Effect of pirfenidone on the short- and long-term outcomes in pulmonary infection-related acute respiratory distress syndrome: a prospective cohort study

Pirfenidone, approved for idiopathic pulmonary fibrosis (IPF), slows lung function decline and reduces fibrosis, including in post-COVID-19 pulmonary fibrosis. Its early use in acute respiratory distress syndrome (ARDS) remains uncertain. This study evaluated the effects of early pirfenidone administration on short- and long-term outcomes in pulmonary infection–related ARDS. In this prospective cohort study, 97 ARDS patients were consecutively recruited and assigned to Pirfenidone ( n = 29), Glucocorticoid ( n = 38), or Control ( n = 30) groups according to the severity and clinical course of the disease by the attending clinical team, all receiving standard care. Short-term outcomes included 28-day mortality, ICU length of stay, and hospital length of stay. Long-term outcomes at 3 and 6 months included chest CT fibrosis score, pulmonary function [forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO)], SpO 2 /FiO 2 ratio, modified Medical Research Council (mMRC) dyspnea score, and Activities of Daily Living (ADL) score. Safety was assessed via adverse events and laboratory parameters. At 6 months, the Pirfenidone Group had significantly lower chest CT fibrosis scores than the Glucocorticoid Group [3.0 (0.0–6.5) vs. 6.0 (4.0–8.0), p < 0.05], which was comparable to that of the Control Group. FVC, SpO 2 /FiO 2 , and ADL scores at 3 and 6 months were significantly higher in the Pirfenidone Group compared with both Glucocorticoid and Control groups (all p < 0.01). Long-term outcomes improved relative to baseline ( p < 0.05). Short-term outcomes, mMRC scores, and safety indicators showed no significant differences among groups ( p > 0.05). No severe drug-related adverse events were observed. Early pirfenidone administration in pulmonary infection–related ARDS enhances long-term functional recovery and reduces fibrosis without increasing safety risks, although it does not significantly impact short-term outcomes. These findings support the consideration of early antifibrotic therapy in ARDS management.