Clinical trials on acute exacerbations of interstitial lung diseases.

Introduction: Acute exacerbations in interstitial lung diseases, especially idiopathic pulmonary fibrosis, remain a significant clinical challenge associated with high mortality. Previously used empirical immunosuppressive therapies, notably cyclophosphamide, have proven ineffective.

Areas covered: A literature search was conducted using the PubMed and ClinicalTrials.gov (NCT) databases for studies published up to March 2025. This review summarizes recent randomized clinical trial data on acute exacerbations, highlighting negative results for cyclophosphamide and recombinant thrombomodulin and positive preventive effects of antifibrotics such as nintedanib and pirfenidone. The evidence supporting vaccination strategies, methodological limitations in trial design, and diagnostic challenges are also discussed.

Expert opinion: Shifting clinical practice away from harmful therapies toward precision medicine approaches, utilizing biomarkers, preventive antifibrotic strategies, and novel therapeutic targets, is essential. International collaboration in clinical research is crucial to improve patient outcomes.