Publications by authors named "Thomas Eiwegger"

90 Publications

Management of allergic diseases in pregnancy.

Allergy 2021 Aug 24. Epub 2021 Aug 24.

Karl Landsteiner University of Health Sciences, Krems, Austria.

Allergic diseases like asthma, allergic rhinitis, food allergy, hymenoptera allergy, or atopic dermatitis are highly prevalent in women of childbearing age and may affect up to 30% of this age group. This review focuses on the management of allergic diseases during pregnancy. Furthermore, we discuss the challenges of counseling women with allergic diseases in the reproductive age, including considerations relevant to the ongoing SARS-CoV-2 pandemic. To create the optimal milieu for the unborn child, a multitude of immunological changes occur during pregnancy which may favor type 2 responses and aggravate disease phenotypes. In co-occurrence with suboptimal preconception disease control, this elevated Th2 responses may aggravate allergic disease manifestations during pregnancy and pose a risk for mother and child. Due to limitations in conducting clinical trials in pregnant women, safety data on anti-allergic drugs during pregnancy are limited. The lack of information and concerns among pregnant patients demands counseling on the benefits of anti-allergic drugs and the potential and known risks. This includes information on the risk for mother and child of disease aggravation in the absence of treatment. By doing so, informed decisions and shared decision-making can take place.
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http://dx.doi.org/10.1111/all.15063DOI Listing
August 2021

EAACI Biologicals Guidelines-Omalizumab for the treatment of chronic spontaneous urticaria in adults and in the paediatric population 12-17 years old.

Allergy 2021 Jul 29. Epub 2021 Jul 29.

Department of Clinical Immunology, Wrocław Medical University, Wroclaw, Poland.

Chronic spontaneous urticaria (CSU) imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity and insufficient efficacy of classical drugs such as H R-antihistamines. Better understanding of the mechanisms has enabled a stratified approach to the management of CSU, supporting the use of targeted treatment with omalizumab. However, many practical issues including selection of responders, the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness still require further clarification. The EAACI Guidelines on the use of omalizumab in CSU follow the GRADE approach in formulating recommendations for each outcome. In addition, future therapeutic approaches and perspectives as well as research priorities are discussed.
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http://dx.doi.org/10.1111/all.15030DOI Listing
July 2021

Establishing Amoxicillin Allergy in Children Through Direct Graded Oral Challenge (GOC): Evaluating Risk Factors for Positive Challenges, Safety, and Risk of Cross-Reactivity to Cephalosporines.

J Allergy Clin Immunol Pract 2021 Jul 19. Epub 2021 Jul 19.

Division of Allergy and Clinical Immunology, Department of Pediatrics, Montreal Children's Hospital, Montreal, QC, Canada; Infectious Diseases and Immunity in Global Health Program, The Research Institute of the McGill University Health Centre, McGill University, Montreal, QC, Canada.

Background: Data on the diagnostic properties of direct oral challenges without the use of skin tests in children with suspected amoxicillin allergy are sparse.

Objective: Assess the use of direct oral challenges.

Methods: A cohort study was conducted between March 2013 and March 2020, in Montreal and Winnipeg. All children referred with reported history of benign reactions (ie, limited to the skin with no mucosal lesions and no vesicles) to amoxicillin were recruited and a 2-step graded oral challenge (GOC) was conducted. Data were collected on demographic characteristics, clinical characteristics, and comorbidities. Eligible children were followed to assess reactions to subsequent use of amoxicillin and to assess the safety of cephalexin use in children with a positive GOC.

Results: Among 1914 children recruited, 1811 (94.6%) tolerated the GOC, 42 (2.2%) developed mild immediate reactions, and 61 (3.2%) developed mild nonimmediate reactions. Among 265 participants who had a negative GOC and reused amoxicillin, 226 (85.3%) reported tolerance and 39 (14.7%) had mild cutaneous reactions. Chronic urticaria (adjusted odds ratio [aOR], 1.16; 95% CI, 1.09-1.23) and an index reaction occurring within 5 minutes of exposure (aOR, 1.09; 95% CI, 1.04-1.14) were associated with immediate reactions during the GOC. Symptoms lasting longer than 7 days (aOR, 1.05; 95% CI, 1.02-1.09) and parental drug hypersensitivity (aOR, 1.04; 95% CI, 1.03-1.06) were associated with nonimmediate reactions. Among those reacting to the GOC, 12.5% reacted with mild cutaneous reactions to cephalexin challenge.

