Aim: The 4th Davos Declaration, convened during the Global Allergy Forum (GAF) in Davos, aimed to elevate patient care for patients with atopic dermatitis (AD) by uniting experts and stakeholders. The forum addressed the high prevalence of AD, with a strategic focus on advancing research, treatment, and management to meet the evolving challenges in the field. Methods: This multidisciplinary forum brought together top leaders from research, clinical practice, policy, and patient advocacy to discuss the critical aspects of AD, including neuroimmunology, environmental factors, comorbidities, and breakthroughs in prevention, diagnosis, and treatment. The discussions were geared towards fostering a collaborative approach to integrate these advancements into practical, patient-centric care. Results The forum underlined the mounting burden of AD, attributing it to significant environmental and lifestyle changes. It acknowledged the progress in understanding AD and in developing targeted therapies but recognized a gap in translating these innovations into clinical practice. Emphasis was placed on the need for enhanced awareness, education, and stakeholder engagement to address this gap effectively and to consider environmental and lifestyle factors in a comprehensive disease management strategy. Conclusion: The 4th Davos Declaration marks a significant milestone in the journey to improve care for people with AD. By promoting a holistic approach that combines research, education, and clinical application, the Forum sets a roadmap for stakeholders to work together to improve patient outcomes in AD, reflecting a commitment to adapt and respond to the dynamic challenges of AD in a changing world.

While the number and types of indoor air pollutants is rising, much is suspected but little is known about the impact of their potentially synergistic interactions, upon human health. Gases, particulate matter, organic compounds, but also allergens and viruses, fall within the ‘pollutant’ definition. Distinct populations, such as children and allergy and asthma sufferers are highly susceptible, while a low socioeconomic background is a further susceptibility factor; however, no specific guidance is available. We spend most of our time indoors; for children, the school environment is of paramount importance and potentially amenable to intervention. The interactions between some pollutant classes have been studied; for example, respiratory viral infection induces hyperresponsiveness to allergens, as well as irritants. However, a lot is missing in respect to understanding interactions between specific pollutants of different classes in terms of concentrations, timing, and sequence, to improve targeting and upgrade standards. SynAir-G is a European Commission-funded project aiming to reveal and quantify synergistic interactions between different pollutants affecting health, from mechanisms to real-life, focusing on the school setting. It will develop a comprehensive and responsive multipollutant monitoring system, advance environmentally friendly interventions, and disseminate the generated knowledge to relevant stakeholders in accessible and actionable formats.

Background: From early life, respiratory viruses are implicated in the development, exacerbation and persistence of respiratory conditions such as asthma. Complex dynamics between microbial communities and host immune responses, shape immune maturation and homeostasis, influencing health outcomes. We evaluated the hypothesis that the respiratory virome is linked to systemic immune responses, using peripheral blood and nasopharyngeal swab samples from preschool-age children in the PreDicta cohort. Methods: Peripheral blood mononuclear cells from 51 children (32 asthmatics, 19 healthy controls), participating in the 2-year multinational PreDicta cohort were cultured with bacterial (Bacterial-DNA, LPS) or viral (R848, Poly:IC, RV) stimuli. Supernatants were analyzed by Luminex for the presence of 22 relevant cytokines. Virome composition was obtained using untargeted high troughput sequencing of nasopharyngeal samples. The metagenomic data were used for the characterization of virome profiles and the presence of key viral families (Picornaviridae, Anelloviridae, Siphoviridae). These were correlated to cytokine secretion patterns, identified through hierarchical clustering and principal component analysis. Results: High spontaneous cytokine release was associated with increased presence of Prokaryotic virome profiles and reduced presence of Eukaryotic and Anellovirus profiles. Antibacterial responses did not correlate with specific viral families or virome profile, however, low antiviral responders had more Prokaryotic and less Eukaryotic virome profiles. Anelloviruses and Anellovirus-dominated profiles were equally distributed amongst immune response clusters. The presence of Picornaviridae and Siphoviridae was associated with low interferon-λ responses. Asthma or allergy did not modify these correlations. Conclusions: Antiviral cytokines responses at a systemic level reflect the upper airway virome composition. Individuals with low innate interferon responses have higher abundance of Picornaviruses (mostly Rhinoviruses) and bacteriophages. Bacteriophages, particularly Siphoviridae appear to be sensitive sensors of host antimicrobial capacity, while Anelloviruses are not affected by TLR-induced immune responses.

