PROFILE OF BRONCHIAL INFLAMMATION AND CLINICAL FEATURES OF MILD BRONCHIAL ASTHMA

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.

asthma, bronchial inflammation patterns, anti-inflammatory therapy

1. Ненашева Н.М. Фенотипы бронхиальной астмы и выбор терапии // Практическая пульмонология. 2014. №2. С.2-11.

2. Панасенко О.М., Сергиенко В.И. Галогенирующий стресс и его биомаркеры // Вестник РАМН. 2010. №1. С.27-39.

3. Пирогов А.Б., Колосов В.П., Перельман Ю.М., Приходько А.Г., Зиновьев С.В., Гассан Д.А., Мальцева Т.А. Особенности воспалительных паттернов бронхов и клинико-функциональная характеристика тяжёлой неконтролируемой астмы у больных с холодовой гиперреактивностью дыхательных путей // Пульмонология. 2016. Т.26, №6. С.701-707. doi:10.18093/086901892016266701707

4. Пирогов А.Б., Приходько А.Г., Перельман Ю.М., Зиновьев С.В. Влияние нейтрофильного компонента бронхиального воспаления на уровень контроля болезни и функцию внешнего дыхания у больных бронхиальной астмой // Бюллетень физиологии и патологии дыхания. 2016. Вып.61. С.16-24. doi: 10.12737/21434

5. Приходько А.Г., Перельман Ю.М., Колосов В.П. Гиперреактивность дыхательных путей. Владивосток: Дальнаука, 2011. 204 с.

6. Федосеев Г.Б., Трофимов В.И., Петрова М.А. Многоликая бронхиальная астма. Диагностика, лечение и профилактика. СПб.: Нордмедиздат, 2011. 344 с.

7. Федосеев Г.Б., Трофимов В.И., Шапорова Н.Л., Александрин В.А., Филиппова Н.А., Крякунов К.Н. В поисках истины: что такое бронхиальная астма? // Пульмонология. 2015. Т.25, №1. С.5-18. doi:10.18093/0869-0189-2015-25-1-5-18

8. Хейхоу Ф.Г. Дж., Кваглино Д. Гематологическая цитохимия: пер. с англ. / под ред. Н.С. Кисляк. М.: Медицина, 1983. 318 с.

9. Bakakos P., Schleich F., Alchanatis M., Louis R. Induced sputum in asthma: From bench to bedside // Curr. Med. Chem. 2011. Vol.18, №10. Р.1415-1422. doi: 10.2174/092986711795328337

10. Bateman E.D., Reddel H.K., Eriksson G., Peterson S., Ostlund O., Sears M.R., Jenkins C., Humbert M., Buhl R., Harrison T.W., Quirce S., O'Byrne P.M. Overall asthma control: the relationship between current control and future risk // J. Allergy Clin. Immunol. 2010. Vol.125, №3. Р.600-608. doi:10.1016/j.jaci.2009.11.033

11. Dusser D., Montani D., Chanez P., de Blic J., Delacourt C., Deschildre A., Devillier P., Didier A., Leroyer C., Marguet C., Martinat Y., Piquet J., Raherison C., Serrier P., Tillie-Leblond I., Tonnel A.B., Tunon de Lara M., Humbert M. Mild asthma: an expert review on epidemiology, clinical characteristics and treatment recommendations // Allergy. 2007. Vol.62, №6. Р.591-604. doi: 10.1111/j.1398-9995.2007.01394.x

12. Global Initiative for Asthma (GINA). Global strategy for asthma management and prevention (Updated 2018). URL: http://www.ginasthma.com.

13. Levy M., Andrews R., Buckingham R., Evans H., Francis C., Houston R., Lowe,D., Nasser S., Paton J., Puri N., Stewart K., Thomas M. Why asthma still kills: The national review of asthma deaths (NRAD). Project Report. Royal College of Physicians, London - Royal College of Physicians. 2014. URL: http://eprints.uwe.ac.uk/23453/1/why-asthma-still-kills-full-report.pdf

14. Levy М. L. Asthma still kills: little change over five decades // NPJ Prim. Care Respir. Med. 2014. №24. Р.14029. doi: 10.1038/npjpcrm.2014.29

15. Lockey R.F. Asthma phenotypes: an approach to the diagnosis and treatment of asthma // J. Allergy Clin. Immunol. Pract. 2014. Vol.2, №6. Р.682-685. doi:10.1016/j.jaip.2014.09.008

16. Papi A., Canonica G.W., Maestrelli P., Paggiaro P., Olivieri D., Pozzi E., Crimi N., Vignola A.M., Morelli P., Nicolini G., Fabbri L.M. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma // N. Engl. J. Med. 2007. Vol.356, №20. Р.2040-2052. doi:10.1056/nejmoa063861

17. Ortega H.G., Yancey S.W., Mayer B., Gunsoy N.B., Keene O.N., Bleecker E.R., Brightling C.E., Pavord I.D. Severe eosinophilic asthma treated with mepolizumab stratified by baseline eosinophil thresholds: a secondary analysis of the DREAM and MENSA studies // Lancet Respir. Med. 2016. Vol.4, №7. Р.549-556. doi: 10.1016/s2213-2600(16)30031-5