A syndromic framework for progressive pulmonary fibrosis

Pulmonary fibrosis comprises a heterogeneous group of interstitial lung diseases (ILDs) with diverse aetiologies 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—together with convergent fibrotic pathways suggest a common biological vulnerability that may influence disease behaviour beyond the original 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. Overall, current evidence supports the view that PPF might represent a clinical syndrome characterised by shared disease trajectories, common clinical needs, and comparable responses to antifibrotic therapy. • Progressive pulmonary fibrosis may represent a clinical syndrome that transcends the underlying aetiology of interstitial lung disease, reflecting shared biological pathways that drive disease progression. • Shared genetic susceptibility factors, although present only in a subset of patients, together with convergent biological pathways—including epithelial injury, aberrant repair responses, fibroblast activation and extracellular matrix deposition—support the concept that diverse fibrotic ILDs may ultimately converge toward common mechanisms driving progressive fibrosis • Functional decline, prognosis, and healthcare needs in progressive pulmonary fibrosis closely resemble those observed in idiopathic pulmonary fibrosis, leading to overlapping clinical management and supportive care requirements. • Randomized clinical trials increasingly support a phenotype-driven therapeutic strategy, with antifibrotic agents demonstrating efficacy across different progressive fibrotic lung diseases. • A syndromic approach to patients with progressive pulmonary fibrosis emphasizes early identification of a progressive phenotype, enabling timely treatment decisions, holistic management, and a shift from aetiology-centred to behaviour-centred care.