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Chronic Respiratory Disease, Vol. 3, No. 3, 149-159 (2006)
DOI: 10.1191/1479972306cd101rs

Pulmonary alveolar proteinosis

O C Ioachimescu

Department of Pulmonary, Allergy and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA, oioac{at}yahoo.com

M S Kavuru

Department of Pulmonary, Allergy and Critical Care Medicine, The Cleveland Clinic Foundation, Cleveland, OH, USA

Pulmonary alveolar proteinosis is a rare syndrome characterized by intra-alveolar accumulation of surfactant components and cellular debris, with minimal interstitial inflammation or fibrosis. The condition has a variable clinical course, from spontaneous resolution to respiratory failure and death due to disease progression or superimposed infections. The standard of care for alveolor proteinosis therapy is represented by whole lung lavage. Important discoveries have been made in the last decade with respect to disease pathogenesis and therapy of both congenital and acquired forms of the disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway has been shown to be involved in the disease pathogenesis of both acquired and congenital disease. Furthermore, anti-GMCSF blocking autoantibodies have been found in the serum and bronchoalveolar lavage fluid and seem to interfere with the surfactant clearance by alveolar macrophages in many acquired cases. In the congenital form, the most common defects identified to date are several mutations of the genes encoding GM-CSF receptor subunits or surfactant proteins. Using GM-CSF as a therapeutic tool has also been shown to be effective in at least half of the acquired cases treated, while the importance of quantitative determination of anti-GM-CSF antibodies before and during the course of the therapy, as well as the autoantibody titer-GM-CSF dose relationship are to be elucidated. The congenital form of the disease does not respond to therapy with GM-CSF, consistent with the known primary defects and differences in disease pathogenesis.

Key Words: autoantibodies • bronchoalveolar lavage • granulocyte-macrophage colony-stimulating factor (GM-CSF) • pulmonary alveolar proteinosis • pulmonary surfactant

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