Особенности клеточного состава индуцированной мокроты и цитокинового профиля при синтропии бронхиальной астмы и ожирения у лиц молодого возраста
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Материалы и методы. В исследовании приняли участие 164 больных БА, которых разделили на 2 группы с учетом ИМТ: в 1-ю группу включены больные БА с ИМТ от 18 до 25 кг/м2, во 2-ю группу вошли больные БА с ИМТ от 30 до 40 кг/м2. Группу контроля составили 40 практически здоровых добровольцев. Оценивали наличие избыточного веса и определяли степень ожирения в соответствии с рекомендациями Всемирной организации здравоохранения. Изучали степень контроля БА, клеточный состав индуцированной мокроты, уровни интерлейкинов ИЛ-2, ИЛ-4, ИЛ-6, ИЛ-8, ИЛ-10, ИЛ-12, ИЛ-15, ИЛ-17, фактора некроза опухоли-α, интерферона-γ в плазме периферической крови.
Результаты. Представлены результаты исследования клеточного профиля индуцированной мокроты и цитокинового профиля у больных БА в зависимости от ИМТ и тяжести заболевания. Полученные результаты свидетельствуют о преобладании эозинофильного типа воспаления в группе больных с ИМТ менее 25 кг/м2, тогда как у пациентов с ожирением определялось преимущественно малогранулоцитарное воспаление. Наиболее высокое содержание ИЛ-17 регистрировали у больных БА с ожирением как в сравнении с показателями больных с нормальным ИМТ, так и с практически здоровыми, что, возможно, является причиной низкого эффекта стероидной терапии у данных больных.
Заключение. Оценка эндотипа перед началом базисной противовоспалительной терапии у больных с впервые диагностированной БА сможет помочь в подборе наиболее оптимального лечения каждому конкретному больному.
Ключевые слова: бронхиальная астма, индуцированная мокрота, цитокины, ожирение.
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Aim. To estimate changes of cellular structure of the induced sputum at young patients with bronchial asthma at interrelations with BMI and level of cytokines in blood plasma.
Materials and methods. 164 patients with bronchial asthma were divided into 2 groups taking into BMI: the 1st group included patients with bronchial asthma and BMI from 18 to 25 kg/m2, patients with bronchial asthma and BMI from 30 to 40 kg/m2 entered into the 2nd group. The group of control was made by 40 almost healthy volunteers. Estimated existence of excess weight and defined obesity degree according to recommendations of World Health Organization. Studied the level of control of bronchial asthma, cellular structure of the induced sputum, the IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, INF-γ levels in plasma of peripheral blood.
Results. There are presented the results of the research of cellular profile of the induced sputum and profile of cytokines at patients with bronchial asthma depending on BMI and severity of the disease. The received results testify to prevalence of eosinophilic type of an inflammation in the group of patients with BMI less than 25 kg/m2 whereas at patients mainly paucigranulation inflammation decided on obesity. The highest content of the Il-17 was registered at patients with bronchial asthma and obesity as in comparison with indicators of patients with normal BMI, and with almost healthy that, perhaps, is the reason of low effect of steroid therapy at these patients.
Conclusion. Endotype assessment before basic antiinflammatory therapy at patients with the first time diagnosed bronchial asthma, will be able to help with selection of the most optimum treatment to each specific patient.
Keywords: bronchial asthma, induced sputum, cytokines, obesity.
2. Telenga ED, Tideman SW, Kerstjens HAM, ten Hacken NHT, Timens W, Postma DS, van den Berge M. Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response. Allergy. 2012; 67(8): 1060-1068.
3. Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: A meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med. 2007; 175: 661-666. doi: 10.1164/rccm.200611-1717OC
4. Camargo CA Jr, Boulet LP, Sutherland ER, Busse WW, Yancey SW, Emmett AH, Ortega HG, Ferro TJ. Body mass index and response to asthma therapy: Fluticasone propionate/salmeterol versus montelukast. J Asthma. 2010; 47: 76-82.
5. Saint-Pierre P, Bourdin A, Chanez P, Daures JP, Godard P. Are overweight asthmatics more difficult to control? Allergy. 2006;61:79-84. doi:10.1111/j.1398-9995.2005.00953.x
6. Sutherland TJT, Cowan JO, Young S, Goulding A, Grant AM, Williamson A, Brassett K, Herbison GP, Taylor DR. The association between obesity and asthma interactions between systemic and airway Inflammation. All AJRCCM. 2008; 178 (5).
7. Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990; 323: 1033-1039. doi: 10.1056/NEJM199010113231505
8. Fahy JV, Kim KW, Liu J, Boushey HA. Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol. 1995; 95: 843-52.
9. Turner MO, Hussack P, Sears MR, Dolovich J, Hargreave FE. Exacerbations of asthma without sputum eosinophilia. Thorax. 1995; 50: 1057-1061.
10. Douwes J, Gibson P, Pekkanen J, Pearce N. Non-eosinophilic asthma: importance and possible mechanisms. Thorax. 2002; 57: 643-648.
11. Kay AB, Phipps S, Robinson DS. The role for eosinophils in airway remodeling in asthma. Tends Immunol. 2004; 25: 477-482. doi: 10.1016/j.it.2004.07.006
12. Reuter S, Heinz A, Sieren M, Wiewrodt R, Gelfand EW, Stassen M, Buhl R, Taube C. Mast cell – derived tumor necrosis factor is essential for allergic airway disease. Eur Respir J. 2008; 31: 773-782. doi: 10.1183/09031936.00058907
13. Douwes J, Gibson P, Pekkanen J, Pearce N. Non-eosinophilic asthma: importance and possible mechanisms. Thorax. 2002; 57: 643-648.
14. Leckie MJ, Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000; 356: 2144-2148.
15. Bryan SA, O’Connor B.J, Matti S, Leckie MJ, Kanabar V, Khan J, Warrington SJ, Renzetti L, Rames A, Bock JA, Boyce MJ, Hansel TT, Holgate ST, Barneset PJ. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000; 356: 2149-2153.
16. Kips JC, O’Connor BJ, Langley SJ, Woodcock A, Kerstjens HA, Postma DS, Danzig M, Cuss F, Pauwels RA. Effect of SCH55700, a humanised anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med. 2003; 167: 1655-1659. doi:10.1164/rccm.200206-525OC
17. Wilson RH, Whitehead GS, Nakano H, Free ME, Kolls JK, Cook DN. Allergic sensitization through the airway primed Th17- dependent neutrophilia and airway hyperresponsiveness. Am J Respir Cm Crit Care. 2009; 180: 720-730.
18. Stern JS, Hirsch J, Blair SN, Foreyt JP, Frank A, Kumanyika SK, Madans JH, Marlatt GA, St Jeor ST, Stunkard AJ. Weighing the options: criteria for evaluating weight-management programs. The Committee to Develop Criteria for Evaluating the Outcomes of Approaches to Prevent and Treat Obesity. Obes Res. 1995; 3 (6): 591-604.
19. Rio-Navarro В, Cisneros-Rivero M, Berber-Eslava A, Espínola-Reyna G, Sienra-Monge J. Exercise induced bronchospasm in asthmatic and non-asthmatic obese children. Allergol Immunopathol (Madr). 2000; 28 (1): 5-11.
20. Shore SA. Obesity and asthma: location, location, location. Eur Respir J. 2013; 41 (2): 253-254. doi: 10.1183/09031936.00128812
21. Авдеев С.Н., Анаев Э.Х., Чучалин А.Г. Применение метода индуцированной мокроты для оценки интенсивности воспаления дыхательных путей. Пульмонология. 1998; 2: 81-85. [Avdeev SN, Anaev EKh, Chuchalin AG. Use of a method of the induced sputum for assessment of intensity of an inflammation of respiratory tracts. Pul'monologiya. 1998;2:81-85. (In Russ.)]
22. Kips JC, Fahy JV, Hargreave FE. Methods for sputum induction and analysis of induced sputum: a method for assessing airway inflammation in asthma. Eur Respir J. 2008; 11: 9-12.
23. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology. 2006; 11:54-61.
24. Ненашева Н.М. Современное представление о фенотипах бронхиальной астмы. Фарматека. 2013; 4: 257. [Nenasheva N. M. The current understanding of the phenotypes of bronchial asthma. Pharmateca. 2013; 4: 257. (In Russ.)]
25. Newton R, Leigh R, Glembycz M. Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung disease. Prarmacology and Therapeutics. 2010;125:286-327.
26. Трофимов В., Миронова Ж. Терапевтически резистентная астма. Врач. 2012;3:2-4. [Trofimov V, Mironova Zh. Therapeutically refractory asthma. Vrach. 2012;3: 2-4. (In Russ.)]
