Characteristics of a Large Cohort of Patients with Autoimmune Pulmonary Alveolar Proteinosis in Japan

• Published in: American journal of respiratory and critical care medicine Vol. 177; no. 7; pp. 752 - 762
• Main Authors: Inoue, Yoshikazu, Trapnell, Bruce C, Tazawa, Ryushi, Arai, Toru, Takada, Toshinori, Hizawa, Nobuyuki, Kasahara, Yasunori, Tatsumi, Koichiro, Hojo, Masaaki, Ichiwata, Toshio, Tanaka, Naohiko, Yamaguchi, Etsuro, Eda, Ryosuke, Oishi, Kazunori, Tsuchihashi, Yoshiko, Kaneko, Chinatsu, Nukiwa, Toshihiro, Sakatani, Mitsunori, Krischer, Jeffrey P, Nakata, Koh, Japanese Center of Rare Lung Diseases Consortium
• Format: Journal Article
• Language: English
• Published: New York, NY Am Thoracic Soc 01.04.2008; American Lung Association; American Thoracic Society
• Subjects: Adolescent; Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Autoantibodies - blood; Autoimmune Diseases - epidemiology; Autoimmune Diseases - physiopathology; Biological and medical sciences; Biomarkers; Biomarkers - blood; Case-Control Studies; Child; Congenital diseases; D. Interstitial Lung Disease; Data collection; Epidemiology; Female; Granulocyte-Macrophage Colony-Stimulating Factor - immunology; Granulocytes; Hospitals; Humans; Incidence; Intensive care medicine; Japan - epidemiology; Lung diseases; Male; Medical sciences; Medical screening; Middle Aged; Natural history; Patients; Pneumology; Prevalence; Pulmonary Alveolar Proteinosis - diagnosis; Pulmonary Alveolar Proteinosis - epidemiology; Pulmonary Alveolar Proteinosis - etiology; Pulmonary hypertension. Acute cor pulmonale. Pulmonary embolism. Pulmonary vascular diseases; Research centers; Risk Factors; Severity of Illness Index; Surfactants; Asia; Japan; United States > US; Autoimmunity; Human; Lung disease; Intensive care; Respiratory disease; Autoantibody; granulocyte/macrophage colony-stimulating factor; Epidemiology; disease severity score; Pulmonary alveolar proteinosis; serum biomarkers; Severity score; Granulocyte macrophage colony stimulating factor; Resuscitation
• ISSN: 1073-449X; 1535-4970
• DOI: 10.1164/rccm.200708-1271OC

Acquired pulmonary alveolar proteinosis (PAP) is a syndrome characterized by pulmonary surfactant accumulation occurring in association with granulocyte/macrophage colony-stimulating factor autoantibodies (autoimmune PAP) or as a consequence of another disease (secondary PAP). Because PAP is rare, prior reports were based on limited patient numbers or a synthesis of historical data. To describe the epidemiologic, clinical, physiologic, and laboratory features of autoimmune PAP in a large, contemporaneous cohort of patients with PAP. Over 6 years, 248 patients with PAP were enrolled in a Japanese national registry, including 223 with autoimmune PAP. Autoimmune PAP represented 89.9% of cases and had a minimum incidence and prevalence of 0.49 and 6.2 per million, respectively. The male to female ratio was 2.1:1, and the median age at diagnosis was 51 years. A history of smoking occurred in 56%, and dust exposure occurred in 23%; instances of familial onset did not occur. Dyspnea was the most common presenting symptom, occurring in 54.3%. Importantly, 31.8% of patients were asymptomatic and were identified by health screening. Intercurrent illnesses, including infections, were infrequent. A disease severity score reflecting the presence of symptoms and degree of hypoxemia correlated well with carbon monoxide diffusing capacity and serum biomarkers, less well with pulmonary function, and not with granulocyte/macrophage colony-stimulating factor autoantibody levels or duration of disease. Autoimmune PAP had an incidence and prevalence higher than previously reported and was not strongly linked to smoking, occupational exposure, or other illnesses. The disease severity score and biomarkers provide novel and potentially useful outcome measures in PAP.