Immunological characteristics of airway inflammation in asthma patients with sensitization to various fungal allergens are not well understood, and the search for new markers is necessary to establish future targets for targeted therapy. The purpose of our study was to assess the levels of eosinophilic inflammation markers of the respiratory tract in patients with severe asthma and allergic bronchopulmonary aspergillosis, depending on the spectrum of fungal sensitization. The study included 31 patients with severe asthma with fungal sensitization and 29 patients with allergic bronchopulmonary aspergillosis (ABPA). The levels of total, specific IgE to fungal allergens and periostin in blood serum were determined by enzyme immunoassay. The study of basophil activation was performed by flow cytometry. The patients with severe asthma and sensitization to Aspergillus spp. and Alternaria spp. had significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp. in the basophil activation test when compared with the group of asthma patients with sensitization to Aspergillus spp. only. In patients with ABPA with combined sensitization, we have found significantly higher levels of eosinophils, periostin, and stimulation index to Alternaria spp. The finding of pronounced eosinophilic type of inflammation in patients with asthma and combined sensitization to thermotolerant and thermolabile fungi may result from aggressive effect of fungal allergens on the barrier functions of bronchial epithelium, which should be taken into account when choosing therapeutic strategy and administration of immunobiological therapy.

Introduction. Allergy to microscopic fungi (micromycetes), which can colonize the respiratory tract, is associated with an eosinophilic endotype of inflammation and severe disease course. Among the hallmarks of fungal allergy, experts identify fixed airways obstruction, bronchiectasis, and fibrosis. Currently, there has been proposed the term “allergic fungal airways disease” (AFAD), which combines various clinical phenotypes, which pathogenesis is based on IgE-mediated allergic reaction against fungal spores colonizing the respiratory tract. According to this approach, the AFAD group includes severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis (ABPA). A promising direction in AFAD treatment implies the use of genetically engineered biological drugs against T-2 inflammation. The aim of the study was to evaluate the prevalence ofAspergillusspp. sensitization and allergic bronchopulmonaryAspergillosis in patients with asthma. Materials and methods. A retrospective single-center registry study was conducted in the I.I. Mechnikov North-Western State Medical University, Ministry of Health of Russian Federation. The study included 523 patients with asthma of varying severity. The level of total and specific blood serum IgE against aeroallergens, includingAspergillusspp., was analyzed by enzyme immunoassay. The diagnosis of asthma was established in accordance with the recommendations of the GINA working group and the Clinical recommendations of the Ministry of Health of the Russian Federation, fungal sensitization and ABPA — in accordance with the recommendations of the ISHAM working group.Results. During the examination of patients with asthma, sensitization toAspergillusspp. recorded in 16.6% cases, severe asthma with sensitization toAspergillusspp. — in 7.4%, ABPA — in 6.1%. In patients with allergic asthma, the prevalence of sensitization toAspergillusspp. was 22%, severe asthma with sensitization toAspergillusspp. — 10.1%, ABLA — 8.1%. Among patients with ABPA, females (64%) aged 40 years and older prevailed. The major clinical manifestations of ABPA were presented as cough (96%) and shortness of breath (76%), CT scan radiological changes were in a form of bronchiectasis (72%). Conclusion. A high prevalence of sensitization toAspergillusspp. in patients with asthma was found. It is necessary to includeAspergillusspp. into the list of tested allergens while examining patients with chronic lung diseases for timely detection of AFAD and prescription of proper anti-inflammatory or antimycotic therapy.

