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

TitleBronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma.
Publication TypePublication
Year2019
AuthorsHalper-Stromberg E, Gillenwater L, Cruickshank-Quinn C, O'Neal WKay, Reisdorph N, Petrache I, Zhuang Y, Labaki WW, Curtis JL, Wells J, Rennard S, Pratte KA, Woodruff P, Stringer KA, Kechris K, Bowler RP
JournalMetabolites
Volume9
Issue8
Date Published2019 Jul 25
ISSN2218-1989
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. FEV/FVC (Forced Expiratory Volume in One Second/Forced Vital Capacity) ratio, emphysema, FEV % 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 FEV/FVC and emphysema. K-means BAL metabolomic signature clustering identified two groups, one with more airway obstruction (34% of subjects, median FEV/FVC 0.67), one with less (66% of subjects, median FEV/FVC 0.77; < 2 × 10). Associations between metabolites and COPD phenotypes are more robustly represented in BAL compared to plasma.

DOI10.3390/metabo9080157
Alternate JournalMetabolites
PubMed ID31349744
PubMed Central IDPMC6724137
Grant ListR01 HL137995 / HL / NHLBI NIH HHS / United States
U01 HL089897 / HL / NHLBI NIH HHS / United States
I01 CX000911 / CX / CSRD VA / United States
P20 HL113445 / HL / NHLBI NIH HHS / United States
K24 HL137013 / HL / NHLBI NIH HHS / United States
R01 HL125583 / HL / NHLBI NIH HHS / United States
U01 HL089856 / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
MS#: 
MS203
Manuscript Full Title: 
Bronchoalveolar Lavage Fluid from COPD Patients Reveals More Compounds Associated with Disease than Matched Plasma.
Manuscript Lead/Corresponding Author Affiliation: 
Clinical Center: Denver (National Jewish Health)
ECI: 
Manuscript Status: 
Published and Public