Background: Although avian coronavirus infectious bronchitis virus (IBV) and SARS-CoV-2 belong to different genera of the Coronaviridae family, exposure to IBV may result in the development of cross-reactive antibodies to SARS-CoV-2 due to homologous epitopes. We aimed to investigate whether antibody responses to IBV cross-react with SARS-CoV-2 in poultry farm personnel who are occupationally exposed to aerosolized IBV vaccines. Methods: We analyzed sera from poultry farm personnel, COVID-19 patients, and pre-pandemic controls. IgG levels against the SARS-CoV-2 antigens S1, RBD, S2, and N and peptides corresponding to the SARS-CoV-2 ORF3a, N, and S proteins as well as whole virus antigens of the four major S1-genotypes 4/91, IS/1494/06, M41, and D274 of IBV were investigated by in-house ELISAs. Moreover, live-virus neutralization test (VNT) was performed. Results: A subgroup of poultry farm personnel showed elevated levels of specific IgG for all tested SARS-CoV-2 antigens compared to pre-pandemic controls. Moreover, poultry farm personnel, COVID-19 patients, and pre-pandemic controls showed specific IgG antibodies against IBV strains. These antibody titers were higher in long-term vaccine implementers. We observed a strong correlation between IBV-specific IgG and SARS-CoV-2 S1-, RBD-, S2-, and N-specific IgG in poultry farm personnel compared to pre-pandemic controls and COVID-19 patients. However, no neutralization was observed for these cross-reactive antibodies from poultry farm personnel using the VNT. Conclusion: We report here for the first time the detection of cross-reactive IgG antibodies against SARS-CoV-2 antigens in humans exposed to IBV vaccines. These findings have implications for future vaccination strategies and possibly cross-reactive T cell immunity.

Microbial metabolism of specific dietary components, such as fiber, contribute to the sophisticated inter-kingdom dialogue in the gut that maintains a stable environment with important beneficial physiological, metabolic, and immunological effects on the host. Historical changes in fiber intake may be contributing to the increase of allergic and hypersensitivity disorders as fiber-derived metabolites are evolutionarily hardwired into the molecular circuitry governing immune cell decision making processes. In this review, we highlight the importance of fiber as a dietary ingredient, its effects on the microbiome, its effects on immune regulation, and potential mechanisms for dietary fibers in the prevention and management of allergic diseases. In addition, we review the human studies examining fiber or prebiotic interventions on asthma and respiratory outcomes, allergic rhinitis, atopic dermatitis, and overall risk of atopic disorders. While exposures, interventions and outcomes were too heterogeneous for meta-analysis, there is significant potential for using fiber in targeted manipulations of the gut microbiome and its metabolic functions in promoting immune health.

World Health Organization Global Air Quality Guideline Recommendations: Executive SummaryAnna Goshua1, Cezmi Akdis2, Kari C. Nadeau3,4 1Stanford School of Medicine, Stanford, CA, USA2Swiss Institute of Allergy and Asthma Research (SIAF), University Zurich, Davos, Switzerland3Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, CA, USA4Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Stanford University, Stanford, CA, USACorresponding Author: Kari C. Nadeau, Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford University, Stanford, CA, USA; Email: [email protected] of Interest: Dr Cezmi Akdis reports research grants from Allergopharma, Idorsia, Swiss National Science Foundation, Christine Kühne-Center for Allergy Research and Education, European Commission’s Horison’s 2020 Framework Programme “Cure”, Novartis Research Institutes, Astra Zeneca, research grants and advisory board from Glaxo Smith-Kline, Sanofi/Regeneron, Scibase, Novartis, and is Editor-in-Chief of Allergy. All other authors declare no conflict of interest.Text Word Count: 1243Abstract Word Count: 147Figure/Table Count: 2Reference Count: 9

There is increasing understanding, globally, that climate change and increased pollution will have a profound and mostly harmful effect on human health. This review brings together international experts to describe both the direct (such as heat waves) and indirect (such as vector-borne disease incidence) impacts of climate change depending on their vulnerability (i.e., diseases) on an international, economic, political and environmental context. This unique review also expands on these issues to address a third category of potential longer-term impacts on global health: famine, population dislocation, and environmental justice and education. This scholarly resource explores these issues fully, linking them to global health in urban and rural settings in developed and developing countries. The review finishes with a practical discussion of action that health professionals around the world in our field can yet take.

