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A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 billion to €1.8 billion, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education. A 10-year national program to improve prevention and management of allergic diseases and asthma was implemented in Finland (population 5.5. million) in 2008-2018. The main aim was to reduce the long-term burden of these conditions. The strategy was changed from traditional avoidance to tolerance and resilience of the population. Health was endorsed instead of medicalization of mild symptoms. Disease severity was reevaluated, and disabling clinical manifestations were given high priority. For health care, 5 quantitative goals and 1 qualitative goal were set. For each of the goals, specific tasks, tools, and outcome evaluation were stipulated. During the program, 376 educational sessions gathered 24,000 health care participants. An information campaign targeted the lay public, and social media was used to contact people. In the 10 years of the program, the prevalence of allergic diseases and asthma leveled off. Asthma caused fewer symptoms and less disability, and 50% fewer hospital days. Food allergy diets in day care and schools decreased by half. Occupational allergies were reduced by 45%. In 2018, the direct and indirect costs of allergic diseases and asthma ranged from €1.5 billion to €1.8 billion, with the 2018 figures being 30% less than in the respective figures in 2007. The Finnish proactive and real-world intervention markedly reduced the public health burden of allergic disorders. The allergy paradigm was revisited to improve management with systematic education. Allergy is a systemic, immunologic, and heterogenous disorder, with variable organ manifestations that change during the life span. They cause a fair amount of disability and costs both for individuals and for society. There are no reports of coordinated action plans to combat allergic conditions in a defined population. In Finland (population 5.5 million), several successful national public health programs to control respiratory diseases have been completed.1Erhola M. Vasankari T. Jormanainen V. Toppila-Salmi S. Herrala J. Haahtela T. 25 years of respiratory health in Finland.Lancet Respir Med. 2019; 7: e16Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar The Finnish Asthma Program 1994-2004 was successful and deployed in many countries.2Selroos O. Kupczyk M. Kuna P. Łacwik P. Bousquet J. Brennan D. et al.National and regional asthma programmes in Europe.Eur Respir Rev. 2015; 137: 474-483Crossref Scopus (64) Google Scholar The latest action plan, the Finnish Allergy Program 2008-2018, was initiated to further reduce the burden on individuals and society by emphasizing prevention. The Finnish Allergy Program was based on an extensive review3von Hertzen L.C. Savolainen J. Hannuksela M. Klaukka T. Lauerma A. Mäkelä M.J. et al.Scientific rationale for the Finnish Allergy Programme 2008-2018: emphasis on prevention and endorsing tolerance.Allergy. 2009; 64: 678-701Crossref PubMed Scopus (54) Google Scholar of the new knowledge regarding immune regulation and the importance of nature relatedness.4Ege M.J. Mayer M. Normand A.C. Genuneit J. Cookson W.O. Braun-Fahrländer C. et al.GABRIELA Transregio 22 Study Group. Exposure to environmental microorganisms and childhood asthma.N Engl J Med. 2011; 364: 701-709Crossref PubMed Scopus (1044) Google Scholar, 5Hanski I. von Hertzen L. Fyhrquist N. Koskinen K. Torppa K. Laatikainen T. et al.Environmental biodiversity, human microbiota, and allergy are interrelated.Proc Natl Acad Sci U S A. 2012; 109: 8334-8339Crossref PubMed Scopus (628) Google Scholar, 6Lynch S.V. Wood R.A. Boushey H. Bacharier L.B. Bloomberg G.R. Kattan M. et al.Effects of early-life exposure to allergens and bacteria on recurrent wheeze and atopy in urban children.J Allergy Clin Immunol. 2014; 134: 593-601Abstract Full Text Full Text PDF PubMed Scopus (259) Google Scholar, 7Haahtela T. Laatikainen T. Alenius H. Auvinen P. Fyhrquist N. Hanski I. et al.Hunt for the origin of allergy - comparing the Finnish and Russian Karelia.Clin Exp Allergy. 2015; 45: 891-901Crossref PubMed Scopus (92) Google Scholar The main aim was to transform the strategy from avoidance to tolerance and resilience. It focused on allergy health (ie, having a good life despite allergies). Reducing unnecessary treatments and measures was important, especially in children and families. Severe allergy and asthma were given attention. Goals for health care, such as standardizing diagnostics,8Heinzerling L. Frew A.J. Bindslev-Jensen C. Bonini S. Bousquet J. Bresciani M. et al.Standard skin prick testing and sensitization to inhalant allergens across Europe-a survey from the GALEN network.Allergy. 2005; 60: 1287-1300Crossref PubMed Scopus (202) Google Scholar halving the prevalence of food allergy diets, and reducing the total costs of allergic diseases and asthma by 20%, were set. The program has now been completed, and it represents a successful change management initiative at the country level. In this review, we present the program's main outcomes and discuss the possibilities of scaling up the experience for other countries and extending it into the future. In Finland and globally, the incidence of asthma and allergic diseases has been increasing for decades.9Haahtela T. Lindholm H. Björksten F. Koskensuo K. Laitinen L.A. Prevalence of asthma in Finnish young men.BMJ. 1990; 301: 266-268Crossref PubMed Scopus (227) Google Scholar,10Bach J.F. The effect of infections on susceptibility to autoimmune and allergic diseases.N Engl J Med. 2002; 347: 911-920Crossref PubMed Scopus (1978) Google Scholar Currently, 30%-40% of Finnish schoolchildren and young adults appear to be sensitized to 1 or more common allergens.11Ruokolainen L. Paalanen L. Karkman A. Laatikainen T. von Hertzen L. Vlasoff T. et al.Significant disparities in allergy prevalence and microbiota between the young people in Finnish and Russian Karelia.Clin Exp Allergy. 2017; 47: 665-674Crossref PubMed Scopus (65) Google Scholar The problem was already discernible in the 1980s, when the first allergy management guideline in Finland was published,12Ministry of Social Affairs and Health, Helsinki, Finland, A statement of an allergy commission. 1983;28;1-105 [in Finnish and Swedish].Google Scholar and also in 1998, when a consensus report was prepared.13The Finnish Medical Association Duodecim and the Academy of Finland 1998. Allergic population – allergy as a publich health problem. Consensus Meeting in Hanasaari 11.11.1998, pp 1-189 [in Finnish].Google Scholar The numbers of patients with allergy and asthma grew in the 1990s, and neither children nor adults received satisfactory allergy care. The 10-year Finnish Asthma Program was based on new information on asthma, primarily as an inflammatory disease.14Haahtela T. Järvinen M. Kava T. Kiviranta K. Koskinen S. Lehtonen K. et al.Comparison of a beta 2-agonist, terbutaline, with an inhaled corticosteroid, budesonide, in newly detected asthma.N Engl J Med. 1991; 325: 388-392Crossref PubMed Scopus (672) Google Scholar In a relatively short period, management was improved and costs were reduced by better early diagnostics and by turning from β2-agonists to inhaled corticosteroids as the first-line medications.15Haahtela T. Tuomisto L.E. Pietinalho A. Klaukka T. Erhola M. Kaila M. et al.A 10 year asthma programme in Finland: major change for the better.Thorax. 2006; 61: 663-670Crossref PubMed Scopus (302) Google Scholar,16Haahtela T. Herse F. Karjalainen J. Klaukka T. Linna M. Leskelä R.L. et al.The Finnish experience to save asthma costs by improving care in 1987-2013.J Allergy Clin Immunol. 2017; 139: 408-414Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar But the main problem of how to prevent asthma and allergic diseases in the first place remained. At the population level, avoidance and fear of all exposure leads to (1) an increased need for treatment, (2) social consequences such as isolation and impairment of daily living, and (3) even serious allergic reactions if exposure (eg, to foods) occurs unexpectedly. Avoidance of allergens is always important for individual patients, especially in cases of severe food allergy, but it requires justified grounds and better-defined time limits. Concern and medicalization became visible as new allergy day care centers, allergy schools, and allergen-free working environments were demanded. At the same time, large trials indicated that the avoidance of allergens to prevent clinical symptoms may not be feasible in the long term.3von Hertzen L.C. Savolainen J. Hannuksela M. Klaukka T. Lauerma A. Mäkelä M.J. et al.Scientific rationale for the Finnish Allergy Programme 2008-2018: emphasis on prevention and endorsing tolerance.Allergy. 2009; 64: 678-701Crossref PubMed Scopus (54) Google Scholar Psychosocial factors should also be addressed, as they play an important role in patient decisions and adherence to treatment. Tolerance and resilience are immunologic, psychological, and societal.17Haahtela T. Anto J.M. Bousquet J. Fast and slow health crises of Homo urbanicus: loss of resilience in communicable diseases, like COVID-19, and non-communicable diseases.Porto Biomed J. 2020; 5: e073Crossref PubMed Google Scholar The allergy paradigm was revisited, and loss of immune balance was regarded as more important than any possible new risk factor. At the population level, endorsing tolerance, especially in children, adolescents, and families, was regarded as central.18Pelkonen A.S. Kuitunen M. Dunder T. Reijonen T. Valovirta E. Mäkelä M.J. et al.Allergy in children: practical recommendations of the Finnish Allergy Programme 2008-2018 for prevention, diagnosis, and treatment.Pediatr Allergy Immunol. 2012; 23: 103-116Crossref PubMed Scopus (33) Google Scholar A major change of attitude was needed among health professionals, patients, and the lay public. To be effective at a public health level, a program needs to change management and have a societal impact. In this review, the program is presented according to the classical change management model of Kotter,19Kotter J. Leading change. Harvard Business School Press, Boston, Mass1996Google Scholar as an example for many other noncommunicable diseases. Allergic diseases are a model of a life course approach, as they often start at birth and usually persist throughout life. A 10-year program was planned, implemented, and monitored to change the management strategy at the national level to care pathways centered around the patient. Health professionals needed help to adapt new ideas and improve the provision of care, patients needed to be involved for shared decision making, and the lay public needed to be informed. This was achieved in close collaboration with policymakers (the Finnish Institute for Health and Welfare) to provide a new national strategy and create grounds for future initiatives. Allergy management is split into several specialities in the medical discipline. The position of allergology as a main speciality, subspeciality, or additional training courses varies from one country to another. In most countries, a coordinated public health approach to management of allergies is lacking. Are specialists providing support for general practitioners and for those working at the grassroots level? Do private sector and public health professionals have the same goal? Overall, allergy services seem widely inadequate.20Diwakar L. Cummins C. Lilford L. Roberts T. Systematic review of pathways for the delivery of allergy services.BMJ Open. 2017; 7e012647Crossref PubMed Scopus (21) Google Scholar Finland was no exception, with cooperation being problematic both between primary and secondary care and between different specialities. However, Finland's small population with a relatively high level of education and well-organized public health care established a population management model and took steps from treatment to prevention. After a consensus meeting involving clinicians with different specialities, epidemiologists, nutritionists, immunologists, patients, citizens, and health officials, a group of experts prepared the 10-year program, which was launched in April 2008 (see Fig E1 in this article's Online Repository at www.jacionline.org).21Haahtela T. von Hertzen L. Mäkelä M. Hannuksela M. Allergy Programme Working GroupFinnish Allergy Programme 2008-2018 - time to act and change the course.Allergy. 2008; 63: 634-645Crossref PubMed Scopus (124) Google Scholar,22Bousquet J. Bieber T. Fokkens W. Kowalski M. Humbert M. Niggemann B. et al.In Allergy, ‘new day has begun’.Allergy. 2008; 63: 631-633Crossref PubMed Scopus (15) Google Scholar The coalition continued as a program steering group. The organization was kept simple and without hierarchies. Strategies were chosen, and goals were set. The key messages targeted all citizens (Table I). For health professionals, 6 goals (5 of which were quantitative) and indicators were tailored (Table II). Each goal had its specific tasks, tools, and evaluation methods. The tasks were the activities or the targets in pursuing the goal (what to do), and the tools were those used to perform the tasks (how to do it). The outcomes were evaluated and verified. The program linked allergy not only with clinical disease but also with allergy health. Mild symptoms, especially in childhood, were regarded as a immune and not as a for or A.S. Kuitunen M. Dunder T. Reijonen T. Valovirta E. 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Recent advances in biological therapies, small molecules and allergen-specific immunotherapy are reshaping the management of immunoallergic diseases, progressively shifting therapeutic goals from short-term disease control toward the possibility of achieving sustained clinical remission. Despite increasing evidence across multiple conditions, a universally accepted and disease-transversal definition of clinical remission (CR) remains lacking. In this review we propose a comprehensive framework for defining clinical remission across a broad spectrum of immune-mediated diseases traditionally managed in Allergy and Clinical Immunology practice, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, chronic urticaria, atopic dermatitis, mastocytosis, food allergy, and eosinophilic esophagitis. Clinical remission is defined as a sustained state of absence of clinically relevant disease manifestations, independently of underlying biological activity; suppression of inflammatory pathways and normalization of biomarkers define biological remission, which may coexist with, but is not required for, clinical remission. We introduce the 3D-CR model, a pragmatic, disease-adaptable framework integrating 3 complementary domains - clinical, biological, and functional - to characterize remission states as complete, partial, or absent. Building on this model, we propose the Allergic Disease Remission Score (ADReS) as a modular tool designed to support standardized assessment, longitudinal follow-up, and cross-disease comparison in clinical trials and real-world settings. These tools are intended as conceptual and research instruments rather than prescriptive algorithms for individual therapeutic decision-making. Finally, we outline a World Allergy Organization call to action advocating for a harmonized global approach to defining, measuring, and implementing clinical remission as a meaningful treatment target. Establishing standardized remission endpoints has the potential to improve patient outcomes, facilitate precision medicine strategies, enhance comparability across studies, and reduce heterogeneity in clinical research and practice worldwide.

