Abstract
Increased airway responsiveness (AR) is frequently associated with bronchiectasis. Roxithromycin is a new semisynthetic macrolide antibiotic that also has anti-inflammatory activities. This study was designed to see whether roxithromycin could favourably alter the degree of AR in patients with bronchiectasis and increased AR. Twenty five children with bronchiectasis, who had an increased AR (defined as a provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (FEV1) (PC20) <25 mg x mL(-1) evaluated by the dosimeter method), were randomized, double-blind into two parallel groups. Thirteen of the children were treated with roxithromycin (4 mg x kg(-1) b.i.d.) for 12 weeks and 12 received placebo. FEV1, sputum purulence and leucocyte scores were assessed every 3 weeks. To estimate AR, high-dose methacholine challenge tests were performed before and after treatment. On the dose-response curve to methacholine, PD20 and maximal response (two indices of AR) were measured. Changes in FEV1 were not observed during the course of the study in both groups. A significant improvement in sputum features was noted after 6 weeks of treatment in the roxithromycin group. After 12 weeks of roxithromycin therapy, the geometric mean (range of 1 SD) of provocative cumulative dose producing a 20% fall in FEV1 (PD20) increased significantly (p<0.01) to 169.2 (83.2-344.2) breath units (BU) (1 BU denotes one inhalation of 1 mg x mL(-1) methacholine) and the mean+/-SD of maximal response decreased significantly (p<0.01) to 32.5+/-6.8%, as compared with the initial values (PD20 87.1 (47.3-160.4) BU; maximal response 40.9+/-7.4%). No significant changes in either parameter were observed in the placebo group. Our results indicate that roxithromycin may decrease the degree of airway responsiveness in patients with bronchiectasis and increased airway responsiveness. Further study is necessary to determine the mechanism by which roxithromycin reduces airway responsiveness in bronchiectasis and its clinical impact.
