DYNAMICS OF INFLAMMATORY-CELLULAR PROFILE OF THE INDUCED SPUTUM IN PATIENTS WITH BRONCHIAL ASTHMA AND COLD AIRWAY HYPERRESPONSIVENESS UNDER BASIC ANTI-INFLAMMATORY THERAPY

2016 ◽  
Vol 1 (60) ◽  
pp. 15-22 ◽  
Author(s):  
Приходько ◽  
Anna Prikhodko ◽  
Пирогов ◽  
Aleksey Pirogov ◽  
Перельман ◽  
...  

The character of changes of inflammatory-cellular pattern of bronchial secretion in patients with asthma in association with cold airway hyperresponsiveness (CAHR) under the influence of standard therapy has been studied little. The aim of the present work is to study dynamics of cellular profile, neutrophilic component of bronchial inflammation under the combination therapy of asthmatics with CAHR. 12 asthma patients with CAHR were studied upon the number of cells of the induced sputum (IS), peroxidase, cytolytic and destructive activity of eosinophils and neutrophils in the sputum, lung function and asthma control with the help of questionnaire Asthma Control Test (АСТ) before and after the therapy with the combination of budesonide/formoterol. Before the therapy the patients had a low level of asthma control (14.4±1.2 points of ACT), FEV1 was 87.4±3.3% from predicted values; in IS neutrophils prevailed (26.4±1.7%) over eosinophils (18.5±2.6%); the level of myeloperoxidase (mean cytochemical coefficient) was 65.9±5.4 pixels. After 48 weeks of the observation only in 58% of patients the criteria of good control of asthma and the improvement of lung function were achieved. In IS there was a decrease of eosinophils (11.4±3.2%; p=0.045); the intensiveness of eosinophils and neutrophils cytolysis dropped; intracellular concentration of myeloperoxidase grew (98.2±14.1 pixels; p=0.0637); destructive changes in granulocytes were registered but the number of neutrophils remained high (34.0±8.2%, р=0.34), which was considered as the factor of stable initiation of inflammation and oxidative stress. Thus, the use of anti-inflammatory treatment regime lasting 48 weeks with combination of budesonide/formoterol oriented to achieve clinical criteria of asthma control in patients with CAHR does not allow to achieve correction of the level of neutrophilic inflammatory component. Quantitative index of neutrophils in IS in these patients has prognostic value for the possible loss of achieved asthma control.

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.


Author(s):  
A. B. Pirogov ◽  
A. G. Prikhodko ◽  
J. M. Perelman

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>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. 


2016 ◽  
Vol 1 (61) ◽  
pp. 16-24 ◽  
Author(s):  
Приходько ◽  
Anna Prikhodko ◽  
Пирогов ◽  
Aleksey Pirogov ◽  
Перельман ◽  
...  

The cell pattern of bronchi inflammatory infiltrate has a significant impact on the course of the disease and may affect the achievement and maintenance of the asthma control. The aim of the study was to determine the influence of neutrophilic component of the bronchial inflammation on the asthma control, lung function and airway responsiveness. 114 patients with mild persistent asthma were assessed upon the level of the asthma control by Asthma Control Test (ACT); lung function (FEV1) by spirometry; airway responsiveness (∆FEV1) to 3-minute isocapnic hyperventilation with cold air (-20ºС) (IHCA) and 3-minute ultrasound inhalation with distilled water (IDW). The cell composition of the induced sputum (IS) was also studied. The patients were divided into groups with low contents of neutrophils in IS (39 people; 1st group) and with high contents of neutrophils (75 people, 2nd group). The contents of neutrophils in the 1st group was 10.9±0.53%, eosinophils – 19.4±2.1%; in the 2nd group – 29.9±1.6% (р=0.0001) and 20.4±1.4% (р=0.66), respectively. By ACT data the people of the 2nd group managed their disease worse than in 1st group (15.0±0.6 and 19.0±0.8 points, respectively; р=0.0001). They also had lower FEV1 (88.0±2.0 and 96.7±2.4%; р=0.009) and more intensive airway response to IHCA and DW (-13.7±1.7% and -11.2±1.9%, respectively) in comparison with the 1st group (-2.7±0.86%; р=0.0001 and -5.3±1.90%; р=0.055). The patients of the 2nd group had a close correlation between baseline neutrophils in IS and ∆FEV1 in response to IHCA (r=-0.22; р=0.045) as well as the content of myeloperoxidase in IS (r=0.31; р=0.0008). A level of myeloperoxidase in IS correlated with ∆FEV1 in response to IDW (r=0.29; р=0.030) in these patients. The increase of neutrophilic component of inflammation in asthma patients worsens the asthma control, lung function and enhances airway responsiveness to exogenous stimuli.


