Pulmonary Fibrosis in Pulmonary Alveolar Proteinosis (PAP): A Multi-centre Computed Tomography (CT) Analysis

<bold>Introduction:</bold> PAP is a rare syndrome marked by the accumulation of surfactant-like material in the alveolar spaces. While progression to pulmonary fibrosis has been observed, its mechanism and prevalence remains unclear. This study evaluates CT features of PAP and their potential role in fibrosis development. <bold>Methods:</bold> This retrospective study analysed CT scans of 73 PAP patients across five centres(Ireland, France, Germany, and USA). Two radiologists independently assessed imaging features, including ground-glass opacification (GGO), crazy paving, septal thickening, subpleural sparing, cyst formation, consolidation, honeycombing, traction bronchiectasis and fibrosis. <bold>Results:</bold> GGO was the most common feature observed 67 patients (91.7%). Fibrosis was present in 20 patients (27.5%). Among 50 patients with follow up CT (median:709.5 days, range: 11 – 5694), 13 (26%) had fibrosis on initial CT. Fibrosis prevalence increased to 40% (20/50) on follow-up. Honeycombing was identified in 7 patients initially, rising to 11. Of the 20 patients with fibrosis on follow up, 11 exhibited de novo fibrosis. No statistical difference was found between these patients and the 30 who did not develop fibrosis, regarding age, smoking history, GM-CSF levels or treatment (whole lung lavage, GM-CSF therapies). Clinical outcomes did not differ significantly between groups. <bold>Conclusion:</bold> Fibrosis was observed in 27.5% of patients, increasing to 40% on follow-up suggesting a progressive fibrotic process in a subset of PAP patients. The absence of a clear clinical correlate or treatment-related factor highlights the need for research into the mechanisms underlying fibrotic transformation in PAP.