Relationship between pulmonary gas transfer, respiratory health-related quality of life (HRQoL), exercise capacity, and surfactant burden in autoimmune pulmonary alveolar proteinosis (aPAP)

<bold>Background:</bold> Molgramostim inhalation solution (MOL) is an investigational recombinant granulocyte-macrophage colony stimulating factor being evaluated for the treatment of aPAP in a Phase 3 clinical trial (IMPALA-2). IMPALA-2 met its primary endpoint, change from baseline to week (wk) 24 in percent predicted diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLco%). DLco% is a standardized measure used to assess gas transfer in aPAP. <bold>Objective:</bold> To evaluate the relationship between DLco% and selected secondary/exploratory endpoints in IMPALA-2. <bold>Methods:</bold> Patients received MOL (300 µg) or placebo (PBO) once daily for 48 wks. Post hoc analyses were conducted in combined MOL and PBO groups to determine the relationship (Spearman correlation coefficients) between changes from baseline in: 1) DLco% and St. George’s Respiratory Questionnaire Total score (SGRQ-T); 2) DLco% and exercise capacity (peak metabolic equivalents [METs]) at wks 24 and 48; 3) DLco% and ground-glass opacity (GGO) HRCT score at wk 24. <bold>Results:</bold> Significant negative correlations were observed between DLco% and SGRQ-T (lower scores = better HRQoL) at wk 24 (r=-0.46, P<0.0001; n=144) and wk 48 (r=-0.46, P<0.0001; n=142). Significant positive correlations were observed between DLco% and peak METs at wk 24 (r=0.40, P<0.0001; n=143) and wk 48 (r=0.38, P<0.0001; n=140). A significant negative correlation was observed between DLco% and GGO scores (lower scores = less surfactant) at wk 24 (r=-0.74, P<0.0001; n=154). <bold>Conclusion:</bold> Results support the clinical relevance of changes in DLco% in aPAP.