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Vol 19, No 4 (2022)

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Original studies

Efficacy and predictors of rapid response to omalizumab therapy in patients with seasonal allergic rhinitis: a cohort study

Fomina D.S., Mukhina O.A., Bobrikova E.N., Lebedkina M.S., Chernov A.A., Lysenko M.A.


BACKGROUND: The availability of anti-IgE therapy for allergic rhinitis has actualized the need to develop variants of this treatment according to predictors of rapid response and techniques of treatment initiation.

AIM: To study the efficacy and predictors of response to omalizumab in patients with seasonal allergic rhinitis.

MATERIALS AND METHODS: Patients with moderate or severe seasonal allergic rhinitis in which traditional treatment for at least 3 months was not effective in the previous pollen season or in the current season were included. The decision to prescribe omalizumab was made based on the visual analog scale (VAS) in the previous or current season. The dosage and frequency of administration (every 2 or 4 weeks) were determined according to the table of values provided in the instructions. The patients were observed for 2 months. At follow-up visits (1 and 2 months later), allergic rhinitis symptom control was assessed using VAS and total nasal symptoms score (TNSS). Therapy was considered effective when the VAS remained <30 or decreased ≥30 after 4 and 8 weeks from the start of therapy, depending on the initiation period.

RESULTS: The study enrolled 30 patients with allergic rhinitis history of 14 years, sensitization to ≥2 groups of allergens in 19 (63.3%) cases and bronchial asthma in 18 (60%). Omalizumab was initiated before the pollen season in 6 (20%) patients and during the season in 24 (80%) patients. After 4 weeks, allergic rhinitis manifestations were controlled in 23 (77%) patients, and by week 8, 100% of the patients with allergic rhinitis had fully responded to therapy. By 4 weeks of follow-up, the severity of allergic rhinitis symptoms on the VAS and TNSS scales decreased by 2.7 and 4.7 times, respectively. The proportion of patients with a slow response by week 4 of therapy was 23%. Body mass index (lower in the “slow” response group) and history of bronchial asthma (2.6 times longer in the “slow” responders) were associated with the achievement of this outcome. No adverse events were recorded.

CONCLUSIONS: In patients with seasonal allergic rhinitis, omalizumab allows the control of disease manifestations after 4 weeks of therapy with its maintenance in the follow-up. Predictors of rapid response have been revealed; however, their clinical significance requires further study.

Russian Journal of Allergy. 2022;19(4):425-434
pages 425-434 views

Anti-IL-4,13 strategy in management of comormid patients in the regional register of severe bronchial asthma

Naumova V.V., Kiseleva D.V., Beltyukov E.K., Starikova Y.R.


BACKGROUND: T2 inflammation underlies bronchial asthma and inflammatory nasal diseases, supporting the concept of a “united airway disease.” Dupilumab, by blocking interleukin-4 and -13 receptors, can improve the clinical and functional parameters and life quality of comorbid patients with T2 diseases.

AIM: To evaluate efficacy of anti-IL4R,13 therapy in patients with severe asthma with chronic inflammatory nasal diseases in real clinical practice.

MATERIALS AND METHODS: The study of dupilumab efficacy was conducted by comparing related populations based on a regional register of patients with severe asthma and concomitant chronic inflammatory nasal diseases. Asthma control achievement and decrease in the rate of patients with uncontrolled asthma were assessed as primary endpoint. The need for bronchodilators and systemic glucocorticosteroids, number of asthma exacerbations, emergency calls and hospitalizations, AQLQ scores, level of peripheral blood eosinophils, and respiratory function were also assessed. Nasal symptoms were assessed using SNOT-22 and VAS. A subgroup analysis of ACT scores was performed depending on chronic inflammatory nasal disease phenotypes.

RESULTS: Within 12 months of dupilumab therapy, ACT increased from 11 (Q1–Q3: 7–13) to 20 (Q1–Q3: 18–24) points (p <0.001). The rate of patients with partially and fully controlled asthma increased from 0 to 57.9% (p <0.001). The need for bronchodilators decreased from 17.5 doses per week (Q1–Q3: 5.8–24.5) to 1.0 (Q1–Q3: 0.0–2.2) (p <0.001). Before the dupilumab therapy, 68.5% of the patients took systemic corticosteroids and, after 12 months, 10.5% of patients (p <0.001). The number of asthma exacerbations decreased from 2.19±1.83 (95% CI 1.28–3.11) to 0.22±0.55 (0.05–0.49) (p <0.001) and hospitalizations from 1.00±1.27 (95% CI 0.37–1.63) to 0.17±0.51 (95% CI 0.09–0.42) (p <0.001). AQLQ scores increased from 2.91 (Q1–Q3: 2.43–3.86) to 5.89 points (Q1–Q3: 4.70–6.58) (p <0.001). The volume of forced exhalation in 1 sec increased from 55.38%±16.66% (95% CI 47.10–63.67) to 81.5%±19.14% (95% CI 71.98–91.02) (p <0.001). SNOT-22 scores decreased from 47±29 (95% CI 34–61) to 25±18 (95% CI 17–34) points (p <0.001) and the VAS score from 7±2 (95% CI 6–8) to 4±2 (95% CI 3–5) (p <0.001).

