Preview

Medical Immunology (Russia)

Advanced search

DIAGNOSTIC MARKERS OF ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS IN PATIENTS WITH BRONCHIAL ASTHMA

https://doi.org/10.15789/1563-0625-2018-4-561-570

Abstract

Studies of probable significance of different immunological mediators for the development of chronic allergic inflammation in patients with allergic bronchopulmonary aspergillosis (ABPA) are necessary in order to specify potential targets for therapeutic intervention and timely diagnosis of the disease. The purpose of present study was to determine the features of immune response regulation, and to identify diagnostic markers associated with development of ABPA in patients with bronchial asthma, and to evaluate clinical and immunological efficacy of specific antimycotic therapy.

The study involved 13 patients with ABPA, 14 patients with bronchial asthma with fungal sensitization (BAFS), 17 patients with bronchial asthma (BA) and 12 apparently healthy individuals. Levels of thymic stromal lymphopoietin (TSLP), thymus and activation-regulated chemokine (TARC), IL-8, as well as levels of total IgE and specific IgE to Aspergillus fumigatus (A. fumigatus) were measured in blood serum by enzyme immunoassay; blood eosinophil counts were also made. Monitoring of these immunological markers in the course of antimycotic therapy was carried out.

Significantly higher numbers of eosinophils, increased levels of total IgE and sIgE for A. fumigatus, as well as TARC and IL-8 in serum were revealed in patients with ABPA when compared to the patients with BA. No significant differences in TSLP content were found between the examined groups of patients. A positive correlation between the levels of sIgE to A. fumigatus and contents of TARC and IL-8, numbers of eosinophils, and total IgE levels confirms the important diagnostic value of proinflammatory cytokines in ABPA patients. In the course of itraconazole medication, a positive clinical and immunological dynamics in ABPA patients was revealed. After 12 weeks of therapy, a significant increase in AST, FEV1 and Tiffno respiratory indexes, along with decreased number of eosinophils, total IgE levels, and a trend towards a decrease in TARC and IL-8 levels were documented. This dynamics confirms clinical efficiency of antifungal drugs when treating chronic allergic inflammation in ABPA patients.

Implementation of modern immunological biomarkers, alongside with traditional indicators, will allow to differentially evaluate a probability for ABLA development in patients with bronchial asthma, to present additional evidence for discerning early stages of the disease, and to conclude about the efficiency of the therapy applied.

About the Authors

Ya. I. Kozlova
North-Western State I.I. Mechnikov Medical University
Russian Federation

PhD (Medicine), Associate Professor, Department of Clinical Mycology, Allergy and Immunology,

194291, St. Petersburg, St. Jago de Cuba str., 1/28



E. V. Frolova
North-Western State I.I. Mechnikov Medical University
Russian Federation

PhD (Medicine), Head, Research Laboratory of Immunology and Allergology, Kashkin Research Institute of Medical Mycology,

St. Petersburg



L. V. Filippova
North-Western State I.I. Mechnikov Medical University
Russian Federation

PhD (Medicine), Senior Research Associate, Research Laboratory of Immunology and Allergology, Kashkin Research Institute of Medical Mycology,

St. Petersburg



A. E. Uchevatkina
North-Western State I.I. Mechnikov Medical University
Russian Federation

PhD (Medicine), Senior Research Associate, Research Laboratory of Immunology and Allergology, Kashkin Research Institute of Medical Mycology,

St. Petersburg



O. V. Aak
North-Western State I.I. Mechnikov Medical University
Russian Federation

PhD (Chemistry), Leading Research Associate, Research Laboratory of Immunology and Allergology, Kashkin Research Institute of Medical Mycology,

St. Petersburg



G. I. Solovyeva
North-Western State I.I. Mechnikov Medical University
Russian Federation


N. N. Klimko
North-Western State I.I. Mechnikov Medical University
Russian Federation


References

1. Климко Н.Н., Козлова Я.И., Хостелиди С.Н., Шадривова О.В., Борзова Ю.В., Васильева Н.В. Распространенность тяжелых и хронических микотических заболеваний в Российской Федерации по модели LIFE program // Проблемы медицинской микологии, 2014. № 1. С. 3-8. [Klimko N.N., Kozlova Ya.I., Khostelidi S.N., Shadrivova О.V., Borzova Yu.V., Vasilyeva N.V. The prevalence of serious and chronic fungal diseases in Russian Federation on LIFE program model. Problemy meditsinskoy mikologii = Problems in Medical Mycology, 2014, no. 1, pp. 3-8. (In Russ.)]