The 2025 World Allergy Organization (WAO) Guidelines for the Classification, Diagnosis, and Treatment of Hereditary Angioedema (HAE) with Consideration of Worldwide Disparities provide a comprehensive, evidence-informed, and globally applicable framework for the care of this rare and potentially life-threatening disorder. HAE is a genetic disease characterized by recurrent episodes of subcutaneous and submucosal swelling, most commonly mediated by bradykinin, and is associated with substantial morbidity, impaired quality of life, and a lifelong risk of fatal laryngeal edema. The Guidelines were developed by an international panel of 40 experts from 22 countries, with representation from all world regions, reflecting the commitment of WAO to geographic diversity, inclusiveness, and global relevance. The development process for these guidelines followed a structured and transparent methodology that integrated systematic literature review, appraisal of real-world evidence, and application of the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) framework adapted for rare diseases, complemented by a formal Delphi consensus process. This approach was specifically designed to address the limitations of conventional evidence hierarchies in rare disorders, while ensuring clinical applicability across heterogeneous healthcare systems and resource settings. A central element of the guidelines is an updated classification of HAE based on underlying pathophysiology and disease endotypes. The traditional distinction between HAE types 1 and 2 is unified under the term HAE with C1 inhibitor deficiency (HAE-C1-INH), reflecting shared biological mechanisms and management principles. The guidelines also recognize an expanding spectrum of HAE with normal C1 inhibitor (HAE-nC1-INH), including forms associated with pathogenic variants in F12, PLG, ANGPT1, KNG1, MYOF, HS3ST6, CPN1, and DAB2IP, as well as cases with currently unidentified genetic causes. The diagnostic strategy emphasizes early clinical recognition based on characteristic features, including recurrent angioedema without urticaria, abdominal or laryngeal involvement, early symptom onset, and family history. A simplified diagnostic algorithm is proposed, prioritizing the C1 inhibitor functional assay as the preferred initial test when performed in a reliable specialized laboratory. Alternative diagnostic pathways are outlined for settings with limited access to specialized testing, including pragmatic combinations of biochemical assays and selective use of genetic testing, particularly relevant for HAE-nC1-INH and family screening. Management recommendations address on-demand treatment of acute attacks, short-term prophylaxis, and individualized long-term prophylaxis. Universal access to on-demand therapy is emphasized for all patients with confirmed HAE, including those who are asymptomatic, given the unpredictable nature of attacks and lifelong risk. Long-term prophylaxis is addressed within a treat-to-target framework aimed at achieving complete disease control and sustained improvement in health-related quality of life, with regular reassessment and shared decision-making. Empowering patients and caregivers through structured education, access to appropriate medications, and integration with specialized referral centers is associated with earlier treatment, reduced healthcare utilization, and improved equity of care and reduced avoidable morbidity and mortality worldwide. The 2025 WAO Guidelines for Hereditary Angioedema establish an evidence-informed, patient-centered, and forward-looking framework for the classification, diagnosis, and management of HAE. By integrating advances in pathophysiology, diagnostics, and therapeutics with global expert consensus and real-world considerations, the guidelines aim to support consistent, equitable, and high-quality care for patients with HAE across regions and healthcare systems.

