Rofael, Sylvia Adel Daniel; (2021) Airway Microbiome in Chronic Lung Disease. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

Chronic lung disease is one of the main causes of morbidity and mortality worldwide. The recent discovery of the lung microbiome has transformed our understanding of the pathophysiology of respiratory infections and chronic lung disease. In the presented PhD thesis, the hypothesis that the composition of the whole microbial community rather than individual pathogens, is critical in the pathogenesis of chronic lung disease has been investigated. The airway microbiome was studied in a spectrum of chronic lung diseases: non-cystic fibrosis bronchiectasis, chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD) in adult survivors of extremely preterm birth and early pulmonary changes in people living with HIV (PLW-HIV) using culture independent approaches: next generation sequencing and quantitative polymerase chain reactions (qPCR). In all forms of the chronic lung diseases studied, a characteristic pattern of bacterial dysbiosis was identified. This was characterised by a significant decline in the bacterial community biodiversity and a shift in the bacterial community composition away from phylum Bacteroidetes; particularly genus Prevotella whose relative abundance was correlated with an important lung function parameter: FEV1% predicted. In PLW-HIV, some potential respiratory pathogens and gut bacteria were enriched in the airway microbiome which may place this population at higher risk to respiratory morbidities and pneumonia. Chronic lung disease is a sector employing extensive antibiotic prescription practices either to treat acute exacerbations, or as prophylaxis therapy. Substantial scientific evidence currently supports the clinical usefulness of macrolide prophylaxis therapy in managing chronic respiratory conditions. In this thesis, I investigated the effect of antibiotics on the homeostasis of the bacterial communities in the airways and how it contributed to the of antimicrobial resistance (AMR) among microbiota. The airway was found to harbour a rich source of AMR determinants and resistant microbiota. The AMR determinants were more related to the antibiotics used as rescue packs for prompt initiation of self-treatment of exacerbations. Antibiotic prophylaxis therapy was associated with lower total bacterial load and suppressed recognised pathogenic bacteria in the airways with minimal effect on the homeostasis of the respiratory microbiota. The airway bacterial community was resilient towards the disturbances caused by antibiotics use. No definite directional shift in the microbiome compositions associated with prophylactic antibiotics was identified at the group level.

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