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

Abstract

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 (13.76mmHg, p<0.001) and P(A-a)O2 (19.44mmHg, 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 (21.02mmHg vs. 8.28mmHg, p<0.001) and P(A-a)O2 (19.63mmHg vs. 9.15mmHg, 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.