BACKGROUND: Characterization of disease endotypes will open a new window for the treatment of allergic rhinitis (AR). Herein we provide the first attempt to identify specific AR phenotypes/endotypes and/or any biomarker/predictor for specific treatment response based on local biological parameters. METHODS: This observational study was carried out in 142 patients with seasonal AR and 20 non-allergic controls. Total IgE levels, specific IgE to 112 allergenic molecules and 92 proinflammatory and immunologic proteins were measured in both serum and nasal secretions (NS). RESULTS: We found increased values of MCPs and MMPs in adults both in NS and serum when compared with pediatric patients (p<.05). MCPs and MMPs might represent two effective predictors of chronic inflammation. CXCL9, CXCL10, CXCL11, MCPs and MMP1 showed an upward trend both in serum and NS for patients with ≥ 3 comorbidities vs non-allergic controls(p<.05). These data suggest the involvement of these chemokines in the late phase of chronic allergic inflammation in the nose. Serum levels of IL-6, IL-8 and IL-10 (p<.05) were significantly higher in patients with AR+asthma compared to patients with different comorbidities. Conversely, serum levels of neurotrophin-3 values (p<.05) were significantly higher in those with AR+eczema vs other comorbidities groups. A subgroup of patients with a nasal hypersecretory state,called “hypersecreter endotype” was characterized by paediatric age, male gender, grass pollen sensitization and distributed among persistent, mild or moderate to severe cases of AR. CONCLUSIONS: Our study sets the groundwork for an AR endotypization at molecular level, which is highly desirable to deliver a patient-tailored approach.

Initial guidelines advised that sensitization to PEG should be taken into consideration in suspected subjects before a recommendation on the administration of vaccines for COVID-19 containing PEG or its cross-reactive analogues. 3 However, PEG shows an important variability in terms of molecular weights and conjugation forms. In that sense, although it is known that PEG-2000 (MW: 2000g/mol) conjugated with lipids is the form contained in the vaccines for COVID-19, there has been great variability in the PEG molecules used in allergy tests to evaluate sensitization of suspected subjects in the context of the current COVID-19 vaccination campaigns. 4 In this context, recent findings have shed light on the specific form of PEG that could be responsible of the hypersensitivity reactions to the mRNA vaccines for COVID-19.

Increased circulating CRTH2+Tregs are associated with asthma control and exacerbation Short running title:Increased circulating CRTH2+Tregs among patients with asthmaTeerapol Chantveerawonga, Sasipa Sangkangjanavanicha,b, Chirawat Chiewchalermsria,c, Panitan Pradubpongsaa, Wat Mitthamsiria, Sarawut Jindaratd, Ming Wange, Mübeccel Akdisf, Milena Sokolowskaf, Cezmi A. Akdisf, Atik Sangasapaviliyaa, Tadech Boonpiyathada,faDivision of Allergy and Clinical Immunology, Department of Medicine, Phramongkutklao Hospital, Bangkok, Thailandb Division of Allergy, Immunology and Rheumatology, Department of Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, ThailandcDepartment of Medicine, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi, ThailanddDepartment of Pharmacology, Phramongkutklao College of Medicine, Bangkok, ThailandeDepartment of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, and the Beijing Key Laboratory of Nasal Diseases, Beijing Institute of Otolaryngology, Beijing, ChinafSwiss Institute of Allergy and Asthma Research (SIAF), University of Zurich, and the Christine Kühne-Center for Allergy Research and Education (CK-CARE), Davos, Switzerland

Immune modulation is a key therapeutic tool for allergic diseases and asthma. It can be achieved in an antigen-specific way via allergen immunotherapy (AIT) or in endotype-driven approach using biologicals that target the major pathways of the type 2 (T2) immune response: IgE, IL-5 and IL-4/IL-13. COVID-19 vaccine provides an excellent opportunity to tackle the global pandemics and is currently being applied in an accelerated rhythm worldwide. It works as well through immune modulation. Thus, as there is an obvious interference between these treatment modalities recommendations on how they should be applied in sequence are expected. The European Academy of Allergy and Clinical Immunology (EAACI) gathered an outstanding expert panel under its Research and Outreach Committee (ROC). This expert panel was called to evaluate the evidence and formulate recommendation on the administration of COVID-19 vaccine in patients with allergic diseases and asthma receiving AIT or biologicals. The panel also formulated recommendations for COVID-19 vaccine in association with biologicals targeting the type 1 or type 3 immune response. In formulating recommendations, the panel evaluated the mechanisms of COVID-19 infection, of COVID-19 vaccine, of AIT and of biologicals and considered the data published for other anti-infectious vaccines administered concurrently with AIT or biologicals.

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