The recently published PROMUSE study performed by the GA2LEN UCARE (Urticaria Centers of Reference and Excellence) and ADCARE (Angioedema Centers of Reference and Excellence) networks found that patient-reported outcome measures (PROMs) are underused in clinical practice for atopic dermatitis (AD) and chronic urticaria (CU). The reasons for this remain unknown. We studied why physicians have reservations about using PROMs, how PROM use is affected by the barriers they perceive, and what the physician demographics/characteristics associated with these barriers are. This is an observational, cross-sectional study where the PROMUSE questionnaire was used and applied to physicians from 45 specialized centers worldwide. Of the 2534 physicians surveyed in the PROMUSE study, 474 who treated patients with AD and CU were included in the analysis. For the 474 physicians who treat AD and CU patients, the most common issues perceived as primary barriers to PROM use were "time constraints" (n = 455/474), "not mandated to complete" (n = 428/474), and "patients dislike PROMs" (n = 425/474). Higher rates of barrier perception were observed for males, younger physicians, and non-specialist physicians. The more barriers physicians perceive, the less frequently PROMs are used, with a strong and significant negative correlation between the number of barriers perceived and the frequency of PROM use. Two of the 15 perceived barriers significantly prevented using PROMs: the belief that PROMs constrain the doctor-patient relationship and the belief that patients dislike them. The underutilization of PROMs in AD and CU is strongly driven by physicians' perceptions that patients dislike them and that they constrain the doctor-patient relationship. This suggests physicians may have deeper insights into the practical shortcomings of current instruments. Therefore, rather than solely focusing on physician education, existing AD and CU PROMs urgently require re-evaluation and co-development with direct patient involvement (eg, Core Outcome Sets) to ensure they are genuinely patient-centered and clinically relevant.

