in vitro activation of AM was highest with ROFA containing leachable V but not with Ni plus V, suggesting that the potency and the mechanism of pulmonary injury will differ between emissions containing V and Ni.

Kales, S. N., J. M. Aldrich, et al. (1998). "Fitness for duty evaluations in hazardous materials firefighters." J Occup Environ Med 40(10): 925-31.

We analyzed results from the medical examinations of 340 hazardous materials firefighters and applied various objective standards in simulated fitness for duty determinations. Ten percent had elevated blood pressures, 13% had far visual acuity worse than 20/30 in one or both eyes, and 38% had abnormal audiometry. The strictest standards for resting blood pressure and corrected visual acuity would have failed 2% and 1% of the cohort, respectively. For audiometry, 0%-5% of the cohort would have failed, depending on the hearing requirements set. The strictest hearing standard did not allow for corrective devices so that few failures would be reversible. Visual and audiometric testing and measurement of resting blood pressure all have significant clinical yields. Studies of simulated firefighting are needed to establish minimum hearing requirements and determine whether corrective devices can be worn safely during duty.

Hauser, R., S. Elreedy, et al. (1998). "Urine vanadium concentrations in workers overhauling an oil-fired boiler." Am J Ind Med 33(1): 55-60.

Since fuel oil ash contains vanadium (V), the measurement of urinary levels of V may provide a biological marker in workers exposed to fuel oil ash. The usefulness of urine V samples as a biological monitoring tool ultimately depends on determining the appropriate time of sampling relative to when exposure occurs. Twenty boilermakers were studied during the overhaul of a large oil-fired boiler. A total of 117 urine samples were collected, 65 start-of-shift (S-O-S) and 52 end-of-shift (E-O-S) samples. Air V exposures were estimated with personal sampling devices and work history diaries. Air V concentrations ranged from 0.36 to 32.19 micrograms V/m3, with a mean +/- SD of 19.1 +/- 10.7, and a median of 18.5. On the first day of work on the overhaul, the V urine levels at the E-O-S (mean +/- SD were 1.53 +/- 0.53, median was 1.52 mg V/g creatinine) were significantly higher than those at the S-O-S (0.87 +/- 0.32, median was 0.83), P = 0.004. However, the V concentrations of the S-O-S urine samples on the last Monday of the study were not significantly different from the S-O-S urine levels on the previous Saturday, a time interval of about 38 hr between the end of exposure and sample collection. The Spearman correlation coefficient (r) between the S-O-S urine V and the workplace concentration of V dust during the previous day was r = 0.35. In summary, the results suggest a rapid initial clearance of V (elevating the E-O-S V concentration on the first day of work relative to the S-O-S concentration), followed by a slow clearance that is not complete 38 hr after the end of exposure, as evidenced by the Monday morning urine V concentrations. The Spearman correlations suggest that the S-O-S urine is preferred to the E-O-S urine for across-shift biological monitoring of V exposure.

Gassert, T. H., H. Hu, et al. (1998). "Long-term health and employment outcomes of occupational asthma and their determinants." J Occup Environ Med 40(5): 481-91.

Occupational asthma is common, yet little is known about long-term outcomes in the United States. A case series of 55 (of 72) occupational asthma patients were interviewed in follow-up 31 (+/- 15) months after removal from the cause to evaluate asthma severity and employment outcomes. Standard criteria were used to rate severity. At follow-up, 54 subjects (98%) had active asthma, of which 26 cases (47%) were "severe." Multivariate analysis showed increased risk of "severe" asthma for women (odds ratio [OR] = 13.8; 95% confidence interval [95% CI] = 1.3 to 151.7) and industrial sector workers (OR = 11.9; 95% CI = 1.3 to 109.8). Thirty-eight subjects (69%) were unemployed, risk being greater for those with "severe" asthma (OR = 20.9; 95% CI = 1.9 to 229.8) and for those without a college degree (OR = 7.3; 95% CI = 1.2 to 43.4). These results indicate that occupational asthma is disabling and probably irreversible for most patients referred to a specialty clinic, despite prolonged removal from causative agents. Women, industrial workers, and those with severe asthma or lack of a college degree appear to be at risk for worse outcomes. Greater efforts at primary and secondary prevention should lessen the burden of long-term illness and unemployment due to occupational asthma.

Xu, X., T. Niu, et al. (1997). "Environmental and occupational determinants of blood pressure in rural communities in China." Ann Epidemiol 7(2): 95-106.

PURPOSE: To identify and characterize major environmental and occupational determinants of blood pressure in rural communities in China. METHODS: In 1993 we conducted a large cross-sectional, community-based study of 20,216 residents aged 15 years or older, from the Yijing area of Anhui Province (8022 men, 12,194 women), one of whom were receiving treatment for hypertension. The mean systolic blood pressure was 116.7 +/- 19.5 mmHg for men and 113.2 +/- 19.4 mmHg for women. RESULTS: The mean diastolic blood pressure was 72.4 +/- 12.1 mmHg for men and 70.4 +/- 11.6 mmHg for women. Age and body mass index were the two most important determinants of blood pressure in this population. With controls for age and body mass index, height and weight remained significant predictors of blood pressure. Multiple linear regression analysis indicated that alcohol consumption, self-reported exposure to noise, drinking of tap water and pond water, occupational exposure to dust/fumes/gases, rice consumption, inferior housing, household crowdedness, and being unmarried were related to increased blood pressure levels. Vegetable intake, frequent consumption of meat at meals, high level of physical activity, exposure to straw-combustion smoke, and pesticide use were negatively associated with blood pressure. CONCLUSIONS: Our study demonstrated that a broad array of demographic, ergonomic, nutritional, and environmental factors are critical determinants of blood pressure in this rural Chinese population.

Wu, M. T., K. T. Kelsey, et al. (1997). "Elevated serum liver enzymes in coke oven and by-product workers." J Occup Environ Med 39(6): 527-33.

Coke oven and by-product workers are potentially exposed to coke oven emissions (COE), which contain hundreds of chemicals and are primarily composed of polycyclic aromatic hydrocarbons (PAH) and volatile organic compounds. Some of these compounds are hepatotoxins. The objective of this study was to examine the relationship between work in coke oven and by-product plants and serum activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), the most commonly performed liver-function tests. The exposed group was composed of current workers who had been employed at least 3 months in the two coke-operation work areas, including one coke oven plant and one by-product plant (Area I: n = 117; Area II: n = 96) of a large steel company in Taiwan. Control subjects (Area III: n = 131), not visiting either coke-operation area in the last 3 months, were collected from the administrative and nonproduction areas in the same company. PAH exposure, as a surrogate of COE, was measured monthly by PM-10 size-selective high-volume-area air samplers in or around these three areas between June and December 1990, as well as between November 1992 and June 1993. The mean total respiratory particulate PAH exposure levels (< 10 microns) between November 1992 and June 1993 in Area I, II, and III were 6.8 x 10(3), 2.1 x 10(3), and 6.5 x 10(1) ng/m3, respectively. AST, ALT, and hepatitis B surface antigen tests were performed in 1994. Workers who showed either AST or ALT levels greater than reference levels (abnormal > 25 IU/L) were regarded as showing "elevated liver enzyme levels." Workers in Area I had AST levels that were 17% higher (95% confidence interval [CI], 3% to 32%]) and ALT levels that were 35% higher (95% CI, 10% to 65%)] than those in Area III after controlling for appropriate confounders. The adjusted odds ratio (Area I vs Area III) for elevated liver enzymes was 4.4 (95% CI, 1.5 to 13.4). In addition, coke oven (n = 91) and by-product workers (n = 26) from Area I had ALT levels 37% and 45% higher, respectively, compared with control subjects from Area III, after adjusting for appropriate confounders. Similar effects are also seen for AST. Workers in Area II had slightly, but not significantly, elevated AST and ALT levels. These results indicate that workers most heavily exposed to COE exhibit elevated aminotransferase levels.

