Clinical characteristics and survival in patients with pulmonary alveolar proteinosis (PAP) with and without pulmonary fibrosis.

<bold>Background:</bold> Pulmonary alveolar proteinosis (PAP) is characterized by surfactant accumulation in alveoli. Its progression to fibrosis is poorly understood. This study was aimed at comparing clinical characteristics, pulmonary function and radiological findings between fibrotic and non-fibrotic PAP patients and identifying potential predictors of fibrosis. <bold>Patients and methods:</bold> This single-center retrospective analysis included consecutive PAP patients. Demographics, lab tests, BAL cytology, PFTs, 6MWT, and HRCT scans were collected at first presentation. Fibrosis was defined as the presence of reticulation, traction bronchiectases, or honeycombing. <bold>Results:</bold> 41 patients (17 F / 24 M) with autoimmune (N=35), secondary (N=3) and hereditary (N=3) PAP were studied; 14 patients had fibrotic and 27 non-fibrotic PAP. Fibrotic PAP patients had lower FVC% (56±5 vs 71±3%, p=0.011), lower DLCO (34±5 vs 55±4%, p=0.004), at time of HRCT. BAL cytology showed less lymphocytes in fibrotic than non fibrotic PAP (26±5 vs 47±10%, p=0.035). GM-CSF antibody titer was higher in the non-fibrotic group (35±9 vs 57±9 mcg/ml, p=0.149). Median survival time was significantly shorter in patients with fibrotic compared to non fibrotic PAP (55 vs 151 months, p=0.012). At Cox regression analysis lung fibrosis was the strongest predictor of death (HR = 10.91, 95% CI: 1.03–115.53; p=0.047). <bold>Conclusions:</bold> Patients with fibrotic PAP have worse lung function impairment, lower BAL lymphocytosis, and shorter survival time. Lung fibrosis seems to be the strongest predictor of mortality in PAP.