Glucocorticoid regulation of clinical and functional manifestations of asthma in patients with different airway response to hyposmolar stimulus during anti-inflammatory therapy

Author(s):  
A. B. Pirogov ◽  
А G. Prikhodko ◽  
А. N. Odireev ◽  
N. V. Ul'yanychev ◽  
V. F. Ul'yanycheva ◽  
...  

Introduction. The role of an alternative adenylate cyclase pathway of hormonal signal transmission under the action of synthetic glucocorticosteroids with the participation of endogenous stress-limiting activity of the adrenal cortex in conjunction with the adaptive capabilities of airway homeostasis in patients with asthma under conditions of osmotic stress has not been studied at present. Aim. To assess the dynamics of cortisol and cyclic adenosin monophosphate (cAMP) in asthma patients with different airway responses to hypoosmolar stimuli when using anti-inflammatory combination therapy with inhaled corticosteroids/long-acting β2 -agonists (ICS/LABA). Materials and methods. 96 patients diagnosed with asthma received combined anti-inflammatory therapy with ICS/LABA for 24 weeks. Group 1 included patients (n=18) with airway hyperresponsiveness to hypoosmolar stimulus, group 2 (n=78) – with no reaction of the bronchi to a 3-minute ultrasonic inhalation of distilled water. At baseline and at the end of treatment, the lung function was studied; to assess the regulatory function of glucocorticoids using non-genomic signaling pathways, the levels of cortisol in blood serum and cAMP in blood leukocytes were determined. Results. Patients of group 1 in comparison with the second one initially had a lower FEV1 ‒ 88.2±5.3 and 98.5±1.7%, respectively (p<0.05), after treatment in both groups there was a slight tendency to an increase in FEV1 (98.5±5.7 and 101.4±2.5%, respectively, p>0.05). The concentration of cortisol and cAMP at baseline and after 24 weeks of therapy in patients of group 1 was 588.7±32.0 and 495.0±48.7 nmol/L, 61.7±5.1 and 76.5±5, 2 pmol/106 cells (p<0.01); in group 2 − 610.5±20.1 and 522.2±15.60 nmol/L (p<0.001), 76.2±2.2 and 90.6±2.5 pmol/106 cells (p<0.001). Conclusion. In asthma patients with airway osmotic hyperresponsiveness, persistent adaptation to osmotic stress is traced, which is combined with a more significant impairment of the lung function and indicates insufficient therapeutic control over glucocorticoid regulation of osmotic stress by the selected volume of ICS/LABA therapy.

Author(s):  
Алексей Пирогов ◽  
Aleksey Pirogov ◽  
Юлий Перельман ◽  
Yuliy Perelman ◽  
Анна Приходько ◽  
...  

Heterogeneity of respiratory tract inflammation determines the clinical course and control of mild asthma. The aim of the research was to study the relationship between clinical and functional parameters and the form of bronchial inflammation in patients with mild persistent asthma against the background of standard basic anti-inflammatory therapy. In 198 patients with mild asthma (the mean age was 41.5±0.7 years old) against the background of maintenance therapy with low doses of inhaled glucocorticosteroids (ICS at a dose ≤500 mcg/day by beclomethasone dipropionate), there were determined the level of asthma control according to the questionnaire Asthma Control Test (ACT), lung function, airway reaction to 3-minute isocapnic hyperventilation with cold (-20ºC) air; there was done the collection of induced sputum (IS). The content of cells in cytograms of IS was assessed. The activity of myeloperoxidase (MPO) (in pixels) was measured by cytochemical method in neutrophilic and eosinophilic granulocytes. Group 1 (n=43; 22%) included patients with the eosinophilic pattern of bronchial inflammation, group 2 (n=155; 78%) included patients with mixed pattern of inflammation. In group 2, unlike the patients of group 1, in the inflammatory profile of infiltrate against the background of high neutrophil content (34.6±1.1 and 10.8±0.5%, respectively; p=0.000001), there was found an increased level of eosinophils (17.0±1.1 vs. 21.2±1.8%, respectively; p=0.048), and there was revealed a higher intragranular deposition of MPO (85.8±3.5 vs. 77.0±3.2 pixels, respectively; p=0.057). The mixed type of inflammation with the dominant neutrophil component and the greatest activity of MPO was associated with more pronounced clinical symptoms of the disease and low level of asthma control (16.0±0.7 vs. 18.7±0.4 ACT points, respectively; p=0.004), lung function decrease (FEV1 was 89.4±1.4 vs. 97.9±2.2%, respectively; p=0.005) and degree of FEV1 drop in response to bronchial provocation by cold air (-10.1±1.1 vs. -3.4±1.1%, respectively; p=0.002), due to insufficient anti-inflammatory effect of the used controller therapy. A discriminant equation is proposed, which can serve as an additional criterion for the effectiveness of anti-inflammatory therapy.


