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

Eitan Halper-Stromberg; Lucas Gillenwater; Charmion Cruickshank-Quinn; Wanda Kay O'Neal; Nichole Reisdorph; Irina Petrache; Yonghua Zhuang; Wassim W Labaki; Jeffrey L Curtis; James Wells; Stephen Rennard; Katherine A Pratte; Prescott Woodruff; Kathleen A Stringer; Katerina Kechris; Russell P Bowler

doi:10.3390/metabo9080157

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

Metabolites. 2019 Jul 25;9(8):157. doi: 10.3390/metabo9080157.

Authors

Eitan Halper-Stromberg^{1

2}, Lucas Gillenwater³, Charmion Cruickshank-Quinn⁴, Wanda Kay O'Neal⁵, Nichole Reisdorph⁶, Irina Petrache^{1

3}, Yonghua Zhuang⁷, Wassim W Labaki⁸, Jeffrey L Curtis⁸, James Wells⁹, Stephen Rennard^{10

11}, Katherine A Pratte³, Prescott Woodruff¹², Kathleen A Stringer¹³, Katerina Kechris¹⁴, Russell P Bowler^{15

16}

Affiliations

¹ School of Medicine, University of Colorado, Aurora, CO 80045, USA.
² Pathology Department, Johns Hopkins University, Baltimore, MD 21287, USA.
³ Department of Medicine, National Jewish Health, Denver, CO 80206, USA.
⁴ Agilent Technologies, Santa Clara, CA 95051, USA.
⁵ Department of Marsico, Lung Institute/Cystic Fibrosis Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁶ Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
⁷ Department of Biostatistics, Colorado School of Public Health, Aurora, CO 80045, USA.
⁸ Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA.
⁹ Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
¹⁰ BioPharmaceuticals R&D, AstraZeneca, Cambridge CB4 0XR, UK.
¹¹ Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68588, USA.
¹² Department of Medicine, UCSF Pulmonary, Critical Care, Allergy and Sleep Medicine, University of California, San Francisco, CA 94143, USA.
¹³ Department of Clinical Pharmacy, College of Pharmacy, University of Michigan, Ann Arbor, MI 48109, USA.
¹⁴ Department of Biostatistics, Colorado School of Public Health, Aurora, CO 80045, USA. katerina.kechris@cuanschutz.edu.
¹⁵ School of Medicine, University of Colorado, Aurora, CO 80045, USA. bowlerr@njhealth.org.
¹⁶ Department of Medicine, National Jewish Health, Denver, CO 80206, USA. bowlerr@njhealth.org.

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.

Keywords: BAL; BALF; COPD; LC–MS; bronchoalveolar lavage; emphysema; mass spectrometry; metabolomics; plasma.

Abstract

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