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Vol 18, No 4 (2021)

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Original studies

Pharmacoeconomic analysis of bronchial asthma prophylaxis in adults and children with allergic rhinitis by means of sublingual allergen-specific immunotherapy

Lemeshko V.A., Ratushnyak S.S., Gorkavenko F.V., Nazarova E.V., Ilina N.I., Omelyanovskiy V.V.

Abstract

BACKGROUND: Allergic rhinitis is the most common chronic allergic disease worldwide, and bronchial asthma (BA) is one of the most severe complications of allergic rhinitis. Clinical studies reported that sublingual allergen-specific immunotherapy can reduce the incidence of bronchial asthma in children and adults. However, allergen-specific immunotherapy is rather expensive and is not reimbursed by the state, which transfers the cost of this therapy to patients.

AIMS: To evaluate the cost-effectiveness of allergen-specific immunotherapy in children and adults with allergic rhinitis and/or allergic rhinoconjunctivitis

MATERIALS AND METHODS: The study hypothesized based on study results by Devillier P. et al. in 2019, to which the incidence of asthma was 13.7% and 17.0% in the sublingual allergen-specific immunotherapy + symptomatic therapy and the symptomatic therapy group, respectively (odds ratio: 0.776, 95% confidence interval [0.622; 0.968]). Pharmacoeconomic study based on decision tree model. Costs taken into account are the following: allergen-specific immunotherapy, symptomatic therapy, diagnostics, and routine follow-up visits due to bronchial asthma, outpatient bronchial asthma drug therapy, and hospitalization due to bronchial asthma. The modeling horizon was 5 years, including 2 years of allergen-specific immunotherapy therapy and 3 years of follow-up.

RESULTS: The cost per patient when using allergen-specific immunotherapy in combination with symptomatic therapy was 166,711.93 rubles, whereas with symptomatic therapy was 101,700.35 rubles. The cost-effectiveness ratio for allergen-specific immunotherapy in combination with symptomatic therapy was 193,177.20 rubles per 1 prevented case of asthma, whereas 122,530.55 rubles for symptomatic therapy for 1 prevented case of bronchial asthma. Thus, the cost of 1 averted bronchial asthma case when using allergen-specific immunotherapy in combination with symptomatic therapy is 57.7% higher than with symptomatic therapy. The cost-benefit analysis result revealed that the incremental cost-utility ratio for an additional year of life adjusted for its quality when performing sublingual allergen-specific immunotherapy in combination with symptomatic therapy compared with symptomatic therapy alone in children and adults was 567,365.48 rubles, which is less than the calculated willingness to pay threshold (RUB 2,248,898.50).

CONCLUSIONS: The comparison results of the cost of 1 added quality adjusted life years and willingness to pay threshold concluded that sublingual allergen-specific immunotherapy in combination with symptomatic therapy compared to symptomatic therapy alone is potentially cost-effective in children and adults with allergic rhinitis.

Russian Journal of Allergy. 2021;18(4):5-17
pages 5-17 views

Plant pollination calendar of the Southern Сoast of Crimea and elimination therapy at the resort

Belyaeva S.N., Pirogova M.E., Govorun M.I.

Abstract

BACKGROUND: Plant pollen can influence the climatotherapy and elimination therapy results of respiratory allergic diseases. Flora diversity and the poorly studied prevalence and etiology of pollinosis on the Southern Coast of Crimea determine the need for aeropalinological studies of this region to optimize the treatment and rehabilitation of patients with respiratory sensitization.

AIMS: To determine the potentially unfavorable periods for the stay of patients with pollen sensitization on the Southern Coast of the Crimea and develop a plant pollination calendar of the Yalta resort

MATERIALS AND METHODS: The research was conducted in the coastal and foothill area of Yalta in 2011–2013. The study determined the content of pollen in plants that are passively deposited from the air onto the glasses-traps using the gravimetric method. The taxonomic belonging of the pollen was established by collecting the plant pollen of the Southern Coast of Crimea.

