Clinical and immunological characteristics of severe bronchial asthma with Aspergillus sensitization
DOI: 10.32364/2587-6821-2021-5-1-10-16
Ya.I. Kozlova1, E.V. Frolova2, A.E. Uchevatkina2, L.V. Filippova2, O.V. Aak2,
V.D. Kuznetsov1, N.V. Vasilieva2, N.N. Klimko1
1I.I. Mechnikov North-Western State Medical University, Saint Petersburg,
Russian Federation
2P.N. Kashkin Research Institute of Medical Mycology, I.I. Mechnikov North-Western
State Medical University, Saint Petersburg, Russian Federation
Aim: to assess the clinical and immunological characteristics of patients with severe bronchial asthma (BA) with Aspergillus sensitization and to study the possibilities of applying basophil activation test (BAT) using flow cytometry to detect mycogenic sensitization.
Patients and Methods: 93 patients with severe BA were examined. Therapy had 4 or 5 steps according to GINA 2019 recommendations. TARC (thymus and activation-regulated chemokine) content, the number of eosinophils, the levels of total IgE and specific IgE to 10 allergens were determined in blood serum by enzyme immunoassay. BAT with Aspergillus fumigatus allergen was performed in vitro using flow cytometry.
Results: Aspergillus sensitization was detected in 33 (35.4%) patients with severe BA. In patients with BA and Aspergillus sensitization, the disease course was uncontrolled, and patients in this group were credibly more likely to receive oral glucocorticosteroids. The number of basophils (activated by the A. fumigatus allergen) and the stimulation index in patients with BA and Aspergillus sensitization were significantly higher than in patients with BA (9.9 (6.0–24.0) % vs. 3.6 (2.0–5.4) %; (p=0.000) and 4.25 (2.49–9.30) vs. 0.94 (0.75–1.16); (p=0.000)). Significant differences in TARC content were obtained in the groups of patients with severe BA and Aspergillus sensitization and patients with BA (625.0 (418.4–875.0) pg/mg versus 406.0 (210.0–561.0) pg/mg; p=0.001). A negative correlation was determined between TARC levels and a decrease in forced expiratory volume in 1 second (FEV1) (r=-0.70, p<0.05), and between positive correlation and absolute eosinophil count (r=0.81, p<0.05) and level of specific IgE to Aspergillus (r=0.36, p<0.05).
Conclusion: Aspergillus sensitization is associated with an uncontrolled BA course. An additional method for diagnosing mycogenic sensitization is the BAT. The TARC concentration can serve as a biomarker of an active inflammatory response.
Keywords: Aspergillus spp., severe bronchial asthma, mycogenic sensitization, basophil activation test, TARC.
For citation: Kozlova Ya.I., Frolova E.V., Uchevatkina A.E. et al. Clinical and immunological characteristics of severe bronchial asthma with Aspergillus sensitization. Russian Medical Inquiry. 2021;5(1):10–16. DOI: 10.32364/2587-6821-2021-5-1-10-16.
About the authors:
1Yana I. Kozlova — Cand. of Sci. (Med.), Associate Professor, Associate Professor of the Department of Clinical Mycology, Allergology and Immunology, I.I. Mechnikov North-Western State Medical University; 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; ORCID iD 0000-0002-4602-2438.
2Ekaterina V. Frolova — Cand. of Sci. (Med.), Head of the Research Laboratory of Immunology and Allergology, P.N. Kashkin Research Institute of Medical Mycology, I.I. Mechnikov North-Western State Medical University; 1/28, Santiago-de-Cuba str., St. Petersburg, 194291, Russian Federation; ORCID iD 0000-0002-7696-2236.
2Alexandra E. Uchevatkina — Cand. of Sci. (Med.), Senior Researcher of the Research Laboratory of Immunology and Allergology, P.N. Kashkin Research Institute of Medical Mycology, I.I. Mechnikov North-Western State Medical University; 1/28, Santiago-de-Cuba str., St. Petersburg, 194291, Russian Federation; ORCID iD 0000-0001-6688-7781.