Wu, M. T., I. F. Mao, et al. (1997). "Serum liver function profiles in coking workers." Am J Ind Med 32(5): 478-86.

Coking workers are regularly exposed to coke oven emissions (COE), which consist mainly of polycyclic aromatic hydrocarbons and volatile organic compounds. In a previous cross-sectional study, we found that coking and by-product workers with heavy exposure to COE in the older of two coke operation areas in Taiwan had higher serum activities of hepatic aminotransferase than the controls. In this study, we further examine the relationship of exposure to COE with liver function profiles in coking workers. Liver function profiles included serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL). The exposed group included 88 workers working 3 months or more in the older coke oven plant. Fifty-nine referents, not visiting the coke operation areas in the last 3 months, came from the administrative area in the same company. Each participant wore a personal monitor that was used to measure benzene soluble fraction (BSF) of total particulates, as a surrogate of COE, for 3 consecutive days between August 1995 and February 1996. Serum liver function profiles, hepatitis B surface antigens, and anti-hepatitis C antibodies were examined in the morning following the exposure measurements. Exposure levels were categorized by exposure situations (high, medium, low) among coking workers. The high exposure group (n = 23) worked topside of the oven. The medium exposure group (n = 44) worked at the sideoven for more than 4 hr/day, whereas the low exposure group (n = 21) worked at the sideoven for less than 4 hr/day and mostly remained in the control rooms. The low exposure group was used as an internal comparison group. The median BSF concentrations for various exposure situations were as follows, high exposure group: 372 micrograms/m3, medium exposure group: 61 micrograms/m3, low exposure group: 49 micrograms/m3, and referents: 10 micrograms/m3. The coking workers (n = 88) did not significantly differ from the referents (n = 59) in any of the liver function profiles. Excluding the referents, workers in the high exposure group had a mean AST level that was 31% higher (95% confidence interval (CI) = 9-57%) and a mean ALT level that was 46% higher (95% CI = 7-98%) than those in the low exposure group after adjusting for appropriate confounders in multivariate models. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/L or ALT > 39 IU/L) was more common in the high exposure group than in the low exposure group (adjusted odds ratio = 4.4; 95% CI = 0.9-22.6). However, these associations were not found in GGT, ALP, or BIL. After controlling for the possible effects of nonoccupational factors on serum activity of AST and ALT, we conclude that increased AST and ALT levels among topside coking workers may be caused by heavy inhalation exposure to COE. Additionally, the adverse hepatic effect seems to be caused by a mixture of hazards, rather than a unique identifiable chemical.

Monson, R. R. and D. C. Christiani (1997). "Summary of the evidence: Occupation and environment and cancer." Cancer Causes Control 8(3): 529-31.

Lee, B. W., K. T. Kelsey, et al. (1997). "The prevalence of pulmonary and upper respiratory tract symptoms and spirometric test findings among newspaper pressroom workers exposed to solvents." J Occup Environ Med 39(10): 960-9.

To investigate the relationship between exposure to organic solvents and the presence of pulmonary and upper respiratory tract mucous membrane symptoms, we conducted a cross-sectional study of 215 newspaper pressroom workers who were occupationally exposed to organic solvent and lubricant mixtures. Thirty-four compositors, who were not occupationally exposed to the solvents or lubricants, served as controls. Pressroom workers and compositors underwent spirometric testing and were also asked about the presence of cough, phlegm, hemoptysis, dyspnea, wheezing, chest tightness, nose or throat irritation, eye irritation, and sinus trouble. The spirometric results did not significantly differ between the two groups. However, the pressroom workers were significantly more likely to report pulmonary or upper respiratory tract mucous membrane symptoms than were compositors (P < 0.005). An exposure-response relationship could be demonstrated when comparing the number of solvents exposed with the total number of symptoms (P < 0.001). Similarly, an exposure-response relationship could be demonstrated when comparing the frequency of use of each of the seven solvents with the total number of symptoms (P < 0.002). Each of these findings was supported in a multivariable linear regression model that adjusted for potential confounders such as age, smoking history, and number of years in the industry. A high prevalence of these symptoms was reported even though the degree of exposure to solvents and lubricants was within the current permissible exposure limits.

Kriebel, D., S. R. Sama, et al. (1997). "A field investigation of the acute respiratory effects of metal working fluids. I. Effects of aerosol exposures." Am J Ind Med 31(6): 756-66.

A study of cross-shift change in pulmonary function was conducted among workers exposed to metal working fluids (MWF) in an automobile parts manufacturing company. Three hundred eighty-six workers (216 machinists exposed to straight or soluble MWFs, and 170 nonmachinists) were studied for 1 day, performing spirometry at the beginning and end of their shift. Airborne concentrations of inhalable particulate, culturable bacteria, and endotoxin were measured. We observed an approximately threefold increase in the incidence of 5% or greater cross-shift decrement in forced expiratory volume during the first second among those with exposures above about 0.15 mg/m3, compared to those with exposures below about 0.08 mg/m3. There was some evidence that chronic respiratory symptoms were more prevalent among machinists than among nonmachinists, notably for chronic cough. Baseline FEV1 was about 3% lower on average among those with soluble MWF exposure compared to nonmachinists. These findings are consistent with earlier studies showing respiratory effects of MWFs.

Kreps, S. E., N. Banzet, et al. (1997). "Molecular biomarkers of early responses to environmental stressors: implications for risk assessment and public health." Rev Environ Health 12(4): 261-80.

Kelsey, K. T., D. Ross, et al. (1997). "Ethnic variation in the prevalence of a common NAD(P)H quinone oxidoreductase polymorphism and its implications for anti-cancer chemotherapy." Br J Cancer 76(7): 852-4.

The NAD(P)H quinone oxidoreductase (NQO1:EC is an important biotransformation enzyme system that is also known to metabolize important novel chemotherapeutic compounds. The gene that codes for this enzyme has recently been found to be polymorphic in humans. Here, we describe the ethnic distribution of the polymorphism and note that this may have implications for anti-tumour drug development and use.

Kales, S. N., G. N. Polyhronopoulos, et al. (1997). "Medical surveillance of hazardous materials response fire fighters: a two-year prospective study." J Occup Environ Med 39(3): 238-47.

Hazardous materials releases can cause substantial morbidity and mortality, and an increasing number of communities have developed hazardous materials (HAZMAT) teams to deal with such incidents. Little is known, however, about the health effects of chemical accidents on HAZMAT team participants. Baseline and periodic medical surveillance of all 40 fire fighters from the Metrofire Haz-mat team was conducted in 1992/1993 and 1995, respectively. A database on incidents responded to by the team during the study period was also developed. From June 1990 through April 1995, the team responded to a total of 34 hazardous materials incidents. No injuries to HAZMAT team members were reported. Few biochemical abnormalities were observed, and those that were could not be linked to specific exposures or incidents. Four individuals had abnormal audiometry on both occasions. There was a trend toward a lower percent predicted FEV1 for the entire group on follow-up: 106 +/- 13% vs 105 +/- 12%, P = 0.07. For fire fighters older than age 35 (n = 21), the percent predicted FEV1 was significantly lower at follow-up: 108 +/- 12% vs 106 +/- 14%, P = 0.01. The results suggest significant noise exposure and exposure to pulmonary irritants, which support the use of baseline and periodic audiometry and spirometry. The potential utility of other laboratory testing is also discussed.

