A cross-sectional and longitudinal analysis has identified key bronchoalveolar lavage (BAL) fluid metabolites that predict early structural lung disease (SLD) and progression to bronchiectasis in children with cystic fibrosis (CF). Some metabolites performed better than established biomarkers, such as neutrophil elastase (NE) and myeloperoxidase (MPO).
This observational study analyzed 84 BAL samples from 67 clinically stable CF children aged 1–5 years across two clinical sites. Untargeted metabolomics was used to detect relevant BAL metabolites. A linear mixed-effects model (LMM) identified metabolites associated with SLD, BAL neutrophil count, NE, and MPO activities. These findings were then validated in an independent longitudinal infant cohort, comparing those who did or did not develop bronchiectasis by age 9.
In the cross-sectional cohort, 10 BAL metabolites, including methionine sulfoxide (MetO), ornithine, and N-acetylmethionine (NAcMet), were significantly associated with SLD and neutrophil-driven inflammation. Percent methionine oxidation (%OxMet) and the arginine-to-ornithine ratio (AOR) also showed consistent associations. MetO, %OxMet, NAcMet, and ornithine predicted future bronchiectasis in the longitudinal cohort. The combination of MetO and ornithine improved predictive sensitivity compared to either alone. Notably, at ages 0–2 years, these metabolite markers outperformed traditional inflammatory biomarkers like NE, MPO, and interleukin-8.
These findings suggest that specific metabolites in BAL fluid, detectable in early CF, reflect key neutrophil-related oxidative and proteolytic processes that contribute to SLD. Their association with early lung injury and future disease progression supports their use as early markers and may guide timely therapy and targeted anti-inflammatory approaches.
