New opportunities in the diagnosis of asthma with sensitization to Aspergillus spp.

Abstract

BACKGROUND: Diagnosis of asthma with sensitization to Aspergillus spp. is becoming increasingly important due to the severe, uncontrolled course of the disease and the possibility of the formation of allergic bronchopulmonary aspergillosis.

AIM: To evaluate the possibility of using the basophil activation test using flow cytometry for the diagnosis of asthma with sensitization to Aspergillus spp.

MATERIALS AND METHODS: 118 patients with asthma were examined. The levels of total IgE and specific IgE to aeroallergens were determined in the blood serum by the enzyme immunoassay. Basophil activation was studied by flow cytometry using the Allergenicity kit (Cellular Analysis of Allergy, Beckman-Coulter, USA). The allergen Aspergillus fumigatus (Alcor Bio, Russia) was used to stimulate basophils.

RESULTS: The first group consisted of 57 patients with asthma without sensitization to Aspergillus spp. The second group included 36 patients with asthma with sensitization to Aspergillus spp. The third group consisted of 25 patients with allergic bronchopulmonary aspergillosis. The number of basophils activated by the Aspergillus fumigatus allergen in patients with asthma with sensitization to Aspergillus spp. and allergic bronchopulmonary aspergillosis was significantly higher than in the asthma group and amounted to 8.1 [5.2; 20.9]% and 84.6 [75.7; 94.0]%, respectively (p < 0.001). The stimulation index in the study groups ranged from 0.7 to 72.6. The optimal diagnostic point (cut off) for identifying patients with asthma with Aspergillus spp. sensitization there was an stimulation index value of more than 2.4, and for patients with allergic bronchopulmonary aspergillosis — 15.95. Among all patients with sensitization to Aspergillus spp. a positive correlation was established between the level of specific IgE to Aspergillus spp. and the percentage of basophils activated by the allergen Aspergillus fumigatus (r = 0.792, p < 0.001) and stimulation index (r = 0.796, p < 0.05).

CONCLUSIONS: The basophil activation test can be used as an additional diagnostic method for asthma with sensitization to Aspergillus spp. and allergic bronchopulmonary aspergillosis.

Keywords

Aspergillus spp. / asthma / basophil activation test

References

[1] Ginasthma.org [Internet]. The Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org/. Accessed: 19.05.2020.

[2] Ginasthma.org [Электронный ресурс]. The Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma (GINA) 2020. Режим доступа: http://www.ginasthma.org/. Дата обращения: 19.05.2020.

[3] Agarwal R. Severe asthma with fungal sensitization. Curr Allergy Asthma Rep. 2011;11(5):403–413. DOI: 10.1007/s11882-011-0217-4

[4] Agarwal R. Severe asthma with fungal sensitization // Curr. Allergy. Asthma Rep. 2011. Vol. 11, No. 5. P. 403–413. DOI: 10.1007/s11882-011-0217-4

[5] Rick E, Woolnough K, Pashley C, Wardlaw AJ. Allergic fungal airway disease. J Investig Allergol Clin Immunol. 2016;26(6):344–354. DOI: 10.18176/jiaci.0122

[6] Rick E., Woolnough K., Pashley C., Wardlaw A.J. Allergic fungal airway disease // J. Investig. Allergol. Clin. Immunol. 2016. Vol. 26, No. 6. P. 344–354. DOI: 10.18176/jiaci.0122

[7] Agarwal R, Nath A, Aggarwal AN, 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(2):138–143. DOI: 10.1111/j.1439-0507.2008.01680x

[8] 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. Vol. 53, No. 2. P. 138–143. DOI: 10.1111/j.1439-0507.2008.01680x

[9] Denning D, O’Driscoll B, Hogaboam C, et al. The link between fungi and asthma: A summary of the evidence. Eur Respir J. 2006;27(3):615–626. DOI: 10.1183/09031936.06.00074705

[10] Denning D., O’Driscoll B., Hogaboam C. et al. The link between fungi and asthma: A summary of the evidence // Eur. Respir. J. 2006. Vol. 27, No. 3. P. 615–626. DOI: 10.1183/09031936.06.00074705

[11] Denning DW, Pleuvry A, Cole DC. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults. Med Mycol. 2013;51(4):361–370. DOI: 10.3109/13693786.2012.738312

[12] Denning D.W., Pleuvry A., Cole D.C. Global burden of allergic bronchopulmonary aspergillosis with asthma and its complication chronic pulmonary aspergillosis in adults // Med. Mycol. 2013. Vol. 51, No. 4. P. 361–370. DOI: 10.3109/13693786.2012.738312

[13] Klimko NN, Kozlova YI, Khostelidi SN, et al. The prevalence of serious and chronic fungal diseases in Russian Federation on LIFE program model. Problems in medical mycology. 2014;16(1):3–9. (In Russ.)

