摘要BACKGROUND:Acute respiratory failure(ARF)is a heterogeneous syndrome in which early differentiation between infection-related and non-infection-related etiologies remains challenging.This study aimed to characterize the inflammatory profile of type Ⅰ ARF and identify candidate biomarkers associated with the infection-related type Ⅰ ARF.METHODS:In this prospective observational cohort study,98 patients with type Ⅰ ARF and 30 healthy controls were enrolled.The plasma levels of 92 inflammation-related proteins were measured using the Olink Inflammation Panels.Type Ⅰ ARF-associated biomarkers were first identified by comparing type Ⅰ ARF patients with healthy controls,followed by the identification of infection-related biomarkers within the type Ⅰ ARF cohort.False discovery rate correction and random forest-based feature ranking were applied.RESULTS:Compared with non-infection-related type Ⅰ ARF(NonInf-ARF),infection-related type Ⅰ ARF(Inf-ARF)was associated with a higher incidence of acute respiratory distress syndrome(ARDS)and greater use of advanced life-support therapies.A comparison with healthy controls identified 64 significantly dysregulated biomarkers,representing the inflammatory features of type ⅠARF.Twenty of the 64 type Ⅰ ARF-associated biomarkers remained significantly different between the Inf-ARF and NonInf-ARF groups(q＜0.05).Neurotrophin-3(NT-3),interleukin-18 receptor 1(IL-18R1),interleukin-18(IL-18),and C-X-C motif chemokine ligand 10(CXCL10)consistently ranked among the top features across the different analytical methods.CONCLUSION:NT-3,IL-18R1,IL-18,and CXCL10 were identified as candidate biomarkers associated with the Inf-ARF,which may provide additional information for early etiologic stratification.