Clinical, functional and immunological characteristics of severe bronchial asthma

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Abstract

BACKGROUND: Bronchial asthma is one of the most common and socially remarkable diseases in humans. The uncontrolled course of asthma remains a leading problem in the management of patients with this disease. Patients who cannot achieve control include a special group with severe asthma.

AIM: Comprehensive assessment of clinical, functional, and immunological features and the pharmacotherapy of severe bronchial asthma in real clinical practice to optimize basic pathogenetic therapy.

MATERIALS AND METHODS: In all, 83 patients diagnosed with severe asthma were examined. Patients with severe asthma were divided into two groups: patients with and without fixed airway obstruction. Plasma concentrations of interleukin (IL)-4, IL-5, IL-9, IL-13, periostin, cathepsin S, and transforming growth factor (TGF)-β were determined via solid-phase enzyme immunoassay. Immune status was investigated using a NAVIOS flow cytometer.

RESULTS: Both groups of severe bronchial asthma patients showed a decrease in helper T-cell and immunoregulatory index levels with simultaneous increases in cytotoxic T lymphocytes, natural killer T cells, naive T lymphocytes, activated T and B lymphocytes, and phagocytic index compared with the controls. No differences were observed in the immune status between the groups, and the resulting changes were independent of the presence or absence of fixed obstruction. Both study groups exhibited increases in the levels of cathepsin S and TGF-β in the plasma compared with the controls. We identified two remarkable risk factors for forming fixed obstruction: taking SABA more than four inhalations per day (odds ratio (OR)=4.2) and FeNO concentration >20 ppb (OR=6.0). A remarkable improvement was observed in the clinical condition of patients with severe asthma with fixed obstruction while receiving genetically engineered biological therapy for a year.

CONCLUSIONS: To date, no unambiguous explanation is available for the mechanisms of implementation of pathobiochemical reactions in the bronchial wall in severe asthma, leading to the development of fixed airway obstruction. Severe asthma is variable and depends on the correct choice of management tactics.

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About the authors

Angelina Yu. Kraposhina

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University; Krasnoyarsk Clinical Regional Hospital

Author for correspondence.
Email: angelina-maria@inbox.ru
ORCID iD: 0000-0001-6896-877X
SPIN-code: 8829-9240

MD, Cand. Sci. (Med.), Associate Professor

Россия, 1 P. Zeleznyak street, 660022 Krasnoyarsk; Krasnoyarsk

Irina V. Demko

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University; Krasnoyarsk Clinical Regional Hospital

Email: demko64@mail.ru
ORCID iD: 0000-0001-8982-5292
SPIN-code: 6520-3233

MD, Dr. Sci. (Med.), Professor

Россия, 1 P. Zeleznyak street, 660022 Krasnoyarsk; Krasnoyarsk

Elena A. Sobko

Professor V.F. Voino-Yasenetsky Krasnoyarsk State Medical University; Krasnoyarsk Clinical Regional Hospital