Kales, S. N., G. N. Polyhronopoulos, et al. (1997). "Mechanisms of and facility types involved in hazardous materials incidents." Environ Health Perspect 105(9): 998-1001.

The purpose of this study was to systematically investigate hazardous materials (hazmat) releases and determine the mechanisms of these accidents, and the industries/activities and chemicals involved. We analyzed responses by Massachusetts' six district hazmat teams from their inception through May 1996. Information from incident reports was extracted onto standard coding sheets. The majority of hazardous materials incidents were caused by spills, leaks, or escapes of hazardous materials (76%) and occurred at fixed facilities (80%). Transportation-related accidents accounted for 20% of incidents. Eleven percent of hazardous materials incidents were at schools or health care facilities. Petroleum-derived fuels were involved in over half of transportation-related accidents, and these accounted for the majority of petroleum fuel releases. Chlorine derivatives were involved in 18% of all accidents and were associated with a wide variety of facility types and activities. In conclusion, systematic study of hazardous materials incidents allows the identification of preventable causes of these incidents.

Kales, S. N., G. N. Polyhronopoulos, et al. (1997). "Injuries caused by hazardous materials accidents." Ann Emerg Med 30(5): 598-603.

STUDY OBJECTIVE: To describe exposures that prehospital and ED personnel may encounter as a result of hazardous material incidents. METHODS: Retrospective analysis of hazardous material incident reports from six district hazardous material teams in Massachusetts from their inception through May 1996. RESULTS: The chemicals most frequently involved were various hydrocarbons and corrosive materials. Chlorine derivatives were involved in 18% of all incidents and 23% of all incidents resulting in victims. Victims were produced by 47 of 162 (29%) incidents. Respiratory exposures were the most frequent type of exposure and resulted in the largest number of victims transported to a hospital. Overall 24 of 26 (92%) incidents with chemical exposures resulted in symptomatic victims and 33 of 35 (94%) incidents produced victims requiring hospital transport. Respiratory symptoms were the most frequent, both in the number of incidents where they were observed and the total number of victims with symptoms. CONCLUSION: Multiple victim transport to EDs from a single hazardous material incident is most likely to result from an inhalation exposure to a respiratory irritant. Information from descriptive studies should allow improved preparation for potential hazardous material victims.

Glencross, P. M., J. M. Weinberg, et al. (1997). "Loss of lung function among sheet metal workers: ten-year study." Am J Ind Med 32(5): 460-6.

One hundred and twenty-two sheet metal workers in New England were examined over a 10-year interval for loss of pulmonary function and the development of asbestosis or asbestos-related pleural fibrosis. Regression models using the generalized estimating equation (GEE) approach were created to investigate the relationship between exposure and pulmonary function after adjusting for smoking status, age, height, and asbestos-related x-ray changes. A history of shipyard work was a significant contributor to the loss of forced vital capacity (FVC). Among smokers, loss in forced expiratory volume at 1 sec (FEV1) also had a significant relationship to prior shipyard work. There was a borderline significant relationship between percentage predicted FEV1 and cumulative years of asbestos exposure in smokers, as well as years-since-initial-exposure in never-smokers. This study supports previous findings of obstructive airway changes in asbestos-exposed workers and identifies shipboard work as an important predictor of loss in pulmonary function even years after shipyard exposure to asbestos has ceased.

Garcia-Closas, M., K. T. Kelsey, et al. (1997). "A case-control study of cytochrome P450 1A1, glutathione S-transferase M1, cigarette smoking and lung cancer susceptibility (Massachusetts, United States)." Cancer Causes Control 8(4): 544-53.

Cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase M1 (GSTM1) genetic polymorphisms are involved in the activation and detoxification of chemical carcinogens found in tobacco smoke; thus they may influence host susceptibility to lung cancer. In this study at Massachusetts General Hospital (Boston, MA, USA) of 416 cases and 446 controls (mostly White) we evaluated the association between the CYP1A1 MspI and GSTM1 polymorphisms and lung cancer risk, and their interaction with cigarette smoke. The CYP1A1 MspI heterozygous genotype was present in 18 percent of cases and 16 percent of controls, and one percent of cases and controls were CYP1A1 MspI homozygous variant. The GSTM1 null genotype was detected in 54 percent of cases and 52 percent of controls. After adjusting for age, gender, pack-years of smoking, and years since quitting smoking, while neither the CYP1A1 MspI heterozygous genotype alone nor the GSTM1 null genotype alone were associated with a significant increase in lung cancer risk, having both genetic traits was associated with a twofold increase in risk (95 percent confidence interval [CI] = 1.0-3.4). Our data did not provide enough evidence for a substantial modification of the effect of pack-years on lung cancer risk by the CYP1A1 MspI and GSTM1 genotypes. However, limitations of our study preclude a conclusion about this potential interaction.

Christiani, D. C. (1997). "[Exposure to organic dust and chronic respiratory diseases]." Pneumologie 51(12): 1098-100.

Christiani, D. C. and R. R. Monson (1997). "Introduction: Cancer in relation to occupational and environmental exposures." Cancer Causes Control 8(3): 269-70.

Cho, S. I., R. Hauser, et al. (1997). "Reproducibility of nasal peak inspiratory flow among healthy adults: assessment of epidemiologic utility." Chest 112(6): 1547-53.

STUDY OBJECTIVE: To assess the reproducibility of nasal peak inspiratory flow (PIFn). PARTICIPANTS: Twelve healthy nonsmoking volunteers were studied. METHODS: Repeated measurements of PIFn and oral (PIFm) peak inspiratory flow were performed for 5 consecutive days. Two methods of inhalation were compared. In the residual volume (RV) method, the forced maximal inspiratory maneuver was initiated from the end of a maximal expiration, while in the functional residual capacity (FRC) method, the maneuver was from the end of a tidal breath. Reproducibility was assessed by the intraclass correlation coefficient. Time trend for the 5 days was assessed by random effect models adjusting for different baseline for each subject. RESULTS: The intraclass correlation coefficient (ICC) of PIFn was 0.89 (lower limit of one-sided 95% confidence interval is 0.80) by the RV method and 0.78 (95% lower limit is 0.63) by the FRC method, suggesting that both methods have good reproducibility. These were similar to the ICCs of PIFm by each method. The FRC method did not show a significant time trend for PIFn. The RV method had a small, but significant, decreasing time trend of a magnitude considered inconsequential for the purpose of epidemiologic study. CONCLUSION: PIFn, measured from either RV or from FRC, showed good reproducibility and can be employed in epidemiologic studies investigating the upper airways' response to air pollutant exposure. Further studies of the relationships between PIFn and signs and symptoms of rhinitis are needed to evaluate the utility of this test for clinical and epidemiologic use.

Xu, X., K. T. Kelsey, et al. (1996). "Cytochrome P450 CYP1A1 MspI polymorphism and lung cancer susceptibility." Cancer Epidemiol Biomarkers Prev 5(9): 687-92.

