Tumor necrosis factor alpha as a marker of systemic and local inflammation in “healthy” smokers

Abstract

Juan M Diez-Pina1, María J Fernandez-Aceñero3, María J Llorente-Alonso2, Salvador Diaz-Lobato4, Sagrario Mayoralas1, Asuncion Florez11Department of Pneumology; 2Department of Biochemistry, Hospital de Móstoles, Móstoles, Madrid, Spain; 3Department of Pathology, Fundacíon Jiménez-Díaz, Madrid, Spain; 4Department of Pneumology, Hospital Ramón y Cajal, Madrid, SpainBackground: Tobacco smoking induces a local and systemic inflammatory reaction and also a decline in pulmonary function. There are some novel noninvasive methods to measure the degree of inflammatory bronchial reaction, including the exhaled breath condensate (EBC) in which several inflammatory markers can be measured, including tumor necrosis factor alpha (TNF-α). There is a clear clinical need to develop methods that allow early detection of smokers at risk of losing pulmonary function.Objectives: The aims of the present study are: 1) to show that smokers show higher levels of TNF-α both in serum and EBC; 2) to analyze the possible influence of gender, age, and weight on this parameter; and 3) to determine a possible association between smoking and pulmonary function parameters and TNF-α levels.Material and methods: We have prospectively analyzed two cohorts of smokers and nonsmokers subjects without any chronic or acute disease (within eight weeks of study initiation). We have performed pulmonary function tests with bronchodilators and also collected EBC and blood samples before smoking cessation. Statistical analysis was performed with SPSS 11.0 for Windows Statistical Package.Results: The study has enrolled 17 patients (8 smokers), 50% of whom were females. Mean age was 38.59 years old (standard deviation, 7.4). The mean number of cigarettes smoked in the smoker group was 26.14 (11.29) cigarettes/day and the mean age when tobacco first began was 15.14 (2.04) years. We have not been able to show any significant differences in TNF-α levels according to age or weight. For the whole series we have not found any significant influence of gender in TNF-α levels, but after dividing the series in smokers and nonsmokers, we have shown higher levels of TNF-α in serum (5.59 [0.26] pg/mL vs 5.56 [0.37] pg/mL; nonsignificant [NS]) and EBC (4.94 [0.41] pg/mL vs 4.22 [0.36] pg/mL; p = 0.031) in male smokers. On the other hand, nonsmoking females showed slightly higher TNF-α levels in serum (5.70 [0.50] pg/mL vs 5.42 [0.29] pg/mL; NS) and EBC (4.54 [0.92] vs 4.11 [0.41 pg/mL]; NS). Smokers had higher TNF-α levels in EBC (4.46 [0.58] pg/mL vs 4.34 [0.62] pg/mL; NS), while serum TNF-α levels were slightly higher in nonsmokers (5.52 [0.56] pg/mL vs 5.50 [0.27] pg/mL; NS). We have not demonstrated any association between tobacco consumption and TNF-α levels. We have not shown any significant relation between pulmonary function and the studied parameters, with only a modest association between forced expiratory volume at one second and forced vital capacity and TNF-α levels in EBC.Conclusion: Smokers show higher TNF-α levels in EBC. Among smokers, males show higher levels of TNF in serum and EBC. We have not confirmed any significant influence of age or weight on TNF-α levels. These levels do not seem to be influenced either by the amount of tobacco or the time since habit began. We have shown a modest relation between pulmonary function and TNF-α levels in EBC.Keywords: inflammatory markers, tumor necrosis factor, exhaled breath condensate, cigarette smoking