Asthma Remission Research Articles

A single infusion of engineered long-lived and multifunctional T cells confers durable remission of asthma in mice.

Asthma, the most prevalent respiratory disease, affects more than 300 million people and causes more than 250,000 deaths annually. Type 2-high asthma is characterized by interleukin (IL)-5-driven eosinophilia, along with airway inflammation and remodeling caused by IL-4 and IL-13. Here we utilize IL-5 as the targeting domain and deplete BCOR and ZC3H12A to engineer long-lived chimeric antigen receptor (CAR) T cells that can eradicate eosinophils. We call these cells immortal-like and functional IL-5 CAR T cells (5TIF) cells. 5TIF cells were further modified to secrete an IL-4 mutein that blocks IL-4 and IL-13 signaling, designated as 5TIF4 cells. In asthma models, a single infusion of 5TIF4 cells in fully immunocompetent mice, without any conditioning regimen, led to sustained repression of lung inflammation and alleviation of asthmatic symptoms. These data show that asthma, a common chronic disease, can be pushed into long-term remission with a single dose of long-lived CAR T cells.

Exploring Definitions and Predictors of Severe Asthma Clinical Remission after Biologic Treatment in Adults.

Rationale: There is no consensus on criteria to include in an asthma remission definition in real life. Factors associated with achieving remission after biologic initiation remain poorly understood. Objectives: To quantify the proportion of adults with severe asthma achieving multidomain-defined remission after biologic initiation and identify prebiologic characteristics associated with achieving remission that may be used to predict it. Methods: This was a longitudinal cohort study using data from 23 countries from the International Severe Asthma Registry. Four asthma outcome domains were assessed in the 1 year before and after biologic initiation. A priori-defined remission cutoffs were: 0 exacerbations/yr, no long-term oral corticosteroid (LTOCS), partly/well-controlled asthma, and percent predicted FEV1 ⩾ 80%. Remission was defined using two (exacerbations + LTOCS), three (+control or +lung function), and four of these domains. The association between prebiologic characteristics and postbiologic remission was assessed by multivariable analysis. Measurements and Main Results: A total of 50.2%, 33.5%, 25.8%, and 20.3% of patients met criteria for two-, three- (+control), three- (+lung function), and four-domain remission, respectively. The odds of achieving four-domain remission decreased by 15% for every additional 10 years of asthma duration (odds ratio, 0.85; 95% confidence interval, 0.73-1.00). The odds of remission increased in those with fewer exacerbations per year, lower LTOCS daily dose, better control, and better lung function before biologic initiation. Conclusions: One in five patients achieved four-domain remission within 1 year of biologic initiation. Patients with less severe impairment and shorter asthma duration at initiation had a greater chance of achieving remission after biologic treatment, indicating that biologic treatment should not be delayed if remission is the goal.

Clinical remission in severe asthma: lights and shadows on an ambitious goal.

The aim of this study was Describe the latest evidence related to the concept of clinical remission in patients with severe asthma, focusing on the lights and shadows of this concept. The idea of clinical remission in severe asthma patients brings about a significant shift in the way asthma is treated and managed. Although there has yet to be unanimous agreement among various scientific societies on the precise definition, this concept can be extremely useful in advancing the treatment of the disease. Asthma is a common respiratory condition that affects more than 300 million people globally. It has variable symptoms and severity levels, with about 10% of patients experiencing severe asthma. While there have been advancements in treatment, severe asthma poses significant challenges. Recent approaches have focused on achieving clinical remission, which goes beyond symptom control to address underlying inflammation and biological processes. Clinical remission criteria include the absence of symptoms, reduced medication usage, and normalized inflammatory markers. Various biologic therapies show promise, with some patients achieving remission. However, remission's definition varies globally, hindering standardization and a valid comparison. Standardizing remission criteria and refining predictive factors are crucial for effective asthma management. Overall, achieving clinical remission offers hope for improved long-term outcomes in severe asthma patients.

