Russian Journal of AllergyRussian Journal of AllergyРоссийский Аллергологический Журнал1810-88302686-682XPublishing House ABV Press41410.36691/RJA414ArticlesСтатьиResearch ArticleFungal sensitization of patients with asthma in St. PetersburgМикогенная сенсибилизация у больных бронхиальной астмой в Санкт-ПетербургеKozlovaY IКозловаЯ Иkozlova510@mail.ruFrolovaE VФроловаЕ ВSobolevA VСоболевА ВAakO VАакО ВUchevatkinaA EУчеваткинаА ЕFilippovaL VФилипповаЛ ВBuryginaE VБурыгинаЕ ВKlimkoN NКлимкоН НNorth-Western State Medical University named after I.I. MechnikovГБОУ ВПО Северо-Западный государственный медицинский университет им. И.И. Мечникова15102015125NO5 (2015)№5 (2015)3810032020Copyright ©; 2015, Pharmarus Print MediaCopyright ©; 2015, Фармарус Принт Медиа2015Pharmarus Print MediaФармарус Принт Медиаhttps://rusalljournal.ru/raj/article/view/414

Background. Fungal sensitization is associated with severe uncontrolled asthma. Connections of specific, micromycetes and fungal allergens with disease development and immunopathogenesis of asthma with fungal sensitization are not well understood. Methods. The study included 120 patients with different grades of asthma severity. Results. Fungal sensitization was detected in 48 patients with asthma (40%). Severe course of asthma with fungal sensitization was identified in 7 patients (14,6%). The main fungal allergens in patients with severe asthma were Alternaria spp. and Aspergillus spp., in patients with mild and moderate course of disease - Aspergillus spp. and Penicillium spp. Increasing of serum total IgE and enhancing the ability of blood cells to produce IL2 and IFN-y in patients with bronchial asthma with fungal sensitization were revealed. The obtained results indicated the important role of Th1 along with Th2 cells in the development of immunopathological process in asthma patients withfungal sensitization. Conclusion. Further research is necessary for determination of clinical and immunological criteria of severe asthma with fungal sensitization and study of the effectiveness of antimycotic therapy.

Цель. Микогенная сенсибилизация ассоциирована и тяжелым неконтролируемым течением бронхиальной астмы. взаимосвязи конкретных микромицетов и грибковых аллергенов с развитием заболевания и иммунопатогенез бронхиальной астмы с микогенной сенсибилизацией в настоящее время изучены недостаточно. Материалы и методы. Обследовали 120 больных бронхиальной астмой различной степени тяжести. Результаты. Микогенную сенсибилизацию выявили у 48 (40%) из 120 пациентов. Тяжелое течение бронхиальной астмы с микогенной сенсибилизацией определили у 7 (14,6%) пациентов. Основными грибковыми аллергенами у больных бронхиальной астмой тяжелого течения были Alternaria spp. и Aspergillus spp., у больных с легким и среднетяжелым течением заболевания - Aspergillus spp. и Pénicillium spp. в результате иммунологического обследования больных бронхиальной астмой с микогенной сенсибилизацией выявлено увеличение уровня общего IgE и повышение способности клеток крови к продукции ИЛ-2 и IFN-y. Полученные результаты свидетельствуют о важной роли Th1 наряду с Th2 в развитии иммунопатологического процесса при бронхиальной астме, отягощенной микогенной сенсибилизацией. Заключение. Необходим дальнейший поиск клинико-иммунологических критериев для определения тяжелой бронхиальной астмы с микогенной сенсибилизацией и изучение эффективности антимикотической терапии.