Perioperative anaphylaxis (POA) is a life-threatening condition with substantial variability in evaluation and management practices. To assess current practices, perceived barriers, and regional differences in POA management among allergists worldwide. A cross-sectional online survey was distributed to World Allergy Organization (WAO) members from March to June 2024. The 39-question survey addressed demographics, clinical practices, diagnostic tools, perceived challenges, and future needs. A total of 249 respondents from 50 countries completed the survey (median age 49 years, 49% female, 94% allergists, and 57% with >15 years of clinical experience). While 70% had access to acute serum tryptase (sAT), only 46% obtained it within the recommended 2-h window. Guideline adherence was low: 63% did not perform skin testing 4-6 weeks post-reaction, and fewer than half routinely tested for latex or chlorhexidine. Regional differences were observed: routine latex and chlorhexidine testing was most common in Europe and United States/Canada and least frequent in Africa and Asia (p = 0.0001); tryptase availability was lower in Africa and Latin America. Most respondents identified a culprit in <65% of cases, with antibiotics reported most frequently in Europe and United States/Canada, followed by neuromuscular blocking agents and non-steroidal anti-inflammatory drugs (NSAIDs). Major barriers included limited access to anesthesia records, testing reagents, and resource-related contrainsts in low-income regions. Respondents expressed the need for guidelines on alternative agents and validated non-irritating skin test concentrations. This international survey highlights substantial regional differences and global barriers in POA evaluation. Improving access to diagnostic resources, enhancing interdisciplinary collaboration, and providing clear guidance on alternative agents and standardized testing methods are essential to optimize worldwide POA management.

Subcutaneous immunotherapy (SCIT), a form of allergy immunotherapy, can alter the natural course of allergic diseases and induce tolerance to causative allergens by modulating type 2 immune responses. While the regulatory effects of SCIT on Th2 cells have been extensively studied, its effects on group 2 innate lymphoid cells (ILC2s) remain poorly understood. In a murine model of asthma, we demonstrated that SCIT increased the production of allergen-specific IgG1, which is analogous to human IgG4. To clarify the role of IgG1 in the mechanisms underlying SCIT, we evaluated its effects on the development of allergic asthma and the proliferation of ILC2s. BALB/c mice were sensitized with ovalbumin (OVA) and Al(OH)3, followed by SCIT consisting of 3 subcutaneous OVA injections at a dose of 1 mg/animal. After SCIT, sera were collected, and total IgG1 was purified using the pH-gradient elution method. ILC2s were isolated from the lungs of OVA-challenged mice and stimulated with IL-33 in the presence of OVA and the purified IgG1 for 72 h, after which cell proliferation was assessed using an ATP assay. For in vivo experiments, the purified IgG1 was intratracheally administered to OVA-challenged asthmatic mice, and airway remodeling and lung leukocyte populations were subsequently analyzed. Animal experiments were approved by the Experimental Animal Research Committee of Setsunan University (approval Nos. K21-1, K22-1, K23-1, K24-1, and K25-1) and conducted in accordance with the ARRIVE 2.0 guidelines. (1) IgG1+ B cells were markedly increased in the lungs of SCIT-treated asthmatic mice (p = 0.0409) and were the most abundant among the 4 IgG+ B-cell subsets. (2) Intratracheal administration of IgG1 derived from SCIT mice (SCIT-IgG1) significantly suppressed epithelial thickening and mucus accumulation, and reduced the numbers of lung ILC2s and eosinophils in the asthma model (p = 0.0034, 0.0341, 0.0246, and 0.0041, respectively). (3) Fc&#x3b3;RIIb expression on lung ILC2s derived from asthmatic mice was significantly increased (p = 0.0004). (4) SCIT-IgG1 significantly suppressed OVA and IL-33-induced in vitro proliferation of ILC2s (p = 0.0018), and this inhibitory effect disappeared in the presence of an anti-Fc&#x3b3;RIIb antibody. SCIT-IgG1 attenuates airway remodeling and limits ILC2 expansion in allergic airway inflammation. Mechanistically, SCIT-IgG1 restrains ILC2 proliferation via Fc&#x3b3;RIIb engagement, revealing an antibody-ILC2 inhibitory axis that likely contributes to the efficacy of allergy immunotherapy and suggests therapeutic strategies that enhance inhibitory Fc&#x3b3;R signaling to control type 2 inflammation.

