Role of macrolide therapy in chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and disability worldwide. The Global Burden of Disease study has concluded that COPD will become the third leading cause of death worldwide by 2020, and will increase its ranking of disability-adjusted life years lost from 12th to 5th. Acute exacerbations of COPD (AECOPD) are associated with impaired quality of life and pulmonary function. More frequent or severe AECOPDs have been associated with especially markedly impaired quality of life and a greater longitudinal loss of pulmonary function. COPD and AECOPDs are characterized by an augmented infl ammatory response. Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identifi ed pathogens in AECOPD and have been generally included in published guidelines for AECOPD management. In addition, they exert broad-ranging, immunomodulatory effects both in vitro and in vivo, as well as diverse actions that suppress microbial virulence factors. Macrolide antibiotics have been used to successfully treat a number of chronic, infl ammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fi brosis associated bronchiectasis, and cystic fi brosis. Data in COPD patients have been limited and contradictory but the majority hint to a potential clinical and biological effect. Additional, prospective, controlled data are required to defi ne any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

Long-term macrolide treatment for chronic respiratory disease

“…There were some correlations between individual inflammatory parameters and weight and spirometric changes, but, in our view, these data did not show any consistent picture that would suggest that these were really important changes [38]. Azithromycin has no direct bactericidal effect on P. aeruginosa, but may reduce the organism virulence by altering biofilm formation, decreasing bacterial adherence to epithelial cells, inhibiting bacterial motility or acting synergistically with other antibiotics [39]. However, further analysis of this same dataset showed that in patients not infected with P. aeruginosa, azithromycin significantly reduced neutrophil counts and serum inflammatory markers within 28 days of initiating treatment [38].…”

Azithromycin Attenuates Pulmonary Inflammation and Emphysema in Smoking-Induced COPD Model in Rats

“…9 Macrolide antibiotics have immunomodulatory, antiinflammatory, and antibacterial effects. 10 Actions observed with macrolides include inhibition of neutrophil accumulation, chemokine and cytokine production, as well as inhibition of adhesion molecule expression. Such effects account, at least partially, for the essential role of macrolide antibacterials in the treatment of patients with diffuse panbronchiolitis, bronchiolitis obliterans syndrome, and bronchiectasis.…”

Azithromycin for Prevention of Exacerbations of COPD

“…We estimated that with enrollment of 1130 subjects, the study would have 90% power to show a significant difference between the two groups in the time to the first acute exacerbation of COPD, assuming that 50% of the participants in the control group 19 and 40% in the azithromycin group 25 would have an acute exacerbation, that the rate of nonadherence would be 20%, and that 6% of participants would die or be lost to follow-up during the study (extrapolated from Niewoehner et al 19 ), with a two-sided type I error of 0.05.…”

“…23 Macrolide antibiotics have immunomodulatory, antiinflammatory, and antibacterial effects. 25 Seven small studies that tested whether macrolides decrease the frequency of acute exacerbations of COPD reported conflicting results. [26][27][28][29][30][31][32] Accordingly, we conducted a large, randomized trial to test the hypothesis that azithromycin decreases the frequency of acute exacerbations of COPD when added to the usual care of these patients.…”