27. Федосеев Г.Б., Трофимов В.И., Рогачева Н.Н., Разумовская Т.С. Роль нейтрофилов и бактериальной инфекции респираторного тракта у больных бронхиальной астмой и хронической обструктивной болезнью легких. Росс. аллергологический журн. 2011; 2: 34-43. [Fedoseev GB, Trofimov VI, Rogacheva NN, Razumovskaya TS. Role of neutrophils and bacterial infection of a respiratory tract at patients with bronchial asthma and chronic obstructive pulmonary disease. Russ allergolog J. 2011; 2: 34-43. (In Russ.)]
28. Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol. 1995; 154: 4719-4725.
29. Shin B, Kwon HS, Park SY, Kim TB, Moon HB, Cho YS. The transition of sputum inflammatory cell profiles is variable in stable asthma patients. Asia Pac Allergy. 2017; 7 (1): 19-28. doi: 10.5415/apallergy.2017.7.1.19
30. Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. Effects of steroid therapy on inflammatory cell subtypes in asthma. Thorax. 2010; 65: 384-390.
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1. World Health Organization. Obesity and Overweight. Fact Sheet No 311; http://www.who.int/mediacentre/factsheets/fs311/en/index.html Date last accessed: May 5, 2011.
2. Telenga ED, Tideman SW, Kerstjens HAM, ten Hacken NHT, Timens W, Postma DS, van den Berge M. Obesity in asthma: more neutrophilic inflammation as a possible explanation for a reduced treatment response. Allergy. 2012; 67(8): 1060-1068.
3. Beuther DA, Sutherland ER. Overweight, obesity, and incident asthma: A meta-analysis of prospective epidemiologic studies. Am J Respir Crit Care Med. 2007; 175: 661-666. doi: 10.1164/rccm.200611-1717OC
4. Camargo CA Jr, Boulet LP, Sutherland ER, Busse WW, Yancey SW, Emmett AH, Ortega HG, Ferro TJ. Body mass index and response to asthma therapy: Fluticasone propionate/salmeterol versus montelukast. J Asthma. 2010; 47: 76-82.
5. Saint-Pierre P, Bourdin A, Chanez P, Daures JP, Godard P. Are overweight asthmatics more difficult to control? Allergy. 2006;61:79-84. doi:10.1111/j.1398-9995.2005.00953.x
6. Sutherland TJT, Cowan JO, Young S, Goulding A, Grant AM, Williamson A, Brassett K, Herbison GP, Taylor DR. The association between obesity and asthma interactions between systemic and airway Inflammation. All AJRCCM. 2008; 178 (5).
7. Bousquet J, Chanez P, Lacoste JY, Barnéon G, Ghavanian N, Enander I, Venge P, Ahlstedt S, Simony-Lafontaine J, Godard P. Eosinophilic inflammation in asthma. N Engl J Med. 1990; 323: 1033-1039. doi: 10.1056/NEJM199010113231505
8. Fahy JV, Kim KW, Liu J, Boushey HA. Prominent neutrophilic inflammation in sputum from subjects with asthma exacerbation. J Allergy Clin Immunol. 1995; 95: 843-52.
9. Turner MO, Hussack P, Sears MR, Dolovich J, Hargreave FE. Exacerbations of asthma without sputum eosinophilia. Thorax. 1995; 50: 1057-1061.
10. Douwes J, Gibson P, Pekkanen J, Pearce N. Non-eosinophilic asthma: importance and possible mechanisms. Thorax. 2002; 57: 643-648.
11. Kay AB, Phipps S, Robinson DS. The role for eosinophils in airway remodeling in asthma. Tends Immunol. 2004; 25: 477-482. doi: 10.1016/j.it.2004.07.006
12. Reuter S, Heinz A, Sieren M, Wiewrodt R, Gelfand EW, Stassen M, Buhl R, Taube C. Mast cell – derived tumor necrosis factor is essential for allergic airway disease. Eur Respir J. 2008; 31: 773-782. doi: 10.1183/09031936.00058907
13. Douwes J, Gibson P, Pekkanen J, Pearce N. Non-eosinophilic asthma: importance and possible mechanisms. Thorax. 2002; 57: 643-648.
14. Leckie MJ, Brinke A, Khan J, Diamant Z, O'Connor BJ, Walls CM, Mathur AK, Cowley HC, Chung KF, Djukanovic R, Hansel TT, Holgate ST, Sterk PJ, Barnes PJ. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000; 356: 2144-2148.
15. Bryan SA, O’Connor B.J, Matti S, Leckie MJ, Kanabar V, Khan J, Warrington SJ, Renzetti L, Rames A, Bock JA, Boyce MJ, Hansel TT, Holgate ST, Barneset PJ. Effects of recombinant human interleukin-12 on eosinophils, airway hyper-responsiveness, and the late asthmatic response. Lancet. 2000; 356: 2149-2153.
