Abstract
Acute respiratory distress syndrome (ARDS) results from overwhelming pulmonary inflammation. Prior bulk RNA sequencing provided limited insights into ARDS pathogenesis. We used single cell RNA sequencing to probe ARDS at a higher resolution. PBMCs of patients with pneumonia and sepsis with early ARDS were compared with those of sepsis patients who did not develop ARDS. Monocyte clusters from ARDS patients revealed multiple distinguishing characteristics in comparison with monocytes from patients without ARDS, including downregulation of SOCS3 expression, accompanied by a proinflammatory signature with upregulation of multiple type I IFN-induced genes, especially in CD16+ cells. To generate an ARDS risk score, we identified upregulation of 29 genes in the monocytes of these patients, and 17 showed a similar profile in cells of patients in independent cohorts. Monocytes had increased expression of RAB11A, known to inhibit neutrophil efferocytosis; ATP2B1, a calcium pump that exports Ca2+ implicated in endothelial barrier disruption; and SPARC, associated with processing of procollagen to collagen. These data show that monocytes of ARDS patients upregulate expression of genes not just restricted to those associated with inflammation. Together, our findings identify molecules that are likely involved in ARDS pathogenesis that may inform biomarker and therapeutic development.
Highlights
The acute respiratory distress syndrome (ARDS) is a clinical syndrome that is often life threatening and affects 3 million people worldwide, accounting for up to 10% of intensive care unit (ICU) admissions [1]
Peripheral blood samples were collected from 4 patients at risk for ARDS with pneumonia and sepsis and 3 patients who had advanced to ARDS with sepsis and pneumonia within 24 hours of initiation of mechanical ventilation (Figure 1A)
Given that serum IL-6 and IFN-γ levels have been associated with poor prognosis in ARDS [29, 30], we examined whether the monocyte populations in the ARDS patients had a defect in SOCS3 expression as compared with cells from patients with sepsis only
Summary
The acute respiratory distress syndrome (ARDS) is a clinical syndrome that is often life threatening and affects 3 million people worldwide, accounting for up to 10% of intensive care unit (ICU) admissions [1]. Its clinical manifestations include acute hypoxemia, noncardiogenic pulmonary edema, and reduced lung compliance (increase in stiffness). Despite decades of intense research and multiple clinical trials, treatment options remain limited, relying on supportive care with invasive mechanical ventilation and efforts to reverse the underlying etiology [3,4,5]. ARDS develops rapidly after the initial insult, and since it is not possible to assess lung injury directly, and no consensus is yet reached regarding biomarkers that can be included in the definition of ARDS, indirect clinical criteria are relied upon for a diagnosis of ARDS [6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
