scholarly journals Immunologic Pathophysiology and Airway Remodeling Mechanism in Severe Asthma: Focused on IgE-Mediated Pathways

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 83
Author(s):  
Shih-Lung Cheng
Keyword(s):  
Severe Asthma ◽  
Immunoglobulin E ◽  
Airway Remodeling ◽  
Real Life ◽  
Allergic Diseases ◽  
Proinflammatory Mediators ◽  
Small Subgroup ◽  
Humanized Monoclonal Antibody ◽  
Severe Allergic Asthma ◽  
Ige Mediated

Despite the expansion of the understanding in asthma pathophysiology and the continual advances in disease management, a small subgroup of patients remains partially controlled or refractory to standard treatments. Upon the identification of immunoglobulin E (IgE) and other inflammatory mediators, investigations and developments of targeted agents have thrived. Omalizumab is a humanized monoclonal antibody that specifically targets the circulating IgE, which in turn impedes and reduces subsequent releases of the proinflammatory mediators. In the past decade, omalizumab has been proven to be efficacious and well-tolerated in the treatment of moderate-to-severe asthma in both trials and real-life studies, most notably in reducing exacerbation rates and corticosteroid use. While growing evidence has demonstrated that omalizumab may be potentially beneficial in treating other allergic diseases, its indication remains confined to treating severe allergic asthma and chronic idiopathic urticaria. Future efforts may be bestowed on determining the optimal length of omalizumab treatment, seeking biomarkers that could better predict treatment response and as well as extending its indications.

scholarly journals Predictors of reversible airway obstruction with omalizumab in severe asthma: a real-life study

2019 ◽  
Vol 13 ◽  
pp. 175346661984127 ◽  
Author(s):  
Paolo Solidoro ◽  
Filippo Patrucco ◽  
Francesca de Blasio ◽  
Luisa Brussino ◽  
Michela Bellocchia ◽  
...  
Keyword(s):  
Airway Obstruction ◽  
Allergic Asthma ◽  
Severe Asthma ◽  
Airway Remodeling ◽  
Real Life ◽  
Forced Expiratory Volume ◽  
Life Study ◽  
Reversible Airway Obstruction ◽  
Number Of Patients ◽  
Severe Allergic Asthma

Background: Omalizumab may modulate airway remodeling in severe asthma. Using forced expiratory volume in 1 second (FEV1) as a surrogate of airway remodeling, we aimed to investigate if an omalizumab add-on in severe allergic asthma may lead to a persistent reversal of airway obstruction and to evaluate the potential biomarkers of airway obstruction reversibility. Methods: Data were collected before (T0) and after omalizumab add-on for 1 year (T1, 32 patients), 2 years (T2, 26 patients) and 4 years (T4, 13 patients). All patients had baseline FEV1 below 80 % predicted (60.5 ± 12.5 %). After omalizumab, 18 patients showed FEV1 normalization (reversible airway obstruction; RAO+) already at T1 (88.7 ± 14.9 %, p < 0.0001) that persisted up to T4 (83.2 ± 7.9, p < 0.01), while 14 patients (RAO−) had FEV1 persistently decreased, from T1 (65.2 ± 8.4%, p < 0.05) up to T4 (61.4 ± 6.2%, not significant). Both groups had significant improvement of symptoms and exacerbations after omalizumab at T1, which persisted up to T4. The comparison between pretreatment characteristics of the two groups showed that RAO+ patients, had higher values of circulating eosinophils, exhaled nitric oxide (FENO), prevalence of rhinitis and nasal polyps, need of oral corticosteroids, shorter asthma duration, higher FEV1 and response to albuterol test. The optimal cut-off points predicting FEV1 normalization after omalizumab add-on were 30.5 ppb for FENO and 305 cells/µl for eosinophils. Conclusions: This study suggests that omalizumab add-on contributes to the persistent reversal of airway obstruction in a consistent number of patients with severe allergic asthma, and this beneficial effect is predicted by elevated pretreatment FENO and circulating eosinophils.

