Association of Pseudomonas aeruginosa infection stage with lung function trajectory in children with cystic fibrosis

Abstract

Background: Pseudomonas aeruginosa (Pa) infection in cystic fibrosis (CF) is characterized in stages: never (prior to first positive culture) to incident (first positive culture) to chronic. The association of Pa infection stage with lung function trajectory is poorly understood and the impact of age on this association has not been examined. We hypothesized that FEV₁ decline would be slowest prior to Pa infection, intermediate after incident infection and greatest after chronic Pa infection.

Methods: Participants in a large US prospective cohort study diagnosed with CF prior to age 3 contributed data through the U.S. CF Patient Registry. Cubic spline linear mixed effects models were used to evaluate the longitudinal association of Pa stage (never, incident, chronic using 4 different definitions) with FEV₁ adjusted for relevant covariates_. Models contained interaction terms between age and Pa stage.

Results: 1,264 subjects born 1992-2006 provided a median 9.5 (IQR 0.25 to 15.75) years of follow up through 2017. 89% developed incident Pa; 39-58% developed chronic Pa depending on the definition. Compared to never Pa, incident Pa infection was associated with greater annual FEV₁ decline and chronic Pa infection with the greatest FEV₁ decline. The most rapid FEV₁ decline and strongest association with Pa infection stage was seen in early adolescence (ages 12-15).

Conclusions: Annual FEV₁ decline worsens significantly with each Pa infection stage in children with CF. Our findings suggest that measures to prevent chronic infection, particularly during the high-risk period of early adolescence, could mitigate FEV₁ decline and improve survival.

Keywords: Cystic fibrosis; Lung function; Pseudomonas aeruginosa.