Cold Airway Hyperresponsiveness Research Articles

Interleukin 8 and bronchial phagocytes in patients with non-allergic asthma and diverse respiratory responses to cold stimulus

Introduction. The role of phagocytes, regulated by interleukin 8 (IL-8), in the formation of the bronchial response to environmental stimuli in patients with asthma is not well understood.Aim. To study the functional activity of IL-8 and the pool of phagocytic cells in the inflammatory pattern of the bronchi in patients with non-allergic asthma during inhalation exposure to cold air.Materials and methods. In 129 patients with mild to moderate asthma, the content of IL-8 and the cellular composition of sputum before and after the bronchoprovocation test with isocapnic hyperventilation with cold air (-20°C) (IHCA) were analyzed.Results. Based on the results of the IHCA by the assessment of changes in FEV1 (Δ,%), 54 patients (1st group) were verified with cold airway hyperresponsiveness (CAHR), the comparison group consisted of asthma patients (2nd group, n=75) who did not respond to the trigger (ΔFEV1 = -18.9±1.2 and -3.3±0.4%; p<0.0001, respectively). The content of neutrophils in sputum before provocation was 41.1±2.2% and 34.5±2.2% (p><0.05), macrophages – 36.2±2.7% and 43.1±2.5% (p> ˂ 0.0001, respectively). The content of neutrophils in sputum before provocation was 41.1±2.2% and 34.5±2.2% (p ˂ 0.05), macrophages – 36.2±2.7% and 43.1±2.5% (p>0.05), respectively. In response to the IHCA in the 1st group, the number of neutrophils increased to 48.2±2.0% (p ˂ 0.05), macrophages decreased to 28.7±2.1% (p ˂ 0.01), and the level of IL-8 increased from 12838±2328 to 17412±2980 pg/mL (p ˂ 0.05). In the 2nd group, the concentration of IL-8 before the IHCA was 14639±2691 pg/mL, after the test 10545±1746 pg/mL (p>0.05); the number of neutrophils after the test 40.0±2.3% (p>0.05); macrophages – 35.8±2.0% (p ˂ 0.01).Conclusion. In asthma patients with CAHR, the inflammatory pattern of the bronchi in response to the cold trigger shows enhanced IL-8 activity and more pronounced changes in the content of phagocytes, mobilized with the involvement of this cytokine.

Profile of MUC5AC and MUC5B mucins expression in asthma patients under cold exposure

Introduction. Cold airway hyperresponsiveness (CAH) is a common condition in patients with asthma, which worsens the clinical course of the disease and the patients’ quality of life. MUC5AC and MUC5B are the main secreted mucins in the respiratory tract, which are involved in normal mucociliary clearance, but also capable of provoking the development of pathological changes in case of dysregulation of their balanced production.Aim. The aim of this study was to determine the dynamics of MUC5AC and MUC5B expression during experimental cooling in patients with asthma depending on the status of CAH.Materials and methods. The study enrolled 98 subjects including 26 patients with chronic non-obstructive bronchitis without exacerbation (control group) and 72 patients with asthma. The expression of MUC5AC, MUC5B and TRPM8 was determined in the upper respiratory tract by quantitative reverse transcription PCR. The production of MUC5AC and MUC5B was also measured in sputum by ELISA. All patients underwent a bronchoprovocation test with isocapnic cold air hyperventilation to detect CAH, and a similar nasal challenge was performed to assess the effect of cooling on the expression of the studied genes.Results. Patients with asthma had 4.22-fold increase in the expression of MUC5AC (p=0.02) in the nasal epithelium as compared with the control group. CAH was associated with an initial 7.33-fold upregulation of MUC5AC (p=0.008) as well as with further increase in MUC5AC expression but a decrease in MUC5B in response to cooling, which was not observed in asthma patients without CAH. Basal TRPM8 expression was associated with baseline level of MUC5AC (ρ=0.41, p=0.04), MUC5B (ρ=0.55, p<0.001) and amount of sputum produced after the cold bronchoprovocation.Conclusion. Asthma patients with CAH demonstrate a more pronounced imbalance in the production of mucins, which is aggravated by cold exposure. This, in turn, can lead to a number of pathological disorders associated with a more severe course of the disease.

