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 inflammatory response. Macrolide antibiotics are macrocyclical lactones that provide adequate coverage for the most frequently identified 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, inflammatory lung disorders including diffuse panbronchiolitis, asthma, noncystic fibrosis associated bronchiectasis, and cystic fibrosis. 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 define any potential treatment effect, the nature of this effect, and the role of bronchiectasis, baseline colonization, and other cormorbidities.

Figure 1

Molecular structure of 14 member macrolides (erythromycin, A), fifteen member compounds (azithromycin, B) and a 16 member compound (C) (Jaffe and Bush 2001).

Figure 2

Molecular targets of macrolides (Tsai and Standiford 2004).

Figure 3

Potential beneficial effects of macrolides in COPD patient.

Figure 4

Levels of induced-sputum inflammatory markers in clarithromycin- and placebo-treated COPD patients before and after treatment. AT, after treatment; BT, before treatment; IL-8, interleukin-8; LTB₄, leukotriene B4; TNF-α, tumor necrosis factor-α. *p < 0.05 before versus after treatment. Copyright © 2004. Reproduced with permission from Basyigit I, Yildiz F, Ozkara SK, et al. 2004. The effect of clarithromycin on inflammatory markers in chronic obstructive pulmonary disease: preliminary data. Ann Pharmacother, 38:783–92.

Figure 5

The effect of clarithromycin and placebo on sputum colony forming units (Cfu) numbers/bacterial (PPM) isolate. Cfu numbers are logged. Weighted bars indicate the mean for the whole group. There was no statistically significant difference between pre- and post-therapy Cfu numbers for both clarithromycin and placebo groups. NS indicates not significant. Copyright © 2004. Reproduced with permission from Banerjee D, Honeybourne D, Khair OA. 2004. The effect of oral clarithromycin on bronchial airway inflammation in moderate-to-severe stable COPD: a randomized controlled trial. Treat Respir Med, 3:59–65.