Advancing the knowledge, understanding and management of respiratory exacerbations of bronchiectasis in children

Abstract

IntroductionBronchiectasis unrelated to cystic fibrosis (CF) remains an under-researched area and is often labelled a "neglected disease". Yet, worldwide it is more common than CF and causes substantial morbidity and mortality in both children and adults.To reduce morbidity and premature mortality from bronchiectasis in adults, interventions should begin in childhood. Diagnosing bronchiectasis early and providing effective treatment, including treating exacerbations, can prevent significant morbidity. Although the importance of recognising and treating exacerbations effectively is well-accepted, there have been no prior randomised trials for managing exacerbations of bronchiectasis in children. The studies in my PhD address several important clinical and research gaps relating to children with bronchiectasis, including its early identification and antibiotic treatment of exacerbations. AimsThe overarching aim of my thesis is to improve knowledge of bronchiectasis, the pre-bronchiectasis state and management of bronchiectasis exacerbations in children.The specific main objectives were to: 1. Identify whether children with a poor response to at least 4-weeks of oral antibiotics predict an increased risk of finding bronchiectasis on a multi-detector computed-tomography (MDCT) scan of the chest. 2. Describe the clinical characteristics, investigations and treatment outcomes for children with chronic suppurative lung disease (CSLD) without radiographic evidence of bronchiectasis. 3. Determine in children with bronchiectasis the effect of oral azithromycin and oral amoxicillinclavulanate (each compared to placebo) on symptom resolution after 14-days treatment of nonsevere (non-hospitalised) acute respiratory exacerbations. 4. Asses in children with bronchiectasis whether oral azithromycin was non-inferior (within a 20% margin) to oral amoxicillin-clavulanate at achieving symptom resolution after 21-days treatment of non-severe (non-hospitalised) acute respiratory exacerbations. iv Vikas Goyal -August 2019 5. Estimate the cost of hospitalised bronchiectasis exacerbations. 6. Undertake a systematic review using Cochrane methodology to assess the effects of inhaled longacting beta-2-agonists (LABA) combined with inhaled corticosteroids (ICS) in children and adults with bronchiectasis during (a) acute exacerbations and (b) stable state.An overview of the major findings for each objective is detailed below:Objective-1 was addressed by studying 144 children undergoing chest CT scans for a chronic wet cough.Among the 105 children with persistent cough despite at least 4-weeks of antibiotics, 88 (83.8%) had bronchiectasis. In contrast, of the 24 children whose cough resolved after 4-weeks of antibiotics, only six (25.0%) received this diagnosis (adjusted OR 20.9; 95%CI 5.36 to 81.8). 1 The study addressing objective-2 is the first to describe children with CSLD. These 22 children lacked features of bronchiectasis on CT scans but had a wet cough unresponsive to oral antibiotics, which resolved with intravenous antibiotics an...