We conducted a case-control study of 207 lung cancer patients and 283 controls to estimate the association of the MspI polymorphism in the cytochrome P450 CYP1A1 gene with lung cancer. The analysis of the CYP1A1 gene polymorphism was performed by RFLP analysis of PCR-amplified DNA. The association of the CYP1A1 polymorphism with lung cancer was assessed by logistic regression using the generalized additive modeling technique to adjust for race, education, smoking status, pack years, time since quitting smoking, asbestos exposures, and family cancer history. The frequencies of the MspI homozygote and heterozygote variant genotypes of CYP1A1 were 1% and 17%, respectively, in both lung cancer patients and controls. A significant association was found between the combined heterozygous and homozygous MspI variant of the CYP1A1 gene and lung cancer; the estimated odds ratio was 2.08 (95% confidence interval, 1.15-3.73). The association remained significant when we excluded the homozygous MspI variant individuals, the non-Caucasians, or the long-time tobacco quitters, and it was not modified by gender or cumulative cigarette consumption. In a specific histological cell type analysis, a positive association was found for each subtype of lung cancer, with no appreciable difference between cell types. In summary, our study demonstrated that the MspI variant CYP1A1 genotype is significantly associated with an increased risk of lung cancer among Caucasians with the odds ratio approximately, equivalent to 2 after controlling for important confounding factors. These results are similar to those obtained from reanalysis of published data on the combined CYP1A1 genotypes in a Japanese population (combined odds ratio, 1.95; 95% confidence interval, 1.17-3.28). Moreover, the elevated risk is noted in heterozygotes, i.e., individuals who carry only one copy of the variant gene.

Xu, X., T. Niu, et al. (1996). "Occupational and Environmental Risk Factors for Asthma in Rural Communities in China." Int J Occup Environ Health 2(3): 172-176.

Respiratory allergens such as dust, gases/fumes, and hay smoke, which are frequently present in agricultural settings, can cause or aggravate asthma. The purpose of this study was to examine the relationships between occupational and environmental exposures and asthma in Chinese rural communities. The study population consisted of 28,946 people 15 years old or older, living in rural areas of Anhui province, China. A modified Mandarin translation of the ATS-DLD questionnaire was administered by trained interviewers to request information about exposures to specific occupational/environmental agents and respiratory disorders. In Huaining, the prevalence of wheezing was 3.8% for men; 2.1% for women; the prevalence of asthma was 1.6% for men; 1.8% for women. In Zongyang, the prevalence of wheezing was 2.7% for men; 1.9% for women; the prevalence of asthma was 1.7% for men; 1.2% for women. With control for potential confounders such as gender, age, residential area, education level, and smoking status, the pooled adjusted odds ratios (ORs) of wheezing and asthma for the group exposed to wood/hay smoke were 1.36 (95% CI: 1.14-1.61) and 1.27 (95% CI: 1.02-1.58), respectively. For coal-stove users, the pooled adjusted ORs were 1.47 (95% CI: 1.09-1.98) for wheezing and 1.51 (95% CI: 1.05-2.17) for asthma. After stratification of the subjects by dust type, the estimated ORs for wheezing were 1.58 (95% CI: 1.02-2.44) among the group exposed to inorganic dust and 3.03 (95% CI: 1.25-7.33) among the group exposed to metal dust. Asthma was not shown to be significantly associated with any specific dust type. Findings of the present study are consistent with previously reported adverse respiratory health effects related to occupational/environmental exposures to wood/hay smoke and dust, and indicate the need for further occupational disease surveillance in rural communities.

LaMontagne, A. D., T. W. Mangione, et al. (1996). "Medical surveillance for ethylene oxide exposure: practices and clinical findings in Massachusetts hospitals." J Occup Environ Med 38(2): 144-54.

The medical surveillance requirements of the Occupational Safety and Health Administration's (OSHA) ethylene oxide (EtO) standard became effective in 1985. However, little is known about the nature of the response of EtO users to this regulatory requirement. In an effort to begin to understand this, we conducted a survey of EtO health and safety in Massachusetts hospitals (n = 92). We determined the cumulative incidence of provision of EtO medical surveillance, the characteristics of the surveillance interventions provided, and the clinical findings of EtO medical surveillance efforts in Massachusetts hospitals. From 1985 to 1993, medical surveillance for EtO exposure was provided one or more times in 62% of EtO-using hospitals. Sixty-five percent of EtO medical surveillance providers reported performance of all five medical surveillance procedures required by OSHA's EtO standard. Medical surveillance provider certification in occupational medicine or nursing, and a greater extent of coverage of written medical surveillance policies, were related to higher likelihoods of fulfillment of OSHA-required procedures. Twenty-seven percent of medical surveillance providers reported detection of EtO-related symptoms or conditions, ranging from mucous membrane irritation to peripheral neuropathy. These findings reveal wide-spread implementation of OSHA-mandated EtO medical surveillance, with concomitant incomplete fulfillment of OSHA-specified procedures. From the provider-based survey, we estimate that one or more workers at 19% of EtO-using Massachusetts hospitals have experienced EtO-related health effects.

Krinzman, S. J., G. T. De Sanctis, et al. (1996). "T cell activation in a murine model of asthma." Am J Physiol 271(3 Pt 1): L476-83.

To determine the mechanisms by which inhaled antigens produce pulmonary inflammation and bronchial hyperreactivity, we have developed a murine model of asthma. BALB/c mice are sensitized and challenged with ovalbumin (OVA). Compared with mice treated with phosphate-buffered saline (PBS), OVA-treated mice developed increased lung resistance, decreased dynamic compliance, and greater methacholine reactivity. Bronchoalveolar lavage fluid revealed significant increases in the proportion of neutrophils and eosinophils. Tissue sections of OVA-treated mice demonstrated goblet cell metaplasia and focal perivascular and peribronchial infiltrates composed of lymphocytes, neutrophils, and eosinophils. Analysis of thoracic lymphocytes via flow cytometry revealed an expansion of both CD4+ and B cell populations, with increased expression of interleukin-2 receptor on CD4+ T cells, indicated increased activation. There was also increased expression of CD44 on CD4+ and CD8+ lymphocytes, suggesting an expansion of the local memory cell population. These findings support the hypothesis that activation of T lymphocytes mediates allergic pulmonary inflammation and bronchial reactivity in asthma.

Krinzman, S. J., G. T. De Sanctis, et al. (1996). "Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model." J Clin Invest 98(12): 2693-9.

Activation of naive T cells requires at least two signals. In addition to the well characterized interaction of the T cell antigen receptor with the antigen/MHC expressed on an antigen-presenting cell, T cell activation also requires costimulation by a second set of signals. The best characterized costimulatory receptor is CD28, which binds to a family of B7 ligands expressed on antigen-presenting cells. In asthma, although activated T cells play a role in the initiation and maintenance of airway inflammation, the importance of T cell costimulation in bronchial hyperresponsiveness had not been characterized. Therefore, we tested the hypothesis that inhibition of the CD28:B7 costimulatory pathway would abrogate airway hyperresponsiveness. Our results show that blockade of costimulation with CTLA4-Ig, a fusion protein known to prevent costimulation by blocking CD28:B7 interactions, inhibits airway hyperresponsiveness, inflammatory infiltration, expansion of thoracic lymphocytes, and allergen-specific responsiveness of thoracic T cells in this murine model of allergic asthma.

Kales, S. N., M. J. Castro, et al. (1996). "Epidemiology of hazardous materials responses by Massachusetts district HAZMAT teams." J Occup Environ Med 38(4): 394-400.

