title: Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.
  
  
  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.
authors.affiliation: Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 754 Ichibannchoh, Asahimachi-Tohri, Niigata 951-8520, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Trapnell
authors.forename: Ryushi
authors.initials: R
authors.lastname: Tazawa
authors.forename: Toru
authors.initials: T
authors.lastname: Arai
authors.forename: Toshinori
authors.initials: T
authors.lastname: Takada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hizawa
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Koichiro
authors.initials: K
authors.lastname: Tatsumi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Hojo
authors.forename: Toshio
authors.initials: T
authors.lastname: Ichiwata
authors.forename: Naohiko
authors.initials: N
authors.lastname: Tanaka
authors.forename: Etsuro
authors.initials: E
authors.lastname: Yamaguchi
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Eda
authors.forename: Kazunori
authors.initials: K
authors.lastname: Oishi
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tsuchihashi
authors.forename: Chinatsu
authors.initials: C
authors.lastname: Kaneko
authors.forename: Toshihiro
authors.initials: T
authors.lastname: Nukiwa
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Sakatani
authors.forename: Jeffrey P
authors.initials: JP
authors.lastname: Krischer
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000276:immunology; D006801:Humans; D015994:Incidence; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D011649:Pulmonary Alveolar Proteinosis / Q000175:diagnosis / Q000453:epidemiology* / Q000209:etiology; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor