Characteristics of a large cohort of patients with autoimmune pulmonary alveolar proteinosis in Japan.
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.
Inoue
Yoshikazu
Y
Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, 754 Ichibannchoh, Asahimachi-Tohri, Niigata 951-8520, Japan.
Trapnell
Bruce C
BC
Tazawa
Ryushi
R
Arai
Toru
T
Takada
Toshinori
T
Hizawa
Nobuyuki
N
Kasahara
Yasunori
Y
Tatsumi
Koichiro
K
Hojo
Masaaki
M
Ichiwata
Toshio
T
Tanaka
Naohiko
N
Yamaguchi
Etsuro
E
Eda
Ryosuke
R
Oishi
Kazunori
K
Tsuchihashi
Yoshiko
Y
Kaneko
Chinatsu
C
Nukiwa
Toshihiro
T
Sakatani
Mitsunori
M
Krischer
Jeffrey P
JP
Nakata
Koh
K
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
D001323:Autoantibodies; D015415:Biomarkers; D016178:Granulocyte-Macrophage Colony-Stimulating Factor