2Larisa V. Filippova — Cand. of Sci. (Med.), Senior Researcher of the Research Laboratory of Immunology and Allergology, P.N. Kashkin Research Institute of Medical Mycology, I.I. Mechnikov North-Western State Medical University; 1/28, Santiago-de-Cuba str., St. Petersburg, 194291, Russian Federation; ORCID iD 0000-003-4167-7440.
2Oleg V. Aak — Cand. of Sci. (Chemistry), Senior Researcher of the Research Laboratory of Immunology and Allergology, P.N. Kashkin Research Institute of Medical Mycology, I.I. Mechnikov North-Western State Medical University; 1/28, Santiago-de-Cuba str., St. Petersburg, 194291, Russian Federation; ORCID iD 0000-0001-8130-7503.
1Valery D. Kuznetsov — post-graduate student of the Department of Clinical Mycology, Allergology and Immunology, I.I. Mechnikov North-Western State Medical University; 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; ORCID iD 0000-0001-9439-4749.
2Natalia V. Vasileva — Dr. of Sci. (Biology), Director of the P.N. Kashkin Research Institute of Medical Mycology; 1/28, Santiago-de-Cuba str, St. Petersburg, 194291, Russia; ORCID iD 0000-0003-3693-5468.
1Nikolay N. Klimko — Dr. of Sci (Med.), Professor, Head of the Department of Clinical Mycology, Allergology and Immunology, I.I. Mechnikov North-Western State Medical University; 41, Kirochnaya str., St. Petersburg, 191015, Russian Federation; ORCID iD 0000-0001-6095-7531.
Contact information: Yana Kozlova, e-mail: kozlova510@mail.ru. Financial Disclosure: no authors have a financial or property interest in any material or method mentioned. There is no conflict of interests. Received 06.04.2020, revised 05.05.2020, accepted 28.05.2020.
2. Murray C.J., Vos T., Lozano R. et al. Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990–2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012;380:2197–2223. DOI: 10.1016/S0140-6736 (12) 61689-4.
3. Wenzel S. Asthma: defining of the persistent adult phenotypes. Lancet. 2006;368:804–813. DOI: 10.1016/S0140-6736 (06) 69290-8.
4. Bush R.K., Portnoy J.M., Saxon A. et al. The medical effects of mold exposure. J. Allergy Clin. Immunol. 2006;117:326–333. DOI: 10.1016/j.jaci.2005.12.001.
5. Knutsen A.P., Bush R.K., Demain J.G. et al. Fungi and allergic lower respiratory tract diseases. J. Allergy Clin. Immunol. 2012;129:280–291. DOI: 10.1016/j.jaci.2011.12.970.
6. Fairs A., Agbetile J., Hargadon B. et al. IgE sensitization to Aspergillus fumigatus is associated with reduced lung function in asthma. Am. J. Respir. Crit Care Med. 2010;182:1362–1368. DOI: 10.1164/rccm.201001-0087OC.
7. Denning D.W., Pashley C., Hartl D. et al. Fungal allergy in asthma–state of the art and research needs. Clin Transl Allergy. 2014;4:14. DOI: 10.1186/2045-7022-4-14.
8. Denning D.W., O’Driscoll B.R., Powell G. et al. Randomized controlled trial of oral antifungal treatment for severe asthma with fungal sensitization: The Fungal Asthma Sensitization Trial (FAST) study. Am. J. Respir. Crit Care Med. 2009;179:11–18. DOI: 10.1164/rccm.200805-737OC.
9. Chung K.P. et al. International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma. Eur. Respir. J. 2014;43:343–373.
10. Agarwal R., Chakrabarti A., Shah D. et al. For the ABPA complicating asthma ISHAM working group 2013. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43:850–873. DOI: 10.1111/cea.12141.
11. Agarwal R., Aggarwal A.N., Gupta D., Jindal S.K. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: Systematic review and meta-analysis. Int. J. Tuberc. Lung Dis. 2009;13:936–944.
12. Agarwal R., Nath A., Aggarwal A.N. et al. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with acute severe asthma in a respiratory intensive care unit in North India. Mycoses. 2010;53:138–143. DOI: 10.1111/j.1439-0507.2008.01680.x.
