Asthma phenotypes have been developed to address the complexities of the disease. However, owing to a lack of longitudinal studies, little is known about the onset as well as the stability of ...phenotypes. Distinguishing phenotypes with regard to the severity or duration of the disease is essential. A phenotype covers the clinically relevant properties of the disease, but does not show the direct relationship to disease etiology and pathophysiology. Different pathogenetic mechanisms might cause similar asthma symptoms and might be operant in a certain phenotype. These putative mechanisms are addressed by the term ‘endotype’. Classification of asthma based on endotypes provides advantages for epidemiological, genetic, and drug‐related studies. A successful definition of endotypes should link key pathogenic mechanisms with the asthma phenotype. Thus, the identification of corresponding molecular biomarkers for individual pathogenic mechanism underlying phenotypes or subgroups within a phenotype is important. Whether newly defined asthma endotypes predict the individual course of asthma has to be validated in longitudinal studies. The accurate endotyping reflects natural history of asthma and should help to predict treatment response. Thus, understanding asthma endotypes might be useful in clinical practice.
Background
To inform the development of the European Academy of Allergy and Clinical Immunology's (EAACI) Guidelines on Allergen Immunotherapy (AIT) for allergic asthma, we assessed the evidence on ...the effectiveness, cost‐effectiveness and safety of AIT.
Methods
We performed a systematic review, which involved searching nine databases. Studies were screened against predefined eligibility criteria and critically appraised using established instruments. Data were synthesized using random‐effects meta‐analyses.
Results
98 studies satisfied the inclusion criteria. Short‐term symptom scores were reduced with a standardized mean difference (SMD) of −1.11 (95% CI −1.66, −0.56). This was robust to a prespecified sensitivity analyses, but there was evidence suggestive of publication bias. Short‐term medication scores were reduced SMD −1.21 (95% CI −1.87, −0.54), again with evidence of potential publication bias. There was no reduction in short‐term combined medication and symptom scores SMD 0.17 (95% CI −0.23, 0.58), but one study showed a beneficial long‐term effect.
For secondary outcomes, subcutaneous immunotherapy (SCIT) improved quality of life and decreased allergen‐specific airway hyperreactivity (AHR), but this was not the case for sublingual immunotherapy (SLIT). There were no consistent effects on asthma control, exacerbations, lung function, and nonspecific AHR.
AIT resulted in a modest increased risk of adverse events (AEs). Although relatively uncommon, systemic AEs were more frequent with SCIT; however no fatalities were reported.
The limited evidence on cost‐effectiveness was mainly available for sublingual immunotherapy (SLIT) and this suggested that SLIT is likely to be cost‐effective.
Conclusions
AIT can achieve substantial reductions in short‐term symptom and medication scores in allergic asthma. It was however associated with a modest increased risk of systemic and local AEs. More data are needed in relation to secondary outcomes, longer‐term effectiveness and cost‐effectiveness.
This EAACI position paper aims at providing a state‐of‐the‐art overview on nonallergic rhinitis (NAR). A significant number of patients suffering from persistent rhinitis are defined as nonallergic ...noninfectious rhinitis (NANIR) patients, often denominated in short as having NAR. NAR is defined as a symptomatic inflammation of the nasal mucosa with the presence of a minimum of two nasal symptoms such as nasal obstruction, rhinorrhea, sneezing, and/or itchy nose, without clinical evidence of endonasal infection and without systemic signs of sensitization to inhalant allergens. Symptoms of NAR may have a wide range of severity and be either continuously present and/or induced by exposure to unspecific triggers, also called nasal hyperresponsiveness (NHR). NHR represents a clinical feature of both AR and NAR patients. NAR involves different subgroups: drug‐induced rhinitis, (nonallergic) occupational rhinitis, hormonal rhinitis (including pregnancy rhinitis), gustatory rhinitis, senile rhinitis, and idiopathic rhinitis (IR). NAR should be distinguished from those rhinitis patients with an allergic reaction confined to the nasal mucosa, also called “entopy” or local allergic rhinitis (LAR). We here provide an overview of the current consensus on phenotypes of NAR, recommendations for diagnosis, a treatment algorithm, and defining the unmet needs in this neglected area of research.
