BACKGROUND Acute exacerbations adversely affect patients with chronic obstructive pulmonary disease (COPD). Macrolide antibiotics benefit patients with a variety of inflammatory airway diseases. METHODS We performed a randomized trial to determine whether azithromycin decreased the frequency of exacerbations in participants with COPD who had an increased risk of exacerbations but no hearing impairment, resting tachycardia, or apparent risk of prolongation of the corrected QT interval. RESULTS A total of 1577 subjects were screened; 1142 (72%) were randomly assigned to receive azithromycin, at a dose of 250 mg daily (570 participants), or placebo (572 participants) for 1 year in addition to their usual care. The rate of 1-year follow-up was 89% in the azithromycin group and 90% in the placebo group. The median time to the first exacerbation was 266 days (95% confidence interval [CI], 227 to 313) among participants receiving azithromycin, as compared with 174 days (95% CI, 143 to 215) among participants receiving placebo (P<0.001). The frequency of exacerbations was 1.48 exacerbations per patient-year in the azithromycin group, as compared with 1.83 per patient-year in the placebo group (P=0.01), and the hazard ratio for having an acute exacerbation of COPD per patient-year in the azithromycin group was 0.73 (95% CI, 0.63 to 0.84; P<0.001). The scores on the St. George’s Respiratory Questionnaire (on a scale of 0 to 100, with lower scores indicating better functioning) improved more in the azithromycin group than in the placebo group (a mean [±SD] decrease of 2.8±12.8 vs. 0.6±11.4, P=0.004); the percentage of participants with more than the minimal clinically important difference of −4 units was 43% in the azithromycin group, as compared with 36% in the placebo group (P=0.03). Hearing decrements were more common in the azithromycin group than in the placebo group (25% vs. 20%, P=0.04). CONCLUSIONS Among selected subjects with COPD, azithromycin taken daily for 1 year, when added to usual treatment, decreased the frequency of exacerbations and improved quality of life but caused hearing decrements in a small percentage of subjects. Although this intervention could change microbial resistance patterns, the effect of this change is not known. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00325897.)
Prone ventilation is feasible and safe, and may reduce mortality in patients with severe ARDS when it is initiated early and applied for most of the day.
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.
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