Abstract
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.
Highlights
The acute respiratory distress syndrome (ARDS) is a lung inflammatory process that develops primarily as a response to respiratory or systemic-induced sepsis, which causes a disproportionate mortality burden in the adult intensive care unit (ICU) and has disabling consequences for years in surviving patients [1,2,3]
We did not observe any association between wb-mtDNA copies and 28-day survival in septic non-ARDS patients, we found a strong association in septic patients who developed ARDS
This indicates that the significant association between the wb-mtDNA copies within 24 h of sepsis diagnosis and 28-day survival observed among all GEN-SEP patients could be explained by those developing ARDS
Summary
The acute respiratory distress syndrome (ARDS) is a lung inflammatory process that develops primarily as a response to respiratory or systemic-induced sepsis, which causes a disproportionate mortality burden in the adult intensive care unit (ICU) and has disabling consequences for years in surviving patients [1,2,3]. ARDS still has no effective and efficient treatment despite multiple studies that have focused on identifying the pathophysiology and improving the prognosis of these patients since it was first described. Lung-protective mechanical ventilation (MV) remains the main standard supportive ARDS treatment [5, 6] and there is no specific pharmacological therapy for it. Identifying specific biomarkers will help to develop early therapeutic and preventive therapies, while assisting in predicting the prognosis of individual ARDS patients [3, 7, 8]
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