[14] Климко Н.Н., Козлова Я.И., Хостелиди С.Н. и др. Распространенность тяжелых и хронических микотических заболеваний в Российской Федерации по модели LIFE program // Проблемы медицинской микологии. 2014. Т. 16, № 1. С. 3–9.

[15] Kosmidis C, Denning D. The clinical spectrum of pulmonary aspergillosis. Thorax. 2015;70(3):270–277. DOI: 10.1136/thoraxjnl.2014.206291

[16] Kosmidis C., Denning D. The clinical spectrum of pulmonary aspergillosis // Thorax. 2015. Vol. 70, No. 3. P. 270–277. DOI: 10.1136/thoraxjnl.2014.206291

[17] Agarwal R, Aggarwal A, Gupta D, Jindal SK. Aspergillus hypersensitivity and allergic bronchopulmonary aspergillosis in patients with bronchial asthma: systematic review and meta-analysis. Int J Tuberc Lung Dis. 2009;13(8):936–944.

[18] Agarwal R., Aggarwal A., 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. Vol. 13, No. 8. P. 936–944.

[19] Goh KJ, Yii ACA, Lapperre TS, 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

[20] Goh K.J., Yii A.C.A., Lapperre T.S. et al. Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma // J. Asthma Allergy. 2017. Vol. 10. P. 131–140. DOI: 10.2147/JAA.S130459

[21] 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(11):1362–1368. DOI: 10.1164/rccm.201001.0087OC

[22] 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. Vol. 182, No. 11. P. 1362–1368. DOI: 10.1164/rccm.201001.0087OC

[23] Kozlova YI, Frolova EV, Uchevatkina AE, et al. Basophile activation test for the diagnostics of fungal sensitization in the patients with cystics fibrosis. Medical Immunology. 2019;21(5):919–928. (In Russ.). DOI: 10.15789/1563-0625-2019-5-919-928

[24] Козлова Я.И., Фролова Е.В., Учеваткина А.Е. и др. Тест акти¬вации базофилов для диагностики аллергического бронхолегочного аспергиллеза у больных муковисцидозом // Медицинская иммунология. 2019. Т. 21, № 5. С. 919–928. DOI: 10.15789/1563-0625-2019-5-919-928

[25] Agarwal R, Chakrabarti A, Shah A, et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clin Exp Allergy. 2013;43(8):850–873. DOI: 10.1111/cea.12141

[26] Agarwal R., Chakrabarti A., Shah A. et al. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria // Clin. Exp. Allergy. 2013. Vol. 43, No. 8. P. 850–873. DOI: 10.1111/cea.12141

[27] Agarwal R, Hazarika B, Gupta D, et al. Aspergillus hypersensi¬tivity in patients with chronic obstructive pulmonary disease: COPD as a risk factor for ABPA? Med Micol. 2010;48(7):988–994. DOI: 10.3109/13693781003743148

[28] Agarwal R., Hazarika B., Gupta D. et al. Aspergillus hypersensitivity in patients with chronic obstructive pulmonary disease: COPD as a risk factor for ABPA? // Med. Micol. 2010. Vol. 48, No. 7. P. 988–994. DOI: 10.3109/13693781003743148

[29] Oppenheimer J, Nelson HS. Skin testing. Ann Allergy Asthma Immunol. 2006;96(2 Suppl 1):S6–12. DOI: 10.1016/S1081-1206(10)60895-2

[30] Oppenheimer J., Nelson H.S. Skin testing // Ann. Allergy Asthma Immunol. 2006. Vol. 96, No. 2 Suppl 1. P. S6–12. DOI: 10.1016/S1081-1206(10)60895-2

[31] Karasuyama H, Tsujimura Y, Оbata K, Mukai K. Role for basophils in systemic anaphylaxis. Chem Immunol Allergy. 2010;95:85–87. DOI: 10.1159/000315939