Aspergillus sppAlternaria sppasthmafungal sensitizationAspergillus sppAlternaria sppcytokinesбронхиальная астмамикогенная сенсибилизацияцитокиныLozano R., Naghavi M., Foreman K. et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012, v. 380, p. 2095-2128.Vos T., Flaxman A.D., Naghavi M. et al. Years lived with disability (YLDs) for 1160 sequelae of 289 diseases and injuries 1990-2010: a systematic analysis for the global burden of disease study 2010. Lancet. 2012, v. 380, p. 2163-2196.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, v. 380, p. 2197-2223.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, v. 51, p. 361-370.Bush A., Zar H.J. WHO universal definition of severe asthma. Curr. Opin. Allergy Clin. Immunol. 2011, v. 11, p. 115-121.Bush R.K., Portnoy J.M., Saxon A., Terr A.I., Wood R.A. The medical effects of mold exposure. J. Allergy Clin. Immunol. 2006, v. 117, p. 326-333.Knutsen A.P., Bush R.K., Demain J.G. et al. Fungi and allergic lower respiratory tract diseases. J. Allergy Clin. Immunol. 2012, v. 129, p. 280-291.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, v. 182, p. 1362-1368.Denning D.W., Pashley C., Hartl D. et al. Fungal allergy in asthma-state of the art and research needs. Clinical and Translational Allergy. 2014, v. 4, p. 14.Ma Y.L., Zhang W.B., Yu B. et al. Prevalence of allergic bronchopulmonary aspergillosis in Chinese patients with bronchial asthma. Zhonghua Jie He He Hu Xi Za Zhi. 2011, v. 34, p. 909-913.Agarwal R.A., 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. Clinical & Experimental Allergy. 2013, v. 43, p. 850-873.Agarwal R., Gupta D., Aggarwal A.N. et al. Clinical significance of hyperattenuating mucoid impaction in allergic bronchopulmonary aspergillosis: an analysis of 155 patients. Chest. 2007, v. 132, p. 1183-1190.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, v. 179, p. 11-18.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, v. 51, p. 361-370.Климко Н.Н., Козлова Я.И., Хостелиди С.Н. и соавт. Распространенность тяжелых и хронических микотических заболеваний в Российской Федерации по модели LIFE program. Проблемы медицинской микологии. 2014, № 16, с. 3-9.Menzies D., Holmes L., McCumesky G. et al. Aspergillus sensitization is associated with airflow limitation and bronchiectasis in severe asthma. Allergy. 2011, v. 66, p. 679-685.Stern D.A., Morgan W.J., Halonen M. Wheezing and bronchial hyper-responsiveness in early childhood as predictors of newly diagnosed asthma in early adulthood: a longitudinal birth-cohort study. Lancet. 2008, v. 372, p. 1058-1064.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, v. 39, p. 1677-1683.Pashley C.H., Fairs A., Free R.C., Wardlaw A.J. DNA analysis of outdoor air reveals a high degree of fungal diversity, temporal variability, and genera not seen by spore morphology. Fungal. Biol. 2012, v. 116, p. 214-224.Knutsen A.P., Bush R.K., Demain J.G. Fungi and allergic lower respiratory tract diseases. J. Allergy Clin. Immunol. 2012, v. 129, p. 280-291.Hogan C., Denning D.W Allergic bronchopulmonary aspergillosis and related allergic syndromes. Semin. Respir. Crit. Care Med. 2011, v. 32, p. 682-692.Roilides E., Simitsopoulou M. Local innate host response and filamentous fungi in patients with cystic fibrosis. Med. Mycol. 2010, v. 48, p. 22-31.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, v. 182, p. 1362-1368.Park S.J., Mehrad B. Innate immunity to Aspergillus species. Clin. Microbiol. Rev. 2009, v. 22, p. 535-551.Agarwal R. Allergic bronchopulmonary aspergillosis: lessons learnt from genetics. Indian J. Chest. Dis. Allied. Sci. 2011, v. 53, p. 137-140.Knutsen A.P. Genetic and respiratory tract risk factors for aspergillosis. ABPA and asthma with fungal sensitization. Med. Mycol. 2006, v. 44, p. 61-70.Knutsen A.P., Kariuki B., Consolino J.D., Warrier M.R. IL-4 alpha chain receptor (IL-4Rα) polymorphisms in allergic bronchopulmonary sspergillosis. Clin. Mol. Allergy. 2006, v. 4, p. 3.Sambatakou H., Pravica V., Hutchinson I.V., Denning D.W. Cytokine profiling of pulmonary aspergillosis. Int. J. Immunogenet. 2006, v. 33, p. 297-302.Agarwal R., Khan A., Aggarwal A.N., Gupta D. Link between CFTR mutations and ABPA: a systematic review and meta-analysis. Mycoses. 2012, v. 55, p. 357-365.Vicencio A.G., Chupp G.L., Tsirilakis K. et al. CHIT1 mutations: genetic risk factor for severe asthma with fungal sensitization? Pediatrics. 2010, v. 126, p. 982-985.Muro M., Mondejar-Lopez P., Moya-Quiles M.R. et al. HLA-DRB1 and HLADQB1 genes on susceptibility to and protection from allergic bronchopulmonary aspergillosis in patients with cystic fibrosis. Microbiol. Immunol. 2013, v. 57, p. 193-197.Shah A., Kala J., Sahay S., Panjabi C. Frequency of familial occurrence in 164 patients with allergic bronchopulmonary aspergillosis. Ann. Allergy Asthma Immunol. 2008, v. 101, p. 363-369.Chishimba L., Niven R.M., Cooley J., Denning D.W. Voriconazole and posaconazole improve asthma severity in allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. J. Asthma. 2012, v. 49, p. 423-433.