Abstract Rationale Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterised by the accumulation of surfactant-like material within the alveolar spaces. Although progression to pulmonary fibrosis has been reported, the underlying mechanisms remains unclear. This study evaluated computed tomography (CT) features of PAP and their potential association with fibrotic progression. Method SCT scans from 73 PAP patients across five centres in Ireland, France, Germany, USA and were retrospectively reviewed. Two radiologists independently assessed imaging features, including ground-glass opacification, crazy paving, septal thickening, subpleural sparing, cyst formation, consolidation, honeycombing, traction bronchiectasis and overall fibrosis. Proportions of fibrosis between groups were compared using Chi-squared statistical testing. Results The mean age was 50.7 years (range 26 to 71), with a slight female predominance (54.8%) and the majority had a smoking history (71.2%). Prior treatments included whole-lung lavage (87.7%), inhaled GM-CSF (26%), subcutaneous GM-CSF (6.8%), rituximab (6.8%), and plasmapheresis (2.7%). The predominant CT pattern was diffuse ground-glass opacification (91.7%), followed by septal thickening (75.3%), crazy paving (63%), and emphysema (31.5%). Fibrotic features were present in 27.4% of patients, including traction bronchiectasis (26%) and honeycombing (13.7%), with fibrosis involving a mean of 10.9% of total lung volume.Among 50 patients with follow-up CT (median 709.5 days, range 11-5694), ground-glass opacification persisted in 94%. Features of fibrosis significantly increased from 26% to 40% (p = 0.0205), specifically traction bronchiectasis (24% to 38%) and honeycombing (14% to 22%). The mean percentage of fibrotic lung also rose significantly from 16.9% to 28.5%(p = 0.0094). Of the 20 patients with fibrosis on follow-up, 19 demonstrated new or worsening changes, and 89% had corresponding parenchymal abnormalities on baseline CT. No significant differences were found between those who developed fibrosis and those who did not with respect to age, smoking history, GM-CSF levels, or prior treatments. Clinical outcomes were similar between groups, though follow-up duration was limited. Conclusion Fibrosis was present in over 27.4% of PAP patients and increased to 40% on serial imaging, suggesting that a subset develops progressive fibrotic change. Although no clear clinical predictors were identified, fibrosis was radiographically preceded by subtle parenchymal abnormalities. These findings highlight the need for further investigation into the mechanisms driving fibrotic transformation in PAP. References: 1. Akira M, Inoue Y, Arai T, et al. Pulmonary Fibrosis on High-Resolution CT of Patients With Pulmonary Alveolar Proteinosis. AJR Am J Roentgenol. 2016;207(3):544-551. doi:10.2214/AJR.15.149823. This abstract is funded by: None
Boyle et al. (Fri,) studied this question.