Effectiveness of granulocyte-macrophage colony-stimulating factor therapy in autoimmune pulmonary alveolar proteinosis: a meta-analysis of observational studies

Chest. 2012 May;141(5):1273-1283. doi: 10.1378/chest.11-0951. Epub 2011 Oct 20.


Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare pulmonary disease caused by functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF). Administration of GM-CSF represents a potential therapeutic strategy in management of aPAP. Herein, we systematically review the efficacy of GM-CSF therapy in aPAP.

Methods: We searched the PubMed and EmBase databases for studies reporting the use of GM-CSF in aPAP. We calculated the proportion with 95% CI to assess the response and relapse rates of GM-CSF therapy in individual studies and pooled them using a random-effects model. Statistical heterogeneity was assessed using the I(2) and Cochran Q tests. Publication bias was analyzed using funnel plot and Egger and Begg-Mazumdar tests.

Results: Our initial searches yielded 1,585 studies. Of these, five observational studies (involving 94 patients) were included for analysis. Three studies used the subcutaneous route, and two studies used the inhalational route for GM-CSF administration. The response rate of GM-CSF varied from 43% to 92%, with the pooled response rate being 58.6% (95% CI, 42.7-72.9). The relapse rate in GM-CSF responders was 29.7% (95% CI, 10.5-60.4). There was no evidence of statistical heterogeneity or publication bias for the outcome of response. GM-CSF therapy was associated with minor complications, such as fever and local complications at the site of administration.

Conclusions: GM-CSF represents a useful approach in the treatment of aPAP. The optimal indication, dose and duration of therapy, and the factors predicting response and relapse need to be defined by future studies.

Publication types

  • Meta-Analysis

MeSH terms

  • Administration, Inhalation
  • Autoantibodies / blood
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / immunology
  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / adverse effects
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use*
  • Humans
  • Injections, Subcutaneous
  • Prospective Studies
  • Pulmonary Alveolar Proteinosis / drug therapy*
  • Pulmonary Alveolar Proteinosis / immunology
  • Recurrence


  • Autoantibodies
  • Granulocyte-Macrophage Colony-Stimulating Factor