Circulating mtDNA Is a Promising Biomarker in Idiopathic Pulmonary Fibrosis

After careful consideration, the American Thoracic Society canceled its annual meeting that was to take place in Philadelphia, Pennsylvania from May 15-20, because of the ongoing coronavirus disease 2019 (COVID-19) pandemic. Although the live events will not proceed as planned, our readers can still find coverage of research that was scheduled to be presented at the meeting. A virtual event is being planned for later this year.

An increase in circulating serum mitochondrial DNA (mtDNA) was associated with worse survival in patients with newly diagnosed idiopathic pulmonary fibrosis, according to study results intended to be presented at the American Thoracic Society (ATS) International Conference. (Select research is slated to be presented in a virtual format later this year.)

Serum samples were obtained from 70 patients (median age, 66 years) at an initial diagnostic workup for idiopathic pulmonary fibrosis. Total DNA were extracted from samples, and quantitative polymerase chain reaction was used to measure mtDNA. The researchers also analyzed patients’ medical records to review patient demographics, laboratory and functional test findings, and prognosis. These factors were assessed to identify correlations with circulating mtDNA.

Overall, patients had a median serum mtDNA level of 693 copies/uL (range, 62-15,101 copies/uL). No differences were found between patients with high mtDNA (>700 copies/uL) and patients with low mtDNA in terms of age, smoking status, body mass index, or pulmonary function. A total of 18 (25.7%) patients had ≥1 acute exacerbation during the median follow-up period of 33.2 months. Patients in the high mtDNA group, however, had significantly worse median survival compared with patients in the low mtDNA group (44 months vs 76 months, respectively; P =.014 by log-rank test).

An additional analysis found that the high mtDNA group had a higher risk of acute exacerbations within 12 months compared with the low mtDNA group (P <.01 by log-rank test). Approximately 66.7% (n=6) of patients in the high mtDNA group who developed an acute exacerbation died within a 6-month period. In contrast, 42.9% (n=3) of patients in the low mtDNA group who developed an acute exacerbation died during within 6 months.

Based on their findings, the researchers suggested that “circulating mtDNA is a promising prognostic biomarker reflecting [acute exacerbation] risk” in patients with newly diagnosed idiopathic pulmonary fibrosis.

Reference

Sakamoto K, Furukawa T, Yamano Y, et al. Increased circulating mitochondrial DNA content predicts fatal complication and worse prognosis in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2020;201:A1088.

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