Long-term observational study on autoimmune pulmonary alveolar proteinosis (aPAP)

[Objective] This study aimed to clarify the detailed long-term clinical courses of aPAP. [Methods] Sixty-four patients (37 men and 27 women, median age of 57) followed-up for more than 3 years (median 7.8 yr) were selected from more than 100 patients with aPAP seen at our referrel center from 2003 to 2024, and retrospectively analyzed by chart review. Diagnosis and the determination of disease severity score (DSS) were based on the previous report (AJRCCM 2008, 177:752). Serum autoantibody levels against GM-CSF (anti-GMAb) were measured over time in 38 patients at baseline (T0), 3 to 5 years later (T1), 5 to 10 years later (T2), and more than 10 years later (T3), according to the follow-up length. [Results] Twenty-nine patients (45%) underwent whole lung lavage (WLL). GM-CSF inhalation therapy was done in 30 (47%) patients. DSS scores at the initial visit were increased (worse) in 10 patients (16%), unchanged in 26 (41%, DSS was 1 in 10 patients whose DSS could not get better), and decreased (better) in 28 (43%) at the last visit. Three patients died from aPAP. Baseline %FVC and the presence of fibrotic pattern by CT scan, but not WLL or GM-CSF inhalation were significant variables for decreased DSS in patients with DSS>1 at the initial visit (n=46) by multivariate logistic regression analysis (%FVC, odds ratio 1.05, p<0.05; fibrotic pattern, odds ratio 0.15, p<0.05). Anti-GMAb levels decreased over time (T1 vs T0, p<0.001; T2 vs T1, p<0.001; T3 vs T2, p<0.001); however, they were not correlated with DSS changes. [Conclusion] The overall clinical course of aPAP is generally favorable. Nevertheless, the importance of GM-CSF inhalation ± WLL should be emphasized to overcome the period of high DSS.