Conclusions: Direct GOCs are an accurate and safe confirmatory to establish true hypersensitivity among children reporting benign reactions to amoxicillin.
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http://dx.doi.org/10.1016/j.jaip.2021.06.057DOI Listing
July 2021

Immunologically relevant aspects of the new COVID-19 vaccines-an ÖGAI (Austrian Society for Allergology and Immunology) and AeDA (German Society for Applied Allergology) position paper.

Allergo J Int 2021 Jun 18:1-14. Epub 2021 Jun 18.

Institute of Pathophysiology and Allergy Research, Centre for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria.

Background: The vaccines against the coronavirus disease 2019 (COVID-19) approved in the European Union represent a decisive step in the fight against the pandemic. The application of these available vaccines to patients with pre-existing immunological conditions leads to a multitude of questions regarding efficacy, side effects and the necessary patient information.

Results: This review article provides insight into mechanisms of action of the currently available severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and summarises the current state of science as well as expert recommendations regarding tolerability of the vaccines. In addition, the potential to develop protective immune responses is determined. A special focus is given on patients under immunosuppression or in treatment with immunomodulatory drugs. Special groups of the population such as children, pregnant women and the elderly are also considered.

Conclusion: Despite the need for a patient-specific risk-benefit assessment, the consensus among experts is that patients with immunological diseases in particular benefit from the induced immune protection after COVID-19 vaccination and do not have an increased risk of side effects.
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http://dx.doi.org/10.1007/s40629-021-00178-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212077PMC
June 2021

Biological treatment in allergic disease.

Allergy 2021 09 12;76(9):2934-2937. Epub 2021 Jun 12.

Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

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http://dx.doi.org/10.1111/all.14954DOI Listing
September 2021

Vaccines and allergic reactions: The past, the current COVID-19 pandemic, and future perspectives.

Allergy 2021 06 4;76(6):1640-1660. Epub 2021 Jun 4.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.
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http://dx.doi.org/10.1111/all.14840DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251022PMC
June 2021

Efficacy and safety of treatment with biologicals for severe chronic rhinosinusitis with nasal polyps: A systematic review for the EAACI guidelines.

Allergy 2021 08 24;76(8):2337-2353. Epub 2021 Mar 24.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

This systematic review evaluates the efficacy and safety of biologicals for chronic rhinosinusitis with nasal polyps (CRSwNP) compared with the standard of care. PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CRSwNP-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. RCTs evaluated (dupilumab-2, omalizumab-4, mepolizumab-2, and reslizumab-1) included 1236 adults, with follow-up of 20-64 weeks. Dupilumab reduces the need for surgery (NFS) or oral corticosteroid (OCS) use (RR 0.28; 95% CI 0.20-0.39, moderate certainty) and improves with high certainty smell evaluated with UPSIT score (mean difference (MD) +10.54; 95% CI +9.24 to +11.84) and quality of life (QoL) evaluated with SNOT-22 (MD -19.14; 95% CI -22.80 to -15.47), with fewer treatment-related adverse events (TAEs) (RR 0.95; 95% CI 0.89-1.02, moderate certainty). Omalizumab reduces NFS (RR 0.85; 95% CI 0.78-0.92, high certainty), decreases OCS use (RR 0.38; 95% CI 0.10-1.38, moderate certainty), and improves high certainty smell (MD +3.84; 95% CI +3.64 to +4.04) and QoL (MD -15.65; 95% CI -16.16 to -15.13), with increased TAE (RR 1.73; 95% CI 0.60-5.03, moderate certainty). There is low certainty for mepolizumab reducing NFS (RR 0.78; 95% CI 0.64-0.94) and improving QoL (MD -13.3; 95% CI -23.93 to -2.67) and smell (MD +0.7; 95% CI -0.48 to +1.88), with increased TAEs (RR 1.64; 95% CI 0.41-6.50). The evidence for reslizumab is very uncertain.
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http://dx.doi.org/10.1111/all.14809DOI Listing
August 2021

EAACI Biologicals Guidelines-dupilumab for children and adults with moderate-to-severe atopic dermatitis.

Allergy 2021 04 27;76(4):988-1009. Epub 2020 Dec 27.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

Atopic dermatitis imposes a significant burden on patients, families and healthcare systems. Management is difficult, due to disease heterogeneity, co-morbidities, complexity in care pathways and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of atopic dermatitis, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based), its cost-effectiveness and long-term safety. The EAACI Guidelines on the use of dupilumab in atopic dermatitis follow the GRADE approach in formulating recommendations for each outcome and age group. In addition, future approaches and research priorities are discussed.
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http://dx.doi.org/10.1111/all.14690DOI Listing
April 2021

EAACI statement on the diagnosis, management and prevention of severe allergic reactions to COVID-19 vaccines.