Аcupuncture as a means of rehabilitation for people with bronchial asthma

The article considers the possibility of using acupuncture as a means of acupuncture in the rehabilitation of adolescents with bronchial asthma. It is noted that bronchial asthma remains one of the dangerous diseases that cause significant mortality among children and adults. The purpose of the study was to study the effect of acupuncture on the state of the function of external breathing during respiratory rehabilitation among people with bronchial asthma in remission. Research methods: analysis of scientific and methodical literature; analysis of outpatient charts of patients, surveys, traditional and calculation methods of determining the main indicators of the external respiratory system, methods of mathematical statistics. It has been shown that adolescents with bronchial asthma have a decrease in external respiratory function indicators. In adolescents with bronchial asthma, there is a decrease in the indicators of the function of external breathing. The deviation of the actual indicators from the appropriate ones was: LVEF – 27%, FLVEF – 38%, FEV1 – 44%, Ntype – 33%, respectively; Tiffno index – 79%, Tweed – 23 p. The expansion of the motor regime and the use of acupuncture reflexology during the remission period contributed to the increase in the indicators of the function of external breathing in the main group compared to the control group: LVEF by 10.47% and 2.36%, LVEF – 13.32% and 1.96%, FEV1 – 19 ,24% and 7.14%, Ntype – 13.72% and 5.34%, IT – 3.7% and 0.17%, Tweed – 11.58% and 5.89%, respectively.
 The use of needle reflexology as a means of acupuncture in respiratory rehabilitation and timely correction of the motor regime will improve bronchial patency, improve the functioning of the respiratory system of the body, increase the work capacity of the younger generation, will contribute to reducing the severity of the disease, limiting the use of drug therapy, and longer remission.

The CORE syndrome: an overlap of severe asthma, obstructive sleep apnea, rhinosinusitis, and esophageal reflux.

Asthma, obstructive sleep apnea (OSA), rhinosinusitis, and esophageal reflux are conditions that may overlap, forming a syndrome known as CORE. Whenever clinical remission of severe asthma (SA) is not achieved, it is essential to investigate the presence of comorbidities, in particular the presence of OSA that may lead to the diagnosis of CORE syndrome. The study was conducted on naive patients with SA and concomitant rhinosinusitis and esophageal reflux, referred to our institute since 2018. Patients who did not experience clinical remission were investigated for OSA through a home sleep apnea test. Subsequently, for those diagnosed with OSA, continuous positive airway pressure (CPAP) was proposed and was re-evaluated after 12months. Six patients with CORE syndrome were enrolled. The mean apnea-hypopnea index (AHI) was 33.25 ± 20.13 events/h, oxygen desaturation index (ODI) was 28.95 ± 19.95 events/h, and time in bed with SaO2 < 90% (T90) was 26.40 ± 27.22% for which continuous positive airway pressure (CPAP) treatment was proposed but only 3 out of 6 patients accepted. After 12months, all CPAP-treated patients manifested a significant reduction in daytime sleepiness (ESS score was 6.33 ± 3.8), an improvement in ACT score (+ 8 (+ 32%), + 9 (+ 36%), and + 14 (+ 56%) points), a discontinuation of oral corticosteroids (OCS), an absence of exacerbations, and an improvement of lung function leading to clinical remission of asthma. Whenever facing SA patients, non-responders to therapy, it is important to suspect the presence of CORE syndrome; in particular, the detection and subsequent treatment of OSA would seem to improve the outcome of such patients.

Diagnosis and therapy of patients with asthma in Germany. Results of the care study RELEVANT

Diagnostic and therapeutic options for asthma have improved with asthma control and remission being of central importance. The RELEVANT study aimed for a nationwide snapshot of current asthma diagnosis and treatment in general practice and specialty care for identification of further aspects for optimization. RELEVANT is a nationwide cross-sectional study using a structured questionnaire. This comprised 14 questions on asthma-related topics covering diagnostics and therapy. Participants were general practitioners/internal medicine specialists and pulmonologists. A total of 1,558 persons took part in the survey. Regarding relevant specific diagnostic procedures for asthma, GPs/internists almost exclusively mentioned pulse oximetry. Among the pulmonologists, fractional exhaled nitric oxide (FeNO) measurement was mentioned, among others. FeNO and blood eosinophils were only mentioned by the pulmonologists as diagnostic and treatment-relevant markers. A total of more than 60% of the GPs/internists surveyed stated that only around 25% or fewer of their patients would voluntarily report restrictions in their everyday lives. Regarding drug treatment, the majority stated that they recognized differences between various ICS/LABA combination therapies. The results indicate a need for optimization, particularly regarding asthma control. This involves both a better assessment by patients' everyday life restrictions and modern ways of assessing asthma control in cooperation between GPs/internal medicine specialists and pulmonologists. One fifth of respondents do not see any differences between various ICS/LABA combinations in daily practice, although there are pharmacodynamic and pharmacokinetic differences.

