1. In patients with pulmonary alveolar proteinosis, use of twice daily inhaled granulocyte-macrophage colony-stimulating factor (GM-CSF) did not improve clinical outcomes of vital capacity or functional walk test compared to placebo treated patients.
2. Laboratory and imaging metrics suggestive of reduced pulmonary disease were noted in GM-CSF treated patients.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Accumulation of surfactant within pulmonary alveoli, often due to autoimmunity against GM-CSF, is the pathologic finding observed in patients with pulmonary alveolar proteinosis. The present treatment to reduce surfactant is lung lavage which is invasive and requires repeated procedures. Preclinical and early clinical studies have shown inhaled GM-CSF can break down surfactant and improve gas exchange, though the efficacy of treatment in patients with mild-to-moderate disease is unknown. The Pulmonary Alveolar Proteinosis GM-CSF Inhalation Efficacy (PAGE) trial randomized patients to receive inhaled GM-CSF or placebo over 24 weeks. The primary outcome of change in alveolar-arterial (AA) gradient between baseline and week 25 showed a significant improvement in the treatment group. Additionally, reduced pulmonary intensity characteristic of reduced fluid was seen in treated patients. Clinical metrics including patient-reported disease outcomes, vital capacity, and functional walk testing were similar in the treatment and placebo groups.
This randomized trial suggests inhaled GM-CSF is improving physiologic gas exchange in pulmonary alveolar proteinosis patient lungs. Validation of clinical efficacy may require longer follow-up, alternate dosing, or study in patients with a different disease severity.
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