title: Free light chains: potential biomarker and predictor of mortality in alpha-1-antitrypsin deficiency and usual COPD.
abstract: BACKGROUND
  Circulating free light chains (FLCs) can alter neutrophil migration, apoptosis and activation and may be a biomarker of autoimmune disease and adaptive immune system activation. These pathogenic roles could be relevant to lung disease in alpha 1 antitrypsin deficiency (A1ATD) and chronic obstructive pulmonary disease (COPD).
  
  
  METHODS
  Total combined (c)FLCs were measured using the FreeLite® assay in 547 patients with A1ATD and 327 patients with usual COPD in the stable state, and assessed for association with clinical phenotype, disease severity, airway bacterial colonisation and mortality. Univariate and multivariate analyses were undertaken.
  
  
  RESULTS
  Circulating cFLCs were static in the stable state when measured on 4 occasions in A1ATD and twice in usual COPD. Levels were inversely related to renal function (A1ATD and COPD p = <0.01), and higher in patients with chronic bronchitis (p = 0.019) and airway bacterial colonisation (p = 0.008). After adjusting for renal function and age the relationship between cFLCs and lung function was weak. Kaplan Meier curves showed that cFLC > normal (43.3 mg/L) significantly associated with mortality in both cohorts (A1ATD p = 0.001, COPD p = 0.013).
  
  
  CONCLUSIONS
  cFLCs may be a promising biomarker for risk stratification in A1ATD and COPD.
authors.affiliation: Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, UK.|ADAPT Project, University Hospital Birmingham, Birmingham, B15 2WB, UK.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Hampson
authors.affiliation: Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, UK.|ADAPT Project, University Hospital Birmingham, Birmingham, B15 2WB, UK.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Stockley
authors.affiliation: Centre for Translational Inflammation Research, University of Birmingham, Birmingham, B15 2WB, UK. a.m.wood@bham.ac.uk.|ADAPT Project, University Hospital Birmingham, Birmingham, B15 2WB, UK. a.m.wood@bham.ac.uk.|Heart of England NHS Foundation Trust, Birmingham, B9 5SS, UK. a.m.wood@bham.ac.uk.
authors.forename: Alice M
authors.initials: AM
authors.lastname: Turner
mesh_terms: D017677:Age Distribution; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015897:Comorbidity; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000175:diagnosis / Q000401:mortality*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012680:Sensitivity and Specificity; D017678:Sex Distribution; D016019:Survival Analysis; D006113:United Kingdom / Q000453:epidemiology; D019896:alpha 1-Antitrypsin Deficiency / Q000097:blood* / Q000401:mortality*
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains
keywords: Alpha 1 antitrypsin deficiency; Chronic obstructive pulmonary disease; Emphysema; Exacerbations; Immunoglobulin light chains; Mortality