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Background: Clinical data indicate that airway inflammation in children with cystic fibrosis (CF) arises early, is associated with structural lung damage, and predicts progression. In bronchoalveolar lavage fluid (BALF) from CFTR mutant mice, several aspects of lipid metabolismare abnormal that contributes to lung disease.We aimed to determine whether lipid pathway dysregulation is also observed in BALF from children with CF, to identify biomarkers of early lung disease and potential therapeutic targets.

Methods: A comprehensive panel of lipids that included Sphingolipids, oxylipins, isoprostanes and lysolipids, all bioactive lipid species known to be involved in inflammation and tissue remodeling, were measured in BALF from children with CF (1–6 years, N = 33) and age-matched non-CF patients with unexplained inflammatory disease (N = 16) by HPLC-MS/MS. Lipid data were correlated with chest CT scores and BALF inflammation biomarkers.

Results: The ratio of long chain to very long chain ceramide species (LCC/VLCC) and lysolipid levels were enhanced in CF compared to non-CF patients, despite comparable neutrophil counts and bacterial load. In CF patients both LCC/VLCC and lysolipid levels correlated with inflammation and chest CT scores. The ceramide precursors Sphingosine, Sphinganine, Sphingomyelin, correlated with inflammation, whilst the oxidative stress marker isoprostane correlated with inflammation and chest CT scores. No correlation between lipids and current bacterial infection in CF (N = 5) was observed.

Conclusions: Several lipid biomarkers of early CF lung disease were identified, which point toward potential disease monitoring and therapeutic approaches that can be used to complement CFTR modulators.


Authors: Bob J. Scholte, Hamed Horati, Mieke Veltmana, Rob J. Vreekenc, Luke W. Garratt, Harm A.W.M. Tiddens, Hettie M. Janssens, Stephen M. Stick on behalf of the Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF). 

Published in Journal of Cystic Fibrosis in April 2019.