Frederick W Woodley1, Emrah Gecili2, Rhonda D Szczesniak3, Chandra L Shrestha4, Christopher J Nemastil5, Benjamin T Kopp6, Don Hayes7. 1. Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus, OH, USA. 2. Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA. 3. Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA; Division of Biostatistics and Epidemiology, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA. 4. Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. 5. Division of Pulmonary Medicine, Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus, OH, USA. 6. Division of Pulmonary Medicine, Nationwide Children's Hospital and the Ohio State University College of Medicine, Columbus, OH, USA; Center for Microbial Pathogenesis, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. 7. Division of Pulmonary Medicine, Cincinnati Children's Hospital Medical Center and University of Cincinnati College of Medicine, Cincinnati, OH, USA. Electronic address: Don.Hayes@cchmc.org.
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.
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.
Authors: Gregory S Sawicki; Edward F McKone; David J Pasta; Stefanie J Millar; Jeffrey S Wagener; Charles A Johnson; Michael W Konstan Journal: Am J Respir Crit Care Med Date: 2015-10-01 Impact factor: 21.405
Authors: Yoshiki Vázquez-Baeza; Alexander A Aksenov; Alexey V Melnik; Embriette Hyde; Andrew C McAvoy; Mingxun Wang; Ricardo R da Silva; Ivan Protsyuk; Jason V Wu; Amina Bouslimani; Yan Wei Lim; Tal Luzzatto-Knaan; William Comstock; Robert A Quinn; Richard Wong; Greg Humphrey; Gail Ackermann; Timothy Spivey; Sharon S Brouha; Nuno Bandeira; Grace Y Lin; Forest Rohwer; Douglas J Conrad; Theodore Alexandrov; Rob Knight; Pieter C Dorrestein; Neha Garg Journal: mSystems Date: 2019-09-24 Impact factor: 6.496