Sweat metabolomics before and after intravenous antibiotics for pulmonary exacerbation in people with cystic fibrosis

Abstract

Background: People with cystic fibrosis (PWCF) suffer from acute unpredictable reductions in pulmonary function associated with a pulmonary exacerbation (PEx) that may require hospitalization. PEx symptoms vary between PWCF without universal diagnostic criteria for diagnosis and response to treatment.

Research question: We characterized sweat metabolomes before and after intravenous (IV) antibiotics in PWCF hospitalized for PEx to determine feasibility and define biological alterations by IV antibiotics for PEx.

Study design and methods: PWCF with PEx requiring hospitalization for IV antibiotics were recruited from clinic. Sweat samples were collected using the Macroduct® Sweat Collection System at admission prior to initiation of IV antibiotics and after completion prior to discharge. Samples were analyzed for metabolite changes using ultra-high-performance liquid chromatography/tandem accurate mass spectrometry.

Results: Twenty-six of 29 hospitalized PWCF completed the entire study. A total of 326 compounds of known identity were detected in sweat samples. Of detected metabolites, 147 were significantly different between pre-initiation and post-completion of IV antibiotics for PEx (average treatment 14 days). Global sweat metabolomes changed from before and after IV antibiotic treatment. We discovered specific metabolite profiles predictive of PEx status as well as enriched biologic pathways associated with PEx. However, metabolomic changes were similar in PWCF who failed to return to baseline pulmonary function and those who did not.

Interpretation: Our findings demonstrate the feasibility of non-invasive sweat metabolomic profiling in PWCF and the potential for sweat metabolomics as a prospective diagnostic and research tool to further advance our understanding of PEx in PWCF.

Keywords: Cystic fibrosis; Metabolomics; Pulmonary exacerbation; Sweat.