Macrolide Therapy Could Reduce Acute Exacerbations in Patients With COPD

Long-term macrolide therapy at low doses may reduce the number of acute exacerbations for patients with chronic obstructive pulmonary disease (COPD), according to a review article in Dovepress.

“It is known to us that over 50% of acute exacerbations are caused by bacterial infections, accompanied by increased airway inflammation. As macrolides have anti-inflammatory, anti-viral, and immunomodulatory effects, scholars have carried out clinical trials to use it to prevent exacerbations of COPD,” researchers said. “However, this method is not generally accepted. We, therefore, try to explore the efficacy of macrolides in preventing the acute exacerbation of COPD by statistical methods.”

Researchers performed a systematic literature search in PubMed, Embase, and the Cochrane Library database. Randomized controlled trials (RCT) that reported long-term use of macrolides for the treatment of COPD were eligible. The search terms used were:

• chronic obstructive pulmonary disease, and
• macrolides or azithromycin or erythromycin or clarithromycin, and
• randomized controlled trials or controlled clinical trials

Studies were considered eligible for inclusion if they were RCTs that enrolled patients with a diagnosis of stable COPD. The initial search yielded 609 studies. The literature search and study selection were independently performed by 2 investigators while 1 investigator mediated disagreements over including specific studies. A total of 10 studies were ultimately selected for inclusion in the meta-analysis.

All patients included had a history of acute exacerbations. A total of 1,521 patients were randomly allocated to the macrolides treatment group while 1,418 were randomly allocated to the control group. The study duration lasted from 3 months to 12 months and 3 of the 10 RCTs were not blinded.

Relevant data were directly derived from the selected studies and included study design, demographic information, macrolides dosing, treatment duration, and assessment of outcomes. COPD exacerbations were defined as an acute worsening of respiratory symptoms which required additional therapy. The primary endpoint was the total number of COPD exacerbations, the median time to first exacerbation, and the rate of exacerbations per patient per year. Secondary endpoints included mortality and hospitalization rates, St George Respiratory Questionnaire scores, incidence of adverse events, and drug resistance.

Researchers respectively extracted results from intention-to-treat data. The results were summarized as risk ratio and corresponding 95% confidence interval by meta-analysis. Between-study heterogeneity was assessed using the I² statistic and the Q-test. A fixed effect model was used for the combining of results if P for the heterogeneity test was greater than or equal to 0.1, or a random effects model was used if it wasn’t. Researchers performed sensitivity analyses on age, gender, smoking history, type, dose, and duration of macrolides administered. They used a funnel plot to evaluate publication bias and P less than 0.05 was considered statistically significant. Data were analyzed with R software Version 3.4 from The R Foundation for Statistical Computing.

Results of the meta-analysis demonstrated a 23% relative risk reduction in COPD exacerbations among patients who received macrolides instead of placebo. The median time to first exacerbation was effectively prolonged among patients who received macrolides compared to those who received placebo. After sub-group analysis, erythromycin was found to be advantageous. Older patients were found to be less responsive to macrolides.

“Our meta-analysis has analyzed and confirmed that long-term low dose usage of macrolides could significantly reduce the frequency of the acute exacerbation of COPD,” researchers said. “The treatment was well tolerated with few adverse reactions, but it was not suitable for the elderly. We recommend that this treatment regimen could be used in patients with GOLD grading C or D because they have a higher risk of acute exacerbation and mortality.”

Researchers stressed the need to further discuss whether macrolide treatment should last for 12 or more months. They stated that more randomized, high quality, double-blind controlled trials with a dedicated design and reliable methods are needed to obtain more comprehensive and objective conclusions about the efficacy of macrolide antibiotics for the treatment of stable COPD.

Reference

Cao Y, Xuan S, Wu Y, Yao X. Effects of long-term macrolide therapy at low doses in stable COPD. Dovepress; 2019;14:1289-1298. doi: 10.2147/COPD.S205075.