Association of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort. Academic Article uri icon

Overview

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).

authors

  • Zhang, William Zhengyang
  • Hoffman, Katherine L
  • Schiffer, Kristen T
  • Oromendia, Clara
  • Rice, Michelle C
  • Barjaktarevic, Igor
  • Peters, Stephen P
  • Putcha, Nirupama
  • Bowler, Russell P
  • Wells, J Michael
  • Couper, David J
  • Labaki, Wassim W
  • Curtis, Jeffrey L
  • Han, Meilan K
  • Paine, Robert
  • Woodruff, Prescott G
  • Criner, Gerard J
  • Hansel, Nadia N
  • Diaz, Ivan
  • Ballman, Karla V
  • Nakahira, Kiichi
  • Choi, Mary E
  • Martinez, Fernando J
  • Choi, Augustine M. K.
  • Cloonan, Suzanne M

publication date

  • April 26, 2021

Research

keywords

  • DNA, Mitochondrial
  • NADH Dehydrogenase
  • Pulmonary Disease, Chronic Obstructive

Identity

PubMed Central ID

  • PMC8074408

Scopus Document Identifier

  • 85104874615

Digital Object Identifier (DOI)

  • 10.1186/s12931-021-01707-x

PubMed ID

  • 33902556

Additional Document Info

volume

  • 22

issue

  • 1