Allergen specific immunotherapy (AIT) is a guideline-approved treatment that can modify the course of allergic rhinitis (AR). The treatment regimen for AIT in pollen-induced AR is more complex due to the impact of pollen exposure and there is no uniform recommendation on the time to initiate AIT for pollen-induced AR. The aim of this study was to investigate whether the initiation timing pre- or post-pollen season (PS) influence efficacy of Artemisia Annua sublingual immunotherapy (SLIT) in patients with allergic rhinitis. This was an open-label multicenter clinical trial. We recruited eligible patients in March 2022 and November 2022 from 3 treatment centers, and initiated SLIT before and after the PS of Artemisia Annua in 2022. Meanwhile, a control group was also set up to receive rescue medicine. Symptoms and medication usage were assessed throughout the PS, efficacy of SLIT was evaluated by comparing changes from baseline in: 1) the combined symptom-medication score (CSMS), 2) total nasal symptom score (TNSS), 3) ocular symptom score (TOSS), and 4) medication score (MS). A linear mixed-effects model (LMM) was employed to analyze the effects of treatment (SLIT vs. control), treatment initiation timing (pre-vs. post-season) on therapeutic outcomes. SLIT significantly alleviated symptoms and reduced medication use compared to control, regardless of whether initiation before or after the PS. Furthermore, the LMM indicated that initiation timing (pre-vs. post-season) did not significantly affect treatment efficacy. There was no significant interaction effect between initiation timing and treatment group. It was also shown that higher pollen concentration was significantly associated with worse symptom severity and increased medication use. This multi-center study further confirms the efficacy of SLIT for Artemisia Annua-induced AR. We demonstrated that initiating SLIT before or after the PS did not affect its therapeutic efficacy by using LMM. This finding addresses a gap regarding the optimal timing for SLIT initiation and provides crucial evidence to inform clinical decision-making, offering greater flexibility in treatment scheduling. NCT05318157; Registered March 22, 2008.

Advances in the understanding of type 2 inflammation have driven the development of novel biologics and small molecules for allergic diseases. New therapies targeting cytokines, receptors, and intracellular pathways offer opportunities to refine disease management and modify long-term outcomes. The World Allergy Organization (WAO) Biologics Therapies in Allergic Diseases Committee conducted this state-of-the-art review. We analyzed current literature on investigational monoclonal antibodies, nanobody-based agents, kinase inhibitors, and small molecules with potential applications in asthma, chronic rhinosinusitis with nasal polyposis, atopic dermatitis, and chronic spontaneous urticaria. Mechanistic considerations, therapeutic targets, and clinical trial outcomes were evaluated to highlight emerging trends in biologic and small-molecule therapy. Biologics targeting IL-4, IL-5, IL-13, IL-31, TSLP, and IgE continue to expand therapeutic options across allergic disorders. Innovations such as Fc-engineered antibodies, bispecific antibodies, and nanobody platforms enhance efficacy, extend half-life, and improve tissue penetration. Novel intracellular inhibitors, including JAK, SYK, and STAT6 degraders, show promise as oral alternatives to injectable therapies. Clinical trials report high efficacy and favorable safety profiles, though variability remains across diseases and endotypes. Pediatric data are limited, and the long-term safety and cost-effectiveness of this approach require further evaluation. Emerging biologics and small molecules are transforming the therapeutic landscape of allergic diseases, providing targeted and personalized interventions. Advances in molecular engineering, particularly nanobody technology and intracellular inhibitors, hold promise for improving patient outcomes and reducing treatment burden. Future research should prioritize long-term safety and standardized approaches to optimize integration of these therapies into clinical practice.

