Бронхиальная астма: федеральные клинические рекомендации по диагностике и лечению

Бронхиальная астма (БА) является гетерогенным заболеванием, при котором требуется выделение различных фенотипов и персонифицированный подход к терапии. При этом несмотря на широкий выбор терапевтических возможностей, у многих пациентов с БА не удается достичь контроля над заболеванием.

Методы. Целевой аудиторией данных клинических рекомендаций являются врачи общей практики, терапевты, педиатры, аллергологи-иммунологи, пульмонологи и врачи функциональной диагностики. Каждый тезис-рекомендация по проведению диагностических и лечебных мероприятий оценивается по шкалам уровней достоверности доказательств от 1 до 5 и шкале оценки уровней убедительности рекомендаций по категориям А, В, С. Клинические рекомендации содержат также комментарии и разъяснения к указанным тезисам-рекомендациям, алгоритмы по диагностике и лечению БА, справочные материалы.

Заключение. По данным представленных клинических рекомендаций освещаются современные сведения об этиологии и патогенезе, классификации, клинических проявлениях, диагностике, лечении и профилактике БА. Клинические рекомендации одобрены Научно-практическим Советом Министерства здравоохранения Российской Федерации (2021). 

1. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention. Updated 2018. Available at: https://ginasthma.org/wp-content/uploads/2018/04/wms-GINA-2018-report-V1.3-002.pdf

2. Chuchalin A.G., Khaltaev N., Аntonov N.S. Chronic respiratory diseases and risk factors in 12 regions of the Russian Federation. Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9 (1): 963–974. DOI: 10.2147/COPD.S67283.

3. Российское респираторное общество. Национальная программа «Бронхиальная астма у детей. Стратегия лечения и профилактика». 4-е изд. М.: 2012.

4. Centers for Disease Control and Prevention. Most recent asthma data. Available at: http://www.cdc.gov/asthma/most_recent_data.htm

5. Krahn M.D., Berka C., Langlois P., Detsky A.S. Direct and indirect costs of asthma in Canada, 1990. CMAJ. 1996; 154 (6): 821–831.

6. Weber E.J., Silverman R.A., Callaham M.L. et al. A prospective multicenter study factors associated with hospital admission among adults with acute asthma. Am. J. Med. 2002; 113 (5): 371–378. DOI: 10.1016/s0002-9343(02)01242-1.

7. Braman S.S., Kaermmerhen J.T. Intensive care of status asthmaticus: A 10-year experience. JAMA. 1990; 264 (3): 366–368. DOI: 10.1001/jama.1990.03450030090038.

8. Salmeron S., Liard R., Elkharrat D. et al. Asthma severity adequacy of management in accident and emergency departments in France: a prospective study. Lancet. 2001; 358 (9282): 629–635. DOI: 10.1016/s0140-6736(01)05779-8.

9. Krishnan V., Diette G.B., Rand C.S. et al. Mortality in patients hospitalized for asthma exacerbations in the United States. Am. J. Respir. Crit. Care Med. 2006; 174 (6): 633–638. DOI: 10.1164/rccm.200601-007OC.

10. Ненашева Н.М. Клинические фенотипы атопической бронхиальной астмы: диагностика и лечение. Saarbrucken: Palmarium Academic Publishing; 2012.

11. Moore W.C., Meyers D.A., Wenzel S.E. et al. Identification of asthma phenotypes using cluster analysis in the severe asthma research program. Am. J. Respir. Crit. Care Med. 2010; 181 (4): 315–323. DOI: 10.1164/rccm.200906-0896OC.

12. Pearce N., Pekkanen J., Beasley R. How much asthma is really attributable to atopy? Thorax. 1999; 54 (3): 268–272. DOI: 10.1136/thx.54.3.268.

13. Mellis C. Respiratory noises: how useful are they clinically? Pediatr. Clin. North Am. 2009; 56 (1): 1–17. DOI: 10.1016/j.pcl.2008.10.003.

14. Cano Garcinuno A., Mora Gandarillas I., SLAM Study Group. Early patterns of wheezing in asthmatic and nonasthmatic children. Eur. Respir. J. 2013; 42 (4): 1020–1028. DOI: 10.1183/09031936.00148712.

15. Just J., Saint-Pierre P., Gouvis-Echraghi R. et al. Wheeze phenotypes in young children have different courses during the preschool period. Ann. Allergy Asthma Immunol. 2013; 111 (4): 256–261. DOI: 10.1016/j.anai.2013.07.002.

16. O’Byrne P.M., Reddel H.K., Eriksson G. et al. Measuring asthma control: a comparison of three classification systems. Eur. Respir. J. 2010; 36 (2): 269–276. DOI: 10.1183/09031936.00124009.

17. Thomas M., Kay S., Pike J. et al. The Asthma Control Test (ACT) as a predictor of GINA guideline-defined asthma control: analysis of a multinational cross-sectional survey. Prim. Care Respir. J. 2009; 18 (1): 41–49. DOI: 10.4104/pcrj.2009.00010.

18. Juniper E.F., Svensson K., Mörk A.C., Ståhl E. Measurement properties and interpretation of three shortened versions of the asthma control questionnaire. Respir. Med. 2005; 99 (5): 553–558. DOI: 10.1016/j.rmed.2004.10.008.

19. Kerkhof M., Tran T.N., van den Berge M. et al. Association between blood eosinophil count and risk of readmission for patients with asthma: Historical cohort study. PLoS One. 2018; 13 (7): e0201143. DOI: 10.1371/journal.pone.0201143.

20. Price D.B., Rigazio A., Campbell J.D. et al. Blood eosinophil count and prospective annual asthma disease burden: a UK cohort study. Lancet Respir. Med. 2015; 3 (11): 849–858. DOI: 10.1016/S2213-2600(15)00367-7.

21. Albers F.C., Licskai C., Chanez P. et al. Baseline blood eosinophil count as a predictor of treatment response to the licensed dose of mepolizumab in severe eosinophilic asthma. Respir. Med. 2019; 159: 105806. DOI: 10.1016/j.rmed.2019.105806.

22. Bush A. Management of asthma in children. Minerva Pediatr. 2018; 70 (5): 444–457. DOI: 10.23736/S0026-4946.18.05351-3.