RESULTS: A total of 19 pollen taxa have been identified in the air of Yalta, of which 10 had sensitizing properties. Cypress (49.7% of pollen of the average annual amount) and most deciduous trees with allergenic pollen (4.7% of pollen) were intensively pollinated in March–April, Poaceae grasses (1.6% of pollen) in May, and weed grasses (1.6% of pollen) in late August to early September. Birch and alder pollen was not detected. On average, 2.2 times less pollen was detected in the coastal area air of the resort than in the foothill area. The plant pollination calendar of the Yalta resort has been developed.

CONCLUSIONS: The intensive cypress pollination period in March–April is least favorable for patients with pollen sensitization to stay on the Southern Coast of the Crimea. Poaceae in May and weeds in late August to early September create an insignificant pollen load. A plant pollination calendar has been developed to predict unfavorable aeropalinological periods and optimize the treatment and rehabilitation of patients with pollen sensitization in the Yalta resort. The best conditions for the treatment and rehabilitation of patients with respiratory allergies have been identified in the coastal area of the resort. The absence of birch and alder pollen in the air contributes to the elimination therapy at the Yalta resort.

Russian Journal of Allergy. 2021;18(4):18-28
pages 18-28 views

Socio-demographic factors of overweight patients with bronchial asthma associated with receiving counseling on weight loss: population study data

Kashutina M.I., Zhernov Y.V., Kontsevaya A.V.

Abstract

BACKGROUND: Asthma and obesity have a close relationship: obesity is a risk factor for asthma, the link of its pathogenesis, a predictor of heavier flow and the worst control. One of the priorities of non-drug therapy of asthma is the fight against overweight. Preventive counseling allows doctors to teach patients the principles of a healthy lifestyle, including controlling body weight. There is no domestic population-based research that reflects the coverage of overweight persons with asthma of the counseling on weight loss in various socio-demographic groups. Thus our study is actual.

AIMS: Determine socio-demographic factors of overweight patients with bronchial asthma living in Russian urban areas associated with receiving counseling on weight loss.

MATERIALS AND METHODS: This study was based on a cross-sectional population-based study “Know Your Heart” (2015–2018, Arkhangelsk, Novosibirsk, n=4504). For this research, we selected overweight patients with asthma (n=167). We applied the CHAID (Chi-Squared Automatic Interaction Detection) decision tree to identify socio-demographic factors associated with receiving weight loss counseling. CHAID method allows for the automated classification of the sample and the detection of relationships between the predictors and the analyzed outcome.

RESULTS: The probability of obtaining counseling on weight loss increased by 1.39 times among retired women with obesity compared with the coverage level of counseling in the studied sample as a whole (61.7%). Among the men, the probability of obtaining counseling on weight loss increased 1.27 times in the presence of obesity. Reducing the likelihood of getting counseling both among women (1.39 times compared with the general indicator) and among men (2.2 times compared with the general indicator) was noted if their weight corresponded to the category of the excess body (BMI 25.0–29.9).

CONCLUSION: 61.7% of the overweight urban population of two regions of Russia with asthma received counseling on weight loss. Groups of overweight patients with asthma, which are statistically significantly less often obtaining counseling on weight loss: persons with BMI 25.0–29.9, regardless of gender, and non-retired women with BMI ≥30.0. The decision tree developed by us will allow allergists-immunologists and doctors of related specialities to be wary of patients from the population groups identified in the study where the activity of conducting preventive counseling is reduced. In turn, this will increase the coverage of preventive counseling for patients with bronchial asthma and, as a result, will contribute to improving asthma control.

Russian Journal of Allergy. 2021;18(4):29-39
pages 29-39 views

Clinical practice guidelines

Asthma

Chuchalin A.G., Avdeev S.N., Aisanov Z.R., Belevskiy A.S., Vasilyeva O.S., Geppe N.A., Ignatova G.L., Kniajeskaia N.P., Malakhov A.B., Meshcheryakova N.N., Nenasheva N.M., Fassakhov R.S., Khaitov R.M., Ilina N.I., Kurbacheva O.M., Astafyeva N.G., Demko I.V., Fomina D.S., Namazova-Baranova L.S., Baranov A.A., Vishneva E.A., Novik G. ., Bobkov A.P., Francuzevica L.Y.