Real-world clinical remission of severe asthma with benralizumab in Spanish adults with severe asthma

Objective Patients with severe eosinophilic asthma experience high risk of exacerbations and reduced quality of life. Benralizumab, a monoclonal antibody binding to IL-5 receptor α subunit, is an approved drug for its treatment. The objective was to describe clinical remission after benralizumab prescription in routine clinical practice. Methods Retrospective multicenter study with data from four hospitals in Valencian Community (Spain) with asthma units between 2019 and 2020. Data was gathered at baseline and after 12 months. We considered clinical remission after 1 year if the patient remained without exacerbations and use of systemic corticosteroids and with good clinical control and normal lung function. Results Data from 139 patients was gathered. At the 12-month follow-up, 44.1% were in clinical remission, since 84.0%, 77.5%, 51.0% and 95.5% of patients did not experience exacerbations, had total asthma control test score of ≥20, prebronchodilator FEV1 of ≥80% and did not use systemic corticosteroids. A significant reduction of long-acting muscarinic antagonists (p = 0.0001), leukotriene receptor antagonists (p = 0.0326), oral corticosteroids (p < 0.0001) and short-acting beta agonists (p = 0.0499) was observed. Baseline factors with greatest individual influence on clinical remission were employment situation, tobacco use, comorbidity number, eosinophil value, number of exacerbations, FEV1, emergency visit number, and ACT, MiniAQLQ and TAI scores. Final analysis of multiple logistic regression indicated that having baseline FEV1 value below 80% increases remission chance 9.7 times a year compared to FEV1 >80%. Conclusion Clinical remission after treatment with benralizumab is achievable in a high percentage of patients with severe asthma eosinophilia not controlled in real life.

Update on asthma 2024 - what the ENT specialist needs to know

The lifetime prevalence of 8.6% of asthma in Germany reflects the high medical and socioeconomic impact of the disease. Asthma treatment goals have changed during the last decades: from symptom control to symptom prevention, with highly effective, disease-modifying anti-asthmatic drugs (DMAADs) aiming at asthma remission. In order to achieve this goal, phenotyping of patients (including an evaluation of allergies and type 2 biomarkers) is crucial for personalized treatment. The identification and effective treatment of concomitant diseases, such as allergic rhinitis or chronic rhinosinusitis with nasal polyps (CRSwNP), plays a major role for successful treatment. This underlines the importance of interdisciplinary collaboration of otolaryngologists and respiratory physicians in the management of patients with asthma. This CME article informs the reader about current guidelines on the diagnosis and treatment of asthma, focusing on clinically relevant recommendations for ENT physicians.

Effect of Azithromycin on Asthma Remission in Adults With Persistent Uncontrolled Asthma: A Secondary Analysis of a Randomized, Double-Anonymized, Placebo-Controlled Trial

