Environmental influences on the pulmonary manifestations of Cystic Fibrosis

Abstract

Cystic fibrosis is a multisystemic monogenic disease with many severe symptoms and complications, primarily in the respiratory and digestive systems. Medical advances have greatly extended the survival of patients with the disease. In parallel population expansion and globalisation have increased exposure to pollution. CF care is managed in specialist centres located in major cities. This PhD examines the relationship between the environment and the pulmonary manifestations of CF.1) A systematic review of environmental factors and cystic fibrosis covers the current literature interrogating factors best modified by policy. 2) I analyse the effect of distance from the attended CF centre on lung function and frequency of exacerbations using multivariate regression. 3) I compare Hospital episode statistics to the CF Registry to investigate for temporal and spatial accuracy. 4) A time series analysis analyses the short-term relationship between air pollution and pulmonary exacerbations using a distributed lag nonlinear model (DLNM). Environmental factors may have an impact on lung health through modulation of infection as well as direct oxidative damage to the lung. Those with a more severe genotype are more likely to bypass their nearest centre and travel further to reach care. Even when accounting for this, bypassing the nearest centre is associated with decreased lung function in older adults. Those in urban areas are more likely to receive IVs in hospitals than at home. Improving and supporting access to home IV therapy could aid demands on specialist care. Temporal data could be improved to allow if linkage was allowed. Particulate matter may increase the risk of hospitalisation with an exacerbation. Patients may compete for specialist beds in London on days with high air pollution. Overall, this thesis shows modifiable environmental factors in CF intersect with healthcare delivery.