Progressive pulmonary fibrosis: a state-of-the-art review

Fibrosing interstitial lung diseases (ILDs) encompasses a large number of diverse conditions, the prototype being idiopathic pulmonary fibrosis (IPF), characterized by irreversible progression, accounting for loss of lung function, exercise intolerance, and complications especially acute exacerbation and respiratory failure leading to early mortality. A significant proportion of patients with fibrosing ILDs other than IPF will develop a progressive phenotype comparable to IPF. Progression occurs despite conventional treatment which, depending on the underlying condition, may include close monitoring, antigen eviction, glucocorticoids, immunosuppressive therapy, and pulmonary rehabilitation. Progressive pulmonary fibrosis (PPF) has a disease course similar to IPF, with worsening respiratory symptoms, decline in lung function, impairment of quality of life, and premature death. In 2019, a phase III trial demonstrated that treatment with the tyrosine kinase inhibitor nintedanib halves disease progression as measured by a decline in forced vital capacity over one year, and contributed to the validation of the PPF concept. In the 2022 international clinical practice guideline, nintedanib received a conditional recommendation to treat patients with PPF. In 2025, it was demonstrated that the phosphodiesterase 4B inhibitor nerandomilast further reduces disease progression in patients with PPF. Other smaller trials have suggested that pirfenidone may also benefit patients with PPF. Several newer compounds are currently being developed for both IPF and PPF. As a diagnosis of PPF identifies patients with fibrotic disease progression, early identification is warranted for the timely initiation of antifibrotic therapy, consideration of lung transplantation if eligible, and holistic care.