BackgroundAsthma remission is a potential treatment goal. Research questionDoes adding azithromycin to standard therapy in patients with persistent uncontrolled asthma induce remission compared to placebo? Study Design and MethodsThis secondary analysis used data from the AMAZES clinical trial – a double-blind placebo-controlled trial that evaluated the safety and efficacy of azithromycin on asthma exacerbations. The primary remission definition (referred to as clinical remission) was zero exacerbations and zero oral corticosteroids (OCS) during the previous six months evaluated at 12 months and Asthma Control Questionnaire (ACQ-5) ≤1 at 12 months. Secondary remission definitions included clinical remission plus lung function criteria (post-bronchodilator FEV1≥80% or post-bronchodilator FEV1≤5% decline from baseline) and complete remission (sputum eosinophils<3% plus the above criteria). Sensitivity analyses explored the robustness of primary and secondary remission definitions. The predictors of clinical remission were identified. Results335 participants (41.5% male; median [Q1, Q3] age 61.01 [51.03, 68.73] years) who completed the 12-month treatment period were included in the analysis. Twelve months treatment with azithromycin induced asthma remission in a subgroup of patients, and a significantly higher proportion in the azithromycin arm achieved both clinical remission (50.6% vs 38.9%; p=0.032) and clinical remission plus lung function criteria (50.8% vs 37.1%; p=0.029) compared with placebo. In addition, a higher proportion of the azithromycin group achieved complete remission (23% vs 13.7%; p=0.058). Sensitivity analyses supported these findings. Baseline factors such as better asthma-related quality of life and absence of OCS burst in the previous year predicted the odds of achieving clinical remission. Azithromycin induced remission in both eosinophilic and noneosinophilic asthma. InterpretationAdults with persistent symptomatic asthma achieved a higher remission rate when treated with azithromycin. Remission on treatment may be an achievable treatment target in moderate/severe asthma, and future studies should consider remission as an outcome measure.

Precision medicine in the diagnosis and treatment of asthma

Due to the availability of disease-modifying anti-asthmatic drugs (DMAADs), especially inhaled steroids (alone or in combination with long-acting bronchodilators), biologics and modern allergen immunotherapy, the treatment of asthma has fundamentally changed. The aims of modern asthma precision medicine are prevention of symptoms and the induction and maintenance of asthma remission (long-term asthma control, freedom from exacerbations and stable lung function without the use of systemic steroids). A treat to target approach is used as for other chronic inflammatory diseases in internal medicine: the aim is to achieve remission by an individually tailored treatment with DMAADs; however, the prerequisite for modern asthma precision medicine is asthma phenotyping, including a detailed medical history, lung function testing, allergological diagnostics and measurement of type 2 markers (blood eosinophils and, if available, exhaled nitric oxide, FeNO).

Targeting Asthma Remission as the Next Therapeutic Step Toward Improving Disease Control

The long-term goal of asthma management is to achieve disease control, comprised of the assessment of two main domains: 1) symptom control and 2) future risk of adverse outcomes. Decades of progress in asthma management have correlated with increasingly ambitious disease control targets. Moreover, introduction of precision medicines, such as biologics, has further expanded the limits of what can be achieved in terms of disease control. It is now believed that clinical remission, a term rarely associated with asthma, may be an achievable treatment goal. An expert framework published in 2020 took the first step towards developing a commonly accepted definition of clinical remission in asthma. However, there remains widespread discussion about the clinical parameters and thresholds that should be included in a standardized definition of clinical remission. This review aims to discuss on-treatment clinical remission as an aspirational outcome in asthma management, drawing on experiences from other chronic diseases where remission has long been a goal. We also highlight the integral role of shared decision-making between patients and healthcare professionals and the need for a common understanding of the individual patient journey to remission as foundational elements in reducing disease burden and improving outcomes for patients with asthma.

A real-world analysis of key asthma remission components in patients treated with benralizumab: the ZEPHYR-4 study

A real-world analysis of key asthma remission components in patients treated with benralizumab: the ZEPHYR-4 study

When sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic questions the role of eosinophils in mediating the clinical expression of the disease: a case report

