Prevention of exacerbations in patients with stable non-cystic fibrosis bronchiectasis: a systematic review and meta-analysis of pharmacological and non-pharmacological therapies

Abstract

BackgroundSeveral pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology.ObjectiveWe conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations.Study selectionMultiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model.Findings30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV1) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD −0.90 (95% CI −1.58 to −0.22)) and improving quality of life scores assessed by the St George’s Respiratory Questionnaire (WMD −6.07 (95% CI −10.7 to −1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy.ConclusionsModerate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations.

Bronchiectasis in Primary Antibody Deficiencies: A Multidisciplinary Approach

“…Overall, the authors found that there is evidence of moderate quality to suggest that the use of prolonged antibiotics may benefit patients with non-CF bronchiectasis, however they did raise concerns about the potential for emergence of antibiotic tolerance with this approach (90). Subsequent systematic reviews and metaanalyses reaffirmed prior findings of a reduction in exacerbation and improvement in QOL scores and pulmonary function indices (82,91). Two large recent randomized control trials, the EMBRACE (Azithromycin for prevention of exacerbations in non-CF bronchiectasis) and BAT (Bronchiectasis and Longterm Azithromycin Treatment) trials, also endorsed the role of azithromycin in non-CF bronchiectasis, the latter of which included five patients with CVID (92,93).…”

“…As discussed previously, despite appropriate immunoglobulin replacement, many patients with antibody deficiencies will still develop bronchiectasis. Patients who should be considered for prophylactic antibiotics include those with three pulmonary infectious exacerbations in 1 year (61,82,83) or who have declining lung function despite appropriate immunoglobulin replacement (84,85). Because macrolide antibiotics have antiinflammatory and anti-microbial properties, they are most commonly used for prophylaxis in patients with bronchiectasis (86)(87)(88).…”

Measuring airway clearance outcomes in bronchiectasis: a review

“…Minimising respiratory exacerbations is a key aim in bronchiectasis management [1] and a major topic for pharmacological research in this disease [72]. Until recently there was no consensus-based definition for a respiratory exacerbation in bronchiectasis research [73].…”

Contemporary Concise Review 2018: Bronchiectasis

“…Several other publications focused on exacerbations, including a systematic review highlighting the paucity of data for pharmacological and non‐pharmacological therapies preventing exacerbations . A clinically practical review that included defining exacerbations, treatment and prevention highlighted and provided evidence‐based guidance to many questions clinicians face when managing exacerbations in children and adults with bronchiectasis; for example, first‐ and second‐line antibiotic treatments, doses, duration and prevention.…”