2. Козлова Я.И., Соболев А.В., Фролова Е.В., Аак О.В., Бурыгина Е.В., Климко Н.Н. Аллергический бронхолегочный аспергиллез у больных бронхиальной астмой // Российский аллергологический журнал, 2015. № 2. С. 37-46. [Kozlova Ya.I., Sobolev A.V., Frolova E.V., Aak O.V., Burygina E.V., Klimko N.N. Allergic bronchopulmonar aspergillosis in asthmatic patients. Rossiyskiy allergologicheskiy zhurnal = Russian Allergology Journal, 2015, no. 2, pp. 37-46. (In Russ.)].

3. Agarwal R. Severe asthma with fungal sensitization. Curr. Allergy Asthma Rep., 2011, Vol. 11, no. 5, pp. 403-413.

4. Agarwal R.A., Chakrabarti A., Shah D., Gupta D., Meis J.F., Guleria R., Moss R., Denning D.W. For the ABPA complicating asthma ISHAM working group 2013. Allergic bronchopulmonary aspergillosis: review of literature and proposal of new diagnostic and classification criteria. Clinical and Experimental Allergy, 2013, Vol. 43, no. 8, pp. 850-873.

5. Becerra-Díaz M., Wills-Karp M., Heller N.M. New perspectives on the regulation of type II inflammation in asthma. F1000Res, 2017, Vol. 6, p. 1014.

6. Carsin A., Romain T., Ranque S., Reynaud-Gaubert M., Dubus J.-C., Mège J.-L., Vitte J. Aspergillus fumigatus in cystic fibrosis: An update on immune interactions and molecular diagnostics in allergic bronchopulmonary aspergillosis. Allergy, 2017, Vol. 72, no. 11, pp. 1632-1642.

7. Chai R., Liu B., Qi F. IL-31, IL-33, and TSLP expression and relation to severity of asthma and rhinitis in Chinese allergic patients. Int. J. Clin. Exp. Pathol., 2017, Vol. 10, no. 2, pp. 1774-1782.

8. Chaudhary N., Marr K.A. Impact of Aspergillus fumigatus in allergic airway diseases. Clin. Transl. Allergy, 2011, Vol. 1, no. 1, p. 4.

9. Chauhan A., Singh M., Agarwal A., Paul N. Correlation of TSLP, IL-33, and CD4+CD25+FOXP3+T regulatory in pediatric asthma. J. Asthma, 2015, Vol. 52, no. 9, pp. 868-872.

10. Denning D.W., Pashley C., Hartl D., Wardlaw A., Godet C., Del Giacco S., Delhaes L., Sergejeva S. Fungal allergy in asthma-state of the art and research needs. Clin. Transl. Allergy, 2014, Vol. 15, no. 4, p. 14.

11. Gibson P.G., Wark P.A., Simpson J.L., Meldrum C., Meldrum S., Saltos N., Boyle M. Induced sputum IL-8 gene expression, neutrophil influx and MMP-9 in allergic bronchopulmonary aspergillosis. Eur. Respir. J., 2003, Vol. 21, pp. 582-588.

12. Goh K.J., Yii A.C.A., Lapperre T.S., Chan A.K., Chew F.T., Chotirmall S.H., Koh M.S. Sensitization to Aspergillus species is associated with frequent exacerbations in severe asthma. J. Asthma Allergy, 2017, Vol. 21, no. 10, pp. 131-140.

13. Hartl D., Latzin P., Zissel G., Krane M., Krauss-Etschmann S., Griese M. Chemokines indicate allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Am. J. Respir. Crit. Care Med., 2006, Vol. 173, no. 12, pp. 1370-1376.

14. Hogan C., Denning D.W. Allergic bronchopulmonary aspergillosis and related allergic syndromes. Semin. Respir. Crit. Care Med., 2011, Vol. 32, no. 6, pp. 682-692.

15. Kennedy J.L., Steinke J.W., Liu L., Negri J., Borish L., Payne S.C. Failure of itraconazole to prevent T-helper type 2 cell immune deviation: Implications for chronic rhinosinusitis. Am. J. Rhinol. Allergy, 2016, Vol. 30, no. 6, pp. 379-384.