Asthma is a chronic respiratory disease characterized by chest tightness, coughing, shortness of breath, and wheezing. Results from the Global Burden of Diseases Study 2021 have shown that asthma poses a notable burden on patients in Malaysia and Singapore (age-standardized prevalence rates of 2461.83 and 3352.79 per 100,000 individuals, and age-standardized disability-adjusted life year rates of 189.06 and 139.99 per 100,000 individuals, respectively). The current study aimed to compare the patterns of asthma symptoms and exacerbations between participants from Malaysia and Singapore, using data from the Singapore/Malaysia Cross-Sectional Genetic Epidemiological Study (SMCGES). The SMCGES has been ongoing since August 2005 at the National University of Singapore; Universiti Tunku Abdul Rahman; and Sunway University. Data on asthma status, symptoms, and exacerbations were obtained via a standardized and validated protocol established by the International Study of Asthma and Allergies in Childhood. Participants who indicated having ever had asthma were classified as recognized asthma cases. Participants recruited in Malaysia (henceforth referred to as "Malaysian subset", n = 4028) and Singapore (henceforth referred to as "Singaporean subset", n = 11,473) were analyzed. Compared to participants from Singapore, those from Malaysia were younger (mean age &#xb1; standard deviation: 21.1 &#xb1; 4.6 vs 22.8 &#xb1; 5.7, P < .001) and more likely to be female (65.0% vs 58.1%, P < .001). The prevalence of recognized asthma was higher among subjects recruited in Singapore than in Malaysia (22.7% vs 12.0%, P < .001). However, asthma symptoms were significantly more prevalent among respondents from Malaysia than from Singapore. These included ever-wheezing (20.8% vs 18.9%, P = .01), wheezing in the past 12 months (15.8% vs 9.2%, P < .001), experiencing a wheezy chest after exercise (11.6% vs 4.0%, P < .001), and experiencing a dry nocturnal cough (13.2% vs 11.4%, P = .004). Participants recruited in Malaysia experienced more daytime asthma attacks (fewer than once a month: 26.1% vs 13.3%, at least once monthly: 3.3% vs 2.6%, P < .001) and nighttime asthma attacks (fewer than once a month: 25.6% vs 10.5%, at least once monthly: 6.1% vs 2.3%, P < .001) than their Singaporean counterparts. As compared to the Singaporean subset, more individuals from the Malaysian subset missed school or work at least once in the past 12 months due to wheezing or asthma (8.0% vs 2.8%, P < .001), visited the general practitioner or specialist for asthma (1-3 visits: 14.2% vs 9.5%, at least 4 visits: 3.4% vs 1.2%, P = .002), visited the emergency department for asthma (at least once: 6.0% vs 1.6%, P < .001), or had been admitted to the hospital for asthma (at least once: 8.1% vs 1.1%, P < .001). The prevalence of recognized asthma was higher in the Singaporean subset than in the Malaysian subset. However, there was a greater proportion of the Malaysian subset than that of Singapore that exhibited higher frequencies of wheezing, wheezing after exercising, and dry nocturnal coughing. Additionally, asthma exacerbations were more frequent in Malaysia than in Singapore. These results suggest that asthma is under-recognized and undermanaged in Malaysia.

Patients with chronic spontaneous urticaria (CSU) often experience diagnostic delays and uncontrolled disease, highlighting the need to improve CSU care. The BRIDGE study, a hybrid type 1 effectiveness-implementation study, evaluated the effectiveness and feasibility of an urticaria care package (UCP) to increase patient-reported outcome (PRO) use in clinical practice and improve CSU care among general practitioners (GPs). Two surveys were conducted, 1 before and 1 after UCP implementation. This report focuses on pre-implementation data regarding the management and knowledge of CSU among GPs in Italy. Eligible GPs were from Lombardy, an administrative region of Italy, who had been in clinical practice for 3-30 years and had access to electronic medical records. GPs completed a self-administered, web-based survey, prior to UCP implementation. Survey questions included the following topics: awareness and knowledge of CSU, use of CSU-specific PROs or other PROs, attitudes towards UCP adoption, implementation climate, and key factors influencing UCP adoption. The analysis included GPs who completed &#x2265;1 item on the pre-implementation survey. The analysis included 95 GPs (mean age: 37.7 years; female: 50.5%; mean time practicing medicine: 10.1 years). On average over the previous 6 months, GPs managed 3.6 patients with suspected CSU, diagnosed 2.3 patients with CSU, treated 2.1 patients for CSU, and referred 3.0 patients with suspected CSU to a dermatologist or allergist. GPs' primary reasons for referral were seeking confirmation of CSU diagnosis (61.0%), seeking the specialist's opinion (51.2%), and not feeling confident in diagnosing or treating patients with CSU (42.7%). Most GPs had little to no knowledge of CSU (60.0%) or were unaware of the existence of CSU guidelines (61.1%). Among those who were aware of the guidelines, 35.1% applied them on a regular basis. Only 14.7% of GPs reported any use of PROs, and none used PROs with patients with CSU in the past 6 months. Lack of time hindered GPs from discussing PROs with patients all the time (28.6%), most of the time (42.9%), or sometimes (28.6%). Most GPs reported no or limited educational support on evidence-based practices from their clinics, and indicated the importance of further education on CSU diagnosis and management (72.6% important; 7.4% very important) and further training on PRO use (61.1% important; 8.4% very important) for enhancing CSU management. Pre-implementation data revealed substantial knowledge gaps in CSU management among GPs in Lombardy, supporting the need for additional training to improve CSU management.

To characterize patients with buckwheat allergy in China and to investigate the associations between clinical manifestations and different buckwheat IgE-binding proteins. Patients diagnosed with buckwheat allergy at the Department of Allergy, Peking Union Medical College Hospital, were followed up between 2023 and 2024 and retrospectively enrolled. Serum allergen-specific IgE (sIgE) levels were measured using the ImmunoCAP system, and buckwheat IgE-binding proteins were identified by immunoblotting. A total of 46 patients with buckwheat allergy were included, with a mean age of 26 &#xb1; 11 years. 45 patients (97.8%) developed immediate allergic reactions after buckwheat ingestion. Anaphylaxis occurred in 33 patients (73.3%). Seventeen patients (37.0%) experienced respiratory allergic symptoms upon exposure to buckwheat husks. The median f11-sIgE level was 10.75 kUA/L (IQR, 3.01-20.38). Fifteen IgE-binding proteins with different molecular weights were identified, among which the 18-19 kDa protein showed the highest positivity rate (100%). The 14 kDa protein was detected more frequently in patients without anaphylaxis than in those with anaphylaxis induced by buckwheat consumption (25% vs 0%, P = 0.016). Sensitization to the 22-24 kDa protein was more common in patients with buckwheat husk allergy than in those with allergy limited to buckwheat ingestion (52.9% vs. 24.1%, P = 0.048). Patients positive for the 22-24 kDa protein had significantly higher f11-sIgE levels than those who were negative (21.85 [5.19-38.05] vs 7.53 [2.84-12.95] kUA/L, P = 0.009). Multivariate logistic regression analysis further showed that sensitization to the 22-24 kDa protein was independently associated with concomitant buckwheat husk allergy (P = 0.027, OR = 5.22, 95% CI: 1.21-22.60). Patients with buckwheat allergy may present with anaphylaxis, and respiratory symptoms upon exposure to buckwheat husks. Sensitization to the 22-24 kDa protein was associated with concomitant buckwheat husk allergy and higher f11-sIgE levels.

