ABSTRACT
In March 2023, the European Forum for Research and Education in Allergy and Airways diseases (EUFOREA) organized its bi-annual Summit in Brussels with expert panel members of EUFOREA, representatives of the EUFOREA patient advisory board, and the EUFOREA board and management teams. Its aim was to define the research, educational and advocacy initiatives to be developed by EUFOREA over the next 2 years until the 10th anniversary in 2025. EUFOREA is an international non-for-profit organization forming an alliance of all stakeholders dedicated to reducing the prevalence and burden of chronic allergic and respiratory diseases via research, education, and advocacy. Based on its medical scientific core competency, EUFOREA offers an evidence-supported platform to introduce innovation and education in healthcare leading to optimal patient care, bridging the gap between latest scientific evidence and daily practice. Aligned with the mission of improving health care, the expert panels of asthma, allergic rhinitis (AR), chronic rhinosinusitis (CRS) & European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS), allergen immunotherapy (AIT) and paediatrics have proposed and elaborated a variety of activities that correspond to major unmet needs in the allergy and respiratory field. The current report provides a concise overview of the achievements, ambitions, and action plan of EUFOREA for the future, allowing all stakeholders in the allergy and respiratory field to be up-dated and inspired to join forces in Europe and beyond.
ABSTRACT
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.
Subject(s)
Environmental Medicine , Nasal Polyps , Nasal Surgical Procedures , Rhinitis , Sinusitis , Adult , Humans , Rhinitis/drug therapy , Chronic Disease , Sinusitis/drug therapy , Delivery of Health CareABSTRACT
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.
Subject(s)
Nasal Polyps , Rhinitis , Sinusitis , Adult , Humans , Nasal Polyps/drug therapy , Rhinitis/drug therapy , Sinusitis/drug therapy , Chronic Disease , Adrenal Cortex Hormones/therapeutic use , Delivery of Health Care , DocumentationABSTRACT
BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.
Subject(s)
Environmental Medicine , Nasal Polyps , Nasal Surgical Procedures , Otolaryngology , Rhinitis , Sinusitis , Adrenal Cortex Hormones/therapeutic use , Adult , Allergists , Antibodies, Monoclonal, Humanized , Chronic Disease , Delivery of Health Care , Humans , Nasal Polyps/therapy , Rhinitis/drug therapy , Sinusitis/drug therapySubject(s)
Environmental Medicine , Nasal Polyps , Nasal Surgical Procedures , Sinusitis , Humans , OmalizumabABSTRACT
Innovative and effective vaccination strategies are the most important lever to address the global SARS-COV2 pandemic. Within months scientists all over the world have developed promising new vaccines, many of which use adenoviral vectors to incorporate immunogenic molecules of SARS-coronavirus in order to elicit effective immune responses. The Gamaleya institute developed the COVID-19 vaccine named Sputnik (Gam-COVID-Vac) using adenoviral vectors ad 26 and ad5 to incorporate a full SARS-Spike Protein for vaccination. Two differing vectors enable so called prime-boost, thus avoiding neutralizing effects against the vector itself, ensuring proper immunogenicity against the vaccine. Current available published evidence has raised controversy among small sample sizes in phase II and early endpoints in phase III studies with Sputnik and scientific community took notice that full study protocols and clinical data haven't been made available yet. Patient subgroups and vaccination efficacy in healthy vaccinated may be at risk in case of partial viral replication of Ad5 vectors or when batch to batch reproducibility is not warranted, as concerns from authorities in Brazil and Slovakia have recently been raised. Final approval by governing health authorities (e.âg. EMA) should therefore be awaited.
