Search

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

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.)

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).)

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: Celiac disease (CeD) is associated with several immune-mediated disorders, but it is unclear whether it is associated with eosinophilic esophagitis (EoE)., Objective: We sought to examine the risk of EoE in patients with biopsy-verified CeD compared with matched controls and siblings., Methods: Using nationwide population-based histopathology data, we identified 27,338 patients with CeD diagnosed in the period 2002 to 2017 in Sweden. Patients with CeD were age- and sex-matched with up to 5 reference individuals (n = 134,987) from the general population. Cox Regression was used to estimate hazard ratios (HRs) for developing biopsy-verified EoE. In a secondary analysis, we used unaffected siblings of patients with CeD as comparators to adjust for intrafamilial confounding., Results: The median age at CeD diagnosis was 27 years, and 63.3% were female patients. During a median follow-up of 8.1 years, 17 patients with CeD and 13 matched reference individuals were diagnosed with EoE. This corresponded to incidence rates of 0.08 versus 0.01 per 1000 person-years, respectively, and an adjusted HR for EoE of 6.65 (95% CI, 3.26-13.81). Compared with their siblings without CeD, patients with CeD were however at a no increased risk of EoE (HR, 1.39; 95% CI, 0.55-3.51)., Conclusions: In this study, individuals with CeD were at a 6.6-fold increased risk of later EoE compared with the general population. This association might be explained by an altered health-seeking behavior or through shared genetic or early environmental factors because the excess risk disappeared in sibling analyses., Competing Interests: This study was supported by grants from Örebro County Council (avtal om läkarutbildning och forskning [ALF]). A.U. is supported by the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Disclosure of potential conflict of interest: A. Uchida consults for Sanofi-Regeneron and AstraZeneca. J. F. Ludvigsson coordinates a study on behalf of the Swedish Inflammatory Bowel Disease Register (SWIBREG), which has received funding from Janssen Corporation; has also received financial support from Merck Sharp and Dohme (MSD) developing an article reviewing national health care registers in China; and is currently discussing potential research collaboration with Takeda. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Authors.)

Background: Asthma was initially described as a risk factor for severe coronavirus disease 2019 (COVID-19), but the uptake of COVID-19 vaccine among young adults with asthma is not well studied., Objective: The aims were to assess COVID-19 vaccine uptake among young adults in general and to explore potential determinants including sociodemographic factors and asthma., Methods: Participants from the population-based birth cohort BAMSE (Barn/Child, Allergy, Milieu, Stockholm, Epidemiology) were included: 4,064 in the study population, 3,064 in a follow-up at age 24 years, and 2,049 in a COVID-19 follow-up (mean age, 26.5 years). Asthma and asthma-associated characteristics were assessed through questionnaires and clinical data. Data on all COVID-19 vaccines registered between January 1, 2021, and February 15, 2023, were extracted from the National Vaccination Register., Results: In the study population (n = 4,064), 53.9% had ≥3 COVID-19 vaccine doses registered. In the 24-year follow-up population (n = 3,064), vaccine uptake differed in relation to education ( P  < .001). Among the participants with university/college education, 65.7% had an uptake of ≥3 doses of vaccine, compared to 54.1% among the participants with elementary school/high school education. Participants with asthma had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.62; 95% confidence interval, 0.41-0.92) and ≥2 compared to peers without asthma. Those with uncontrolled disease also had decreased odds of receiving ≥3 doses (adjusted odds ratio = 0.30; 95% confidence interval, 0.13-0.66) and ≥2 compared to participants with controlled asthma., Conclusions: COVID-19 vaccine uptake among young adults is lower in individuals from households with lower socioeconomic status and among those with asthma, including uncontrolled asthma., Competing Interests: Supported by grants from the 10.13039/501100004359Swedish Research Council, the 10.13039/501100006636Swedish Research Council for Health, Working Life and Welfare, 10.13039/501100001862Formas, Swedish Asthma and Allergy Research Foundation, the Swedish Heart–Lung Foundation, and Region Stockholm (ALF project, and for cohort and database maintenance). Disclosure of potential conflict of interest: E. Melén reports personal fees from AstraZeneca, Chiesi, Sanofi, and Novartis outside the submitted work. The rest of the authors declare that they have no relevant conflicts of interest., (© 2024 The Authors.)

