title: CYFRA 21-1 as a disease severity marker for autoimmune pulmonary alveolar proteinosis.
abstract: OBJECTIVE
  Serum markers, including Krebs von den Lungen (KL-6), surfactant protein (SP)-D, SP-A and carcinoembryonic antigen (CEA), are reported to reflect autoimmune pulmonary alveolar proteinosis (APAP) disease severity. We evaluated serum CYFRA21-1 levels as a marker of APAP.
  
  
  METHODS
  In addition to KL-6, SP-D and CEA, we prospectively measured serum CYFRA 21-1 levels in 48 patients with APAP, consecutively diagnosed between 2002 and 2010. Diagnostic usefulness of CYFRA 21-1 was determined from 68 patients with interstitial lung diseases by receiver operator characteristic curve analysis. We evaluated the association between these serum markers and other disease severity markers, including pulmonary function parameters, alveolar-arterial oxygen gradient, British Medical Research Council score reflecting shortness of breath, and disease severity score. CYFRA 21-1 localization in the lung was examined by immunohistochemistry.
  
  
  RESULTS
  Receiver operator characteristic curve demonstrated that CYFRA 21-1 effectively identified APAP. Serum CYFRA 21-1 levels at diagnosis were significantly associated with the measured disease severity parameters. Following whole lung lavage (n = 10) and granulocyte-macrophage colony-stimulating factor (GM-CSF) inhalation (n = 20), serum CYFRA 21-1 levels were significantly decreased. Responders (n = 11) to GM-CSF inhalation revealed significantly higher serum CYFRA 21-1 levels than non-responders (n = 9). Serum CYFRA 21-1 appeared to be a significant predictor of effectiveness of GM-CSF based on regression analysis. Immunohistochemistry showed that CYFRA 21-1 was localized on hyperplastic alveolar type II cells and lipoproteinaceous substances in alveoli.
  
  
  CONCLUSIONS
  Serum CYFRA 21-1 is a sensitive and useful serum marker for diagnosis and evaluation of disease severity of APAP, and may predict the response to GM-CSF inhalation.
authors.affiliation: Department of Respiratory Medicine, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.|Department of Diffuse Lung Diseases and Respiratory Failure, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Arai
authors.affiliation: Department of Diffuse Lung Diseases and Respiratory Failure, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Division of Clinical Trial, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Chikatoshi
authors.initials: C
authors.lastname: Sugimoto
authors.affiliation: Department of Internal Medicine, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Department of Internal Medicine, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Nakao
authors.affiliation: Department of Internal Medicine, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Takeuchi
authors.affiliation: Department of Diffuse Lung Diseases and Respiratory Failure, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Matsumuro
authors.affiliation: Department of Diffuse Lung Diseases and Respiratory Failure, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Hirose
authors.affiliation: Bioscience Medical Research Center, Niigata University Medical and Dental Hospital, Niigata, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Nakata
authors.affiliation: Department of Internal Medicine, National Hospital Organization, Kinki-Chuo Chest Medical Center, Osaka, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hayashi
mesh_terms: D000951:Antigens, Neoplasm / Q000097:blood*; D001327:Autoimmune Diseases / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053539:Keratin-19 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011649:Pulmonary Alveolar Proteinosis / Q000097:blood* / Q000175:diagnosis / Q000276:immunology; D012720:Severity of Illness Index
chemical_list: D000951:Antigens, Neoplasm; D053539:Keratin-19; C102012:antigen CYFRA21.1
keywords: alveolar epithelial hyperplasia; granulocyte-macrophage colony-stimulating factor; inhalation therapy; rare lung disease; whole lung lavage