2021 ◽  
Vol 30 ◽  
pp. 096368972110249
Author(s):  
G Adas ◽  
Z Cukurova ◽  
K Kart Yasar ◽  
R Yilmaz ◽  
N Isiksacan ◽  
...  

The aim of this clinical trial was to control the cytokine storm by administering mesenchymal stem cells (MSCs) to critically-ill COVID-19 patients, to evaluate the healing effect, and to systematically investigate how the treatment works. Patients with moderate and critical COVID-19 clinical manifestations were separated as Group 1 (moderate cases, n = 10, treated conventionally), Group 2 (critical cases, n = 10, treated conventionally), and Group 3 (critical cases, n = 10, treated conventionally plus MSCs transplantation therapy of three consecutive doses on treatment days 0, 3, and 6, (as 3 × 106 cells/kg, intravenously). The treatment mechanism of action was investigated with evaluation markers of the cytokine storm, via biochemical parameters, levels of proinflammatory and anti-inflammatory cytokines, analyses of tissue regeneration via the levels of growth factors, apoptosis markers, chemokines, matrix metalloproteinases, and granzyme-B, and by the assessment of the immunomodulatory effects via total oxidant/antioxidant status markers and the levels of lymphocyte subsets. In the assessment of the overall mortality rates of all the cases, six patients in Group-2 and three patients in Group-3 died, and there was no loss in Group-1. Proinflammatory cytokines IFNγ, IL-6, IL-17A, IL-2, IL-12, anti-inflammatory cytokines IL-10, IL-13, IL-1ra, and growth factors TGF-β, VEGF, KGF, and NGF levels were found to be significant in Group-3. When Group-2 and Group-3 were compared, serum ferritin, fibrinogen and CRP levels in Group-3 had significantly decreased. CD45 +, CD3 +, CD4 +, CD8 +, CD19 +, HLA-DR +, and CD16 + / CD56 + levels were evaluated. In the statistical comparison of the groups, significance was only determined in respect of neutrophils. The results demonstrated the positive systematic and cellular effects of MSCs application on critically ill COVID-19 patients in a versatile way. This effect plays an important role in curing and reducing mortality in critically ill patients.


2020 ◽  
Vol 9 (6) ◽  
pp. 1899 ◽  
Author(s):  
Robert Schönbauer ◽  
Michael Lichtenauer ◽  
Vera Paar ◽  
Michael Emich ◽  
Monika Fritzer-Szekeres ◽  
...  

Background: Low levels of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) were reported in patients with coronary artery disease, heart failure, chronic kidney disease and diabetes mellitus. Soluble cluster differentiation 163 (sCD163) serum levels are related to M2 macrophages, having anti-inflammatory attributes. As sport is well-known for its anti-inflammatory and cardioprotective effects we aimed to investigate the influence of eight months of physical activity on serum sCD163 and sTWEAK levels. Methods: In total, 109 subjects with at least one cardiovascular risk factor were asked to perform endurance training within the calculated training pulse for eight months. Overall, 98 finished the study. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. The cohort was divided into four groups, dependent on their baseline performance and performance gain. sCD163 and sTWEAK were measured at baseline and after two, six and eight months by ELISA. Results: Those participants who had a performance gain of ≤2.9% (mean gain 12%) within eight months showed a significant increase in sTWEAK (group 2: from 133 to 200 pg/mL, p = 0.002 and group 4: from 166 to 212 pg/mL, p = 0.031) and sCD163 levels (group 2: from 255 to 348 ng/mL, p = 0.035 and group 4: from 247 to 288 ng/mL, p = 0.025) in contrast to subjects without performance gain (sTWEAK: group 1: from 161 to 177 pg/mL, p = 0.953 and group 3: from 153 to 176 pg/mL, p = 0.744; sCD163: group 1: from 289 to 256 ng/mL, p = 0.374 and group 4: from 291 to 271 ng/mL, p = 0.913). Baseline sCD163 correlated with erythrocyte count, hematocrit, ASAT and lipoprotein a, the presence of hypertension and a BMI > 30 kg/m2. Conclusion: Regular physical activity leads to a significant increase in sCD163 and sTWEAK levels of up to 37% and 50%, respectively. It is well-known that physical activity prevents or retards the onset and genesis of chronic inflammatory disease. One possible way of how training evolves its beneficial effect might be by modifying the inflammation status using the sTWEAK–sCD163 axis. Brief Summary: Regular physical activity leads to a significant increase in sTWEAK and sCD163 levels. Both factors are diminished in patients with chronic (inflammation-based) diseases, such as coronary artery disease, heart failure, pulmonary artery hypertension, chronic kidney disease and diabetes mellitus. It seems that the amounts of soluble TWEAK and CD163 are essential for a healthy balance and modulation between pro- and anti-inflammatory processes, and regular physical training could use the sCD163–sTWEAK axis to unfold its beneficial effect.


