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BAL Inflammatory Markers Can Predict Pulmonary Exacerbations in Children With Cystic Fibrosis

Alya Ishak¹, Stephen M Stick¹, Lidija Turkovic²

¹Department of Respiratory and Sleep Medicine, Perth Children's Hospital, Perth, Australia; Telethon Kids Institute, Perth, Australia.

|July 6, 2020

Insights

Inflammatory markers in bronchoalveolar lavage (BAL) fluid can predict pulmonary exacerbations in young children with cystic fibrosis. Early detection through these markers may lead to timely treatment and reduced long-term lung damage.

Area of Science:

Pediatric Pulmonology
Respiratory Medicine
Biomarkers in Cystic Fibrosis

Background:

Pulmonary exacerbations in cystic fibrosis (CF) involve airway inflammation and can cause irreversible lung damage.
Early identification of exacerbations is crucial for timely treatment and mitigating long-term morbidity in CF patients.

Purpose of the Study:

To determine if inflammatory markers in bronchoalveolar lavage (BAL) fluid can predict pulmonary exacerbations in children with cystic fibrosis.
To assess the association between specific inflammatory markers and the risk of pulmonary exacerbation in young CF patients.

Main Methods:

Longitudinal analysis of children aged 0-7 years from the AREST CF study (2005-2015).
Analysis of inflammatory markers (IL-8, neutrophil elastase, neutrophil percentage) from annual BAL fluid.
Kaplan-Meier curves and Weibull regression used to analyze time to pulmonary exacerbation within 6 months post-BAL, adjusting for clinical variables.

Main Results:

Nine hundred seventy-six BAL samples from 308 children were analyzed.
High IL-8, neutrophil elastase, and neutrophil percentage in BAL fluid were significantly associated with an increased risk of pulmonary exacerbation.
These inflammatory markers remained significant predictors even after adjusting for clinical variables.

Conclusions:

Inflammatory markers in BAL fluid are significant predictors of pulmonary exacerbations in young children with cystic fibrosis.
Developing noninvasive methods to measure lung inflammation could aid in routine CF surveillance.

Read full analysis

Abstract

Background:

Pulmonary exacerbations in cystic fibrosis are characterized by airway inflammation and may cause irreversible lung damage. Early identification of such exacerbations may facilitate early initiation of treatment, thereby potentially reducing long-term morbidity.

Research Question:

Is it possible to predict pulmonary exacerbations in children with cystic fibrosis, using inflammatory markers obtained from BAL fluid?

Study Design And Methods:

A longitudinal analysis was conducted of children aged 0 to 7 years included in the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF) study between 2005 and 2015. The association between inflammatory markers from annual BAL fluid and time to pulmonary exacerbation requiring hospital admission in the 6-month period post-BAL was analyzed using Kaplan-Meier curves and Weibull regression, adjusting for annually repeated measurements. Admissions for Pseudomonas eradication were excluded in the main analysis, because of the standard policy in participating centers to treat Pseudomonas in-hospital.

Results:

Nine hundred seventy-six BAL samples from 308 children were analyzed. After exclusion of admissions for Pseudomonas eradication (n = 43), there were 145 pulmonary exacerbations recorded within 6 months of BAL; median time to exacerbation was 31 days (interquartile range, 9-100). In univariate analyses, high IL-8 (hazard ratio [HR], 2.25 for 75th vs 25th percentile; 95% CI, 1.87-2.72), neutrophil elastase (HR, 3.00; 95% CI, 2.03-4.42), and high neutrophil percentage (HR, 1.80 for 75th vs 25th percentile; 95% CI, 1.56-2.04) were all significantly associated with risk for a pulmonary exacerbation (P < .001). The inflammatory markers remained significant predictors after adjustment for clinical predictive variables.

Interpretation:

Inflammatory markers in BAL fluid are significant predictors of pulmonary exacerbations in young children with cystic fibrosis. The development of noninvasive measures of lung inflammation may facilitate routine surveillance of cystic fibrosis.

Keywords:

bronchoscopy cystic fibrosis pediatrics predictive biomarkers pulmonary exacerbation

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