Pulmonary alveolar proteinosis GM-CSF inhalation efficacy trial in Japan

INTERVENTION: Intervention type:DRUG. Intervention1:GM‐CSF inhalation therapy, Dose form:INJECTION, Route of administration:INHALATIONAL, intended dose regimen:125mcg BID inhalation for 7days and 7days without inhalation, 12 cycles. Control intervention1:placebo controlled, Dose form:INJECTION, Route of administration:INHALATIONAL, Intended dose regimen:placebo BID inhalation for 7days and 7days without inhalation, 12 cycles. CONDITION: autoimmune pulmonary alveolar proteinosis PRIMARY OUTCOME: improvement in alveolar‐arterial difference of oxygen pressure . Timepoint:24 weeks. SECONDARY OUTCOME: QOL, pulmonary function, HRCT, serum markers. Timepoint: 24 weeks. INCLUSION CRITERIA: 1. age over 16 years and below 80 years (as of the date of registration). 2. can provide signed informed consent. 3. willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures specified in the protocol (including short‐term hospital admission). 4. Autoimmune pulmonary alveolar proteinosis diagnosed by both HR‐CT and biopsy and/or BAL as well as increased GM‐CSF antibodies in serum more than 1mcg/ml. 5. PaO2 < 70 mmHg after 5 minutes spine position at room air, or PaO2 < 75 mmHg after 5 minutes spine position at room air and with symptom(s) including cough, sputum and exertional dyspnea