Hazardous materials releases can cause substantial morbidity and mortality, but very few studies have systemically investigated them. We analyzed responses by Massachusetts' six district hazardous materials (HAZMAT) teams from the time of their inception through February 1994. Spills, leaks, and other escapes of materials caused or contributed to 67 of 85 (79%) incidents. Transportation-related accidents accounted for 13 of 83 (16%), whereas the remainder of the releases occurred at fixed facilities. The chemicals most frequently involved were various hydrocarbons and corrosive materials. Most incidents (60 of 85 [70%]) had no reported injuries. Civilians were injured in 18 of 85 (21%) incidents; regular fire fighter and/or police were injured in eight of 85 (9%) incidents; and HAZMAT team members in one of 85 incidents (1%). Systematic study is needed to identify preventable causes of HAZMAT responses as well as ideas for better control of secondary health effects.

Hauser, R., C. Daskalakis, et al. (1996). "A regression approach to the analysis of serial peak flow among fuel oil ash exposed workers." Am J Respir Crit Care Med 154(4 Pt 1): 974-80.

We investigated the association between exposure to fuel oil ash and acute airway obstruction in 31 boilermakers and 31 utility workers during the overhaul of a large oil-fired boiler. Air flow was assessed with self-recorded serial peak expiratory flow rate measurements (PEFR) using a mini-Wright meter. Exposure to thoracic particulates with an aerodynamic diameter of 10 gm or smaller (PM10) was assessed using personal sampling devices and detailed work diaries. All subjects were male, with an average age of 43 yr, and an average of 18 yr at their current trade. Average PM10 exposure on work days was 2.75 mg/m3 for boilermakers and 0.57 mg/m3 for utility workers. Three daily PEFR measurements (start-of-shift, end-of-shift, and bed-time) were analyzed simultaneously, using Huber linear regression. After adjustment for job title, welder status, age, height, smoking, and weld-years, for each mg/m3 increase in PM10, the estimated decline in PEFR was 13.2 L/min (p = 0.008) for end-of-shift, 9.9 L/min (p = 0.045) for bed-time, and 6.6 L/min (p = 0.26) for start-of-shift of the following day. This decline of the exposure effect over the 24-h period that follows was statistically significant (p = 0.004). No other factors were found to significantly modify the effect of exposure. Our results suggest that occupational exposure to fuel oil ash is associated with significant acute decrements in peak flow.

Christiani, D. C. (1996). "Organic dust exposure and chronic airway disease." Am J Respir Crit Care Med 154(4 Pt 1): 833-4.

Christiani, D. C. (1996). "Utilization of biomarker data for clinical and environmental intervention." Environ Health Perspect 104 Suppl 5: 921-5.

Of the 189 air toxics listed in the Clean Air Act, a substantial number are important in potentially causing adverse health effects in several organ systems. Although the major health effects are manifested as respiratory diseases, especially airways disease, these agents may cause cancer and premature mortality, probably from cardiopulmonary disease. Validated biologic markers may be useful in identifying early effects to improve our understanding of exposure-response relationships and clarify susceptibility. However, the knowledge obtained from epidemiologic studies utilizing these new molecular tools will reduce morbidity and mortality from air toxics only when they can be applied effectively in the prevention and control of disease. Intervention strategies using these markers can be used to identify etiologic factors and assess the effectiveness of exposure reduction, and, in some instances, chemoprevention. This paper illustrates examples of these intervention strategies and reviews the current strengths and limitations of environmental molecular epidemiology in controlling disease caused by air toxics.

Cheng, T. J., D. C. Christiani, et al. (1996). "Increased micronucleus frequency in lymphocytes from smokers with lung cancer." Mutat Res 349(1): 43-50.

We investigated whether lung cancer was associated with an increased micronucleus (MN) frequency in lymphocytes in a case-control study. Epidemiological data were obtained by an interviewer-administered questionnaire and included information on smoking history, intake of dietary micronutrients, general medical history, environmental and occupational exposures to mutagens and carcinogens, and family history of cancer. A modified cytokinesis-block method was used to determine individual MN frequency. Polymorphisms in glutathione S-transferase class mu were determined by PCR analysis. Overall, 55 controls and 42 cases were studied. MN frequency in cases and controls was not associated with age, smoking, metabolic genetic polymorphisms, environmental and occupational exposures, or medical history. Female controls had a significantly higher MN frequency than male controls (p = 0.05). Overall, MN frequency was significantly higher in cases than in controls (p < 0.01). Twenty-four cases (57%) had an MN frequency higher than the upper 95% confidence interval of the mean value for controls (11.5 MNs/1000 binucleated cells). Further analysis showed that, cases who were current and former smokers had significantly higher MN frequencies than controls (p = 0.04); this difference was not seen in the group that had never smoked. The significantly higher MN frequency among cases with a history of smoking may be attributable to the presence of lung neoplasm per se or to the interaction of smoking with endogenous factors associated with the development of lung cancer.

Xu, X., D. W. Dockery, et al. (1995). "Association of air pollution with hospital outpatient visits in Beijing." Arch Environ Health 50(3): 214-20.

Data collected at a community-based hospital in Beijing, China, were analyzed in an assessment of the association of air pollution with daily outpatient visits. Total suspended particle (TSP) measurements were available for 210 d (mean, 388 micrograms/m3; maximum, 1,255 micrograms/m3), and sulfur dioxide (SO2) measurements were available for 2 d (mean, 119 micrograms/m3; maximum, 478 micrograms/m3). The average number of daily hospital outpatient visits was 1,386; approximately 8.5% of these visits were to the surgery department, 7.9% were to the pediatrics department, and 20.6% were to the internal medicine department. A large increase in nonsurgery outpatient visits was observed in association with increases in both SO2 and TSP in linear regression models, after adjusting for temperature, humidity, season, and day of the week. The estimated effects (in which the most polluted days were compared with the least polluted days) on nonsurgery outpatient visits were increases of 20% (SE = 5%) and 17% (SE = 4%) in association with increases in SO2 and TSP, respectively. In a department-specific analysis, the association was found to be 1.5- to 2.0-fold stronger for pediatrics and internal medicine visits than for other types of visits. The separate associations of SO2 and TSP with internal medicine visits remained statistically significant when both SO2 and TSP were considered simultaneously and when adjustment was made for surgery visits. SO2 and TSP were found to be significant, independent predictors of internal medicine visits in both winter and summer.(ABSTRACT TRUNCATED AT 250 WORDS)

Wiencke, J. K., K. T. Kelsey, et al. (1995). "Correlation of DNA adducts in blood mononuclear cells with tobacco carcinogen-induced damage in human lung." Cancer Res 55(21): 4910-4.

The formation of carcinogen-DNA adducts within the respiratory epithelium is thought to be a critical factor in the induction of lung cancer from tobacco smoke. A reliable surrogate measure of carcinogen damage to the lung would be of great value in molecular epidemiological studies of cancer risk. The validity of measurements of DNA adducts formed from hydrophobic aromatic hydrocarbons in peripheral blood mononuclear cells (MNCs) was investigated by comparing the levels of aromatic DNA adducts detected in lung tissue from 31 lung cancer patients with those detected in MNCs from the same individuals using the 32P-postlabeling assay. The associations of smoking history and intake of dietary antioxidants with adduct levels also were assessed. Tissue-specific, as well as common DNA adducts were detected in lung and blood; total MNC adduct levels were highly correlated with total lung adducts. After smoking cessation, adduct levels appeared to decay in both tissues at similar rates. Multivariate analyses (Poisson regression modeling) indicated that dietary antioxidant intake (carotenoids, vitamin A, and retinol) modified the levels of aromatic DNA adducts in both the lungs and blood. Of all models tested, the optimal one for predicting lung adduct levels included the measure of blood MNC adduct levels only. Therefore, blood MNCs are a valid surrogate tissue for estimating the burden of DNA adducts in respiratory tissue in molecular epidemiological studies.