Allergy 2021 06;76(6):1629-1639

Immunomodulation and Tolerance Group, Allergy and Clinical Immunology, Inflammation, Repair and Development, National Heart and Lung Institute, Imperial College London. Asthma UK Centre in Allergic Mechanisms of Asthma, London, UK.

The first approved COVID-19 vaccines include Pfizer/BioNTech BNT162B2, Moderna mRNA-1273 and AstraZeneca recombinant adenoviral ChAdOx1-S. Soon after approval, severe allergic reactions to the mRNA-based vaccines that resolved after treatment were reported. Regulatory agencies from the European Union, Unites States and the United Kingdom agree that vaccinations are contraindicated only when there is an allergy to one of the vaccine components or if there was a severe allergic reaction to the first dose. This position paper of the European Academy of Allergy and Clinical Immunology (EAACI) agrees with these recommendations and clarifies that there is no contraindication to administer these vaccines to allergic patients who do not have a history of an allergic reaction to any of the vaccine components. Importantly, as is the case for any medication, anaphylaxis may occur after vaccination in the absence of a history of allergic disease. Therefore, we provide a simplified algorithm of prevention, diagnosis and treatment of severe allergic reactions and a list of recommended medications and equipment for vaccine centres. We also describe potentially allergenic/immunogenic components of the approved vaccines and propose a workup to identify the responsible allergen. Close collaboration between academia, regulatory agencies and vaccine producers will facilitate approaches for patients at risks, such as incremental dosing of the second injection or desensitization. Finally, we identify unmet research needs and propose a concerted international roadmap towards precision diagnosis and management to minimize the risk of allergic reactions to COVID-19 vaccines and to facilitate their broader and safer use.
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http://dx.doi.org/10.1111/all.14739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8013422PMC
June 2021

Basophil activation test shows high accuracy in the diagnosis of peanut and tree nut allergy: The Markers of Nut Allergy Study.

Allergy 2021 06 29;76(6):1800-1812. Epub 2020 Dec 29.

Translational Medicine, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

Background: Peanut and tree nut allergies are the most important causes of anaphylaxis. Co-reactivity to more than one nut is frequent, and co-sensitization in the absence of clinical data is often obtained. Confirmatory oral food challenges (OFCs) are inconsistently performed.

Objective: To investigate the utility of the basophil activation test (BAT) in diagnosing peanut and tree nut allergies.

Methods: The Markers Of Nut Allergy Study (MONAS) prospectively enrolled patients aged 0.5-17 years with confirmed peanut and/or tree nut (almond, cashew, hazelnut, pistachio, walnut) allergy or sensitization from Canadian (n = 150) and Austrian (n = 50) tertiary pediatric centers. BAT using %CD63 basophils (SSClow/CCR3pos) as outcome was performed with whole blood samples stimulated with allergen extracts of each nut (0.001-1000 ng/mL protein). BAT results were assessed against confirmed allergic status in a blinded fashion to develop a generalizable statistical model for comparison to extract and marker allergen-specific IgE.

Results: A mixed effect model integrating BAT results for 10 and 100 ng/mL of peanut and individual tree nut extracts was optimal. The area under the ROC curve (AUROC) was 0.98 for peanut, 0.97 for cashew, 0.92 for hazelnut, 0.95 for pistachio, and 0.97 for walnut. The BAT outperformed sIgE testing for peanut or hazelnut and was comparable for walnut (AUROC 0.95, 0.94, 0.92) in a sub-analysis in sensitized patients undergoing OFC.

Conclusions: Basophil activation test can predict allergic clinical status to peanut and tree nuts in multi-nut-sensitized children and may reduce the need for high-risk OFCs in patients.
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http://dx.doi.org/10.1111/all.14695DOI Listing
June 2021

Emollients for the prevention of atopic dermatitis.

Allergy 2021 08 28;76(8):2641-2643. Epub 2020 Nov 28.

Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

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http://dx.doi.org/10.1111/all.14650DOI Listing
August 2021

Use of biologicals in allergic and type-2 inflammatory diseases during the current COVID-19 pandemic: Position paper of Ärzteverband Deutscher Allergologen (AeDA), Deutsche Gesellschaft für Allergologie und Klinische Immunologie (DGAKI), Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA), Österreichische Gesellschaft für Allergologie und Immunologie (ÖGAI), Luxemburgische Gesellschaft für Allergologie und Immunologie (LGAI), Österreichische Gesellschaft für Pneumologie (ÖGP) in co-operation with the German, Austrian, and Swiss ARIA groups, and the European Academy of Allergy and Clinical Immunology (EAACI).

Allergol Select 2020 7;4:53-68. Epub 2020 Sep 7.