Airway neutrophils and myeloperoxidase in asthma patients with cold-induced bronchoconstriction

Introduction. The role of neutrophil inflammation of the bronchi in patients with asthma in the devel­opment and manifestation of cold airway hyperresponsiveness (CAHR) has not been sufficiently studied.Aim. To assess the level of neutrophils and the activity of myeloperoxidase (MPO) in the bronchi of asthma patients with cold-induced bronchospasm.Materials and methods. In 138 patients with mild-to-moderate asthma with CAHR, the level of asthma control (ACT), lung function (FEV1), cellular composition of sputum was examined before and after the bronchoprovo­cation test by isocapnic hyperventilation with cold air (IHCA). In sputum samples, the percentage of neutrophils, eosino­phils, and bronchial epithelial cells (structurally intact cylindrical ciliated and goblet cells) was assessed; the concentration and activity of MPO in neutrophils were studied by the cytochemical method.Results. The patients were divided into three groups: group 1 (n=94) - patients with mild cold-induced bronchospasm, group 2 (n=28) - with moderate broncho­spasm, group 3 (n=16) - with severe bronchospasm (AFEV1=- 13.5±0.3, -24.6±0.5, -36.9±1.5%, respectively). Patients did not differ in the level of asthma control (16 [12; 21]; 16 [13; 20] and 16 [12; 21] ACT points, respectively). Patients of the third group had lower values of bronchial patency in comparison with the first and second groups: FEV1 79.4±3.2; 92.4±1.7 (p<0.01); 92.1±2.9% and FEF25-75 46.4±4.3; 66.1±2.5 (p<0.001); 63.2±4.0% (p<0.01). In sputum after the IHCA test in groups 2 and 3, an increase in the number of neutrophils was recorded from 35.5±3.9 to 46.0±3.8% (p<0.05) and from 39.0±3.8 to 52, 4±4.4% (p<0.05), respectively, while the number of neutrophils in group 1 did not change (43.2±2.4 and 44.3±2.1%). The concentration of MPO in response to the IHCA test in all groups significantly increased by more than 30% (p<0.05).Conclusion. The mobilization of neutrophils in a mixed pattern of airway inflammation in asthma pa­tients is associated with worsening of cold-induced bronchospasm. An increase in the content of MPO in neutrophil gran­ules in response to the action of cold air is aimed at enhancing the secretion of the enzyme in the interstitium, activating its oxidative activity in the respiratory tract, and escalating the oxidative/halogenating stress that accompanies broncho­spasm.

Bronchial inflammatory profile in interferon-gamma-mediated immune response in asthma patients during airway response to cold stimulus

Abstract Objective To evaluate the inflammatory pattern and the interferon (IFN)-γ in the bronchial secretion of asthma patients in response to acute cold bronchoprovocation. Material and methods We enrolled 42 patients with asthma. We assessed asthma by Asthma Control Test, the lung function by spirometry before and after the bronchodilator test, followed by collecting induced sputum. The next day, we collected exhaled breath condensate (EBC) and conducted a 3-minute isocapnic hyperventilation with cold air (IHCA), followed by collecting spontaneously produced sputum. Results Group 1 included 20 patients with cold airway hyperresponsiveness (CAHR), and group 2 included 22 patients without CAHR. In both groups, a high level of neutrophils in bronchial secretion was observed before and after IHCA. In response to IHCA, the number of epitheliocytes in the sputum decreased to a greater extent in patients of group 1. The baseline epitheliocytes and the concentration of IFN-γ after IHCA had an inverse relationship (r = −0.60; P = 0.017). The baseline IFN-γ in EBC before and after IHCA was lower in group 1. Airway response to cold exposure directly correlated with IFN-γ levels after IHCA (Rs = 0.42; P = 0.014). Conclusion In asthma patients with CAHR, there is a relationship between the persistence of mixed inflammation and the level of IFN-γ in the bronchi. IFN-γ in response to IHCA is decreased with increased cytokine utilization during cold bronchospasm, which is accompanied by the mobilization of neutrophils and the shift in the cytokine spectrum of the respiratory tract towards the T helper cells (Th) 1 immune response.

