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Several studies have reported clinical improvements in cystic fibrosis (CF) patients on macrolide antibiotics although the mechanism of action remains unclear. We conducted an open-label study of azithromycin (500 mg daily for 2 weeks) in 9 adult CF patients to explore 3 possible mechanisms: up-regulation of the multi-drug resistance (MDR) or cystic fibrosis transmembrane regulator (CFTR) proteins, correction of epithelial ion transport and reduced bacterial adherence. End-points included nasal potential difference (PD) measurements, nasal epithelial MDR and CFTR mRNA levels and Pseudomonas aeruginosa adherence to nasal epithelium. Forced expiratory volume in the 1st second (FEV(1)) increased significantly after 2 weeks of azithromycin (pre- 41.1 [5.0]%; post- 44.6 [5.8]%; P<0.05), although improvements in forced vital capacity (FVC) did not reach significance (pre- 61.3 [4.0]%; post- 67.1 [5.4]%, NS). Before treatment all subjects had nasal PD measurements characteristic of CF. Treatment led to no significant group differences in any measures of either sodium absorption or chloride secretion. Neither CFTR nor MDR mRNA levels had altered significantly and the adherence of P. aeruginosa did not decrease. We conclude that these are unlikely to be significant contributing mechanisms accounting for the consistent beneficial results observed in clinical trials of macrolides in CF.

Original publication

DOI

10.1016/j.rmed.2005.07.016

Type

Journal article

Journal

Respir Med

Publication Date

04/2006

Volume

100

Pages

687 - 697

Keywords

ATP Binding Cassette Transporter, Subfamily B, Member 1, Adult, Anti-Bacterial Agents, Azithromycin, Cell Adhesion, Cystic Fibrosis, Cystic Fibrosis Transmembrane Conductance Regulator, Female, Forced Expiratory Volume, Humans, Ion Transport, Male, Nasal Mucosa, Pseudomonas aeruginosa, RNA, Messenger, Up-Regulation, Vital Capacity