23. Rath N., Raje N., Rosenwasser L. Immunoglobulin E as a biomarker in asthma. Immunol. Allergy Clin. North Am. 2018; 38 (4): 587–597. DOI: 10.1016/j.iac.2018.06.007.

24. Ahlstedt S., Murray C.S. In vitro diagnosis of allergy: how to interpret IgE antibody results in clinical practice. Prim. Care Respir. J. 2006; 15 (4): 228–236. DOI: 10.1016/j.pcrj.2006.05.004.

25. Miller M.R., Hankinson J., Brusasco V. et al. Standardisation of spirometry. Eur. Respir. J. 2005; 26 (2): 319–338. DOI: 10.1183/09031936.05.00034805.

26. Levy M.L., Quanjer P.H., Booker R. et al. Diagnostic spirometry in primary care: Proposed standards for general practice compliant with American Thoracic Society and European Respiratory Society recommendations. Prim. Care Respir. J. 2009; 18 (3): 130–147. DOI: 10.4104/pcrj.2009.00054.

27. Российское респираторное общество. Методические рекомендации по использованию метода спирометрии. М.; 2016. Доступно на: http://www.spulmo.ru

28. Pellegrino R., Viegi G., Brusasco V. et al. Interpretative strategies for lung function tests. Eur. Respir. J. 2005; 26 (5): 948–968. DOI: 10.1183/09031936.05.00035205.

29. Tan W.C., Vollmer W.M., Lamprecht B. et al. Worldwide patterns of bronchodilator responsiveness: results from the Burden of Obstructive Lung Disease study. Thorax. 2012; 67 (8): 718–726. DOI: 10.1136/thoraxjnl-2011-201445.

30. Crapo R.O., Casaburi R., Coates A.L. et al. Guidelines for methacholine and exercise challenge testing-1999. Am. J. Respir. Crit. Care Med. 2000; 161 (1): 309–329. DOI: 10.1164/ajrccm.161.1.ats11-99.

31. Swartz E., Lang D. When should a methacholine challenge be ordered for a patient with suspected asthma? Cleve Clin. J. Med. 2008; 75 (1): 37–40. DOI: 10.3949/ccjm.75.1.37.

32. Parsons J.P., Hallstrand T.S., Mastronarde J.G. et al. An official American Thoracic Society clinical practice guideline: exerciseinduced bronchoconstriction. Am. J. Respir. Crit. Care Med. 2013; 187 (9): 1016–1027. DOI: 10.1164/rccm.201303-0437ST.

33. Reddel H.K., Taylor D.R., Bateman E.D. et al. An official American Thoracic Society/European Respiratory Society statement: Asthma control and exacerbations: standardizing endpoints for clinical asthma trials and clinical practice. Am. J. Respir. Crit. Care Med. 2009; 180 (1): 59–99. DOI: 10.1164/rccm.200801-060ST.

34. Brouwer A.F., Brand P.L. Asthma education and monitoring: what has been shown to work. Paediatr. Respir. Rev. 2008; 9 (3): 193–199. DOI: 10.1016/j.prrv.2008.03.001.

35. Beydon N., Davis S.D., Lombardi E. et al. An official American Thoracic Society/European Respiratory Society statement: pulmonary function testing in preschool children. Am. J. Respir. Crit. Care Med. 2007; 175 (12): 1304–1345. DOI: 10.1164/rccm.200605-642ST.

36. Graham B.L., Steenbruggen I., Miller M.R. et al. Standardization of spirometry 2019 update: An official American Thoracic Society and European Respiratory Society technical statement. Am. J. Respir. Crit. Care Med. 2019; 200 (8): e70–88. DOI: 10.1164/rccm.201908-1590ST.

37. American Thoracic Society, European Respiratory Society. ATS/ ERS Recommendations for standardized procedures for the online and offline measurement of exhaled lower respiratory nitric oxide and nasal nitric oxide, 2005. Am. J. Respir. Crit. Care Med. 2005; 171 (8): 912–930. DOI: 10.1164/rccm.200406-710ST.

38. Schleich F.N., Manise M., Sele J. et al. Distribution of sputum cellular phenotype in a large asthma cohort: predicting factors for eosinophilic vs neutrophilic inflammation. BMC Pulm. Med. 2013; 13: 11. DOI: 10.1186/1471-2466-13-11.

39. Dweik R.A., Boggs P.B., Erzurum S.C. et al. An official ATS clinical practice guideline: interpretation of exhaled nitric oxide levels (FENO) for clinical applications. Am. J. Respir. Crit. Care Med. 2011; 184 (5): 602–615. DOI: 10.1164/rccm.9120-11ST.

40. Malo J.L., Côte J., Cartier A. et al. How many times per day should peak expiratory flow rates be assessed when investigating occupational asthma? Thorax. 1993; 48 (12): 1211–1217. DOI: 10.1136/thx.48.12.1211.

41. Baur X., Huber H., Degens P.O. et al. Relation between occupational asthma case history, bronchial methacholine challenge, and specific challenge test in patients with suspected occupational asthma. Am. J. Ind. Med. 1998; 33 (2): 114–122. DOI: : https://doi.org/10.1002/(sici)1097-0274(199802)33:2<114::aid-ajim3>3.0.co;2-y

42. Fishwick D., Barber C.M., Bradshaw L.M. et al. Standards of care for occupational asthma. Thorax. 2008; 63 (3): 240–250. DOI: 10.1136/thx.2007.083444.

43. Mapp C.E., Saetta M., Maestrelli P., Fabbri L. Occupational asthma. In: Mapp C.E., ed. Occupational Lung Disorders. European Respiratory Monograph. Sheffield: ERS; 1999; 4 (Monogr. 11): 255–285.

44. Bousquet J., Heinzerling L., Bachert C. et al. Practical guide to skin prick tests in allergy to aeroallergens. Allergy. 2012; 67 (1): 18–24. DOI: 10.1111/j.1398-9995.2011.02728.x.

45. Ait-Khaled N., Enarson D.A., Chiang C.Y. et al. Management of asthma: a guide to the essentials of good clinical practice. Paris: International Union Against Tuberculosis and Lung Disease; 2008.