Effectiveness and Safety Studies of Omalizumab in Children and Adolescents With Moderate-To-Severe Asthma

2021 ◽  
pp. 089719002110382
Author(s):  
Lu Cheng ◽  
Tianrui Yang ◽  
Xiang Ma ◽  
Yuling Han ◽  
Yongtai Wang
Keyword(s):  
Children And Adolescents ◽  
Allergic Asthma ◽  
Severe Asthma ◽  
Fixed Effects ◽  
Vital Capacity ◽  
Immunoglobulin E ◽  
Meta Analysis ◽  
Fixed Effects Model ◽  
Significant Difference ◽  
Severe Allergic Asthma

Background Omalizumab is currently approved for the treatment of moderate-to-severe allergic asthma in patients 6 years and older. Objective To assess the effectiveness and safety of subcutaneous omalizumab as an add-on therapy option for moderate–severe allergic asthma in patients aged 6—20 years old. Methods The studies published from July, 1970 to May, 2021 were searched from the electronic databases which followed keywords: (“anti-IgE” OR “anti-immunoglobulin E” OR “anti-IgE antibody” OR “omalizumab” OR “rhuMAb-E25” OR “Xolair”) AND “asthma” AND (“child” OR “children” OR “adolescents” OR “youth” OR “teenager” OR “kids” OR “pediatric”). Thirteen studies were pooled to determine the effectiveness and safety of omalizumab. Efficacy endpoints were evaluated using a fixed-effects model or a random-effects model depending on heterogeneity. Safety endpoints were evaluated by odds ratio. Results Thirteen studies were included. In this meta-analysis, our results showed that fractional exhaled nitric oxide and asthma control test scores were significantly improved with omalizumab treatment. Serum immunoglobulin E was also decreased in children with moderate-to-severe asthma after treatment with omalizumab. The analysis found that there was no significant difference between pre-and post-treatment in forced expiratory volume in one second/ forced vital capacity ratio, forced expiratory flow between 25 and 75% of vital capacity, or FEV1. Overall, more adverse events occurred with omalizumab compared to placebo. However, the degree was mild to moderate. Conclusion This meta-analysis indicates that omalizumab is safe and effective to treat children and adolescents with moderate-to-severe asthma.

scholarly journals IgE-Related Chronic Diseases and Anti-IgE-Based Treatments

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Arnau Navinés-Ferrer ◽  
Eva Serrano-Candelas ◽  
Gustavo-J Molina-Molina ◽  
Margarita Martín
Keyword(s):  
Allergic Asthma ◽  
Chronic Diseases ◽  
Chronic Urticaria ◽  
Inhaled Corticosteroids ◽  
Systemic Mastocytosis ◽  
Airway Remodeling ◽  
Clinical Manifestations ◽  
Allergic Diseases ◽  
Severe Allergic Asthma ◽  
Prophylactic Use

IgE is an immunoglobulin that plays a central role in acute allergic reactions and chronic inflammatory allergic diseases. The development of a drug able to neutralize this antibody represents a breakthrough in the treatment of inflammatory pathologies with a probable allergic basis. This review focuses on IgE-related chronic diseases, such as allergic asthma and chronic urticaria (CU), and on the role of the anti-IgE monoclonal antibody, omalizumab, in their treatment. We also assess the off-label use of omalizumab for other pathologies associated with IgE and report the latest findings concerning this drug and other new related drugs. To date, omalizumab has only been approved for severe allergic asthma and unresponsive chronic urticaria treatments. In allergic asthma, omalizumab has demonstrated its efficacy in reducing the dose of inhaled corticosteroids required by patients, decreasing the number of asthma exacerbations, and limiting the effect on airway remodeling. In CU, omalizumab treatment rapidly improves symptoms and in some cases achieves complete disease remission. In systemic mastocytosis, omalizumab also improves symptoms and its prophylactic use to prevent anaphylactic reactions has also been discussed. In other pathologies such as atopic dermatitis, food allergy, allergic rhinitis, nasal polyposis, and keratoconjunctivitis, omalizumab significantly improves clinical manifestations. Omalizumab acts in two ways: by sequestering free IgE and by accelerating the dissociation of the IgE-Fcεreceptor I complex.

scholarly journals Atypical Food protein-induced enterocolitis syndrome in children: Is IgE sensitization an issue longitudinally?

