The moving target of progressive pulmonary fibrosis: insights for future clinical trials

Progressive pulmonary fibrosis (PPF) is a recently proposed construct to identify individuals with fibrotic interstitial lung disease (ILD) other than idiopathic pulmonary fibrosis (IPF) who develop an IPF-like trajectory, characterised by fibrotic progression despite conventional therapy [1]. PPF leads to excessive extracellular matrix deposition following injury to the alveolar epithelium, leading to architectural distortion, impaired gas exchange and functional decline [2]. Common aetiologies that develop PPF include connective tissue disease-associated ILD, unclassifiable ILD, fibrotic hypersensitivity pneumonitis and other idiopathic interstitial pneumonias [3]. Clinically, PPF typically presents with worsening dyspnoea, exercise limitation, reduced pulmonary function and hypoxaemia, negatively impacting quality of life, imparting a heavy humanistic burden on patients and caregivers, and leading to substantial economic burden [4, 5]. The disease course of PPF is comparable to that of idiopathic pulmonary fibrosis, with worse survival than most malignancies [6].