Macrolides for the Treatment of Chronic Sinusitis, Asthma, and COPD. Part 1

Preliminary data from studies of patients with COPD have shown improvements in symptom scores and FEV1 after macrolide treatment. As biological response modifiers, macrolides have the potential to improve the outcomes of patients with inflammatory airway diseases. Large scale, placebo-controlled clinical trials designed to assess long-term efficacy and safety in these diseases are warranted.

Key words: anti-inflammatory activity; asthma; clarithromycin; COPD; erythromycin; macrolides; roxithromycin; sinusitis

Abbreviations: IL = interleukin; PCR = polymerase chain reaction; TNF = tumor necrosis factor

Learning objectives:

1. To understand the clinical data on the efficacy of macrolides for the treatment of chronic sinusitis, asthma, and COPD.

2.    To realize that large-scale, placebo-controlled studies determining the efficacy and safety of macrolides for the treatment of chronic sinusitis, asthma, or COPD are warranted.

3.    To be aware of the prevalence and the significant economic burden that chronic sinusitis, asthma, and COPD have on society.

4.    To understand the effects of macrolides on neutrophils.

5.    To understand the effects of macrolides on airway inflammation.

he role of macrolide antibiotics for the treatment of upper and lower respiratory tract infections is well-established. Based on a consistent record of efficacy, the newer macrolides, clarithromycin (Bi-axin; Abbott Pharmaceuticals; Abbott Park, IL) and azithromycin (Zithromax; Pfizer Pharmaceuticals; New York, NY), are currently recommended by several agencies/medical societies for first-line (or alternative) treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute bacterial sinusitis, and streptococcal pharyngitis. Perhaps less appreciated is a long-standing and relatively consistent body of literature that suggests that macrolides act as biological response modifiers, attenuating respiratory tract inflammation.

Independent of their potent antimicrobial activity, 14-membered and 15-membered macrolides possess anti-inflammatory properties that may contribute to clinical benefits observed in patients with airway inflammation (Table 1). Macrolides can normalize bronchial and nasal mucus secretion and/or properties, and may reduce bronchial hyperresponsiveness and sputum purulence. Macrolides also affect neutrophil migration, the oxidative burst in phagocytes, the production of proinflammatory cytokines, and eosinophilic inflammation. The clinical impact of these effects in patients with chronic sinusitis, asthma, and COPD is the focus of this article. The results of studies in which patients with chronic sinusitis, asthma, or COPD received a macrolide are summarized.

Chronic Sinusitis

Chronic sinusitis is one of the most common diseases in the United States, affecting 14% of the population.6 It is a burdensome clinical illness, significantly diminishing quality of life.

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