2009 ◽  
Vol 107 (2) ◽  
pp. 408-416 ◽  
Author(s):  
Roberto Torchio ◽  
Alessandro Gobbi ◽  
Carlo Gulotta ◽  
Raffaele Dellacà ◽  
Marco Tinivella ◽  
...  

We investigated whether obesity is associated with airway hyperresponsiveness in otherwise healthy humans and, if so, whether this correlates with a restrictive lung function pattern or a decreased number of sighs at rest and/or during walking. Lung function was studied before and after inhaling methacholine (MCh) in 41 healthy subjects with body mass index ranging from 20 to 56. Breathing pattern was assessed during a 60-min rest period and a 30-min walk. The dose of MCh that produced a 50% decrease in the maximum expiratory flow measured in a body plethysmograph (PD50MCh) was inversely correlated with body mass index ( r2 = 0.32, P < 0.001) and waist circumference ( r2 = 0.25, P < 0.001). Significant correlations with body mass index were also found with the maximum changes in respiratory resistance ( r2 = 0.19, P < 0.001) and reactance ( r2 = 0.40, P < 0.001) measured at 5 Hz. PD50MCh was also positively correlated with functional residual capacity ( r2 = 0.56, P < 0.001) and total lung capacity ( r2 = 0.59, P < 0.001) in men, but not in women. Neither PD50MCh nor body mass index correlated with number of sighs, average tidal volume, ventilation, or breathing frequency. In this study, airway hyperresponsiveness was significantly associated with obesity in otherwise healthy subjects. In obese men, but not in women, airway hyperresponsiveness was associated with the decreases in lung volumes.


Medicina ◽  
2009 ◽  
Vol 45 (12) ◽  
pp. 943 ◽  
Author(s):  
Guoda Pilkauskaitė ◽  
Kęstutis Malakauskas ◽  
Raimundas Sakalauskas

International guidelines indicate that the main criterion of asthma management is asthma control level. The aim of this study was to assess asthma control and its relation with age, gender, and lung function. Material and methods. A total of 106 family physicians and 13 pulmonologists and allergists took part in this study. Each doctor had selected 10–15 asthma patients and had sent invitations to them by post. On the visit day, the patients themselves filled in the Asthma Control Test. The doctors interviewed the patients and filled in a special questionnaire. Pulmonologists and allergists also assessed lung function by performing spirometry. According to the results of the Asthma Control Test, the disease control level was indicated as “totally controlled” (25 points), “well controlled” (24–20 points), and “uncontrolled” (19 points or less). Results. A total of 876 asthma patients were examined. Uncontrolled asthma was diagnosed to 56.2% of the patients, 36.5% of patients had well controlled and 7.3% totally controlled asthma. There was no significant difference in asthma control level comparing men and women. A correlation between asthma control level and age was found revealing poorer asthma control in older patients. Ninety-five percent of patients were treated with inhaled steroids; most of them had used inhaled steroids in combination with long-acting β2 agonists. It was found that lung function correlated with clinical symptoms of asthma, the demand of shortacting β2 agonists, and asthma control level. Conclusion. The study showed that uncontrolled asthma was diagnosed to more than half of the patients, despite most of them used inhaled steroids. Asthma control was worsening with the age of patients with asthma and it correlated with lung function. We suggest that periodical assessment of asthma control should help to optimize asthma management.