German, Austrian, and Swiss ARIA groups.

Background: Since the beginning of the COVID-19 pandemic, the treatment of patients with allergic and atopy-associated diseases has faced major challenges. Recommendations for "social distancing" and the fear of patients becoming infected during a visit to a medical facility have led to a drastic decrease in personal doctor-patient contacts. This affects both acute care and treatment of the chronically ill. The immune response after SARS-CoV-2 infection is so far only insufficiently understood and could be altered in a favorable or unfavorable way by therapy with monoclonal antibodies. There is currently no evidence for an increased risk of a severe COVID-19 course in allergic patients. Many patients are under ongoing therapy with biologicals that inhibit type 2 immune responses via various mechanisms. There is uncertainty about possible immunological interactions and potential risks of these biologicals in the case of an infection with SARS-CoV-2.

Materials And Methods: A selective literature search was carried out in PubMed, Livivo, and the internet to cover the past 10 years (May 2010 - April 2020). Additionally, the current German-language publications were analyzed. Based on these data, the present position paper provides recommendations for the biological treatment of patients with allergic and atopy-associated diseases during the COVID-19 pandemic.

Results: In order to maintain in-office consultation services, a safe treatment environment must be created that is adapted to the pandemic situation. To date, there is a lack of reliable study data on the care for patients with complex respiratory, atopic, and allergic diseases in times of an imminent infection risk from SARS-CoV-2. Type-2-dominant immune reactions, as they are frequently seen in allergic patients, could influence various phases of COVID-19, e.g., by slowing down the immune reactions. Theoretically, this could have an unfavorable effect in the early phase of a SARS-Cov-2 infection, but also a positive effect during a cytokine storm in the later phase of severe courses. However, since there is currently no evidence for this, all data from patients treated with a biological directed against type 2 immune reactions who develop COVID-19 should be collected in registries, and their disease courses documented in order to be able to provide experience-based instructions in the future.

Conclusion: The use of biologicals for the treatment of bronchial asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, and spontaneous urticaria should be continued as usual in patients without suspected infection or proven SARS-CoV-2 infection. If available, it is recommended to prefer a formulation for self-application and to offer telemedical monitoring. Treatment should aim at the best possible control of difficult-to-control allergic and atopic diseases using adequate rescue and add-on therapy and should avoid the need for systemic glucocorticosteroids. If SARS-CoV-2 infection is proven or reasonably suspected, the therapy should be determined by weighing the benefits and risks individually for the patient in question, and the patient should be involved in the decision-making. It should be kept in mind that the potential effects of biologicals on the immune response in COVID-19 are currently not known. Telemedical offers are particularly desirable for the acute consultation needs of suitable patients.
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http://dx.doi.org/10.5414/ALX02166EDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480069PMC
September 2020

Differentiating Between β-Lactam-Induced Serum Sickness-Like Reactions and Viral Exanthem in Children Using a Graded Oral Challenge.

J Allergy Clin Immunol Pract 2021 02 6;9(2):916-921. Epub 2020 Sep 6.

Department of Pediatrics, Division of Allergy and Clinical Immunology, Montreal Children's Hospital, Montreal, Quebec, Canada.

Background: Serum sickness-like reactions (SSLRs) are defined by the presence of rash (primarily urticaria) and joint complaints (arthralgia/arthritis) that are believed to occur due to a non-IgE-mediated response to medications. However, similar reactions can occur due to viral infections, and it can be difficult to distinguish between the two. This may lead to unnecessary avoidance of the culprit antibiotic.

Objective: We aimed to evaluate children presenting with suspected SSLRs through a graded oral challenge (GOC).

Methods: All children referred to the Montreal Children's Hospital for potential antibiotic allergy (β-lactam or other antibiotics) and a clinical presentation compatible with SSLR were recruited for the study between March 2013 and February 2020. A standardized survey with questions on treatment, symptoms, and associated factors was completed, and a GOC (10% and subsequently 90% of the oral antibiotic dose) was conducted. Patients with a negative GOC were contacted annually to query on subsequent antibiotic use.

Results: Among 75 patients presenting with suspected SSLRs, the median age was 2.0 years and 46.7% were males. Most reactions were attributed to amoxicillin. Among the 75 patients, 2.7% reacted immediately (within 1 hour) to a GOC and 4.0% had a nonimmediate reaction. Of the 43 patients successfully contacted, 20 reported subsequent culprit antibiotic use of whom 25.0% had a subsequent mild reaction (macular/papular rash).

