BAL inflammatory markers can predict pulmonary exacerbations in children with cystic fibrosis.Chest. 2020 Jul 02 [Online ahead of print]Chest
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.
Is it possible to predict pulmonary exacerbations in children with cystic fibrosis using inflammatory markers obtained from bronchoalveolar lavage (BAL) fluid?
and Methods: A longitudinal analysis of children aged 0-7 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 six-month period post-BAL was analysed using Kaplan-Meier curves and Weibull regression, adjusting for annually repeated measurements. Admissions for Pseudomonas eradication were excluded in the main analysis, due to the standard policy in participating centres to treat Pseudomonas in-hospital.
976 BAL samples from 308 children were analysed. After exclusion of admissions for Pseudomonas eradication (n=43), there were 145 pulmonary exacerbations recorded within six months of BAL; median time-to-exacerbation was 31 days (interquartile range 9-100). In univariate analyses, high interleukin-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<0.001). The inflammatory markers remained significant predictors after adjustment for clinical predictive variables.
Inflammatory markers in BAL fluid are significant predictors of pulmonary exacerbations in young children with cystic fibrosis. The development of non-invasive measures of lung inflammation may facilitate routine surveillance of cystic fibrosis.