2013 ◽  
Vol 3 (8) ◽  
pp. 276-282
Author(s):  
Johnbull Jumbo ◽  
◽  
Bamidele Olaiya Adeniyi ◽  
Gregory Efosa Erhabor

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Panek Michał ◽  
Stawiski Konrad ◽  
Kuna Piotr

Abstract Background TGF-β and its receptors play a crucial role in asthma pathogenesis, bronchial hyperreactivity, and bronchial remodeling. Expression of isoforms 1–3 of TGFβ cytokine is influenced by tagging polymorphisms in the TGFβ1, TGFβ2 and TGFβ3 gene, and these SNPs may be associated with the risk of asthma development and severity as well as with other diseases. Polymorphic forms of TGF-β1, TGF-β2 and TGF-β3 genes regulate the degree of bronchial inflammation, deterioration of lung functional parameters in spirometry and elevated level of total IgE. All this results in intensification of disease symptoms. According to current GINA 2020 guidelines, the Asthma Control Test (ACT™) should be applied to assess asthma symptoms. Methods An analysis of polymorphisms localized in TGF-β1, TGF-β2 and TGF-β3 genes was conducted on 652 DNA samples with an application of the MassARRAY® system using the mass spectrometry technique MALDI TOF MS. The degree of asthma control was evaluated with ACT™. Results The occurrence of the T / C genotype in rs8109627 (p = 0.0171) in the TGF-β1 gene is significantly associated with a higher ACT result (controlled asthma) in a multivariate linear regression analysis model after using backward stepwise selection of variables. In addition, in the linear model for prediction of ACT score we showed SNP rs8109627 (p = 0.0497) in the TGF-β1 gene (improvement of the disease control - controlled asthma) and rs2796822 (p = 0.0454) in the TGF-β2 gene (deterioration of the diseases control - uncontrolled asthma) significantly modify the degree of asthma control. Discussion We described clinical significance of two SNPs in two genes TGF-β1 and TGF-β2, as yet unknown. We proved that the use of both genotypes and MAC allows to create a moderately correct prognostic model which is about 70% efficient on the entire set of analyzed SNPs in TGF-β1, TGF-β2, and TGF-β3 genes.


2020 ◽  
Author(s):  
Michał Gabriel Panek ◽  
Konrad Stawiski ◽  
Piotr Bolesław Kuna

Abstract Background: TGF-β and its receptors play a key role in asthma pathogenesis, bronchial hyperreactivity and bronchial remodeling. Expression of isoforms 1–3 of TGFβ cytokine is influenced by tagging polymorphisms in the TGFβ1, TGFβ2 and TGFβ3 gene, and these SNPs may be associated with the risk of asthma development and severity as well as with other diseases. Polymorphic forms of TGF-β1, TGF-β2 and TGF-β3 genes regulate the degree of bronchial inflammation, deterioration of lung functional parameters in spirometry and elevated level of total IgE. All this results in intensification of disease symptoms. According to current GINA 2020 guidelines, the Asthma Control Test (ACT™) should be applied to assess asthma symptoms. Methods: An analysis of polymorphisms localized in TGF-β1, TGF-β2 and TGF-β3 genes was conducted on 652 DNA samples with an application of the MassARRAY® system using the mass spectrometry technique MALDI TOF MS. The degree of asthma control was evaluated with ACT™. Results: The occurrence of the T / C genotype in rs8109627 (p = 0.0171) in the TGF-β1 gene is significantly associated with a higher ACT result (controlled asthma) in a multivariate linear regression analysis model after using backward stepwise selection of variables. In addition, in the linear model for prediction of ACT score we showed SNP rs8109627 (p = 0.0497) in the TGF-β1 gene (improvement of the disease control - controlled asthma) and rs2796822 (p = 0.0454) in the TGF-β2 gene (deterioration of the diseases control - uncontrolled asthma) significantly modify the degree of asthma control. Discussion: We described clinical significance of two SNPs in two genes TGF-β1 and TGF-β2, as yet unknown. We proved that the use of both genotypes and MAC allows to create a moderately correct prognostic model which is about 70% efficient on the entire set of analyzed SNPs in TGF-β1, TGF-β2, and TGF-β3 genes.


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