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Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases. authorsversion epub_ahead_of_print

In order to summarize recent research on the prevention of allergies-particularly asthma-and stimulate new activities for future initiatives, a virtual workshop sponsored by the EAACI Clemens von Pirquet foundation and EUFOREA was held in October 2021. The determinants of the "allergic march" as well as the key messages from intervention studies were reviewed by an international faculty of experts. Several unmet needs were identified, and a number of priorities for future studies were proposed.

BACKGROUND: This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline. METHODS: We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18 449 participants: 29 randomized controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarized narratively because studies were too heterogeneous to conduct meta-analysis. RESULTS: It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. There was also insufficient evidence about the impact of most anaphylaxis management and prevention strategies. Adrenaline is regularly used for first-line emergency management of anaphylaxis but little robust research has assessed its effectiveness. Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. We searched for but found little or no comparative effectiveness evidence about strategies such as fluid replacement, oxygen, glucocorticosteroids, methylxanthines, bronchodilators, management plans, food labels, drug labels and similar. CONCLUSIONS: Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it.

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

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence-based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including healthcare professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow-up of patients. © 2019 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Allergen immunotherapy (AIT) is a proven therapeutic option for the treatment of allergic rhinitis and/or asthma. Many guidelines or national practice guidelines have been produced but the evidence- based method varies, many are complex and none propose care pathways. This paper reviews care pathways for AIT using strict criteria and provides simple recommendations that can be used by all stakeholders including health professionals. The decision to prescribe AIT for the patient should be individualized and based on the relevance of the allergens, the persistence of symptoms despite appropriate medications according to guidelines as well as on the availability of good-quality and efficacious extracts. Allergen extracts cannot be regarded as generics. Immunotherapy is selected by specialists for stratified patients. There are no currently available validated biomarkers that can predict AIT success. In adolescents and adults, AIT should be reserved for patients with moderate/severe rhinitis or for those with moderate asthma who, despite appropriate pharmacotherapy and adherence, continue to exhibit exacerbations that appear to be related to allergen exposure, except in some specific cases. Immunotherapy may be even more advantageous in patients with multimorbidity. In children, AIT may prevent asthma onset in patients with rhinitis. mHealth tools are promising for the stratification and follow up of patients. © 2019 Dustri-Verlag Dr. Karl Feistle. All rights reserved.

Allergic rhinoconjunctivitis (AR) is an allergic disorder of the nose and eyes affecting about a fifth of the general population. Symptoms of AR can be controlled with allergen avoidance measures and pharmacotherapy. However, many patients continue to have ongoing symptoms and an impaired quality of life; pharmacotherapy may also induce some side-effects. Allergen immunotherapy (AIT) represents the only currently available treatment that targets the underlying pathophysiology, and it may have a disease-modifying effect. Either the subcutaneous (SCIT) or sublingual (SLIT) routes may be used. This Guideline has been prepared by the European Academy of Allergy and Clinical Immunology's (EAACI) Taskforce on AIT for AR and is part of the EAACI presidential project “EAACI Guidelines on Allergen Immunotherapy.” It aims to provide evidence-based clinical recommendations and has been informed by a formal systematic review and meta-analysis. Its generation has followed the Appraisal of Guidelines for Research and Evaluation (AGREE II) approach. The process included involvement of the full range of stakeholders. In general, broad evidence for the clinical efficacy of AIT for AR exists but a product-specific evaluation of evidence is recommended. In general, SCIT and SLIT are recommended for both seasonal and perennial AR for its short-term benefit. The strongest evidence for long-term benefit is documented for grass AIT (especially for the grass tablets) where long-term benefit is seen. To achieve long-term efficacy, it is recommended that a minimum of 3 years of therapy is used. Many gaps in the evidence base exist, particularly around long-term benefit and use in children. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

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, H 1 -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. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

