Association of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort.

TitleAssociation of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort.
Publication TypePublication
Year2021
AuthorsZhang WZ, Hoffman KL, Schiffer KT, Oromendia C, Rice MC, Barjaktarevic I, Peters SP, Putcha N, Bowler RP, J Wells M, Couper DJ, Labaki WW, Curtis JL, Han MK, Paine R, Woodruff PG, Criner GJ, Hansel NN, Diaz I, Ballman KV, Nakahira K, Choi ME, Martinez FJ, Choi AMK, Cloonan SM
JournalRespir Res
Volume22
Issue1
Pagination126
Date Published2021 Apr 26
ISSN1465-993X
KeywordsAged, Disease Progression, DNA, Mitochondrial, Exercise Tolerance, Female, Forced Expiratory Volume, Humans, Longitudinal Studies, Lung, Male, Middle Aged, NADH Dehydrogenase, Prospective Studies, Pulmonary Disease, Chronic Obstructive, Severity of Illness Index, Smokers, smoking, Surveys and Questionnaires, Time Factors, United States, Walk Test
Abstract

BACKGROUND: There is a lack of mechanism-driven, clinically relevant biomarkers in chronic obstructive pulmonary disease (COPD). Mitochondrial dysfunction, a proposed disease mechanism in COPD, is associated with the release of mitochondrial DNA (mtDNA), but plasma cell-free mtDNA has not been previously examined prospectively for associations with clinical COPD measures.METHODS: P-mtDNA, defined as copy number of mitochondrially-encoded NADH dehydrogenase-1 (MT-ND1) gene, was measured by real-time quantitative PCR in 700 plasma samples from participants enrolled in the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) cohort. Associations between p-mtDNA and clinical disease parameters were examined, adjusting for age, sex, smoking status, and for informative loss to follow-up.RESULTS: P-mtDNA levels were higher in participants with mild or moderate COPD, compared to smokers without airflow obstruction, and to participants with severe COPD. Baseline increased p-mtDNA levels were associated with better CAT scores in female smokers without airflow obstruction and female participants with mild or moderate COPD on 1-year follow-up, but worse 6MWD in females with severe COPD. Higher p-mtDNA levels were associated with better 6MWD in male participants with severe COPD. These associations were no longer significant after adjusting for informative loss to follow-up.CONCLUSION: In this study, p-mtDNA levels associated with baseline COPD status but not future changes in clinical COPD measures after accounting for informative loss to follow-up. To better characterize mitochondrial dysfunction as a potential COPD endotype, these results should be confirmed and validated in future studies.TRIAL REGISTRATION:  ClinicalTrials.gov NCT01969344 (SPIROMICS).

DOI10.1186/s12931-021-01707-x
Alternate JournalRespir Res
PubMed ID33902556
PubMed Central IDPMC8074408
Grant ListHHSN268200900017C / HL / NHLBI NIH HHS / United States
HHSN268200900018C / HL / NHLBI NIH HHS / United States
HHSN268200900014C / HL / NHLBI NIH HHS / United States
HHSN268200900020C / HL / NHLBI NIH HHS / United States
HHSN268200900016C / HL / NHLBI NIH HHS / United States
R01 HL132198 / HL / NHLBI NIH HHS / United States
HHSN268200900015C / HL / NHLBI NIH HHS / United States
U01 HL137880 / HL / NHLBI NIH HHS / United States
U24 HL141762 / HL / NHLBI NIH HHS / United States
HHSN268200900013C / HL / NHLBI NIH HHS / United States
R01 HL148215 / HL / NHLBI NIH HHS / United States
HHSN268200900019C / HL / NHLBI NIH HHS / United States
MS#: 
MS194
Manuscript Full Title: 
Association of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort.
Manuscript Lead/Corresponding Author Affiliation: 
Weill Cornell Medical Center
ECI: 
Manuscript Status: 
Published and Public