Serum biomarkers as prognostic factors of autoimmune pulmonary alveolar proteinosis after whole lung lavage

Abstract

Background and aim: Whole lung lavage (WLL) is an effective therapy for autoimmune pulmonary alveolar proteinosis (APAP). The aim of this study is to clarify the prognostic factors after WLL in APAP, especially focusing on serum biomarkers. Subjects and Methods: 21 patients had been treated by WLL (total 26 laveges) in our institution from 2001 to 2015, as our prospective consecutive cohort of PAP. We measured serum biomarkers levels (KL-6, SP-D, SP-A, CEA, CYFRA, anti GM-CSF autoantibody) before (baseline levels) and one month after WLL. We analyzed the baseline biomarkers and the % decline of each biomarker (baseline and one month after WLL), changes of disease severity score (DSS) defined by AaDO 2 , efficacy of WLL defined by improvement of DSS, and recurrence-free survival (RFS) afterwards. Recurrence was defined by additional treatment or admission after WLL. Result: Baseline characteristics (M/F; 14/7, median age; 51.9 y.o., median DSS; 3, median % FVC: 77.0%, and median %DLco: 44.4%) had no significant relationship with efficacy or RFS time. Efficacy of WLL was predicted by baseline SP-A levels, delta SP-D, SP-A, CEA and CYFRA (Logistic analysis: p=0.0461, 0.0276, 0.0151, 0.0012, and 0.0040, respectively). RFS time was significantly longer in the patients with larger delta of CEA (cut-off level: 44.4%) and CYFRA (cut-off level: 56.6%) than the patients with smaller delta of the each biomarker (p=0.0212, p=0.0477, respectively). Serum levels of KL-6 and anti GM-CSF antibody had no significant relationship with efficacy of WLL and RFS time. Conclusion: Delta biomarkers levels, especially CEA and CYFRA, can predict efficacy of WLL and recurrence of APAP after WLL.