Email: sobko29@mail.ru
ORCID iD: 0000-0002-9377-5213
SPIN-code: 9132-6756

MD, Dr. Sci. (Med.), Professor

Россия, 1 P. Zeleznyak street, 660022 Krasnoyarsk; Krasnoyarsk

References

  1. Zaytsev AA. Bronchial asthma in adults: Key issues of diagnosis and pharmacotherapy. Russ Med J. 2015;(18):1096–1100. (In Russ).
  2. Avdeev SN, Nenasheva NM, Zhudenkov KV, et al. Prevalence, morbidity, phenotypes and other characteristics of severe bronchial asthma in Russian Federation. Pulmonologiya. 2018;28(3):341–358. (In Russ). doi: 10.18093/0869-0189-2018-28-3-341-358
  3. Vennera MD, Picado C, Herráez L, et al. Factors associated with severe uncontrolled asthma and the perception of control by physicians and patients. Arch Bronconeumol. 2014;50(9):384–391. doi: 10.1016/j.arbres.2014.03.002
  4. Leckie MJ, Brinke TA, Khan J. Effects of an interleukin-5 blocking monoclonal antibody on eosinophils, airway hyper-responsiveness, and the late asthmatic response. The Lancet. 2000;356(9248): 2144–2148. doi: 10.1016/S0140-6736(00)03496-6
  5. Svenningsen S, Nair P. Asthma Endotypes and an overview of targeted therapy for asthma. Front Med. 2017;(4):158. doi: 10.3389/fmed.2017.00158
  6. Sergeeva GR, Emelyanov AV, Korovina OV, et al. Severe bronchial asthma: Characteristics of patients in clinical practice. Ther Arch. 2015;87(12):26–31. (In Russ). doi: 10.17116/terarkh2015871226-31
  7. Konstantellou E, Papaioannou AI, Loukides S, et al. Persistent airflow obstruction in patients with asthma: Characteristics of a distinct clinical phenotype. Respir Med. 2015;109(11):404–409. doi: 10.1016/j.rmed.2015.09.009
  8. Ciebiada M, Domagała M, Gorska-Ciebiada M, Gorski P. Risk factors associated with irreversible airway obstruction in nonsmoking adult patients with severe asthma. Allergy Asthma Proc. 2014;35(5):72–79. doi: 10.2500/aap.2014.35.3785
  9. Bennett GH, Carpenter L, Hao W, et al. Risk factors and clinical outcomes associated with fixed airflow obstruction in older adults with asthma. Ann Allergy Asthma Immunol. 2018;120(2):164–168. doi: 10.1016/j.anai.2017.10.004
  10. Haddad A, Gaudet M, Plesa M, et al. Neutrophils from severe asthmatic patients induce epithelial to mesenchymal transition in healthy bronchial epithelial cells. Respir Res. 2019;20(1):234. doi: 10.1186/s12931-019-1186-8
  11. Nair P, Pizzichini MM, Kjarsgaard M, et al. Mepolizumab for prednisone-dependent asthma with sputum eosinophilia. N Engl J Med. 2009;360(10):985–993. doi: 10.1056/NEJMoa0805435
  12. Nair P. Anti-interleukin-5 monoclonal antibody to treat severe eosinophilic asthma. N Engl J Med. 2014;371(13):1249–1251. doi: 10.1056/NEJMe1408614
  13. Wenzel S. Severe asthma: From characteristics to phenotypes to endotypes. Clin Exp Allergy. 2012;42(5):650–658. doi: 10.1111/j.1365-2222.2011.03929.x
  14. Cosmi L, Liotta F, Maggi L, Annunziato F. Role of type 2 innate lymphoid cells in allergic diseases. Curr Allergy Asthma Rep. 2017;17(10):66. doi: 10.1007/s11882-017-0735-9
  15. Licari A, Castagnoli R, Brambilla I, et al. New approaches for identifying and testing potential new anti-asthma agents. Expert Opin Drug Discov. 2018;13(1):51–63. doi: 10.1080/17460441.2018.1396315
  16. Flood-Page P, Swenson C, Faiferman I, et al. A study to evaluate safety and efficacy of mepolizumab in patients with moderate persistent asthma. Am J Respir Crit Care Med. 2007;176(11): 1062–1071. doi: 10.1164/rccm.200701-085OC
  17. Hirose K, Iwata A, Tamachi T, Nakajima H. Allergic airway inflammation: Key players beyond the Th2 cell pathway. Immunol Rev. 2017;278(1):145–161. doi: 10.1111/imr.12540
  18. Viksman ME, Maianskiy AN. Characteristics of the opsonin factors according to the reaction of nitroblue tetrazolium reduction by human neutrophils. Bulletin of experimental biology and medicine. 1980;89(2):214–215.
  19. Gelfand E, Hinks TS. Is there a role for type 2 CD8+ T cells in patients with steroid-resistant asthma? J Allergy Clin Immunol. 2019;144(3):648–650. doi: 10.1016/j.jaci.2019.07.02
  20. Matangkasombut P, Marigowda G, Ervine A, et al. Natural killer T cells in the lungs of patients with asthma. J Allergy Clin Immunol. 2009;123(5):1181–1185. doi: 10.1016/j.jaci.2009.02.013
  21. Koh YI, Shim JU, Wi J, Kwon YE. The role of natural killer T cells in the pathogenesis of acute exacerbation of human asthma. Int Arch Allergy Immunol. 2012;158(2):131–141. doi: 10.1159/000330908
  22. Kim HY, De Kruyff RH, Umetsu DT. The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol. 2010;11(7):577–584. doi: 10.1038/ni.1892
  23. Sobotic B, Vizovisek M, Vidmar R, et al. Proteomic identification of cysteine Cathepsin substrates shed from the surface of cancer cells. Mol Cell Proteomics. 2015;14(8):2213–2228. doi: 10.1074/mcp.M114.044628

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