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Abstract Severe asthma in children carries an unacceptable treatment burden, yet its rarity means clinical experience in treating it is limited, even among specialists. Practical guidance is needed to support clinical decision-making to optimize treatment for children with this condition. This modified Delphi convened 16 paediatric pulmonologists and allergologists from northern Europe, all experienced in treating children with severe asthma. Informed by interviews with stakeholders involved in the care of children with severe asthma (including paediatricians, nurses and carers), and an analysis of European guidelines, the experts built a consensus focused on the gaps in existing guidance. Explored were considerations for optimizing care for patients needing biologic treatment, and for selecting home or hospital delivery of biologics. This consensus is aimed at clinicians in specialist centres, as well as general paediatricians, paediatric allergologists and paediatric pulmonologists who refer children with the most severe asthma to specialist care. Consensus is based on expert opinion and is intended for use alongside published guidelines. Our discussions revealed three key facets to optimizing care. Firstly, early asthma detection in children presenting with wheezing and/or dyspnoea is vital, with a low threshold for referral from primary to specialist care. Secondly, children who may need biologics should be referred to and managed by specialist paediatric asthma centres; we define principles for the specialist team members, tests, and expertise necessary at such centres, as well as guidance on when homecare biologics delivery is and is not appropriate. Thirdly, shared decision-making is essential at all stages of the patient’s journey: clear, concise treatment plans are vital for patient/carer self-management, and structured processes for transition from paediatric to adult services are valuable. The experts identified the potential for specialist paediatric asthma nurses to play a significant role in facilitating multidisciplinary working. Through this project is agreed a framework of practical advice to optimize the care of children with severe asthma. We encourage clinicians and policymakers to implement this practical advice to enhance patient care.

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 Aims Mobile Airways Sentinel NetworK (MASK) belongs to the Fondation Partenariale MACVIA-LR of Montpellier, France and aims to provide an active and healthy life to rhinitis sufferers and to those with asthma multimorbidity across the life cycle, whatever their gender or socio-economic status, in order to reduce health and social inequities incurred by the disease and to improve the digital transformation of health and care. The ultimate goal is to change the management strategy in chronic diseases. Methods MASK implements ICT technologies for individualized and predictive medicine to develop novel care pathways by a multi-disciplinary group centred around the patients. Stakeholders Include patients, health care professionals (pharmacists and physicians), authorities, patient’s associations, private and public sectors. Results MASK is deployed in 23 countries and 17 languages. 26,000 users have registered. EU grants (2018) MASK is participating in EU projects (POLLAR: impact of air POLLution in Asthma and Rhinitis, EIT Health, DigitalHealthEurope, Euriphi and Vigour). Lessons learnt (i) Adherence to treatment is the major problem of allergic disease, (ii) Self-management strategies should be considerably expanded (behavioural), (iii) Change management is essential in allergic diseases, (iv) Education strategies should be reconsidered using a patient-centred approach and (v) Lessons learnt for allergic diseases can be expanded to chronic diseases.

Abstract A Good Practice is a practice that works well, produces good results, and is recommended as a model. MACVIA-ARIA Sentinel Network (MASK), the new Allergic Rhinitis and its Impact on Asthma (ARIA) initiative, is an example of a Good Practice focusing on the implementation of multi-sectoral care pathways using emerging technologies with real life data in rhinitis and asthma multi-morbidity. The European Union Joint Action on Chronic Diseases and Promoting Healthy Ageing across the Life Cycle (JA-CHRODIS) has developed a checklist of 28 items for the evaluation of Good Practices. SUNFRAIL (Reference Sites Network for Prevention and Care of Frailty and Chronic Conditions in community dwelling persons of EU Countries), a European Union project, assessed whether MASK is in line with the 28 items of JA-CHRODIS. A short summary was proposed for each item and 18 experts, all members of ARIA and SUNFRAIL from 12 countries, assessed the 28 items using a Survey Monkey-based questionnaire. A visual analogue scale (VAS) from 0 (strongly disagree) to 100 (strongly agree) was used. Agreement equal or over 75% was observed for 14 items (50%). MASK is following the JA-CHRODIS recommendations for the evaluation of Good Practices.

This research examined the problems experienced by women who work in the informal sector of the city of Riobamba due to receiving poor and lower incomes than men. The main objective was to analyze the influence that gender has on wages of women in this sector, to establish strategies that can promote more equitable development. Qualitative and quantitative approaches were used using inductive and deductive methods. Data were collected through a survey and analyzed using the Chi square test. The results showed that women's wages were dependent on their gender, conditioned by a sociocultural environment that has not evolved, especially in the informal sectors made up mostly of rural population. Also, the presence of child labor was evident, and wages could not cover the basic needs of women who identified as heads of household with family responsibilities of between three to five people. The strategy identified to promote equity in the recognition and value of fair work without distinction of gender was based on the following elements: the implementation of inclusion policies and control, training of young women in non-traditional trades, promotion of changes in traditional patterns in households, and policies to combat poverty with a gender focus for sustainable social development. Keywords: gender, equity, salary, strategies, socioeconomic, management. Resumen La investigación plantea la problemática que viven las mujeres que trabajan en el sector informal de la ciudad de Riobamba debido a su condición de género para percibir ingresos deficientes e inferiores a los hombres, el objetivo principal es analizar la incidencia que tiene el género en el salario de las mujeres de este sector para el establecimiento de estrategias que promuevan un desarrollo más equitativo. La metodología investigativa considera estudios analíticos, correlacionales, exploratorios, de campo, un enfoque cuali- cuantitativo, con métodos inductivos y deductivos, usando técnicas como la encuesta, considerado la relación de dependencia a través del Chi cuadrado para la comprobación de la hipótesis, como resultados principales se puede encontrar que la incidencia del género en los salarios de las mujeres es dependiente, condicionado por un ambiente sociocultural que no ha evolucionado sobre todo en los sectores informales conformados en su mayoría por población rural, se evidencia la presencia del trabajo infantil y salarios que no pueden cubrir las necesidades básicas de mujeres que se identifican como jefes de hogar con cargas familiares de entre 3 a 5 personas, se plantea como solución la estrategia para promover la equidad en el reconocimiento y puesta en valor del trabajo equitativo sin distinción de género basada en 5 elementos: la implementación de políticas de inclusión y control, la capacitación de las jóvenes en oficios no tradicionales, promoción de cambios de patrones tradicionales en los hogares, políticas de combate a la pobreza con enfoque de género para un desarrollo social sustentable. Palabras clave: género, equidad, salario, estrategias, socioeconómicas, gestión.

