Smoking is a strong independent risk factor for indeterminate and false negative IGRA results

Objectives: 10-40% of IGRA results are indeterminate or false negative. HIV infection, old age and immunosuppressive treatment are known risk factors, but in many cases the reason remains unknown. The aim of this study was to identify risk factors for indeterminate and false negative TB results. Materials and methods: 80 HIV-positive and 112 HIV-negative patients with bacteriologically confirmed pulmonary TB were included and tested with the QuantiFERON-TB (QFT-IT) and a Luminex based IP-10 test. By multivariate analysis the following parameters were tested as risk factors for an indeterminate or false negative QFT-IT or IP-10 test result: HIV-infection, age>50 years, smoking and alcohol consumption. Results: Smokers (28/192) had a higher risk of an indeterminate or false negative result by both the QFT-IT (OR 7.1, CI: 2.2-23.0) and the IP-10 test (OR 11.2, CI: 3.3-37.8). ORs for HIV-infection was 3.6 (CI: 1.8-7.5) and 5.3 (CI: 2.2-11.8) respectively. Antigen levels were lower in smokers for both IFN-γ (median 22 vs. 79.5 pg/ml, p Positivity rate (incl. indeterminate results) was lower for smokers by both the QFT-IT (50 vs. 74%, p=0.03) and the IP-10 test (42 vs. 76, p Apart from HIV-infection no other parameter tested was identified as a risk factor for a false negative or indeterminate result by either test. Conclusion: Smoking increases the risk of having a false negative or indeterminate IGRA results. IGRA test results should be interpreted with care in smokers.