Dynamics of blood and sputum eosinophils in asthma patients with cold airway hyperresponsiveness during cold air provocation

Author(s):  
Juliy M. Perelman ◽  
Aleksey B. Pirogov ◽  
Anna G. Prikhodko ◽  
Elena V. Ushakova ◽  
Victor P. Kolosov
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. 


Author(s):  
Juliy M. Perelman ◽  
Anna G. Prikhodko ◽  
Ekaterina Y. Kochegarova ◽  
Larisa Y. Oshur ◽  
Evgeniya Y. Afanaseva

2012 ◽  
Vol 10 (3) ◽  
pp. 383-392 ◽  
Author(s):  
M. Malerba ◽  
B. Ragnoli ◽  
A. Radaeli ◽  
F.L.M. Ricciardolo

Current approaches to control asthma do not involve direct assessment of airway inflammation. The aim of this study is to assess whether the therapeutic adjustments of steroid treatment according to a stepwise algorithm based on sputum Eosinophils (sEos) and fractioned exhaled Nitric Oxide (FeNO) were effective in maintaining the stability of a group of stable asthmatic patients during a twelvemonth follow-up. Fourteen asthmatic patients, treated for asthma according to a previously published protocol, were enrolled in the study. The patients underwent clinical evaluation, pulmonary function tests, measuring of airway hyperresponsiveness to methacholine, and determination of FeNO and sEos at visit 1. These procedures were repeated after 6 and 12 months (Visits 2 and 3, respectively). Symptoms score gradually improved during the study (p=0.008), no changes were observed in the frequency of clinical asthma exacerbations or in airway hyperresponsiveness to methacholine. At the end of the study both sEos and FeNO were significantly improved (p=0.011 and p=0.003, respectively) and at visit 3 the median steroid dose was reduced (p=0.039) in accordance with the improving of symptoms score, FeNO and sEos values. A direct relationship was observed between the difference of FeNO values and the difference of sEos registered between visits 1 and 2 (r2=609, p0.001) and between visits 2 and 3 (r2=646, p<0.001). In conclusion, long-term titration of asthma inhaled steroid treatment based on sEos and FeNO values was able to provide long-term clinical stability and improvement to the asthmatic patients studied, without significant increases in the steroid dose.


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.


2021 ◽  
Vol 12 ◽  
Author(s):  
Hariharan Subramanian ◽  
Tanwir Hashem ◽  
Devika Bahal ◽  
Ananth K. Kammala ◽  
Kanedra Thaxton ◽  
...  

Asthma prevalence has increased considerably over the decades and it is now considered as one of the most common chronic disorders in the world. While the current anti-asthmatic therapies are effective for most asthma patients, there are 5-10% subjects whose disease is not controlled by such agents and they account for about 50% of the asthma-associated healthcare costs. Such patients develop severe asthma (SA), a condition characterized by a dominant Th1/Th17 cytokine response that is accompanied by Type 2 (T2)-low endotype. As JAK (Janus Kinase) signaling is very important for the activation of several cytokine pathways, we examined whether inhibition of JAKs might lessen the clinical and laboratory manifestations of SA. To that end, we employed a recently described murine model that recapitulates the complex immune response identified in the airways of human SA patients. To induce SA, mice were sensitized with house dust mite extract (HDME) and cyclic (c)-di-GMP and then subsequently challenged with HDME and a lower dose of c-di-GMP. In this model, treatment with the JAK inhibitor, Ruxolitinib, significantly ameliorated all the features of SA, including airway hyperresponsiveness and lung inflammation as well as total IgE antibody titers. Thus, these studies highlight JAKs as critical targets for mitigating the hyper-inflammation that occurs in SA and provide the framework for their incorporation into future clinical trials for patients that have severe or difficult-to manage asthma.


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