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. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Background: There is a need to establish the effectiveness, cost-effectiveness, and safety of allergen immunotherapy (AIT) for the prevention of allergic disease. Methods: Two reviewers independently screened nine international biomedical databases. Studies were quantitatively synthesized using random-effects meta-analyses. Results: A total of 32 studies satisfied the inclusion criteria. Overall, meta-analysis found no conclusive evidence that AIT reduced the risk of developing a first allergic disease over the short term (RR = 0.30; 95% CI: 0.04–2.09) and no randomized controlled evidence was found in relation to its longer-term effects for this outcome. There was, however, a reduction in the short-term risk of those with allergic rhinitis developing asthma (RR = 0.40; 95% CI: 0.30–0.54), with this finding being robust to a pre-specified sensitivity analysis. We found inconclusive evidence that this benefit was maintained over the longer term: RR = 0.62; 95% CI: 0.31–1.23. There was evidence that the risk of new sensitization was reduced over the short term, but this was not confirmed in the sensitivity analysis: RR = 0.72; 95% CI: 0.24–2.18. There was no clear evidence of any longer-term reduction in the risk of sensitization: RR = 0.47; 95% CI: 0.08–2.77. AIT appeared to have an acceptable side effect profile. Conclusions: AIT did not result in a statistically significant reduction in the risk of developing a first allergic disease. There was, however, evidence of a reduced short-term risk of developing asthma in those with allergic rhinitis, but it is unclear whether this benefit was maintained over the longer term. We are unable to comment on the cost-effectiveness of AIT. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis (ARC). To inform the development of recommendations, we sought to critically assess the systematic review evidence on the effectiveness, safety and cost-effectiveness of AIT for ARC. Methods: We undertook a systematic overview, which involved searching nine international biomedical databases from inception to October 31, 2015. Studies were independently screened by two reviewers against pre-defined eligibility criteria and critically appraised using the Critical Appraisal Skills Programme (CASP) Systematic Review Checklist for systematic reviews. Data were descriptively synthesized. Results: Our searches yielded a total of 5932 potentially eligible studies, from which 17 systematic reviews met our inclusion criteria. Eight of these were judged to be of high, five moderate and three low quality. These reviews suggested that, in carefully selected patients, subcutaneous (SCIT) and sublingual (SLIT) immunotherapy resulted in significant reductions in symptom scores and medication requirements. Serious adverse outcomes were rare for both SCIT and SLIT. Two systematic reviews reported some evidence of potential cost savings associated with use of SCIT and SLIT. Conclusions: We found moderate-to-strong evidence that SCIT and SLIT can, in appropriately selected patients, reduce symptoms and medication requirements in patients with ARC with reassuring safety data. This evidence does however need to be interpreted with caution, particularly given the heterogeneity in the populations, allergens and protocols studied. There is a lack of data on the relative effectiveness, cost-effectiveness and safety of SCIT and SLIT. We are now systematically reviewing all the primary studies, including recent evidence that has not been incorporated into the published systematic reviews. © 2017 The Author(s).

Background: The European Academy of Allergy and Clinical Immunology (EAACI) is in the process of developing Guidelines on Allergen Immunotherapy (AIT) for Allergic Rhinoconjunctivitis. To inform the development of clinical recommendations, we undertook a systematic review to assess the effectiveness, cost-effectiveness, and safety of AIT in the management of allergic rhinoconjunctivitis. Methods: We searched nine international biomedical databases for published, in-progress, and unpublished evidence. Studies were independently screened by two reviewers against predefined eligibility criteria and critically appraised using established instruments. Our primary outcomes of interest were symptom, medication, and combined symptom and medication scores. Secondary outcomes of interest included cost-effectiveness and safety. Data were descriptively summarized and then quantitatively synthesized using random-effects meta-analyses. Results: We identified 5960 studies of which 160 studies satisfied our eligibility criteria. There was a substantial body of evidence demonstrating significant reductions in standardized mean differences (SMD) of symptom (SMD −0.53, 95% CI −0.63, −0.42), medication (SMD −0.37, 95% CI −0.49, −0.26), and combined symptom and medication (SMD −0.49, 95% CI −0.69, −0.30) scores while on treatment that were robust to prespecified sensitivity analyses. There was in comparison a more modest body of evidence on effectiveness post-discontinuation of AIT, suggesting a benefit in relation to symptom scores. Conclusions: AIT is effective in improving symptom, medication, and combined symptom and medication scores in patients with allergic rhinoconjunctivitis while on treatment, and there is some evidence suggesting that these benefits are maintained in relation to symptom scores after discontinuation of therapy. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Sante). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing.

Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Santé). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing. © 2016 The Author(s).