Background: Bronchopulmonary Dysplasia (BPD) in infants born prematurely is a risk factor for chronic airway obstruction later in life. The distribution of T cell subtypes in the large airways is largely unknown., Objective: To characterize cellular and T cell profiles in the large airways of young adults with a history of BPD., Methods: Forty-three young adults born prematurely (preterm (n = 20), BPD (n = 23)) and 45 full-term-born (asthma (n = 23), healthy (n = 22)) underwent lung function measurements, and bronchoscopy with large airway bronchial wash (BW). T-cells subsets in BW were analyzed by immunocytochemistry., Results: The proportions of both lymphocytes and CD8 + T cells in BW were significantly higher in BPD (median, 6.6%, and 78.0%) when compared with asthma (3.4% and 67.8%, p = 0.002 and p = 0.040) and healthy (3.8% and 40%, p < 0.001 and p < 0.001). In all adults born prematurely (preterm and BPD), lymphocyte proportion correlated negatively with forced vital capacity (r= -0.324, p = 0.036) and CD8 + T cells correlated with forced expiratory volume in one second, FEV 1 (r=-0.448, p = 0.048). Correlation-based network analysis revealed that lung function cluster and BPD-birth cluster were associated with lymphocytes and/or CD4 + and CD8 + T cells. Multivariate regression analysis showed that lymphocyte proportions and BPD severity qualified as independent factors associated with FEV 1 ., Conclusions: The increased cytotoxic T cells in the large airways in young adults with former BPD, suggest a similar T-cell subset pattern as in the small airways, resembling features of COPD. Our findings strengthen the hypothesis that mechanisms involving adaptive and innate immune responses are involved in the development of airway disease due to preterm birth., (© 2024. The Author(s).)

Background: Moderate-to-late preterm birth (32 to <37 weeks of gestation) has been associated with impaired lung function in adolescence, but data in adulthood and physiological phenotyping beyond spirometry are scarce. We aimed to investigate lung function development from adolescence into young adulthood and to provide physiological phenotyping in individuals born moderate-to-late preterm., Methods: Lung function data from individuals born moderate-to-late preterm (n=110) and term (37 to <42 weeks of gestation, n=1895) in the Swedish birth cohort BAMSE were used for analysis and included dynamic spirometry, fractional exhaled nitric oxide and multiple breath nitrogen wash-out. Data from 16- and 24-year follow-ups were analysed using regression models stratified on sex and adjusted for smoking. Data-driven latent class analysis was used to phenotype moderate-to-late preterm individuals at 24 years, and groups were related to background factors., Results: Males born moderate-to-late preterm had lower forced expiratory volume in 1 s (FEV 1 ) at 24 years of age (-0.28 z-score, p=0.045), compared to males born term. In females, no difference was seen at 24 years, partly explained by a significant catch up in FEV 1 between 16 and 24 years (0.18 z-score, p=0.01). Lung function phenotypes described as "asthma-like", "dysanapsis-like" and "preterm reference" were identified within the preterm group. Maternal overweight in early pregnancy was associated with "asthma-like" group membership (OR 3.59, p=0.02)., Conclusion: Our results show impaired FEV 1 at peak lung function in males born moderate-to-late preterm, while females born moderate-to-late preterm had significant catch up between the ages of 16 and 24 years. Several phenotypes of lung function impairment exist in individuals born moderate-to-late preterm., Competing Interests: Conflict of interest: G. Wang reports receiving lecture fees from Sanofi outside the submitted work. Conflict of interest: E. Melén reports payment for lectures and/or advisory board fees from ALK, AstraZeneca, Chiesi, Novartis and Sanofi, outside the submitted work. Conflict of interest: The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Background: We evaluated the independent and joint effects of air pollution, land/built environment characteristics, and ambient temperature on all-cause mortality as part of the EXPANSE project., Methods: We collected data from six administrative cohorts covering Catalonia, Greece, the Netherlands, Rome, Sweden, and Switzerland and three traditional cohorts in Sweden, the Netherlands, and Germany. Participants were linked to spatial exposure estimates derived from hybrid land use regression models and satellite data for: air pollution [fine particulate matter (PM 2.5 ), nitrogen dioxide (NO₂), black carbon (BC), warm season ozone (O 3 )], land/built environment [normalized difference vegetation index (NDVI), distance to water, impervious surfaces], and ambient temperature (the mean and standard deviation of warm and cool season temperature). We applied Cox proportional hazard models accounting for several cohort-specific individual and area-level variables. We evaluated the associations through single and multiexposure models, and interactions between exposures. The joint effects were estimated using the cumulative risk index (CRI). Cohort-specific hazard ratios (HR) were combined using random-effects meta-analyses., Results: We observed over 3.1 million deaths out of approximately 204 million person-years. In administrative cohorts, increased exposure to PM 2.5 , NO 2 , and BC was significantly associated with all-cause mortality (pooled HRs: 1.054, 1.033, and 1.032, respectively). We observed an adverse effect of increased impervious surface and mean season-specific temperature, and a protective effect of increased O 3 , NDVI, distance to water, and temperature variation on all-cause mortality. The effects of PM 2.5 were higher in areas with lower (10th percentile) compared to higher (90th percentile) NDVI levels [pooled HRs: 1.054 (95% confidence interval (CI) 1.030-1.079) vs. 1.038 (95% CI 0.964-1.118)]. A similar pattern was observed for NO 2 . The CRI of air pollutants (PM 2.5 or NO 2 ) plus NDVI and mean warm season temperature resulted in a stronger effect compared to single-exposure HRs: [PM 2.5 pooled HR: 1.061 (95% CI 1.021-1.102); NO 2 pooled HR: 1.041 (95% CI 1.025-1.057)]. Non-significant effects of similar patterns were observed in traditional cohorts., Discussion: The findings of our study not only support the independent effects of long-term exposure to air pollution and greenness, but also highlight the increased effect when interplaying with other environmental exposures., 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 Dimakopoulou, Nobile, de Bont, Wolf, Vienneau, Ibi, Coloma, Pickford, Åström, Sommar, Kasdagli, Souliotis, Tsolakidis, Tonne, Melén, Ljungman, de Hoogh, Vermeulen, Vlaanderen, Katsouyanni, Stafoggia and Samoli.)

