This Article Full Text Full Text (PDF) Online Supplement All Versions of this Article: 200708-1271OCv1 177/7/752    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Inoue, Y. PubMed PubMed Citation Articles by Inoue, Y.

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

¹ Department of Diffuse Lung Diseases and Respiratory Failure, Clinical Research Center, National Hospital Organization (NHO) Kinki-Chuo Chest Medical Center, Osaka, Japan; ² Divisions of Pulmonary Biology and Medicine, Children's Hospital Research Foundation, Cincinnati, Ohio; ³ Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan; ⁴ Niigata University Medical and Dental Hospital, Niigata, Japan; ⁵ Tsukuba University Hospital, Tsukuba, Japan; ⁶ Department of Respirology, Graduate School of Medicine, Chiba University, Chiba, Japan; ⁷ Division of Respiratory Medicine, International Medical Center of Japan, Tokyo, Japan; ⁸ Dokkyo University, Koshigaya Hospital, Tochigi, Japan; ⁹ Chofu Hospital, Tokyo, Japan, ¹⁰ Division of Respiratory Medicine and Allergology, Department of Medicine, Aichi Medical University School of Medicine, Aichi, Japan; ¹¹ NHO Sanyo Hospital, Ube, Japan; ¹² Research Institute for Microbial Diseases, Osaka University, Osaka, Japan; ¹³ Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan; and ¹⁴ University of South Florida, Tampa, Florida

Correspondence and requests for reprints should be addressed to Koh Nakata, M.D., Ph.D., Professor and Chairman, Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 754 Ichibannchoh, Asahimachi-Tohri, Niigata 951-8520, Japan. E-mail: radical{at}med.niigata-u.ac.jp

Rationale: 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.

Objectives: To describe the epidemiologic, clinical, physiologic, and laboratory features of autoimmune PAP in a large, contemporaneous cohort of patients with PAP.

Methods: Over 6 years, 248 patients with PAP were enrolled in a Japanese national registry, including 223 with autoimmune PAP.

Measurements and Main Results: 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.

Conclusions: 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.

Key Words: epidemiology • serum biomarkers • disease severity score • granulocyte/macrophage colony-stimulating factor • autoantibody

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject 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. What This Study Adds to the Field Autoimmune PAP had an incidence and prevalence higher than previously reported and was not strongly linked to smoking, occupational exposure, or other illnesses.