2019 ◽  
Vol 100 (1) ◽  
pp. 135-139
Author(s):  
L I Allakhverdiyeva ◽  
N G Sultanova ◽  
A O Dzhafarova

Aim. To study the state of the cytokine response in children with atopic bronchial asthma during pharmacological correction with vitamin D. Methods. 63 children aged 3-17 years with atopic bronchial asthma of varying severity were examined. As a control group, 10 practically healthy children of the same age who had no history of allergic manifestations and no hereditary complications, were examined. The patients were divided into two groups matched by age: group 1 included 33 patients with mild (n=20) and moderate (n=13) bronchial asthma who received only basic anti-inflammatory therapy according to the severity of asthma; group 2 included 30 children with mild (n=18) and moderate (n=12) bronchial asthma who received basic anti-inflammatory therapy with vitamin D containing Tridrop [3 drops (1500 IU) per day for 1 month]. Patients were assessed for interleukin-2, -13 and -17 in the blood serum using a solid-phase enzyme-linked immunosorbent assay before and after treatment. Results. The results obtained made it possible to clarify the changes in the cytokine spectrum in patients with atopic bronchial asthma in the course of the disease and the effect of pharmacological correction with vitamin D on it. The mean level of interleukin-2 in group 1 remained practically unchanged, the value of this cytokine was 2.77±1.51 pg/ml (p >0.05). In group 2, the mean interleukin-2 level increased to 5.07±1.02 pg/ml (p <0.01). The mean level of interleukin-13 in group 1 patients increased but not significantly, but in group 2 a decrease of interleukin-13 to 11.3±3.8 pg/ml (p <0.05) was registered. Interleukin-17 decreased by 2.6 times in group 2 (4.8±1.6 pg/ml, p <0.01). In group 1 there was no significant change in the level of interleukin-17, in all children it remained elevated (p >0.05). Conclusion. Pharmacological correction with vitamin D on the background of basic anti-inflammatory therapy promotes the positive dynamics of the level of cytokines during the treatment of atopic bronchial asthma, which is related to the ability of vitamin D to regulate the function of Th2 and, as a result, to reduce the synthesis of interleukin-13 and -17, which participate in the pathogenesis of allergies and play an important protective role in bronchial asthma.


2012 ◽  
Vol 9 (1) ◽  
pp. 29-36
Author(s):  
A V Emelyanov ◽  
L A Goryachkina ◽  
N G Astafeva ◽  
R S Fassakhov ◽  
B A Chernyak ◽  
...  

The aim of the study which included 2311 patients (aged 18—80 yrs), examined by 100 physicians (57% allergists, 37% pulmonologists and 7% general practitioner) in 18 Russian cities, was to assess the prevalence of allergic rhinitis in patients with asthma, as well as to evaluate the specifics of the course of these diseases, when concomitant or not. The study design included one outpatient visit, followed by the completion of studyspecific case report forms and Asthma Control Questionnaire (ACQ) validated for use in Russia. The vast majority (88%)of asthma patients had concomitant allergic rhinitis (Group 1). Patients with asthma only (Group 2) were older (50,6±0,78 vs 41,9±0,35 yr, p


2018 ◽  
Vol 20 (6) ◽  
pp. 913-920
Author(s):  
M. V. Antonyuk ◽  
T. A. Gvozdenko ◽  
T. P. Novgorodtseva ◽  
T. I. Vitkina ◽  
B. I. Geltser ◽  
...  