46. Papadopoulos N.G., Arakawa H., Carlsen K.H. et al. International consensus on (ICON) pediatric asthma. Allergy. 2012; 67 (8): 976– 977. DOI: 10.1111/j.1398-9995.2012.02865.x.

47. Намазова-Баранова Л.С., Баранов А.А., Хаитов Р.М., ред. Аллергология и иммунология. М.: Педиатръ; 2020.

48. Doherty G., Bush A. Diagnosing respiratory problems in young children. Practitioner. 2007; 251 (1697): 20, 22–25.

49. Gibson P.G., Powell H., Coughlan J. et al. Self-management education and regular practitioner review for adults with asthma. Cochrane Database Syst. Rev. 2003: (1): CD001117. DOI: 10.1002/14651858.CD001117.

50. Fishwick D., D’Souza W., Beasley R. The asthma self-management plan system of care: What does it mean, how is it done, does it work, what models are available, what do patients want and who needs it? Patient Educ. Couns. 1997; 32 (Suppl. 1): S21–33. DOI: 10.1016/s0738-3991(97)00093-1.

51. Ramnath V.R., Clark S., Camargo C.A. Jr. Multicenter study of clinical features of sudden-onset versus slower-onset asthma exacerbations requiring hospitalization. Respir. Care. 2007; 52 (8): 1013–1020. Available at: http://rc.rcjournal.com/content/52/8/1013

52. Geelhoed G.C., Landau L.I., Le Souef P.N. Evaluation of SaO2 as a predictor of outcome in 280 children presenting with acute asthma. Ann. Emerg. Med. 1994; 23 (6): 1236–1241. DOI: 10.1016/s0196-0644(94)70347-7.

53. Atta J.A., Nunes M.P.T., Fonseca-Guedes C.H.F. et al. Patient and physician evaluation of the severity of acute asthma exacerbations. Braz. J. Med. Biol. Res. 2004; 37 (9): 1321–1330. DOI: 10.1590/s0100-879x2004000900006.

54. Nowak R.M., Tomlanovich M.C., Sarkar D.D. et al. Arterial blood gases and pulmonary function testing in acute bronchial asthma. Predicting patient outcomes. JAMA. 1983; 249 (15): 2043–2046. DOI: 10.1001/jama.1983.03330390047030.

55. White C.S., Cole R.P., Lubetsky H.W., Austin J.H. Acute asthma: Admission chest radiography in hospitalized adult patients. Chest. 1991; 100 (1): 14–16. DOI: 10.1378/chest.100.1.14.

56. Taylor D.R., Bateman E.D., Boulet L.P. et al. A new perspective on concepts of asthma severity and control. Eur. Respir. J. 2008; 32 (3): 545–554. DOI: 10.1183/09031936.00155307.

57. O’Byrne P.M., FitzGerald M., Bateman E.D. et al. Inhaled combined budesonide-formoterol as needed in mild asthma. N. Engl. J. Med. 2018; 378 (20): 1865–1876. DOI: 10.1056/NEJMoa1715274.

58. Bateman E.D., Reddel H.K., O’Byrne P.M. et al. As-needed budesonide-formoterol versus maintenance budesonide in mild asthma. N. Engl. J. Med. 2018; 378 (20): 1877–1887. DOI: 10.1056/NEJMoa1715275.

59. Papi A., Canonica G.W., Maestrelli P. et al. Rescue use of beclomethasone and albuterol in a single inhaler for mild asthma. N. Engl. J. Med. 2007; 356 (20): 2040–2052. DOI: 10.1056/NEJMoa063861.

60. Авдеев С.Н., Айсанов З.Р., Архипов В.В. и др. Принципы выбора терапии для больных легкой бронхиальной астмой: Согласованные рекомендации РААКИ и РРО. Практическая пульмонология. 2017; (1): 82–92. Доступно на: https://atmosphere-ph.ru/modules/Magazines/articles/pulmo/pp_1_2017_82.pdf.

61. Pauwels R.A., Pedersen S., Busse W.W. et al. Early intervention with budesonide in mild persistent asthma: a randomised, double-blind trial. Lancet. 2003; 361 (9363): 1071–1076. DOI: 10.1016/S0140-6736(03)12891-7.

62. O’Byrne P.M., Barnes P.J., Rodriguez-Roisin R. et al. Low dose inhaled budesonide and formoterol in mild persistent asthma: the OPTIMA randomized trial. Am. J. Respir. Crit. Care Med. 2001; 164 (8, Pt 1): 1392–1397. DOI: 10.1164/ajrccm.164.8.2104102.

63. Adams N.P., Bestall J.B., Malouf R. et al. Inhaled beclomethasone versus placebo for chronic asthma. Cochrane Database Syst. Rev. 2005 (1): CD002738. DOI: 10.1002/14651858.CD002738.pub2.

64. Wilson A.M., Dempsey O.J., Sims E.J., Lipworth B.J. A comparison of topical budesonide and oral montelukast in seasonal allergic rhinitis and asthma. Clin. Exp. Allergy. 2001; 31 (4): 616–624. DOI: 10.1046/j.1365-2222.2001.01088.x.

65. Philip G., Nayak A.S., Berger W.E. et al. The effect of montelukast on rhinitis symptoms in patients with asthma and seasonal allergic rhinitis. Curr. Med. Res. Opin. 2004; 20 (10): 1549–1558. DOI: 10.1185/030079904x3348.

66. Guevara J.P., Ducharme F.M., Keren R. et al. Inhaled corticosteroids versus sodium cromoglycate in children and adults with asthma. Cochrane Database Syst. Rev. 2006; 2006 (2): CD003558. DOI: 10.1002/14651858.CD003558.pub2.

67. Bisgaard H., Zielen S., Garcia-Garcia M.L. et al. Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma. Am. J. Respir. Crit. Care Med. 2005; 171 (4): 315–322. DOI: 10.1164/rccm.200407-894OC.

68. Matsuse H., Tsuchida T., Fukahori S. et al. Retrospective cohort study of leukotriene receptor antagonist therapy for preventing upper respiratory infection-induced acute asthma exacerbations. Allergy Rhinol. (Providence). 2013; 4 (3): e127–131. DOI: 10.2500/ar.2013.4.0062.