Background
Molecular biomarkers that identify the phenotype of blood eosinophilia were evaluated in adult asthmatics, and their relationship with clinically significant asthma outcomes was assessed. ...Patients were clustered based on their molecular fingerprint.
Methods
At inclusion, 64 patients were evaluated for phenotypic traits, sputum and blood eosinophilia, exhaled NO, serum cytokines and chemokines, total serum IgE, lung function (LF), and airway hyper‐responsiveness (AHR). Within‐patient changes were evaluated in 44 patients 6 weeks later.
Results
Lung function, asthma control, and monocyte chemotactic protein‐1 (MCP‐1) were identified as the most important distinguisher and blood eosinophilia as second most important identifier in principal component analysis. A robust relationship was observed between blood eosinophilia and IL‐5, IL‐13, and eosinophil‐derived neurotoxin (EDN), which stayed consistent after 6 weeks. Serum IL‐5 and IL‐13 were the two best, followed by EDN as separators of high vs low blood eosinophilia. Periostin did not identify blood or sputum eosinophilia, even after stratification for total IgE, and did not correlate with IL‐5, IL‐13, eotaxin, or EDN. IL‐5 and IL‐13 showed strong correlations with AHR and monocyte chemoattractant protein (MCP)‐1 with asthma severity and fast LF decline. The presence of high or low expression of MCP‐1, eotaxin, and IL‐8 identified two separate blood eosinophilia patient clusters linked to asthma severity.
Conclusion
Serum IL‐5 and IL‐13 are reliable biomarkers for the blood eosinophilia asthma phenotype. High or low expression of MCP‐1, eotaxin, and IL‐8 discriminates between eosinophilic asthma severity clusters.
Nasal allergen challenge (NAC) is an important tool to diagnose allergic rhinitis. In daily clinical routine, experimentally, or when measuring therapeutic success clinically, nasal allergen ...challenge is fundamental. It is further one of the key diagnostic tools when initiating specific allergen immunotherapy. So far, national recommendations offered guidance on its execution; however, international divergence left many questions unanswered. These differences in the literature caused EAACI to initiate a task force to answer unmet needs and find a consensus in executing nasal allergen challenge. On the basis of a systematic review containing nasal allergen challenges of the past years, task force members reviewed evidence, discussed open issues, and studied variations of several subjective and objective assessment parameters to propose a standardized way of a nasal allergen challenge procedure in clinical practice. Besides an update on indications, contraindications, and preparations for the test procedure, main recommendations are a bilaterally challenge with standardized allergens, with a spray device offering 0.1 mL per nostril. A systematic catalogue for positivity criteria is given for the variety of established subjective and objective assessment methods as well as a schedule for the challenge procedure. The task force recommends a unified protocol for NAC for daily clinical practice, aiming at eliminating the previous difficulty of comparing NAC results due to unmet needs.
Inflammation, structural, and functional abnormalities within the airways are key features of asthma. Although these processes are well documented, their expression varies across the heterogeneous ...spectrum of asthma. Type 2 inflammatory responses are characterized by increased levels of eosinophils, FeNO, and type 2 cytokines in blood and/or airways. Presently, type 2 asthma is the best‐defined endotype, typically found in patients with allergic asthma, but surprisingly also in nonallergic patients with (severe) asthma. The etiology of asthma with non‐type 2 inflammation is less clear. During the past decade, targeted therapies, including biologicals and small molecules, have been increasingly integrated into treatment strategies of severe asthma. These treatments block specific inflammatory pathways or single mediators. Single or composite biomarkers help to identify patients who will benefit from these treatments. So far, only a few inflammatory biomarkers have been validated for clinical application. The European Academy of Allergy & Clinical Immunology Task Force on Biomarkers in Asthma was initiated to review different biomarker sampling methods and to investigate clinical applicability of new and existing inflammatory biomarkers (point‐of‐care) to support diagnosis, targeted treatment, and monitoring of severe asthma. Subsequently, we discuss existing and novel targeted therapies for asthma as well as applicable biomarkers.
