Macrolides for the Treatment of Chronic Sinusitis, Asthma, and COPD. Part 2

Between 1990 and 1992, sinusitis-associated symptoms resulted in > 70 million days of restricted activity. The economic impact of the disease is also staggering, with health-care expenditures in the United States attributable to sinusitis estimated to be about $5.8 billion annually.

Nasal congestion, increased quantity and tenacity of secretions, facial pain, and fatigue are common among patients with chronic sinusitis. Hyperplastic changes in the mucosa, hypertrophy, and hypersecretion of the nasal and paranasal sinus mucosa are typical, as is an inflammatory infiltrate containing lymphocytes, plasma cells, neutrophils, and eosino-phils. Hyperplastic and hypertrophic changes of the nasal mucosa cause narrowing of the drainage route from the paranasal sinuses and sinus cavities, leading to mucosal congestion and edema. Hypersecretion disturbs mucociliary clearance. Obstruction of the sinus ostia creates an increasingly hypoxic environment within the sinus, and leads to inflammation and an ideal culture medium within the sinus cavity. Maintaining ostia patency is critical to reversing the cycle of sinusitis. As summarized below, there is accumulating evidence that macrolides may alter the natural history of chronic sinusitis, which is characterized by elevated levels of inflammatory mediators (eg, granulocyte macrophage colony-stimulating factor, interleukin [IL]-3, and IL-8). Macrolides may inhibit the vicious cycle of cytokine production, neutrophil recruitment, and impaired mucociliary function at the site of inflammation, thereby interrupting the prolonged inflammation of chronic sinusitis.

Clinical Experience

Clinical reports of macrolide use in patients with chronic sinusitis come primarily from small, open-label case series. Consistent across the studies have been improvements in sinusitis symptoms, shrinkage in the size of nasal polyps, and a decrease in levels of proinflammatory cytokines in nasal secretions. Most of the clinical experiences demonstrating the favorable anti-inflammatory effects of macrolides on patients with chronic sinusitis have been published in the Japanese literature. A summary of articles describing the clinical experience with macrolides in patients with chronic sinusitis is presented in Table 2.

Data from the beginning of the last decade from Kikuchi and coworkers17 from Japan documented improvement of sinusitis signs and symptoms in 50 to 100% of patients who were given macrolide therapy. The investigators treated 26 postoperative patients with persistent sinus symptoms following sinus surgery using erythromycin, 600 mg per day for an average of 7.9 months. Also published in the Japanese literature were the results of studies by Nishi and Suzuki.

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