Conclusions: This is the first and largest pediatric study to assess SSLR using a GOC. Our findings suggest that using a GOC is safe and appropriate for differentiating between β-lactam-induced SSLR and viral exanthem in this population.
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http://dx.doi.org/10.1016/j.jaip.2020.08.047DOI Listing
February 2021

Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma.

Allergy 2020 12 30;75(12):3039-3068. Epub 2020 Sep 30.

Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, Switzerland.

Modern health care requires a proactive and individualized response to diseases, combining precision diagnosis and personalized treatment. Accordingly, the approach to patients with allergic diseases encompasses novel developments in the area of personalized medicine, disease phenotyping and endotyping, and the development and application of reliable biomarkers. A detailed clinical history and physical examination followed by the detection of IgE immunoreactivity against specific allergens still represents the state of the art. However, nowadays, further emphasis focuses on the optimization of diagnostic and therapeutic standards and a large number of studies have been investigating the biomarkers of allergic diseases, including asthma, atopic dermatitis, allergic rhinitis, food allergy, urticaria and anaphylaxis. Various biomarkers have been developed by omics technologies, some of which lead to a better classification of distinct phenotypes or endotypes. The introduction of biologicals to clinical practice increases the need for biomarkers for patient selection, prediction of outcomes and monitoring, to allow for an adequate choice of the duration of these costly and long-lasting therapies. Escalating healthcare costs together with questions about the efficacy of the current management of allergic diseases require further development of a biomarker-driven approach. Here, we review biomarkers in diagnosis and treatment of asthma, atopic dermatitis, allergic rhinitis, viral infections, chronic rhinosinusitis, food allergy, drug hypersensitivity and allergen immunotherapy with a special emphasis on specific IgE, the microbiome and the epithelial barrier. In addition, EAACI guidelines on biologicals are discussed within the perspective of biomarkers.
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http://dx.doi.org/10.1111/all.14582DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7756301PMC
December 2020

Efficacy and safety of treatment with omalizumab for chronic spontaneous urticaria: A systematic review for the EAACI Biologicals Guidelines.

Allergy 2021 01 7;76(1):59-70. Epub 2020 Sep 7.

Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

This systematic review evaluates the efficacy and safety of omalizumab for chronic spontaneous urticaria (CSU). PubMed, Embase, and Cochrane Library were searched for RCTs. Critical and important CSU-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Ten RCTs including 1620 subjects aged 12 to 75 years old treated with omalizumab for 16 to 40 weeks were evaluated. Omalizumab 150 mg does not result in clinically meaningful improvement (high certainty) of the urticaria activity score (UAS)7 (mean difference (MD) -5; 95%CI -7.75 to -2.25), and the itch severity score (ISS)7 (MD -2.15; 95% CI -3.2 to -1.1) does not increase (moderate certainty) quality of life (QoL) (Dermatology Life Quality Index (DLQI); MD -2.01; 95%CI -3.22 to -0.81) and decreases (moderate certainty) rescue medication use (MD -1.68; 95%CI -2.95 to -0.4). Omalizumab 300 mg results in clinically meaningful improvements (moderate certainty) of the UAS7 (MD -11.05; 95%CI -12.87 to -9.24), the ISS7 (MD -4.45; 95%CI -5.39 to -3.51), and QoL (high certainty) (DLQI; MD -4.03; 95% CI -5.56 to -2.5) and decreases (moderate certainty) rescue medication use (MD -2.04; 95%CI -3.19 to -0.88) and drug-related serious AEs (RR 0.77; 95%CI 0.20 to 2.91).
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http://dx.doi.org/10.1111/all.14547DOI Listing
January 2021

Modeling the conversion between specific IgE test platforms for nut allergens in children and adolescents.

Allergy 2021 03 16;76(3):831-841. Epub 2020 Aug 16.

Translational Medicine Program, Research Institute, Hospital for Sick Children, Toronto, ON, Canada.

Background: Multiplex tests allow for measurement of allergen-specific IgE responses to multiple extracts and molecular allergens and have several advantages for large cohort studies. Due to significant methodological differences, test systems are difficult to integrate in meta-analyses/systematic reviews since there is a lack of datasets with direct comparison. We aimed to create models for statistical integration of allergen-specific IgE to peanut/tree nut allergens from three IgE test platforms.

Methods: Plasma from Canadian and Austrian children/adolescents with peanut/tree nut sensitization and a cohort of sensitized, high-risk, pre-school asthmatics (total n = 166) were measured with three R&D multiplex IgE test platforms: Allergy Explorer version 1 (ALEX) (Macro Array Dx), MeDALL-chip (Mechanisms of Development of Allergy) (Thermo Fisher), and EUROLINE (EUROIMMUN). Skin prick test (n = 51) and ImmunoCAP (Thermo Fisher) (n = 62) results for extracts were available in a subset. Regression models (Multivariate Adaptive Regression Splines, local polynomial regression) were applied if >30% of samples were positive to the allergen. Intra-test correlations between PR-10 and nsLTP allergens were assessed.

