Risk factors for age at initial Pseudomonas acquisition in the cystic fibrosis epic observational cohort

Abstract

Background Risk factors for initial Pseudomonas aeruginosa (Pa) acquisition, particularly environmental exposures, are poorly understood. We aimed to identify such risk factors in order to inform prevention strategies and identify high-risk populations. Methods The study cohort included all participants in the U.S. EPIC Observational Study who had no prior Pa-positive respiratory cultures (N=889). Cox proportional hazard models were used to test the effects of factors on age at first Pa-positive respiratory culture. Results Cystic fibrosis (CF) genotype functional class had an important effect on age at initial Pa acquisition (hazard ratio (HR) comparing minimal to residual CFTR function 2.87 (95% CI 1.88, 4.39)). None of the modifiable risk factors evaluated, including cigarette smoke, hot tub use, breastfeeding, or daycare, was associated with age at Pa acquisition. Similarly, newborn screening was not associated with age at Pa acquisition (HR 0.85, 95% CI 0.66, 1.09). Key associations were validated in a CF Foundation National Patient Registry replication cohort. Conclusions Given the ubiquitous presence of Pa in the environment, it may be that many imposed lifestyle changes will have less impact on age at initial Pa acquisition than genetic determinants.

Infection Prevention and Control Guideline for Cystic Fibrosis: 2013 Update

“…1 In the United States, an observational study of children with newly acquired P. aeruginosa did not find that hot tub use was associated with age at P. aeruginosa acquisition but did find that swimming pool use in the previous year was protective. 308 These findings may reflect the relatively healthy pulmonary status of the children with CF enrolled in this study.…”

Early Childhood Risk Factors for Decreased FEV1at Age 6-7 Years in Young Children with Cystic Fibrosis

“…It is likely that the earlier acquisition of P. aeruginosa allows more time for phenotypes to develop that are associated with pulmonary exacerbations and/or lower FEV 1 % predicted, for example, mucoidy (34,35). Our prior primary analysis of the entire EPIC OBS cohort found no modifiable risk factors for P. aeruginosa acquisition (12). In contrast to the findings of the current analysis, Zemanick and colleagues found, among EPIC OBS participants at least 6 years of age, no significant change in the slope of FEV 1 % predicted after initial acquisition of P. aeruginosa (36).…”

“…The EPIC Observational Study is a U.S. national prospective study designed to define risk factors for age at initial acquisition of P. aeruginosa (12). Participants were enrolled between 2004 and 2006, when P. aeruginosa eradication therapy was already in widespread use: in 2006, 97% of the EPIC OBS sites reported prescribing antibiotics for P. aeruginosa acquisition "often" or "always" on the annual site survey of clinical practices.…”

“…The design of the EPIC OBS has been described previously (12). Children with an established diagnosis of CF (13) and not more than 12 years of age were enrolled at 59 accredited U.S. CF care centers between 2004 and 2006.…”

“…Study data were collected at each clinical encounter via the Cystic Fibrosis Foundation National Patient Registry (CFFNPR) and study-specific forms (12). CFFNPR data collected at each encounter included results of respiratory cultures obtained as part of routine clinical care, weight and height percentiles, and FEV 1 % predicted (beginning at age 6).…”