Some taxes may limit microeconomic growth. A greater growth of SMEs that use RISE as part of their administration, especially grocery stores, has been identified in the commercial sector in the city of Macas, Morona canton, Morona Santiago province, Ecuador. This has led to a lack of knowledge about their profitability because the nature of the tax can lead to reduced use of accounting tools. Therefore, the objective of this research was to analyze the accounting administration of RISE and its impact on the profitability of these businesses, and to propose the design of a tool that could contribute to the development of efficient management of the local microeconomic businesses. A deductive quantitative approach was used and data were collected through a survey and interviews. The Chi square test was used to analyze the results. According to the findings, the limitations faced by businesses that use this tax included the generation of monthly income that does not cover the monthly basic basket. Based on the results, we proposed a strategy for the efficient management of the microeconomy that is made up of four tools: conscious strategic planning, administration without tax barriers, efficient accounting tools, and the sustainable development of the company. Keywords: administration, accounting, microeconomics, RISE, management, taxation. Resumen Algunos impuestos pueden limitar el crecimiento microeconómico, en la ciudad de Macas, cantón Morona, provincia de Morona Santiago, Ecuador se ha identificado un mayor crecimiento de PYMEs del sector comercial, de manera especial tiendas de abastos quienes utilizan el RISE como parte de su administración, lo que ha provocado un deficiente conocimiento real de su rentabilidad debido a la naturaleza misma del impuesto que lleva a un uso deficiente y casi nulo de los las herramientas contables, el trabajo tiene como objetivo analizar la administración contable del RISE y su incidencia en la rentabilidad de estos negocios que permitan el diseño de una herramienta que aporte al desarrollo de la gestión eficiente de la microeconomía local, se analizan datos obtenidos a partir de un estudio de tipo deductivo de enfoque cuantitativo, metodología de tipo analítico, correlacional, de campo que aplica instrumentos la recolección de información como la encuesta y entrevista, determina la dependencia de las variables identificadas a través del Chi cuadrado, e identifica como parte de los resultados las limitaciones a las que los negocios que utilizan este impuesto tienen como es la generación de ingresos mensuales que no llegan a cubrir la canasta básica mensual; plantea como parte de la solución al problema la Estrategia para la gestión eficiente de la Microeconomía que se compone cuatro herramientas: la planificación estratégica consciente, administración sin barreras tributarias, herramientas contables eficientes, el desarrollo sustentable de la empresa. Palabras clave: administración, contabilidad, microeconomía, rise, gestión, tributación.

Abstract mHealth, such as apps running on consumer smart devices is becoming increasingly popular and has the potential to profoundly affect healthcare and health outcomes. However, it may be disruptive and results achieved are not always reaching the goals. Allergic Rhinitis and its Impact on Asthma (ARIA) has evolved from a guideline using the best evidence-based approach to care pathways suited to real-life using mobile technology in allergic rhinitis (AR) and asthma multimorbidity. Patients largely use over-the-counter medications dispensed in pharmacies. Shared decision making centered around the patient and based on self-management should be the norm. Mobile Airways Sentinel networK (MASK), the Phase 3 ARIA initiative, is based on the freely available MASK app (the Allergy Diary, Android and iOS platforms). MASK is available in 16 languages and deployed in 23 countries. The present paper provides an overview of the methods used in MASK and the key results obtained to date. These include a novel phenotypic characterization of the patients, confirmation of the impact of allergic rhinitis on work productivity and treatment patterns in real life. Most patients appear to self-medicate, are often non-adherent and do not follow guidelines. Moreover, the Allergy Diary is able to distinguish between AR medications. The potential usefulness of MASK will be further explored by POLLAR (Impact of Air Pollution on Asthma and Rhinitis), a new Horizon 2020 project using the Allergy Diary.

This paper reviews current status of the unified approach known as integrated safety assessment (ISA), as well as the associated SCAIS (simulation codes system for ISA) computer platform. These constitute a proposal, which is the result of collaborative action among the Nuclear Safety Council (CSN), University of Madrid (UPM), and NFQ Solutions S.L, aiming to allow independent regulatory verification of industry quantitative risk assessments. The content elaborates on discussions of the classical treatment of time in conventional probabilistic safety assessment (PSA) sequences and states important conclusions that can be used to avoid systematic and unacceptable underestimation of the failure exceedance frequencies. The unified ISA method meets this challenge by coupling deterministic and probabilistic mutual influences. The feasibility of the approach is illustrated with some examples of its application to a real size plant.

Las tortugas marinas de la especie Chelonia agassizi navegan anualmente cientos de kilómetros en mar abierto para llegar a sus áreas de reproducción y anidación. Se cree que esta tarea se realiza mediante el uso de información magnética terrestre y de aquella derivada de los atributos físicos de dichas áreas. Así, la geomorfología, topografía y geofísica de las playas natales pudieran facilitar a las tortugas el identificarlas. Este estudio describe estos elementos en las playas de Colola y Maruata, sitios de anidación de C. agassizi en México. Colola, en el oeste, es una playa elongada de 4.8 km de longitud y 150 m de ancho, limitada al norte por depósitos fluviales costeros. Maruata, en el este, es una playa curva de 2.3 km de longitud y 40 m de ancho bordeada por depósitos fluviales costeros al noreste y por pendientes coluviales de depósito volcano-sedimentarias en el sureste. Levantamientos topográficos y observaciones de campo realizados en Colola (otoño 1998/primavera 2000), documentaron que los perfiles de playa cambian durante y entre estaciones reproductivas. En Maruata las anomalías magnéticas tienen un rango de valores de 50 nT a nivel del mar a > 350 nT en el Cerro Vigía. El vector de campo geomagnético varia en inclinación e intensidad con la latitud a partir de la horizontal en Islas Galápagos hasta cerca de los 45° en el sur de México y de 30,000 nT a > 40,000 nT, respectivamente. Localmente la inclinación e intensidad en Colola y Maruata muestran valores de 44.87° y 40364 nT y 44.85° y 40353 nT, respectivamente. Estos parámetros pudiesen imponer limitaciones a la ecología sensorial de las tortugas. doi: https://doi.org/10.22201/igeof.00167169p.2010.49.4.129

