Clinical features of autoimmune pulmonary alveolar proteinosis from a large international patient cohort: baseline data from the IMPALA trial

IMPALA is an international Phase III, double-blind, placebo-controlled, randomized trial of inhaled recombinant human GM-CSF (molgramostim) in patients with moderate-severe autoimmune pulmonary alveolar proteinosis (APAP). As prior reports on APAP were from patient cohorts limited to single centers and/or single countries, baseline results from IMPALA offer unique potential insights: 138 eligible APAP patients from 30 sites in 18 countries were enrolled in IMPALA. Compared to other cohorts, IMPALA patients have relatively severe disease as demonstrated by an alveolar-arterial difference in oxygen tension (A-aDO2) of 40.6 ±18.0 mmHg and disease severity score (DSS) of 2.9 ±1.1 (data are mean ±SD). Whereas most series report a 2:1 male predominance, 43 % of subjects in IMPALA are female. The diffusion capacity for carbon monoxide (DLCO) was reduced at 48.6 ±16.3 % of predicted. The arterial O2 was reduced at 66.0 ±11.6 mmHg and reflected by a blood hemoglobin concentration of 15.3 ±1.9 g/L . Serum lactate dehydrogenase (LDH) was elevated in 72% of patients and correlated well with physiological measures. A-aDO2 and DLCO% were the strongest predictors of LDH. The 6-minute walk distance was 436 ±128 m and correlated with other physiological measures. Quality of life was reduced as measured by a Saint George’s Respiratory Questionnaire total score of 40.9 ±19.0 but, interestingly, did not significantly correlate with objective physiological measures. Results demonstrate that APAP patients in the IMPALA cohort have moderately-severe lung disease based on abnormal physiological measures, a high DSS, and poor quality of life.