Introduction. Aspergillus fumigatus is able not only to sensitize patients with atopy, but also to colonize the respiratory tract, remaining a constant source of allergens due to the small spore size and thermal tolerance. Currently, the role of micromycetes in the immunopathogenesis of asthma has been poorly studied. The objective was to evaluate the features of the immune response regulation in patients with allergic bronchopulmonary aspergillosis (ABPA) or asthma with sensitization to A. fumigatus. Materials and methods. There were enrolled 15 patients with ABPA, 10 patients with asthma with sensitization to A. fumigatus, 16 patients with asthma without sensitization to A. fumigatus. The control group consisted of 16 apparently healthy volunteers. All patients underwent a clinical and functional examination. The subpopulations of blood lymphocytes were assessed by flow cytometry. The A. fumigatus allergen was added to peripheral blood samples to evaluate the production of IFN, IL-10 and IL-13. The serum cytokine levels in cell culture supernatants, as well as total IgE, A. fumigatus-specific IgE (sIgE) as well as thymus and activation-regulated chemokine (TARC) level were measured by enzyme-linked immunosorbent assay. Results. Significantly higher serum levels of total IgE, A. fumigatus-specific sIgE and TARC were found in patients with ABPA and asthma with sensitization to A. fumigatus compared to patients with asthma without sensitization to A. fumigatus. The results of lymphocyte immunophenotyping revealed significant excess of memory Th2 cells and T-regulatory cells in all patients with asthma compared to the control group. The count of Tfh2 was higher but memory Th17.1 cells were lower in patients with sensitization to A. fumigatus compared to those of apparently healthy volunteers. Patients with ABPA had significantly higher count of memory Th2 cells and TARC level compared to patients with asthma sensitized to A. fumigatus. The increased activity of memory Th2 cells is confirmed by increased secretion of IL-13 and IL-10 following along with decreased IFN production in response to specific fungal allergen stimulation of blood cells compared to the patients with asthma and the control group. A positive correlation was revealed between the count of memory Th2 cells and the levels of sIgE, IgE, TARC, a negative correlation with FEV1. Conclusion. Thus, exposure to A. fumigatus significantly enhances the activity of memory Th2 cells in patients with asthma which can lead to severe disease course and development of allergic bronchopulmonary aspergillosis. The features of the immune response identified dictate a need for a personalized approach to choose therapeutic tactics in such patients.

Background. To estimate the frequency of fungal sensitization and allergic bronchopulmonary aspergillosis in patients with asthma or cystic fibrosis. Methods. The study included 205 patients with asthma and 190 patients with cystic fibrosis. For detection of fungal sensitization specific IgE antibodies in the blood serum with «AllergoELISA-specific IgE» test system and biotinylated fungal allergens were determined. Mycological examination included microscopy and cultural study of respiratory biomaterials. According to the indications, a CAT scan of the chest was performed. Results. The incidence of fungal sensitization in patients with asthma was 35,6%, CI [29,1%; 42,6%], in patients with cystic fibrosis - 56,8% [49,5%; 64%]. In patients with severe asthma the main fungal allergens were Alternaria spp. (70%) and Aspergillus spp. (60%); in patients with cystic fibrosis: Candida spp. - 73%, Alternaria spp. - 34%, Aspergillus spp. - 27%. The incidence of allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma was 5,3%, in patients with cystic fibrosis - 5,7%. Conclusion Early detection of ABPA in patients with asthma and cystic fibrosis is very important as it changes the therapeutic measures of patients’ management and prevents progression of bronchiectasis and respiratory failure. Determination of specific Aspergillus spp. IgE antibodies in vitro is a necessary stage of diagnosis of ABPA in patients at risk.

The formation of fungal biofilms remains a serious medical problem.In particular, once biofilms are formed, they display high levels of resistance against most common antifungals.Candida albicans and Candida dubliniensis are closely related organisms with respect to morphology and phylogeny, but differ in their expression of virulence-associated proteins involved in adherence and biofilm development.Complement receptor 3-related protein (CR3-RP) is one of the key surface antigens expressed by many pathogenic Candida species associated with adherence and biofilm formation.The main objective of this research was to investigate the role of the polyclonal antibody (Ab) directed against antigen CR3-RP in the inhibition of biofilm formation of C. albicans and C. dubliniensis using different in vitro, ex vivo and in vivo models, and to assess a potential effect of Ab treatment on preformed biofilm of both species.Effectiveness of polyclonal antibody anti-CR3-RPAb directed against surface antigen CR3-RP in the biofilm development of Candida albicans and Candida dubliniensis

