Specialty: Pulmonary Medicine
Brigham and Women’s and Faulkner Hospitals
1153 Centre Street
Jamaica Plain, MA 02130
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.
Israel, E., T. R. Banerjee, et al. (2001). "Effects of inhaled glucocorticoids on bone density in premenopausal women." N Engl J Med 345(13): 941-7.
BACKGROUND: Inhaled glucocorticoids are the most commonly used medications for the long-term treatment of patients with asthma. Whether long-term therapy with inhaled glucocorticoids reduces bone mass, as oral glucocorticoid therapy does, is controversial. In a three-year prospective study, we examined the relation between the dose of inhaled glucocorticoids and the rate of bone loss in premenopausal women with asthma. METHODS: We studied 109 premenopausal women, 18 to 45 years of age, who had asthma and no known conditions that cause bone loss and who were treated with inhaled triamcinolone acetonide (100 microg per puff). We measured bone density by dual-photon absorptiometry at base line, at six months, and at one, two, and three years. Serum osteocalcin and parathyroid hormone and urinary N-telopeptide, cortisol, and calcium excretion were measured serially. We measured inhaled glucocorticoid use by means of monthly diaries, supported by the use of an automated actuator-monitoring device. RESULTS: Inhaled glucocorticoid therapy was associated with a dose-related decline in bone density at both the total hip and the trochanter of 0.00044 g per square centimeter per puff per year of treatment (P= 0.01 and P=0.005, respectively). No dose-related effect was noted at the femoral neck or the spine. Even after the exclusion of all women who received oral or parenteral glucocorticoids at any time during the study, there was still an association between the decline in bone density and the number of puffs per year of use. Serum and urinary markers of bone turnover or adrenal function did not predict the degree of bone loss. CONCLUSIONS: Inhaled glucocorticoids lead to a dose-related loss of bone at the hip in premenopausal women.
O'Donnell, W. J., W. Pieciak, et al. (1998). "Clearance of Pneumocystis carinii cysts in acute P carinii pneumonia: assessment by serial sputum induction." Chest 114(5): 1264-8.
STUDY OBJECTIVES: To determine the feasibility of repeat sputum induction in acute Pneumocystis carinii pneumonia (PCP) and to define the rate of clearance of P carinii cysts from the respiratory tract of HIV-seropositive patients with acute PCP. DESIGN: Prospective cohort evaluation. SETTING: University medical center. PARTICIPANTS: Twenty-four HIV-seropositive subjects with acute PCP. MEASUREMENTS: Sputum induction for P carinii 2, 3, 4, and 6 weeks after initial diagnosis, and follow-up for 1 year. RESULTS: Eighty-eight percent of subjects had residual cysts at 2 weeks, 76% at 3 weeks, 29% at 4 weeks, and 24% at 6 weeks postdiagnosis. A prior AIDS-defining illness (p = 0.033) or prior PCP (p = 0.004) predicted relapse within 6 months, but persistent cysts at 3 weeks did not; 8 of 16 sputum-positive subjects and 1 of 5 sputum-negative subjects experienced a relapse within 6 months (p = 0.34). Secondary prophylaxis with trimethoprim-sulfamethoxazole was associated with a reduced risk of relapse. CONCLUSIONS: Serial sputum induction coupled with direct fluorescent antibody staining is a feasible, noninvasive method of respiratory tract surveillance for the eradication of P carinii during and after acute PCP. Three-quarters of HIV-seropositive patients with acute PCP have persistent cysts in their lungs at the end of antimicrobial treatment, despite clinical recuperation, but only one quarter have residual cysts 6 weeks postdiagnosis. A prior AIDS-defining illness and prior PCP are positively associated, and subsequent trimethoprim-sulfamethoxazole prophylaxis is negatively associated, with relapse within 6 months, while persistent organisms at 3 weeks do not appear to be a significant predictor of relapse risk.
Fine, M. J., L. J. Hough, et al. (1997). "The hospital admission decision for patients with community-acquired pneumonia. Results from the pneumonia Patient Outcomes Research Team cohort study." Arch Intern Med 157(1): 36-44.