Background: Few studies have investigated the influence of body mass index (BMI) trajectories on lung function covering the entire growth period., Methods: We conducted a prospective study using data from the Swedish BAMSE birth cohort. Latent class mixture modelling was employed to examine the diversity in BMI z-scores from birth to 24 years of age. Participants with four or more BMI z-scores were included (n=3204, 78.4%). Pre-bronchodilator spirometry was tested at 8, 16 and 24 years, while post-bronchodilator spirometry, multiple-breath nitrogen washout (for lung clearance index) and urinary metabolomics data were assessed at 24 years., Results: Six distinct BMI development groups were identified. Compared to the stable normal BMI group, the accelerated increasing BMI group exhibited reduced pre- and post-bronchodilator forced expiratory volume in 1 s (FEV 1 )/forced vital capacity (FVC) ratio z-scores (pre: β= -0.26, 95% CI -0.44- -0.08; post: β= -0.22, 95% CI -0.39- -0.05), along with elevated lung clearance index (0.30, 95% CI 0.22-0.42) at 24 years. The persistent high BMI group demonstrated lower FEV 1 (-0.24, 95% CI -0.42- -0.05) and FVC (-0.27, 95% CI -0.45- -0.01) z-score growth between 16 and 24 years, and elevated lung clearance index (0.20, 95% CI 0.03-0.39) at 24 years. However, those impairments were not observed in the accelerated resolving BMI group. Conversely, the persistent low BMI group displayed persistently decreased FEV 1 and FVC from 8 to 24 years, as well as decreased lung function growth. Additionally, histidine-related metabolites were associated with pre- and post-bronchodilator FEV 1 (hypergeometric false discovery rate=0.008 and <0.001, respectively)., Conclusions: Early interventions aiming for normal BMI during childhood may contribute to improved lung health later in life., Competing Interests: Conflicts of interest: N. Hernandez-Pacheco reports grants from European Academy of Allergy and Clinical Immunology (EAACI) and European Respiratory Society (ERS), and payment for lectures from OMNI PREX S.L., outside the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2025.)

Background: Atopic dermatitis (AD) affects individuals of all ages, and the first-line treatment are emollients and topical corticosteroids. There is insufficient knowledge about factors possibly affecting the drug utilization of young adults with AD., Objectives: To describe the drug utilization of young adults with AD in relation to sex, socio-economic status and disease severity., Methods: A cross-sectional study based on the 24-year follow-up from the population-based BAMSE (Children, Allergy, Milieu, Stockholm, Epidemiology Survey) birth cohort linked with dispensing data from the National Drug Register (n = 2912). Self-reported AD and socio-economic status were defined from questionnaire data and disease severity was determined through the clinical examination and Patient-Oriented Eczema Measure questionnaire., Results: The prevalence of AD in young adults was 17.7% (n = 516) and 45.5% of them were dispensed at least one drug for the treatment of AD during the study period (January 2016 to June 2019). Topical corticosteroids (TCS) were the most common drugs (32.9%) followed by emollients (21.7%). A larger proportion of men were dispensed TCS than women (39.0% vs. 29.1%: p-value = 0.020). A larger proportion of young adults with moderate-to-severe AD were dispensed TCS than those with mild AD (52.6% vs. 35.3%: p-value = 0.026). No one was dispensed the recommended amount of emollients and less than five individuals were dispensed the recommended amount of TCS for mild disease. Male sex (adj.OR 1.54, 95% CI 1.06-2.34) and moderate-to-severe AD (adj.OR 2.62, 95% CI 1.59-4.31) were associated with dispensation of TCS., Conclusions: A large proportion of young adults with AD was undertreated or untreated. Sex and disease severity did affect the dispensing patterns of investigated drugs., (© 2024 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Introduction: By recent estimates, 40% of children worldwide are exposed to second-hand smoke (SHS), which has been associated with adverse health outcomes. While numerous studies have linked maternal smoking during pregnancy (MSDP) to widespread differences in child blood DNA methylation (DNAm), research specifically examining postnatal SHS exposure remains sparse. To address this gap, we conducted epigenome-wide meta-analyses to identify associations of postnatal SHS and child blood DNAm., Methods: Six cohorts from the Pregnancy And Childhood Epigenetics (PACE) Consortium (total N = 2,695), with SHS data and child blood DNAm (aged 7-9 years) measured with the Illumina 450K array were included in the meta-analysis. Linear regression models adjusted for covariates were fitted to examine the association between the number of household smokers in postnatal life (0, 1, 2+) and child blood DNAm. Sensitivity models without adjusting for MSDP and restricted to mothers who did not smoke during pregnancy were evaluated., Results: Our analysis revealed significant associations (False Discovery Rate < 0.05) between household postnatal SHS exposure and DNAm at 11 CpGs in exposed children. Nine CpGs were mapped to genes (MYO1G, FAM184B, CTDSPL2, LTBP3, PDE10A, and FIBCD1), while 2 CpGs were located in open sea regions. Notably, all except 2 CpGs (mapped to FIBCD1 and CTDSPL2) have previously been linked to either personal smoking habits or in utero exposure to smoking. The models restricted to non-smoking mothers provided similar results. Importantly, several of these CpGs and their associated genes are implicated in conditions exacerbated by or directly linked to SHS., Conclusions: Our findings highlight the potential biological effects of SHS on blood DNAm. These findings support further research on epigenetic factors mediating deleterious effects of SHS on child health and call for public health policies aimed at reducing exposure, particularly in environments where children are present., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Asthma is associated with impaired lung function; however, it is uncertain if a lower childhood lung function is associated with asthma onset and persistence during adolescence. The aims of the present study were to investigate the association between childhood lung function and onset and persistence of asthma during adolescence., Methods: In the population-based BAMSE (Sweden), PIAMA (Netherlands) and MAAS (UK) birth cohorts, we analysed the association of forced expiratory volume in 1 s (FEV 1 ), forced vital capacity (FVC), FEV 1 /FVC and forced expiratory volume at 75% of FVC at age 8 years with asthma onset and persistence in adolescence (age 12-16 years) using cohort-specific logistic regression analysis followed by meta-analysis., Results: In the BAMSE, PIAMA and MAAS cohorts, asthma incidence in adolescence was 6.1% (112/1824), 3.4% (36/1050) and 5.0% (39/779), respectively. Persistent asthma from childhood to adolescence was observed in 8.2%, 6.4% and 7.7% of all subjects within the respective cohorts. A higher FEV 1 % predicted and FEV 1 /FVC at age 8 years was associated with a lower odds for adolescent-onset asthma: OR 0.98 (95% CI 0.97-1.00) and 0.97 (0.94-0.99). These associations remained significant also when restricting the analyses to subjects with no wheezing or asthma treatment in childhood. A higher FEV 1 /FVC at age 8 years was associated with a lower odds for asthma persistence in adolescence (0.96 (0.93-0.99)). Sex by lung function interaction analysis was not significant., Conclusions: A higher lung function at school age was associated with a lower risk of adolescent-onset asthma, predominantly in males. This indicates that a lower lung function in childhood may precede and or potentially contribute to asthma incidence and persistence., Competing Interests: Conflict of interest: H.J.L. Koefoed, A. Ullah, S.K. Merid, L. Lowe, R. Vermeulen, M.M. Kere, U. Gehring, A. Bergström, J. Hallberg and J.M. Vonk have no conflicts of interest to report. G.H. Koppelman reports grant support from Netherlands Lung Foundation, TEVA the Netherlands, GSK, Vertex, Ubbo Emmius Foundation, European Union (H2020) and Zon-MW outside the submitted work; and lecture and/or advisory fees from GSK, AstraZeneca, Sanofi, Boehringer Ingelheim and Pure-IMS (money to institution). E. Melén reports lecture and/or advisory board fees from ALK, Airsonett, AstraZeneca, Chiesi, Novartis and Sanofi outside the submitted work. C.S. Murray reports grants from GSK, lecture fees from Sanofi, Novartis and GSK, and support for attending meetings and/or travel from Sanofi. I. Kull reports lecture fees from AstraZeneca outside the submitted work. A. Custovic reports personal fees from Novartis, Sanofi, Stallergenes Greer, AstraZeneca, GSK ad La Roche-Posay, outside the submitted work. A. Simpson reports grants from the Medical Research Council, J.P. Moulton Charitable Foundation and Asthma UK (grants to institution)., (Copyright ©The authors 2024.)

