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

Dept of Pediatrics, College of Medicine, Seoul National University, Chongno Ku, Korea.
European Respiratory Journal (Impact Factor: 7.64). 06/1997; 10(5):994-9. DOI: 10.1183/09031936.97.10050994
Source: PubMed


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.

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    • "Quality assessment items are shown in Table 2. Eight trials were classified as having high quality [15]–[17], [21]–[24], [26] and one as low quality [25] according to Jadad scoring system. All were randomized trials, but the methods to generate the randomization sequence were accurately reported in 5 studies [15]–[17], [23], [26]. "
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    ABSTRACT: A systematic review and meta-analysis was conducted to evaluate the efficacy and safety of macrolide therapy in adults and children with bronchiectasis. We searched the PUBMED, EMBASE, CENTRAL databases to identify relevant studies. Two reviewers evaluated the studies and extracted data independently. The primary outcome was the number of bronchiectasis exacerbations. Secondary outcomes included exacerbation-related admissions, quality of life (QoL), spirometry, 6-minute walk test (6MWT) and adverse events. Nine eligible trials with 559 participants were included. Six were conducted on adults, and the remaining on children. Macrolide therapy significantly reduced the number of patients experiencing one or more exacerbation in adults [risk ratio (RR) = 0.59; 95% CI, 0.40 to 0.86; P = 0.006; I2 = 65%] and children [RR = 0.86; 95% CI, 0.75-0.99; P = 0.04; I2 = 0%], but not the number of patients with admissions for exacerbation. Macrolide therapy was also associated with reduced frequency of exacerbations in adults (RR = 0.42; 95% CI, 0.29 to 0.61; P<0.001; I2 = 64%) and children (RR = 0.50; 95% CI, 0.35 to 0.71; P<0.001). Pooled analyses suggested that spirometry, including FEV1 and FVC, were significantly improved in adults but not in children. Macrolide therapy improved the QoL (WMD, -6.56; 95% CI, -11.99 to -1.12; P = 0.02; I2 = 86%) but no significant difference in 6MWT (WMD, 4.15; 95% CI, -11.83 to 20.13; P = 0.61; I2 = 31%) and the overall adverse events (RR, 0.96; 95% CI, 0.82 to 1.13; P = 0.66; I2 = 0%) in adults. However, reports of diarrhea and abdominal discomforts were higher with macrolide therapy. Macrolide maintenance therapy, both in adults and children, was effective and safe in reducing bronchiectasis exacerbations, but not the admissions for exacerbations. In addition, macrolide administration in adults was associated with improvement in QoL and spirometry, but not 6WMT. Future studies are warranted to verify the optimal populations and clarify its potential effects on antimicrobial resistance.
    Full-text · Article · Mar 2014 · PLoS ONE
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    • "Study or Subgroup Altenburg 2013 Cymbala 2005 Koh 1997 Liu 2012 Serisier 2013 Tsang 1999 Wong 2012 "
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    ABSTRACT: Long-term macrolides are increasingly being prescribed for stable bronchiectasis. This meta-analysis assessed the clinical effect of this treatment in bronchiectasis. A systematic review and meta-analysis were carried out. All randomized, controlled trials (RCT) comparing long-term macrolides with placebo and/or usual medical care, with outcome measures relating to efficacy and safety were selected. Nine RCT recruiting 530 patients were included. Compared with placebo and/or usual medical care, long-term macrolides significantly reduced the risk of the exacerbations (number of participants with exacerbations (relative risk = 0.70, 95% confidence interval (CI) 0.60-0.82, P < 0.00001); average exacerbations per participant (weighted mean difference = -1.01, 95% CI -1.35 to -0.67, P < 0.00001)), the St George's Respiratory Questionnaire total scores (weighted mean difference = -5.39 95% CI -9.89 to -0.88, P = 0.02), dyspnoea scale (weighted mean difference = -0.31 95% CI -0.42 to -0.20, P < 0.00001), 24-h sputum volume (P < 0.00001), and attenuated the decline of forced expiratory volume in 1 s (weighted mean difference 0.02 L, 95% CI 0.00-0.04, P = 0.01). Eradication of pathogens (P = 0.06), overall rate of adverse events (P = 0.61), and emergence of new pathogens (P = 0.61) were not elevated, while gastrointestinal events increased significantly with macrolides (P = 0.0001). Macrolide resistance increased, but a meta-analysis was not possible due to the diversity of parameters. Long-term use of macrolides appears to be a treatment option for stable bronchiectasis. The results of this review justify further investigation about adding this intervention to the treatment regimens of bronchiectasis.
    Preview · Article · Jan 2014 · Respirology
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    • "The marked paucity of RCTs [21,55] is reflected in the existence of only a single (small) published placebo-controlled RCT in children with bronchiectasis [21,56]. That study described a reduction in sputum purulence and airway hyper-responsiveness in children receiving roxithromycin (n = 13) [57]. There are no RCTs on the management of bronchiectasis exacerbations in children [58]. "
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    ABSTRACT: Background Despite bronchiectasis being increasingly recognised as an important cause of chronic respiratory morbidity in both indigenous and non-indigenous settings globally, high quality evidence to inform management is scarce. It is assumed that antibiotics are efficacious for all bronchiectasis exacerbations, but not all practitioners agree. Inadequately treated exacerbations may risk lung function deterioration. Our study tests the hypothesis that both oral azithromycin and amoxicillin-clavulanic acid are superior to placebo at improving resolution rates of respiratory exacerbations by day 14 in children with bronchiectasis unrelated to cystic fibrosis. Methods We are conducting a bronchiectasis exacerbation study (BEST), which is a multicentre, randomised, double-blind, double-dummy, placebo-controlled, parallel group trial, in five centres (Brisbane, Perth, Darwin, Melbourne, Auckland). In the component of BEST presented here, 189 children fulfilling inclusion criteria are randomised (allocation-concealed) to receive amoxicillin-clavulanic acid (22.5 mg/kg twice daily) with placebo-azithromycin; azithromycin (5 mg/kg daily) with placebo-amoxicillin-clavulanic acid; or placebo-azithromycin with placebo-amoxicillin-clavulanic acid for 14 days. Clinical data and a paediatric cough-specific quality of life score are obtained at baseline, at the start and resolution of exacerbations, and at day 14. In most children, blood and deep nasal swabs are also collected at the same time points. The primary outcome is the proportion of children whose exacerbations have resolved at day 14. The main secondary outcome is the paediatric cough-specific quality of life score. Other outcomes are time to next exacerbation; requirement for hospitalisation; duration of exacerbation; and spirometry data. Descriptive viral and bacteriological data from nasal samples and blood markers will also be reported. Discussion Effective, evidence-based management of exacerbations in people with bronchiectasis is clinically important. Yet, there are few randomised controlled trials (RCTs) in the neglected area of non-cystic fibrosis bronchiectasis. Indeed, no published RCTs addressing the treatment of bronchiectasis exacerbations in children exist. Our multicentre, double-blind RCT is designed to determine if azithromycin and amoxicillin-clavulanic acid, compared with placebo, improve symptom resolution on day 14 in children with acute respiratory exacerbations. Our planned assessment of the predictors of antibiotic response, the role of antibiotic-resistant respiratory pathogens, and whether early treatment with antibiotics affects duration and time to the next exacerbation, are also all novel. Trial registration Australia and New Zealand Clinical Trials Register (ANZCTR) number ACTRN12612000011886.
    Full-text · Article · Aug 2012 · Trials
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