Certain transient receptor potential (TRP) channels including TRPM8 and TRPA1 are widely expressed in the respiratory tract and have been shown to be the receptors of cigarette smoke and particulate matter—the main causative factors of chronic obstructive pulmonary disease (COPD). The aim of the study was to investigate the effect of TRPM8 and TRPA1 polymorphisms on COPD predisposition and lung function in COPD patients. The study enrolled 143 COPD patients and 104 smokers with post-bronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 70%. Lung function was measured by spirometry. TRPM8 and TRPA1 polymorphisms were genotyped by LATE-PCR. None of the polymorphisms significantly influenced COPD predisposition after correction for covariates and multiple testing. Among COPD patients, the TT genotype of TRPA1 rs7819749 was significantly associated with higher degree of bronchial obstruction. In addition, we established that carriers of the C allele of TRPM8 rs11562975 more commonly had post-bronchodilator FEV1 < 60% (OR 3.2, 95%CI (1.14–8.94), p = 0.03) and revealed the effect of TRPA1 rs959976 and TRPM8 rs17865682 on bronchodilator response in COPD. Thus, the obtained results suggest possible involvement of TRPM8 and TRPA1 in COPD pathogenesis, indicating the necessity to further investigate their functional role in this pathology.

Asthma is a widespread chronic disease of the bronchopulmonary system with a heterogeneous course due to the complex etiopathogenesis. Natural-climatic and anthropogenic factors play an important role in the development and progression of this pathology. The reception of physical and chemical environmental stimuli and the regulation of body temperature are mediated by thermosensory channels, members of a subfamily of transient receptor potential (TRP) ion channels. It has been found that genes encoding vanilloid, ankyrin, and melastatin TRP channels are involved in the development of some asthma phenotypes and in the formation of exacerbations of this pathology. The review summarizes modern views on the role of high and low temperatures in airway inflammation in asthma. The participation of thermosensory TRP channels (vanilloid, ankyrin, and melastatin TRP channels) in the reaction to high and low temperatures and air humidity as well as in the formation of bronchial hyperreactivity and respiratory symptoms accompanying asthma is described. The genetic aspects of the functioning of thermosensory TRP channels are discussed. It is shown that new methods of treatment of asthma exacerbations caused by the influence of temperature and humidity should be based on the regulation of channel activity.

The effect of single nucleotide polymorphisms (SNP) of TRPV4 gene on the development of airway hyperresponsiveness (39.7% of cases) in response to the decrease in osmolarity under inspiration of distilled water aerosol was studies in 189 patients with uncontrolled bronchial asthma. rs6606743 SNP was found to significantly contribute to the development of osmotic airway hyperresponsiveness. Analysis of the dominant genetic model revealed substantial prevalence of AG + GG genotype frequency in the group of patients with asthma with osmotic hyperresponsiveness in comparison with the patients who had negative response to bronchoprovocation. In addition, carriers of GG or AG genotypes had significantly more profound decrease of lung function parameters in relation to A homozygous patients.

Background: Role of interferon-gamma (IFNγ) in asthma remains controversial. While certain studies found association of this cytokine with severe asthma and bronchial hyperresponsiveness, the other ones established its rather beneficial effect on mucin secretion and asthma development. Objectives: The aim of the study was to investigate IFNγ levels in exhaled breath condensate (EBC) of asthma patients. Methods: The study included 46 patients with asthma (mostly newly diagnosed - 52% and moderate - 30%) and 23 patients with chronic bronchitis. Mean age of patients was 38.1±1.60 years. Among asthma patients, 78% had uncontrolled disease according to ACQ5. Lung function was tested by spirometry. IFNγ was measured in EBC by BD cytometric bead array method with enhanced sensitivity. Results: Asthma patients had higher level of IFNγ than patients of control group (2654 (1328.9; 3123.9) fg/ml vs. 1872 (1707.8; 2506.3) fg/ml) but the difference was not significant. IFNγ was increased in moderate asthma (2199 (1764.8; 2519) fg/ml) compared to newly diagnosed asthma (1666 (928.8; 2048.5), p=0.01). Moreover, IFNγ was positively correlated with ACQ5 score (R=0.39, p=0.01). In uncontrolled asthma concentration of the cytokine was more than two times higher compared to patients with partially or fully controlled disease (2807 (1512.9; 3123.9) fg/ml vs. 1158 (995.5; 1589.6) fg/ml, p=0.02). 10-days treatment with oral glucocorticoids decreased IFNγ from the initial (2654 (1328.9; 3123.9) fg/ml) to “normal” values (1790 (1124.4; 3070.1) fg/ml, p=0.08). Conclusions: Our observations suggest detrimental effect of IFNγ in asthma pathogenesis. The study was supported by RFBR (#18-54-53019).

Introduction. It is known that bitter taste receptors (TAS2R) are localized in many organs and tissues including the respiratory tract. The functional characteristics of some TAS2R indicate their significant impact on the activity of mucociliary transport, cytokine production, and smooth muscle tone. Thus, TAS2R are often considered as promising targets for the therapy of asthma. Aim. To determine the effect of TAS2R20 polymorphisms on the development of asthma and the characteristics of the disease course. Materials and methods. The study included 230 patients with asthma of varying severity and 208 relatively healthy volunteers. Asthma control was determined using the Asthma Control Questionnaire and lung function were measured by spirometry. Single nucleotide polymorphisms (SNPs) TAS2R20 rs79420812, rs10845281, and rs61912291 were genotyped by PCR with melting analysis of oligonucleotide probes or amplification products. Total immunoglobulin E (IgE) levels in serum were determined using enzyme immunoassay. Results. Carriage of the TT genotype for rs61912291 was associated with uncontrolled asthma after adjustment for gender, age, and smoking status (OR 2.6, 95%CI (1.30-5.07), p=0.007). The same genotype was associated with signs of bronchial obstruction: a decrease in FEV₁ to less than 80% (OR 5.42, 95%CI (1.48-19.87), p=0.01) and FEV₁ /FVC to less than 70% (OR 2.44, 95%CI (1.43-4.18), p=0.001) after adjustment for gender, age, and smoking status. In addition, the homozygous state for the T allele for rs61912291 SNP was more common in asthma patients with IgE level of more than 100 IU/ml (OR 2.6 95%CI (1.22-5.54), p=0.01 after adjustment for gender, age and smoking status). Conclusion. SNPs of TAS2R20 do not affect the development of asthma but may be associated with the features of the disease course. Carriage of the TT genotype for rs61912291 SNP adversely affects the control of asthma, airway patency and is accompanied by an increased IgE level.