Circulating vitamin B12 concentrations during pregnancy are associated with offspring health. Foetal DNA methylation changes could underlie these associations. Within the Pregnancy And Childhood Epigenetics Consortium, we meta-analysed epigenome-wide associations of circulating vitamin B12 concentrations in mothers during pregnancy ( n  = 2,420) or cord blood ( n  = 1,029), with cord blood DNA methylation. Maternal and newborn vitamin B12 concentrations were associated with DNA methylation at 109 and 7 CpGs, respectively (False Discovery Rate P -value <0.05). Persistent associations with DNA methylation in the peripheral blood of up to 482 children aged 4-10 y were observed for 40.7% of CpGs associated with maternal vitamin B12 and 57.1% of CpGs associated with newborn vitamin B12. Of the CpGs identified in the maternal meta-analyses, 4.6% were associated with either birth weight or gestational age in a previous work. For the newborn meta-analysis, this was the case for 14.3% of the identified CpGs. Also, of the CpGs identified in the newborn meta-analysis, 14.3% and 28.6%, respectively, were associated with childhood cognitive skills and nonverbal IQ. Of the 109 CpGs associated with maternal vitamin B12, 18.3% were associated with nearby gene expression. In this study, we showed that maternal and newborn vitamin B12 concentrations are associated with DNA methylation at multiple CpGs in offspring blood ( P FDR <0.05). Whether this differential DNA methylation underlies associations of vitamin B12 concentrations with child health outcomes, such as birth weight, gestational age, and childhood cognition, should be further examined in future studies.

Atopic dermatitis (AD) is a common inflammatory skin condition and prior genome-wide association studies (GWAS) have identified 71 associated loci. In the current study we conducted the largest AD GWAS to date (discovery N = 1,086,394, replication N = 3,604,027), combining previously reported cohorts with additional available data. We identified 81 loci (29 novel) in the European-only analysis (which all replicated in a separate European analysis) and 10 additional loci in the multi-ancestry analysis (3 novel). Eight variants from the multi-ancestry analysis replicated in at least one of the populations tested (European, Latino or African), while two may be specific to individuals of Japanese ancestry. AD loci showed enrichment for DNAse I hypersensitivity and eQTL associations in blood. At each locus we prioritised candidate genes by integrating multi-omic data. The implicated genes are predominantly in immune pathways of relevance to atopic inflammation and some offer drug repurposing opportunities., (© 2023. Springer Nature Limited.)