69. Ducharme F.M., Ni Chroinin M., Greenstone I., Lasserson T.J. Addition of long-acting beta2-agonists to inhaled corticosteroids versus same dose inhaled corticosteroids for chronic asthma in adults and children. Cochrane Database Syst. Rev. 2010; (5): CD005535. DOI: 10.1002/14651858.CD005535.pub2.

70. Woodcock A., Vestbo J., Bakerly N.D.et al. Effectiveness of fluticasone furoate plus vilanterol on asthma control in clinical practice: an open-label, parallel group, randomised controlled trial. Lancet. 2017; 390 (10109): 2247–2255. DOI: 10.1016/S0140-6736(17)32397-8.

71. Cates C.J., Karner C. Combination formoterol and budesonide as maintenance and reliever therapy versus current best practice (including inhaled steroid maintenance), for chronic asthma in adults and children. Cochrane Database Syst. Rev. 2013; (4): CD007313 DOI: 10.1002/14651858.CD007313.pub3.

72. Papi A., Corradi M., Pigeon-Francisco C. et al. Beclometasone– formoterol as maintenance and reliever treatment in patients with asthma: a double-blind, randomised controlled trial. Lancet Respir. Med. 2013; 1 (1): 23–31. DOI: 10.1016/S2213-2600(13)70012-2.

73. Patel M., Pilcher J., Pritchard A. et al. Efficacy and safety of maintenance and reliever combination budesonide/formoterol inhaler in patients with asthma at risk of severe exacerbations: a randomised controlled trial. Lancet Respir. Med. 2013; 1 (1): 32–42. DOI: 10.1016/S2213-2600(13)70007-9.

74. Bateman E.D., Harrison T.W., Quirce S. et al. Overall asthma control achieved with budesonide/formoterol maintenance and reliever therapy for patients on different treatment steps. Respir. Res. 2011; 12 (1): 38. DOI: 10.1186/1465-9921-12-38.

75. Ni Chroinin M., Lasserson T.J., Greenstone I., Ducharme F.M. Addition of long-acting beta-agonists to inhaled corticosteroids for chronic asthma in children. Cochrane Database Syst. Rev. 2009; 8 (3): CD007949. DOI: 10.1002/14651858.CD007949.

76. Vaessen-Verberne A.A., van den Berg N.J., van Nierop J.C. et al. Combination therapy salmeterol/fluticasone versus doubling dose of fluticasone in children with asthma. Am. J. Respir. Crit. Care Med. 2010; 182 (10): 1221–1227. DOI: 10.1164/rccm.201002-0193OC.

77. Peters S.P., Kunselman S.J., Icitovic N. et al. Tiotropium bromide step-up therapy for adults with uncontrolled asthma. N. Engl. J. Med. 2010; 363 (18): 1715–1726. DOI: 10.1056/NEJMoa1008770.

78. Bateman E.D., Kornmann O., Schmidt P. et al. Tiotropium is noninferior to salmeterol in maintaining improved lung function in B16- Arg/Arg patients with asthma. J. Allergy Clin. Immunol. 2011; 128 (2): 315–322. DOI: 10.1016/j.jaci.2011.06.004.

79. Kerstjens H.A., Casale T.B., Bleeker E.R. et al. Tiotropium or salmeterol as add-on therapy to inhaled corticosteroids for patients with moderate symptomatic asthma: two replicate, double-blind, placebo-controlled, parallel-group, active-comparator, randomised trials. Lancet Respir. Med. 2015; 3 (5): 367–376. DOI: 10.1016/S2213-2600(15)00031-4.

80. Kew K.M., Dahri K. Long-acting muscarinic antagonists (LAMA) added to combination long-acting beta2-agonists and inhaled corticosteroids (LABA/ICS) versus LABA/ICS for adults with asthma. Cochrane Database Syst. Rev. 2016; (1): CD011721. DOI: 10.1002/14651858.CD011721.pub2.

81. Rodrigo G.J., Neffen H. Efficacy and safety of tiotropium in schoolage children with moderate-to-severe symptomatic asthma: a systematic review. Pediatr. Allergy Immunol. 2017; 28 (6): 573–578. DOI: 10.1111/pai.12759.

82. Rodrigo G.J., Castro-Rodriguez J.A. What is the role of tiotropium in asthma? A systematic review with meta-analysis. Chest. 2015; 147 (2): 388–396. DOI: 10.1378/chest.14-1698.

83. Kerstjens H.A., Disse B., Schröder-Babo W. et al. Tiotropium improves lung function in patients with severe uncontrolled asthma: a randomized controlled trial. J. Allergy Clin. Immunol. 2011; 128 (2): 308–314. DOI: 10.1016/j.jaci.2011.04.039.

84. Kerstjens H.A., Engel M., Dahl R. et al. Tiotropium in asthma poorly controlled with standard combination therapy. N. Engl. J. Med. 2012; 367 (13): 1198–1207. DOI: 10.1056/NEJMoa1208606.

85. FitzGerald M., Moroni-Zentgraf P., Engel M. et al. Once-daily tiotropium Respimat® add-on therapy improves symptom control across severtiies of symptomatic asthma, independent of allergic status. Poster 64426 presented at the American Thoracic Society 2015 International Conference. Denver, USA; 2015.

86. Lee L.A., Bailes Z., Barnes N. et al. Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial. Lancet Respir. Med. 2021; 9 (1): 69–84. DOI: 10.1016/S2213-2600(20)30389-1.

87. O’Byrne P.M., Naya I.P., Kallen A. et al. Increasing doses of inhaled corticosteroids compared to adding long-acting inhaled beta2-agonists in achieving asthma control. Chest. 2008; 134 (6): 1192–1199. DOI: 10.1378/chest.08-1018.

88. Lee L.A., Bailes Z., Barnes N. et al. Efficacy and safety of once-daily single-inhaler triple therapy (FF/UMEC/VI) versus FF/VI in patients with inadequately controlled asthma (CAPTAIN): a double-blind, randomised, phase 3A trial. Lancet Respir. Med. 2021; 9 (1): 69–84. DOI: 10.1016/S2213-2600(20)30389-1.

89. Price D.B., Hernandez D., Magyar P. et al. Randomised controlled trial of montelukast plus inhaled budesonide versus double dose inhaled budesonide in adult patients with asthma. Thorax. 2003; 58 (3): 211–216. DOI: 10.1136/thorax.58.3.211.