Efficiency of using a short-acting β2-agonist for the relief of acute cold bronchospasm in asthma patients with cold airway hyperresponsiveness

Excessive sensitivity of the respiratory tract to physical and chemical environmental triggers can vary for many reasons, reducing the therapy effectiveness in a patient with asthma. Aim of the study was to investigate the effectiveness of a short-acting bronchodilator in patients with asthma for the relief of acute cold bronchospasm after a test of isocapnic cold air hyperventilation (ICHV). Material and methods. In 281 (161 women; 120 men, p > 0.05) asthma patients with cold airway hyperresponsiveness (CAHR), the change in airway patency (FEV1) and the efficacy of short-acting β2-agonists (SABA) after a 3-minute isocapnic hyperventilation with cold (–20 ºС) air. Results. According to clinical data, patients had persistent asthma, mean age 35 (26; 44) years, 49 % of patients smoked, ACT 16 (12; 20) points, FEV1 90.0 ± 1.0 % predicted, FEV1/VC 71.4 ± 0.6 %, the increase in FEV1 after inhalation of SABA (∆FEV1β) was 11.1 (5.1; 20.5) %. The change in FEV1 for the ICHV varied within –16 (–22.0; –12.0) %. The use of SABA after the IHCV showed different efficacy for relief of an attack of cold bronchospasm. The median value of ∆FEV1β after ICHV was 21.1 (11.6; 33.3) %, with a range of –48.6 to 108.2 %. In the general group, there was a direct relationship between the level of asthma control in terms of ACT points and the baseline FEV1 (Rs = 0.17; p = 0.007), MEF25-75 (Rs = 0.18; p = 0.008), ∆FEV1β in response to SABA (Rs = –0.17; p = 0.0104), as well as the severity of the bronchial response to the ICHV (Rs = 0.15; p = 0.014). The latter, in turn, correlated with ∆FEV1β after ICHV (Rs = –0.28; p < 0.0001) after HCI. Conclusions. There is a differentiated airway response to SABA after acute cold bronchoprovocation. The results obtained can serve as an important tool for phenotyping of asthma patients with CAHR for the medication correction of сold bronchospasm.

Th1, Th2 cytokines in airway response to acute cold exposure in patients with bronchial asthma

Introduction. The concept of the interaction of multidirectional cytokines that control the cellular and humoral immune response in the cold bronchospasm in asthma has been little studied.Aim. To evaluate the role of Th1 and Th2 cytokines in the formation of the airway response to a cold stimulus in patients with asthma.Materials and methods. The spectrum of cytokines (IFN-γ, IL-17А, TNFα, IL-1β, IL-2, IL-6, IL-4), protein IP-10 (chemokine CXCL10), MMP9 metalloproteinase and TIMP1 protein in exhaled breath condensate before and after 3-minute isocapnic hyperventilation with cold (-20ºС) air (IHCA) has been studied in 37 patients.Results. Patients were divided into two groups: group 1 (n=11) consisted of individuals with cold airway hyperresponsiveness (CAHR), group 2 – 26 individuals with no response to IHCA (ΔFEV1 IHCA = -16.5±2.3 and -1.5±0.85%, respectively, p<0.0001). Pro-inflammatory cytokines TNFα, IL-2, IL-1β, and IL-6 had a predominant effect on the development of CAHR. IFN-γ was considered as a central regulator of the bronchial response to a cold stimulus, the increase in the level of which in cold bronchospasm relative to the group without CAHR (399,52 [237,1; 753,23] and 237,99 [57,63; 304,84] fg/mL, respectively, p<0.05) was accompanied by an increase in the concentration of IFN-γ-induced protein IP-10 (201.12 [199.4; 398.81] and 167.33 [132.94; 212.77] fg/mL, respectively (p<0.05). The absence of dynamics of IL-4 concentration in response to IHCA testified to the minimal involvement of IL-4 in the implementation of CAHR. The involvement of IL-17A could be associated with the activity of Th1 cytokines and the cold-activated proteolysis-antiproteolysis system involved in bronchial remodeling ‒ metalloproteinase MMP9 and a specific inhibitor of metalloproteinases TIMP1, the values of the latter two were higher in individuals with CAHR after the IHCA test.Conclusion. In patients with asthma, in the implementation of cold bronchospasm, the dominance of the Th1 immune response and a decrease in the functional activity of Th2 cytokines are observed.

Interleukin 8 and bronchial eosinophils in patients with asthma and cold airway hyperresponsiveness

