Pulmonary alveolar proteinosis

Eur Respir Rev. 2011 Jun;20(120):98-107. doi: 10.1183/09059180.00001311.


Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic "crazy paving" pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement.

Publication types

  • Review

MeSH terms

  • Autoimmunity
  • Biopsy
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / immunology
  • Genetic Predisposition to Disease
  • Granulocyte-Macrophage Colony-Stimulating Factor / genetics
  • Humans
  • Immunotherapy
  • Mutation
  • Plasmapheresis
  • Predictive Value of Tests
  • Pulmonary Alveolar Proteinosis* / diagnosis
  • Pulmonary Alveolar Proteinosis* / epidemiology
  • Pulmonary Alveolar Proteinosis* / genetics
  • Pulmonary Alveolar Proteinosis* / immunology
  • Pulmonary Alveolar Proteinosis* / physiopathology
  • Pulmonary Alveolar Proteinosis* / therapy
  • Pulmonary Surfactant-Associated Proteins / genetics
  • Rare Diseases*
  • Respiratory Function Tests
  • Risk Factors
  • Therapeutic Irrigation
  • Tomography, X-Ray Computed
  • Treatment Outcome


  • Pulmonary Surfactant-Associated Proteins
  • Granulocyte-Macrophage Colony-Stimulating Factor