Epidemiological research on the relationship between diet and asthma has increased in the last decade. Several components found in foods have been proposed to have a series of antioxidant, ...anti‐allergic and anti‐inflammatory properties, which can have a protective effect against asthma risk. Several literature reviews and critical appraisals have been published to summarize the existing evidence in this field. In the context of this EAACI Lifestyle and asthma Task Force, we summarize the evidence from existing systematic reviews on dietary intake and asthma, using the PRISMA guidelines. We therefore report the quality of eligible systematic reviews and summarize the results of those with an AMSTAR score ≥32. The GRADE approach is used to assess the overall quality of the existing evidence. This overview is centred on systematic reviews of nutritional components provided in the diet only, as a way to establish what type of advice can be given in clinical practice and to the general population on dietary habits and asthma.
Food allergy can result in considerable morbidity, impairment of quality of life, and healthcare expenditure. There is therefore interest in novel strategies for its treatment, particularly food ...allergen immunotherapy (FA‐AIT) through the oral (OIT), sublingual (SLIT), or epicutaneous (EPIT) routes. This Guideline, prepared by the European Academy of Allergy and Clinical Immunology (EAACI) Task Force on Allergen Immunotherapy for IgE‐mediated Food Allergy, aims to provide evidence‐based recommendations for active treatment of IgE‐mediated food allergy with FA‐AIT. Immunotherapy relies on the delivery of gradually increasing doses of specific allergen to increase the threshold of reaction while on therapy (also known as desensitization) and ultimately to achieve post‐discontinuation effectiveness (also known as tolerance or sustained unresponsiveness). Oral FA‐AIT has most frequently been assessed: here, the allergen is either immediately swallowed (OIT) or held under the tongue for a period of time (SLIT). Overall, trials have found substantial benefit for patients undergoing either OIT or SLIT with respect to efficacy during treatment, particularly for cow's milk, hen's egg, and peanut allergies. A benefit post‐discontinuation is also suggested, but not confirmed. Adverse events during FA‐AIT have been frequently reported, but few subjects discontinue FA‐AIT as a result of these. Taking into account the current evidence, FA‐AIT should only be performed in research centers or in clinical centers with an extensive experience in FA‐AIT. Patients and their families should be provided with information about the use of FA‐AIT for IgE‐mediated food allergy to allow them to make an informed decision about the therapy.
Hymenoptera venom allergy is a potentially life‐threatening allergic reaction following a honeybee, vespid, or ant sting. Systemic‐allergic sting reactions have been reported in up to 7.5% of adults ...and up to 3.4% of children. They can be mild and restricted to the skin or moderate to severe with a risk of life‐threatening anaphylaxis. Patients should carry an emergency kit containing an adrenaline autoinjector, H1‐antihistamines, and corticosteroids depending on the severity of their previous sting reaction(s). The only treatment to prevent further systemic sting reactions is venom immunotherapy. This guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on Venom Immunotherapy as part of the EAACI Guidelines on Allergen Immunotherapy initiative. The guideline aims to provide evidence‐based recommendations for the use of venom immunotherapy, has been informed by a formal systematic review and meta‐analysis and produced using the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included representation from a range of stakeholders. Venom immunotherapy is indicated in venom‐allergic children and adults to prevent further moderate‐to‐severe systemic sting reactions. Venom immunotherapy is also recommended in adults with only generalized skin reactions as it results in significant improvements in quality of life compared to carrying an adrenaline autoinjector. This guideline aims to give practical advice on performing venom immunotherapy. Key sections cover general considerations before initiating venom immunotherapy, evidence‐based clinical recommendations, risk factors for adverse events and for relapse of systemic sting reaction, and a summary of gaps in the evidence.
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