Allergic rhinitis (AR) is one of the most common diseases. Basic AR therapy includes both antihistamines of the second generation for per os administration in mild AR, and intranasal corticosteroids in the treatment of moderate AR. In clinical practice, oral antihistamines (in combination with intranasal corticosteroids) can be rationally replaced with intranasal antihistamines. Momate Rhino Advance nasal spray (a combination of azelastine hydrochloride and mometasone furoate) is promising medication when used as firstline therapy in the treatment of moderate and severe manifestations of AR

Background. To determine the frequency of allergic bronchopulmonary aspergillosis in patients with asthma and to study the dynamics of immunological parameters in patients with allergic bronchopulmonary aspergillosis during antimycotic therapy. Methods. During investigation of 176 patients with asthma the group of patients with allergic bronchopulmonary aspergillosis was isolated. Allergological (skin tests with fungal allergens, serum total IgE, specific IgE to fungal allergens), immunological (IFN-γ, IL-10) and mycological (microscopy and culture of respiratory samples) examination was performed. Computer tomography of the chest was done when indicated. Results. In patients with asthma frequency of sensitization to Aspergillus spp. was 27%, with allergic bronchopulmonary aspergillosis - 4%. The increased activity of T-helper type 2 in patients with allergic bronchopulmonary aspergillosis (n=7) was revealed. After itraconazole treatment during 24 weeks serum total IgE reduced (p=0,04), spontaneous and induced production of IFN-γ ratio was normalized. The reduction of the absolute number of eosinophils in 4 (80%) patients, decreased production of sIgE to Aspergillus spp. in 3 (60%) patients were noted. Conclusion. All patients with severe asthma needed additional allergological and mycological examination for the detection of allergic bronchopulmonary aspergillosis. Itraconazole therapy was effective, reduced fungal burden, and resulted to restoring of Th2/Th1 imbalance in patients with allergic bronchopulmonary aspergillosis.

One of the most common problems in basic treatment of allergic rhinoconjunctivitis (ARC) is concomitant viral infection. In these cases antiviral and immunomodulatory medications adding to the therapy could be useful. Recent data showed clinical efficacy of a new medication - allergoferon (recombinant human interferon α -2b + loratadine) in ARC treatment. The pharmacological action of allergoferon is achieved due to its antihistaminic, anti-itching, anti-exudative, anti-inflammatory, immunomodulatory, and antiviral properties. In this study clinical efficacy and safety of allergoferon in the treatment of allergic rhinoconjunctivitis has been shown.

Цель. Определить частоту развития аллергического бронхолегочного аспергиллеза у больных бронхиальной астмой и изучить динамику иммунологических показателей у больных аллергическим бронхолегочным аспергиллезом на фоне применения антимикотической терапии. Материалы и методы. При обследовании 176 больных бронхиальной астмой выделена группа пациентов с аллергическим бронхолегочным аспергиллезом. Проведено аллергологическое (кожные тесты с грибковыми аллергенами, уровень общего IgE, аллерген-специфических IgE к грибковым аллергенам), иммунологическое (IFN-γ, IL-10) и микологическое (микроскопия и посев респираторных биосубстратов) обследование. По показаниям выполняли компьютерную томографию органов грудной клетки. Результаты. У больных бронхиальной астмой частота сенсибилизации к Aspergillus spp. составила 27%, аллергического бронхолегочного аспергиллеза - 4%. Установлена повышенная активность T-хелперов 2-го типа у больных аллергическим бронхолегочным аспергиллезом (n=7). После применения итраконазола в течение 24 нед снизился уровень общего IgE (p=0,04), нормализовалось соотношение спонтанной и индуцированной продукции IFN-γ. Отмечено снижение абсолютного числа эозинофилов у 4 (80%) пациентов, ослабление продукции аллерген-специфического IgE к Aspergillus spp. у 3 (60%) больных. Заключение. Всем больным тяжелой бронхиальной астмой показано дополнительное аллергологическое и микологическое обследование для выявления аллергического бронхолегочного аспергиллеза. Применение итраконазола с целью снижения грибковой нагрузки и восстановления Th2/Th1-дисбаланиа эффективно у больных аллергическим бронхолегочным аспергиллезом.

