Pulmonary Alveolar Proteinosis GM-CSF Inhalation Efficacy Trial in Japan

Inclusion criteria

• Age over 16 years and below 80 years (as of the date of registration).
• Can provide signed informed consent.
• 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).
• Autoimmune pulmonary alveolar proteinosis diagnosed by both HR-CT and biopsy and/or BAL as well as GM-CSF antibodies in serum positive.
• 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

Exclusion criteria

• Diagnosed as secondary or hereditary pulmonary alveolar proteinosis
• WBC of 12,000/mm3 or more
• Fever of 38 degree celsius or more
• Severe edema
• History of malignant disease within recent 5 years (not applied to the treated cases of uterine carcinoma in situ and local basal cell carcinoma)
• Complication of cardiovascular diseases including congestive heart failure, angina pectoris, hemorrhagic tendency, etc with severe condition.
• Complication of respiratory diseases such as pulmonary infectious disease(incl. pulmonary tuberculosis), bronchial asthma, lung fibrosis ,interstitial pneumonitis, or bronchiectasis, in which the evaluations of safety and efficacy of GM-CSF therapy are considered as difficult.
• History or complication of infectious diseases which require systemic administration of antibiotics, antifungal or antiviral agents within recent 2 weeks.
• Treatment with other cytokines
• Pregnant or possibly pregnant women, lactating women, and women who desire to become pregnant during the study period
• Patients who have been treated with whole-lung lavage, repeated segmental-lung lavage, or rituximab within 6 months before the start of the study (this criterion does not apply to patients for whom 6 months or more have elapsed after their last lavage or rituximab)
• Severe liver dysfunction (AST > 100 IU/L and/or ALT > 100 IU/L and/or T-bil >3.0mg/dL)
• Severe renal dysfunction (Ccr < 30 mL/min, calculated by Cockcroft-Gault (CG) formula)
• Previous experience of severe and unexplained side-effects during aerosol delivery of any kind of medicinal product
• Treatment with oral or intravenous administration or inhalation of corticosteroids.
• Treatment with other inhaled drugs.
• Previously treated with GM-CSF before the start of the study.
• Demonstrate hypersensitivity to GM-CSF agent.
• Other patients judged to be inappropriate for the study by the attending physician (e.g., patients who are unlikely to complete treatment or are uncooperative).