Association of plasma mitochondrial DNA with COPD severity and progression in the SPIROMICS cohort.
Respir Res
; 22(1): 126, 2021 Apr 26.
Article
em En
| MEDLINE
| ID: mdl-33902556
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).Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
DNA Mitocondrial
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Doença Pulmonar Obstrutiva Crônica
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NADH Desidrogenase
Tipo de estudo:
Clinical_trials
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Diagnostic_studies
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Observational_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
País como assunto:
America do norte
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article