Chronic wet cough in children and further exploration of protracted bacterial bronchitis

Abstract

Chronic wet cough (i.e. lasting > 4 weeks) is common in children and is associated with significant burden on children, families and the healthcare system. Although some clinicians view chronic cough in children as trivial, for parents, chronic cough is associated with significant quality of life impairment, which improves when the cough resolves.Further, chronic cough in children may signify the presence of underlying lung disease, such as bronchiectasis.Prior to this thesis, my supervisors were the first to define the clinical entity of protracted bacterial bronchitis (PBB) in children. PBB is characterised by chronic wet cough, response to antibiotics (suggestive of bacterial infection of the airways) and absence of pointers indicating an alternative cause for cough. This early research demonstrated the existence of a recognisable pattern of lower airway inflammation and bacterial infection in children with chronic wet cough. However, many questions relating to chronic wet cough and PBB remained.This thesis explored the clinical, demographic, immunological and microbiological characteristics of children with chronic wet cough and PBB, with specific focus on viruses and viral-bacterial interactions. A longitudinal 2-year cohort study was also undertaken to describe the natural history of PBB. The medium-term risk of bronchiectasis (BE), in children with PBB, was evaluated; with the over-arching aim of identifying a link between these two conditions and identifying specific risk factors for a diagnosis of bronchiectasis.The objectives of the thesis were, to:1. Examine and contrast the lower airway findings of children with different types of cough (wet and dry) compared to no cough, with respect to infection and inflammation.2. Evaluate the sensitivity, specificity and predictive values of nasopharyngeal aspirate (NPA) for detecting viruses in bronchoalveolar lavage (BAL); and determine the relationship between infection and lower airway neutrophilic inflammation in children with non-acute respiratory illness. III 3. Evaluate the major human adenovirus genotypes/species, and relationships to bacterial co-infection, in children with PBB and BE.4. Delineate the clinical and laboratory characteristics of children with PBB with a specific focus on viruses.5. Determine the 2-year outcomes and risk factors for BE and recurrent PBB, in children with PBB.6. Undertake a systematic review on the efficacy of short-course antibiotic therapy for bronchiectasis in children and review specific treatment options for cough in children in general practice.Five of these objectives have been published (as 6 papers) and presented as chapters.The remaining chapter (objective 5) has been submitted to a peer-reviewed journal. An overview of the major findings, with respect to each chapter is detailed below:Objective-1 is a study on 232 children undergoing bronchoscopy for evaluation of respiratory symptoms. Children were grouped using a cough nature symptom-based approach into "wet cough," "dry cough" and "no cough". Children ...