Wang, X., D. C. Christiani, et al. (1995). "Mutations in the p53 gene in lung cancer are associated with cigarette smoking and asbestos exposure." Cancer Epidemiol Biomarkers Prev 4(5): 543-8.

It has been proposed that the patterns of mutations in the p53 tumor suppressor gene will provide clues to the mechanisms of cancer occurrence. Cigarette smoking is known to be the greatest risk factor for lung cancer. Epidemiological evidence has also implicated radon and asbestos as exposures that significantly increase this disease risk; asbestos exposure synergistically enhances the lung cancer risk of smokers. Previous studies of the mutational spectra of the p53 gene in lung cancer have shown cigarette smoke and radon exposure to be associated with the induction of particular lesions or classes of lesions. We have investigated the p53 gene in surgically resectable lung cancers in 85 patients from the Massachusetts General Hospital. We found 25 (29%) patients to have somatic p53 mutations in their tumors. The patients with p53 mutations who were current smokers were significantly older (75.1 versus 59.8 years; P < 0.01 and had smoked for significantly more years (56.8 versus 41.2 years; P < 0.01) than had those without p53 changes. Consistent with other reports, we observed a large number (40%) of G:C to T:A transversion mutations, noting that their occurrence increased with increasing cumulative exposure to cigarette smoke. Interestingly, we also found that p53 mutations occurred significantly more frequently in patients with a history of occupational exposure to asbestos [3 of 60 (5%) for patients without p53 mutations versus 5 of 25 (20%) of those with p53 mutations; P < 0.05].(ABSTRACT TRUNCATED AT 250 WORDS)

Nelson, H. H., J. K. Wiencke, et al. (1995). "Ethnic differences in the prevalence of the homozygous deleted genotype of glutathione S-transferase theta." Carcinogenesis 16(5): 1243-5.

In humans the glutathione S-transferase (GST) genes encode four classes of proteins (GST) important in the detoxification of reactive electrophiles. Recently, a gene deletion polymorphism was discovered within the GST class theta locus that leads to a functional deficiency in GST theta activity within circulating red blood cells. In this study we have examined the ethnic distribution of this polymorphism using a polymerase chain reaction (PCR)-based genotyping method. Five different ethnic groups were studied: North American Caucasians, African-Americans, Mexican-Americans, Chinese and Koreans. The prevalence of the null genotype was highest among Chinese (64.4%), followed by Koreans (60.2%), African-Americans (21.8%) and Caucasians (20.4%), whereas the prevalence was lowest among Mexican-Americans (9.7%). Interestingly, the prevalence of the deleted genotype in Caucasians differed significantly when 257 individuals drawn from a nation wide organization were compared with 185 people from the New England area (23.7 versus 15.7%, P < 0.05, chi 2 test). These results indicate that there are major differences in the prevalence of this trait attributable to ethnicity and that ethnic origin even among Caucasians should be considered in studies of gene-environment interaction involving this polymorphism.

Marshall, M. D., S. N. Kales, et al. (1995). "Are reference intervals for carboxyhemoglobin appropriate? A survey of Boston area laboratories." Clin Chem 41(10): 1434-8.

CO is a leading cause of poisoning deaths in the US today. Treating physicians use the carboxyhemoglobin (COHb) % saturation to guide the diagnosis and treatment of CO intoxication. We conducted a telephone survey of hospitals and laboratories in the Boston area, focusing on methodology for COHb determination and accompanying COHb reference intervals. Among 130 facilities, 23 (18%) provide COHb analysis. All facilities that perform the COHb test utilize dedicated multiwave-length photometry. Reference intervals for COHb varied widely among facilities. Eight of 21 (38%) facilities give unacceptably high "normal intervals" for nonsmokers when compared with values available in the literature. Thirteen of 20 (65%) use reference intervals for smokers that are too low, and 3 of 20 (15%) use values that are too high. These reference values provided by the testing facilities may be misleading to the ordering physicians unfamiliar with background COHb saturations. This may lead to misdiagnoses, false reassurances, and perhaps less aggressive treatment than might be warranted. The results of this study argue for wider adoption of COHb reference intervals supported by the current literature.

Hauser, R., S. Elreedy, et al. (1995). "Upper airway response in workers exposed to fuel oil ash: nasal lavage analysis." Occup Environ Med 52(5): 353-8.

OBJECTIVES--Among other constituents, fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated. METHODS--A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter < or = 10 microns (PM10) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking. RESULTS--Personal sampling (one to 10 hour time weighted average) showed a range of PM10 concentrations of 50 to 4510 micrograms/m3, and respirable vanadium dust concentration of 0.10 to 139 micrograms/m3. In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM10 or respirable vanadium dust exposure could not be found. CONCLUSION--A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash.

Hauser, R., S. Elreedy, et al. (1995). "Airway obstruction in boilermakers exposed to fuel oil ash. A prospective investigation." Am J Respir Crit Care Med 152(5 Pt 1): 1478-84.

We prospectively investigated the lower airway response in boilermakers overhauling an oil-powered boiler. We studied 26 male boilermakers with a mean age (SD) of 43.3 (8.6) yr. Pre-exposure spirometry and methacholine challenge tests were performed before beginning the boiler overhaul; postexposure tests were performed after approximately 4 wk of work on the boiler. Exposure to particulates with an aerodynamic diameter of 10 microns and smaller (PM10) and respirable vanadium dust were estimated using daily work diaries and a personal sampling device for respirable particles. Using these estimates, we calculated average and peak exposure between pre- and postexposure tests for each subject. The average PM10 concentration ranged from 1.44 to 6.69 mg/m3, with a mean (SD) of 3.22 (1.42) mg/m3; the average vanadium concentration ranged from 2.2 to 31.3, with a mean (SD) of 12.2 (9.1) micrograms/m3. The mean postexposure fall in FEV1 was 140 +/- 160 ml (p < 0.01); 24 of 26 subjects had a drop in FEV1. For each subject, the adjusted change in FEV1 (delta FEV1.adj) was calculated by dividing the change in FEV1 by the average of the pre- and postexposure FEV1 values. The delta FEV1.adj was regressed, controlling age and current smoking status, on average and peak exposure to both PM10 and vanadium. There was a dose-response relationship between average and peak PM10 exposure and delta FEV1.adj: beta = -0.91% per mg/m3, p = 0.08 and beta = -1.03% per mg/m3, p = 0.03, respectively. However, there was no relationship between delta FEV1.adj and respirable vanadium dust concentration. Furthermore, there was no postexposure change in nonspecific airway responsiveness. In summary, we found a significant fall in FEV1 and a dose-response relationship between delta FEV1.adj and average and peak PM10 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Garcia-Closas, M. and D. C. Christiani (1995). "Asbestos-related diseases in construction carpenters." Am J Ind Med 27(1): 115-25.

