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.)

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Tiotropium reduces COPD exacerbations and may reduce related health care utilization in patients with moderate to severe COPD.

BACKGROUND Retrospective studies have shown that statins decrease the rate and severity of exacerbations, the rate of hospitalization, and mortality in chronic obstructive pulmonary disease (COPD). We prospectively studied the efficacy of simvastatin in preventing exacerbations in a large, multicenter, randomized trial. METHODS We designed the Prospective Randomized Placebo-Controlled Trial of Simvastatin in the Prevention of COPD Exacerbations (STATCOPE) as a randomized, controlled trial of simvastatin (at a daily dose of 40 mg) versus placebo, with annual exacerbation rates as the primary outcome. Patients were eligible if they were 40 to 80 years of age, had COPD (defined by a forced expiratory volume in 1 second [FEV1] of less than 80% and a ratio of FEV1 to forced vital capacity of less than 70%), and had a smoking history of 10 or more pack-years, were receiving supplemental oxygen or treatment with glucocorticoids or antibiotic agents, or had had an emergency department visit or hospitalization for COPD within the past year. Patients with diabetes or cardiovascular disease and those who were taking statins or who required statins on the basis of Adult Treatment Panel III criteria were excluded. Participants were treated from 12 to 36 months at 45 centers. RESULTS A total of 885 participants with COPD were enrolled for approximately 641 days; 44% of the patients were women. The patients had a mean (±SD) age of 62.2±8.4 years, an FEV1 that was 41.6±17.7% of the predicted value, and a smoking history of 50.6±27.4 pack-years. At the time of study closeout, the low-density lipoprotein cholesterol levels were lower in the simvastatin-treated patients than in those who received placebo. The mean number of exacerbations per person-year was similar in the simvastatin and placebo groups: 1.36±1.61 exacerbations and 1.39±1.73 exacerbations, respectively (P = 0.54). The median number of days to the first exacerbation was also similar: 223 days (95% confidence interval [CI], 195 to 275) and 231 days (95% CI, 193 to 303), respectively (P = 0.34). The number of nonfatal serious adverse events per person-year was similar, as well: 0.63 events with simvastatin and 0.62 events with placebo. There were 30 deaths in the placebo group and 28 in the simvastatin group (P = 0.89). CONCLUSIONS Simvastatin at a daily dose of 40 mg did not affect exacerbation rates or the time to a first exacerbation in patients with COPD who were at high risk for exacerbations. (Funded by the National Heart, Lung, and Blood Institute and the Canadian Institutes of Health Research; STATCOPE ClinicalTrials.gov number, NCT01061671.)

Abstract. Capping protein nucleates the assembly of actin filaments and stabilizes actin filaments by binding to their barbed ends. We describe here a novel isoform of the/~ subunit of chicken capping protein, the/32 isoform, which arises by alternative splicing. The chicken/31 isoform and the t2 isoform are identical in their amino acid sequence except for a short region at the COOH terminus; this region of the/3 subunit has been implicated in binding actin. Human and mouse cDNAs of the fll and t2 isoforms also were isolated and among these vertebrates, the COOH-terminal region of each isoform is highly conserved. In contrast, comparison of the sequences of the vertebrate fl subunit COOH-termini to those of lower eukaryotes shows no similarities.The t2 isoform is the predominant isoform of nonmuscle tissues and the fll isoform, which was first characterized in studies of capping protein from chicken muscle, is the predominant isoform of muscle tissues, as shown by immunoblots probed with isoform-specific antibodies and by RNAse protection analysis of mRNAs. The/32 isoform also is a component of dynactin complex from brain, which contains the actin-related protein Arpl. Both/~-subunit isoforms are expressed in cardiac muscle but they have nonoverlapping subcellular distributions. The fll isoform is at Z-discs of myofibrils, and the ~2 isoform is enriched at intercalated discs; in cardiac myocytes grown in culture, the t2 isoform also is a component of cell-cell junctions and at sites where myofibrils contact the sarcolemma. The biochemical basis for the differential distribution of capping protein isoforms is likely due to interaction with specific proteins at Z-discs and cell-cell junctions, or to preferential association with different actin isoforms. Thus, vertebrates have developed isoforms of capping protein that associate with distinct actin-filament arrays. F UNI)AMeNTAt. processes of biological systems include generation of asymmetric shapes and movement. The actin cytoskeleton is an essential component of these processes, which are often dynamic and take on diverse forms in different cell types and tissues. Within a single cell, distinct populations of actin filaments can exist, some of which may be formed by a distinct actin isoform. The different actin filament arrays contain several different actinbinding proteins, which likely interact with actin to regulate its assembly. Many of the actin-binding proteins also are expressed as isoforms which may contribute to generate diversity in the organization of actin filaments in cells and tissues.Capping protein is a candidate for regulating actin filament assembly in vivo. In vitro, capping protein nucleates filament