Inhaled granulocyte-macrophage colony stimulating factor for mild-to-moderate autoimmune pulmonary alveolar proteinosis - a phase II randomized study for 6 months and follow-up to 24 months

Abstract

<jats:title>Abstract</jats:title> <jats:p>Background: Treatment of autoimmune pulmonary alveolar proteinosis (aPAP) by inhaled granulocyte-macrophage colony stimulating factor (GM-CSF) is considered safe and effective. Evidences of benefit from GM-CSG inhalation for mild to moderate aPAP patients are limited. Methods: In this multicenter, randomized, open-labeled clinical trial, 36 aPAP patients with mild to moderate disease severity were randomized into either GM-CSF treatment group or control group. Inhaled GM-CSF was prescribed for 6 months, and patients were followed-up for another 18 months without treatment. Physiological features of the patients were analyzed.Results: There were 36 patients (19 in treatment group, 17 in control group) included. No significant difference in primary endpoints measured by the change of alveolar arterial oxygen gradient (A-aDO2) from the baseline value 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±10.64mmHg, 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 at 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 than 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.</jats:p>