This study compares the efficacy of monthly subcutaneous injections of 150 mg versus 300 mg omalizumab in patients with seasonal allergic rhinitis (AR) caused by cypress pollen allergy and with total immunoglobulin E (IgE) levels below 100 IU/ml, aiming to provide a basis for individualized treatment in the population with low total IgE. This single-center, randomized, double-blind, placebo-controlled trial enrolled 60 patients with seasonal allergic rhinitis induced by cypress pollen and total IgE levels below 100 IU/mL. Participants were randomly assigned (1:1) to receive a single subcutaneous injection of either 300 mg omalizumab or 150 mg omalizumab plus placebo within 5 days prior to the pollen season onset. The endpoints included daily symptom and medication scores (dSS, dMS, CSMS), Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) score, Allergic Rhinitis Control Test (ARCT) score, and nasal resistance. Among the 54 patients ultimately included in the analysis (27 in each group), the 300 mg group demonstrated significantly better outcomes than the 150 mg group in the CSMS (1.1 &#xb1; 0.1 vs 1.6 &#xb1; 0.1, P= 0.007), dSS (0.6 &#xb1; 0.1 vs 0.8 &#xb1; 0.1, P= 0.016), and ocular symptom score (0.5 &#xb1; 0.1 vs 0.7 &#xb1; 0.1, P= 0.003). The total RQLQ score in the 300 mg group was significantly lower than that in the 150 mg group during both the peak and late phases of the pollen season (P< 0.05). Furthermore, the ARCT score during the peak phase was significantly better in the 300 mg group (P= 0.011), and nasal resistance was significantly reduced (P= 0.020). No drug-related adverse reactions occurred in either group. In patients with seasonal AR and total IgE levels of less than 100 IU/ml, a monthly dose of 300 mg omalizumab provided greater improvement in symptoms, quality of life, and nasal ventilation function compared with the 150 mg dose. This suggests that a higher individualized dosing strategy should be considered for such patients. National Medical Research Registration and Filing Information System (MR-11-25-016855), registered 27 February 2025.

[This corrects the article DOI: 10.1016/j.waojou.2021.100613.].

Optimal care for allergic patients requires several key conditions. First, patients should have access to well-educated and well-trained specialists and primary care physicians. Training and education should be competence-based, for example, following the principles of the CanMEDS framework tailored to the field of allergy. Physicians should not only be medical experts but also communicators and collaborators, leaders and health advocates, scholars, and professionals. Well-designed training programs should aim at standards of care and harmonisation of clinical practice. Also, the ethical aspects of care should be taken into account. Second, recognizing that allergy is a systemic disease that transcends the boundaries of medical disciplines, collaboration among healthcare professionals is essential for high-quality allergy care. This necessitates facilities capable of delivering multidisciplinary care, ideally through the establishment of well-organized allergy centres. Not only physicians but also nurses, dieticians, psychologists and pharmacists should play a role. Given that interventions and treatments can have a significant impact, effective communication and collaboration with the patient are essential. To give the patient a voice, one can use shared decision-making. Shared decision making may enhance adherence, outcomes, and patient satisfaction.

Allergic inflammation underlies several diseases such as asthma, rhinitis, and atopic dermatitis). It involves a great array of cells and molecules of innate and adaptive immunity. Components of the innate inflammatory pathways, among them epithelium receptors, alarmins and ILC2, are the earliest participants in some inflammatory processes, mainly the house dust mite induced bronchial inflammation in asthma. The importance of innate mechanisms, not only as a necessary step for inducing adaptive Th2 response but also to maintain chronic inflammation, is being increasingly recognized in recent years. In addition, the specificity of the Th2 cells and IgE is not only a crucial component of allergic inflammation but allows also identification of the causal inducers and their effects on eosinophils, neutrophils, and basophils recruitment and activation. The regulatory mechanisms of the allergic responses include Treg and Breg activity but the most important action to control this process is stopping the specific allergen exposure. However, this is very difficult to achieve in asthma because, in general, not all the allergens involved can be identified; in addition, non-immune pathways play also a role. Since most people exposed to proallergic environments do not develop allergic diseases and it is well known that these conditions run in families, their genetic and epigenetic influences are a matter of intensive research. In this review we make an update of the basic mechanisms of allergic inflammation, trying to identify important pathways that involve both innate and adaptive immunity, including environmental factors that can modify important regulators of immunity such as intestinal microbiota and air pollution.