Introduction. Cold airway hyperresponsiveness (CAHR) is common in patients with asthma. The effect of inhaled corticosteroid/long-acting β2-agonist therapy (ICS / LABA) on its severity, and the role of IL-8, and the eosino-philic profile of bronchial inflammation have not been studied. Aim. To study the dynamic relationship between the level of IL-8 and eosinophilic inflammation in the bronchi of asthma patients with CAHR using anti-inflammatory combined therapy with ICS / LABA. Materials and methods. Patients with asthma (n=59) received ICS / LABA for 24 weeks. The level of disease control (ACT, points), cellular composition of induced sputum (IS), bronchial response (ΔFEV1IHCA, %) to 3-minute isocapnic hyperventilation with cold (-20ºС) air (IHCA) was assessed. Exhaled breath condensate (EBC) was collected before and after the IHCA, in which the concentration of IL-8 (pg/mL) was determined. Results. Group 1 included 28 patients with CAHR (ΔFEV1IHCA = -14.1 ± 1.7%), group 2 included 31 patients with no response to cold bronchoprovocation (ΔFEV1IHCA = - 3.0 ± 2.4 %, p < 0.0001). Initially, patients of groups 1 and 2 had no differences in ACT (16.8±0.6 and 15.7 ± 0.8 points), FEV1 (92.5 ± 3.6 and 87.8 ± 2.2%), the number of eosinophils in sputum (8.0 ± 2.4 and 4.7 ± 1.3%, respectively, p > 0.05). The concentration of IL-8 before and after the IHCA test in group 1 was 131.2 ± 18.0 and 146.3 ± 23.5 pg/mL, respectively (p > 0.05), in group 2 it was 130.5 ± 8.8 and 149.9 ± 18.4 pg/mL, respectively (p>0.05). After treatment, the airway response to the IHCA significantly decreased in group 1 (ΔFEV1IHCA = - 8.8 ± 1.5 %, p < 0.01), in group 2 it remained unchanged (- 3.6 ± 1.3 %, p > 0.05). The level of asthma control in group 1 increased to 20.7 ± 1.6 ACT points (p < 0.01), in group 2 – up to 19.7 ± 1.7 (p < 0.05). The lung function did not change. After treatment, the level of IL-8 before and after the IHCA in group 1 did not change (89.8 ± 11.7 and 85.5 ± 7.8 pg/mL, p > 0.05), as did the number of eosinophils (8.0 ± 2.4 and 6.2 ± 3.1 %, p > 0.05). In group 2, the level of IL-8 before and after IHCA decreased from 89.2 ± 7.7 to 73.9 ± 10.3 pg/mL (p < 0.01), the concentration of eosinophils decreased from 4.7 ± 1.3 up to 1.5 ± 0.57 % (p < 0.05). Conclusion. 24-week therapy with ICS/LABA in patients with CAHR leads to improved asthma control, a decrease in the severity of cold bronchospasm, without being accompanied by changes in the level of IL-8, which affects the dynamics of the concentration of eosinophils in the bronchi.

Клеточный профиль мокроты и активность миелопероксидазы у больных бронхиальной астмой с холодовой гиперреактивностью дыхательных путей

Th e aim of the research. To study the infl ammation pattern, myeloperoxidase activity and the content of the epithelium in the bronchi of patients with bronchial asthma (BA) with diff erent forms of airway hyperresponsiveness to physical stimuli. Material and methods. Th e degree of asthma control, pulmonary function, and cellular composition of induced sputum were studied in 142 BA patients with various forms of airway hyperresponsiveness to indirect provoking triggers. In cytological smears, the number of neutrophils, eosinophils, bronchial epithelial cells was counted. A cytochemical study of myeloperoxidase activity in sputum neutrophils was carried out. Results. It has been established that BA patients with combined airway hyperresponsiveness to various physical stimuli have lower asthma control, a higher number of eosinophils in sputum, a higher level of myeloperoxidase in neutrophils, and a lower percentage of intact bronchial epithelium compared to patients with isolated cold airway hyperresponsiveness. A close relationship was found between the level of eosinophils and the number of intact epitheliocytes (Rs=-0.52, p<0.001). In patients with combined airway hyperresponsiveness, a relationship was found between the activity of myeloperoxidase in neutrophils and the severity of the bronchial response to isocapnic hyperventilation with cold air (R=-0.33; p<0.05). Conclusion. Activation of the peroxidase function of neutrophils and stimulation of the eosinophil activity, which leads to destruction of the epithelium and a decrease in the content of normal epitheliocytes, are associated with a greater severity of airway hyperresponsiveness to cold and the addition of reactions to other stimuli

P1-10: Indicators of the pituitary-thyroid system in asthma patients with cold airway hyperresponsiveness without manifestation of thyroid lesion, living in endemic goiter area.

P1-10: Indicators of the pituitary-thyroid system in asthma patients with cold airway hyperresponsiveness without manifestation of thyroid lesion, living in endemic goiter area.