European Innovation Partnership on Active and Healthy Ageing Reference Site MACVIA-France, European Structural and Development Funds of Region Languedoc Roussillon Allergic diseases often occur early in life and persist throughout life. This life-course perspective should be considered in allergen immunotherapy. In particular it is essential to understand whether this al treatment may be used in old age adults. The current paper was developed by a working group of AIRWAYS integrated care pathways for airways diseases, the model of chronic respiratory diseases of the European Innovation Partnership on active and healthy ageing (DG CONNECT and DG Sante). It considered (1) the political background, (2) the rationale for allergen immunotherapy across the life cycle, (3) the unmet needs for the treatment, in particular in preschool children and old age adults, (4) the strategic framework and the practical approach to synergize current initiatives in allergen immunotherapy, its mechanisms and the concept of active and healthy ageing. Imperial Coll London, Natl Heart & Lung Inst, Royal Brompton Hosp NHS, London, England UPMC Paris 06, Sorbonne Univ,Dept Pneumol & Addictol,UMR S 1136, Hop Arnaud de Villeneuve,CHRU Montpellier, IPLESP,Equipe EPAR,Unite Allergol, F-75013 Paris, France Univ S Florida, Morsani Coll Med, Tampa, FL USA Univ Zurich, Swiss Inst Allergy & Asthma Res SIAF, Christine Kuhne Ctr Allergy Res & Educ CK CARE, Davos, Switzerland Univ Hosp Ghent, ENT Dept, Upper Airways Res Lab URL, Ghent, Belgium IQ4U Consultants Ltd, London, England Osped Riuniti, Univ Hosp, Allergy Unit, Dept Internal Med, Ancona, Italy Med Univ Vienna, Dept Pathophysiol & Allergy Res, Ctr Pathophysiol Infectiol & Immunol, Vienna, Austria Univ Naples 2, Rome, Italy CNR, IFT, Rome, Italy Univ Genoa, Allergy & Resp Dis Clin, DIMI, IRCCS AOU San Martino IST, Genoa, Italy Hosp Univ Vall dHebron, Allergy Sect, Dept Internal Med, Barcelona, Spain Montpellier UPMC Univ Paris 06, Sorbonne Univ,UMRS 1136, Hop Arnaud de Villeneuve,Equipe EPAR IPLESP, Div Allergy,Dept Pulmonol,Univ Hosp Montpellier, Paris, France Nova Southeastern Univ, Ft Lauderdale, FL USA Univ Hosp Strasbourg, Div Allergy, Chest Dis Dept, Strasbourg, France Univ Versailles St Quentin, Suresnes, France Foch Hosp, Dept Airway Dis, Clin Pharmacol Unit, UPRES EA 220, Suresnes, France Rangueil Larrey Hosp, Dept Resp Dis, Toulouse, France Univ Palermo, Di Bi MIS, Palermo, Italy Kings Coll London, Guys & St Thomas NHS Trust, London, England Imperial Coll London, Natl Heart & Lung Inst, Allergy & Clin Immunol Sect, London, England Childrens Hosp, Dept Pediat Pulmonol & Allergy, Aarau, Switzerland Bambino Gesu Pediat Hosp, Dept Pediat, Div Allergy, Rome, Italy Kings Coll London, Allergy Acad, London, England Erasmus MC, Dept Internal Med, Bldg Rochussenstr, Rotterdam, Netherlands Hosp San Bernardo, Unidad Alergia & Asma, Salta, Argentina Helsinki Univ Hosp, Skin & Allergy Hosp, Helsinki, Finland Odense Univ Hosp, Hans Christian Andersen Childrens Hosp, Odense, Denmark Katholieke Univ Leuven, Univ Hosp Leuven, Clin Dept Otorhinolaryngol Head & Neck Surg, Louvain, Belgium Secretary Immunotherapy Interest Grp EAACI, Allergy Learning & Consulting, Copenhagen, Denmark UPMC Univ Paris, Sorbonne Univ,Hop Enfants Armand Trousseau,INSERM, Inst Pierre Louis Epidemiol & Sante Publ,Equipe E, Allergol Dept,Ctr Asthme & Allergies,UMR S 1136, Paris, France Hosp Sirio Libanes, Sao Paulo, Brazil Univ Hosp Montpellier, Montpellier, France UPMC Paris 06, Sorbonne