BACKGROUND: The hospital admission decision directly influences the magnitude of resource use in patients with community-acquired pneumonia, yet little information exists on how medical practitioners make this decision. OBJECTIVES: To determine which factors medical practitioners consider in making the hospital admission decision and which health care services they believe would allow ambulatory treatment of low-risk hospitalized patients with community-acquired pneumonia. METHODS: Medical practitioners responsible for the hospital admission decision for low-risk patients with community-acquired pneumonia were asked to describe patient characteristics at initial examination that influenced the hospitalization decision, and to identify the health care services that would have allowed initial outpatient treatment of hospitalized patients. RESULTS: A total of 292 medical practitioners completed questionnaires for 472 (76%) of the 624 low-risk patients eligible for this study. Although all patients had a predicted probability of death of less than 4%, practitioners estimated that 5% of outpatients and 41% of inpatients had an expected 30-day risk of death of more than 5%. Univariate analyses identified 3 practitioner-rated factors that were nearly universally associated with hospitalization: hypoxemia (odds ratio, 173.3; 95% confidence interval, 23.8-1265.0), inability to maintain oral intake (odds ratio, 53.3; 95% confidence interval, 12.8-222.5), and lack of patient home care support (odds ratio, 54.4; 95% confidence interval, 7.3-402.6). In patients without these 3 factors, logistic regression analysis demonstrated that practitioner-estimated risk of death of more than 5% had a strong independent association with hospitalization (odds ratio, 18.4; 95% confidence interval, 6.1-55.7). Practitioners identified home intravenous antibiotic therapy and home nursing observation as services that would have allowed outpatient treatment of more than half (68% and 59%, respectively) of the patients initially hospitalized for treatment. CONCLUSIONS: Practitioners' survey responses suggest that the availability of outpatient intravenous antimicrobial therapy and home nursing care would allow outpatient care for a large proportion of low-risk patients who are hospitalized for community-acquired pneumonia. These data also suggest that methods to improve practitioners' identification of low-risk patients with community-acquired pneumonia could decrease the hospitalization of such patients. Future studies are required to help physicians identify which low-risk patients could safely be treated in the outpatient setting on the basis of clinical information readily available at presentation.
Simon, P. M., A. Pope, et al. (1989). "Naloxone does not alter response to hypercapnia or resistive loading in chronic obstructive pulmonary disease." Am Rev Respir Dis 139(1): 134-8.
To assess the role of endogenous opioid peptides in ventilatory control in patients with chronic obstructive lung disease, we measured the ventilatory and mouth occlusion pressure responses to hypercapnia and the compensatory response to an inspiratory resistive load in 11 male patients with COPD before and after intravenous administration of naloxone or placebo on 2 separate days. There were no statistically significant differences between naloxone and placebo administration in any index of ventilatory response to CO2 or resistive loading. When an inspiratory resistive load was added during CO2 rebreathing, minute ventilation at PETCO2 = 50 mm Hg in all 11 patients decreased significantly (p less than 0.05) with placebo and naloxone. In response to the inspiratory resistive load, in eight of the 11 patients mouth occlusion pressure (P0.1) did not increase; these eight subjects were classified as noncompensators. Naloxone did not affect the P0.1 response to inspiratory resistive loading, either in the group as a whole or in the subgroup of eight patients classified as noncompensators. Our study was unable to demonstrate that increased activity of endogenous opioid peptides suppresses the ventilatory response to CO2 or resistive loading in patients with chronic obstructive lung disease.
Simon, P. M., R. M. Schwartzstein, et al. (1989). "Distinguishable sensations of breathlessness induced in normal volunteers." Am Rev Respir Dis 140(4): 1021-7.
Various theories about the genesis of dyspnea have often assumed that the sensation is similar from patient to patient and is generated by a single underlying mechanism. To investigate whether breathlessness induced in normal volunteers by different stimuli represents one or more than one sensation, we studied 30 subjects in whom breathlessness was induced by each of 8 different stimuli: breath-holding, CO2 inhalation, inhalation of CO2, with ventilation voluntarily targeted below the level dictated by chemical drive, breathing with a resistive load, breathing with an elastic load, voluntary elevation of functional residual capacity, voluntary limitation of tidal volume, and exercise. For each stimulus, subjects were asked to choose description of their sensation(s) of breathlessness from a questionnaire listing 19 descriptors. The responses from this questionnaire were evaluated using cluster analysis to search for relationships among descriptors and to identify natural groupings. We found that distinct groups of descriptors emerged, i.e., subjects could distinguish different sensations of breathlessness. In addition, we found an association between certain descriptor groups and stimuli. We conclude that the term breathlessness may encompass multiple sensations, and, therefore, may not be explainable by a single physiologic mechanism.
