Impact of allergen immunotherapy in allergic asthma.
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ABSTRACT:
SUBMITTER: Zhang W
PROVIDER: S-EPMC5994829 | biostudies-literature | 2018 Jun
REPOSITORIES: biostudies-literature
Publications
Impact of allergen immunotherapy in allergic asthma.
Zhang Wenming W Lin Chunrong C Sampath Vanitha V Nadeau Kari K
Immunotherapy 20180323 7
Although traditional pharmacological approaches improve outcomes in disease management for allergic asthma, these fail to modify the underlying immune responses. Allergen immunotherapy remains the only etiological therapy for the treatment of respiratory allergies for which clinical efficacy has been demonstrated through several well-controlled studies. In this review, we examine evidence from the past 5 years regarding the impact of allergen immunotherapy on allergic asthma to inform practition ...[more]
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Project description:The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing the EAACI Guidelines for Allergen Immunotherapy (AIT) for Allergic Asthma. We seek to critically assess the effectiveness, cost-effectiveness and safety of AIT in the management of allergic asthma.We will undertake a systematic review, which will involve searching international biomedical databases for published, in progress and unpublished evidence. Studies will be independently screened against pre-defined eligibility criteria and critically appraised using established instruments. Data will be descriptively and, if possible and appropriate, quantitatively synthesised.The findings from this review will be used to inform the development of recommendations for EAACI's Guidelines on AIT.
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Project description:There is clinical uncertainty about the effectiveness and safety of allergen immunotherapy (AIT) for the treatment of allergic asthma.To undertake a systematic overview of the effectiveness, cost-effectiveness and safety of AIT for the treatment of allergic asthma.We searched nine electronic databases from inception to October 31, 2015. Systematic reviews were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme quality assessment tool for systematic reviews. Data were descriptively and thematically synthesized.We identified nine eligible systematic reviews; these focused on delivery of AIT through the following routes: subcutaneous (SCIT; n = 3); sublingual (SLIT; n = 4); and both SCIT and SLIT (n = 2). This evidence found that AIT delivered by SCIT and SLIT can improve medication and symptom scores and measures of bronchial hyper-reactivity. The impact on measures of lung function or asthma control was however less clear. We found no systematic review level evidence on the cost-effectiveness of SCIT or SLIT. SLIT had a favorable safety profile when compared to SCIT, particularly in relation to the risk of systemic reactions.AIT has the potential to achieve reductions in symptom and medication scores, but there is no clear or consistent evidence that measures of lung function can be improved. Bearing in mind the limitations of synthesizing evidence from systematic reviews and the fact that these reviews include mainly dated studies, a systematic review of current primary studies is now needed to update this evidence base, estimate the effectiveness of AIT on asthma outcomes and to investigate the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT.
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Project description:BackgroundAllergic rhinitis and asthma are important public health concerns, yet there is no consensus about the benefits and harms of allergen-specific immunotherapy to treat these conditions. We performed an umbrella review of systematic reviews summarizing the current evidence for the benefits and harms of subcutaneous immunotherapy (SCIT) and sublingual immunotherapy (SLIT).MethodsWe searched MEDLINE, Embase, the Cochrane Library and the grey literature from Jan. 1, 2010 to Nov. 20, 2016 for systematic reviews of randomized controlled trials or prospectively controlled studies involving children or adults with allergic rhinitis or asthma. Outcomes were summarized narratively (benefits: total combined symptom-medication score, symptom score, medication score, disease-specific quality of life, adherence; harms: anaphylaxis, death, local and systemic reactions).ResultsTwenty-three systematic reviews were included. SCIT and SLIT were more effective than placebo for most outcomes. SCIT was better than SLIT at improving medication and symptom scores, with no differences in quality of life; however, data were limited for this comparison. Anaphylaxis and death were infrequently reported. Few reviews assessed benefits or harms among children.InterpretationAllergen immunotherapy appears to be effective among patients with allergic rhinitis and asthma. The safety of allergen immunotherapy is not conclusively established, although death and anaphylaxis appear to be rare. PROSPERO no.: CRD42015024590.
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Project description:It is unclear if allergen immunotherapy (AIT) can reduce allergy effector cell activation. We evaluated the basophil response during Dermatophagoides pteronyssinus (Der p) subcutaneous immunotherapy (SCIT) and its relationship to allergen-specific immunoglobulin G4 (sIgG4) in allergic rhinitis and/or asthma patients. The study included 55 subjects, of which 35 cases received Der p SCIT and 20 controls received standard medications. Symptom and medication scores (SMSs), sIgG4 levels, specific immunoglobulin E (sIgE) levels, allergen-induced basophil activation tests (BATs) in whole blood, and BAT inhibition assays in serum were determined at weeks 0, 4, 12, 16, 52, and 104 of SCIT. Levels of Der p sIgG4 in SCIT patients significantly increased after 12 weeks of treatment compared to week 0. Serum obtained from SCIT patients significantly inhibited basophil activation after 12 weeks of treatment. Removal of immunoglobulin G4 (IgG4) antibodies at week 104 reduced the ability of serum to block basophil activation. An increase of Der p sIgG4 rather than reduction of Der p sIgE correlated with the reduction of basophil activation during SCIT. The sIgG4 antibodies may compete with sIgE binding to allergens to form an immunoglobulin E (IgE)-allergen complex. SCIT reduced the sensitivity of allergen-triggered basophil activation in Der p allergic rhinitis and/or asthma patients through induction of sIgG4.
