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(Chest. 2006;130:227-237.)
© 2006 American College of Chest Physicians

An Open-Label Trial of Granulocyte Macrophage Colony Stimulating Factor Therapy for Moderate Symptomatic Pulmonary Alveolar Proteinosis*

Saiprakash B. Venkateshiah, MD, FCCP; Tom D. Yan, MD; Tracey L. Bonfield, PhD; Mary Jane Thomassen, PhD; Moulay Meziane, MD; Carmen Czich, RN and Mani S. Kavuru, MD, FCCP

* From the Department of Pulmonary, Allergy and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH.

Correspondence to: Mani S. Kavuru, MD, FCCP, The Cleveland Clinic Foundation, 9500 Euclid Ave, Mail Code A-90, Cleveland, OH 44109; e-mail: kavurum{at}ccf.org

Abstract

Pulmonary alveolar proteinosis (PAP) is a rare idiopathic autoimmune lung disease in adults characterized by the accumulation of lipoproteinaceous material within the alveoli of the lung. The natural history of this disease is poorly defined. Current therapy of bilateral whole-lung lavage (WLL) under general anesthesia is invasive and has its limitations. Data suggest that relative granulocyte macrophage colony stimulating factor (GM-CSF) deficiency may be involved in the pathogenesis of this disease. There have been several case series that have described clinical improvement with exogenous GM-CSF therapy in a subset of patients with PAP. We describe the results of a prospective, open-label clinical trial of daily subcutaneous GM-CSF therapy in a group of adult patients with idiopathic PAP. In this series of 25 patients, the largest reported to date, administration of GM-CSF improved oxygenation as assessed by a 10 mm Hg decrease in alveolar-arterial oxygen gradient, as well as improvement in other clinical and quality of life parameters in 12 of 25 patients (48%) with moderate symptomatic disease who completed the trial. In addition, the serum anti–GM-CSF antibody titer correlated with lung disease activity and was a predictor for responsiveness to therapy. These data indicate that subcutaneous GM-CSF therapy is a promising alternative to WLL for symptomatic patients with PAP.

Key Words: antibodies • granulocyte macrophage colony stimulating factor • immunotherapy • pulmonary alveolar proteinosis






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