Abstract

Asthma is one of the most common respiratory tract diseases (approximately 7% of adults and 10% of adolescents and children suffer from asthma in the Russian Federation). The occurrence frequency of asthma does not depend on sex or age in the population. The number of patients with asthma worldwide increased annually. The majority of patients with asthma respond well to conventional therapies and successful disease control, but 20%–30% of patients have severe phenotypes of asthma resisting known medicines, therefore they rarely achieve asthma control. Patients with severe asthma frequently need hospitalizations (up to 30%) and intensive care (4%–7%).

The clinical asthma guideline aimed to optimize patient care, up-to-date information about the epidemiology, and disease etiology and pathogenesis. Herein, presented the actual data about asthma classification, its clinical signs, modern diagnostics (clinical, laboratory, and instrumental), and differential diagnostics of asthma. Studies reported asthma treatment, rehabilitation, and prevention in the guideline. The authors describe in detail the existing healthcare options for patients with asthma, diasgnostics features, and care in partial groups of population (adolescents, pregnant or nursing women, and persons with occupational, exercise-induced, or severe phenotype asthma).

The clinical guidelines are recommended for medical doctors (independently from qualification), under- and postgraduate students, universities tutors, residents, and researchers.

Russian Journal of Allergy. 2021;18(4):40-106
pages 40-106 views

Reviews

Altered skin microbiome: The most important symptom of atopic dermatitis

Tamrazova O.B., Glukhova E.A., Tamrazova A.V., Dubovets N.F.

Abstract

The progressively increased incidence of atopic dermatitis among children and increased persistence in adulthood, combined with an inevitably decreased quality of life of patients, determine the relevance of studying the development mechanisms of this disease not only for dermatology but also for the entire health care system. Thus, the prerequisites for the emergence of new pathogenetic concepts and the search for the most effective therapeutic modalities arise. Currently, atopic dermatitis is considered as the interaction of endogenous (impaired immune response and insufficient epidermal barrier function) and exogenous (exposure to allergens, chemical or physical irritants, and microorganisms) factors.

Environmental factors, such as temperature and humidity, genetic makeup, antibiotic use, and good hygiene, play a critical role in skin microbiome maintenance and stability. Normally, the skin microbiota is mainly formed by bacteria of the genus Staphylococcus, Propionibacterium, Corynebacterium, and Streptococcus. In 70% of patients with atopic dermatitis, colonization of Staphylococcus aureus is observed on the affected skin, whereas on the unaffected skin in 39%, which secondarily contributes to the development of immune imbalance and increased skin xerosis. This fact determines the importance of basic therapy, which, on one hand, helps to strengthen the epidermal barrier, and on the other, normalizes the microbiome of the skin, thereby reducing the colonization of Staphylococcus aureus.

The normal skin microbiome suppresses the activity of immune-inflammatory responses and regulates pH, lipid synthesis, and transepidermal water loss. Thus, skin microbiome normalization is the key to successful therapy and long-term remission of atopic dermatitis.

Russian Journal of Allergy. 2021;18(4):107-115
pages 107-115 views

Active tolerance development in allergy to cow-based milk proteins

Galimova A.A., Vyazankina S.S., Makarova S.G., Ereshko O.A.