CONCLUSIONS: Dupilumab improved asthma and nasal symptoms control, improved quality of life and respiratory function, and reduce asthma exacerbations and hospitalizations. Patients with severe asthma and comorbid allergic rhinitis and chronic rhinosinusitis with polyps responded better to dupilumab therapy than patients with chronic rhinosinusitis without polyps.

Russian Journal of Allergy. 2022;19(4):435-446
pages 435-446 views

The role of fine suspended particles of atmospheric air in the formation of eosinophilic inflammation in T2-endotype of asthma

Skorokhodkina O.V., Khakimova M.R., Timerbulatova G.A., Bareycheva O.A., Saleeva L.Е., Sharipova R.G., Ablayeva A.V., Fatkhutdinova L.M.


BACKGROUND: Allergens induce eosinophilic inflammation in the T2 endotype of asthma. However, much less is known about the role of non-specific factors (suspended particles in the atmospheric air-PM).

AIMS: To define eosinophilic inflammation on the basis of several biomarkers in the T2 endotype of asthma exposed to PM.

MATERIALS AND METHODS: We studied 150 patients with asthma, and 61 patients with T2 endotype of asthma (ages 18–65 years) were enrolled. Group 1 included 34 patients with allergic asthma, and group 2 included 27 patients with non-allergic asthma. Moreover, 30 healthy matched controls without asthma and other allergic diseases were enrolled in the study. Clinical examination and allergy testing were performed. Additionally, serum levels of IL-33, IL-25, IL-4, IL-5, IL-13, DPP4 (multiplex assay), and periostin (ELISA) were evaluated. The analyses of the average annual concentrations (Avr) and the maximal annual concentrations (MaxAvr) of PM2.5 and PM10 in Kazan were conducted using the database of the Center for Hygiene and Epidemiology in the Republic of Tatarstan, being averaged over the period from 2014 to 2020 years in monitoring points at residential areas. Statistical analyses were performed using R version 4.0.5. The study was funded by RFBR (Project no. 19-05-50094).

RESULTS: We detected increased blood eosinophil count and IL-5 levels in patients with asthma. High levels of total IgE (p=0.0001) that correlated with IL-4 levels were observed only in patients with allergic asthma (rS=0.38; p=0.045). Moreover, elevated IL-25 levels were found in patients with allergic asthma (p=0.009). No significant differences in IL-13 levels in patient with asthma were found. The regression analysis revealed that the PM2.5Avr increase by 1 mcg/m3 increases IL-33 and IL-25 levels, but the PM10Avr increase raises the IL-25 levels only in patients with non-allergic asthma. No significant increase in IL-25 and IL-33 levels under exposure to PM2.5Avr and PM 10Avr was detected in patients with allergic asthma.

CONCLUSIONS: The results of this study indicate the pivotal role of fine suspended particles in the development and maintenance of eosinophilic inflammation in patients with non-allergic asthma.

Russian Journal of Allergy. 2022;19(4):447-459
pages 447-459 views

Age-related features of sensitization to chicken egg white in children with allergic diseases

Snovskaya M.A., Semikina E.L., Makarova S.G., Ereshko O.A., Yasakov D.S., Galimova A.A.


BACKGROUND: International studies have shown that egg allergy is one of the main causes of IgE-mediated food allergies in children.

THIS STUDY AIMED TO analyze the frequency and rate of sensitization to white egg of Russian children, depending on the sex and age.

MATERIALS AND METHODS: Anti-egg white-specific IgE antibodies were measured in children with symptoms of food allergy, such as nausea, vomiting, stool disorder developing after eating, mucosal edema, upper respiratory tract edema, urticaria, and exacerbation of eczema (4981 patients aged 6 months to 18 years). The frequency and degree of sensitization in various age groups were analyzed.

