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Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema.

ABSTRACT: 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.

SUBMITTER: Gillenwater LA

PROVIDER: S-EPMC7999201 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema.

Gillenwater Lucas A LA Kechris Katerina J KJ Pratte Katherine A KA Reisdorph Nichole N Petrache Irina I Labaki Wassim W WW O'Neal Wanda W Krishnan Jerry A JA Ortega Victor E VE DeMeo Dawn L DL Bowler Russell P RP

Metabolites 20210311 3

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 a ...[more]

PMID: 33799786

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Project description:BackgroundWith advancing age, the composition of leukocyte subpopulations in peripheral blood is known to change, but how this change differs between men and women and how it relates to frailty is poorly understood. Our aim in this exploratory study was to investigate whether frailty is associated with changes in immune cell subpopulations and whether this differs between men and women. Therefore, we performed in-depth immune cellular profiling by enumerating a total of 37 subpopulations of T cells, B cells, NK cells, monocytes, and neutrophils in peripheral blood of 289 elderly people between 60-87 years of age. Associations between frailty and each immune cell subpopulation were tested separately in men and women and were adjusted for age and CMV serostatus. In addition, a random forest algorithm was used to predict a participant's frailty score based on enumeration of immune cell subpopulations.ResultsIn the association study, frailty was found to be associated with increased numbers of neutrophils in both men and in women. Frailer women, but not men, showed higher numbers of total and CD16- monocytes, and lower numbers of both CD56+ T cells and late differentiated CD4+ TemRA cells. The random forest algorithm confirmed all the findings of the association studies in men and women. In men, the predictive accuracy of the algorithm was too low (5.5%) to warrant additional conclusions on top of the ones derived from the association study. In women however, the predictive accuracy was higher (23.1%), additionally revealing that total T cell numbers and total lymphocyte numbers also contribute in predicting frailty.ConclusionsIn-depth immune cellular profiling revealed consistent associations of frailty with elevated numbers of myeloid cell subpopulations in both men and women. Furthermore, additional associations were found between frailty and lower numbers of some T cell subpopulations, in women only. Thus, our study indicates sex-specific associations of immune subpopulations with frailty. We hope that our study will prompt further investigation into the sex-specific immune mechanisms associated with the development of frailty.

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Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema.

Publications

Metabolomic Profiling Reveals Sex Specific Associations with Chronic Obstructive Pulmonary Disease and Emphysema.

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