Oxidative stress and abnormal bioactive lipids in early cystic fibrosis lung disease

Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF)

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


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 metabolism are 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.

Original languageEnglish
Pages (from-to)781-789
Number of pages9
JournalJournal of Cystic Fibrosis
Issue number6
Early online date26 Apr 2019
Publication statusPublished - Nov 2019


Dive into the research topics of 'Oxidative stress and abnormal bioactive lipids in early cystic fibrosis lung disease'. Together they form a unique fingerprint.

Cite this