[32] Karasuyama H., Tsujimura Y., Оbata K., Mukai K. Role for basophils in systemic anaphylaxis // Chem. Immunol. Allergy. 2010. Vol. 95. P. 85–87. DOI: 10.1159/000315939

[33] Sanz ML, Gamboa PM, De Weck AL. Cellular tests in the diagnosis of drug hypersensitivity. Curr Pharm Des. 2008;14(27):2803–2808. DOI: 10.2174/138161208786369722

[34] Sanz M.L., Gamboa P.M., De Weck A.L. Cellular tests in the diagnosis of drug hypersensitivity // Curr. Pharm. Des. 2008. Vol. 14, No. 27. P. 2803–2808. DOI: 10.2174/138161208786369722

[35] Hausmann OV, Gentinetta T, Bridts CH, Ebo DG. The basophil activation test in immediate-type drug allergy. Immunol Allergy Clin North Am. 2009;29(3):555–566. DOI: 10.1016/j.iac.2009.04.011

[36] Hausmann O.V., Gentinetta T., Bridts C.H., Ebo D.G. The basophil activation test in immediate-type drug allergy // Immunol. Allergy Clin. North. Am. 2009. Vol. 29, No. 3. P. 555–566. DOI: 10.1016/j.iac.2009.04.011

[37] Potapińska O, Górska E, Zawadzka-Krajewska A, et al. The usefulness of CD203c expression measurement on basophils after activation with grass pollen and Dermatophagoides pteronyssinus antigens. Preliminary study. Pneumonol Alergol Pol. 2009;77(2):138–144. (In Polish)

[38] Potapińska O., Górska E., Zawadzka-Krajewska A. et al. The usefulness of CD203c expression measurement on basophils after activation with grass pollen and Dermatophagoides pteronyssinus antigens. Preliminary study // Pneumonol. Alergol. Pol. 2009. Vol. 77, No. 2. P. 138–144. (In Polish)

[39] Knol EF, Mul FP, Jansen H, et al. Monitoring human basophil activation via CD63 monoclonal antibody 435. J Allergy Clin Immunol. 1991;88(3 Pt 1):328–338. DOI: 10.1016/0091-6749(91)90094-5

[40] Knol E.F., Mul F.P., Jansen H. et al. Monitoring human basophil activation via CD63 monoclonal antibody 435 // J. Allergy Clin. Immunol. 1991. Vol. 88, No. 3 Pt 1. P. 328–338. DOI: 10.1016/0091-6749(91)90094-5

[41] Kang MG, Song WJ, Park HK, et al. Basophil activation test with food additives in chronic urticaria patients. Clin Nutr Res. 2014;3(1):9–16. DOI: 10.7762.2Fcnr.2014.3.1.9

[42] Kang M.G., Song W.J., Park H.K. et al. Basophil activation test with food additives in chronic urticarial patients // Clin. Nutr. Res. 2014. Vol. 3, No. 1. P. 9–16. DOI: 10.7762.2Fcnr.2014.3.1.9

[43] Boumiza R, Debard AL, Monneret G. The basophil activation test by flow cytometry: recent development in clinical studies, standardization and emerging perspectives. Clin Mol Allergy. 2005;3:9. DOI: 10.1186/1476-7961-3-9

[44] Boumiza R., Debard A.L., Monneret G. The basophil activation test by flow cytometry: recent development in clinical studies, standardization and emerging perspectives // Clin. Mol. Allergy. 2005. Vol. 3. P. 9. DOI: 10.1186/1476-7961-3-9

[45] Chirumbolo S, Vella A, Ortolani R, et al. Differential response of human basophil activation markers: a multiparameter flow cytometry approach. Clin Mol Allergy. 2008;6:12. DOI: 10.1186/1476-7961-6-12

[46] Chirumbolo S., Vella A., Ortolani R. et al. Differential response of human basophil activation markers: a multiparameter flow cytometry approach // Clin. Mol. Allergy. 2008. Vol. 6. P. 12. DOI: 10.1186/1476-7961-6-12

[47] Mikkelsen S, Bibby BM, Dolberg MKB, et al. Basophil sensitivity through CD63 or CD203c is a functional measure for specific immunotherapy. Clin Mol Allergy. 2010;8(1):2. DOI: 10.1186/1476-7961-8-2