90. Vaquerizo M.J., Casan P., Castillo J. et al. Effect of montelukast added to inhaled budesonide on control of mild to moderate asthma. Thorax. 2003; 58 (3): 204–210. DOI: 10.1136/thorax.58.3.204.

91. Tamaoki J., Kondo M., Sakai N. et al. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group. Am. J. Respir. Crit. Care Med. 1997; 155 (4): 1235–1240. DOI: 10.1164/ajrccm.155.4.9105060.

92. Rodrigo G.J., Neffen H., Castro-Rodriguez J.A. Efficacy and safety of subcutaneous omalizumab vs placebo as addon therapy to corticosteroids for children and adults with asthma: a systematic review. Chest. 2011; 139 (1): 28–35. DOI: 10.1378/chest.10-1194.

93. Normansell R., Walker S., Milan S.J. et al. Omalizumab for asthma in adults and children. Cochrane Database Syst. Rev. 2014; (1): CD003559. DOI: 10.1002/14651858.CD003559.pub4.

94. Castro M., Zangrilli J., Wechsler M.E. et al. Reslizumab for inadequately controlled asthma with elevated blood eosinophil counts: results from multicenter, parallel, double-blind, randomized, placebo-controlled, phase 3 trials. Lancet Respir. Med. 2015; 3 (5): 355–366. DOI: 10.1016/S2213-2600(15)00042-9.

95. Pavord I.D., Korn S., Howarth P. et al. Mepolizumab for severe eosinophilic asthma (DREAM): a multicentre, double-blind, placebo-controlled trial. Lancet. 2012; 380 (9842): 651–659. DOI: 10.1016/S0140-6736(12)60988-X.

96. Ortega H.G., Liu M.C., Pavord I.D. et al. Mepolizumab treatment in patients with severe eosinophilic asthma. N. Engl. J. Med. 2014; 371 (13): 1198–1207. DOI: 10.1056/NEJMoa1403290.

97. Bel E.H., Wenzel S.E., Thompson P.J. et al. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N. Engl. J. Med. 2014; 371 (13): 1189–1197. DOI: 10.1056/NEJMoa1403291.

98. FitzGerald J.M., Bleecker E.R., Nair P. et al. Benralizumab, an anti-interleukin-5 receptor α monoclonal antibody, as add-on treatment for patients with severe, uncontrolled, eosinophilic asthma (CALIMA): a randomized, double-blind, placebo-controlled phase 3 trial. Lancet. 2016; 388 (10056): 2128–2141. DOI: 10.1016/S0140-6736(16)31322-8.

99. Bleecker E.R, FitzGerald J.M., Chanez P. et al. Efficacy and safety of benralizumab for patients with severe asthma uncontrolled with high-dosage inhaled corticosteroids and long-acting β2 -agonists (SIROCCO): a randomized, multicentre, placebo-controlled phase 3 trial. Lancet. 2016; 388 (10056): 2115–2127. DOI: 10.1016/S0140-6736(16)31324-1.

100. Castro M., Corren J., Pavord I.D. et al. Dupilumab efficacy and safety in moderate-to-severe uncontrolled asthma. N. Engl. J. Med. 2018; 378 (26): 2486–2496. DOI: 10.1056/NEJMoa1804092.

101. Rabe K.F., Nair P., Brusselle G. et al. Efficacy and safety of dupilumab in glucocorticoid-dependent severe asthma. N. Engl. J. Med. 2018; 378 (26): 2475–2485. DOI: 10.1056/NEJMoa1804093.

102. Zayed Y., Kheiri B., Banifadel M. et al. Dupilumab safety and efficacy in uncontrolled asthma: a systematic review and meta-analysis of randomized clinical trials. J. Asthma. 2018; 56 (10): 1110–1119. DOI: 10.1080/02770903.2018.1520865.

103. Global Initiative for Asthma. Difficult-to-treat and severe asthma in adolescent and adult patients: diagnosis and management. A GINA Pocket Guide for Health Professionals. 2019. Available at: www.ginasthma.org

104. Chung K.F., Wenzel S.E., Brozek J.L. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur. Respir. J. 2014; 43 (2): 343–373. DOI: 10.1183/09031936.00202013.

105. Rivington R.N., Boulet L.P., Côté J. et al. Efficacy of Uniphyl, salbutamol, and their combination in asthmatic patients on highdose inhaled steroids. Am. J. Respir. Crit. Care Med. 1995; 151 (2, Pt 1): 325–332. DOI: 10.1164/ajrccm.151.2.7842186.

106. Vogelberg C., Moroni-Zentgraf P., Lronaviciute-Klimantaviciene M. et al. A randomized dose-ranging study of tiotropium Respimat in children with symptomatic asthma despite inhaled corticosteroids. Repir. Res. 2015; 16 (1): 20. DOI: 10.1186/s12931-015-0175-9.

107. Guo J.J., Tsai K., Kelton C.M.L. et al. Risk of serious asthma exacerbations associated with long-acting beta agonists among patients with asthma: a retrospective cohort study. Ann. Allergy Asthma Immunol. 2011; 106 (3): 214–222. DOI: 10.1016/j.anai.2010.12.008.

108. Melani A.S., Bonavia M., Cilenti V. et al. Inhaler mishandling remains common in real life and is associated with reduced disease control. Respir. Med. 2011; 105 (6): 930–938. DOI: 10.1016/j.rmed.2011.01.005.

109. Fink J.B., Rubin B.K. Problems with inhaler use: a call for improved clinician and patient education. Respir. Care. 2005; 50 (10): 1360–1375. Available at: http://rc.rcjournal.com/content/50/10/1360

110. Basheti I.A., Reddel H.K., Armour C.L., Bosnic-Anticevich S.Z. Improved asthma outcomes with a simple inhaler technique intervention by community pharmacists. J. Allergy Clin. Immunol. 2007; 119 (6): 1537–1538. DOI: 10.1016/j.jaci.2007.02.037.

111. Honkoop P.J., Loymans R.J.B., Termeer E.H. et al. Asthma control cost-utility randomized trial evaluation (ACCURATE): the goals of asthma treatment. BMC Pulm. Med. 2011; 11: 53. DOI: 10.1186/1471-2466-11-53.