Background: We have previously developed Core Outcome Measures sets for Severe Asthma (COMSA) by multi-stakeholder consensus. There are no patient-centred tools to quantify response to biologics for severe asthma. We aimed to develop paediatric and adult CompOsite iNdexes For Response in asthMa (CONFiRM) incorporating clinical parameters and patient-reported quality of life (QoL)., Methods: International expert healthcare professionals (HCPs) and patients with severe asthma were invited to: 1) develop consensus levels of clinically relevant changes for each outcome measure within COMSA; 2) use multicriteria decision analysis to develop the CONFiRM scores and 3) assess their internal validity. A separate group of HCPs evaluated CONFiRM's external validity., Results: Five levels of change for each COMSA outcome were agreed. Severe exacerbations and maintenance oral corticosteroids use were rated as most important in determining both paediatric and adult CONFiRM scores. There was strong agreement between HCPs and patients, although patients assigned greater importance to QoL. The CONFiRM score quantified response to a biological from -31 (deterioration) to 69 (best possible response). Paediatric and adult CONFiRMs had good discriminative ability for a sufficient (AUC≥0.92) and a substantial (AUC≥0.95) response to biologics. Both CONFiRMs demonstrated excellent external validity (Spearman correlation coefficients 0.9 and 0.8 for paediatric and adult respectively (p<0.0001))., Conclusions: We have developed novel patient-centred paediatric and adult CONFiRMs which include QoL measures. CONFiRMs should allow a more holistic understanding of response for the patient and a standardised assessment of the effectiveness of biologics between studies. Further research is needed to prospectively validate CONFiRM scores., (Copyright ©The authors 2024.)

Introduction: Snus is suggested as a risk factor for cardiometabolic disease, but little is known about health effects in young populations, particularly in women. We aimed to investigate associations between snus and cardiometabolic health markers among young men and women., Method: This study was conducted within the BAMSE birth cohort and included participants followed up around 24 years (n=2256) and 26 years (n=1011). Snus use was assessed at 24 years by questionnaires. Cardiometabolic health markers were recorded at clinical examinations at 24 and 26 years. Associations between snus use and cardiometabolic markers were assessed by multivariable linear regression., Results: Snus was used by 6.4% (n=81) among women and 21.9% (n=219) among men. Compared to no tobacco use, daily exclusive snus use among women at 24 years was associated with higher body mass index (BMI) (adjusted β: 1.93 kg/m2, 95% CI: 0.54, 3.33) and waist circumference (WC) (aβ: 3.80 cm, 95% CI: 0.41, 7.18) at 24 years, and with higher BMI (aβ: 2.73 kg/m2, 95% CI: 0.53-4.93) at 26 years. Among men, using ≥4 cans/week was associated with increased BMI (aβ: 2.48 kg/m2, 95% CI: 0.73, 4.24) and a tendency toward increased body fat (aβ: 2.31%, 95% CI: -0.53, 5.14) at 26 years. Snus use was not associated with glycemic status or blood pressure., Conclusion: Our results suggest that snus is associated with increased BMI, and possibly other measures of adiposity, among young women and heavy using young men. Given the cross-sectional study design, the results should be interpreted with caution., Implications: We found cross-sectional associations between snus use and measures of increased adiposity in a cohort of Swedish young adults, including BMI and waist circumference among women and BMI among heavy snus using men. We did not find associations between snus use and body fat %, glycemic status or blood pressure. This is one of few studies to investigate health effect of snus among both women and men as well as cardiometabolic health markers in young adults. Given the recent trends of increased snus use among young adults, our findings highlight the need for further research on snus on cardiometabolic health., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.)

