Whole-Blood Mitochondrial DNA Copies Are Associated With the Prognosis of Acute Respiratory Distress Syndrome After Sepsis

Hernández-Beeftink, Tamara; Guillen-Guio, Beatriz; Rodríguez-Pérez, Héctor; Marcelino-Rodríguez, Itahisa; Lorenzo-Salazar, Jose M.; Corrales, Almudena; Prieto-González, Miryam; Rodríguez-Pérez, Aurelio; Carriedo, Demetrio; Blanco, Jesús; Ambrós, Alfonso; González-Higueras, Elena; Casanova, Nancy G.; González-Garay, Manuel; Espinosa, Elena; Muriel, Arturo; Domínguez, David; de Lorenzo, Abelardo García; Añón, José M.; Soro, Marina; Belda, Javier; Garcia, Joe G. N.; Villar, Jesús; Flores, Carlos

Acute respiratory distress syndrome (ARDS) is an inflammatory process of the lungs that develops primarily in response to pulmonary or systemic sepsis, resulting in a disproportionate death toll in intensive care units (ICUs). Given its role as a critical activator of the inflammatory and innate immune responses, previous studies have reported that an increase of circulating cell-free mitochondrial DNA (mtDNA) is a biomarker for fatal outcome in the ICU. Here we analyzed the association of whole-blood mtDNA (wb-mtDNA) copies with 28-day survival from sepsis and sepsis-associated ARDS. We analyzed mtDNA data from 687 peripheral whole-blood samples within 24 h of sepsis diagnosis from unrelated Spanish patients with sepsis (264 with ARDS) included in the GEN-SEP study. The wb-mtDNA copies were obtained from the array intensities of selected probes, with 100% identity with mtDNA and with the largest number of mismatches with the nuclear sequences, and normalized across the individual-probe intensities. We used Cox regression models for testing the association with 28-day survival. We observed that wb-mtDNA copies were significantly associated with 28-day survival in ARDS patients (hazard ratio = 3.65, 95% confidence interval = 1.39–9.59, p = 0.009) but not in non-ARDS patients. Our findings support that wb-mtDNA copies at sepsis diagnosis could be considered an early prognostic biomarker in sepsis-associated ARDS patients. Future studies will be needed to evaluate the mechanistic links of this observation with the pathogenesis of ARDS.