Influence of Neutrophilic Component of Bronchial Inflammation on the Level of Disease Control and Lung Function in Patients With Asthma

Bulletin Physiology and Pathology of Respiration

Перельман²,

Perelman

et al. 2018

Self Cite

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.

Section: результаты исследования и их обсуждениеunclassified

Section: таблицаunclassified

Profile of Bronchial Inflammation and Clinical Features of Mild Bronchial Asthma

Bulletin Physiology and Pathology of Respiration

Перельман²,

Perelman

et al. 2018

Self Cite

“…В проведенных нами ранее исследованиях, касающихся деструкции эпителия бронхов у больных тяжелой БА с ХГДП, эскалация эпителиальной дисфункции, потенцирующей хроническое воспаление, супрессию антиоксидантной и иммунной защиты, ремоделирование бронхов [19], рассматривалась в качестве морфологического маркера инертности достижения уровня контроля над болезнью [9]. Характер массивного повреждения эпителия, с преобладанием III и IV классов деструкции, как один из параметров ремоделирования слизистой оболочки бронхов, в этом случае ассоциировался со смешанным паттерном бронхиального воспаления [8], активация нейтрофильного пула которого оказывала негативное влияние на клинические параметры тяжёлой неконтролируемой БА [7,8].…”

Section: таблица 1 клинико-функциональная характеристика больных (м±M)unclassified

“…Стимуляция активированными нейтрофилами повреждения, апоптоза и некроза эпителия обусловлена экзоцитозом при дегрануляции, деструкции и цитолизе гранулоцитов лизосомальных ферментов, таких, как миелопероксидаза, которые обеспечивают генерацию активных форм кислорода и галогенов [6][7][8], свободнорадикальным повреждением крист митохондрий, разрушением эндоплазматического ретикулума с последующей гибелью эпителия [20]. Считается, что в этом случае сигналы апоптоза передаются в эпителий не по прямому пути, от лигирования рецептора смерти до активации каспазного каскада и гибели клеток, а по пути, опосредованному деэнергизацией эпителиоцитов [20].…”

Section: таблица 1 клинико-функциональная характеристика больных (м±M)unclassified

Features of Structural Organization of Goblet Epithelium of Bronchi in Asthma Patients With Cold Airway Hyperresponsiveness

Bulletin Physiology and Pathology of Respiration

Зиновьев²,

Zinovev

et al. 2018

Self Cite

In 46 patients with mild persistent asthma the collection and cytological study of the induced sputum (IS) was done to assess the inflammatory pattern of bronchi, structural organization of bronchial epithelium and secretory goblet cells; the level of the disease control by the data of the validated questionnaire Asthma Control Test was found out; the base lung function (FEV1) was determined; the response of airways to standard 3-minute isocapnic hyperventilation by cold (-20ºC) air (IHCA) was studied. By the results of IHCA test the patients were divided into 2 groups: with cold airway hyperresponsiveness (1st group) and without any response to IHCA test (2nd group). The patients of the 1st group in comparison with the ones of the 2nd group had a lower level of spirometric parameters and control over the disease. In the 1st group there were found more significant changes in the structural organization and destructive-cytological activity of goblet cells against the decrease of a number of epithelial cells of IM and activation of a neutrophilic pool under eosinophilic pattern of inflammation. The patients with cold airway hyperresponsiveness were found to have a close correlation between identified disorders in the structural organization of the goblet epithelium, the number of neutrophils of IS and severity of the bronchial response to IHCA test. The association of disorganization of the goblet epithelium and bronchial response to cold stimulus against the features of inflammatory pattern can be considered a risk factor of escalation of mucociliary insufficiency and worsening of clinical course of a disease and the level of asthma control.

“…Кроме того, в настоящее время курение рассматривается в ряду механизмов бронхиальной гиперреактивности, достоверный риск развития которой у курильщиков характеризуется доза-ýффект-зависимостью, а увеличение тяжести коррелирует с нарастанием интенсивности и продолжительности курения, выраженных в показателе «пачка/лет» [9]. В выполненных нами ранее работах установлено, что индукция нейтрофилами повреждения и некроза бронхиального ýпителия у больных БА опосредована осуществляемым при дегрануляции, деструкции и цитолизе гранулоцитов ýкзоцитозом лизосомальных ферментов, в частности миелопероксидазы [10], обеспечивающей гене-рацию наряду с активными формами кислорода (АФК) высокоактивных форм галогенов, что, в свою очередь, приводит к утяжелению течения болезни [11].…”

Section: Introductionunclassified

The influence of smoking on the formation of airway hyperresponsiveness to cold and the course of destructive-cytological processes in the goblet cells of the bronchial epithelium in patients with asthma

Prikhodko

Кolosov

et al. 2019

Bûll. sib. med.

Tobacco smoking in patients with asthma can intensify the bronchi mucosa damage and significantly worsen the course of the disease.Aim. To assess the influence of tobacco smoking on the clinical manifestations of the disease, airway response to cold air exposure and destructive-cytological processes in the goblet cells of bronchial epithelium in patients with asthma.Materials and methods. In 145 patients with asthma their asthma control level was determined by the Аsthma Control Test, lung function (FEV1 , %) and airway response (∆FEV1 , %) to a 3-minute isocapnic hyperventilation (–20 °С) of cold air (IHCA) were evaluated, and induced sputum (IS) was collected. In cytograms of IS a percentage content, the index of cell destruction (ICD) and the index of cytolysis intensiveness (IC) were assessed; histochemically the activity of myeloperoxidase (MPO) and the contents of glycoproteins were identified. The 1st group included 102 non-smokers and the 2nd group included 43 smokers.Results. In IS of patients of the 2nd group in comparison with the 1st one we found intensification of the destructive (ICD = 0.47 ± 0.02 and 0.40 ± 0.02, respectively, р = 0.044) and cytolytic activity of goblet cells (IC = 0.22 ± 0.03 and 0.15 ± 0.02, respectively, р = 0.047) with the domination of the number of completely destroyed cells (21.7 ± 2.4 vs. 14.5 ± 1.6%, р = 0.043) and the decrease in the number of cells with a normal structure (52.5 ± 2.1 vs. 60.5 ± 3.1%, р = 0.047). For smokers it was typical to have high contents of neutrophils in IS (34.1 ± 3.0 vs. 23.9 ± 1.4%, respectively, р = 0.0006) and high level of myeloperoxidase in granulocytes of bronchi (94.3 ± 5.4 vs. 80.7 ± 3.6 pixels, р = 0.037). Smokers responded more actively to IHCA (∆FEV1 was –13.7 ± 2.6 vs. –7.9 ± 1.2%, respectively, р = 0.032), and the degree of the response correlated with the indices of destructive-cytological activity of IS cells.Conclusion. Tobacco smoking in patients with asthma leads to the disturbance of the structure of goblet epithelium in the bronchi with the intensification of destructive-cytological processes, which is accompanied by a decrease in the level of glycoproteins in cytoplasm, an increase in the secretory activity of the goblet cells, neutrophilia, growth of oxidative peroxidase activity of granulocytes, worsening of the bronchial conductance, and intensification of airway response to cold air.