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American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 215-235, (2002)
© 2002 American Thoracic Society

State of the Art

Pulmonary Alveolar Proteinosis

Progress in the First 44 Years

John F. Seymour and Jeffrey J. Presneill

Ludwig Institute for Cancer Research, Melbourne Tumour Biology Branch, and the Intensive Care Unit, The Royal Melbourne Hospital, Parkville, Australia

Correspondence and requests for reprints should be addressed to Dr. John F. Seymour, Division of Hematology/Medical Oncology, Peter MacCallum Cancer Institute, St. Andrew's Place, East Melbourne, Victoria, 3002, Australia. E-mail: jseymour{at}petermac.unimelb.edu.au

Pulmonary alveolar proteinosis is a rare clinical syndrome that was first described in 1958. Subsequently, over 240 case reports and small series have described at least 410 cases in the literature. Characterized by the alveolar accumulation of surfactant components with minimal interstitial inflammation or fibrosis, pulmonary alveolar proteinosis has a variable clinical course ranging from spontaneous resolution to death with pneumonia or respiratory failure. The most effective proven treatment—whole lung lavage—was described soon after the first recognition of this disease. In the last 8 years, there has been rapid progress toward elucidation of the molecular mechanisms underlying both the congenital and acquired forms of pulmonary alveolar proteinosis, following serendipitous discoveries in gene-targeted mice lacking granulocyte-macrophage colony-stimulating factor (GM-CSF). Impairment of surfactant clearance by alveolar macrophages as a result of inhibition of the action of GM-CSF by blocking autoantibodies may underlie many acquired cases, whereas congenital disease is most commonly attributable to mutations in surfactant protein genes but may also be caused by GM-CSF receptor defects. Therapy with GM-CSF has shown promise in approximately half of those acquired cases treated, but it is unsuccessful in congenital forms of the disease, consistent with the known differences in disease pathogenesis.

Key Words: pulmonary alveolar proteinosis • granulocyte-macrophage colony-stimulating factor • pulmonary surfactants • bronchoalveolar lavage • autoantibodies




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