Results: Using two regression methods, we demonstrated the ability to model allergen-specific relationships with acceptable measures of fit (r  = 94%-56%) for peanut and tree nut sIgE testing at the extract and molecular-level, in order from highest to lowest: Ara h 2, Ara h 6, Jug r 1, Ana o 3, Ara h 1, Jug r 2, and Cor a 9.

Conclusion: Our models support the notion that quantitative conversion is possible between sIgE multiplex platforms for extracts and molecular allergens and may provide options to aggregate data for future meta-analysis.
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http://dx.doi.org/10.1111/all.14529DOI Listing
March 2021

Efficacy and safety of dupilumab for moderate-to-severe atopic dermatitis: A systematic review for the EAACI biologicals guidelines.

Allergy 2021 01 4;76(1):45-58. Epub 2020 Oct 4.

Department of Clinical Immunology, Department of Clinical Immunology, University of Wroclaw, Wroclaw, Poland.

This systematic review evaluates the efficacy, safety and economic impact of dupilumab compared to standard of care for uncontrolled moderate-to-severe atopic dermatitis (AD). Pubmed, EMBASE and Cochrane Library were searched for RCTs and health economic evaluations. Critical and important AD-related outcomes were considered. The risk of bias and the certainty of the evidence were assessed using GRADE. Seven RCTs including 1845 subjects >12 years treated with dupilumab 16 to 52 weeks were evaluated. For adults, there is high certainty that dupilumab decreases SCORAD (MD -30,72; 95% CI -34,65% to -26,79%) and EASI-75 (RR 3.09; 95% CI 2.45 to 3.89), pruritus (RR 2.96; 95% CI 2.37 to 3.70), rescue medication (RR 3.46; 95% CI 2.79 to 4.30), sleep disturbance (MD -7.29; 95% CI -8.23 to -6.35) and anxiety/depression (MD -3.08; 95% CI -4.41 to -1.75) and improves quality of life (MD -4.80; 95% CI -5.55 to -4.06). The efficacy for adolescents is similar. Dupilumab-related adverse events (AEs) slightly increase (low certainty). The evidence for dupilumab-related serious AE is uncertain. The incremental cost-effectiveness ratio ranged from 28 500 £ (low certainty) to 124 541 US$ (moderate certainty). More data on long-term safety are needed both for children and for adults, together with more efficacy data in the paediatric population. Registration: PROSPERO (CRD42020153645).
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http://dx.doi.org/10.1111/all.14510DOI Listing
January 2021

Does the Use of the "Proseek Multiplex Oncology I Panel" on Peritoneal Fluid Allow a Better Insight in the Pathophysiology of Endometriosis, and in Particular Deep-Infiltrating Endometriosis?

J Clin Med 2020 Jun 26;9(6). Epub 2020 Jun 26.

Department of Obstetrics and Gynecology, Medical University of Vienna, 1090 Vienna, Austria.

Endometriosis appears to share certain cancer-related processes, such as cell attachment, invasion, proliferation and neovascularization, some of which can also be found in other healthy tissues. In order to better understand the altered milieu of the peritoneal cavity, while acknowledging the reported similarities between endometriosis and neoplastic processes, we applied a multiplex oncology panel to search for specific biomarker signatures in the peritoneal fluid of women with endometriosis, women with deep-infiltrating endometriosis (DIE), as well as controls. In total, 84 patients were included in our study, 53 women with endometriosis and 31 controls. Ninety-two proteins were measured in prospectively collected peritoneal fluid (PF) samples, using the "Proseek Multiplex Oncology I Panel". We first compared patients with endometriosis versus controls, and in a second step, DIE versus endometriosis patients without DIE. Out of the 92 analyzed proteins, few showed significant differences between the groups. In patients with endometriosis, ICOS ligand, Endothelial growth factor, E-selectin, Receptor tyrosine-protein kinase erbB-2, Interleukin-6 receptor alpha, Vascular endothelial growth factor receptor 2, Fms-related tyrosine kinase 3 ligand, C-X-C motif chemokine 10, Epididymal secretory protein E4 and Folate receptor-alpha were decreased, while Interleukin-6 and Interleukin-8 were increased compared to controls. Looking at patients with DIE, we found Chemokine ligand 19, Stem cell factor, Vascular endothelial growth factor D, Interleukin-6 receptor alpha and Melanoma inhibitory activity to be increased compared to endometriosis patients without DIE. We have shown a distinct regulation of the immune response, angiogenesis, cell proliferation, cell adhesion and inhibition of apoptosis in PF of patients with endometriosis compared to controls. The specific protein pattern in the PF of DIE patients provides new evidence that DIE represents a unique entity of extrauterine endometriosis with enhanced angiogenetic and pro-proliferative features.
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http://dx.doi.org/10.3390/jcm9062009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7355450PMC
June 2020

Immunology of COVID-19: Mechanisms, clinical outcome, diagnostics, and perspectives-A report of the European Academy of Allergy and Clinical Immunology (EAACI).