P9‐15: Examination of the inflammatory pattern of the bronchi in asthma patients with cold airway hyperresponsiveness with controller antiinflammatory therapy

P9‐15: Examination of the inflammatory pattern of the bronchi in asthma patients with cold airway hyperresponsiveness with controller antiinflammatory therapy

P2‐13: Cold‐shock proteins are upregulated in asthma patients with cold airway hyperresponsiveness and provoke increase in MUC5AC expression under cooling

P2‐13: Cold‐shock proteins are upregulated in asthma patients with cold airway hyperresponsiveness and provoke increase in <i>MUC5AC</i> expression under cooling

P9‐34: Seasonal dynamics of cold airway hyperresponsiveness in asthma patients

P9‐34: Seasonal dynamics of cold airway hyperresponsiveness in asthma patients

P9‐22: Dynamics of asthma control and lung function in patients with stable persistent cold airway hyperresponsiveness

P9‐22: Dynamics of asthma control and lung function in patients with stable persistent cold airway hyperresponsiveness

Comparative characteristics of the quality of life of asthma patients with different types of airway hyperresponsiveness to physical stimules

Aim. To compare the nature and degree of influence of different types of airway hyperresponsiveness (AHR) on the general and specific quality of life (QoL) of patients with asthma and control over the disease.Materials and methods. 234 patients with mild-to-moderate asthma, aged from 18 to 60 years old, were interviewed and examined. Depending on the presence of one or another type of AHR, 4 groups were formed: group 1 included 60 patients with cold AHR, group 2 – 75 patients with hypoosmotic AHR, group 3 – 35 patients with hyperosmotic AHR, group 4 – 64 patients with exercise-induced bronchoconstriction (EIB). QoL and the state of the emotional sphere were assessed using the SF-36, AQLQ, HADS questionnaires. The level of asthma control was determined using the ACT questionnaire. Lung function was assessed by spirometry.Results. When comparing QoL between groups, statistical differences were obtained for most of the SF-36 scales, with the exception of the domains “Role Physical” (RP) and “Bodily Pain” (BP), and their presence and significance varied depending on the types of AHR being compared. The lowest QoL indices were found in group 1 of patients with cold AHR according to the domains “Physical Activity” (PA), RP, BP, and “Role Emotional” (RE). The lowest indices for the domains “General Health” (GH), “Vitality” (V) and “Mental health” (MH) were found in the respondents of the 2nd group. Most of the highest QoL indicators in the compared groups were found in patients of group 4 with EIB in the domains PA, RP, V, RE, and MH. When carrying out a comparative analysis, the maximum number of significant differences was found between the groups with cold AHR and EIB. A comparative study of QoL using a special AQLQ questionnaire showed the lowest indices for the “Activity” and “Symptoms” domains in groups 1 and 2 of asthma patients. In addition, in group 1, the minimum QoL values were recorded for the “General QoL” domain (3.6±0.2 points), and in group 2, for the “Environment” domain (2.9±0.3 compared with 3.9±0.2 points in group 3, p&lt;0.01).Conclusion. This study has demonstrated the multifaceted effect of AHR on health-related QoL, dependent on sensitivity to a particular physical stimulus and the season of maximum trigger action. The subjective assessment of psychosocial functioning is most differentiated according to the GH domain of the SF-36 questionnaire. The greatest negative impact on the QoL indices is exerted by the cold and hypoosmotic AHR, the least – by the EIB. The assessment of QoL allows to get a full picture of the perception of the patient's health level at the moment and in the given conditions.