RESULTS: In this study, 29.5% of the children had anti-egg white IgE antibodies. Low (31.6%, IgE=0.35–0.69 kU/L) and moderate (40.2%, IgE=0.70–3.5 kU/L) sensitizations were the most common. An extremely high level of anti-egg white antibodies (IgE >50.0 kU/L) was observed in 6.2% of the patients. In the first year of life, sensitization was detected in 39% of the cases. In older age groups, the frequency of positive responses decreased. compared with those in the younger groups. The dependence of sensitization frequencies on sex was found in children aged >12 years. Frequencies of egg sensitization in girls aged 12–14 and 14–18 were statistically significantly lower than those in boys of the same age. The dependence of the response severity on the patient’s age was also noted: a decrease in the frequency of highly positive responses and an increase in proportion of patients with medium or low IgE levels in the older group. The severity of the IgE response decreased by age 12 and 14 years in girls and boys, respectively.

CONCLUSION: The detection frequency of specific IgE antibodies to the extract of allergens of chicken egg white was the highest in children in the first year of life. These parameters decrease in older children; аfter the age of 12, the response severity and frequency were associated with the patient’s sex. The tendency of the number of patients with chicken egg white allergen-specific IgE antibodies and their quantitative level in adolescence to decrease may be evidence of the development of tolerance to this food product.

Russian Journal of Allergy. 2022;19(4):460-471
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The role of IL-33 and IL-1β in the development of persistent allergic rhinitis in overweight/obese children

Koroleva A.E., Bekezin V.V., Sergeeva I.N., Volkova E.A., Meshkova R.Y.


BACKGROUND: Few works were devoted to the study of the role of cytokines in children with allergic rhinitis (AR) with comorbid obesity.

AIMS: To study the level of cytokines interleukin (IL)1β, IL-33, IL-6, tumor necrosis factor (TNF)-α, and total IgE in the blood serum of overweight/obese children with intermittent and persistent AR.

MATERIALS AND METHODS: This cross-sectional observational study analyzed 69 children aged 7–10 years with AR in the remission period and was conducted from November 2020 to February 2021. All children went through a comprehensive examination for 3 days, including the definition of the serum concentrations IL-1β, IL-33, IL-6, TNF-α, and total IgE. Before blood sampling, children did not use nasal glucocorticosteroids, antileukotriene drugs for the last 4 weeks, and antihistamines for the last 7 days. Bioimpedansometry was used to assess the body weight by calculating the %FM (percentage of body fat mass).

RESULTS: The study included 44 children with AR and overweight/obesity (group I) and 25 children with AR and normal body weight (group II). The analysis of AR showed that in group I, intermittent AR was detected in 11 (25.0%) children (subgroup IA), whereas a persistent course was found in 33 children (75.0%) (subgroup IB). In group II, intermittent AR was detected in 13 (52.0%) children (subgroup IIA), whereas persistent AR in 12 children (48.0%) (subgroup IIB). The level of IL-1β in the blood serum was significantly higher in the subgroup IB than in subgroup IA (p=0.009). The concentration of IL-33 in children with persistent AR and obesity was significantly lower than that in children with intermittent AR and obesity (p=0.039). The level of IL-33 in the serum negatively correlated with %FM in group IA (r=-0.6673, p=0.035). The concentration of IL-1β negatively correlated with %FM in group IIB (r=-0,738, p=0,037). The levels of IL-6, TNF, and total IgE in obese children did not depend on the severity of AR.

CONCLUSIONS: The predictors of persistent AR in children with obesity are a decrease in the level of IL-33 and an increase in IL-1β in the blood serum. The negative correlation between the degree of obesity and IL-33 concentration in children with intermittent AR opens a window of opportunity for the personified management of children with AR and comorbid obesity.

Russian Journal of Allergy. 2022;19(4):472-482
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Development and implementation in outpatient practice of an electronic computer program “Diagnostics of bronchial asthma in children”

Faizullina R.M., Samigullina N.V.


BACKGROUND: Currently, the criteria for the differential diagnosis of bronchial asthma and several respiratory diseases in children, accompanied by bronchial obstruction syndrome, remain insufficiently effective. Moreover, timely administration of anti-inflammatory therapy is important.

AIM: To develop and introduce a computer program for the timely diagnosis of asthma in children and appointment of basic therapy into outpatient practice.

MATERIALS AND METHODS: A comparative comprehensive analysis of risk factors for disease development in 155 children with bronchial asthma and 155 clinically healthy children who suffered episodes of bronchial obstruction at an early age was conducted, and a computer program that allows timely diagnosis of asthma was developed. The program was tested during the observation of 68 children with episodes of bronchial obstruction.

RESULTS: Sixty-two most significant signs (disease predictors) were established, which formed the basis of the computer program “Diagnostics of bronchial asthma in children.” The application of the program in clinical conditions showed a high consistency of the result with the conclusion of an allergist-immunologist. The sensitivity and specificity of the method were 88.2% and 94.1%, respectively (p <0.05). The program was introduced into outpatient practice.

