Infectious Disease

In Pediatric CF, Lung Function Worsens With Each P aeruginosa Infection Stage

Annual forced expiratory volume in 1 second (FEV1) decline is significantly worse with each Pseudomonas aeruginosa (P. aeruginosa) infection stage among children with cystic fibrosis (CF), according to study findings published in the Journal of Cystic Fibrosis.

In patients with CF, lung function trajectory for the 3 stages of P. aeruginosa (never/prior to first culture; incident/at first positive culture; and chronic) is not well understood. Researchers assessed the association of P. aeruginosa infection stage with longitudinal FEV1 trajectory in children with CF using data from the Early Pseudomonas Infection Control (EPIC) Observational Study (ClinicalTrials.gov Identifier: NCT00676169).

EPIC enrolled children with CF aged 0 to 12 years between 2004 and 2006 at 59 CF centers. Participants had no prior lifetime respiratory isolation of P. aeruginosa or were P. aeruginosa negative for at least 2 years. The current analysis included 1264 EPIC participants (72%) who had been diagnosed with CF by age 3, had at least 1 respiratory culture in the year before the first recorded FEV1, and had at least 2 FEV1 measurements from ages 6 to 21.

The investigators used linear mixed effects models to analyze the association of P. aeruginosa stage with longitudinal percent predicted FEV1 (ppFEV1) and age. Separate analyzes were performed for 4 different definitions of P. aeruginosa used in medical literature.

Our findings suggest that measures to prevent chronic infection, particularly during the high-risk period of early adolescence, could mitigate FEVu003csubu003e1u003c/subu003e decline and improve survival.

For the study cohort, mean (SD) age at first ppFEV1 was 6.67 (0.70) years, and 51% were female. The median (interquartile range [IQR]) follow-up was 9.5 (0.25-15.75) years.

Of the cohort, 89% of the children developed incident P. aeruginosa at a median (IQR) age of 2.9 (1.1-7.1) years, and 39% to 58% chronic developed P. aeruginosa infection (depending on the definition) with a median (IQR) age at chronic infection of 7.1 (2.9-11.4) to 10.6 (6.9-13.9) years.

Because similar results were observed with the 4 different definitions of chronic P. aeruginosa, the study authors reported results using the chronic P. aeruginosa definition from Green et al (3 P. aeruginosa-positive years over 4 years). The median number of cultures per participant per year of age was 4 (IQR [3-6] before incident infection, and 5 [5-6] later).

Incident P. aeruginosa occurred in 63% of participants before the first recorded FEV1 measurement. FEV1 measurements at each year of age were stable between ages 8 to 13 years and then declined. The proportion of children without P. aeruginosa infection decreased with age, and the proportion of those with chronic P. aeruginosa increased.

The estimated mean ppFEV1 was greatest before P. aeruginosa infection, decreased with initial P. aeruginosa, and was the lowest with chronic P. aeruginosa infection, and this effect increased with age. In addition, decline in ppFEV1 was the lowest before the initial P. aeruginosa infection, higher after incident P. aeruginosa infection, and the highest with chronic P. aeruginosa infection, especially after age 12 years.

The participants’ mean ppFEV1 was comparable in the 3 infection stages at ages 8 and 12 but was significantly different by age 16. The annual decrease in ppFEV1 was comparable in the 3 infection stages at age 8 but was significantly different at ages 12 and 16. At age 12, the annual decline was greatest across all infection stages and slowed by age 16.

Among several limitations, causality cannot be inferred in the observational study, and many respiratory cultures were from oropharyngeal samples, which are more sensitive than specific for lower airway P. aeruginosa infection. So, FEV1 was characterized using percent of the predicted value rather than z scores.

“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,” stated the investigators.

This article originally appeared on Pulmonology Advisor

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