Subject(s)
COVID-19 Vaccines , COVID-19 , Antibodies, Neutralizing , Antibodies, Viral , Humans , RNA, Viral , Reproducibility of Results , SARS-CoV-2 , VaccinationABSTRACT
Allergic reactions against mRNA COVID-19 vaccine are yet uncommon, but due to the high number of people who get this vaccination anaphylaxis will be seen. This is especially so in people who are sensitized to components of the vaccine. This article focuses on practical aspects of diagnostic possibilities, prevention, recognition and therapy of anaphylactic reactions. High-risk population, who should not get vaccinated; as well as people who need allergy diagnostics before vaccinations are discussed. In opinion of allergy experts patients with atopic allergies or venom allergies do not have a higher risk regarding anaphylaxic reaction due to COVID vaccination.
Subject(s)
Anaphylaxis , COVID-19 , Vaccines , Anaphylaxis/diagnosis , Anaphylaxis/etiology , Anaphylaxis/prevention & control , BNT162 Vaccine , COVID-19 Vaccines , Humans , RNA, Messenger , SARS-CoV-2 , VaccinationABSTRACT
Vaccinations are the gold-standard in order to prevent dangerous infectious diseases. Within 12 months since the RNA sequence of SARS-COV2 has been published already two RNA vaccines against COVID-19 have been licensed and are broadly used in many relevant parts of the world. Matching the challenge of an unprecedented global pandemic unique collaborative approaches have made available several vaccines based on a variety of technological platforms that are under current development. This article explains the characteristics, biology and pharmacology of subunit-vaccines, inactivated and attenuated vaccines, Virus-like-Particle vaccines, recombinant strategies based on adenoviral vectors and newly developed and first time in human licensed RNA-vaccines that came into scope recently. Allergic reactions against the vaccine and its components have been reported but are yet uncommon, however need good documentation such as other side-effects and immune-phenomena. In rare cases where allergy against vaccine components such as PEGs is considered, such PEGs can be tested using a skin-prick test. Development of innovative vaccine technology and antiviral medication is of strategic relevance in the best sense of "pandemic preparedness" for the future.
Subject(s)
COVID-19 , Hypersensitivity , BNT162 Vaccine , COVID-19 Vaccines , Humans , RNA, Messenger , RNA, Viral , SARS-CoV-2 , VaccinationABSTRACT
With BNT162b2 (approved in the EC on 27th of December 2020) and mRNA-1273 (approved in the EC on 6th of January 2021) for the first time ever two RNA-vaccines received conditional approval within the EC in order to effectively combat the SARS-COV2 pandemic. The emergence of sporadic cases of anaphylaxis following vaccination with these new compounds and the identification of PEGs (polyethylenglycols) as potential, widely used but yet usually unknown culprits have led to uncertainty among treating physicians and patients. The aim of this article series is to summarize current available pathophysiological and clinical information (part 1), to describe the characteristics of the vaccines (part 2) and to provide practical solutions for diagnosis and treatment of potential allergy against mRNACovid19 vaccines.
Subject(s)
COVID-19 , Hypersensitivity , Vaccines , BNT162 Vaccine , COVID-19 Vaccines , Humans , RNA, Messenger , RNA, Viral , SARS-CoV-2 , VaccinationABSTRACT
BACKGROUND: The burden of allergic diseases is of particular relevance for the economy and the social welfare and health insurance framework. Allergic rhinitis (AR) has a life-time prevalence of approximately 30% and is one of the most common chronic diseases with considerable socioeconomic impact thus leading to substantial direct, indirect and intangible costs. This article explores the common hypothesis that allergen-specific immunotherapy (ASIT) saves national economic expenses in the long term in comparison to other standard symptomatic treatment or no therapy. METHODS: We conducted a selective search and analysis of the literature in PubMed and Medline including otherwise listed publications in German. Using a predefined model and data extrapolation over 9 years for data from different sources and short-term clinical studies we further discuss the problems and difficulties in analyzing heterogeneous datasets. RESULTS: Using a health-economic model with currently available and accepted variables ASIT proves to be cost-effective in comparison to symptomatic treatment in allergic rhinitis; however, numerous parameters from other models have to be controlled, such as adherence to therapy and therapy discontinuation, heterogeneous costs for different treatment modalities, effect sizes with respect to symptoms including cross-influences with symptomatic rescue medication, duration of efficacy after treatment discontinuation and asthma protection. DISCUSSION: The personal appraisal of the authors demonstrates not only the current knowledge but also the problems in health economical evaluation of ASIT in allergic diseases.
