Environmental risk factors for the initial acquisition of Pseudomonas aeruginosa in young children with cystic fibrosis

Thesis (Ph.D.)--University of Washington, 2013

<italic>Pseudomonas aeruginosa</italic> (<italic>Pa</italic>) is the sentinel respiratory pathogen in cystic fibrosis (CF) patients. <italic>Pa</italic> respiratory tract infection typically occurs early in life; however, risk factors for initial <italic>Pa</italic> acquisition remain poorly understood. Although <italic>Pa</italic> in CF patients is generally acquired from the environment, to date, few studies have investigated specific environmental factors and their associations with initial <italic>Pa</italic> acquisition. To address several gaps in the current literature regarding initial <italic>Pa</italic> acquisition, we conducted three retrospective studies to evaluate the potential role of environmental risk factors for initial <italic>Pa</italic> acquisition in young CF patients using data from the Cystic Fibrosis Foundation National Patient Registry, 2003-2009. First, we examined whether there was seasonal variation in rates of initial <italic>Pa</italic> acquisition and further evaluated potential seasonal variation within different climate zones. Second, we investigated whether there was residual spatial dependence of time to initial <italic>Pa</italic> acquisition. Third, we evaluated the association of early life exposure to ambient air pollution (particulate matter <2.5 microns, PM_2.5) and time to <italic>Pa</italic> acquisition. Results of the Poisson regression models evaluating seasonal acquisition of initial <italic>Pa</italic> demonstrated an increased rate of acquisition in summer (Incidence rate ratio [IRR]: 1.22; 95% confidence interval [CI]: 1.08, 1.39) and autumn (IRR: 1.34; 95% CI: 1.18, 1.52) seasons, compared to winter. Seasonal patterns were also found to differ by climate zones. In the spatial analysis of initial <italic>Pa</italic> acquisition, which employed a hierarchical Bayesian Weibull regression accommodating interval censored outcomes and using state of residence as the level of analysis, a moderately elevated spatial residual relative risk was found. An estimated 95% interval for the residual hazard ratio under one of the fitted models was 0.64 to 1.57 and the strongest positive association was observed in Southern states. Finally, an increase in PM_2.5 exposure of 10 µg/cubic meter was associated with a 24% increase risk of <italic>Pa</italic> acquisition (95% confidence interval: 1-51%) in multivariate Weibull regression analysis. The results of these studies suggest that environmental factors play a role in initial <italic>Pa</italic> acquisition in CF patients. Future studies to more fully elucidate the roles of these factors from both the individual and the pathogen perspectives could provide insight into the etiology of <italic>Pa</italic> acquisition in CF patients and inform prevention strategies.