To investigate the association between cathepsin S (CTSS) and the severity and prognosis of pneumonia-related acute respiratory distress syndrome (p-ARDS).

This study was a single-center prospective observational study. Twenty-three patients with p-ARDS admitted to the intensive care unit of the Second Hospital of Tianjin Medical University between July 2022 and December 2022 were included as the p-ARDS group. Ten patients with pneumonia alone who were admitted to the respiratory ward during the same period were selected as the pneumonia group. Matched bronchoalveolar lavage fluid (BALF) and serum samples were collected from both groups. The levels of CTSS, interleukin 6 (IL-6), IL-8, and lung surfactant protein D (SP-D) were determined using a Luminex^® magnetic bead multiplex kit. The levels of CTSS were compared based on clinical diagnosis, severity of lung injury, and clinical outcomes. The clinical utility of CTSS was assessed using the receiver operating characteristic (ROC) curve, Spearman correlation, and logistic regression analyses.

Among the p-ARDS group, 10 patients were classified with mild lung injury, 9 with moderate lung injury, and 4 with severe lung injury. Within 28 days of admission, 10 patients in the p-ARDS group died, resulting in a mortality rate of 43.5% (10/23). The level of CTSS in BALF (CTSS^BALF) was higher in the p-ARDS group than in the pneumonia group [94 (76, 103) × 10³ ng/L vs. 15 (5, 54) × 10³ ng/L, Z = 4.152, P < 0.001], whereas there was no significant difference in serum CTSS levels between the two groups [6 (4, 10) × 10³ ng/L vs. 6 (4, 7) × 10³ ng/L, Z = 0.407, P = 0.684]. ROC curve analysis demonstrated that the CTSS^BALF level could effectively distinguish p-ARDS from common pneumonia [area under the curve (AUC) = 0.961, 95% confidence interval (CI) (0.829, 0.998), P < 0.001]. The CTSS^BALF levels were observed to increase with the worsening severity of lung injury and were negatively correlated with the oxygenation index (r = -0.689, P < 0.001). According to the clinical outcomes at 28 days after hospitalization, the 23 p-ARDS patients were divided into a death group (10 cases) and a survival group (13 cases). Among the p-ARDS patients, the non-survivors showed significantly higher CTSS^BALF levels compared to survivors (Z = 2.729, P = 0.006). Logistic regression analysis revealed a trend of an independent correlation between CTSS^BALF and 28-day mortality, but the result did not reach statistical significance [odds ratio = 1.409, 95%CI (0.974, 2.038), P = 0.069].

CTSS^BALF may serve as a valuable biomarker for diagnostic grading and prognostic assessment of patients with p-ARDS.