Pulmonary hypertension during high-dose GM-CSF therapy of autoimmune pulmonary alveolar proteinosis
Ali Ataya, Stephen Mitchel, Brenna Carey, Jeffrey Sippel, Cormac McCarthy, Bruce C. Trapnell
https://doi.org/10.1002/pul2.70020
Abstract
To the editor,
Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by alveolar surfactant accumulation, progressive dyspnea, and hypoxemic respiratory insufficiency, and in some patients, secondary infections, pulmonary fibrosis, respiratory failure, and death.1 GM-CSF (granulocyte/macrophage colony-stimulating factor) autoantibodies cause aPAP by blocking GM-CSF signaling, which impairs alveolar macrophage functions including surfactant clearance.2
Inhaled GM-CSF is a pharmacologic approach in development as therapy of aPAP that restores GM-CSF-dependent macrophage functions including surfactant clearance. Several studies, including two controlled clinical trials, reported that inhaled recombinant GM-CSF (rGM-CSF) is effective and safe as therapy of aPAP when administered at daily doses of 250–300 μg.3-5 Clinical experience and small studies suggest the existence of a dose–response relationship for inhaled rGM-CSF therapy of aPAP.6 Notwithstanding, no controlled studies have identified a treatment dose, frequency, or duration needed to achieve maximum therapeutic benefit or studied the safety of higher doses.
We describe an aPAP patient who developed transient pulmonary hypertension while receiving “high-dose” inhaled rGM-CSF (sargramostim).