title: Serum KL-6 is a predictor of outcome in pulmonary alveolar proteinosis.
abstract: BACKGROUND
  Pulmonary alveolar proteinosis (PAP) is a rare disorder characterised by abundant alveolar accumulation of surfactant lipoproteins. Serum levels of KL-6, high molecular weight human MUC1 mucin, are increased in the majority of patients with PAP. The prognostic significance of KL-6 in PAP is still unknown. Aim of the study was to evaluate whether serum KL-6 levels correlate with the outcome of the disease.
  
  
  METHODS
  From 2006 to 2012, we prospectively studied 33 patients with primary autoimmune PAP. We measured serum KL-6 levels by ELISA (Eisai, Tokyo, Japan), and evaluated the correlation between initial KL-6 levels and clinical variables. Disease progression was defined as deterioration of symptoms, and/or lung function, and/or chest imaging.
  
  
  RESULTS
  The initial serum KL-6 levels were significantly correlated with the baseline PaO2, A-aDO2, DLCO, VC and TLC (p=0.042, 0.012, 0.012, 0.02 and 0.013, respectively). The change over time of serum KL-6 correlated with the change over time of DLCO (p=0.017). The initial serum KL-6 levels were significantly higher in patients with disease progression than in those with remission (p<0.001). At a cut-off level of 1526 U/mL, the initial serum KL-6 level predicted disease progression (Se 81%, Sp 94%). At a cut-off level of 2157 U/mL, the initial serum KL-6 predicted the necessity of repeated whole lung lavage (Se 83%, Sp 96%). In the multivariate analysis, the initial serum level of KL-6 was the strongest predictor of disease progression (HR 9.41, p=0.008).
  
  
  CONCLUSIONS
  Serum KL-6 seems to predict outcome in PAP.
authors.affiliation: Department of Pneumology/Allergy, Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany.
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonella
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Ohshimo
authors.forename: Cai
authors.initials: C
authors.lastname: Miaotian
authors.forename: Matthias
authors.initials: M
authors.lastname: Griese
authors.forename: Josune
authors.initials: J
authors.lastname: Guzman
authors.forename: Ulrich
authors.initials: U
authors.lastname: Costabel
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018396:Mucin-1 / Q000097:blood*; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011649:Pulmonary Alveolar Proteinosis / Q000097:blood* / Q000503:physiopathology; D012129:Respiratory Function Tests; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; C060192:MUC1 protein, human; D018396:Mucin-1
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