BackgroundThe advent of biologics has resulted in major progress in the treatment of severe T2 high asthmatics. There are currently several classes of biologics approved for severe asthma including anti-immunoglobulin E, anti-interleukin-5/interleukin 5R, anti-interleukin 4/interleukin 13R, and anti-thymic stromal lymphopoietin.Case presentationsHere we report the case of a 55-year-old Caucasian man with severe eosinophilic atopic asthma, who sequentially benefited from a treatment with mepolizumab, an anti-interleukin-5 monoclonal antibody, followed by treatment with dupilumab, an anti-interleukin-4/interleukin-13R antibody, the switch being justified by a flare-up of dermatitis while on mepolizumab. Overall, the patient has been followed for 72 months, including 42 months on mepolizumab and 30 months on dupilumab. Close monitoring of exacerbations, asthma control, lung function, asthma quality of life, and biomarkers shows that both biologics reduced asthma exacerbation and provided an improvement in asthma control and quality of life, with the patient achieving remission after 30 months on dupilumab. However, the effects of the two biologics on the biomarkers were very different, with mepolizumab controlling eosinophilic inflammation and dupilumab reducing serum immunoglobulin E and fractional exhaled nitric oxide levels.ConclusionThe originality of this case resides in the description of clinical status and biomarker evolution after a sequential use of mepolizumab and dupilumab in a severe atopic eosinophilic asthmatic. It shows that mepolizumab reduces exacerbation and improves asthma control by curbing eosinophilic inflammation whereas dupilumab provides asthma remission without controlling airway eosinophilic inflammation.

Asthma therapy concepts through the ages.

The development and approval of DMAADs ("disease-modifying anti-asthmatic drugs"), in particular inhaled steroids (alone or in combination with long-acting bronchodilators), biologics and modern allergen immunotherapies, has fundamentally changed the asthma therapy concept from symptom control to symptom prevention. This concept is linked to the new asthma treatment goal of asthma remission: long-term absence of symptoms (good asthma control), absence of exacerbations, and stable lung function, without the use of systemic steroids for asthma therapy. Three types of asthma remission are distinguished: spontaneous remission (e.g., childhood asthma), remission "off treatment" (e.g., after successful allergen immunotherapy), and remission "on treatment" (e.g., during inhaled therapy or biologic therapy). A treat-to-target approach is used, as in rheumatoid arthritis or chronic inflammatory bowel disease: The goal is to achieve asthma remission, through individually tailored treatment with highly effective drugs with minimal side effects. However, this requires precise phenotyping of the patient, including detailed history taking, pulmonary function diagnostics, allergological diagnostics, and measurement of type 2 biomarkers.

Rhizoma Dioscoreae Nipponicae Relieves Asthma by Inducing the Ferroptosis of Eosinophils and Inhibiting the p38 MAPK Signaling Pathway.

Rhizoma Dioscoreae Nipponicae (RDN) is a traditional Chinese medicine that widely applied in the treatment of human diseases. This study aims to explore the therapeutic potential of RDN in asthma and the underlying mechanisms. A mouse model of asthma was established by the stimulation of ovalbumin (OVA). HE staining was performed to detect the pathological injuries of tracheal tissues. The protein expression of collagen I, FN1, α-SMA (airway remodeling markers), and p-p38 (a marker of the p38 MAPK pathway) were detected by Western blot. Eosinophils were then isolated from the model mice. Cell viability and ROS level were measured by CCK-8 and Flow cytometry, respectively. The mRNA expression of GPX4 and ACSL4 (ferroptosis markers) in eosinophils were measured by qRT-PCR. RDN significantly reduced the numbers of total cells and eosnophils in bronchoalveolar lavage fluid (BALF), inhibited inflammatory cell infiltration, and down-regulated remodeling markers (Collagen I, FN1, and α-SMA) in OVA-induced mice. The p38 MAPK pathway was blocked by the intervention of RDN in the model mice, and its blocking weakens the poor manifestations of OVA-induced asthma. In addition, RDN induced the ferroptosis of eosnophils both in vitro and in vivo. Blocking of the p38 MAPK pathway also enhanced the ferroptosis of eosnophils in vitro, evidenced by the decreased cell viability and GPX4 expression, and increased ROS level and ACSL4 expression. RDN induced the ferroptosis of eosinophils through inhibiting the p38 MAPK pathway, contributing to the remission of asthma.

Investigating Forkhead Box O Transcription Factor 1 Gene's Relation to Immunoglobulin E in House Dust Mite-Allergic Asthma Patients.