Lahive, K. C., J. W. Weiss, et al. (1988). "Low dose aminophylline selectively increases upper airway motor activity in normals." Respir Physiol 72(2): 163-70.
Because certain pharmacologic agents differentially influence upper airway and diaphragm motor activity, we postulated that the adenosine antagonist theophylline might preferentially increase alae nasi activity in human subjects. Using a double-blinded, randomized, placebo controlled design, we studied the effect of low dose aminophylline (1-2 mg/kg) on alae nasi and diaphragm surface electromyographic (EMG) activity. Seven healthy volunteers served as subjects for two trials on separate days. Subjects breathed from a close circuit while end tidal PCO2 was held constant in the eucapnic range. During each trial we recorded EMG signals from the alae nasi and diaphragm before and after intravenous infusion of either aminophylline or placebo. After the administration of aminophylline, the mean alae nasi EMG signal increased 87 +/- 31 (SD)% (P less than 0.005) while the mean diaphragmatic EMG signal did not change. There was no significant change in either the alae nasi or diaphragmatic EMG signal after placebo. There was no change in minute ventilation, tidal volume, or respiratory frequency after either aminophylline or placebo. We speculate that low dose aminophylline produces a selective increase in upper airway muscle activity through stimulation of the reticular activating system.
Lahive, K. C., J. W. Weiss, et al. (1988). "Alpha-methyldopa selectively reduces alae nasi activity." Clin Sci (Lond) 74(5): 547-51.
1. Sedatives such as the benzodiazepines and alcohol reduce upper airway muscle activity. We hypothesized that a sedating antihypertensive, alpha-methyldopa, might have similar effects. To investigate this hypothesis we studied the effect of alpha-methyldopa on alae nasi electromyographic (EMG) activity during hypercapnia. 2. We studied ten healthy subjects and three subjects with obstructive sleep apnoea during CO2-stimulated breathing. In a preliminary study four subjects demonstrated a fall in alae nasi EMG activity 4 h after the ingestion of 500 mg of alpha-methyldopa during CO2 rebreathing. 3. In six additional normal subjects and three subjects with obstructive sleep apnoea, we studied the alae nasi EMG activity during steady-state hypercapnia with PCO2 held constant 5 torr (0.7 kPa) above baseline. On 2 separate days we studied subjects before and 2 h after they had ingested 750 mg of alpha-methyldopa or placebo. 4. In the normal subjects the mean alae nasi EMG activity fell by 34% 2 h after ingestion of alpha-methyldopa (P less than 0.05) without a change in other ventilatory parameters. 5. In the sleep apnoea group the individual mean alae nasi EMG activity fell 16-49%, with ventilation and tidal volume falling in one patient. 6. We conclude that alpha-methyldopa selectively reduces upper airway motor activity.
Schwartzstein, R. M., K. Lahive, et al. (1987). "Cold facial stimulation reduces breathlessness induced in normal subjects." Am Rev Respir Dis 136(1): 58-61.
Patients with breathlessness commonly describe subjective relief when seated near an open window or in front of a fan. Previous studies suggest that a flow of air or application of cold solutions to the face, nasal mucosa, or pharynx may alter ventilation. We hypothesized that a flow of cold air directed against the cheek would reduce the sensation of breathlessness associated with loaded breathing. Sixteen subjects breathed on a device with an inspiratory resistive load (63 cm H2O/L/s) while PCO2 was maintained at 55 torr for 5 min. All studies were performed 4 times with each subject, twice with cold air directed against the cheek (4 degrees to 10 degrees C, 4 km/h) and twice with no flow on the subject. Subjects were asked to rate their breathlessness using a modified Borg scale. Cold air directed on the face reduced breathlessness induced by an inspiratory resistive load and hypercapnia (6.2 +/- 1.7 Borg scale units with no flow, 5.1 +/- 1.7 with cold air; p less than 0.002) without causing a significant reduction in ventilation. This effect was not observed when cold air was directed to the leg and does not appear to be associated with a reduction in the ventilatory response to hypercapnia or with initiation of the diving reflex. We conclude that cold air directed against the cheek significantly reduces dyspnea associated with the combination of hypercapnia and an inspiratory resistive load.