ATP-binding cassette (ABC) transporters are proteins responsible for active transport of various compounds, from small ions to macromolecules, across membranes. Proteins from this superfamily also pump drugs out of the cell resulting in multidrug resistance. Based on the cellular functions of ABC-transporters they are commonly associated with diseases like cancer and cystic fibrosis. To understand the molecular mechanism of this critical family of integral membrane proteins, structural characterization is a powerful tool which in turn requires successful recombinant production of stable and functional protein in good yields. In this review we have used high resolution structures of ABC transporters as a measure of successful protein production and summarized strategies for prokaryotic and eukaryotic proteins, respectively. In general, Escherichia coli is the most frequently used host for production of prokaryotic ABC transporters while human embryonic kidney 293 (HEK293) cells are the preferred host system for eukaryotic proteins. Independent of origin, at least two-steps of purification were required after solubilization in the most used detergent DDM. The purification tag was frequently cleaved off before structural characterization using cryogenic electron microscopy, or crystallization and X-ray analysis for prokaryotic proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Both depression and respiratory disease are common today in young populations. However, little is known about the relationship between them., Aims: This study aims to explore the association between depression in childhood to early adulthood and respiratory health outcomes in early adulthood, and the potential underlying mechanisms., Method: A prospective study was conducted based on the Swedish BAMSE (Barn, Allergi, Miljö, Stockholm, Epidemiologi [Children, Allergy, Milieu, Stockholm, Epidemiology]) birth cohort ( n = 4089). We identified clinically diagnosed depression through the dispensation of antidepressants, using national register data confirmed by self-reported diagnosis. At the 24-year follow-up, respiratory health was assessed via questionnaires and clinical evaluation. Metabolic and inflammatory profiles were analysed to explore potential mechanisms., Results: Among the 2994 participants who provided study data, 403 (13.5%) had depression at any time point from around age 10 to 25 years. Depression was associated with higher risks of any chronic bronchitis symptoms (odds ratio = 1.58, 95% CI 1.21-2.06) and respiratory symptoms (odds ratio = 1.41, 95% CI 1.11-1.80) in early adulthood, independent of body mass index (BMI) and smoking status. Compared to individuals without depression, those with depression had a higher fat mass index (FMI (β = 0.48, 95% CI 0.22-0.74)) and increased blood levels of fibroblast growth factor 21 and Interleukin-6 in early adulthood. These markers together with FMI were found to partly mediate the association between depression and respiratory symptoms (total mediation proportion: 19.8 and 15.4%, respectively, P < 0.01)., Conclusions: Depression in childhood to early adulthood was associated with an increased risk of respiratory ill-health in early adulthood, independently of smoking. Metabolic and inflammatory dysregulations may underlie this link.

Background: Numerous studies have investigated links between body mass index (BMI) trajectories and cardiovascular risk, yet discrepancies in BMI measurement duration and timing of the cardiovascular-related outcome evaluation have led to inconsistent findings., Methods: We included participants from the Swedish birth cohort (BAMSE) and applied latent class mixture modeling to identify BMI trajectories using data of multiple BMI measures (≥ 4 times) from birth until 24-year follow-up (n = 3204). Subsequently, we analyzed the associations of BMI trajectories with lipids (n = 1974), blood pressure (n = 2022), HbA1c (n = 941), and blood leukocytes (n = 1973) using linear regression. We also investigated the circulating levels of 92 inflammation-related proteins (n = 1866) across BMI trajectories., Results: Six distinct BMI groups were identified, denoted as increasing-persistent high (n = 74; 2.3%), high-accelerated increasing (n = 209; 6.5%), increasing-accelerated resolving (n = 142; 4.4%), normal-above normal (n = 721; 22.5%), stable normal (n = 1608; 50.2%), and decreasing-persistent low (n = 450; 14.1%) BMI groups. The increasing-persistent high and high-accelerated increasing BMI groups had higher levels of total cholesterol [mean difference (95% confidence intervals): 0.30 (0.04-0.56) and 0.16 (0.02-0.31) mmol/L], triglyceride, low-density lipoprotein, hemoglobin A1C [3.61 (2.17-5.54) and 1.18 (0.40-1.98) mmol/mol], and low-density lipoprotein/high-density lipoprotein ratios, but a lower level of high-density lipoprotein than the stable normal BMI group. These two groups also had higher leukocyte cell counts and higher circulating levels of 28 inflammation-related proteins. No increased cardiometabolic markers were observed in the increasing-accelerated resolving BMI group., Conclusions: Participants with persistently high or accelerated increasing BMI trajectories from birth to young adulthood have elevated levels of cardiometabolic risk markers at young adulthood than those with stable normal BMI. However, a raised BMI in childhood may not be inherently harmful to cardiometabolic health, provided it does not persist into adulthood., (© 2024. The Author(s).)