House dust mite (HDM)-allergic asthma is an abnormal immune response to extrinsic aeroallergens found in human vicinities. Studying the role of the associated immunity biomarkers and their interplay helps in discovering novel therapeutic strategies that can be used in adjunct with effective long-term immunotherapy. This study investigates the total serum IgE, FoxO1, and Sirtuin 1 (SIRT1) gene expressions in HDM-allergic asthma patients. We enrolled 40 patients for each of the following three groups: an HV group of healthy volunteers and HDM/AA and HDM/SCIT groups of HDM-allergic asthma patients who did not and who did receive immunotherapy before recruitment in this study, respectively. The results elucidated that total IgE was strikingly elevated in the HDM/AA group and showed little decline in the HDM/SCIT group. Both FoxO1 and SIRT1 gene expressions showed the highest levels in the HDM/SCIT group. There was a negative correlation between total IgE and both FoxO1 and SIRT1 in the HDM/AA group while there was a positive correlation with SIRT1 in the HDM/SCIT group. In conclusion, the interplay of the three immunity biomarkers related to HDM-allergic asthma after the course of immunotherapy treatment suggests further, broader studies on the feasibility of their role as immunity biomarkers in the control and remission of HDM-allergic asthma.

Direct comparative study of the effectiveness of mepolizumab and dupilumab in patients with severe non-allergic eosinophilic asthma

Introduction. Biologics for severe asthma (SA) treatment are widely used in real clinical practice. But there are very few direct comparative studies at the moment.Aim. To compare mepolizumab and dupilumab effectiveness in patients with non-allergic eosinophilic SA in real clinical practice using regional register of Sverdlovsk region.Materials and methods. The data of patients with non-allergic eosinophilic SA treated with dupilumab (n = 23) and mepolizumab (n = 19) were analyzed. Therapy effectiveness was determined according to BARS and patients’ proportion who achieved asthma remission, dynamics of ACT, AQLQ, FEV1, blood eosinophils, frequency of short-acting bronchodilators use and systemic glucocorticosteroids (SGCS) demand, frequency of asthma exacerbations and hospitalizations.Results. Within 12 months of targeted therapy a good response to biologics according to BARS in 77.8% of patients on dupilumab and in 82.4% of patients on mepolizumab (p = 1.000) was revealed. Remission of SA (without FEV1) was achieved in 62.5% of patients in dupilumab group and in 68.8% of patients in mepolizumab group (p = 1.000). Remission of SA (with FEV1) was achieved in 43.8% of patients on dupilumab and in 56.2% of patients on mepolizumab (p = 0.724). There were statistically significant improvements for all separately analyzed indicators in each observation group. Statistically significant differences after a year of therapy between groups were recorded in terms of eosinophil levels (p &lt; 0.001) and nasal symptoms assessed using the SNOT-22 questionnaire (p = 0.048) in favour of mepolizumab.Conclusions. Patients with non-allergic eosinophilic SA have good response to both dupilumab and mepolizumab. The drugs equally improve disease control, life quality, reduce the need for relievers and SGCS, show a similar safety level.

Investigating the T regulatory cells and Sirtuin-I serum level in immunotherapy treated house dust mite allergic asthma patients

Objectives House dust mite aeroallergens are predominant triggers of frequent asthma attacks among adults and children. The intensity of asthma and immune reaction necessitates treatment alternatives based on adjusting chosen immunity biomarkers to control the exacerbation of symptoms and establish long-term immune tolerance. In this study, we selected CD4+CD25+Foxp3+ regulatory T cells (Tregs), FOXP3, and Sirtuin-1 as they are known to have a potential role in the immune reaction in different allergic diseases. We investigated their interplay during HDM allergic asthma and its respective immunotherapy. Methods Eighty-four subjects were divided into 3 groups; healthy controls (CT), HDM asthma patients without immunotherapy (WOIT), and HDM asthma patients treated with subcutaneous immunotherapy for 6 months before recruitment (WIT). They were enrolled according to the pulmonary function, skin prick tests, and HDM-specific IgE. CD4+ CD25+ and CD4+ CD25+ FOXP3+hi T cells Cell percentages, FOXP3 gene expression, and Sirtuin-1 (Sirt1) serum level were analyzed. Results We found that there is a significant difference between WOIT and WIT groups in the CD4+ CD25+ and CD4+ CD25+ FOXP3+hi T cell percentages. While there is no statistically significant difference between WOIT and WIT groups in FOXP3 level. On the controversy, the SIRT1 level in the CT group (4.53 ± 3.880) significantly decreased in the WOIT and WIT groups. Conclusion This study revealed that both CD4 CD25 and CD4 CD25 high FOXP3 cell percentages increased in the WIT group and declined in the WOIT group. While, FOXP3 gene expression increased in both groups. In addition, the Sirt1 serum level showed some improvement in WIT group after a serious drop in the WOIT group comparing with the CT group. The modulation of these biomarkers for the remission and control of allergic asthma can be a prognostic outcome of immunotherapy which needs to be confirmed by larger scale studies.

