Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis

Pulmonary alveolar proteinosis (PAP) is a rare lung disease characterized b y the accumulation of lipoproteinaceous material within the alveoli. Recent data suggest that granulocyte-macrophage colony- stimulating factor (GM-CS F) may be involved in the pathogenesis of PAP. To extend this understanding and clarify whether GM-CSF replacement confers benefit, we report the prel iminary results for the first four patients in an open-label study of GM-CS F treatment for moderate exacerbation of PAP. All four patients had idiopat hic PAP confirmed by open lung biopsy. Subcutaneous GM-CSF was self-adminis tered once daily for 12 wk (dose escalation from 3 to 9 mu g/kg/d). Respons e was assessed from symptom scores, arterial blood gas measurements, pulmon ary function testing, and chest radiographs. Three of the four patients exp erienced symptomatic, physiologic, and radiographic improvement with GM-CSF . Responders experienced sufficient improvement in oxygenation as to elimin ate the need for supplemental oxygen, and one patient was removed from the waiting list for lung transplantation. Improved oxygenation was not apparen t until 8 to 12 wk after the start of therapy. Notably, expected increases in the peripheral white blood cell count did not occur, suggesting lack of a hematopoietic response to exogenous GM-CSF in PAP. We conclude that GM-CS F appears to benefit a subset of patients with adult PAP, and may represent an alternative to whole-lung lavage in treating the disease.