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

Respir Res. 2021 Apr 26;22(1):126. doi: 10.1186/s12931-021-01707-x.


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: NCT01969344 (SPIROMICS).

Keywords: COPD; Mitochondrial dysfunction; SPIROMICS; mtDNA.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • DNA, Mitochondrial / blood
  • DNA, Mitochondrial / genetics*
  • Disease Progression
  • Exercise Tolerance
  • Female
  • Forced Expiratory Volume
  • Humans
  • Longitudinal Studies
  • Lung / physiopathology
  • Male
  • Middle Aged
  • NADH Dehydrogenase / blood
  • NADH Dehydrogenase / genetics*
  • Prospective Studies
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Severity of Illness Index
  • Smokers
  • Smoking / adverse effects
  • Surveys and Questionnaires
  • Time Factors
  • United States
  • Walk Test


  • DNA, Mitochondrial
  • NADH Dehydrogenase
  • NADH dehydrogenase subunit 1, human

Associated data