Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma

Authors

Eitan Halper-Stromberg, University of Colorado
Lucas Gillenwater, National Jewish Health
Charmion Cruickshank-Quinn, Agilent Technologies
Wanda Kay O'Neal, University of North Carolina at Chapel Hill
Nichole Reisdorph, University of Colorado Anschutz Medical Campus
Irina Petrache, University of Colorado
Yonghua Zhuang, Colorado School of Public Health
Wassim W. Labaki, University of Michigan - Ann Arbor
Jeffrey L. Curtis, University of Michigan - Ann Arbor
James Wells, Cincinnati Children's Hospital Medical Center
Stephen I. Rennard, University of Nebraska Medical CenterFollow
Katherine A. Pratte, National Jewish Health
Prescott Woodruff, University of California, San Francisco
Kathleen A. Stringer, University of Michigan - Ann Arbor
Katerina Kechris, Colorado School of Public Health
Russell P. Bowler, University of Colorado

Document Type

Article

Journal Title

Metabolites

Publication Date

2019

Volume

9

Abstract

Smoking causes chronic obstructive pulmonary disease (COPD). Though recent studies identified a COPD metabolomic signature in blood, no large studies examine the metabolome in bronchoalveolar lavage (BAL) fluid, a more direct representation of lung cell metabolism. We performed untargeted liquid chromatography-mass spectrometry (LC-MS) on BAL and matched plasma from 115 subjects from the SPIROMICS cohort. Regression was performed with COPD phenotypes as the outcome and metabolites as the predictor, adjusted for clinical covariates and false discovery rate. Weighted gene co-expression network analysis (WGCNA) grouped metabolites into modules which were then associated with phenotypes. K-means clustering grouped similar subjects. We detected 7939 and 10,561 compounds in BAL and paired plasma samples, respectively. FEV1/FVC (Forced Expiratory Volume in One Second/Forced Vital Capacity) ratio, emphysema, FEV1 % predicted, and COPD exacerbations associated with 1230, 792, eight, and one BAL compounds, respectively. Only two plasma compounds associated with a COPD phenotype (emphysema). Three BAL co-expression modules associated with FEV1/FVC and emphysema. K-means BAL metabolomic signature clustering identified two groups, one with more airway obstruction (34% of subjects, median FEV1/FVC 0.67), one with less (66% of subjects, median FEV1/FVC 0.77; p < 2 × 10-4). Associations between metabolites and COPD phenotypes are more robustly represented in BAL compared to plasma.

DOI Link

10.3390/metabo9080157

ISSN

2218-1989

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Halper-Stromberg, Eitan; Gillenwater, Lucas; Cruickshank-Quinn, Charmion; O'Neal, Wanda Kay; Reisdorph, Nichole; Petrache, Irina; Zhuang, Yonghua; Labaki, Wassim W.; Curtis, Jeffrey L.; Wells, James; Rennard, Stephen I.; Pratte, Katherine A.; Woodruff, Prescott; Stringer, Kathleen A.; Kechris, Katerina; and Bowler, Russell P., "Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma" (2019). Journal Articles: Pulmonary & Critical Care Med. 32.
https://digitalcommons.unmc.edu/com_pulm_articles/32