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Original Research: Genetic and Developmental Disorders |

Metabolomic Evaluation of Neutrophilic Airway Inflammation in Cystic FibrosisMetabolomics of Neutrophilic Airway Inflammation

Charles R. Esther, Jr, MD, PhD; Raymond D. Coakley, MD; Ashley G. Henderson, MD; Yi-Hui Zhou, PhD; Fred A. Wright, PhD; Richard C. Boucher, MD
Author and Funding Information

From the Division of Pediatric Pulmonology (Dr Esther), the Cystic Fibrosis and Pulmonary Research and Treatment Center (Drs Coakley, Henderson, and Boucher), and the Department of Biostatistics (Drs Zhou and Wright), University of North Carolina at Chapel Hill, Chapel Hill, NC.

CORRESPONDENCE TO: Charles R. Esther Jr, MD, PhD, Pediatric Pulmonology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599; e-mail: Charles_Esther@med.unc.edu


Part of this article has been presented in abstract form (Zhou Y, Wright F, Boucher RC, Esther CR Jr. Metabolomic evaluation of cystic fibrosis airways disease. Am J Respir Crit Care Med. 2013;187:A1165).

FUNDING/SUPPORT: This study was supported by the National Institutes of Health (NIH) [Grant P42-ES005948 to Dr Zhou and Grant P30-ES010126 to Dr Wright]; the NIH/National Heart, Lung, and Blood Institute [Grant K23-HL089708 to Dr Esther and Grants HL34322, HL107168, P01-HL08808, P30-DK065988 (5-52184), P01-HL110873, and P50-HL107168 to Dr Boucher]; and the NIH/National Institute of Environmental Health Sciences [Grant P30-ES10126 to Dr Esther].

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(2):507-515. doi:10.1378/chest.14-1800
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BACKGROUND:  Metabolomic evaluation of cystic fibrosis (CF) airway secretions could identify metabolites and metabolic pathways involved in neutrophilic airway inflammation that could serve as biomarkers and therapeutic targets.

METHODS:  Mass spectrometry (MS)-based metabolomics was performed on a discovery set of BAL fluid samples from 25 children with CF, and targeted MS methods were used to identify and quantify metabolites related to neutrophilic inflammation. A biomarker panel of these metabolites was then compared with neutrophil counts and clinical markers in independent validation sets of lavage from children with CF and adults with COPD compared with control subjects.

RESULTS:  Of the 7,791 individual peaks detected by positive-mode MS metabolomics discovery profiling, 338 were associated with neutrophilic inflammation. Targeted MS determined that many of these peaks were generated by metabolites from pathways related to the metabolism of purines, polyamines, proteins, and nicotinamide. Analysis of the independent validation sets verified that, in subjects with CF or COPD, several metabolites, particularly those from purine metabolism and protein catabolism pathways, were strongly correlated with neutrophil counts and were related to clinical markers, including airway infection and lung function.

CONCLUSIONS:  MS metabolomics identified multiple metabolic pathways associated with neutrophilic airway inflammation. These findings provide insight into disease pathophysiology and can serve as the basis for developing disease biomarkers and therapeutic interventions for airways diseases.

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