Antifibrotic therapy in patients with acute lung injury: a systematic review and meta-analysis

Background: Pulmonary fibrosis is a progressive and often irreversible condition that can develop following acute lung injury (ALI), particularly in patients requiring prolonged mechanical ventilation. Antifibrotic agents such as pirfenidone and nintedanib slow fibrosis progression in idiopathic pulmonary fibrosis, but their role in post-ALI fibrosis remains unclear. This meta-analysis aimed to evaluate the effects of antifibrotic therapy on mortality and secondary outcomes in patients with ALI. Methods: We searched Embase, PubMed, and Cochrane up to 17 March 2025 for randomized controlled trials and observational studies comparing antifibrotic therapy to standard care in patients with ALI. The primary outcome was all-cause mortality at the longest follow-up available. Secondary outcomes were length of hospital stay and radiological and functional findings. Results: We identified six studies (two randomized, two propensity matched and two case control studies) for a total of 697 COVID-19 patients and no study performed on non-COVID-19 patients. Antifibrotic therapy was associated with a significant reduction in all-cause mortality compared to the control group (16.1% vs. 23.9%, OR 0.61, 95% CI 0.40–0.93, p = 0.02, I2 = 40%). The number needed to treat to prevent one death was 13. There was no significant difference in length of hospital stay between the antifibrotic and control groups. Individual studies reported improvements in computed tomography severity scores and pulmonary function parameters in the antifibrotic group. Conclusions: This meta-analysis suggests that antifibrotic therapy might reduce mortality in patients with ALI. Improvements in radiological and functional outcomes indicate a potential role for antifibrotic agents in modifying disease progression. Further well-designed randomized controlled trials are necessary to confirm these results and determine the optimal use of antifibrotic therapy in post-ALI fibrosis. The PROSPERO Registration: The study protocol was prospectively registered in PROSPERO (registration number CRD420251001885).