Assessing infection and inflammation in people with cystic fibrosis using their breath: A pilot longitudinal study

Abstract Cystic fibrosis transmembrane conductance regulator (CFTR) modulators have revolutionized cystic fibrosis (CF) management, but airway infections and inflammation persist. This study evaluates longitudinal exhaled breath profiles and identifies volatile organic compounds (VOCs) that correlate with sputum bacterial load and neutrophil elastase (NE) levels during ivacaftor and/or antibiotic treatment. Eight people with CF (pwCF) with a heterozygous R117H CFTR mutation and chronic lung infection with Pseudomonas aeruginosa (Pa) and/or Staphylococcus aureus were enrolled in a longitudinal study at St. Vincent’s University Hospital in Dublin, Ireland. Breath samples and sputum samples were collected at multiple time points. Correlation analyses were performed between VOC abundances and bacterial load or NE levels. We observed temporal changes in breath profile across the eight subjects during the ivacaftor and/or antibiotic treatment. Within Pa-infected subjects, 54 VOCs showed consistent directional Pearson correlation and at least moderate repeated measures correlation (rmcorr) coefficient (rrm) with bacterial load, including the 12 VOCs previously reported as Pa-associated markers. Similarly, within Sa-infected subjects, we identified eight VOCs that showed consistent directional correlation and at least moderate rrm with bacterial load, including four previously reported Sa-associated markers. Additionally, we identified 7 exploratory VOC candidates that consistently correlated with changes in NE levels, each demonstrating a general weak rrm across eight subjects. This study demonstrates that breath profiles of pwCF change over time during ivacaftor and/or antibiotic treatment. Identifying specific breath VOCs whose levels correlate with Pa or Sa CFU/mL, as well as NE levels, supports further evaluation of exhaled breath VOCs as non-invasive markers for monitoring airway infection and inflammation in pwCF.