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Project description:BackgroundAllergen-specific immunotherapy (AIT) is the only curative treatment for type-1 allergies, but sometimes shows limited therapeutic response as well as local and systemic side effects. Limited control of local inflammation and patient symptoms hampers its widespread use in severe allergic asthma.ObjectiveOur aim was to evaluate whether AIT is more effective in suppression of local inflammation if performed under the umbrella of short-term non-specific immunomodulation using a small molecule inhibitor of JAK pathways.MethodsIn C57BL/6J mice, a model of ovalbumin (OVA)-induced allergic airway inflammation and allergen-specific immunotherapy was combined with the administration of Tofacitinib (TOFA, a FDA-approved JAK inhibitor) from 48 hours prior to 48 hours after therapeutic OVA-injection. The effect of TOFA on human FOXP3+CD4+ T cells was studied in vitro.ResultsAIT combined with short-term TOFA administration was significantly more effective in suppressing total cell and eosinophil infiltration into the lung, local cytokine production including IL-1β and CXCL1 and showed a trend for the reduction of IL-4, IL-13, TNF-α and IL-6 compared to AIT alone. Furthermore, TOFA co-administration significantly reduced systemic IL-6, IL-1β and OVA-specific IgE levels and induced IgG1 to the same extent as AIT alone. Additionally, TOFA enhanced the induction of human FOXP3+CD4+ T cells.ConclusionsThis proof of concept study shows that JAK inhibition did not inhibit tolerance induction, but improved experimental AIT at the level of local inflammation. The improved control of local inflammation might extend the use of AIT in more severe conditions such as polyallergy, asthma and high-risk patients suffering from mastocytosis or anaphylaxis.
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Project description:Asthma is a complex syndrome associated with episodic decompensations provoked by aeroaller-gen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately inform biomarker-driven therapy. A better understanding of the pathophysiological pathways driving allergic exacerbations is needed. We hypothesized that disease-associated pathways could be identified in humans by unbiased metabolomics of bron-choalveolar fluid (BALF) during the peak inflammatory response provoked by a bronchial aller-gen challenge. We analyzed BALF metabolites in samples from 12 volunteers who underwent segmental bronchial antigen provocation (SBP-Ag). Metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS) followed by pathway analysis and cor-relation with airway inflammation. SBP-Ag induced statistically significant changes in 549 fea-tures that mapped to 72 uniquely identified metabolites. From these features, two distinct induci-ble metabolic phenotypes were identified by the principal component analysis, partitioning around medoids (PAM) and k-means clustering. Ten index metabolites were identified that in-formed the presence of asthma-relevant pathways, including unsaturated fatty acid produc-tion/metabolism, mitochondrial beta oxidation of unsaturated fatty acid, and bile acid metabolism. Pathways were validated using proteomics in eosinophils. A segmental bronchial allergen chal-lenge induces distinct metabolic responses in humans, providing insight into pathogenic and pro-tective endotypes in allergic asthma.
2022-06-09 | PXD033172 | Pride
Project description:Allergen-specific immunotherapy (SIT) involves the repeated administration of allergenic extracts to atopic individuals over a period of 3 to 5 years either subcutaneously (SCIT) or sublingually (SLIT) for the treatment of allergic respiratory diseases, including asthma and allergic rhinitis (AR). In studies, SCIT and SLIT have been shown to improve existing symptoms of asthma and AR and to also have the capability to cause disease-modifying changes of the underlying atopic condition so as to prevent new allergic sensitization as well as arrest progression of AR to asthma. Recent evidence suggests that immunotherapy brings about these effects through actions that use T-regulatory cells and blocking antibodies such as IgG(4) and IgA(2,) which can then result in an "immune deviation" from a T-helper (Th) 2 cell pattern to a Th1 cell pattern. Numerous meta-analyses and studies have been performed to evaluate the existing data among these studies, with the consensus recommendation favoring the use of immunotherapy because of its potential to modify existing diseases. Significant adverse reactions can occur with immunotherapy, including anaphylaxis and, very rarely, death. A primary factor in considering SIT is its potential to provide long-lasting effects that are able to be sustained well after its discontinuation. Given the significant burden these allergic diseases impose on the health-care system, SIT appears to be a cost-effective adjunctive treatment in modifying the existing disease state.
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