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Open AccessArticle

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

School of Medicine, University of Colorado, Aurora, CO 80045, USA
Pathology Department, Johns Hopkins University, Baltimore, MD 21287, USA
Department of Medicine, National Jewish Health, Denver, CO 80206, USA
Agilent Technologies, Santa Clara, CA 95051, USA
Department of Marsico, Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Department of Biostatistics, Colorado School of Public Health, Aurora, CO 80045, USA
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Division of Pulmonary Biology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH 45229, USA
BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0XR, UK
Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68588, USA
Department of Medicine, UCSF Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA 94143, USA
Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA
Authors to whom correspondence should be addressed.
Authors contributed equally.
Metabolites 2019, 9(8), 157;
Received: 25 June 2019 / Revised: 12 July 2019 / Accepted: 18 July 2019 / Published: 25 July 2019
(This article belongs to the Special Issue Metabolomics and Chronic Obstructive Lung Diseases)
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. View Full-Text
Keywords: metabolomics; COPD; emphysema; mass spectrometry; LC–MS; bronchoalveolar lavage; BAL; BALF; plasma metabolomics; COPD; emphysema; mass spectrometry; LC–MS; bronchoalveolar lavage; BAL; BALF; plasma
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Halper-Stromberg, E.; Gillenwater, L.; Cruickshank-Quinn, C.; O’Neal, W.K.; Reisdorph, N.; Petrache, I.; Zhuang, Y.; Labaki, W.W.; Curtis, J.L.; Wells, J.; Rennard, S.; Pratte, K.A.; Woodruff, P.; Stringer, K.A.; Kechris, K.; Bowler, R.P. Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma. Metabolites 2019, 9, 157.

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