[48] Mikkelsen S., Bibby B.M., Dolberg M.K.B. et al. Basophil sensitivity through CD63 or CD203c is a functional measure for specific immunotherapy // Clin. Mol. Allergy. 2010. Vol. 8, No. 1. P. 2. DOI: 10.1186/1476-7961-8-2

[49] Buhring HJ, Seiffert M, Giesert C, et al. The basophil activation marker deined by antibody 97A6 is identical to the ectonucleotide pyrophosphatase/phosphodiesterase 3. Blood. 2001;97(10):3303–3305. DOI: 10.1182/blood.v97.10.3303

[50] Buhring H.J., Seiffert M., Giesert C. et al. The basophil activation marker deined by antibody 97A6 is identical to the ectonucleotide pyrophosphatase/phosphodiesterase 3 // Blood. 2001. Vol. 97, No. 10. P. 3303–3305. DOI: 10.1182/blood.v97.10.3303

[51] Chirumbolo S, Vella A, Ortolani R, et al. Differential response of human basophil activation markers: a multiparameter flow cytometry approach. Clin Mol Allergy. 2008;6:12. DOI: 10.1186/1476-7961-6-12

[52] Chirumbolo S., Vella A., Ortolani R. et al. Differential response of human basophil activation markers: a multiparameter flow cytometry approach // Clin. Mol. Allergy. 2008. Vol. 6. P. 12. DOI: 10.1186/1476-7961-6-12

[53] Shabanov DV, Lazarenko LL, Fedoskova TG, Rybnikova EA. Diagnostics of Hymenoptera venom allergy. Russian medical journal. 2019;27(3):40–44. (In Russ.)

[54] Шабанов Д.В., Лазаренко Л.Л., Федоскова Т.Г., Рыбникова Е.А. Особенности диагностики аллергии к яду перепончатокрылых насекомых // Российский медицинский журнал. 2019. Т. 27, № 3. С. 40–44.

[55] Sinelnikova NA, Bychkova NV, Kalinina NM. Features of immune response and basophil activation in children with chronic urticaria. Medical Immunology (Russia). 2015;17(1):39–46. (In Russ.). DOI: 10.15789/1563-0625-2015-1-39-46

[56] Синельникова Н.А., Бычкова Н.В., Калинина Н.М. Особенности иммунного ответа и активации базофилов у детей с хронической крапивницей // Медицинская иммунология. 2015. Т. 17, № 1. С. 39–46. DOI: 10.15789/1563-0625-2015-1-39-46

[57] Gernez Y, Dunn CE, Everson C, et al. Blood basophils from cystic fibrosis patients with allergic bronchopulmonary aspergillosis are primed and hyper-responsive to stimulation by aspergillus allergens. J Cyst Fibros. 2012;11(6):502–510. DOI: 10.1016/j.jcf.2012.04.008

[58] Gernez Y., Dunn C.E., Everson C. et al. Blood basophils from cystic fibrosis patients with allergic bronchopulmonary aspergillosis are primed and hyper-responsive to stimulation by aspergillus allergens // J. Cyst. Fibros. 2012. Vol. 11, No. 6. P. 502–510. DOI: 10.1016/j.jcf.2012.04.008

[59] Gernez Y, Waters J, Mirković B, et al. Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis. Eur Respir J. 2016;47(1):177–185. DOI: 10.1183/13993003.01068-2015

[60] Gernez Y., Waters J., Mirković B. et al. Blood basophil activation is a reliable biomarker of allergic bronchopulmonary aspergillosis in cystic fibrosis // Eur. Respir. J. 2016. Vol. 47, No. 1. P. 177–185. DOI: 10.1183/13993003.01068-2015

[61] Mircovic B, Lavelle GM, Azim AA, et al. The basophil surface marker CD203C identifies Aspergillus species sensitization in patients with cystic fibrosis. J Allergy Clin Immunol. 2016;137(2):436–443. DOI: 10.1016/j.jaci.2015.07.045

[62] Mircovic B., Lavelle G.M., Azim A.A. et al. The basophil surface marker CD203C identifies Aspergillus species sensitization in patients with cystic fibrosis // J. Allergy Clin. Immunol. 2016. Vol. 137, No. 2. P. 436–443. DOI: 10.1016/j.jaci.2015.07.045

RIGHTS & PERMISSIONS

Kozlova Y.I., Uchevatkina A.E., Filippova L.V., Aak O.V., Kuznetsov V.D., Frolova E.V., Vasilyeva N.V., Klimko N.N.