Inhaled GM-CSF Reduces the Need for Whole Lung Lavage (WLL) and Improves Gas Exchange in Autoimmune Pulmonary Alveolar Proteinosis (aPAP) Patients

<bold>Rationale:</bold> WLL is a widely accepted treatment for aPAP but does not correct myeloid cell dysfunction or reverse the cause of underlying pathology. In contrast, inhaled recombinant GM-CSF is a promising pharmacologic approach that restores alveolar macrophage functions including surfactant clearance. We evaluate WLL followed by inhaled GM-CSF (sargramostim) as therapy of aPAP¹. <bold>Methods:</bold> 18 patients with moderate-to-severe aPAP were enrolled, received a baseline WLL, were randomized into GM-CSF and Control groups receiving inhaled sargramostim or no scheduled therapy, respectively, and followed for 30 months after WLL. Outcome measures included ‘rescue’ WLL for disease progression, assessment of arterial blood gases, pulmonary function, computed tomography, health status, biomarkers, and adverse events. Patients requiring rescue WLL were considered to have failed their assigned intervention group. <bold>Results:</bold> The primary end point, the time to first rescue WLL, was longer in GM-CSF-treated patients than Controls (30 vs 18 months; n=9/group; P=0.0078). Seven (78%) Control patients and only 1 (11%) GM-CSF-treated patient required rescue WLL – a 7-fold increase in relative risk (P=0.015). Compared to Controls, GM-CSF-treated patients also had greater improvement in PaO2, A-aDO2, DLco%, and aPAP biomarkers. No serious adverse events were reported. <bold>Conclusions:</bold> This long-term, prospective, randomized trial1 demonstrated inhaled sargramostim following WLL reduced the requirement for WLL, improved lung function, and was safe in aPAP patients. WLL plus inhaled sargramostim may be useful as combined therapy for aPAP.¹Eur Respir J. 2024;63(1):2301233.