Subject(s)
Asthma , Desensitization, Immunologic , Rhinitis, Allergic , Allergens , Asthma/economics , Asthma/therapy , Cost-Benefit Analysis , Desensitization, Immunologic/economics , Humans , Rhinitis, Allergic/economics , Rhinitis, Allergic/therapyABSTRACT
BACKGROUND: Allergen immunotherapy (AIT) is an effective treatment for allergic rhinoconjunctivitis (AR) with or without asthma. It is important to note that due to the complex interaction between patient, allergy triggers, symptomatology and vaccines used for AIT, some patients do not respond optimally to the treatment. Furthermore, there are no validated or generally accepted candidate biomarkers that are predictive of the clinical response to AIT. Clinical management of patients receiving AIT and efficacy in randomised controlled trials for drug development could be enhanced by predictive biomarkers. METHOD: The EAACI taskforce reviewed all candidate biomarkers used in clinical trials of AR patients with/without asthma in a literature review. Biomarkers were grouped into seven domains: (i) IgE (total IgE, specific IgE and sIgE/Total IgE ratio), (ii) IgG-subclasses (sIgG1, sIgG4 including SIgE/IgG4 ratio), (iii) Serum inhibitory activity for IgE (IgE-FAB and IgE-BF), (iv) Basophil activation, (v) Cytokines and Chemokines, (vi) Cellular markers (T regulatory cells, B regulatory cells and dendritic cells) and (vii) In vivo biomarkers (including provocation tests?). RESULTS: All biomarkers were reviewed in the light of their potential advantages as well as their respective drawbacks. Unmet needs and specific recommendations on all seven domains were addressed. CONCLUSIONS: It is recommended to explore the use of allergen-specific IgG4 as a biomarker for compliance. sIgE/tIgE and IgE-FAB are considered as potential surrogate candidate biomarkers. Cytokine/chemokines and cellular reponses provided insight into the mechanisms of AIT. More studies for confirmation and interpretation of the possible association with the clinical response to AIT are needed.
Subject(s)
Asthma/diagnosis , Asthma/therapy , Conjunctivitis, Allergic/diagnosis , Conjunctivitis, Allergic/therapy , Desensitization, Immunologic , Rhinitis, Allergic/diagnosis , Rhinitis, Allergic/therapy , Allergens/immunology , Asthma/immunology , Basophils/immunology , Basophils/metabolism , Biomarkers , Conjunctivitis, Allergic/immunology , Cytokines/metabolism , Desensitization, Immunologic/methods , Humans , Immunoglobulin E/immunology , Immunoglobulin G/immunology , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Prognosis , Rhinitis, Allergic/immunology , Treatment OutcomeABSTRACT
Interferon-γ (IFN-γ) and interleukin-4 (IL-4) are key effector cytokines for the differentiation of T helper type 1 and 2 (Th1 and Th2) cells. Both cytokines induce fate-decisive transcription factors such as GATA3 and TBX21 that antagonize the polarized development of opposite phenotypes by direct regulation of each other's expression along with many other target genes. Although it is well established that mesenchymal cells directly respond to Th1 and Th2 cytokines, the nature of antagonistic differentiation programs in airway epithelial cells is only partially understood. In this study, primary normal human bronchial epithelial cells (NHBEs) were exposed to IL-4, IFN-γ, or both and genome-wide transcriptome analysis was performed. The study uncovers an antagonistic regulation pattern of IL-4 and IFN-γ in NHBEs, translating the Th1/Th2 antagonism directly in epithelial gene regulation. IL-4- and IFN-γ-induced transcription factor hubs form clusters, present in antagonistically and polarized gene regulation networks. Furthermore, the IL-4-dependent induction of IL-24 observed in rhinitis patients was downregulated by IFN-γ, and therefore IL-24 represents a potential biomarker of allergic inflammation and a Th2 polarized condition of the epithelium.
