Macrolides for the Treatment of Chronic Sinusitis, Asthma, and COPD. Part 3

Following treatment with clarithromycin, 400 mg daily for 4 weeks, significant improvements in mucociliary clearance, volume of secretions, cough frequency, and dyspnea-on-exertion were documented in 32 patients with sinobron-chial syndrome. Low-dose roxithromycin (Rulid; Albert-Roussel Pharma GmbH; Wiesbaden, Germany) was shown to significantly improve the aeration of all four sinuses and to significantly reduce neutrophil and IL-8 levels in the nasal discharge of 12 patients with chronic sinusitis.

The first article describing the use of macrolides in patients with chronic sinusitis appeared in the English literature in 1996. Hashiba and Baba treated 45 chronic sinusitis patients with clarithromycin, 400 mg daily for 8 to 12 weeks. Improvements in symptoms and rhinoscopic findings were directly related to the duration of macrolide therapy. The investigators noted improvement rates of 5%, 48%, 63%, and 71%, respectively, after 2, 4, 8, and 12 weeks of therapy. After 12 weeks of therapy, 64% of patients had reduced viscosity of nasal secretions, 56% had reduced quantity of nasal secretions, 62% had reduced postnasal drip, and 51% had reduced nasal obstruction. Clinical benefit in patients with chronic sinusitis also was observed following long-term administration of roxithromycin, 150 mg daily.

The following year, Rubin and associates reported on the results of a study in which the nasal mucus properties in 10 healthy volunteers were compared to those in 10 patients with purulent rhinitis before and after treatment with clarithromycin, 500 mg twice daily for 2 weeks. Before the initiation of therapy with the macrolide, secretions from those patients with rhinitis had statistically significantly decreased wetability and sneeze clear-ability, and had statistically significantly increased the percentage of solids and cohesion, compared to those in secretions from the healthy subjects. After clarithromycin therapy, the secretions from the healthy adults without nasal symptoms were similar, based on rheology, hydration, cohesion, and transportability, to that of rhinitis patients. The secretion volume decreased by > 10-fold (p < 0.01), and mucociliary transportability increased by 30% (p = 0.005). Secretory response to methacholine was not affected by clarithromycin, suggesting that the effect of the macrolide on mucus properties was based on the modulation of inflammation.

In a prospective, open-label study conducted at a single center in the United States, 25 patients (mean age, 45 years) with chronic sinusitis were treated with clarithromycin, 500 mg twice daily for 14 days. The diagnosis of chronic sinusitis was established based on history, physical examination findings, and the results of an ear-nose-throat evaluation and CT scan. Biopsy specimens of the maxillary sinus mucosa were obtained prior to the initiation of macrolide therapy and 7 days after its completion.

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