Combination of bronchial asthma (BA) and obesity is a difficult-to-control phenotype. Studies of inflammatory process with respect to severity of the disease are important for understanding the potential influence of obesity on the BA clinical course. The objective of this study was to determine cytokine profile in patients with mild BA combined with obesity. The study involved fifty-three patients with partially controlled mild BA. The patients were recruited as volunteers and signed an informed consent. The first observation group consisted of 27 asthma patients with normal body weight, the second observation group consisted of 26 patients with BA combined with obesity. A control group included 25 healthy volunteers. All the patients underwent clinical and laboratory examination in accordance with clinical standards for BA and obesity. The levels of TNFα, IL-2, IL-4, IL-6, IL-10 were evaluated in blood serum by means of flow cytometry. The ratios of proand anti-inflammatory cytokines (TNFα/IL-4, TNFα/IL-10, IL-6/IL-4, IL-6/IL-10) were calculated. Asthma patients with obesity (the 2nd group) had elevated levels of IL-2 over control group and group 1, by 38% and 44% respectively(p < 0.05). The concentration of proinflammatory cytokines TNFα and IL-6 was significanty increased in the both patient groups. Mean TNFα level was increased 2.5 times (p < 0.05), and IL-6 levels were increased by 30% (p < 0.05) in the 1st group as compared to the controls. TNFα and IL-6 concentrations showed a 3-fold increase over control values (p < 0.05) in the 2nd group. The level of antiinflammatory cytokine IL-4 was increased in patients with BA, independently of body mass. It should be noted that the concentration of this cytokine in obese patients was higher by 29% than in patients with normal body weight. IL-10 levels in patients from the 2nd group were reduced more than 2 times than in the 1st group. The patients of the 1st group showed a decrease in the IL-6/IL-10 index, in comparison with control parameters, thus indicative of an imbalance due to the elevation of the anti-inflammatory IL-10 cytokine. Among BA patients with obesity (group 2) the TNFα/IL-10 and IL-6/IL-10 indexes were higher than those of the control group (2.3- and 5.5-fold, respectively) and the group 1 (2.6- and 2.5-fold, respectively). Dynamics of these indexes confirms the systemic nature of inflammation and a predominance of non-atopic  inflammation in asthma patients with obesity. Thus, features of the cytokine profile in BA with obesity consist of a significant increase in pro-inflammatory IL-2, IL-6, TNFα cytokines, and a relative decrease in anti-inflammatory IL- 10 cytokine. The development of BA with obesity, even in mild-severity BA, is accompanied by development of a cytokine disbalance, which is typical for a mixed-type inflammation, with a prevalence of neutrophil inflammation. 


2021 ◽  
pp. 22-27
Author(s):  
Vita Skoryk

The aim of the study. To compare the effectiveness of methylprednisolone, dexamethasone and tocilizumab in patients with severe coronavirus disease. Identify the most appropriate treatment option. Materials and methods. Patients of group 1 (n=20) received for anti-inflammatory purposes tocilizumab at a dose of 600–800 mg. Patients in group 2 (n=82) received pulse therapy with methylprednisolone. Patients in group 3 (n=20) received dexamethasone 6 mg / day. Data are presented as M [25–75]. Statistical analysis of the results was performed using the program "Statistica 10". Significance of differences in indicators was assessed using the nonparametric Wilcoxon test. The results were considered reliable at values of p <0.05. Results. The severe course of coronavirus disease with the development of cytokine storm and respiratory distress syndrome is characterized by an increase in markers of inflammation: in group 1 the median CRP was 89.2 g / l, in group 2 – 64.2 g / l, and in 3 – 76.2 g / l, and did not differ significantly between groups (p> 0.05). The level of IL-6 in group 1 was 61.8 pg / ml, in group 2 – 64.6 pg / ml, and in group 3 – 46.5 pg / ml without significant differences between groups (p> 0.05). The level of ferritin in all groups exceeded normal values. Conclusions The most favourable result was obtained when using methylprednisolone: it was possible to reduce the mortality rate to 59.8 %. The relative risk of developing VTE was significantly higher in groups 1 and 3 (RR12 6.8 [2.7–16.8] p12 <0.0001, RR23 0.15 [0.06–0.35] p23 <0.0001), which gives grounds to confirm the presence of anticoagulant activity in methylprednisolone