112. Eber E., Midulla F., eds. Paediatric Respiratory Medicine. ERS Handbook. 1st edn. Charlesworth Press; 2013. Available at: https://dl.uswr.ac.ir/bitstream/Hannan/140448/1/9781849840385.pdf

113. Abramson M.J., Puy R.M., Weiner J.M. Injection allergen immunotherapy for asthma. Cochrane Database Syst. Rev. 2010; (8): CD001186. DOI: 10.1002/14651858.CD001186.pub2.

114. Tao L., Shi B., Shi G., Wan H. Efficacy of sublingual immunotherapy for allergic asthma: retrospective meta-analysis of randomized, double-blind and placebo-controlled trials. Clin. Respir. J. 2014; 8 (2): 192–205. DOI: 10.1111/crj.12058.

115. Virchow J.C., Backer V., Kuna P. et al. Efficacy of a house dust mite sublingual allergen immunotherapy tablet in adults with allergic asthma: a randomized clinical trial. JAMA. 2016; 315 (16): 1715–1725. DOI: 10.1001/jama.2016.3964.

116. Mosbech H., Deckelmann R., de Blay F. et al. Standardized quality (SQ) house dust mite sublingual immunotherapy tablet (ALK) reduces inhaled corticosteroid use while maintaining asthma control: a randomized, double-blind, placebo-controlled trial. J. Allergy Clin. Immunol. 2014; 134 (3): 568–575.e7. DOI: 10.1016/j.jaci.2014.03.019.

117. Hondras M.A., Linde K., Jones A.P. Manual therapy for asthma. Cochrane Database Syst. Rev. 2005; (2): CD001002. DOI: 10.1002/14651858.CD001002.pub2.

118. Cooper S., Oborne J., Newton S. et al. Effect of two breathing exercises (Buteyko and pranayama) in asthma: a randomized controlled trial. Thorax. 2003; 58 (8): 674–679. DOI: 10.1136/thorax.58.8.674.

119. Авдеев С.Н., Айсанов З.Р., Белевский А.С. и др. Пути улучшения диагностики и лечения больных бронхиальной астмой врачами первичного звена. Пульмонология. 2019; 29 (4): 457– 467. DOI: 10.18093/0869-0189-2019-29-4-457-467.

120. Perrin K., Wijesinghe M., Healy B., et al. Randomised controlled trial of high concentration versus titrated oxygen therapy in severe exacerbations of asthma. Thorax. 2011; 66 (11): 937–941. DOI: 10.1136/thx.2010.155259.

121. Edmonds M.L., Milan S.J., Camargo C.A. et al. Early use of inhaled corticosteroids in the emergency department treatment of acute asthma. Cochrane Database Syst. Rev. 2012; (12): CD002308. DOI: 10.1002/14651858.CD002308.pub2.

122. Cates C.J., Welsh E.J., Rowe B.H. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst. Rev. 2013; (9): CD000052. DOI: 10.1002/14651858.CD000052.pub3.

123. Rodrigo G.J., Rodrigo C., Hall J.B. Acute asthma in adults: a review. Chest. 2004; 125 (3): 1081–1102. DOI: 10.1378/chest.125.3.1081.

124. Hasegawa T., Ishihara K., Takakura S. et al. Duration of systemic corticosteroids in the treatment of asthma exacerbation; a randomized study. Intern. Med. 2000; 39 (10): 794–797. DOI: 10.2169/internalmedicine.39.794.

125. Jones A.M., Munavvar M., Vail A. et al. Prospective, placebo-controlled trial of 5 vs 10 days of oral prednisolone in acute adult asthma. Respir. Med. 2002; 96 (11): 950–954. DOI: 10.1053/rmed.2002.1369.

126. Авдеев С.Н., Жестков А.В., Лещенко И.В. и др. Небулизированный будесонид при тяжелом обострении бронхиальной астмы: сравнение с системными стероидами. Мультицентровое рандомизированное контролируемое исследование. Пульмонология. 2006; (4): 58–67. Доступно на: https://journal.pulmonology.ru/pulm/article/view/1476.

127. Овчаренко С.И., Переделъская О.А., Морозова Н.В., Маколкин В.И. Небулайзерная терапия бронхолитиками и суспензией Пульмикорта® в лечении тяжелых обострений бронхиальной астмы. Пульмонология. 2003; (6): 75–83. Доступно на: https://journal.pulmonology.ru/pulm/article/view/2597/2029.

128. Ediger D., Coşkun F., Kunt Uzaskan E. et al. Clinical effectiveness of nebulized budesonide in the treatment of acute asthma attacks. Tuberkuloz ve Toraks Dergisi. 2006; 54 (2): 128–136. Available at: http://www.tuberktoraks.org/managete/fu_folder/2006-02/2006-54-2-128-136.pdf

129. Higenbottam T., Britton J., Lawrence D. et al. Comparison of nebulised Budesonide and Prednisolone in severe asthma exacerbation in adults. BioDrugs. 2000; 14 (4): 247–254. DOI: 10.2165/00063030-200014040-00004.

130. Chien J.W., Ciufo R., Novak R. et al. Uncontrolled oxygen administration and respiratory failure in acute asthma. Chest. 2000; 117 (3): 728–733. DOI: 10.1378/chest.117.3.728.

131. Rodrigo G.J., Rodriquez Verde M., Peregalli V., Rodrigo C. Effects of short-term 28% and 100% oxygen on PaCO2 and peak expiratory flow rate in acute asthma: a randomized trial. Chest. 2003; 124 (4): 1312–1317. DOI: 10.1378/chest.124.4.1312.

132. Rodrigo G.J., Castro-Rodriguez J.A. Anticholinergics in the treatment of children and adults with acute asthma: a systematic review with meta-analysis. Thorax. 2005; 60 (9): 740–746. DOI: 10.1136/thx.2005.040444.

133. Camargo C.A. Jr, Spooner C.H., Rowe B.H. Continuous versus intermittent beta-agonists in the treatment of acute asthma. Cochrane Database Syst. Rev. 2003; (4): CD001115. DOI: 10.1002/14651858.CD001115.

134. Nair P., Milan S.J., Rowe B.H. Addition of intravenous aminophylline to inhaled beta(2)-agonists in adults with acute asthma. Cochrane Database Syst. Rev. 2012; (12): CD002742. DOI: 10.1002/14651858.CD002742.pub2.

