(41) Association of Pseudomonas aeruginosa Infection Stage with Lung Function Trajectory In Children with CF>

Background: The effect of chronic Pseudomonas aeruginosa (Pa) infection on lung function trajectory in people with CF is not known. We aimed to evaluate the association of longitudinal lung function (percent predicted forced expiratory volume in 1 second, ppFEV₁) with different stages of Pa infection (never, incident, chronic) using 4 definitions of chronic Pa in a U.S. national cohort of children with CF.

Methods: Participants in the Early Pseudomonas Infection Control Observational Study (EPIC-OBS) diagnosed with CF prior to age 3 contributed encounter-based data through the U.S. CF Patient Registry 1992-2017. Follow-up was censored at the time of solid organ transplant or gaps in culture or FEV₁ data >2 years. Cubic spline linear mixed effects models were used to evaluate the association of Pa stage with longitudinal ppFEV_1. Participants contributed to the Pa never FEV₁ curve until they acquired incident Pa, at which point they began contributing to the incident Pa FEV₁ curve. If they developed chronic Pa, they then shifted to contributing to the chronic Pa FEV₁ curve. Models contained interaction terms between age and Pa stage (never, incident, or chronic) and were adjusted for birth cohort, diagnosis following a positive newborn screen, sex at birth, race, ethnicity, insurance at first FEV₁, CFTR genotype (minimal vs. residual function) and the following time-varying covariates: CF-related diabetes, modulator use (ivacaftor, lumacaftor/ivacaftor) and respiratory culture positive for other individual CF pathogens. We employed 4 chronic Pa definitions¹: a) 2 Pa+ years over 3 years; b) 3 Pa+ years over 4 years; c) 3 Pa+ age-quarters over 2 years; d) 2 Pa+ age-quarters over 1 year.

Results: 1,264 subjects born 1992-2006 provided a median 9.5 (IQR 0.25 to 15.75) years of follow up. 89% developed incident Pa; 39% - 58% developed chronic Pa depending on the definition. Model estimates were similar across all chronic Pa definitions, so we show results using definition (b) (3 Pa+ years over 4 years) in the Figure. The top panel shows the model estimates of FEV₁ (mean and 95% confidence intervals) by age and Pa stage. The bottom panel shows the number of FEV₁ values available at each age for each Pa stage. The estimated mean ppFEV₁ is lower after initial Pa acquisition and lower still after chronic Pa infection at all ages; this effect increases with age. Similarly, the slope of ppFEV₁ decline is greater among those with chronic Pa, particularly after age 12.

Conclusions: Pa infection stage is associated with lower FEV₁pp and more rapid decline, particularly after age 12, in children with CF, even after adjustment for relevant covariates and regardless of chronic Pa definition. Measures to prevent chronic Pa infection could potentially slow FEV₁ decline and improve long-term outcomes.

Acknowledgements: This work was supported by CFF OBSERV13K0 and CUTTIN18XX1, BAMSHA18XX0, and KNOWLE18XX0. We thank all the PwCF who participated in the EPIC Observational Study and all the site PIs and RCs

References: Rosenfeld M, Faino A, et al Comparing encounter-based and annualized chronic Pseudomonas infection definitions in cystic fibrosis. .J Cyst Fibros. 2022 Jan;21(1):40-44. .PMID: 34393091