Despite the high prevalence of chronic obstructive pulmonary disease (COPD), there continues to be a large gap in our understanding of disease pathogenesis and mechanisms accounting for large variability in disease phenotype. Untargeted metabolomics is an ideal approach to uncover the metabolic basis of disease, as well as discover unique drug target opportunities aimed at these nodal metabolic drivers of disease. There are very limited data from metabolomics studies from plasma/ serum and exhaled breath condensate that suggest certain metabolic pathways or metabolites might predict the presence and/or severity of COPD phenotypes. We hypothesize that: 1) smokers with COPD will have a metabolomics signature that is distinct from healthy non-COPD smokers; 2) this signature will be associated with clinically relevant manifestations of disease (e.g., GOLD classification, PFT); and 3) metabolomics signatures will be race-specific. The availability of biosamples from a well-characterized population of smokers with and without COPD, combined with our established in-house metabolomics expertise, will allow us to robustly test these novel hypotheses. 

• Patient recruitments were successfully completed at PKUHSC and Michigan Medicine. Samples of both BAL and serum from PKUHSC were transferred to Michigan Medicine for analyses.
• Metabolomics analyses on both PKUHSC cohort and US Spiromics cohort were completed.
• 1 PhD student and 1 faculty from PUHSC received extensive training at Michigan Medicine, mentored by Drs. Stringer, Han and Standiford.

1. Wenqi Diao, MD; Wassim W. Labaki, MD; MeiLan K. Han, MD; Larisa Yeomans, PhD; Yihan Sun, PharmD; Zyad Smiley, BS; Jae Hyun Kim, BS; Cora McHugh, BS; Pingchao Xiang; Ning Shen, MD; Xiaoyan Sun; Chenxia Guo; Ming Lu, MD; Theodore J. Standiford, MD; Bei He, MD; Kathleen A. Stringer, PharmD. Disruption of histidine and energy homeostasis in chronic obstructive pulmonary disease (submitted; International Journal of COPD).
2. Wassim W. Labaki, Tian Gu, Susan Murray, Jeffrey L. Curtis, Larisa Yeomans, Russell P. Bowler, R. Graham Barr, Eric A. Hoffman, Alejandro P. Comellas, Nadia N. Hansel, Christopher B. Cooper, Richard E. Kanner, Robert Paine III, Gerard J. Criner, Mark T. Dransfield, Merry-Lynn N. McDonald, Jerry A. Krishnan, Eugene R. Bleecker, Stephen P. Peters, Prescott G. Woodruff, Wanda K. O’Neal, Wenqi Diao, Bei He, Fernando J. Martinez, Theodore J. Standiford, Kathleen A. Stringer*, MeiLan K. Han*. Serum amino acid concentrations and clinical outcomes in smokers: SPIROMICS metabolomics study (in revision, Nature Communications).

Grants:

1. NIH/NHLBI K23 (Labaki, W.) Metabolomic alterations in patients with COPD. Submitted in June 2019. Under review. 
2. NIH R01 (Standiford, T., Li, Y). Submitted in June 2019. Under review.