Azithromycin for Bronchial Asthma in Adults: An Effectiveness Trial

Abstract

on behalf of the AZMATICS (AZithroMycin-Asthma Trial In Community Settings) Study GroupBackground: Macrolides have antimicrobial and anti-inflammatory properties that may be useful in the treatment of chronic asthma.Methods: We performed a randomized, placebo-controlled, double-blinded effectiveness trial of 12 weekly doses of adjunctive azithromycin, with follow-up to 1 year after randomization, in adults with persistent asthma. Measurements included overall asthma symptoms, asthma quality of life (AQL), and asthma control. Eligible subjects who declined to participate in randomization were offered enrollment into a parallel open-label (OL) azithromycin treatment arm.Results: Of 304 adult asthma patients screened, 97 (32%) were enrolled: 38 were randomized to azithromycin, 37 were randomized to placebo, and 22 opted in as OL subjects. OL subjects had higher rates of severe persistent asthma compared with randomized subjects (32% vs 8%, respectively; P ‫؍‬ .012). At 1 year, compared with the placebo arm, subjects randomized to azithromycin were more likely to have an AQL score >1 unit increase compared with baseline, but this difference was not statistically significant (36% vs 21% for placebo; P ‫؍‬ .335). Compared with placebo, OL subjects had significant improvements in overall asthma symptoms from baseline (P ‫؍‬ .0196), AQL (P ‫؍‬ .0006), and asthma control (P ‫؍‬ .0148).Conclusions: Adults with asthma who were randomized to azithromycin did not show statistically significant improvement in asthma outcomes, although the study was underpowered to detect clinical improvement in 15% (number needed to treat ‫؍‬ 7). Adults with severe persistent asthma who elected OL treatment documented clinical improvements in asthma symptoms, AQL, and asthma control that persisted after completion of OL azithromycin (number needed to treat ‫؍‬ 2). (J Am Board Fam Med 2012;25:442-459.)

Meta-Analysis of the Adverse Effects of Long-Term Azithromycin Use in Patients with Chronic Lung Diseases

“…Besides its antibacterial activity, its anti-inflammatory roles have been increasingly recognized (3,4). In recent years, macrolide antibiotics have been explored in several clinical trials for their effects on patients with CLD, including COPD, asthma, cystic fibrosis (CF), and non CFbronchiectasis (3,(5)(6)(7)(8)(9)(10)(11)(12)(13). Recently, several meta-analyses collected the data and confirmed that the long-term use of macrolides improves the quality of life of CLD patients by improving lung function and decreasing the frequency of acute exacerbations (14,15).…”

Development of a Population Pharmacokinetic Model To Describe Azithromycin Whole-Blood and Plasma Concentrations over Time in Healthy Subjects

“…In addition, long-term therapy with 250-mg daily doses of AZI for 1 year was shown to decrease the frequency of exacerbations in COPD patients (14), and longterm treatment with 250 mg thrice weekly was effective in prevention and treatment of BOS in lung transplant patients (25). The promising clinical data on AZI efficacy in patients with bronchiectasis or severe persistent asthma need to be confirmed in randomized, placebo-controlled studies (16,27,33,34).…”

“…Twice-weekly dosing of 250 mg was assessed in patients with asthma or COPD with or without a loading dose, and a dose of 500 mg twice weekly was tested in patients with bronchiectasis (27)(28)(29). Finally, onceweekly dosing was evaluated in patients with asthma (600 mg once weekly with a loading dose of 1,800 mg or 1,000 mg once weekly) and CF (1,000 to 1,250 mg or the pediatric equivalent) (10,12,(30)(31)(32)(33). Other reported regimens included 500 mg daily for 6 days, followed by 250 mg daily for 6 days, and weekly dosing of 250 mg daily for 3 days thereafter (in patients with bronchiectasis) and 500 mg daily over 3 days every 3 weeks (in patients with COPD) (34,35).…”

Cardiovascular Diseases and Other Evidence for Primary Care Clinical Practice

“…Hahn et al 14 had difficulty getting patients with chronic obstructive pulmonary disease to agree to a randomized trial of azithromycin for chronic obstructive pulmonary disease; many just wanted the medication. It took many investigators in multiple practice-based research networks to recruit patients, yet they still were not able to include as many participants as desirable.…”