There is not much information about the prevalence of allergic diseases in high altitudes in central Asia; and even less on their potential risk of protective factors. A survey using the Global Asthma Network (GAN) methods was carried out in adolescents 13-14 years of age in Naryn (Kyrgyzstan), a small population with a cold, high-altitude, strongly continental climate. GAN questionnaires were self-administered in the school setting and height and weight measured in standardized way. The association between potential risk factors and the different disease indicators, as defined in previous GAN repots was expressed as crude or adjusted odds ratios after logistic regression analyses. A total of 2673 were included in the analyses (participation rate, 93%). Indicators of asthma were 3.1%, 1.7% and 2.8% for current symptoms, severe current symptoms and asthma ever, respectively. The corresponding figures for rhinoconjunctivitis and eczema were: 13.3%, 1.7%, 16.0%; and 2.9%, 0.9%, 4.9%. Consistent factors associated with at least 1 indicator of asthma, rhinoconjunctivitis, or eczema were: increased physical activity, frequent paracetamol use, and low olive oil intake. Higher burger intake and higher BMI were associated only with current rhinoconjunctivitis. Truck traffic was associated only with eczema ever. The prevalence of disease indicators of asthma, rhinoconjunctivitis, and eczema in Naryn are among the lowest in the world. The positive association between exercise and most allergy indicators, and the inverse association between olive oil intake and asthma, deserve further attention.

In recent years, treatment options for patients with uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) have been expanded with biologics. Definitions of uncontrolled severe disease differ across international recommendations and the prescription of biologics depends on national reimbursement criteria. We aimed to evaluate the indication for biologic treatment, based on international recommendations, in a real-world cohort of CRSwNP patients. CRS patients who visited the outpatient ENT clinic of 10 tertiary centres from 7 European countries were invited to use the Galenus Health mobile application monitoring their disease. The proportion of patients who fulfilled biologic indication criteria according to EUFOREA 2021 and EPOS/EUFOREA 2023 recommendations was evaluated. A total of 281 CRS patients were recruited of which 227 (82.1%) were diagnosed as CRSwNP. Out of these 227 patients, 21 patients with prior biologic use were excluded, resulting in a cohort of 206 patients. A total of 28.7% (50/174) and 47.6% (81/170) of CRSwNP patients, met the EUFOREA 2021 or EPOS/EUFOREA 2023 criteria for indication for biologic treatment, respectively. Biologic treatment was initiated at the time of inclusion in the cohort in 18.9% (39/206) of CRSwNP patients. According to international recommendations, 29-48% of CRSwNP patients in tertiary centres may be a candidate for biologic treatment. EPOS/EUFOREA2023 criteria were more inclusive than EUFOREA 2021 criteria with respect to biologic indication for CRSwNP. National reimbursement criteria prevail over international recommendations for actual biologic prescription and are less restrictive in some countries.

IgE-mediated food allergy (FA) represents an increasing global health burden, with rising prevalence and limited therapeutic options beyond allergen avoidance and emergency management. The approval of omalizumab as the first biologic to reduce reactions after accidental food exposure marks a turning point in FA care. While randomized controlled trials (RCTs) have demonstrated its efficacy in raising reaction thresholds and reducing allergic responses, real-world studies provide complementary evidence capturing outcomes relevant to everyday life. This review integrates evidence from sources of observational studies, including cohort, case series, and case reports evaluating omalizumab in patients with FA, including complex phenotypes and populations typically excluded from RCTs. Real-world data demonstrate that omalizumab can prevent severe reactions in atypical and non-ingestive FA phenotypes, increase reaction thresholds as monotherapy, and enable dietary liberalization in a substantial proportion of patients. Observational cohorts consistently report improvements in food allergy-related quality of life, reduced anxiety, and enhanced confidence in food management. Omalizumab appears effective and well tolerated across complex populations, including patients with multiple comorbidities and very high total IgE levels, even beyond currently approved dosing limits. Emerging evidence also suggests that FA may require disease-specific dosing paradigms distinct from those used in asthma. Real-world evidence complements RCTs findings by highlighting the multidimensional benefits of omalizumab in FA, encompassing clinical protection, dietary freedom, and psychosocial well-being as well as dose fine-tuning and off-label scenarios. These data support its broader clinical value and inform future research, dosing strategies, and personalized application in routine care.

Cow's milk allergy is the most common food allergy in infants. While early peanut consumption can reduce peanut allergy risk, the effects of cow's milk formula consumption patterns on milk sensitization and allergy are not well understood. To examine the association between early cow's milk formula consumption patterns and cow's milk sensitization and allergy in high-risk infants. We conducted a secondary cross-sectional analysis of 416 infants (3-15 months) from the CoFAR study, categorized by milk consumption patterns: hospital consistent, hospital inconsistent, home only, and non-consumers. Group differences were assessed using Kruskal-Wallis and post-hoc tests. Univariate and multivariate logistic regression models estimated associations with cow's milk sensitization and allergy. Hospital consistent infants had smaller SPT wheal sizes and less sensitization than hospital inconsistent and non-consumers. Early inconsistent consumption was associated with higher odds of sensitization (OR = 2.45; 95% CI: 1.24-5.05), while non-consumption was associated with lower allergy odds (OR = 0.39; 95% CI: 0.21-0.69). As clinical CMA diagnosis requires prior ingestion with reaction, lower allergy rates among non-consumers may reflect limited exposure opportunities rather than a protective effect. Home-only consumption did not significantly affect risk. Early cow's milk formula consumption patterns were associated with differences in cow's milk sensitization and allergy outcomes in high-risk infants. Consistent exposure was associated with lower sensitization, whereas non-consumption was associated with lower allergy prevalence, highlighting the potential role of early feeding practices in allergy prevention.