2021 ◽  
Vol 49 (3) ◽  
pp. 73-82
Author(s):  
Athina Papadopoulou ◽  
Theano Lagousi ◽  
Elpiniki Hatzopoulou ◽  
Paraskevi Korovessi ◽  
Stavroula Kostaridou ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Cow’S Milk ◽  
Food Protein ◽  
Cow's Milk ◽  
T Helper 2 ◽  
Term Evaluation ◽  
Ige Mediated ◽  
Trigger Mechanisms

Background: Food Protein-Induced Enterocolitis Syndrome (FPIES) is a clinically well-characterised, non-Immunoglobulin E (IgE)-mediated food allergy syndrome, yet its rare atypical presen-tation remains poorly understood.Objective: Aim of this study was to present the 10-year experience of a referral centre high-lighting the atypical FPIES cases and their long-term outcome.Methods: FPIES cases were prospectively evaluated longitudinally in respect of food outgrowth and developing other allergic diseases with or without concomitant IgE sensitisation.Results: One hundred subjects out of a total of 14,188 referrals (0.7%) were identified. At pre-sentation, 15 patients were found sensitised to the offending food. Fish was the most frequent eliciting food, followed by cow’s milk and egg. Tolerance acquisition was earlier for cow’s milk, followed by egg and fish, while found not to be protracted in atypical cases. Resolution was not achieved in half of the fish subjects during the 10-year follow-up time. Sensitisation to food was not related to infantile eczema or culprit food, but was related to sensitisation to aeroallergens. In the long-term evaluation, persistence of the FPIES or aeroallergen sensitisation was significantly associated with an increased hazard risk of developing early asthma symptoms. Conclusion: Sensitisation to food was related neither to eczema or culprit food nor to tolerance acquisition but rather to the development of allergic asthma through aeroallergen sen-sitisation. In addition to an IgE profile at an early age, FPIES persistence may also trigger mechanisms switching FPIES cases to a T-helper 2 cells immune response later in life, predis-posing to atopic respiratory symptoms; albeit further research is required.

scholarly journals Omalizumab: Clinical Use for the Management of Asthma

2012 ◽  
Vol 6 ◽  
pp. CCRPM.S7793 ◽  
Author(s):  
Neil C. Thomson ◽  
Rekha Chaudhuri
Keyword(s):  
Clinical Trials ◽  
Allergic Asthma ◽  
Inhaled Corticosteroids ◽  
Airway Remodeling ◽  
Final Report ◽  
Duration Of Treatment ◽  
Main Adverse Effect ◽  
Humanized Monoclonal Antibody ◽  
Severe Allergic Asthma ◽  
Long Acting

Omalizumab, a humanized monoclonal antibody that binds circulating IgE antibody, is a treatment option for patients with moderate to severe allergic asthma whose asthma is poorly controlled with inhaled corticosteroids and inhaled long-acting β2 agonist bronchodilators. This review considers the mechanism of action, pharmacokinetics, efficacy, safety and place in management of omalizumab in asthma and focuses particularly on key articles published over the last three years. Omalizumab reduces IgE mediated airway inflammation and its effect on airway remodeling is under investigation. Recent long-term clinical trials confirm the benefits of omalizumab in reducing exacerbations and symptoms in adults and in children with moderate to severe allergic asthma. No clinical or immunological factor consistently predicts a good therapeutic response to omalizumab in allergic asthma. In responders, the duration of treatment is unclear. The main adverse effect of omalizumab is anaphylaxis, although this occurs infrequently. Preliminary data from a five-year safety study has raised concerns about increased cardiovascular events and a final report is awaited. Clinical trials are in progress to determine whether omalizumab has efficacy in the treatment of non-allergic asthma.

Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) In Paediatric Severe Allergic Asthma – A Romanian Perspective

2021 ◽  
Author(s):  
Berghea Elena Camelia ◽  
Mihaela Balgradean ◽  
Carmen Pavelescu ◽  
Catalin Cirstoveanu ◽  
Claudia Toma ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Lung Function ◽  
Allergic Asthma ◽  
Asthma Control ◽  
Immunoglobulin E ◽  
Real Life ◽  
First Year ◽  
Severe Exacerbation ◽  
Exacerbation Rate ◽  
Severe Allergic Asthma

