Background: Acute respiratory distress syndrome (ARDS) is a heterogeneous condition dependent on the causal trigger and inflammatory response. Hyperinflammatory responses influence outcome and response to therapy. We aimed to analyse circulating inflammatory profiles in ARDS with different triggers to uncover potential therapeutic implications.

Methods: Clinical data and serum samples were collected at time of ICU admission from patients with acute respiratory failure due to streptococcal infectious (n=23), viral infection (COVID-19 n=15; influenza n=14) and acute exacerbation of interstitial lung disease (AE-ILD; n=10) on mechanical ventilation. A set of 30 cytokines/chemokines and other soluble factors were measured via flow cytometry-based multiplex immunoassay. Differentially abundant analytes were correlated with clinical parameters.

Results: The mean age was 57 years and 22,5% were female. At admission, all patients were mechanically ventilated and partially on VV-ECMO support (37% viral; 22% streptococcal and 60% AE-ILD). The inflammatory pattern was well differentiated between ARDS triggers: In streptococcal ARDS, IL17A, IL6, IL10, MIP3A and IL8 were significantly enriched. In AE-ILD, TNFa, LTA, IL4 and IL12p70 were significantly enriched, whereas in viral ARDS, IP10 and ITAC were enriched vs AE-ILD and streptococcal disease.

Chemo-attractants for neutrophils and lymphocytes such as MIP3A (CCL20) and CXCL1 (GROA) were highly associated with organ dysfunction.

Conclusion: Circulating inflammatory profiles in ARDS were well differentiated dependent on trigger and associated with physiological markers of organ dysfunction.