16. Latzin P., Hartl D., Regamey N., Frey U., Schoeni M.H., Casaulta C. Comparison of serum markers for allergicbronchopulmonary aspergillosis in cystic fibrosis. Eur. Respir. J., 2008, Vol. 31, pp. 36-42.

17. Margalit A., Kavanagh K. The innate immune response to Aspergillus fumigatus at the alveolar surface. FEMS Microbiol. Rev., 2015, Vol. 39, no. 5, pp. 670-687.

18. Masaki K., Fukunaga K., Matsusaka M., Kabata H., Tanosaki T., Mochimaru T., Kamatani T., Ohtsuka K., Baba R., Ueda S., Suzuki Y., Sakamaki F., Oyamada Y., Inoue T., Oguma T., Sayama K., Koh H., Nakamura M., Umeda A., Kamei K., Izuhara K., Asano K., Betsuyaku T. Characteristics of severe asthma with fungal sensitization. Ann Allergy Asthma Immunol., 2017, Vol. 119, no. 3, pp. 253-257.

19. McAllister F., Henry A., Kreindler J.L., Dubin P.J., Ulrich L., Steele C., Finder J.D., Pilewski J.M., Carreno B.M., Goldman S.J., Pirhonen J., Kolls J.K. Role of IL-17A, IL-17F, and the IL-17 receptor in regulating growth-related oncogene-alpha and granulocyte colony-stimulating factor in bronchial epithelium: implications for airway inflammation in cystic fibrosis. J. Immunol., 2005, Vol. 175, no. 1, pp. 404-412.

20. Murdock B.J., Shreiner A.B., McDonald R.A., Osterholzer J.J., White E.S., Toews G.B., Huffnagle G.B. Coevolution of Th1, Th 2, and Th 17 responses during repeated pulmonary exposure to Aspergillus fumigatus conidia. Infect. Immun., 2011, Vol. 79, no. 1, pp. 125-135.

21. Porter P., Susarla S.C., Polikepahad S., Qian Y., Hampton J., Kiss A., Vaidya S., Sur S., Ongeri V., Yang T., Delclos G.L., Abramson S., Kheradmand F., Corry D.B. Link between allergic asthma and airway mucosal infection suggested by proteinase-secreting household fungi. Mucosal Immunol., 2009, Vol. 2, no. 6, pp. 504-517.

22. Shah A., Paniabi C. Allergic bronchopulmonary aspergillosis: a perplexing clinical entity. Allergy Asthma Immunology Res., 2016, Vol. 8, no. 4, pp. 282-297.

23. Wang Y.H., Liu Y.J. Thymic stromal lymphopoietin, OX40-ligand, and interleukin-25 in allergic responses. Clin. Exp. Allergy, 2009, Vol. 39, no. 6, pp. 798-806.

24. Wark P.A., Hensley M.J., Saltos N., Boyle M.J., Toneguzzi R.C., Epid G.D., Simpson J.L., McElduff P., Gibson P.G. Anti-inflammatory effect of itraconazole in stable allergic bronchopulmonary aspergillosis: A randomized controlled trial. J. Allergy Clin. Immunol., 2003, Vol. 111, no. 5, pp. 952-257.

25. Ying S., O’Connor B., Ratoff J., Meng Q., Fang C., Cousins D., Zhang G., Gu S., Gao Z., Shamji B., Edwards M.J., Lee T.H., Corrigan C.J. Expression and cellular provenance of thymic stromal lymphopoietin and chemokines in patients with severe asthma and chronic obstructive pulmonary disease. J. Immunol., 2008, Vol. 181, no. 4, pp. 2790-2798.


Review

For citations:


Kozlova Ya.I., Frolova E.V., Filippova L.V., Uchevatkina A.E., Aak O.V., Solovyeva G.I., Klimko N.N. DIAGNOSTIC MARKERS OF ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS IN PATIENTS WITH BRONCHIAL ASTHMA. Medical Immunology (Russia). 2018;20(4):561-570. (In Russ.) https://doi.org/10.15789/1563-0625-2018-4-561-570

Views: 1375


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1563-0625 (Print)
ISSN 2313-741X (Online)