Abstract

Food allergy is a potentially life-threatening condition without approved pathogenetic treatments other than eliminating the causal allergen and relief of acute allergic conditions. Immunoglobulin G-mediated form of food allergy remains a serious and growing problem worldwide. Its prevalence is steadily increasing and is a severe psychosocial and economic burden for patients and their families. Cow-based milk and products are important components of a child’s diet, which are introduced at their first year of life, which can cause allergic reactions. The traditional management of children with cow-based milk allergy includes eliminating the dairy-free diet, and a significant number of patients form milk protein tolerance by the age of 5 years. However, with persistent forms of allergy to cow-based milk proteins, the need for “active” tactics of patient management to form tolerance arises. Oral immunotherapy is a promising approach to food allergy treatments based on a gradually increased allergen by analogy with standardized immunotherapy for respiratory allergens until reaching a maintenance dose. Each stage of oral immunotherapy should be considered as a personalized therapy.

This review contains an analysis of available studies on the effectiveness of oral immunotherapy in the treatment of cow-based milk protein allergy.

Russian Journal of Allergy. 2021;18(4):116-125
pages 116-125 views

Short communications

Treatment forms of house dust mites allergens intended for allergen-specific immunological therapy

Berzhets V.M., Vasilyeva A.V., Petrova N.S., Khlgatian S.V., Petrova S.Y., Emelyanova O.Y., Nesterenko L.N.

Abstract

BACKGROUND: The growth of allergic diseases dictates the necessity to develop new forms of therapeutic allergens since therapy with native water-salt extracts of allergens is unsafe and convenient. The risk of systemic side effects during allergen-specific immunotherapy sets the task for researchers to create modern therapeutic forms of allergens with high immunogenic and low allergenic activity. Our laboratory has been developing preparations for the diagnosis and treatment of house dust mites allergies for many years.

AIMS: To create modern therapeutic forms of allergen preparations from house dust mites of the genus Dermatophagoides that are intended for allergen-specific immunotherapy

MATERIALS AND METHODS: Physicochemical and immunobiological methods, such as electrophoresis in polyacrylamide gel, micropoint immunoblot, solid-phase enzyme-linked immunosorbent assay, and the reaction of binding inhibition of allergen-specific immunoglobulin E in the sera of patients were used to study the obtained preparations.

RESULTS: A technology has been developed to obtain a granular dosage form of a mixed allergen from Dermatophagoides pteronyssinus and Dermatophagoides farinae mites for sublingual use. This treatment form has successfully passed preclinical tests, has a pronounced immunogenic activity, and reduced allergenicity, and is convenient for pediatric practice. Allergoids, which are chemically modified preparations, are obtained to reduce allergenicity and increase therapeutic allergen immunogenicity. A succinylated monomeric house dust mites allergoid Dermatophagoides pteronyssinus was created and studied with the National Research Center, Institute of Immunology Federal Medical-Biological Agency of Russia. The study of the immunobiological properties of the obtained preparation showed that the monomeric allergoid has increased immunogenic and decreased allergenic activity contrary to the native water-salt extract.

CONCLUSIONS: The created forms of mite allergens can be used to treat patients who are sensitized to house dust mites of the genus Dermatophagoides after clinical trials.

Russian Journal of Allergy. 2021;18(4):126-134
pages 126-134 views

Case reports

Experience of anti-Immunoglobulin E-therapy in children with chronic inducible urticaria

Larkova I.A., Revyakina V.A.

Abstract

Based on clinical cases, the authors present their own experience of successful anti-Immunoglobulin E-therapy using omalizumab at 300 mg every 4 weeks with clinical manifestations of chronic inducible urticaria in children, such as cholinergic urticaria and cold urticaria, which was observed without chronic spontaneous urticaria symptoms. Concurrently, the patient with cold urticaria had a complete response after the first injection, with a total course of treatment of 6 months, whereas the patient with cholinergic urticaria did not immediately receive therapy and needed a 12-month course of treatment with strict administration regimen adherence for 4 weeks. All patients have achieved sustained disease remission.

Russian Journal of Allergy. 2021;18(4):135-139
pages 135-139 views

Clinical characteristics of chronic spontaneous urticaria in patients with Common variable immune deficiency and hypogammaglobulinemia

Latysheva T.V., Latysheva E.A., Danilycheva I.V., Frolov E.A.