Background: Very long-chain (VLC) polyunsaturated fatty acids (PUFA) have been hypothesized to influence the risk of allergic disease. The aim of the study was to investigate the role of plasma levels of omega-3 (n-3) and omega-6 (n-6) PUFA in childhood and adolescence, for the development of rhinitis and allergic sensitization up to young adulthood., Methods: The study included n = 933 participants from the BAMSE cohort. Proportions of n-3 and n-6 PUFA in plasma phospholipids were analyzed at 8 and 16 years using gas chromatography. Associations between PUFA and rhinitis as well as allergic sensitization, analyzed by IgE reactivity against airborne allergens, up to age 24 years were analyzed by generalized estimating equations and logistic regression models., Results: High plasma levels of VLC n-3 PUFA as well as the n-6 PUFA arachidonic acid (AA) at 8 years were inversely associated with rhinitis (overall OR up to 24 years: 0.72, 95% CI 0.55, 0.0.93 and 0.69 [0.53, 0.89], respectively) and aeroallergen sensitization (0.64 [0.49, 0.83] and 0.71 [0.54, 0.92], respectively). However, excluding prevalent cases at 8 years attenuated the associations., Conclusion: Plasma levels of n-3 and certain n-6 PUFA in childhood were inversely associated with allergic sensitization and allergic rhinitis up to young adulthood. The association may to some extent be explained by persistent childhood disease, rather than new incident cases in adolescence and young adulthood. To what extent these associations are driven by dietary PUFA intake versus metabolism remains to be clarified for the prevention of rhinitis and allergic sensitization., (© 2024 The Author(s). Pediatric Allergy and Immunology published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care. 1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Rationale: The benefits of improved air quality on asthma remain understudied. Objectives: Our aim was to investigate associations of changes in ambient air pollution with incident asthma from school age until young adulthood in an area with mostly low air pollution levels. Methods: Participants in the BAMSE (Swedish abbreviation for Children, Allergy, Environment, Stockholm, Epidemiology) birth cohort from Stockholm without asthma before the 8-year follow-up were included ( N  = 2,371). We estimated the association of change in individual-level air pollutant exposure (particulate matter with an aerodynamic diameter ≤ 2.5 μm [PM 2.5 ] and ≤ 10 μm [PM 10 ], black carbon [BC], and nitrogen oxides [NO x ]) from the first year of life to the 8-year follow-up with asthma incidence from the 8-year until the 24-year follow-up. Multipollutant trajectories were identified using the group-based multivariate trajectory model. We also used parametric G-computation to quantify the asthma incidence under different hypothetical interventions regarding air pollution levels. Results: Air pollution levels at residency decreased during the period, with median reductions of 5.6% for PM 2.5 , 3.1% for PM 10 , 5.9% for BC, and 26.8% for NO x . A total of 395 incident asthma cases were identified from the 8-year until the 24-year follow-up. The odds ratio for asthma was 0.89 (95% confidence interval [CI], 0.80-0.99) for each interquartile range reduction in PM 2.5 (equal to 8.1% reduction). Associations appeared less clear for PM 10 , BC, and NO x . Five multipollutant trajectories were identified; the largest reduction trajectory displayed the lowest odds of asthma (odds ratio, 0.55; 95% CI, 0.31-0.98) compared with the lowest reduction trajectory. If the PM 2.5 exposure had not declined up to the 8-year follow-up, the hypothetical asthma incidence was estimated to have been 10.9% higher (95% CI, 0.8-20.8%). Conclusions: A decrease in PM 2.5 levels during childhood was associated with a lower risk of incident asthma from school age to young adulthood in an area with relatively low air pollution levels, suggesting broad respiratory health benefits from improved air quality.

Socioeconomic inequalities in the exposome have been found to be complex and highly context-specific, but studies have not been conducted in large population-wide cohorts from multiple countries. This study aims to examine the external exposome, encompassing individual and environmental factors influencing health over the life course, and to perform dimension reduction to derive interpretable characterization of the external exposome for multicountry epidemiological studies. Analyzing data from over 25 million individuals across seven European countries including 12 administrative and traditional cohorts, we utilized domain-specific principal component analysis (PCA) to define the external exposome, focusing on air pollution, the built environment, and air temperature. We conducted linear regression to estimate the association between individual- and area-level socioeconomic position and each domain of the external exposome. Consistent exposure patterns were observed within countries, indicating the representativeness of traditional cohorts for air pollution and the built environment. However, cohorts with limited geographical coverage and Southern European countries displayed lower temperature variability, especially in the cold season, compared to Northern European countries and cohorts including a wide range of urban and rural areas. The individual- and area-level socioeconomic determinants (i.e., education, income, and unemployment rate) of the urban exposome exhibited significant variability across the European region, with area-level indicators showing stronger associations than individual variables. While the PCA approach facilitated common interpretations of the external exposome for air pollution and the built environment, it was less effective for air temperature. The diverse socioeconomic determinants suggest regional variations in environmental health inequities, emphasizing the need for targeted interventions across European countries.

Asthma is a descriptive label for an obstructive inflammatory disease in the lower airways manifesting with symptoms including breathlessness, cough, difficulty in breathing, and wheezing. From a clinician's point of view, asthma symptoms can commence at any age, although most patients with asthma-regardless of their age of onset-seem to have had some form of airway problems during childhood. Asthma inception and related pathophysiologic processes are therefore very likely to occur early in life, further evidenced by recent lung physiologic and mechanistic research. Herein, we present state-of-the-art updates on the role of genetics and epigenetics, early viral and bacterial infections, immune response, and pathophysiology, as well as lifestyle and environmental exposures, in asthma across the life course. We conclude that early environmental insults in genetically vulnerable individuals inducing abnormal, pre-asthmatic airway responses are key events in asthma inception, and we highlight disease heterogeneity across ages and the potential shortsightedness of treating all patients with asthma using the same treatments. Although there are no interventions that, at present, can modify long-term outcomes, a precision-medicine approach should be implemented to optimize treatment and tailor follow-up for all patients with asthma.

Competing Interests: Supported by grants from the Swedish Research Council; the 10.13039/501100004359Swedish Research Council for 10.13039/100018696Health, Working Life, and Welfare; Formas; the Swedish Asthma and Allergy Research Foundation; the Swedish Heart-Lung Foundation; and Region Stockholm (the ALF project, and for cohort and database maintenance). Disclosure of potential conflict of interest: E. Melén reports personal fees from 10.13039/100004325AstraZeneca, Chiesi, Sanofi, and Novartis outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest.