Seasonal dynamics of cold airway hyperresponsiveness in patients with asthma

Introduction. Cold air-induced bronchoconstriction in patients with asthma, leading to a breakdown in disease control, is one of the most serious problems in the northern countries of the world.Aim. To assess the seasonal dynamics of the airway response (ΔFEV1CA) to cold bronchoprovocation in asthma patients with cold airway hyperresponsiveness (CAHR).Materials and methods. Out of 513 asthma patients who underwent primary bronchoprovocation testing, 273 patients (140 women; 133 men) with diagnosed CAHR took part in the retrospective analysis. The design objectification of clinical data using the Asthma Control Test questionnaire (ACT, Quality Metric Inc., 2002), a screening questionnaire for identifying clinical symptoms of response to low ambient temperature in everyday life; assessment of the lung function; bronchoprovocation test of 3-minute isocapnic hyperventilation with cold (-20ºC) air (IHCA).Results. At the time of testing, the average age of patients was 34.8±0.87 years, FEV1 88.5±1.3% of predicted, FEV1/VC 70.9±0.7%; ACT 16 (12; 19) points. On average in the group, ΔFEV1CA was -19.2±0.6%. The frequency of CAHR detection in the winter was 22%, spring – 34%, summer – 22%, autumn – 24% (p&gt;0.05). The minimum changes in FEV1 in response to IHCA were recorded in May-June (mean value ΔFEV1CA -16.2±1.3 and -14.5±1.6%, respectively) and were significantly less in comparison with February (-21.9±2.3%, p˂0.05) and April (-23.0±2.36%, p˂0.01). A correlation has been found between the monthly mean values of meteorological parameters and CAHR, as well as the value of ACT in points and ΔFEV1 (r=0.16; p=0.018).Conclusion. Seasonal changes in the strength of the action of meteorological factors produce a change in the response of the airways to cold bronchoprovocation, and contribute to the loss of asthma control. The maximum values of CAHR fall on February-April, August, November. The data obtained reflect the presence of a complex interaction of physical environmental factors in the induction of seasonal fluctuations of CAHR, which requires a search for specific mechanisms for the formation of altered airway reactivity associated with the characteristics of molecular reception of low temperatures and humidity in the human airways.

Thyroid and pituitary-adrenal activity in patients with asthma and endemic subclinical hypothyroidism in response of respiratory tract to a cold stimulus

Introduction. In patients with uncontrolled asthma, the stress-induced production of glucocorticosteroids in response to a cold bronchoprovocation test is increased, which is associated with an increase in the level of thyroidstimulating hormone (TSH), characteristic of the syndrome of subclinical hypothyroidism (SH). The peculiarities of thyroid hormone metabolism and changes in pituitary-adrenal homeostasis that develop in asthma in a goiter-endemic region under the influence of cold stress factors on the respiratory system are poorly studied.Aim. To assess the activity of the pituitary-thyroid and pituitary-adrenal systems in response to bronchoprovocation with cold air in asthma patients with cold airway hyperresponsiveness (CAHR) and SH living in conditions of goiter endemic in the Amur Region.Materials and methods. In 34 asthma patients with CAHR, without symptoms of thyroid diseases, the level of disease control was assessed using the Asthma Control Test (ACT) questionnaire. Lung function and airway reaction to a cold stimulus (ΔFEV1IHCA) during 3-minute isocapnic hyperventilation with cold (-20ºC) air (IHCA) were measured. Methods of immunological diagnostics in the blood of patients before and after the IHCA test were used to measure the concentrations of thyroid-stimulating (TSH) and adrenocorticotropic (ACTH) hormones, common and active forms of thyroxine (T4) and triiodothyronine (T3), thyroglobulin (TG), autoantibodies to thyroperoxidase (AB-TPO), cortisol. The content of cyclic adenosine monophosphate (cAMP) was determined in leukocytes.Results. The patients were divided into two groups: group 1 included 25 patients with an initially low (&lt;4.0) TSH level (2.39±0.18 mU/L), group 2 included 9 patients with an initially high (&gt;4, 0) TSH level (4.80±0.46 mU/L, p&lt;0.0001). The ACT control level in groups 1 and 2 was 16.6±1.0 and 15.3±1.5 points (p&gt;0.05), base FEV1 was 95.8±3.3 and 81.0±5.4% (p=0.026), ΔFEV1IHCA -11.9±0.96 and -13.5±2.7 (p&gt;0.05), respectively. In group 1, in response to IHCA, the level of free T4 increased from 14.2±0.70 to 15.2±0.71 pmol/L (p&lt;0.05), free T3 from 3.73±0.24 to 4.15±0.21 nmol/L (p&lt;0.05). In group 2, a lower level of free T4 was recorded, both before (12.2±1.52 pmol/L) and after IHCA (11.6±1.60 pmol/L, p=0.041). In addition, in group 2 patients, the cortisol concentration at baseline and after IHCA (516.6±31.6 and 397.4±40.4 nmol/L, p&lt;0.05) was significantly lower than in group 1 (628.3±27.5 and 608.3±34.1 nmol/L, p=0.042; p=0.002, respectively). A close correlation was found between ΔFEV1 and the T4 level before (r=0.54; p&lt;0.01) and after the test (r=0.41; p&lt;0.05), with the amount of cAMP up to (r=0.58; p=0.008) and after the test (r=0.47; p=0.009), as well as the correlation between ΔМEF50 and the initial level of cortisol in the blood serum (r=0.50; p=0.002).Conclusion. In asthma patients with CAHR living in the region of cold climate and goiter endemic, the presence of SH can be considered as a prognostic sign of the development of dysadaptation of the respiratory system to cold exposure.