Subject(s)
Bronchi/pathology , Interferon-gamma/immunology , Interleukin-4/immunology , Interleukins/metabolism , Respiratory Mucosa/physiology , Rhinitis, Allergic/immunology , Th2 Cells/immunology , Adult , Cell Differentiation , Cells, Cultured , Female , Gene Expression Profiling , Gene Expression Regulation/immunology , Gene Regulatory Networks , Humans , Interleukins/genetics , Male , Middle Aged , Primary Cell Culture , Respiratory Mucosa/pathology , Rhinitis, Allergic/diagnosis , Th1 Cells/immunology , Young AdultABSTRACT
Diagnosis early in life, sensitization, asthma endotypes, monitoring of disease and treatment progression are key motivations for the exploration of biomarkers for allergic rhinitis and allergic asthma. The number of genes related to allergic rhinitis and allergic asthma increases steadily; however, prognostic genes have not yet entered clinical application. We hypothesize that the combination of multiple genes may generate biomarkers with prognostic potential. The current review attempts to group more than 161 different potential biomarkers involved in respiratory inflammation to pave the way for future classifiers. The potential biomarkers are categorized into either epithelial or infiltrate-derived or mixed origin, epithelial biomarkers. Furthermore, surface markers were grouped into cell-type-specific categories. The current literature provides multiple biomarkers for potential asthma endotypes that are related to T-cell phenotypes such as Th1, Th2, Th9, Th17, Th22 and Tregs and their lead cytokines. Eosinophilic and neutrophilic asthma endotypes are also classified by epithelium-derived CCL-26 and osteopontin, respectively. There are currently about 20 epithelium-derived biomarkers exclusively derived from epithelium, which are likely to innovate biomarker panels as they are easy to sample. This article systematically reviews and categorizes genes and collects current evidence that may promote these biomarkers to become part of allergic rhinitis or allergic asthma classifiers with high prognostic value.
Subject(s)
Asthma/etiology , Asthma/metabolism , Biomarkers , Hypersensitivity/etiology , Hypersensitivity/metabolism , Airway Remodeling , Animals , Antigens, Surface/metabolism , Asthma/diagnosis , Asthma/prevention & control , Environmental Exposure/adverse effects , Genetic Predisposition to Disease , Humans , Hypersensitivity/prevention & control , Immune System/cytology , Immune System/immunology , Immune System/metabolism , MicrobiotaABSTRACT
BACKGROUND: The number of injections in the dose escalation of subcutaneous immunotherapy (SCIT) is small for some currently used hypoallergenic allergoids, but can still be inconvenient to patients and can impair compliance. The aim of this trial was to compare safety and tolerability of an accelerated to the conventional dose escalation scheme of a grass pollen allergoid. METHODS: In an open label phase II trial, 122 patients were 1:1 randomized for SCIT using a grass pollen allergoid with an accelerated dose escalation comprising only 4 weekly injections (Group I) or a conventional dose escalation including 7 weekly injections (Group II). Safety determination included the occurrence of local and systemic adverse events. Tolerability was assessed by patients and physicians. RESULTS: Treatment-related adverse events were observed in 22 (36.1 %) patients in Group I and 15 (24.6 %) in Group II. Local reactions were reported by 18 patients in Group I and 11 in Group II. Five Grade 1 systemic reactions (WAO classification) were observed in Group I and 2 in Group II. Grade 2 reactions occurred 3 times in Group I and 2 times in Group II. Tolerability was rated as "good" or "very good" by 53 (86.9 %) patients in Group I and 59 (100 %) in Group II by investigators. Forty-eight patients in Group I (80.0 %) and 54 in Group II (91.5 %) rated tolerability as "good" or "very good". CONCLUSIONS: The dose escalation of a grass pollen allergoid can be accelerated with safety and tolerability profiles comparable to the conventional dose escalation.