Background: Chronic obstructive pulmonary disease (COPD) is caused by interactions between many factors across the life course, including genetics. A proportion of COPD may be due to reduced lung growth in childhood. We hypothesized that a polygenic risk score (PRS) for COPD is associated with lower lung function already in childhood and up to adulthood., Methods: A weighted PRS was calculated based on the 82 association signals ( p  ≤ 5 × 10 -8 ) revealed by the largest GWAS of airflow limitation (defined as COPD) to date. This PRS was tested in association with lung function measures (FEV 1 , FVC, and FEV 1 /FVC) in subjects aged 4-50 years from 16 independent cohorts participating in the Chronic Airway Diseases Early Stratification (CADSET) Clinical Research Collaboration. Age-stratified meta-analyses were conducted combining the results from each cohort (n = 45,406). These findings were validated in subjects >50 years old., Findings: We found significant associations between the PRS for airflow limitation and: (1) lower pre-bronchodilator FEV 1 /FVC from school age (7-10 years; β: -0.13 z-scores per one PRS z-score increase [-0.15, -0.11], q -value = 7.04 × 10 -53 ) to adulthood (41-50 years; β: -0.16 [-0.19, -0.13], q -value = 1.31 × 10 -24 ); and (2) lower FEV 1 (from school age: 7-10 years; β: -0.07 [-0.09, -0.05], q -value = 1.65 × 10 -9 , to adulthood: 41-50 years; β: -0.17 [-0.20, -0.13], q -value = 4.48 x 10 -20 ). No effect modification by smoking, sex, or a diagnosis of asthma was observed., Interpretation: We provide evidence that a higher genetic risk for COPD is linked to lower lung function from childhood onwards., Funding: This study was supported by CADSET, a Clinical Research Collaboration of the European Respiratory Society., Competing Interests: NH-P was supported with a Medium-Term Research Fellowship by the European Academy of Allergy and Clinical Immunology (EAACI) and a Long-Term Research Fellowship by the European Respiratory Society (ERS) (LTRF202101-00861), and lecture honoraria from OMNIPREX, S.L (outside of the submitted work). LLa was supported by the Fund for Scientific Research Flanders (Grant 3G037618), lecture honoraria from IPSA vzw, a non-profit organization facilitating lifelong learning for health care providers, and Chiesi; and consulting fees from AstraZeneca, all paid to the institution. LLa also declares unpaid membership of faculty board and faculty committees of the European Respiratory Society and Belgian Respiratory Society. LB received support from the K.G. Jebsen Center for Genetic Epidemiology funded by Stiftelsen Kristian Gerhard Jebsen; Faculty of Medicine and Health Sciences, NTNU; The Liaison Committee for Education, Research and Innovation in Central Norway; and the Joint Research Committee between St Olavs Hospital and the Faculty of Medicine and Health Sciences, NTNU. YS was supported by a grant from the China Scholarship Council. AL declares consulting fees regarding presentation of spirometry from Diagnostica Ltb and lecture honoraria from AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. AC reports research grants funded by MRC, EPSRC, and Wellcome Trust; consulting fees from Worg Pharmaceuticals; lecture honoraria from GlaxoSmithKline, AstraZeneca, Stallergens-Greer, and Sanofi; and unpaid membership of a board of officers of the World Allergy Organization. GK was supported by grants from ZON-MW, Lung Foundation of the Netherlands, UBBO EMMIUS Foundation, GSK, Vertex, European Union (H2020 program), TEVA the Netherlands; consulting fees from AstraZeneca and PURE IMS; lecture fees from AstraZeneca, Boehringer Ingelheim and Sanofi; and participation as a chair at the exquAIro foundation (AI education for medicine and pharma). RF received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No. 101044387), Instituto de Salud Carlos III (PI18/00018, PI21/00735), SEPAR and Serra Hunter Program. AA reports research grants, consulting fees, and lecture honoraria by GlaxoSmithKline, AstraZeneca, Menarini, Chiesi, and Sanofi; and unpaid roles as Chair Board of Directors of GOLD and Co-chair of CADSET. MS received funding from ERC under the European Union's Horizon 2020 research and innovation program (grant agreement No. 949906). EM is supported by grants from the EU (ERC, TRIBAL No 757919). EM also declares advisory board and lecture fees from ALK, AstraZeneca, and Chiesi outside the submitted work. The rest of the authors declare no conflicts of interest that might be perceived to influence the interpretation of this article., (© 2024 The Author(s).)

