A syndromic framework for progressive pulmonary fibrosis

Pulmonary fibrosis comprises a heterogeneous group of interstitial lung diseases (ILDs) with diverse etiologies but often convergent clinical behaviour. Idiopathic pulmonary fibrosis (IPF) represents the prototypical fibrotic ILD; however, a substantial proportion of patients with non-IPF fibrotic ILDs develop a progressive pulmonary fibrosis (PPF) phenotype characterised by irreversible functional decline, worsening symptoms, increased healthcare utilisation, and excess mortality. Although traditionally classified according to underlying cause, accumulating epidemiological, clinical, and biological evidence indicates that once progression emerges, fibrotic ILDs share common trajectories that transcend etiologic boundaries. Across IPF and non-IPF PPF, longitudinal decline in forced vital capacity represents the dominant marker of disease activity and prognosis, with similar rates of deterioration and comparable mortality risk. Shared genetic susceptibility factors—particularly variants affecting telomere maintenance and epithelial integrity—support the existence of convergent biological vulnerability influencing disease behaviour rather than diagnosis. Clinically, patients with PPF exhibit symptom burden, quality-of-life impairment, risk of acute exacerbations, and need for advanced supportive care that largely overlap with those observed in IPF. Randomised clinical trials further reinforce this convergence, demonstrating that antifibrotic therapies attenuate lung function decline across IPF and PPF populations. Together, these observations support conceptualising PPF as a clinical syndrome, defined by shared trajectories, unmet needs, and phenotype-driven therapeutic responsiveness.