title: Negative effect of smoking on the performance of the QuantiFERON TB gold in tube test.
abstract: BACKGROUND
  False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. Cigarette smoking is known to increase the risk of tuberculosis (TB) and to impair Interferon-gamma (IFN-γ) responses to antigenic challenge, but the impact of smoking on IGRA performance is not known. The aim of this study was to evaluate the effect of smoking on IGRA performance in TB patients in a low and high TB prevalence setting respectively.
  
  
  METHODS
  Patients with confirmed TB from Denmark (DK, n = 34; 20 smokers) and Tanzania (TZ, n = 172; 23 smokers) were tested with the QuantiFERON-TB Gold In tube (QFT). Median IFN-γ level in smokers and non smokers were compared and smoking was analysed as a risk factor for false negative and indeterminate QFT results.
  
  
  RESULTS
  Smokers from both DK and TZ had lower IFN-γ antigen responses (median 0.9 vs. 4.2 IU/ml, p = 0.04 and 0.4 vs. 1.6, p < 0.01), less positive (50 vs. 86%, p = 0.03 and 48 vs. 75%, p < 0.01) and more false negative (45 vs. 0%, p < 0.01 and 26 vs. 11%, p = 0.04) QFT results. In Tanzanian patients, logistic regression analysis adjusted for sex, age, HIV and alcohol consumption showed an association of smoking with false negative (OR 17.1, CI: 3.0-99.1, p < 0.01) and indeterminate QFT results (OR 5.1, CI: 1.2-21.3, p = 0.02).
  
  
  CONCLUSIONS
  Cigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status.
authors.affiliation: Clinical Research Centre, Copenhagen University Hospital Hvidovre, Kettegårds Alle 30, 2650, Hvidovre, Denmark.
authors.forename: Martine G
authors.initials: MG
authors.lastname: Aabye
authors.forename: Thomas Stig
authors.initials: TS
authors.lastname: Hermansen
authors.forename: Morten
authors.initials: M
authors.lastname: Ruhwald
authors.forename: George
authors.initials: G
authors.lastname: Praygod
authors.forename: Daniel
authors.initials: D
authors.lastname: Faurholt-Jepsen
authors.forename: Kidola
authors.initials: K
authors.lastname: Jeremiah
authors.forename: Maria
authors.initials: M
authors.lastname: Faurholt-Jepsen
authors.forename: Nyagosya
authors.initials: N
authors.lastname: Range
authors.forename: Henrik
authors.initials: H
authors.lastname: Friis
authors.forename: John
authors.initials: J
authors.lastname: Changalucha
authors.forename: Aase B
authors.initials: AB
authors.lastname: Andersen
authors.forename: Pernille
authors.initials: P
authors.lastname: Ravn
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003718:Denmark / Q000453:epidemiology; D005260:Female; D015658:HIV Infections / Q000150:complications; D006801:Humans; D007371:Interferon-gamma; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D013636:Tanzania / Q000453:epidemiology; D014376:Tuberculosis / Q000175:diagnosis / Q000453:epidemiology*; D055815:Young Adult
chemical_list: D007371:Interferon-gamma