Allergic bronchopulmonary aspergillosis (ABPA) is a caused by hypersensitivity to Aspergillus spp. antigens, is the lung disease, which occurs in patients with asthma or cystic fibrosis and is characterized by poor control of background disease and development of respiratory failure. According to experts opinion the number of patients with ABPA is about four million people in the world and 175 000 persons in Russian Federation. The clinical course improvement, prevention of progression and prophylaxis of bronchiectasis depend on timely and correct diagnosis of the disease. International Society of Human and Animal Mycology (ISHAM) formed a working group «ABPA in patients with asthma» for worldwide collaboration with physicians and researchers. The working group proposed new diagnostic criteria. This report presents a clinical case of ABPA in asthmatic patient. The diagnosis is established according criteria proposed by R. Agarwal et al., 2013.

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.

Recovering from bacterial infections in the first years of life reduces further risk of allergic diseases. Effects of bacterial immunomodulator Broncho Vaxom on immune system to certain extent repeats the immune response that occurs during penetration of the pathogen in the body. Bacterial antigens orchestrate cellular and humoral immune responses, stimulate innate immunity, normalize cytokine balance, and are promising in the treatment of respiratory allergic diseases.

Background. To identify differences in sensitization to widespread allergens in patients with common allergic diseases: allergic rhinitis, bronchial asthma, angioedema, allergic urticaria and atopic dermatitis. Materials and methods. Determination of sIgE in serum using commercial and domestic reagent kits («AllergoI-FA-specific IgE» and biotinylated allergens of «Alcor Bio», St. Petersburg) was conducted in patients with allergic rhinitis, bronchial asthma, angioedema, allergic urticaria and atopic dermatitis. Results. There was a significant similarity between the spectrum of sensitization in patients with allergic rhinitis and asthma In atopic dermatitis patients the increasing of frequency of food and especially mold sensitization was estimated. The high degree of correlation between the moulds, plants and food allergens in atopic dermatitis was observed. Conclusion. The results obtained in the study can be interesting for physicians in allergological examination and for the researchers to identify new cross-reactive allergens.

Background. Determination of prevalence of allergic rhinitis in patients with an allergy in the practice of an allergist, identification of the range of sensitization to common allergens in patients of different age groups, demonstration of the early diagnosis importance. Materials and methods. Determination of specific IgE in serum by MAST-HLA panels (36 allergens, Russian Panel IV, Hitachi Diagnostics, USA) was performed for 610 patients with rhinitis. For 269 of them a comprehensive clinical examination including cytological, bacteriological and mycological study of nasal swab was carried out. Results. Allergic rhinitis was diagnosed in 55,9% of the patients, infectious rhinitis was found in 28,7%, non-allergic rhinitis with eosinophilia syndrome is set in 6,1% of individuals. IgE to pollen was present in 53,9% of cases, to house dust— in 45,0% to house dust mites — in 29,0%, to mold allergens — in 14,5%. The frequency of children sensitization com -pared with adults to dog’s epithelium was higher by 1,4 times, the cat’s epithelium — by 1,3 times, to cockroaches — by 1,8 times, to house dust mites — by more than 2-fold, to food — by 2—3-fold. The clinical case demonstrates the importance of early diagnosis of disease. The choice of medicines for treatment was discussed. Conclusion. Given that the debut of allergic rhinitis in most of the examined patients occurred in childhood, the early examination of allergy in children is reasonable for the purpose of adequate therapy.