Type 2 immunity in the skin and lungs

Allergy, Journal Year: 2020, Volume and Issue: 75(7), P. 1582 - 1605

Published: April 22, 2020

Abstract There has been extensive progress in understanding the cellular and molecular mechanisms of inflammation immune regulation allergic diseases skin lungs during last few years. Asthma atopic dermatitis (AD) are typical type 2 responses. interleukin (IL)‐25, IL‐33, thymic stromal lymphopoietin essential cytokines epithelial cells that activated by allergens, pollutants, viruses, bacteria, toxins derive Th2 innate lymphoid (ILC) produce secrete such as IL‐4, IL‐5, IL‐9, IL‐13. IL‐4 IL‐13 activate B to class‐switch IgE also play a role T‐cell eosinophil migration inflammatory tissues. contributes maturation, activation, nitric oxide production differentiation epithelia, mucus well smooth muscle contraction, extracellular matrix generation. open tight junction barrier cause leakiness lungs. IL‐5 acts on recruitment, survival eosinophils. IL‐9 general phenotype enhancing all aspects, eosinophilia. Type ILC contribute AD asthma activity cells, eosinophils, their cytokines. Currently, five biologics licensed suppress via IgE, its receptor, receptor alpha. Some patients with severe disease have little evidence hyperactivity do not respond which target this pathway. Studies responder nonresponder demonstrate complexity these diseases. In addition, primary deficiency related regulatory development, signaling, Omenn syndrome, combined deficiencies, immunodysregulation, polyendocrinopathy, enteropathy, X‐linked DOCK8, STAT3, CARD11 help our importance redundancy various components. The present review aims highlight recent advances immunity discuss sources, targets, roles AD.

Language: Английский

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Phenotypes and endotypes of adult asthma: Moving toward precision medicine

Journal of Allergy and Clinical Immunology, Journal Year: 2019, Volume and Issue: 144(1), P. 1 - 12

Published: July 1, 2019

Language: Английский

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Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma. A systematic review for the EAACI Guidelines ‐ recommendations on the use of biologicals in severe asthma

Allergy, Journal Year: 2020, Volume and Issue: 75(5), P. 1023 - 1042

Published: Feb. 8, 2020

Abstract Five biologicals have been approved for severe eosinophilic asthma, a well‐recognized phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab reslizumab (alphabetical order) compared to standard care asthma. PubMed, Embase Cochrane Library were searched identify RCTs health economic evaluations, published in English. Critical important asthma‐related outcomes each biologicals. The risk bias certainty evidence assessed using GRADE. 19 (three three five reslizumab), including subjects 12 75 years old (except also 6‐11 old), ranging from 56 weeks evaluated. All reduce exacerbation rates with high evidence: benralizumab incidence rate ratio (IRR) 0.53 (95% CI 0.39 0.72), dupilumab 0.43 0.32 0.59), mepolizumab IRR 0.49 0.38 0.66), 0.56 0.40 0.77) 0.46 0.37 0.58). Benralizumab, daily dose oral corticosteroids (OCS) evidence. probably improve asthma control, QoL FEV 1 , without reaching minimal difference (moderate certainty). slightly increase drug‐related adverse events (AE) serious AE (low very low evidence). incremental cost‐effectiveness per quality‐adjusted life year value is above willingness pay threshold all Potential savings are driven by decrease hospitalizations, emergency primary visits. There that exacerbations reducing OCS. moderate improving QoL, . More data on long‐term needed together more paediatric population.

Language: Английский

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Introducing the Endotype Concept to Address the Challenge of Disease Heterogeneity in Type 1 Diabetes

Diabetes Care, Journal Year: 2019, Volume and Issue: 43(1), P. 5 - 12

Published: Nov. 21, 2019

The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility complex; rates progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, therapeutic intervention efficacy vary widely. Mechanistic immunopathological studies typically show patchiness across subjects, undermining conclusions regarding pathways. Without better understanding, heterogeneity represents a major barrier both to deciphering pathogenesis translational effort designing, conducting, interpreting trials disease-modifying agents. This realization comes during period unprecedented change in medicine, with emphasis on greater individualization precision. For complex disorders such diabetes, option maintaining "single disease" approach appears untenable, notion individualizing each patient's care, obliging us conceptualize less terms phenotypes (observable characteristics) more endotypes (underlying biological mechanisms). Here, we provide our view an dissect diabetes. Using lessons from other diseases data gathered date, aim delineate roadmap through which field can incorporate endotype concept into laboratory practice. We predict will accelerate implementation precision medicine has potential impact research, trial design, management.

