Negative effect of smoking on the performance of the QuantiFERON TB gold in tube test

Martine G Aabye,Morten Ruhwald,Thomas Stig Hermansen,Henrik Friis,Nyagosya Range,Daniel Faurholt-Jepsen,George Praygod,Aase B Andersen,Maria Faurholt-Jepsen,Pernille Ravn,John Changalucha,Kidola Jeremiah

doi:10.1186/1471-2334-12-379

Abstract

BackgroundFalse 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.MethodsPatients 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.ResultsSmokers 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).ConclusionsCigarette smoking was associated with false negative and indeterminate IGRA results in both a high and a low TB endemic setting independent of HIV status.

Highlights

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem
A meta-analysis published in 2011 pooled results from 23 studies of the most widely used IGRA, the QuantiFERON-TB Gold In tube test (QFT) and found that an average of 20% of patients with active TB have a false negative or indeterminate QFT result [3]
These findings suggest a negative effect of smoking on the immune defense which in theory might affect the performance of immunodiagnostic tests, such as the IGRAs

Summary

Introduction

False negative and indeterminate Interferon Gamma Release Assay (IGRA) results are a well documented problem. A recently published study found that mice infected with M. tuberculosis (M.tb.) and later exposed to tobacco smoke had reduced Interferon-gamma (IFN-γ) responses following T-cell stimulation [16] This is in accordance with other recent studies in humans showing that exposure to tobacco smoke reduces IFN-γ production in epithelial cells after antigenic challenge [17] and impairs IFN-γ mediated signaling [18,19,20] and vaccine efficacy [21,22]. These findings suggest a negative effect of smoking on the immune defense which in theory might affect the performance of immunodiagnostic tests, such as the IGRAs

Objectives

Methods

Results

Conclusion