Secondary Outcomes of a Pilot Randomized Trial of Azithromycin Treatment for Asthma

Abstract

Objectives:The respiratory pathogen Chlamydia pneumoniae (C. pneumoniae) produces acute and chronic lung infections and is associated with asthma. Evidence for effectiveness of antichlamydial antibiotics in asthma is limited. The primary objective of this pilot study was to investigate the feasibility of performing an asthma clinical trial in practice settings where most asthma is encountered and managed. The secondary objectives were to investigate (1) whether azithromycin treatment would affect any asthma outcomes and (2) whether C. pneumoniae serology would be related to outcomes. This report presents the secondary results.Design:Randomized, placebo-controlled, blinded (participants, physicians, study personnel, data analysts), allocation-concealed parallel group clinical trial.Setting:Community-based health-care settings located in four states and one Canadian province.Participants:Adults with stable, persistent asthma.Interventions:Azithromycin (six weekly doses) or identical matching placebo, plus usual community care.Outcome Measures:Juniper Asthma Quality of Life Questionnaire (Juniper AQLQ), symptom, and medication changes from baseline (pretreatment) to 3 mo posttreatment (follow-up); C. pneumoniae IgG and IgA antibodies at baseline and follow-up.Results:Juniper AQLQ improved by 0.25 (95% confidence interval; −0.3, 0.8) units, overall asthma symptoms improved by 0.68 (0.1, 1.3) units, and rescue inhaler use decreased by 0.59 (−0.5, 1.6) daily administrations in azithromycin-treated compared to placebo-treated participants. Baseline IgA antibodies were positively associated with worsening overall asthma symptoms at follow-up (p = 0.04), but IgG was not (p = 0.63). Overall asthma symptom improvement attributable to azithromycin was 28% in high IgA participants versus 12% in low IgA participants (p for interaction = 0.27).Conclusions:Azithromycin did not improve Juniper AQLQ but appeared to improve overall asthma symptoms. Larger community-based trials of antichlamydial antibiotics for asthma are warranted.

Azithromycin for Bronchial Asthma in Adults: An Effectiveness Trial

“…Outcomes of the AZMATICS study also support findings of Hahn et al 22 and Sutherland et al, 26 who reported lesser or no benefit associated with macrolide treatment in subjects with mild to moderate asthma. However, all 3 studies were underpowered to detect clinically significant effects in milder asthma.…”

“…It is possible that other mechanisms, such as denial, cognitive dissonance, or both, could have promoted systematic misreporting by OL subjects. A true treatment effect is supported by the strength and consistency of the results (including 2 validated instruments, the AQL questionnaire and the asthma control questionnaire), by agreement with our blinded pilot results 22 and by the results of the principal investigator's (DLH) previous prospective observational cohort study that included patients with confirmed C. pneumoniae infections. 38 Although exploratory analyses suggest that smoking may have a significant modifying effect, AZMATICS was underpowered for subgroup analyses.…”

“…Elevated levels of C. pneumoniae-specific immunoglobulin A antibodies predicted worsening of asthma symptoms. 22 AQL improved by 0.25 units, but the change was not statistically significant. Simpson et al 24 performed an efficacy trial in nonsmoking adults with severe refractory asthma who were randomized to 8 weeks of clarithromycin or placebo and were followed for an additional 4 weeks after treatment.…”

“…[17][18][19][20][21][22][23][24][25][26] A 2005 Cochrane review concluded that there was insufficient evidence to confirm or refute the role of macrolide treatment in chronic asthma. 1 Since 2005, 3 additional trials of macrolides in chronic adult asthma have reported patient-oriented outcomes.…”

“…1 Since 2005, 3 additional trials of macrolides in chronic adult asthma have reported patient-oriented outcomes. 22,24,26 Hahn et al 22 (our pilot) performed a practice-based effectiveness trial that included mainly patients with mild to moderate asthma who were randomized to 6 weekly doses of azithromycin or placebo. Outcomes of interest included asthma symptoms, AQL, and levels of C. pneumoniae-specific antibodies up to 3 months after the completion of treatment.…”