13. O’Driscoll B.R., Powell G., Chew F. et al. Comparison of skin prick tests with specific serum immunoglobulin e in the diagnosis of fungal sensitization in patients with severe asthma. Clin. Exp. Allergy. 2009;39:1677–1683. DOI: 10.1111/j.1365-2222.2009.03339.x.
14. Goh K.J., Yii A.C.A., Lapperreet T.S. et al. Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma. J Asthma Allergy. 2017;10:131–140. DOI: 10.2147/JAA.S130459.
15. Agarwal R., Noel V., Aggarwal A.N. et al. Clinical significance of Aspergillus sensitisation in bronchial asthma. Mycoses. 2011;54:531–539. DOI: 10.1111/j.1439-0507.2010.01971.x.
16. Menzies D., Holmes L., McCumesky G. et al. Aspergillus sensitization is associated with airflow limitation and bronchiectasis in severe asthma. Allergy Eur. J. Allergy Clin. Immunol. 2011;66:679–685. DOI: 10.1111/j.1398-9995.2010.02542.x.
17. Moss R.B. Allergic bronchopulmonary aspergillosis and Aspergillus infection in cystic fibrosis. Curr. Opin. Pulm. Med. 2010;16:598–603. DOI: 10.1097/MCP.0b013e32833e24a6.
18. Bafadhel M., McKenna S., Agbetile J. et al. Aspergillus fumigatus during stable state and exacerbations of COPD. Eur. Respir. J. 2014;43:64–71. DOI: 10.1183/09031936.00162912.
19. Шабанов Д.В., Лазаренко Л.Л., Федоскова Т.Г., Рыбникова Е.А. Особенности диагностики аллергии к яду перепончатокрылых насекомых. РМЖ. 2019;3:40–44. [Shabanov D.V., Lazarenko L.L., Fedoskova T.G., Rybnikova E.A. Diagnostics of Hymenoptera venom allergy. RMJ. 2019;3:40–44 (in Russ.)]. DOI: 10.15789/1563-0625-2015-1-39-46.
20. Синельникова Н.А., Бычкова Н.В., Калинина Н.М. Особенности иммунного ответа и активации базофилов у детей с хронической крапивницей. Медицинская иммунология. 2015;1:39–46. [Sinelnikova N.A., Bychkova N.V., Kalinina N.M. Features of immune response and basophil activation in children with chronic urticaria. Meditsinskaya immunologiya. 2015;17:39–46 (in Russ.)]. DOI: 10.15789/1563-0625-2015-1-39-46.
21. Agarwal R. Severe asthma with fungal sensitization. Curr. Allergy Asthma Rep. 2011;11:403–413. DOI: 10.1007/s11882-011-0217-4.
22. Chotirmall S.H., Al-Alawi M., Mirkovic B. et al. Aspergillus-associated airway disease, inflammation, and the innate immune response. Biomed Res. Int. 2013;2013:723129. DOI: 10.1155/2013/723129.
23. Becerra-Díaz M., Wills-Karp M., Heller N.M. New perspectives on the regulation of type II inflammation in asthma. F1000Res. 2017;6:1014.
24. Margalit A., Kavanagh K. The innate immune response to Aspergillus fumigatus at the alveolar surface. FEMS Microbiol. Rev. 2015;39:670–687. DOI: 10.1093/femsre/fuv018.
25. Hartl D., Latzin P., Zissel G. et al. Chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Am. J. Respir. Crit Care Med. 2006;173:1370–1376. DOI: 10.1164/rccm.200508-1271OC.
26. Latzin P., Hartl D., Regamey N. et al. Comparison of serum markers for allergicbronchopulmonary aspergillosis in cystic fibrosis. Eur. Respir. J. 2008;31:36–42. DOI: 10.1183/09031936.00078107.
27. Козлова Я.И., Фролова Е.В., Филиппова Л.В. и др. Диагностические маркеры аллергического бронхолегочного аспергиллеза. Медицинская иммунология. 2018;4:561–570. [Kozlova Y.I., Frolova E.V., Filippova L.V. et al. Diagnostic markers of allergic bronchopulmonary aspergillosis in patients with bronchial asthma. Meditsinskaya immunologiya. 2018;4:561–570 (in Russ.)]. DOI: 10.15789/1563-0625-2018-4-561-570.
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