Background: Children with severe asthma suffer from recurrent symptoms and impaired quality of life despite advanced treatment. Underlying causes of severe asthma are not completely understood, although genetic mechanisms are known to be important., Objective: The aim of this study was to identify gene regulatory enhancers in leukocytes, to describe the role of these enhancers in regulating genes related to severe and mild asthma in children, and to identify known asthma-related SNPs situated in proximity to enhancers., Methods: Gene enhancers were identified and expression of enhancers and genes were measured by Cap Analysis Gene Expression (CAGE) data from peripheral blood leukocytes from children with severe asthma (n = 13), mild asthma (n = 15), and age-matched controls (n = 9)., Results: From a comprehensive set of 8,289 identified enhancers, we further defined a robust sub-set of the high-confidence and most highly expressed 4,738 enhancers. Known single nucleotide polymorphisms, SNPs, related to asthma coincided with enhancers in general as well as with specific enhancer-gene interactions. Blocks of enhancer clusters were associated with genes including TGF-beta, PPAR and IL-11 signaling as well as genes related to vitamin A and D metabolism. A signature of 91 enhancers distinguished between children with severe and mild asthma as well as controls., Conclusions: Gene regulatory enhancers were identified in leukocytes with potential roles related to severe and mild asthma in children. Enhancers hosting known SNPs give the opportunity to formulate mechanistic hypotheses about the functions of these SNPs., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background: Many studies reported associations between long-term exposure to environmental factors and mortality; however, little is known on the combined effects of these factors and health. We aimed to evaluate the association between external exposome and all-cause mortality in large administrative and traditional adult cohorts in Europe., Methods: Data from six administrative cohorts (Catalonia, Greece, Rome, Sweden, Switzerland and the Netherlands, totaling 27,913,545 subjects) and three traditional adult cohorts (CEANS-Sweden, EPIC-NL-the Netherlands, KORA-Germany, totaling 57,653 participants) were included. Multiple exposures were assigned at the residential addresses, and were divided into three a priori defined domains: (1) air pollution [fine particulate matter (PM 2.5 ), nitrogen dioxide (NO₂), black carbon (BC) and warm-season Ozone (warm-O 3 )]; (2) land/built environment (Normalized Difference Vegetation Index-NDVI, impervious surfaces, and distance to water); (3) air temperature (cold- and warm-season mean and standard deviation). Each domain was synthesized through Principal Component Analysis (PCA), with the aim of explaining at least 80% of its variability. Cox proportional-hazards regression models were applied and the total risk of the external exposome was estimated through the Cumulative Risk Index (CRI). The estimates were adjusted for individual- and area-level covariates., Results: More than 205 million person-years at risk and more than 3.2 million deaths were analyzed. In single-component models, IQR increases of the first principal component of the air pollution domain were associated with higher mortality [HRs ranging from 1.011 (95% CI: 1.005-1.018) for the Rome cohort to 1.076 (1.071-1.081) for the Swedish cohort]. In contrast, lower levels of the first principal component of the land/built environment domain, pointing to reduced vegetation and higher percentage of impervious surfaces, were associated with higher risks. Finally, the CRI of external exposome increased mortality for almost all cohorts. The associations found in the traditional adult cohorts were generally consistent with the results from the administrative ones, albeit without reaching statistical significance., Discussion: Various components of the external exposome, analyzed individually or in combination, were associated with increased mortality across European cohorts. This sets the stage for future research on the connections between various exposure patterns and human health, aiding in the planning of healthier cities., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Nobile, Dimakopoulou, Åström, Coloma, Dadvand, de Bont, de Hoogh, Ibi, Katsouyanni, Ljungman, Melén, Nieuwenhuijsen, Pickford, Sommar, Tonne, Vermeulen, Vienneau, Vlaanderen, Wolf, Samoli and Stafoggia.)

Background: Airway obstruction is defined by spirometry as a low forced expiratory volume in 1 s (FEV 1 ) to forced vital capacity (FVC) ratio. This impaired ratio may originate from a low FEV 1 (classic) or a normal FEV 1 in combination with a large FVC (dysanaptic). The clinical implications of dysanaptic obstruction during childhood and adolescence in the general population remain unclear., Aims: To investigate the association between airway obstruction with a low or normal FEV 1 in childhood and adolescence, and asthma, wheezing and bronchial hyperresponsiveness (BHR)., Methods: In the BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology; Sweden) and PIAMA (Prevention and Incidence of Asthma and Mite Allergy; the Netherlands) birth cohorts, obstruction (FEV 1 :FVC ratio less than the lower limit of normal, LLN) at ages 8, 12 (PIAMA only) or 16 years was classified as classic (FEV 1 1 ≥LLN) obstruction. Cross-sectional and longitudinal associations between these two types of obstruction and respiratory health outcomes were estimated by cohort-adjusted logistic regression on pooled data., Results: The prevalence of classic obstruction at ages 8, 12 and 16 in the two cohorts was 1.5%, 1.1% and 1.5%, respectively. Dysanaptic obstruction was slightly more prevalent: 3.9%, 2.5% and 4.6%, respectively. Obstruction, regardless of FEV 1 , was consistently associated with higher odds of asthma (dysanaptic obstruction: OR 2.29, 95% CI 1.40 to 3.74), wheezing, asthma medication use and BHR compared with the normal lung function group. Approximately one-third of the subjects with dysanaptic obstruction in childhood remained dysanaptic during adolescence., Clinical Implications: Children and adolescents with airway obstruction had, regardless of their FEV 1 level, a higher prevalence of asthma and wheezing. Follow-up and treatment at these ages should be guided by the presence of airway obstruction., Competing Interests: Competing interests: GHK reports grant support from the Netherlands Lung Foundation, TEVA the Netherlands, GSK, Vertex, Ubbo Emmius Foundation, European Union (H2020) and ZonMW outside the submitted work. GHK reports lecture and/or advisory fees from GSK, AstraZeneca and PureIMS (money to institution). EM reports lecture and/or advisory board fees from ALK, Airsonett, AstraZeneca, Chiesi, Novartis and Sanofi outside the submitted work. GW reports lecture fees from Sanofi outside the submitted work., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The prevalence of peanut allergy is about 2% and mostly lifelong. Studies of oral immunotherapy (OIT) with peanut (the daily oral intake of an initially low and then increasing dose of peanut) often show problematic side effects, but there are indications of better safety and effect in younger children compared with older children and adults., Objective: To determine the safety and effectiveness of peanut OIT with a slow up-dosing strategy and low maintenance dose in children aged 1 to 3 years who were allergic to peanut, through a 1-year interim analysis., Method: In a randomized controlled trial (2:1 ratio), 75 children, median age 31 months (interquartile range [IQR], 23-40 months) were assigned to receive peanut OIT (n = 50) or peanut avoidance (n = 25)., Results: In the OIT and avoidance groups, 43 of 50 and 20 of 25 children, respectively, performed the 1-year open oral peanut challenge. A cumulative dose of 750 mg peanut protein after 1 year was tolerated by 72% (36 of 50 children) in the OIT group compared with 4% (1 of 25) in the avoidance group (P < .001). Median tolerated cumulative dose was 2,750 mg (IQR, 275-5,000 mg) peanut protein in the OIT group compared with 2.8 mg (IQR, 0.3-27.8 mg) in the avoidance group (P < .001). Of the doses administered at home during the first year of OIT, 1.4% resulted in adverse events and 79% were mild, and three doses of epinephrine were given at home to two individuals., Conclusion: In children aged 1 to 3 years, peanut OIT with the combination of slow up-dosing and low maintenance dose seems safe and effective after 1 year., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)