Abstract

Chronic spontaneous urticaria is a prevalent disease that is associated with various autoimmune, infectious (viral, bacterial, parasitic), and non-infectious inflammatory pathologies, and could occur in the symptom complex of other diseases, such as primary immunodeficiencies. Nowadays, data on the features of chronic spontaneous urticaria in patients with primary immunodeficiencies are accumulating. Common variable immune deficiency takes a special place in clinical practice among primary immunodeficiencies with impaired antibody synthesis and is associated with late-onset in adulthood, as well as the heterogeneity of its clinical manifestations, such as infectious and non-infectious complications, which can serve as a background for chronic urticaria development. Intravenous Immunoglobulin (IVIg) replacement therapy is the mainstay of treatment and prevention of infectious complications in these patients; however, immunomodulatory and anti-inflammatory effects can occur in high doses.

Herein, presented two clinical cases of patients with common variable immune deficiency and one with hypogammaglobulinemia who suffer from chronic spontaneous urticaria. The peculiarities of IVIg replacement therapy at urticaria were noted in these patients. The discussion presents the review of world literature and proposes key features for further investigations.

Russian Journal of Allergy. 2021;18(4):140-148
pages 140-148 views

Chronic spontaneous urticaria or urticarial vasculitis?

Dorofeeva I.V., Danilycheva I.V., Shuljenko A.E.

Abstract

Chronic spontaneous urticaria is the spontaneous appearance of blisters, angioedema, or both for >6 weeks that affects up to 0.5%–5% of the population, mainly females. Spontaneous wheals and/or angioedema, severe skin itching that leads to depression and anxiety, sleep disturbances, sexual dysfunction, and activity of daily life and work restrictions. Other diseases sometimes occur under the guise of chronic spontaneous urticaria.

Urticarial vasculitis is a vasculitis of the small skin vessels, characterized by the duration of persistent skin rashes in combination with histopathological features of leukocytoclastic vasculitis. Differential diagnosis of chronic spontaneous urticaria and urticarial vasculitis is conducted in the case of an atypical clinical picture of urticaria. Wheals lasted for >24 h, often accompanied by burning and pain, and leaving behind purpura or residual hyperpigmentation.

Herein, described a case of urticarial vasculitis in a patient that required a differential diagnosis of chronic spontaneous urticaria and urticarial vasculitis several years after the disease onset. Successful treatment was conducted with a combination of antihistamines, glucocorticosteroids, hydroxychloroquine, and omalizumab.

Russian Journal of Allergy. 2021;18(4):149-155
pages 149-155 views

Book reviews

Publication of the 4th edition of “Immunology” by academician of the Russian Academy of Sciences Rakhim M. Khaitov

Gushchin I.S.

Abstract

A landmark event for specialists in immunology and specialties related to immunology took place this year. A fourth edition of the textbook, “Immunology,” has been published by the famous Russian immunologist and academician of the Russian Academy of Sciences, Rakhim Musaevich Khaitov. Compared to the previous edition issued in 2018, this version is a substantially updated and revised version, replenished with information obtained during this relatively short period by world immunology, one of the most rapidly developing areas of scientific knowledge. With all the complexity of modern immunology, this training manual has achieved a perfect form, consistent, and accessible presentation of the material following the latest international data. Attention is drawn to the appropriate placement of perfectly done illustrations that explain the text material and create liveliness, interest, and accessibility to its development. Special attention should be paid since the reader is fully prepared for easier perception of special clinic-oriented information, particularly, on allergies in the chapter, “Allergic diseases,” which was presented following the principles of evidence-based medicine, modern international and national guidelines, and consensus documents after getting acquainted with the deeply and easily presented material on the structure and function of the immune system.

Undoubtedly, the textbook will be an irreplaceable guide for students and teachers of medical and biological educational institutions, researchers, and doctors of various specialties interested in immunology and allergology.

Russian Journal of Allergy. 2021;18(4):156-159
pages 156-159 views

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