Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema
Lucas A. Gillenwater,
Katerina J. Kechris,
Katherine A. Pratte,
Nichole Reisdorph,
Irina Petrache,
Wassim W. Labaki,
Wanda O’Neal,
Jerry A. Krishnan,
Victor E. Ortega,
Dawn L. DeMeo,
Russell P. Bowler
Affiliations
Lucas A. Gillenwater
Computational Bioscience Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Katerina J. Kechris
Department of Biostatistics and Informatics, Colorado School of Public Health, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Katherine A. Pratte
Division of Medicine, National Jewish Health, Denver, CO 80206, USA
Nichole Reisdorph
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
Irina Petrache
Division of Medicine, National Jewish Health, Denver, CO 80206, USA
Wassim W. Labaki
Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Wanda O’Neal
Cystic Fibrosis/Pulmonary Research and Treatment Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Jerry A. Krishnan
Breathe Chicago Center, University of Illinois at Chicago, Chicago, IL 60608, USA
Victor E. Ortega
Center for Precision Medicine, Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27157, USA
Dawn L. DeMeo
Channing Division of Network Medicine, and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA
Russell P. Bowler
Division of Medicine, National Jewish Health, Denver, CO 80206, USA
Susceptibility and progression of lung disease, as well as response to treatment, often differ by sex, yet the metabolic mechanisms driving these sex-specific differences are still poorly understood. Women with chronic obstructive pulmonary disease (COPD) have less emphysema and more small airway disease on average than men, though these differences become less pronounced with more severe airflow limitation. While small studies of targeted metabolites have identified compounds differing by sex and COPD status, the sex-specific effect of COPD on systemic metabolism has yet to be interrogated. Significant sex differences were observed in 9 of the 11 modules identified in COPDGene. Sex-specific associations by COPD status and emphysema were observed in 3 modules for each phenotype. Sex stratified individual metabolite associations with COPD demonstrated male-specific associations in sphingomyelins and female-specific associations in acyl carnitines and phosphatidylethanolamines. There was high preservation of module assignments in SPIROMICS (SubPopulations and InteRmediate Outcome Measures In COPD Study) and similar female-specific shift in acyl carnitines. Several COPD associated metabolites differed by sex. Acyl carnitines and sphingomyelins demonstrate sex-specific abundances and may represent important metabolic signatures of sex differences in COPD. Accurately characterizing the sex-specific molecular differences in COPD is vital for personalized diagnostics and therapeutics.