Relationship of granulocytic inflammation of bronches with the level of asthma control in patients with cold airway hyperresponsiveness under inhalation therapy of extrafine beclomethasone/formoterol

Introduction. Obstruction of small airways in asthma is accompanied by greater hypersensitivity to nonspecific irritants and inflammation activity, which is associated with a worsening of the clinical course of the disease. The combination of beclomethasone dipropionate/formoterol fumarate (BDP/FF), used in the form of an extrafine metered dose aerosol, is capable of having an anti-inflammatory effect on the small airways. Dynamic changes in the structure and function of granulocytes of inflammatory bronchial infiltrate after exposure to cold air in patients with asthma treated with BDP/FF have been little studied.Aim. To study the nature of changes in eosinophil and neutrophil pools of bronchial granulocytes in asthma patients with cold airway hyperresponsiveness (CAHR) during long-term therapy with extrafine BDP/FF.Materials and methods. The clinical study involved 25 asthma patients with CAHR. The design of the work included a questionnaire survey of patients using the Asthma Control Test (ACT) questionnaire, spirometry (Easy on PC, ndd Medizintechnik AG, Switzerland), an isocapnic hyperventilation by cold air (IHCA), collection and cytological examination of induced and spontaneously produced sputum. The examination was carried out at the beginning and after 12 weeks of BDP/FF therapy (100/6 μg, twice a day).Results. 12-week treatment with extrafine BDP/FF led to an improvement in asthma control (ACT increased from 17.1±1.1 to 22.5±0.5 points, p˂0.001) and patency of small bronchi (increase in МEF50 was 0.47±0.21 L/s, МEF25-75 – 0.42±0.17 L/s). BDP/FF therapy had a positive effect on cellular inflammation, leading to a decrease in the number of eosinophils in sputum from 9.5 (3.0; 19.5) to 2.2 (1.3; 4.7)% (p˂0,05). A decrease in the number of eosinophils was also observed after cold bronchoprovocation: from 9.0 (2.8; 15.4) to 4.7 (2.8; 7.8)% (p˂0.05). There was no dynamics in neutrophils after BDP/FF treatment before and after IHCA (59.9±1.3 and 57.1±2.0%, respectively, p&gt;0.05).Conclusion. Improvement of disease control in asthma patients with CAHR after 12 weeks of therapy with extrafine BDP/FF is associated with the regulation of eosinophilic inflammation, a decrease in the number of eosinophils in the airways and suppression of the activity of the neutrophilic pool of bronchial granulocytes in response to cold bronchoprovocation.

Technology for determining clinical-anamnestic markers of cold and osmotic airway hyperresponsiveness

Introduction . The high labor intensity of instrumental tests to detect cold/osmotic hyperresponsiveness of the airways raises the question of finding alternative options for identifying individuals sensitive to cold air and high ambient humidity. Aim . Development and validation of questionnaires for the detection of cold and osmotic airway hyperresponsiveness. Materials and methods . A survey was conducted according to a specially developed questionnaire of 191 patients with mild and moderate persistent asthma in order to identify clinical symptoms of response to low temperature and high humidity of the environment in everyday life and after performing acute bronchoprovocation tests: 3-minute isocapnic hyperventilation with cold (-20ºC) air and 3-minute inhalation of ultrasonically nebulized distilled water. Results . The main clinical symptoms in individuals sensitive to cold and/or high environmental humidity are the occurrence of breathlessness and/or shortness of breath, coughing, labored breathing, distant wheezing under the influence of cold or moisture triggers. In individuals with cold airway hyperresponsiveness, a high predictive value was obtained for the “breathlessness/shortness of breath” symptom (sensitivity and specificity 88.2 and 86.9%). In individuals with osmotic airway hyperresponsiveness, a high predictive value included two symptoms – “breathlessness/shortness of breath”, “appearance of distant wheezing”(sensitivity and specificity 88.4 and 85.3%). On the basis of the data obtained, two screening questionnaires have been developed, containing keys for a quick diagnosis of cold and osmotic airway hyperresponsiveness. The questionnaires were tested on 840 respondents from the Amur Gas Processing Plant. Conclusion . The information provided is important for assessing the health of the population living in severe climatic conditions, the population of people involved in working in these regions. The proposed screening questionnaires can be used to develop prevention programs for people whose profession is associated with a high risk of respiratory infections when working in cold conditions or high humidity conditions.

