Albert, Richard

Abstract Rationale Daily azithromycin decreases acute exacerbations of chronic obstructive pulmonary disease (AECOPD), but long-term side effects are unknown. Objectives To identify the types of exacerbations most likely to be reduced and clinical subgroups most likely to benefit from azithromycin, 250 mg daily, added to usual care. Methods Enrollment criteria included irreversible airflow limitation and AECOPD requiring corticosteroids, emergency department visit, or hospitalization in the prior year or use of supplemental oxygen. Recurrent events and cumulative incidence analyses compared treatment received for AECOPD by randomization group, stratified by subgroups of interest. Cox proportional hazards models estimated treatment effects in subgroups adjusted for age, sex, smoking status, FEV1% predicted, concomitant COPD medications, and oxygen use. Measurements and Main Results Azithromycin was most effective in reducing AECOPD requiring both antibiotic and steroid treatment (n = 1,113; cumulative incidence analysis, P = 0.0002; recurrent events analysis, P = 0.002). No difference in treatment response by sex (P = 0.75), presence of chronic bronchitis (P = 0.19), concomitant inhaled therapy (P = 0.29), or supplemental oxygen use (P = 0.23) was observed. Older age and milder Global Initiative for Chronic Obstructive Lung Disease stage were associated with better treatment response (P = 0.02 and 0.04, respectively). A significant interaction between treatment and current smoking was seen (P = 0.03) and azithromycin did not reduce exacerbations in current smokers (hazard ratio, 0.99; 95% confidence interval, 0.71–1.38; P = 0.95). Conclusions Azithromycin is most effective in preventing AECOPD requiring both antibiotic and steroid treatment. Adjusting for confounders, we saw no difference in efficacy by sex, history of chronic bronchitis, oxygen use, or concomitant COPD therapy. Greater efficacy was seen in older patients and milder Global Initiative for Chronic Obstructive Lung Disease stages. We found little evidence of treatment effect among current smokers. Clinical trial registered with www.clinicaltrials.gov (NCT0011986 and NCT00325897).

Abstract The prone position improves gas exchange in many patients with ARDS. Animal studies have indicated that turning prone restores ventilation to dorsal lung regions without markedly compromising ventral regions. To investigate a potential mechanism by which this might occur, the relative volume of lung located directly under the heart was measured in the supine and prone positions in seven patients. Four axial tomographic sections between the carina and the diaphragm were analyzed (Sections 1 through 4). When supine, the percent of the total lung volume located under the heart increased from 7 ± 4% to 42 ± 8%, and from 11 ± 4% to 16 ± 4% in Sections 1 through 4, in the left and right lungs, respectively. When prone, the percent of left and right lung volume located under the heart was ≤ 1 and ≤ 4 %, respectively, in all four sections (p < 0.05 for each section, supine versus prone). Although a large fraction of the lung, particularly on the left, is located directly under the heart in supine patients, and would be subject to the compressive force resulting from heart weight, almost no lung is located under the heart when patients are prone and the compressive force of the heart is directed towards the sternum.