Language: Английский

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Allergen Immunotherapy in Children User’s Guide

Pediatric Allergy and Immunology, Journal Year: 2020, Volume and Issue: 31(S25), P. 1 - 101

Published: May 1, 2020

Abstract Allergen immunotherapy is a cornerstone in the treatment of allergic children. The clinical efficiency relies on well‐defined immunologic mechanism promoting regulatory T cells and downplaying immune response induced by allergens. Clinical indications have been well documented for respiratory allergy presence rhinitis and/or asthma, to pollens dust mites. Patients who had an anaphylactic reaction hymenoptera venom are also good candidates allergen immunotherapy. Administration currently mostly either subcutaneous injections or sublingual administration. Both methods extensively studied pros cons. Specifically children, choice method administration according patient's profile important. Although widely used, there need improvement. More particularly, biomarkers prediction success treatments needed. strength may be boosted use better adjuvants. Finally, novel formulations might more efficient improve adherence treatment. This user's guide reviews current knowledge aims provide guidance healthcare professionals taking care children undergoing

Language: Английский

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EAACI Biologicals Guidelines—Recommendations for severe asthma

Allergy, Journal Year: 2020, Volume and Issue: 76(1), P. 14 - 44

Published: June 2, 2020

Abstract Severe asthma imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co‐morbidities, complexity in care pathways differences between national or regional Better understanding of the mechanisms has enabled stratified approach management severe asthma, supporting use targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection certain biological (as they all target overlapping phenotypes), definition response, strategies enhance responder rate, duration treatment its regimen (in clinic home‐based) cost‐effectiveness. The EAACI Guidelines biologicals follow GRADE formulating recommendations for each outcome. In addition, algorithm proposed, together future approaches research priorities.

Language: Английский

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Astegolimab (anti-ST2) efficacy and safety in adults with severe asthma: A randomized clinical trial

Journal of Allergy and Clinical Immunology, Journal Year: 2021, Volume and Issue: 148(3), P. 790 - 798

Published: April 16, 2021

The IL-33/ST2 pathway is linked with asthma susceptibility. Inhaled allergens, pollutants, and respiratory viruses, which trigger exacerbations, induce release of IL-33, an epithelial-derived "alarmin." Astegolimab, a human IgG2 mAb, selectively inhibits the IL-33 receptor, ST2. Approved biologic therapies for severe mainly benefit patients elevated blood eosinophils (type 2-high), but limited options are available low 2-low). Inhibiting signaling may target pathogenic pathways in wider spectrum asthmatics.This study evaluated astegolimab efficacy safety asthma.This double-blind, placebo-controlled, dose-ranging (ZENYATTA [A Study to Assess Efficacy Safety MSTT1041A Participants With Uncontrolled Severe Asthma]) randomized 502 adults subcutaneous placebo or 70-mg, 210-mg, 490-mg doses every 4 weeks. primary endpoint was annualized exacerbation rate (AER) at week 54. Enrollment caps ensured ∼30 who were eosinophil-high (≥300 cells/μL) ∼95 eosinophil-low (<300 per arm.Overall, adjusted AER reductions relative 43% (P = .005), 22% .18), 37% .01) 490-mg, 70-mg astegolimab, respectively. Adjusted comparable overall population: 54% .002), 14% .48), 35% .05) astegolimab. Adverse events similar astegolimab- placebo-treated groups.Astegolimab reduced broad population patients, including those eosinophil-low, inadequately controlled, asthma. Astegolimab safe well tolerated.

Language: Английский

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Nutrition and the Immune System: A Complicated Tango

Nutrients, Journal Year: 2020, Volume and Issue: 12(3), P. 818 - 818

Published: March 19, 2020

Enthusiasm exists for the potential of diet to impact immune system, prevent disease and its therapeutic potential. Herein, we describe challenge nutrition scientists in defining this relationship through case studies diets nutrients context allergic autoimmune diseases. Moderate-quality evidence from both human intervention observational suggest that individual can influence systemic markers function inflammation; numerous challenges exist demonstrating defined nutrient interventions on clearly influencing immune-mediated-clinical endpoints. A growing body suggests further consideration dietary patterns, system gut microbiome composition function, subsequent epigenetic modifications are needed improve our understanding diet-immune interactions.

Language: Английский

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Pharmacogenomics: current status and future perspectives

Nature Reviews Genetics, Journal Year: 2023, Volume and Issue: 24(6), P. 350 - 362

Published: Jan. 27, 2023

Language: Английский

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Advances and highlights in biomarkers of allergic diseases

Allergy, Journal Year: 2021, Volume and Issue: 76(12), P. 3659 - 3686

Published: Sept. 14, 2021

During the past years, there has been a global outbreak of allergic diseases, presenting considerable medical and socioeconomical burden. A large fraction diseases is characterized by type 2 immune response involving Th2 cells, innate lymphoid eosinophils, mast M2 macrophages. Biomarkers are valuable parameters for precision medicine as they provide information on disease endotypes, clusters, diagnoses, identification therapeutic targets, monitoring treatment efficacies. The availability powerful omics technologies, together with integrated data analysis network-based approaches can help clinically useful biomarkers. These biomarkers need to be accurately quantified using robust reproducible methods, such reliable point-of-care systems. Ideally, samples should collected quick, cost-efficient noninvasive methods. In recent plethora research directed toward finding novel diseases. Promising include sputum serum periostin exhaled nitric oxide. Several other biomarkers, pro-inflammatory mediators, miRNAs, eicosanoid molecules, epithelial barrier integrity, microbiota changes diagnosis in serum, body fluids air. Herein, we review studies asthma, chronic urticaria, atopic dermatitis, rhinitis, rhinosinusitis, food allergies, anaphylaxis, drug hypersensitivity allergen immunotherapy. addition, discuss COVID-19 within perspective recommendations management asthmatic patients during pandemic.

Language: Английский

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