Allergy 2020 10;75(10):2445-2476

Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA.

With the worldwide spread of the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulting in declaration of a pandemic by the World Health Organization (WHO) on March 11, 2020, the SARS-CoV-2-induced coronavirus disease-19 (COVID-19) has become one of the main challenges of our times. The high infection rate and the severe disease course led to major safety and social restriction measures worldwide. There is an urgent need of unbiased expert knowledge guiding the development of efficient treatment and prevention strategies. This report summarizes current immunological data on mechanisms associated with the SARS-CoV-2 infection and COVID-19 development and progression to the most severe forms. We characterize the differences between adequate innate and adaptive immune response in mild disease and the deep immune dysfunction in the severe multiorgan disease. The similarities of the human immune response to SARS-CoV-2 and the SARS-CoV and MERS-CoV are underlined. We also summarize known and potential SARS-CoV-2 receptors on epithelial barriers, immune cells, endothelium and clinically involved organs such as lung, gut, kidney, cardiovascular, and neuronal system. Finally, we discuss the known and potential mechanisms underlying the involvement of comorbidities, gender, and age in development of COVID-19. Consequently, we highlight the knowledge gaps and urgent research requirements to provide a quick roadmap for ongoing and needed COVID-19 studies.
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http://dx.doi.org/10.1111/all.14462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361752PMC
October 2020

Anwendung von Biologika bei allergischen und Typ-2-entzündlichen Erkrankungen in der aktuellen Covid-19-Pandemie: Positionspapier des Ärzteverbands Deutscher Allergologen (AeDA)A, der Deutschen Gesellschaft für Allergologie und klinische Immunologie (DGAKI)B, der Gesellschaft für Pädiatrische Allergologie und Umweltmedizin (GPA)C, der Österreichischen Gesellschaft für Allergologie und Immunologie (ÖGAI)D, der Luxemburgischen Gesellschaft für Allergologie und Immunologie (LGAI)E, der Österreichischen Gesellschaft für Pneumologie (ÖGP)F in Kooperation mit der deutschen, österreichischen, und schweizerischen ARIA-GruppeG und der Europäischen Akademie für Allergologie und Klinische Immunologie (EAACI)H.

Allergo J 2020 24;29(4):14-27. Epub 2020 Jun 24.

Helmholtz-Zentrum, Biedersteiner Str. 29, 80802 München, Germany.

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http://dx.doi.org/10.1007/s15007-020-2553-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289636PMC
June 2020

A compendium answering 150 questions on COVID-19 and SARS-CoV-2.

Allergy 2020 10 20;75(10):2503-2541. Epub 2020 Jul 20.

Department of Immunology and Pathology, Monash University, Melbourne, Vic., Australia.

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a "cytokine storm" leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.
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http://dx.doi.org/10.1111/all.14449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323196PMC
October 2020

COVID-19 pandemic: Practical considerations on the organization of an allergy clinic-An EAACI/ARIA Position Paper.

Allergy 2021 03;76(3):648-676

Institute of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.

Background: The coronavirus disease 2019 (COVID-19) has evolved into a pandemic infectious disease transmitted by the severe acute respiratory syndrome coronavirus (SARS-CoV-2). Allergists and other healthcare providers (HCPs) in the field of allergies and associated airway diseases are on the front line, taking care of patients potentially infected with SARS-CoV-2. Hence, strategies and practices to minimize risks of infection for both HCPs and treated patients have to be developed and followed by allergy clinics.

Method: The scientific information on COVID-19 was analysed by a literature search in MEDLINE, PubMed, the National and International Guidelines from the European Academy of Allergy and Clinical Immunology (EAACI), the Cochrane Library, and the internet.

Results: Based on the diagnostic and treatment standards developed by EAACI, on international information regarding COVID-19, on guidelines of the World Health Organization (WHO) and other international organizations, and on previous experience, a panel of experts including clinicians, psychologists, IT experts, and basic scientists along with EAACI and the "Allergic Rhinitis and its Impact on Asthma (ARIA)" initiative have developed recommendations for the optimal management of allergy clinics during the current COVID-19 pandemic. These recommendations are grouped into nine sections on different relevant aspects for the care of patients with allergies.