CONCLUSION: The data obtained determine the possibility of using the proposed computer program as a tool for the timely diagnosis of bronchial asthma in children.

Russian Journal of Allergy. 2022;19(4):483-493
pages 483-493 views

Systematic reviews

Genetic risk factors of food allergy: a review of genome-wide studies

Kutas U.V., Fedorova O.S., Bragina E.Y.


BACKGROUND: Food allergy (FA) is an urgent problem for public health worldwide. This disease reduces the quality of life of patients and increases the risk of developing unpredictable anaphylactic reactions.

AIM: Conduct an analysis of genetic studies in cohorts of patients with FA aimed at assessing the role of genetic factors in the development of this pathology.

MATERIALS AND METHODS: The results of genome-wide association studies aimed at studying the influence of genetic factors in FA development. The review includes original articles published for the period from January 1, 2012 to December 31, 2021.

RESULTS: This systematic review analyzed data on the relationship of genetic variations associated with FA. Eight studies were analyzed, and the maximum effect with the development of IgE-mediated FA on peanuts was found for the rs10018666 variant of the SLC2A9 gene in Europeans. Some allergens associated with specific loci have been found, for example, variants rs9273440 (HLA-DQB1), rs115218289 (ITGA6), rs10018666 (SLC2A9), and others are unique to peanut. Associated variants are predominantly associated with disorders of the innate/adaptive immune response and functioning of the epithelial barrier, confirming their leading role in FA development. In addition to associations with FA, most of the identified genes affect the development of other “allergic march” phenotypes, including atopic dermatitis, bronchial asthma, allergic rhinitis, and non-allergic (type 2 diabetes mellitus, Parkinson’s disease, myocardial infarction, and others) diseases.

CONCLUSIONS: Summarizing the results of genome-wide associative studies, it should be noted that the development of food allergies involves variants localized both in known atopic and newly identified loci that are not related to the development of other allergic diseases. The peculiarities of the structure of food sensitization and the lack of research on the susceptibility to food allergies in Russia determine the direction of further scientific research in this area.

Russian Journal of Allergy. 2022;19(4):494-507
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Specificity of the condition of the skin barrier in patients with congenital epidermolysis bullosa as a factor of transcutaneous sensitization by food allergens

Galimova A.A., Makarova S.G., Murashkin N.N.


Congenital epidermolysis bullosa is a heterogeneous group of hereditary dermatoses resulting from a pathogenic variant of the genome-encoding proteins of the dermo-epidermal junction. Epidermolysis bullosa is mainly manifested as the formation of blisters and erosions on the skin and mucous membranes in response to minor mechanical action. Itching is one of the most common symptoms of epidermolysis bullosa, reduces the quality of life, and causes additional skin damage.

The influence of comorbid pathology, which can increase itching, is not excluded. Skin inflammation secondary to a disruption in the skin barrier, wound-healing cascades, and unregulated activation of epidermal sensitive nerve endings are involved in the pathophysiology of itching at the molecular and cellular levels. Diffuse damage to the skin and mucous membranes, leading to the loss of their barrier properties, contributes to the excessive intake of antigens, including allergens of food and non-food origin, and to transcutaneous sensitization. However, food sensitization and food allergy in these patients have not been sufficiently studied. Understanding the causes of these processes may be crucial for the development of optimized techniques for managing children with congenital epidermolysis bullosa and improvement of their quality of life.

This review summarizes updated data on clinical and genetic aspects of congenital epidermolysis bullosa.

Russian Journal of Allergy. 2022;19(4):508-518
pages 508-518 views

Case reports

The significance of component-resolved allergy diagnostics in atopic dermatitis patients when prescribing allergen-specific immunotherapy

Elisyutina O.G., Fedenko E.S., Smolnikov E.V., Litovkina A.O., Shtyrbul O.V.


The paper presents clinical cases of patients with severe atopic dermatitis with polyvalent sensitization in an adult patient and in a pediatric patient. Standard topical and systemic therapy proved to be an insufficiently effective strategy in these patients. Both patients underwent component-resolved allergy diagnostics, which made it possible to identify the causally significant components of allergens, sensitization to which affects the course of atopic dermatitis. On the basis of the survey, indications for allergen-specific immunotherapy with causally significant allergens were determined. The treatment made it possible to achieve non-drug remission not only of atopic dermatitis but also of concomitant respiratory allergic diseases.

The cases demonstrate the efficacy and safety of allergen-specific immunotherapy in patients with proven sensitization to causally significant allergens based on component allergy diagnostics.

Russian Journal of Allergy. 2022;19(4):519-533
pages 519-533 views

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