Univ, Equipe EPAR, UMR S 1136,IPLESP, Paris, France Ackermann Hanf & Kleine Tebbe, Outpatient Clin & Clin Res Ctr, Allergy & Asthma Ctr Westend, Berlin, Germany German Soc Otorhinolaryngol HNS, Ctr Rhinol & Allergol, Wiesbaden, Germany Univ Med Ctr Utrecht, Dept Immunol & Dermatol Allergol, Utrecht, Netherlands Med Univ Lodz, Lodz, Poland ARIA, Mexico City, DF, Mexico Hosp Med Sur, AAAAI, Mexico City, DF, Mexico Capital Reg Denmark, Res Ctr Prevent & Hlth, Copenhagen, Denmark Rigshosp, Dept Clin Expt Res, Copenhagen, Denmark Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark Charite Med Univ, Pediat Pneumol & Immunol, Berlin, Germany Gentofte Univ Hosp, Allergy Clin, Danish Allergy Ctr, Hellerup, Denmark Klinikum Univ Koln AoR, IMSIE, Cologne, Germany Hosp Clin Barcelona, Unitat Rinol & Clin Olfacte, ENT Dept, Clin & Expt Resp Immunoallergy,IDIBAPS,CIBERES, Barcelona, Catalonia, Spain Padua Gen Univ Hosp, Dept Women & Child Hlth, Food Allergy Referral Ctr Veneto Reg, Padua, Italy Univ Athens, Allergy Unit, Pediat Clin 2, Athens, Greece Univ Genoa, Allergy & Resp Dis, IRCCS San Martino IST, Genoa, Italy ASST Grande Osped Metropolitano Niguarda, Pzza Osped Maggiore, Milan, Italy Univ Med Mannheim, Dept Otorhinolaryngol Head & Neck Surg, Mannheim, Germany Heidelberg Univ, Med Fac Mannheim, Heidelberg, Germany Ctr Rhinol & Allergol, Wiesbaden, Germany Univ Aberdeen, Acad Primary Care, Div Appl Hlth Sci, Primary Care Resp Med, Aberdeen, Scotland RiRL, Cambridge, England Optimum Patient Care Ltd, Singapore, Singapore Hosp Infantil Univ Nino Jesus, Allergy Sect, Madrid, Spain Ludwig Maximillian Univ, Dept Dermatol & Allergol, Munich, Germany Med Univ Warsaw, Dept Prevent Environm Hazards & Allergol, Warsaw, Poland Royal Natl Throat Nose & Ear Hosp, London, England UCL, London, England Univ Zurich Hosp, Clin Trials Ctr, Zurich, Switzerland Imperial Coll London, Natl Heart & Lung Inst, Allergy & Clin Immunol Inflammat Repair & Dev Sec, Immunomodulat & Tolerance Grp,Fac Med, London, England MRC, London, England Asthma UK Ctr Allerg Mechanisms Asthma, London, England Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Asthma UK Ctr Appl Res, Med Informat Ctr, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland SLAAI, Asuncion, Paraguay Univ Fed Sao Paulo, Programa Posgrad Pediat & Ciencias Aplicadas Pedi, Dept Pediat EPM, Sao Paulo, Brazil Med Univ Graz, Dept Dermatol & Venerol, Graz, Austria Allergy Outpatient Clin Reumannplatz, Vienna, Austria Complejo Hosp Navarra, Serv Alergol, Pamplona, Spain Univ Amsterdam, Acad Med Ctr, Dept Expt Immunol, Amsterdam, Netherlands Univ Amsterdam, Acad Med Ctr, Dept Otorhinolaryngol, Amsterdam, Netherlands Univ Bari, Sch Med, Unit Geriatr Immunoallergol, Interdisciplinary Dept Med, Bari, Italy Complejo Hosp Univ Santiago de Compostela, Dept Allergy, Santiago De Compostela, Spain Med Univ Graz, Dept Paediat, Resp & Allerg Dis Div, Graz, Austria Charite Univ Med Berlin, Klin Dermatol Venerol & Allergol, Allergie Ctr Charite, Berlin, Germany European Innovat Partnership Act & Hlth Ageing Re, MAlad Chron Vleillissement Actif Languedoc Roussi, Paris, France INSERM, VIMA, Epidemiol & Publ Hlth Approaches, U1168,Ageing & Chron Dis, Paris, France Univ Versailles St Quentin En Yvelines, UVSQ, UMR S 1168, Versailles, France CHRU, 371 Ave Doyen Gaston Giraud, F-34295 Montpellier 5, France Programa de Pòs‑Graduação em Pediatria e Ciências Aplicadas à Pediatria, Departamento de Pediatria EPM, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil Web of Science