Better approach for autoimmune pulmonary alveolar proteinosis treatment: inhaled or subcutaneous granulocyte-macrophage colony-stimulating factor: a meta-analyses

Background: Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare pulmonary disease caused by functional deficiency of granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF therapy in aPAP has been reported effective in some studies. This meta-analyses aimed to evaluate whether GM-CSF therapy, including inhaled and subcutaneous GM-CSF have therapeutic effect in aPAP patients.

Methods: We analyzed 10 studies searched from PubMed, EmBase, Web of Science, Wiley Online Library and Cochrane Collaboration databases to evaluate the pooled effects of GM-CSF treatment in aPAP patients.

Results: Ten observational studies involving 115 aPAP patients were included. The pooled analyses of response rate (81%, p < 0.001), relapse rate (22%, p = 0.009), PaO₂ (13.76 mmHg, p < 0.001) and P(A-a)O₂ (19.44 mmHg, p < 0.001) showed that GM-CSF treatment was effective on aPAP patients. Further analyses showed that inhaled GM-CSF treatment was more effective than subcutaneous GM-CSF therapy, including a higher response rate (89% vs. 71%, p = 0.023), more improvements in PaO₂ (21.02 mmHg vs. 8.28 mmHg, p < 0.001) and P(A-a)O₂ (19.63 mmHg vs. 9.15 mmHg, p < 0.001).

Conclusions: As two routes of exogenous GM-CSF treatment, inhaled and subcutaneous were both proven to have effect on aPAP patients. Furthermore, inhaled GM-CSF therapy showed a higher response rate, more improvements on PaO₂ and P(A-a)O₂ than subcutaneous GM-CSF treatment in aPAP patients, suggesting inhaled GM-CSF therapy could have more benefits on aPAP patients. Therefore, GM-CSF therapy, especially inhaled GM-CSF, might be a promising therapeutic option in treating aPAP.