Conclusions: This international Position Paper provides recommendations on operational plans and procedures to maintain high standards in the daily clinical care of allergic patients while ensuring the necessary safety measures in the current COVID-19 pandemic.
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http://dx.doi.org/10.1111/all.14453DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323448PMC
March 2021

Production of allergen-specific immunotherapeutic agents for the treatment of food allergy.

Crit Rev Biotechnol 2020 Sep 9;40(6):881-894. Epub 2020 Jun 9.

National Food Institute, Technical University of Denmark, Kgs. Lyngby, Denmark.

Allergen-specific immunotherapy (IT) is emerging as a viable avenue for the treatment of food allergies. Clinical trials currently investigate raw or slightly processed foods as therapeutic agents, as trials using food-grade agents can be performed without the strict regulations to which conventional drugs are subjected. However, this limits the ability of standardization and may affect clinical trial outcomes and reproducibility. Herein, we provide an overview of methods used in the production of immunotherapeutic agents for the treatment of food allergies, including processed foods, allergen extracts, recombinant allergens, and synthetic peptides, as well as the physical and chemical processes for the reduction of protein allergenicity. Commercial interests currently favor producing standardized drug-grade allergen extracts for therapeutic use, and clinical trials are ongoing. In the near future, recombinant production could replace purification strategies since it allows the manufacturing of pure, native allergens or sequence-modified allergens with reduced allergenicity. A recurring issue within this field is the inadequate reporting of production procedures, quality control, product physicochemical characteristics, allergenicity, and immunological properties. This information is of vital importance in assessing therapeutic standardization and clinical safety profile, which are central parameters for the development of future therapeutic agents.
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http://dx.doi.org/10.1080/07388551.2020.1772194DOI Listing
September 2020

Considerations on biologicals for patients with allergic disease in times of the COVID-19 pandemic: An EAACI statement.

Allergy 2020 11;75(11):2764-2774

Translational Medicine Program, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON, Canada.

The outbreak of the SARS-CoV-2-induced coronavirus disease 2019 (COVID-19) pandemic re-shaped doctor-patient interaction and challenged capacities of healthcare systems. It created many issues around the optimal and safest way to treat complex patients with severe allergic disease. A significant number of the patients are on treatment with biologicals, and clinicians face the challenge to provide optimal care during the pandemic. Uncertainty of the potential risks for these patients is related to the fact that the exact sequence of immunological events during SARS-CoV-2 is not known. Severe COVID-19 patients may experience a "cytokine storm" and associated organ damage characterized by an exaggerated release of pro-inflammatory type 1 and type 3 cytokines. These inflammatory responses are potentially counteracted by anti-inflammatory cytokines and type 2 responses. This expert-based EAACI statement aims to provide guidance on the application of biologicals targeting type 2 inflammation in patients with allergic disease. Currently, there is very little evidence for an enhanced risk of patients with allergic diseases to develop severe COVID-19. Studies focusing on severe allergic phenotypes are lacking. At present, noninfected patients on biologicals for the treatment of asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, or chronic spontaneous urticaria should continue their biologicals targeting type 2 inflammation via self-application. In case of an active SARS-CoV-2 infection, biological treatment needs to be stopped until clinical recovery and SARS-CoV-2 negativity is established and treatment with biologicals should be re-initiated. Maintenance of add-on therapy and a constant assessment of disease control, apart from acute management, are demanded.
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http://dx.doi.org/10.1111/all.14407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7300800PMC
November 2020

EAACI Biologicals Guidelines-Recommendations for severe asthma.

Allergy 2021 01 10;76(1):14-44. Epub 2020 Aug 10.

Department of Biochemistry and Molecular Biology, Chemistry School, Complutense University of Madrid, Madrid, Spain.

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 and differences between national or regional healthcare systems. Better understanding of the mechanisms has enabled a stratified approach to the management of severe asthma, supporting the use of targeted treatments with biologicals. However, there are still many issues that require further clarification. These include selection of a certain biological (as they all target overlapping disease phenotypes), the definition of response, strategies to enhance the responder rate, the duration of treatment and its regimen (in the clinic or home-based) and its cost-effectiveness. The EAACI Guidelines on the use of biologicals in severe asthma follow the GRADE approach in formulating recommendations for each biological and each outcome. In addition, a management algorithm for the use of biologicals in the clinic is proposed, together with future approaches and research priorities.
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http://dx.doi.org/10.1111/all.14425DOI Listing
January 2021
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