135. Ayres J.G. Classification and management of brittle asthma. Br. J. Hosp. Med. 1997; 57 (8): 387–389.

136. Kolbe J., Fergusson W., Garrett J. Rapid onset asthma: a severe but uncommon manifestation. Thorax. 1998; 53 (4): 241–247. DOI: 10.1136/thx.53.4.241.

137. Rowe B.H., Bretzlaff J.A., Bourdon C. et al. Magnesium sulfate for treating exacerbations of acute asthma in the emergency department. Cochrane Database Syst. Rev. 2000; (2): CD001490. DOI: 10.1002/14651858.CD001490.

138. FitzGerald J.M. Magnesium sulfate is effective for severe acute asthma treated in the emergency department. West J. Med. 2000; 172 (2): 96. DOI: 10.1136/ewjm.172.2.96-a.

139. Gallegos-Solorzano M.C., Perez-Padilla R., Hernandez-Zenteno R.J. Usefulness of inhaled magnesium sulfate in the coadjuvant management of severe asthma crisis in an emergency department. Pulm. Pharmacol. Ther. 2010; 23 (5): 432–437. DOI: 10.1016/j.pupt.2010.04.006.

140. Rodrigo G.J., Castro-Rodriguez J.A. Heliox-driven beta2-agonists nebulization for children and adults with acute asthma: a systematic review with meta-analysis. Ann. Allergy Asthma Immunol. 2014; 112 (1): 29–34. DOI: 10.1016/j.anai.2013.09.024.

141. Pozin N., Montesantos S., Katz I. et al. Calculated ventilation and effort distribution as a measure of respiratory disease and Heliox effectiveness. J. Biomech. 2017; 60: 100–109. DOI: 10.1016/j.jbiomech.2017.06.009.

142. Silverman R.A., Nowak R.M., Korenblat P.E. et al. Zafirlukast treatment for acute asthma: evaluation in a randomized, doubleblind, multicenter trial. Chest. 2004; 126 (5): 1480–1489. DOI: 10.1378/chest.126.5.1480.

143. Ramsay C.F., Pearson D., Mildenhall S., Wilson A.M. Oral montelukast in acute asthma exacerbations: a randomised, doubleblind, placebo-controlled trial. Thorax. 2011; 66 (1): 7–11. DOI: 10.1136/thx.2010.135038.

144. Gupta D., Hath A., Agarwal R., Behera D. A prospective randomized controlled trial on the efficacy of noninvasive ventilation in severe acute asthma. Respir. Care. 2010; 55 (5): 536–543. Available at: http://rc.rcjournal.com/content/55/5/536

145. Georgopoulos D., Burchardi H. Ventilation strategies in adult patients with status asthmaticus. Eur. Respir. Mon. 1998; 3: 45–83.

146. Авдеев С.Н. Респираторная поддержка при астматическом статусе. В кн.: Чучалин А.Г., ред. Бронхиальная астма у взрослых: клинические рекомендации. М.: Атмосфера; 2002: 130– 155.

147. Kuyper L.M., Pare P.D., Hogg J.C. et al. Characterization of airway plugging in fatal asthma. Am. J. Med. 2003; 115 (1): 6–11. DOI: 10.1016/s0002-9343(03)00241-9.

148. National library of Medicine. Expert panel report 3: Guidelines for the diagnosis and management of asthma: Clinical practice guidelines. 2007. Available at: https://www.ncbi.nlm.nih.gov/books/NBK7232/

149. Grunfeld A., FitzGerald J. Discharge considerations for adult asthmatic patients treated in emergency departments. Can. Respir. J. 1996; 3 (5): 322–327. DOI: 10.1155/1996/254627.

150. Edmonds M.L., Milan S.J., Brenner B.E. et al. Inhaled steroids for acute asthma following emergency department discharge. Cochrane Database Syst. Rev. 2012; (12): CD002316. DOI: 10.1002/14651858.CD002316.pub2.

151. Rowe B.H., Bota G.W., Fabris L. et al. Inhaled budesonide in addition to oral steroids to prevent asthma relapse following discharge from the emergency department: a randomized controlled trial. JAMA. 1999; 281 (22): 2219–2226. DOI: 10.1001/jama.281.22.2119.

152. Schatz M., Rachelefsky G., Krishnan J.A. Follow-up after acute asthma episodes: what improves future outcomes? Proc. Am. Thorac. Soc. 2009; 6 (4): 386–393. DOI: 10.1513/pats.p09st6.

153. Jaffuel D., Fabry-Vendrand C., Darnal E. et al. Perception of oral corticosteroids in adult patients with asthma in France. J. Asthma. 2021; 58 (7): 946–957. DOI: 10.1080/02770903.2020.1748048.

154. Beckhaus A.A., Riutort M.C., Castro-Rodriguez J.A. Inhaled versus systemic corticosteroids for acute asthma in children: a systematic review. Pediatr. Pulmonol. 2014; 49 (4): 326–334. DOI: 10.1002/ppul.22846.

155. Wilson N.M., Silverman M. Treatment of acute, episodic asthma in preschool children using intermittent high dose inhaled steroids at home. Arch. Dis. Child. 1990; 65 (4): 407–410. DOI: 10.1136/adc.65.4.407.

156. Su X.M., Yu N., Kong L.F., Kang J. Effectiveness of inhaled corticosteroids in the treatment of acute asthma in children in the emergency department: a meta-analysis. Ann. Med. 2014; 46 (1): 24–30. DOI: 10.3109/07853890.2013.859855.

157. Rohrer V., Schmidt-Trucksäss A. [Impact of exercise, sport and rehabilitation therapy in asthma and COPD]. Ther. Umsch. 2014; 71 (5): 295–300. DOI: 10.1024/0040-5930/a000516 (in German).

158. Hennenberger P.K., Liang X., Lilienberg L. et al. Occupational exposures associated with severe exacerbation of asthma. Int. J. Tuberc. Lung. Dis. 2015; 19 (2): 244–250. DOI: 10.5588/ijtld.14.0132.

159. Oland A.A., Booster G.D., Bender B.G. Psychological and lifestyle risk factors for asthma exacerbations and morbidity in children. World Allergy Organ. J. 2017; 10 (1): 35. DOI: 10.1186/s40413-017-0169-9.