Complex diseases are caused by a combination of genetic, lifestyle, and environmental factors and comprise common noncommunicable diseases, including allergies, cardiovascular disease, and psychiatric and metabolic disorders. More than 25% of Europeans suffer from a complex disease, and together these diseases account for 70% of all deaths. The use of genomic, molecular, or imaging data to develop accurate diagnostic tools for treatment recommendations and preventive strategies, and for disease prognosis and prediction, is an important step toward precision medicine. However, for complex diseases, precision medicine is associated with several challenges. There is a significant heterogeneity between patients of a specific disease-both with regards to symptoms and underlying causal mechanisms-and the number of underlying genetic and nongenetic risk factors is often high. Here, we summarize precision medicine approaches for complex diseases and highlight the current breakthroughs as well as the challenges. We conclude that genomic-based precision medicine has been used mainly for patients with highly penetrant monogenic disease forms, such as cardiomyopathies. However, for most complex diseases-including psychiatric disorders and allergies-available polygenic risk scores are more probabilistic than deterministic and have not yet been validated for clinical utility. However, subclassifying patients of a specific disease into discrete homogenous subtypes based on molecular or phenotypic data is a promising strategy for improving diagnosis, prediction, treatment, prevention, and prognosis. The availability of high-throughput molecular technologies, together with large collections of health data and novel data-driven approaches, offers promise toward improved individual health through precision medicine., (© 2023 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Seasonal variations in environmental exposures at birth or during gestation are associated with numerous adult traits and health outcomes later in life. Whether DNA methylation (DNAm) plays a role in the molecular mechanisms underlying the associations between birth season and lifelong phenotypes remains unclear., Methods: We carried out epigenome-wide meta-analyses within the Pregnancy And Childhood Epigenetic Consortium to identify associations of DNAm with birth season, both at differentially methylated probes (DMPs) and regions (DMRs). Associations were examined at two time points: at birth (21 cohorts, N = 9358) and in children aged 1-11 years (12 cohorts, N = 3610). We conducted meta-analyses to assess the impact of latitude on birth season-specific associations at both time points., Results: We identified associations between birth season and DNAm (False Discovery Rate-adjusted p values < 0.05) at two CpGs at birth (winter-born) and four in the childhood (summer-born) analyses when compared to children born in autumn. Furthermore, we identified twenty-six differentially methylated regions (DMR) at birth (winter-born: 8, spring-born: 15, summer-born: 3) and thirty-two in childhood (winter-born: 12, spring and summer: 10 each) meta-analyses with few overlapping DMRs between the birth seasons or the two time points. The DMRs were associated with genes of known functions in tumorigenesis, psychiatric/neurological disorders, inflammation, or immunity, amongst others. Latitude-stratified meta-analyses [higher (≥ 50°N), lower (< 50°N, northern hemisphere only)] revealed differences in associations between birth season and DNAm by birth latitude. DMR analysis implicated genes with previously reported links to schizophrenia (LAX1), skin disorders (PSORS1C, LTB4R), and airway inflammation including asthma (LTB4R), present only at birth in the higher latitudes (≥ 50°N)., Conclusions: In this large epigenome-wide meta-analysis study, we provide evidence for (i) associations between DNAm and season of birth that are unique for the seasons of the year (temporal effect) and (ii) latitude-dependent variations in the seasonal associations (spatial effect). DNAm could play a role in the molecular mechanisms underlying the effect of birth season on adult health outcomes., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The complex interplay of multiple environmental factors and cardiovascular has scarcely been studied. Within the EXPANSE project, we evaluated the association between long-term exposure to multiple environmental indices and stroke incidence across Europe., Methods: Participants from three traditional adult cohorts (Germany, Netherlands and Sweden) and four administrative cohorts (Catalonia [region Spain], Rome [city-wide], Greece and Sweden [nationwide]) were followed until incident stroke, death, migration, loss of follow-up or study end. We estimated exposures at residential addresses from different exposure domains: air pollution (nitrogen dioxide (NO 2 ), particulate matter < 2.5 μm (PM 2.5 ), black carbon (BC), ozone), built environment (green/blue spaces, impervious surfaces) and meteorology (seasonal mean and standard deviation of temperatures). Associations between environmental exposures and stroke were estimated in single and multiple-exposure Cox proportional hazard models, and Principal Component (PC) Analyses derived prototypes for specific exposures domains. We carried out random effects meta-analyses by cohort type., Results: In over 15 million participants, increased levels of NO 2 and BC were associated with increased higher stroke incidence in both cohort types. Increased Normalized Difference Vegetation Index (NDVI) was associated with a lower stroke incidence in both cohort types, whereas an increase in impervious surface was associated with an increase in stroke incidence. The first PC of the air pollution domain (PM 2.5 , NO 2 and BC) was associated with an increase in stroke incidence. For the built environment, higher levels of NDVI and lower levels of impervious surfaces were associated with a protective effect [%change in HR per 1 unit = -2.0 (95 %CI, -5.9;2.0) and -1.1(95 %CI, -2.0; -0.3) for traditional adult and administrative cohorts, respectively]. No clear patterns were observed for distance to blue spaces or temperature parameters., Conclusions: We observed increased HRs for stroke with exposure to PM 2.5 , NO 2 and BC, lower levels of greenness and higher impervious surface in single and combined exposure models., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The concept of "one-airway-one-disease", coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma. We observed significant differences in the topology of the interactomes and in the pathways associated to each phenotype. In rhinitis alone, identified pathways included cell cycle, cytokine signalling, developmental biology, immune system, metabolism of proteins and signal transduction. In rhinitis and asthma multimorbidity, most pathways were related to signal transduction. The remaining few were related to cytokine signalling, immune system or developmental biology. Toll-like receptors and IL-17-mediated signalling were identified in rhinitis alone, while IL-33 was identified in rhinitis in multimorbidity. On the other hand, few pathways were associated with both phenotypes, most being associated with signal transduction pathways including estrogen-stimulated signalling. The only immune system pathway was FceRI-mediated MAPK activation. In conclusion, our findings suggest that rhinitis alone and rhinitis and asthma multimorbidity should be considered as two distinct diseases., (© 2023. Springer Nature Limited.)

