Effect of roxithromycin on airway responsiveness in children with bronchiectasis: a double-blind, placebo-controlled study

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.

Effects of erythromycin onPseudomonas aeruginosaadherence to collagen and morphologyin vitro

“…Administration of low-dose EM, probably by the inhibition of glycoconjugate release [18], reduces sputum production in patients with bronchorrhoea [19] and DPB [7,9]. Low-dose EM, with unclear mechanisms, also reduces airway responsiveness in patients with bronchiectasis [20]. A recent study by the authors has shown that an 8-week administration period of low-dose EM (500 mg b.i.d) significantly reduced sputum volume and improved lung function in steady state severe idiopathic bronchiectasis.…”

Long-term macrolide therapy in chronic inflammatory airway diseases

“…Only two were randomised double-blind placebo-controlled trials. KOH et al [37] showed a significant decrease in airway responsiveness to methacholine in children with bronchiectasis (and increased airway responsiveness) who received roxithromycin (n513) for 12 weeks compared to controls (n512). There was no change in spirometric results, but, by 6 weeks, significant improvements in sputum purulence scores were observed in the treatment arm.…”

Long-term macrolide treatment for chronic respiratory disease

“…According to the vicious cycle hypothesis, if infection is the primary driver of airway inflammation, bacterial clearance through the use of short-or long-term antibiotic therapy would be expected to reduce airway inflammation, allow airway healing and modify the long-term course of the disease. Until very recently, the role of macrolide therapy in non-CF bronchiectasis had only been investigated in studies that were small, of short duration and did not assess clinical relevant outcomes, such as pulmonary exacerbations and quality of life [44][45][46][47]. In a recently published, randomised, double-blind, placebo-controlled trial, 141 patients (aged o18 years) with a diagnosis of bronchiectasis as defined by HRCT and at least one pulmonary exacerbation requiring antibiotic treatment in the previous year, were assigned to receive azithromycin 500 mg three times per week or placebo for 6 months in a 1:1 ratio [48].…”