To assess the association of minimal parenchymal fibrosis and pleural plaques with respiratory functional impairment, we conducted a survey of 631 asbestos-exposed construction carpenters. This population had a relatively low prevalence of radiographic abnormalities and lung function impairment. Pleural plaques was the asbestos-related disease most prevalent, followed by interstitial fibrosis with predominantly low profusion scores. The most frequent functional impairment was the obstructive pattern, followed by restrictive and mixed patterns. After adjusting for potential confounders, the presence of pleural plaques was significantly associated with a mixed respiratory pattern of impairment (OR = 3.7, 95% CI 1.4-12.3). Furthermore, our data were consistent with a weak association between pleural plaques and a predominantly restrictive defect (OR-1.3, 95% CI 0.4-3.9). This study also suggested an association between minimally detectable profusions and both obstructive (OR = 1.9, 95% CI 0.6-6.3) and mixed (OR = 1.6, 95% CI 0.3-7.1) defects. Although only 631 of a potential 7,649 active and retired union members participated in this first-time survey and were relatively young, these findings add new evidence to the functional importance of pleural fibrosis and minimal parenchymal fibrosis.

Christiani, D. C., T. Niu, et al. (1995). "Occupational Stress and Dysmenorrhea in Women Working in Cotton Textile Mills." Int J Occup Environ Health 1(1): 9-15.

The authors conducted a cross-sectional study of 895 never-smoking female textile workers, aged 20-40 years, employed in three cotton textile mills in Anhui Province, China, to assess the association of self-reported occupational stress with dysmenorrhea. Stress was assessed by means of a questionnaire incorporated into a larger, general health survey of textile workers. Dysmenorrhea was defined as abdominal/pelvic pain during menses. Proportions of no/low, moderate, and high levels of occupationally-related emotional stress among all the subjects were 56%, 23%, and 21%, respectively. The overall prevalence of dysmenorrhea in the population was 59.7%. The adjusted odds ratios of dysmenorrhea for women who had moderate and high levels of occupational stress relative to those with low levels were 1.6 (95% CI:1.1-2.2) and 2.3 (95% CI:1.6-3.4), suggesting an exposure-response relationship. The estimated odds ratio based on assigned scores (0, 1, and 2 assigned for no/low, moderate, and high degrees of occupational stress) was 1.5 (95% CI:1.3-1.8). In the analyses stratified by the mills and the women's job titles, a positive association was found in all groups. The association remained significant (OR = 1.6, 95% CI:1.3-2.0) when the analysis was restricted to those women with only one reported livebirth pregnancy. The findings suggest that high degrees of occupational stress predispose female textile workers to dysmenorrhea.

Cheng, T. J., D. C. Christiani, et al. (1995). "Glutathione S-transferase mu genotype, diet, and smoking as determinants of sister chromatid exchange frequency in lymphocytes." Cancer Epidemiol Biomarkers Prev 4(5): 535-42.

Polymorphisms in inherited metabolic traits and intake of dietary antioxidants have been reported to be associated with risk for the development of lung cancer in smokers. This increased risk of lung cancer is presumably attributable to the accumulation of DNA damage. We conducted a study to investigate whether genetic metabolic variants and antioxidant consumption affected the sister chromatid exchange (SCE) level in lymphocytes. Study subjects were 78 friends and spouses of cases from a case-control study of lung cancer designed to investigate the association of metabolic polymorphisms with lung cancer. The metabolic traits studied included glutathione S-transferase class mu and variants of P-450 isoenzymes CYP1A1 and CYP2D6. Intake of antioxidants including vitamins A, C, and E and selenium was determined through the administration of a validated, semiquantitative food frequency questionnaire. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was also obtained in an interviewer-administered questionnaire. Smoking status was found to be significantly associated with SCE frequency. In addition SCE frequency decreased with the period of time since quitting smoking. The presence of one or more glutathione S-transferase class mu alleles was associated with significantly lower SCE. Higher intake of vitamin A and selenium was also inversely associated with SCE level. Thus, the results suggest that glutathione S-transferase class mu and the intake of vitamin A and selenium may modulate the accumulation of chromosomal damage in lymphocytes.

Cheng, T. J., D. C. Christiani, et al. (1995). "Comparison of sister chromatid exchange frequency in peripheral lymphocytes in lung cancer cases and controls." Mutat Res 348(2): 75-82.

Cytogenetic alterations have been associated with the occurrence of many cancers. However, limited data exist to address whether increased chromosomal changes in surrogate normal tissue are similarly associated with malignancy. As part of an ongoing case-control study of lung cancer, we have studied the factors that affect sister chromatid exchange (SCE) frequency in lymphocytes from lung cancer patients. Further, we sought to investigate whether the factors that affect SCE frequencies were comparable in lung cancer cases and controls. Cases had newly diagnosed, operable primary lung cancer. Controls were friends and spouses of cases. Detailed information on smoking, family history of cancer, medical history, and environmental and occupational exposures was obtained in an interviewer-administered questionnaire. Intake of antioxidants was also determined through the administration of a validated semiquantitative food frequency questionnaire. Metabolic traits studied included the polymorphic glutathione-S-transferase class mu (GST-mu) and variants of P450 isoenzymes CYP1A1 and CYP 2D6. Overall, 78 cases and 78 controls were included in the analysis. Although there was a small number of lung cancer patients who had never smoked in the study (9% of cases), these patients had higher SCE frequencies than current or former smokers. This suggests that factors associated with genomic instability may also play a role in the pathogenesis of lung cancer. The best fit model for SCE frequency, which had been previously generated from control data alone, included age, gender, smoking, GST-mu, and vitamin A intake. However, when this model was applied to lung cancer patients, smoking was not associated with an elevated SCE frequency. Thus, it is not clear that SCE frequency data in prevalent lung cancer cases and controls are comparable.

Cheng, T. J., D. C. Christiani, et al. (1995). "Mutant frequency at the hprt locus in human lymphocytes in a case-control study of lung cancer." Mutat Res 332(1-2): 109-18.

A clonal assay to determine the mutant frequency (MF) at the hypoxanthine-guanine phosphoribosyl transferase (hprt) locus in human lymphocytes has been used by a number of investigators to study exposure to mutagens and carcinogens in a variety of populations. We have studied hprt MF in 106 subjects (40 controls and 66 cases) enrolled in a case-control investigation of lung cancer. Epidemiological data collected included smoking history, intake of dietary micronutrients, and occupational and environmental exposures as well as medical history, all obtained from an interviewer-administered questionnaire. All subjects were also genotyped for the known polymorphism in glutathione S-transferase class mu (GST-mu). In analysis of cases and controls, hprt MF was not associated with age, smoking, the polymorphism in GST mu, dietary intake, occupational exposures, family history of cancer or usage of medications. Since MF and cloning efficiency (CE) are not independent when CE is low, further analysis in cases and controls with a CE greater than or equal to 30% (27 cases and 22 controls) was also conducted. In analysis of controls, hprt MF increased with age and was inversely associated with intake of folate and vitamins A and C. The presence of lung cancer was not associated with hprt MF. Thus, our study supports the previous observation that dietary components may affect the MF at the hprt locus.

Xu, X., M. Ding, et al. (1994). "Association of rotating shiftwork with preterm births and low birth weight among never smoking women textile workers in China." Occup Environ Med 51(7): 470-4.

