Portal de Periódicos da CAPES

Therapeutic Whole Lung Lavage

2002; Elsevier BV; Volume: 122; Issue: 4 Linguagem: Inglês

10.1378/chest.122.4.1123

1931-3543

Mani S. Kavuru, Marc J. Popovich,

Medical Imaging and Pathology Studies

Pulmonary alveolar proteinosis (PAP) is characterized clinically by nonresolving pulmonary infiltrates and hypoxemia in patients in their third and fourth decades, and it occurs with a male predominance. This disease is quite remarkable for flooding of the alveoli with lipoproteinaceous material, yet with minimal local lung inflammation or distortion of architecture on biopsy, for reasons that are unknown. The last 8 years have seen some remarkable advances into the pathophysiology of this disease, through transgenic murine models that have clearly established that hematopoietic growth factor (granulocyte-macrophage colony stimulating factor [GM-CSF]) is critical for local regulation of surfactant homeostasis. Additional human studies have clearly linked the presence of a circulating, neutralizing anti–GM-CSF antibody in adults with idiopathic PAP. 1 Kitamura T Uchild K Tanaka N et al. Serological diagnosis of idiopathic pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2000; 162: 658-662 Crossref PubMed Scopus (179) Google Scholar 2 Bonfield TL Russell D Burgess S et al. Autoantibodies against granulocyte-macrophage colony-stimulating factor (GM-CSF) are diagnostic for pulmonary alveolar proteinosis. Am J Respir Cell Mol Biol. 2002; (in press) Google Scholar Therefore, in the current paradigm, there are three major clinical subtypes of PAP: the most common adult idiopathic variety, which is presumably autoimmune (with a circulating anti–GM-CSF antibody); a neonatal variety that is likely due to a defect in surfactant proteins B or C or the common β-chain of the GM-CSF receptor; and secondary PAP associated with occupational exposures or immunologic disorders. To date, there have been no reports of the presence of an antibody in the neonatal variety. Preliminary reports from several groups indicate that a subset of adult patients with idiopathic PAP respond favorably to GM-CSF therapy. 3 Seymour JF Presneill JJ Schoch OD et al. Therapeutic efficacy of granulocyte-macrophage colony-stimulating factor in patients with idiopathic acquired alveolar proteinosis. Am J Respir Crit Care Med. 2001; 163: 523-531 Crossref Scopus (199) Google Scholar 4 Kavuru MS Sullivan EJ Piccin R et al. Exogenous granulocyte-macrophage colony-stimulating factor administration for pulmonary alveolar proteinosis. Am J Respir Crit Care Med. 2000; 161: 1143-1148 Crossref PubMed Scopus (152) Google Scholar