Inhaled granulocyte-macrophage colony stimulating factor for mild-to-moderate autoimmune pulmonary alveolar proteinosis - a six month phase II randomized study with 24 months of follow-up

Orphanet J Rare Dis. 2020 Jul 2;15(1):174. doi: 10.1186/s13023-020-01450-4.


Background: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) is considered safe and effective. Evidence of benefit from GM-CSG inhalation for mild to moderate aPAP patients is limited.

Methods: In this multicenter, randomized, open-labeled clinical trial, 36 aPAP patients with mild to moderate disease severity were randomized into either the GM-CSF treatment group or control group. Inhaled GM-CSF was prescribed for 6 months, and patients received follow-up for another 18 months without treatment. Physiological features of the patients were analyzed.

Results: There were 36 patients (19 in the treatment group, 17 in the control group) included. There were no significant differences in the primary endpoints as measured by the change of alveolar arterial oxygen gradient (A-aDO2) from the baseline values to the values obtained during treatment or during the following 18-month non-treatment observation period [control group vs. treatment group: 0.51 ± 12.09 mmHg vs. -0.35 ± 13.76 mmHg, p = 0.848 (3 month); 1.85 ± 11.21 mmHg vs. 7.31 ± 8.81 mmHg, p = 0.146 (6 months); 6.05 ± 11.14 mmHg vs. 6.61 ± 10.64 mmHg, p = 0.899 (24 months)]). Percentage of diffusion capacity predicted (DLCO%) and percentage of total lung capacity predicted (TLC%), however, were significantly improved in the treatment group by the end of the study (P = 0.010 and 0.027). St. George Respiratory questionnaire (SGRQ) scores were better after 6 months treatment with GM-CSF compared to the control group, and the benefits of treatment were maintained throughout the observation period. No severe side effects were observed during the study.

Conclusion: Six months of inhaled GM-CSF treatment had no effect on the alveolar-arterial oxygen gradient in patients with mild to moderate pulmonary alveolar proteinosis. There were changes in some clinical or laboratory measures, but no clinically important changes were noted at the end of study. (Clinical Trial Registry: NCT02243228, Registered on September 17, 2014, ).

Keywords: Autoimmune pulmonary alveolar proteinosis; Granulocyte-macrophage colony stimulating factor; Inhalation.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Follow-Up Studies
  • Granulocyte-Macrophage Colony-Stimulating Factor / therapeutic use
  • Granulocytes
  • Humans
  • Macrophage Colony-Stimulating Factor
  • Pulmonary Alveolar Proteinosis* / drug therapy


  • Macrophage Colony-Stimulating Factor
  • Granulocyte-Macrophage Colony-Stimulating Factor

Associated data