Host, environmental and genetic determinants of respiratory disease pathogenesis and management in children

Abstract

Respiratory disease has a substantial adverse impact on the health outcomes and quality of life in children. There are significant gaps in our understanding concerning common respiratory diseases in children. These include the influence of environmental factors, the prognosis and management of protracted bacterial bronchitis (PBB), and the response to common asthma medications. This MD by publication thesis provides a critical appraisal of five peer reviewed manuscripts produced between 2017 and 2024 that attempt to address these key research priority areas.
Publication one describes the impact of several potentially modifiable environmental risk factors on respiratory outcomes in young children from the GO-CHILD birth cohort. These include the benefits of prolonged breast feeding as well as the adverse impact of daycare attendance and traffic pollution. Publication two focuses specifically on the location of household damp and mould on respiratory outcomes from the same cohort. Visible damp in the child’s bedroom was associated with increased respiratory symptoms and reliever and corticosteroid inhaler prescription. Publication three characterises the 5-year outcomes fora cohort of children from the Queensland Children’s Hospital with PBB. Bronchiectasis was diagnosed in 9.6% of children and a clinician diagnosis of asthma at final follow-up in 27%. Whilst mean PBB episodes decreased significantly over time, more than two thirds had ongoing respiratory symptoms in their final 12-months of follow-up. Publication four describes the first randomised controlled trial (RCT) comparing the duration of antibiotic treatment for children with PBB. There was no difference in cough clinical cure between 2-weeks vs 4-weeks of amoxicillin-clavulanate, however children in the 4-week group had a significantly longer time to next wet cough exacerbation. Publication five details the first RCT to compare genotype-guided asthma controller prescribing to standard care in 12-18year-olds. Controller prescribing based on β2 adrenergic receptor (ADRB2) genotype resulted in a significant improvement in asthma quality of life questionnaire score, but the difference was less than anticipated. Young people with the homozygous AA genotype showed the greatest benefit.
This body of work has addressed key unmet research needs in paediatric respiratory disease and forms the basis for ongoing research to prevent recurrent PBB, impact public health policy around household damp, and develop further evidence for the implementation of genotype-based prescribing in children’s asthma.

Date of Award	May 2025
Original language	English
Awarding Institution	University of Brighton
Supervisor	Somnath Mukhopadhyay (Supervisor)