Background: Asthma is the most common chronic disease affecting children and altering their quality of life. The severity of asthma is often modulated by immunoglobulin E (IgE)-mediated allergen sensitization and is associated with comorbid allergic dis-eases. Omalizumab is a humanized monoclonal antibody anti-IgE, the first biological therapy approved to treat patients aged &ge;6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omali-zumab in Romanian paediatric patients with severe allergic asthma. Methods: In this observational real-life study, 12 children aged 6 to 18 years, (mean age 12.4 years ) with severe allergic asthma received Omalizumab as an add-on treatment. The levels of asthma control, exacerbations, lung function and adverse events were evaluated at baseline and after the first year of treatment. Results: We noticed general improvements in total asthma symptom scores and the rate of exacerbation of severe asthma. Omalizumab increased the initial variables of lung function, and no serious adverse reactions were reported. FEV1 improved statistically significant after one year of treatment with Omalizumab, [&Delta;FEV1 (% pred.) =18.3, and similarly, &Delta;MEF50 (%) = 25.8]. The mean severe exacerbation rates due to asthma decreased from 4.1 (2.8 SD) to 1.15 (0.78 SD) during the treatment year (p&lt;0.0001) with Omalizumab. Conclusions: Treatment with Omalizumab can be an effective and safe therapeutic option for Romanian children with severe allergic asthma, providing clinically relevant in-formation on asthma control and exacerbation rate in children and adolescents. The results highlighted the effect of Omalizumab in young patients, starting from the first year of treatment.

A new score to predict allergic march in patients with IgE‐mediated cow milk allergy

2019 ◽  
Vol 40 (3) ◽  
pp. 187-192 ◽  
Author(s):  
Francisco Gil ◽  
Mikel Mendizabal ◽  
Ana Amezqueta ◽  
Elena Aznal ◽  
Teodoro Durá ◽  
...  
Keyword(s):  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Cow Milk ◽  
Multivariate Logistic Regression Model ◽  
High Grade ◽  
Milk Allergy ◽  
Increased Risk ◽  
Cow Milk Allergy ◽  
Ige Mediated ◽  
Allergic March

Background: Cow milk allergy (CMA) is the most common food allergy in infants. Some patients will express, in the future, other allergic diseases (allergic march). Objective: To evaluate if a new scoring system could determine the risk of developing allergic march. Methods: A retrospective observational cohort study of subjects who were immunoglobulin E (IgE) mediated was conducted. We defined a risk score for atopy (RSA), including clinical and laboratory variables. Three risk groups were defined according to the RSA. We defined as dependent variables atopy (one or more allergic diseases) and atopy+ (two or more allergic diseases). A multivariate logistic regression model was created, which included RSA and the type of formula (high-grade extended hydrolyzed formula [EHF] with Lactobacillus rhamnosus GG (LGG), high-grade EHF without LGG, and other formulas). Results: A total of 211 patients were recruited. When we analyzed the risk of atopy+, we found an increased risk for RSA intermediate-risk (odds ratio [OR 2.08] [95% confidence interval {CI}, 0.95‐4.56) and high-risk (OR 24.74 [95% CI, 6.26‐97.73]) groups, and a decreased risk for the subjects fed with high-grade EHF (OR 0.42 [95% CI, 0.20‐0.87]) and also in those subjects fed with high-grade EHF plus LGG (OR 0.30 [95% CI, 0.09‐0.98]). Conclusion: RSA is a simple and useful tool to predict the risk of developing other allergic diseases in patients with IgE-mediated CMA.

scholarly journals Clinical Experience with Anti-IgE Monoclonal Antibody (Omalizumab) in Pediatric Severe Allergic Asthma—A Romanian Perspective

Children ◽  
2021 ◽  
Vol 8 (12) ◽  
pp. 1141
Author(s):  
Elena Camelia Berghea ◽  
Mihaela Balgradean ◽  
Carmen Pavelescu ◽  
Catalin Gabriel Cirstoveanu ◽  
Claudia Lucia Toma ◽  
...  
Keyword(s):  
Lung Function ◽  
Children And Adolescents ◽  
Allergic Asthma ◽  
Asthma Control ◽  
Immunoglobulin E ◽  
Real Life ◽  
First Year ◽  
Severe Exacerbation ◽  
Exacerbation Rate ◽  
Severe Allergic Asthma