1035 married women workers in three modern textile mills in Anhui, China were surveyed to investigate the association of rotating shiftwork with low birth weight and preterm birth in 1992. Information on reproductive health, occupational exposure history, and other covariates including age at pregnancy, time and duration of leave from job since pregnancy, and mill location was obtained by trained nurses with a standardised questionnaire. This analysis was limited to 845 women (887 live births), who were middle or high school graduates, never smokers, and non-alcohol drinkers. About 72% of the women worked an eight day cycle with shift changes every two days throughout pregnancy. Mean gestational age was 38.8 and 39.0 weeks for shift and regular schedule workers, respectively. Multiple linear regression was used to adjust for confounding factors including maternal age at pregnancy, order of live birth, mill location, job title, occupational exposure to dust/gases/fumes, stress, carrying and lifting of heavy loads, working in a squat position, time and duration of leave from the job since pregnancy, and indoor coal combustion for heating. The adjusted difference in gestational age associated with rotating shifts was statistically significant (beta = -0.44 (SE 0.20) weeks.) Mean birth weights were 3248 g and 3338 g for rotating shift workers and regular schedule workers respectively. The estimated effect of rotating shiftwork on birth weight was -79 (SE 42) g. When the analysis was restricted to first order live births or to production workers, the estimated effects of rotating shiftwork on both gestational age and birth weight were significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Smith, C. M., K. T. Kelsey, et al. (1994). "Inherited glutathione-S-transferase deficiency is a risk factor for pulmonary asbestosis." Cancer Epidemiol Biomarkers Prev 3(6): 471-7.

Pulmonary diseases attributable to asbestos exposure constitute a significant public health burden, yet few studies have investigated potential genetic determinants of susceptibility to asbestos-related diseases. The glutathione-S-transferases are a family of conjugating enzymes that both catalyze the detoxification of a variety of potentially cytotoxic electrophilic agents and act in the generation of sulfadipeptide leukotriene inflammatory mediators. The gene encoding glutathione-S-transferase class mu (GSTM-1) is polymorphic; approximately 50% of Caucasian individuals have a homozygous deletion of this gene and do not produce functional enzyme. Glutathione-S-transferase mu (GST-mu) deficiency has been previously reported to be associated with smoking-induced lung cancer. We conducted a cross-sectional study to examine the prevalence of the homozygous deletion for the GSTM-1 gene in members of the carpentry trade occupationally exposed to asbestos. Members of the United Brotherhood of Carpenters and Joiners of America attending their 1991 National Union conference were invited to participate. Each participant was offered a chest X-ray and was asked to complete a comprehensive questionnaire and have their blood drawn. All radiographs were assessed for the presence of pneumoconiosis in a blinded fashion by a National Institute for Occupational Safety and Health-certified International Labor Office "B" reader. Individual GSTM-1 status was determined using polymerase chain reaction methods. Six hundred fifty-eight workers were studied. Of these, 80 (12.2%) had X-ray abnormalities associated with asbestos exposure. Individuals genetically deficient in GST-mu were significantly more likely to have radiographic evidence of nonmalignant asbestos-related disease than those who were not deficient (chi 2 = 5.0; P < 0.03).(ABSTRACT TRUNCATED AT 250 WORDS)

Korrick, S. A., K. M. Rest, et al. (1994). "Use of state workers' compensation data for occupational carpal tunnel syndrome surveillance: a feasibility study in Massachusetts." Am J Ind Med 25(6): 837-50.

The purpose of this study was to determine the feasibility of using Massachusetts workers' compensation data for passive surveillance of occupational carpal tunnel syndrome (OCTS). Workers' compensation claims for OCTS (n = 358) and for possible cases of OCTS (n = 1,121) active during the first 6 months of 1989 were identified. The availability and distribution of demographic and employment descriptors were assessed. Medical records on a sample of the claims were reviewed to validate the diagnosis of OCTS. Age, gender, and occupation were available for less than 47% of the reported cases of OCTS. The majority (88%) of cases on whom medical record review was performed had a physician's diagnosis of carpal tunnel syndrome (CTS), and most of this group had confirmatory nerve conduction studies or electromyography. However, there were fundamental limitations to workers' compensation based disease surveillance in Massachusetts, including underascertainment of cases, potential ascertainment biases, delayed case reporting, limited access to specific diagnostic information, and incomplete and sometimes inaccurate information. These limitations are likely to be applicable in many, if not most, states and must be made clear in any analyses based on workers' compensation data.

Kelsey, K. T., F. Xia, et al. (1994). "Genotoxicity to human cells induced by air particulates isolated during the Kuwait oil fires." Environ Res 64(1): 18-25.

In an effort to examine the potential of exposure to soot from the 1991 oil fires in the Kuwait desert for inducing genetic effects we studied the in vitro genotoxicity of this material. Air particulates isolated near the Kuwait oil fires were studied using three assays. Dose-dependent increases were observed for both sister chromatid exchanges in human peripheral blood lymphocytes and mutation at the hprt locus in the metabolically competent human lymphoblast cell line AHH-1. Similar magnitudes of response were seen using these two assays when testing a standard air particulate sample which had been isolated from the Washington, DC, area. Using the 32P-postlabeling assay, no increase in DNA adduct formation was observed in AHH-1 cells treated with particulates isolated from sampling in Kuwait.

Kales, S. N. and D. C. Christiani (1994). "Progression of chronic obstructive pulmonary disease after multiple episodes of an occupational inhalation fever." J Occup Med 36(1): 75-8.

A carding machine operator in a synthetic fabric plant experienced marked symptomatic deterioration of obstructive pulmonary disease after multiple episodes of an occupational inhalation fever. Polytetrafluoroethylene was used in the industrial process and polymer fume fever is suspected as a cause of his febrile illnesses. A state industrial hygiene inspection revealed that major repairs had been performed on an air scrubber system in close proximity to the patient's work area after he had left the plant because of disability. We believe that this case provides further evidence that polymer fume fever is not always a benign, self-limited illness, especially when workers suffer multiple episodes and/or have underlying pulmonary disease.

Kales, S. N., F. Pentiuc, et al. (1994). "Pseudoelevation of carboxyhemoglobin levels in firefighters." J Occup Med 36(7): 752-6.

Carbon monoxide is a common and potentially lethal exposure documented by an elevated carboxyhemoglobin (COHb) level. We conducted an investigation of unexpectedly high carboxyhemoglobin levels in a group of firefighters. Twelve of 34 (35%) nonsmokers tested had levels greater than 4% COHb and 9 of 34 (26%) had levels of 10% or higher. Quadruplicate blood samples from hospital staff and firefighters were sent in duplicate to the original laboratory, which used manual spectrophotometry, and to a second reference facility using a cooximeter. Cooximeter results were lower and also more reproducible. By cooximetry, all 24 nonsmoking firefighters retested had COHb levels less than 3%. Cooximetry is widely available and is the most suitable methodology in clinical situations. Spurious results despite the use of a large reference laboratory argue for the standardization of analytic methods for COHb among laboratories.

Kales, S. N., J. Feldman, et al. (1994). "Carboxyhemoglobin levels in patients with cocaine-related chest pain." Chest 106(1): 147-50.

Carboxyhemoglobin (COHb) levels were measured in patients who came to an emergency department complaining of acute chest pain. For subjects not receiving prior oxygen therapy, those with cocaine-related chest pain (n = 10) had a higher mean COHb level than a comparison group (n = 28) with nonischemic chest pain (4.50 +/- 2.40 vs 2.73 +/- 0.66; p < 0.05). Four of the seven (57 percent) who smoked crack had COHb levels greater than 4.5 percent, while only one of six (17 percent) smokers of only tobacco had such a level. These findings suggest an additional mechanism, the formation of COHb, which could aggravate cocaine-induced cardiotoxicity.