Hydrolytic enzymes of airway neutrophilic granulocytes in patients with asthma under cold stimuli exposure

Introduction . The labilization of lysosomal membranes with the release of a wide range of lysosomal enzymes of pro-inflammatory and proapoptotic action, which have a high hydrolytic potential, is one of the essential components of adaptive changes in cells under stress. The participation of hydrolytic enzymes of phagocytes in cellular reactions of inflammation and adaptation to cold stress in patients with asthma has been little studied. Aim . To study the activity of neutrophil hydrolases of bronchi in patients with asthma under cold-induced stress. Materials and methods. In patients with persistent asthma (n=13), lung function (FEV 1 ,%), airway response (∆FEV 1 IHCA ,%) to standard 3-minute isocapnic hyperventilation with cold air (IHCA) were determined by spirometry. The collection of induced and spontaneously produced sputum after the IHCA was carried out. The activity of acidic (AP) and alkaline (ALP) phosphatases, adenosine triphosphatase (ATPase) was detected in sputum neutrophils by cytochemical methods. The assessment of the reaction to the activity of hydrolases was carried out by the semi-quantitative Kaplow method with the distribution of cells into groups depending on the color intensity of the product formed during the interaction of the enzyme with the substrate, and the subsequent calculation of the average cytochemical index (ACI) of the enzymatic activity. Results . The baseline FEV 1 , averaged 97.9±5.3%, ∆FEV 1 IHCA -2.0 (-8.0; 2.0)%. Under the influence of a cold stimulus against the background of a mixed pattern of bronchial inflammation in patients, the following was recorded: an increase in the ACI AP of neutrophils (from 1.11±0.06 to 1.42±0.06; p˂0.01), an increase in the number of cells with an average degree of AP activity (from 23.4±1.94 to 40.1±4.30%; p˂0.01) and a decrease in the number of cells with a negative reaction to AP (from 15.1±3,58 to 5.2±2.78%; p˂0.05), a tendency to an increase in the number of neutrophils with a high degree of ATPase activity (from 3.50±2.70 to 7.22±2.64%) and ALP (from 13.7±4.22 to 15.7±3.46%). Conclusion . The activation of AP of neutrophils under cold-induced stress indicates the possibility of an increase in the acidity of the interstitium, stimulation of damage and vulnerability to cold effects of the desmo-epithelial barrier of the bronchi and is regarded as a criterion for a high risk of cold airway hyperresponsiveness in asthma patients with a mixed inflammation phenotype.

Peculiarities of pulmonary mechanics and gas exchange in asthma patients with different types of reaction to cold and osmotic stimuli

Introduction. The airway constriction due to bronchospasm can lead to more pronounced disturbances of regional ventilation and limit gas exchange in patients with bronchial asthma. Aim. To study the features of the mechanics of respiration and gas exchange in asthma patients with different types of reaction to cold and hypoosmolar stimuli. Materials and methods. The design involved a comprehensive four-day examination of 367 patients with persistent asthma with an analysis of the baseline spirometric parameters and their dynamics for the administration of a β 2 -agonist, after bronchoprovocation testing – isocapnic hyperventilation with cold air (-20ºC) (IHCA), inhalation of ultrasonically nebulized distilled water (IDW). Lung was assessed using bodyplethysmography, capnovolumetry, measurements of the diffusion capacity of the lungs. Results. A comparative analysis was carried out after the distribution of patients into groups according to the types of response to the IHCA and IDW samples. Group 1 included patients with airway hyperresponsiveness to both stimuli (cold and osmotic); group 2 – patients with cold airway hyperresponsiveness, group 3 – patients with osmotic airway hyperresponsiveness, group 4 – patients who did not respond to both stimuli. The patients of group 1 controlled asthma symptoms to a lesser extent, smoked more often, had lower baseline values of bronchial patency indices and a high increase in FEV1 per inhalation of a short-acting β 2 -agonist; in 71% of patients, increased bronchial resistance was registered, which in one third was combined with high residual volume. In these patients, a close relationship was found between the capnovolumetry indicator (dMM/dV 3 ) and the diffusion capacity of the lungs (TL CO ) (Rs=0.42; p˂0.05), as well as with FEV 1 (Rs=-0.23; p˂0.05) and MOC 25-75 (Rs=-0.24; p˂0.05). Conclusion. Asthma patients with combined airway hyperresponsiveness to cold and osmotic stimuli are characterized by more significant disturbances in the mechanics of respiration and gas exchange, affecting both the peripheral and central parts of the respiratory tract.