2018 ◽  
Vol 75 (1) ◽  
pp. 39-45
Author(s):  
Dragan Koruga ◽  
Nenad Baletic ◽  
Kristina Tot-Veres ◽  
Aleksandar Peric

Background/Aim. Impulse oscillometry (IOS) is a method for estimating lung function which is used for early detection of bronchial hyperresponsiveness (BHR) and asthma. The aim of the study was to determine the prevalence of BHR, the correlation between spirometry and IOS and sensitivity and specificity of IOS in proving BHR in patients with persistent allergic rhinitis. Methods. The study included 81 patients with allergic rhinitis. From all of them, medical history was taken, allergy testing was done, as well as measurements of parameters of lung function by the IOS and spirometry before and after nonspecific bronchial provocation test with histamin via Aerosol provocative system. Changes of the IOS parameters to fall in FEV1 of 20% were measured and compared with changes in the spirometry parameters. After bronchial challenge test subjects were divided into two groups: the group with BHR (group 1) and that without BHR (group 2). Results. The mean age of participants was 25.7 ? 5.7 years, and 50.5% were men. Out of the total number of subjects with allergy rhinitis, 56 (58.9%) had a positive BPT. After bronchoprovocation an average increase in the group 1 was 88.15% for Rrs5, 111.98% for Fres, and for AX 819.69%. The high degree of correlation between the IOS and spirometry was proven in the group 2, while the whole group 1 had a weak correlation between parameters of these two methods. High sensitivity and low specificity for Rrs5 and Fres compared to FEV1 in diagnosing BHR was proven. Conclusion. The study demonstrated a high prevalence of BHR in the study group of patients with persistent allergic rhinitis, poor correlation in relation to the spirometric measurements in the group with BHR and a high sensitivity and low specificity of IOS for the detection of early changes in the airways.


Author(s):  
N. L. Perelman

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<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.


2020 ◽  
Vol 12 (6) ◽  
pp. 71-76
Author(s):  
V. A. Shirokov ◽  
A. V. Potaturko ◽  
N. L. Terekhov

Nonsteroidal anti-inflammatory drugs (NSAIDs) and muscle relaxants are used orally or intramuscularly (IM) to treat lumbar ischialgia caused by musculoskeletal disorders or radiculopathy. A comparative study has been conducted to investigate the efficacy and safety of the NSAID meloxicam (Amelotex®) injected intramuscularly and into the trigger points in combination with tolperisone and B-group vitamins for lumbar ischialgia.Patients and methods. The investigation enrolled 62 patients aged 30–60 years with lumbar ischialgia, who were randomized into three equal groups. Group 1 patients were injected with meloxicam 1.5 ml (15 mg of its active ingredient) into the trigger points daily for 3 days, followed by one 15-mg tablet daily for 14 days; Group 2 received IM meloxicam 15 mg daily for 3 days, followed by one 15-mg tablet daily for 14 days; Group 3 had IM meloxicam 15 mg daily for 3 days, followed by one 15-mg tablet daily for 14 days in combination with tolperisone (Calmirex®) as tablets: 150 mg (Day 1 of therapy), 300 mg (Day 2), and 450 mg daily (Day 3 until the end of therapy). All the patients received IM Vitamin B complex (Compligam B®) 2 ml for 5 days. The treatment efficiency was evaluated using the pain visual analogue scale (VAS), the Oswestry disability questionnaire, and the McGill pain questionnaire, the range of motion, and the severity of neurodystrophic syndrome.Results and discussion. All the patient groups showed a rapid and substantial pain reduction on the VAS and a functional activity improvement according to the Oswestry scale, which made it possible to complete the treatment within an average of 9.6 days. Groups 3 and 1 exhibited a faster improvement and, as a result, a shorter therapy duration on 8.6±1.2 and 9.2±0.9 days than did Group 2 (8.6±1.2 days). On day 2 of treatment, there was a more considerable pain reduction on the VAS in Group 1 that received meloxicam injections into the trigger zones. The administration of meloxicam intramuscularly and into the trigger zones in combination with tolperisone and vitamin B complex was noted to be safe and well tolerated.Conclusion. The injection of Amelotex into the trigger zones is highly effective and safe in treating lumbar ischialgia. An NSAID (meloxicam) in combination with a muscle relaxant (tolperisone) speeds up recovery and shortens the duration of NSAID intake.


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