Changes in airway inflammation with pseudomonas eradication in early cystic fibrosis

Luke W. Garratt, Oded Breuer, Craig J. Schofield, Samantha A. McLean, Daniel R. Laucirica, Rabindra Tirouvanziam, Barry S. Clements, Anthony Kicic, Sarath Ranganathan, Stephen M. Stick, on behalf of AREST CF

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Background: Neutrophil elastase is a significant risk factor for structural lung disease in cystic fibrosis, and Pseudomonas aeruginosa airway infection is linked with neutrophilic inflammation and substantial respiratory morbidity. We aimed to evaluate how neutrophil elastase (NE) activity changes after P. aeruginosa eradication and influences early disease outcomes. Methods: We assessed participants in the AREST CF cohort between 2000 and 2018 who had P. aeruginosa cultured from their routine annual bronchoalveolar lavage (BAL) fluid and who underwent eradication treatment and a post eradication BAL. Factors associated with persistent P. aeruginosa infection, persistent neutrophilic inflammation following eradication and worse structural lung disease one year post-eradication were evaluated. Results: Eighty-eight episodes (3 months to 6 years old) of P. aeruginosa infection were studied. Eradication was successful in 84.1% of episodes. Median activity of NE was significantly reduced post-eradication from 9.15 to 3.4 nM (p = 0.008) but persisted in 33 subjects. High post-eradication NE levels were associated with an increased risk for P. aeruginosa infection in the next annual visit (odds ratio=1.7, 95% confidence interval 1.1–2.7, p = 0.014). Post-eradication NE levels (difference, 0.8; 95% confidence interval, 0.1–1.5) and baseline bronchiectasis computed tomography (CT) score (difference, 0.4; 95% confidence interval, 0.1–0.8) were the best predictors of bronchiectasis progression within 1 year (backward stepwise linear regression model, R2= 0.608, P<0.001), independent of eradication. Conclusion: In children with CF, NE activity may persist following successful P. aeruginosa eradication and is significantly associated with bronchiectasis progression. Evaluating strategies to diminish neutrophilic inflammation is essential for improving long-term outcomes.

Original languageEnglish
Pages (from-to)941-948
Number of pages8
JournalJournal of Cystic Fibrosis
Volume20
Issue number6
DOIs
Publication statusPublished - Nov 2021

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