16. Kips JC, O’Connor BJ, Langley SJ, Woodcock A, Kerstjens HA, Postma DS, Danzig M, Cuss F, Pauwels RA. Effect of SCH55700, a humanised anti-human interleukin-5 antibody, in severe persistent asthma: a pilot study. Am J Respir Crit Care Med. 2003; 167: 1655-1659. doi:10.1164/rccm.200206-525OC
17. Wilson RH, Whitehead GS, Nakano H, Free ME, Kolls JK, Cook DN. Allergic sensitization through the airway primed Th17- dependent neutrophilia and airway hyperresponsiveness. Am J Respir Cm Crit Care. 2009; 180: 720-730.
18. Stern JS, Hirsch J, Blair SN, Foreyt JP, Frank A, Kumanyika SK, Madans JH, Marlatt GA, St Jeor ST, Stunkard AJ. Weighing the options: criteria for evaluating weight-management programs. The Committee to Develop Criteria for Evaluating the Outcomes of Approaches to Prevent and Treat Obesity. Obes Res. 1995; 3 (6): 591-604.
19. Rio-Navarro В, Cisneros-Rivero M, Berber-Eslava A, Espínola-Reyna G, Sienra-Monge J. Exercise induced bronchospasm in asthmatic and non-asthmatic obese children. Allergol Immunopathol (Madr). 2000; 28 (1): 5-11.
20. Shore SA. Obesity and asthma: location, location, location. Eur Respir J. 2013; 41 (2): 253-254. doi: 10.1183/09031936.00128812
21. [Avdeev SN, Anaev EKh, Chuchalin AG. Use of a method of the induced sputum for assessment of intensity of an inflammation of respiratory tracts. Pul'monologiya. 1998;2:81-85. (In Russ.)]
22. Kips JC, Fahy JV, Hargreave FE. Methods for sputum induction and analysis of induced sputum: a method for assessing airway inflammation in asthma. Eur Respir J. 2008; 11: 9-12.
23. Simpson JL, Scott R, Boyle MJ, Gibson PG. Inflammatory subtypes in asthma: assessment and identification using induced sputum. Respirology. 2006; 11:54-61.
24. [Nenasheva N. M. The current understanding of the phenotypes of bronchial asthma. Pharmateca. 2013; 4: 257. (In Russ.)]
25. Newton R, Leigh R, Glembycz M. Pharmacological strategies for improving the efficacy and therapeutic ratio of glucocorticoids in inflammatory lung disease. Prarmacology and Therapeutics. 2010;125:286-327.
26. [Trofimov V, Mironova Zh. Therapeutically refractory asthma. Vrach. 2012;3: 2-4. (In Russ.)]
27. [Fedoseev GB, Trofimov VI, Rogacheva NN, Razumovskaya TS. Role of neutrophils and bacterial infection of a respiratory tract at patients with bronchial asthma and chronic obstructive pulmonary disease. Russ allergolog J. 2011; 2: 34-43. (In Russ.)]
28. Cox G. Glucocorticoid treatment inhibits apoptosis in human neutrophils. Separation of survival and activation outcomes. J Immunol. 1995; 154: 4719-4725.
29. Shin B, Kwon HS, Park SY, Kim TB, Moon HB, Cho YS. The transition of sputum inflammatory cell profiles is variable in stable asthma patients. Asia Pac Allergy. 2017; 7 (1): 19-28. doi: 10.5415/apallergy.2017.7.1.19
30. Cowan DC, Cowan JO, Palmay R, Williamson A, Taylor DR. Effects of steroid therapy on inflammatory cell subtypes in asthma. Thorax. 2010; 65: 384-390.
1 ФГБОУ ВО ГБОУ ВПО «Красноярский государственный медицинский университет им. профессора В.Ф. Войно-Ясенецкого» Минздрава РФ, Красноярск, Россия;
2 Красноярское ГБУЗ «Красноярская краевая больница», Красноярск, Россия
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I.А. SOLOVEVA 1,2, E.A. SOBKO 1,2, I.V. DEMKO 1,2, A.Yu. KRAPOSHINA 1, M.M. LOKTIONOVA 1, N.V. GORDEEVA 1,2
1 Krasnoyarsk state medical university named after prof. V.F. Voino-Yasenetsky, Krasnoyarsk, Russia;
2 Regional Clinical Hospital, Krasnoyarsk, Russia