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.

1 -Федеральное государственное бюджетное научное учреждение «Дальневосточный научный центр физиологии и патологии дыхания»: 675000, Благовещенск, ул. Калинина, 22; 2 -Федеральное государственное бюджетное образовательное учреждение высшего образования «Амурская государственная медицинская академия» Министерства здравоохранения Российской Федерации: 675013, Благовещенск, ул. Горького, 95 РезюмеПерсистенция воспаления дыхательных путей у больных бронхиальной астмой (БА) способствует развитию тяжелого неконтролируемо го течения болезни. Цель. Изучение особенностей воспалительных паттернов и клинико функциональных параметров тяжелой неконт ролируемой БА. Материалы и методы. В холодный период года (ноябрь -март) проведено обследование больных (n = 25) в возрасте от 45 до 55 лет с установленным диагнозом тяжелой неконтролируемой БА при помощи определения реактивности дыхательных путей на хо лодовой стимул по данным анамнестического тестирования, исследования функции внешнего дыхания по стандартной методике, цито логического и цитохимического исследования индуцированной мокроты (ИМ). Результаты. По данным анализа цитограмм ИМ больные были разделены на 2 группы: 1 я (n = 11) -с эозинофильным (> 2 % эозинофилов), 2 я (n = 14) -со смешанным (≥ 2 % эозинофилов + ≥ 61 % нейтрофилов) паттернами воспаления. Оксидативная функция лейкоцитов, оцениваемая по уровню миелопероксидазы в клет ках, степени деструкции и интенсивности цитолиза, доминировала во 2 й группе. У пациентов этой группы выявлены более выраженные симптомы и большее число случаев обострения БА, тенденция к снижению уровня контроля над болезнью по вопроснику Asthma Control Test, более значимое снижение максимальной объемной скорости в момент выдоха 25, 50 и 75 % форсированной жизненной емкости лег ких соответственно. Холодовая гиперреактивность дыхательных путей (ХГДП) по клинически значимым признакам установлена у боль ных 2 й (n = 12) и 1 й (n = 3) групп. Показано, что проявления тяжести течения болезни, нарушения вентиляционной функции легких и частота развития ХГДП у больных тяжелой неконтролируемой БА сопряжены с паттерном воспаления бронхов. Заключение. Смешан ный воспалительный паттерн связан с утяжелением течения БА и более сложной проблемой контроля над болезнью. Ключевые слова: тяжелая неконтролируемая бронхиальная астма, холодовая гиперреактивность дыхательных путей, паттерны вос паления бронхов. AbstractThe aim of this study was to investigate airway inflammation patterns and clinical and functional features of severe uncontrolled asthma. Methods. The study involved 25 patients aged 45 to 55 years with severe uncontrolled asthma. Medical history was analyzed. Lung function tests, cytological and cytochemical investigation of induced sputum were performed in all patients. Asthma control was assessed using the Asthma Control Test ques tionnaire. Results. The patients were divided into groups: with eosinophilic (> 2% of eosinophils; n = 11) or mixed (≥ 2% of eosinophils and ≥ 61% of neutrophils; n = 14) airway inflammation patterns according to induced s...

The aim of the research was to study the state of the bronchial mucosa epi-thelium in relation to the severity of clinical manifestations in severe uncon-trolled asthma depending on the pattern of inflammation and the presence of cold airway hyperresponsiveness. Materials and methods. In 48 patients with severe uncontrolled asthma, there were assessed asthma symptoms, clinical signs of cold airway hyperre-sponsiveness, and lung function; the samples of slides were analyzed in the cytological examination of the sputum; the degree of damage to epithelial cells and granulocytes was estimated using the total cell destruction index (CDI). Results. According to the analysis of sputum cytograms, the patients were divided into two groups: group I (22 patients) included persons with eosin-ophilic inflammation pattern (31.0±3.1% of eosinophils and 22.0±2.2% of neutrophils), group II (26 patients) was with mixed inflammation pattern (7.2±1.4 and 71.8±4.2%, respectively). The patients of group II had lower disease control according to Asthma Control Test (ACT; 12.1±0.7 and 17.8±0.2 points, respectively; р

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.

The aim of this study was to assess effects of antiinflammatory therapy with leukotriene receptor antagonists (LTA) and/or combination of an inhaled corticosteroid (ICS) and a long-acting β2-agonist (LABA) on the clinical course and airway inflammatory patterns in patients with severe asthma and cold air-provoked bronchial hyperresponsiveness. Methods. Asthma symptoms, lung function, and spontaneous sputum cytology were assessed at baseline and after 24 weeks of the therapy. Subgroup analysis was performed for patients with sputum eosinophils < 61% and sputum neutrophils < 61%. Eosinophilic patients were treated with fluticasone propionate/salmeterol, neutrophilic patients with treated with fluticasone propionate/salmeterol plus montelukast during 24 weeks. The control of the disease was assessed using Asthma Control Test (ACT). Results. After 24-wk treatment, eosinophilic patients improves asthma control from 10.9 ± 0.5 to 19.6 ± 1.3 according to ACT questionnaire (р < 0.001), FEV1 improved from 45.9 ± 3.7% pred. to 79.2 ± 2.2% pred. (р < 0.001). Sputum eosinophil number decreased from 27.9 ± 2.1% to 7.1 ± 1.9% (р < 0.001); sputum neutrophil number decreased from 21.1 ± 2.1% to 8.7 ± 2.3% (р < 0.001). In neutrophilic patients, ACT score improved from 8.9 ± 0.6 to 15.9 ± 1.2 (р < 0.001), FEV1 improved from 42.9 ± 2.6% pred. to 72.3 ± 2.5% pred. (р < 0.001). Sputum neutrophil number decreased from 76.8 ± 3.7 to 52.2 ± 4.3 % (р < 0.001); Sputum eosinophil number decreased from 8.1 ± 0.7% to 6.2 ± 0.4% (р < 0.05). After 24 weeks of the treatment, partial control of asthma (ACT 20 -24) was achieved in 63% and 29% of patients in eosinophilic and neutrophilic groups, respectively (χ2 = 1.81; р > 0.05) after treatment. Conclusion. Adding montelukast to the combined therapy with fluticasone propionate/salmeterol in patients with severe asthma, cold air-provoked bronchial hyperresponsiveness and increased sputum neutrophils did not resulted in better control of the disease. The analysis of airway inflammatory pattern could be used as an additional marker to predict treatment efficiency.