Clinical remission in severe asthma with biologic therapy: an analysis from the UK Severe Asthma Registry.

Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort. This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline. 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria. 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required.

Study of association of the polymorphism rs1799883 of the &lt;i&gt;FABP2&lt;/i&gt; gene in children with bronchial asthma associated with obesity

Introduction. Currently, there is a separate phenotype “bronchial asthma – obesity”, manifested by a more severe course of the disease, low rates of achieving asthma control, resistance to basic therapy. Asthma, like obesity, is recognized as a classic example of multifactorial diseases, which are based on a rather complex gene network. The active search for genetic markers characterizing individual characteristics of human metabolism continues. Of particular interest are the genes involved in the regulation of fat and carbohydrate metabolism.Aim. Analysis of associations of polymorphic loci Ala54Thr (G163A) of the FABP2 gene with bronchial asthma of varying severity and control of asthma in children.Materials and methods. 161 children with bronchial asthma in remission were examined by a continuous sampling method, of which 59 patients with obesity of 1-3 degrees without concomitant endocrine pathology. The examination included general clinical, functional, and instrumental methods. The level of asthma control was determined according to the GINA criteria (2018). The biochemical study was carried out on an automatic analyzer SAPPHIRE 400 (Japan). The study of gene polymorphisms was carried out by real-time polymerase chain reaction using sets of “Metabolism” (Research and Production Company “Litekh”, Moscow) on the CFX-96 Biorat device (USA).Results. We have not identified associations of the presence of polymorphic loci of the FABP2 gene with obesity. It was determined that in children with bronchial asthma, the frequency of carrying the homozygous genotype Thr/Thr and the minor allele Thr increased by 1.5 times compared to the control group (OR 9.043; 95%CI [2,093–39,073], p=0.0011 and OR 2.946; 95%CI [1,698‒5,111], p=0.001, respectively), and in children with bronchial asthma with and without asthma control, the carriage of the homozygous Thr/Thr genotype and the rare A allele increased the risk of uncontrolled bronchial asthma (OR 2.42; 95%CI [1.23‒4.79], p=0.03 and OR 1.75; 95%CI [1,119‒2,736], p=0.01), the frequency of the homozygous Ala/Ala genotype and the frequent Ala allele was detected 1.5 times more often in children with bronchial asthma associated with obesity (OR 2.176; 95%CI [1.001‒4.727], p=0.0008 and OR 2.378; 95%CI [1.495‒3.780], p=0.0002, respectively).Conclusion. Although we have not identified associations of the presence of polymorphic loci of the FABP2 gene with obesity, it has been shown that children with Ala54Thr+Thr54Тhr genotypes have significantly higher glucose levels (4.9±0.06 mmol/L compared with carriers of the Ala54Ala genotype 4.0±0.06 mmol/L, p&lt;0.001), cholesterol (4.8±0.4 mmol/L compared with carriers of the Ala54Ala genotype 3.93±0.1 mmol/L, p&lt;0.05) and low density lipoproteins (2.55±0.09 mmol/L compared with carriers of the Ala54Ala genotype 2.26±0.1 mmol/L, p&lt;0.05). There is an obvious need for further investigation of the effect of gene polymorphism on the indicators of carbohydrate and lipid metabolism, depending on the nature of diets. These issues require further study as part of the search for probable cause-and-effect relationships and the creation of personalized programs depending on polymorphic gene variants.