160. Aarniala B.S., Poussa T., Kvarnström J. et al. Immediate and long term effects of weight reduction in obese people with asthma: randomised controlled study. BMJ. 2000; 320 (7238): 827–832. DOI: 10.1136/bmj.320.7238.827.

161. Hasegawa K., Tsugawa Y., Lopez B.L. et al. Body mass index and risk of hospitalization among adults presenting with asthma exacerbation to the emergency department. Ann. Am. Thorac. Soc. 2014; 11 (9): 1439–1444. DOI: 10.1513/AnnalsATS.201406-270BC.

162. Gamble J., Stevenson M., Heaney L.G. A study of a multi-level intervention to improve non-adherence in difficult to control asthma. Respir. Med. 2011; 105 (9): 1308–1315. DOI: 10.1016/j.rmed.2011.03.019.

163. Wenzel S. Severe asthma in adults. Am. J. Respir. Crit. Care Med. 2005; 172 (2): 149–160. DOI: 10.1164/rccm.200409-1181PP.

164. Petsky H.L., Cates C.J., Lasserson T.J. et al. A systematic review and meta-analysis: tailoring asthma treatment on eosinophilic markers (exhaled nitric oxide or sputum eosinophils). Thorax. 2012; 67 (3): 199–208. DOI: 10.1136/thx.2010.135574.

165. Wang Y., Wang C.Z., Lin K.X. et al. Comparison of inhaled corticosteroid combined with theophylline and double-dose inhaled corticosteroid in moderate to severe asthma. Respirology. 2005; 10 (2): 189–195. DOI: 10.1111/j.1440-1843.2005.00697.x.

166. Murphy V.E., Gibson P.G. Asthma in pregnancy. Clin. Chest Med. 2011; 32 (1): 93–110. DOI: 10.1016/j.ccm.2010.10.001.

167. Dombrowski M.P., Schatz M., Wise R. et al. Asthma during pregnancy. Obstet. Gynecol. 2004; 103 (1): 5–12. DOI: 10.1097/01.AOG.0000103994.75162.

168. 168. Zacharasiewicz A. Maternal smoking in pregnancy and its influence on childhood asthma. ERJ Open Res. 2016; 2 (3): 00042–2016. DOI: 10.1183/23120541.00042-2016.

169. Eltonsy S., Forget A., Blais L. Beta2-agonists use during pregnancy and the risk of congenital malformations. Birth. Defects Res. A Clin. Mol. Teratol. 2011; 91 (11): 937–947. DOI: 10.1002/bdra.22850.

170. Schatz M. Asthma treatment during pregnancy. What can be safely taken? Drug Saf. 1997; 16 (5): 342–350. DOI: 10.2165/00002018-199716050-00005.

171. Lim A., Stewart K., König K., George J. Systematic review of the safety of regular preventive asthma medications during pregnancy. Ann. Pharmacother. 2011; 45 (7-8): 931–945. DOI: 10.1345/aph.1P764.

172. NAEPP Expert Panel Report. Managing asthma during pregnancy: recommendations for pharmacologic treatment – 2004 update. J. Allergy Clin. Immunol. 2005; 115 (1): 34–46. DOI: 10.1016/j.jaci.2004.10.023.

173. Wendel P.J., Ramin S.M., Barnett-Hamm C. et al. Asthma treatment in pregnancy: a randomized controlled study. Am. J. Obstet Gynecol. 1996; 175 (1): 150–154. DOI: 10.1016/s0002-9378(96)70265-x.

174. Giles W., Murphy V. Asthma in pregnancy: a review. Obstet. Med. 2013; 6 (2): 58–63. DOI: 10.1258/OM.2012.120008.

175. Michaud P.A., Suris J.C., Viner R. The adolescent with a chronic condition: epidemiology, developmental issues and health care provision. Geneva: World Health Organization; 2007. Available at: https://apps.who.int/iris/handle/10665/43775?locale-attribute=ru&-mode=full

176. Baur X., Sigsgaard T., Aasen T.B. et al. Guidelines for the management of work-related asthma. Eur. Respir. J. 2012; 39 (3): 529–545. DOI: 10.1183/09031936.00096111.

177. Henneberger P.K., Patel J.R., de Groene G.J. et al. The effectiveness of removal from exposure and reduction of exposure for managing occupational asthma: summary of an updated Cochrane systematic review. Am. J. Ind. Med. 2020; 64 (3): 165–169. DOI: 10.1002/ajim.23208.

178. Papadopoulos N.G., Arakawa H., Carlsen K.H. et al. International consensus on (ICON) pediatric asthma. Allergy. 2012; 67 (8): 976–997. DOI: 10.1111/j.1398-9995.2012.02865.x.

179. Баранов А.А., Хаитов Р.М., ред. Аллергология и иммунология: клинические рекомендации для педиатров. 3-е изд. М.: Союз педиатров России; 2011

180. Zeiger R.S., Schatz M., Zhang F. et al. Elevated exhaled nitric oxide is a clinical indicator of future uncontrolled asthma in asthmatic patients on inhaled corticosteroids. J. Allergy Clin. Immunol. 2011; 128 (2): 412–414. DOI: 10.1016/j.jaci.2011.06.008.

181. Schatz M., Sorkness C.A., Li J.T. et al. Asthma Control Test: reliability, validity, and responsiveness in patients not previously followed by asthma specialists. J. Allergy Clin. Immunol. 2006; 117 (3): 549–556. DOI: 10.1016/j.jaci.2006.01.011.

182. Schatz M., Mosen D.M., Kosinski M. et al. Validity of the asthma control test completed at home. Am. J. Manag. Care. 2007; 13 (12): 661–667.

183. Liu A.H., Zeiger R., Sorkness C. et al. Development and cross-sectional validation of the childhood asthma control test. J. Allergy Clin. Immunol. 2007; 119 (4): 817–825. DOI: 10.1016/j.jaci.2006.12.662.

184. Juniper E.F., O’Byrne P.M., Guyatt G.H. et al. Development and validation of a questionnaire to measure asthma control. Eur. Respir. J. 1999; 14 (4): 902–907. DOI: 10.1034/j.1399-3003.1999.14d29.x.