Background: Asthma is the most common chronic disease affecting children, with a negative impact on their quality of life. Asthma is often associated with comorbid allergic diseases, and its severity may be modulated by immunoglobulin E (IgE)-mediated allergen sensitization. Omalizumab is a humanized monoclonal anti-IgE antibody, the first biological therapy approved to treat patients aged ≥6 years with severe allergic asthma. The primary objective of our study was to investigate the efficacy and safety of Omalizumab in Romanian children with severe allergic asthma. Methods: In this observational real-life study, 12 children and adolescents aged 6 to 18 years (mean 12.4 years) with severe allergic asthma received Omalizumab as an add-on treatment. Asthma control, exacerbations, lung function, and adverse events were evaluated at baseline and after the first year of treatment. Results: We observed general improvement in total asthma symptom scores and reduction in the rate of exacerbation of severe asthma. Omalizumab treatment was associated with improvement in the measures of lung function, and no serious adverse reactions were reported. FEV1 improved significantly after one year of treatment with Omalizumab [ΔFEV1 (% pred.) = 18.3], and [similarly, ΔMEF50 (%) = 25.8]. The mean severe exacerbation rate of asthma decreased from 4.1 ± 2.8 to 1.15 ± 0.78 (p < 0.0001) during the year of treatment with Omalizumab. Conclusions: This study showed that Omalizumab can be an effective and safe therapeutic option for Romanian children and adolescents with severe allergic asthma, providing clinically relevant information on asthma control and exacerbation rate in children and adolescents. The results demonstrated the positive effect of Omalizumab in young patients with asthma, starting from the first year of treatment.

scholarly journals Allergic diseases at an early age

2021 ◽  
pp. 141-145
Author(s):  
Ksenya S. Melnikova ◽  
Elena D. Kuwshinowa ◽  
Vera A. Reviakina
Keyword(s):  
Immunoglobulin E ◽  
Allergic Diseases ◽  
Early Age ◽  
Gastrointestinal Manifestations ◽  
Insect Allergy ◽  
Ige Mediated ◽  
Main Factors ◽  
High Level ◽  
Allergic Contact ◽  
Therapy And Diagnosis

In recent years, there has been a sharp increase in the incidence of allergic diseases (ADs), mainly in countries with a high level of development. Particularly noted is the increase in the prevalence of AZs in young children, among which cutaneous and gastrointestinal manifestations of allergy are the most common. These include atopic dermatitis (ATD), urticaria, gastrointestinal manifestations associated in most cases with food allergy, as well as contact allergic dermatitis, and insect allergy. The leading mechanism of development is immunoglobulin E (IgE)-mediated reactions. There are three main factors that predispose to AZ: genetic, direct contact with an allergen, and external environmental factors. The article deals with the causes, manifestations, therapy and diagnosis of a number of allergic diseases: urticaria, allergic contact dermatitis, insect allergy and some methods of therapy.

scholarly journals Severe pediatric asthma with a poor response to omalizumab: a report of three cases and three-dimensional bronchial wall analysis

2022 ◽  
Vol 50 (1) ◽  
pp. 030006052110704
Author(s):  
Mitsuru Tsuge ◽  
Masanori Ikeda ◽  
Yoichi Kondo ◽  
Hirokazu Tsukahara
Keyword(s):  
Severe Asthma ◽  
Wall Thickness ◽  
Airway Remodeling ◽  
Airflow Obstruction ◽  
Three Dimensional ◽  
Treatment Resistance ◽  
Poor Response ◽  
Airway Wall ◽  
Bronchial Wall ◽  
Severe Allergic Asthma

Omalizumab is used for the treatment of persistent severe allergic asthma in adults and children. However, some patients remain symptomatic even after omalizumab treatment. In bronchial asthma, chronic inflammation of the bronchial wall causes thickening of the airway wall, resulting from irreversible airway remodeling. Progression of airway remodeling causes airflow obstruction, leading to treatment resistance. We report three Japanese children with severe asthma who had a poor response to omalizumab treatment. They had a long period of inadequate management of asthma before initiating omalizumab. Even after omalizumab treatment, their symptoms persisted, and the parameters of spirometry tests did not improve. We hypothesized that omalizumab was less effective in these patients because airway wall remodeling had already progressed. We retrospectively evaluated the bronchial wall thickness using a three-dimensional bronchial wall analysis with chest computed tomography. The bronchial wall thickness was increased in these cases compared with six responders. Progressed airway wall thickness caused by airway remodeling may be associated with a poor response to omalizumab in children with severe asthma.

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