Post coronavirus disease-19 (post COVID-19) is mainly studied in clinical populations and less is known about post COVID-19 in a young general population. The aim of the study is to investigate the prevalence and symptoms of post COVID-19 and its potential risk factors in young adults. Participants from the Swedish population-based birth cohort BAMSE were included (n = 2022, mean age 26.5 years). Post COVID-19 was assessed through a questionnaire and defined as symptoms after confirmed COVID-19 (registry-based or self-reported positive test) lasting for ≥ 2 months. In total, 681 participants had had confirmed COVID-19. Among them, 112 (16.5%) fulfilled the definition of post COVID-19 (17.8% in females, 14.5% in males, p = 0.26). The most common post COVID-19 symptoms were altered smell and taste (68.8%), dyspnea (33.7%) and fatigue (30.4%). Overall, no major risk factors for post COVID-19 were identified except for being bedbound during COVID-19. However, asthma and rhinitis were associated with the post COVID-19 symptom dyspnea, migraine with altered smell and taste, and lower self-rated health with fatigue. In conclusion, post COVID-19 symptoms are common, also among young adults in the general population. Although not life-threatening, it could have a considerable impact on public health due to the high prevalence and long-term symptoms., (© 2023. The Author(s).)

Background: Epidemiological studies suggest beneficial associations between dietary fibre intake, lung function and chronic respiratory symptoms in adults. Our aim was to investigate the association between dietary fibre intake in childhood and respiratory health up to adulthood., Methods: The individual fibre intake of 1956 participants from the Swedish population-based birth cohort BAMSE was estimated from 98- and 107-item food frequency questionnaires at ages 8 and 16 years, respectively. At 8, 16 and 24 years, lung function was measured by spirometry. Respiratory symptoms (cough, mucus production, breathing difficulties/wheeze) were assessed by questionnaires, and airway inflammation by exhaled nitric oxide fraction ( F ENO ) (≥25 ppb) at 24 years. Longitudinal associations with lung function were analysed by mixed-effects linear regression; associations with respiratory symptoms and airway inflammation were analysed by logistic regression, adjusting for potential confounders., Results: There were no associations between fibre intake at 8 years, as total and from different sources, spirometry measurements and respiratory symptoms at 24 years. Higher fruit fibre intake tended to be inversely associated with airway inflammation at 24 years (OR 0.70, 95% CI 0.48-1.00), which became non-significant after exclusion of participants with food-related allergic symptoms (OR 0.74, 95% CI 0.49-1.10). No associations between fibre intake at 8 and 16 years as an updated lagged exposure and spirometry measurements up to 24 years were observed., Conclusion: In this longitudinal study, we observed no consistent association between dietary fibre intake in childhood and lung function or respiratory symptoms up to adulthood. Further research on dietary fibre in relation to respiratory health across the life course is needed., Competing Interests: Conflict of interest: The authors have no conflicts of interest to disclose., (Copyright ©The authors 2023.)

Allergic rhinitis is the most common chronic disease in Sweden, with impact on quality of life and with a heavy economic burden for the society. More than 20 years have passed since national recommendations were launched, and meanwhile both ARIA (Allergic rhinitis and its impact of asthma) and EUFOREA (The European Forum for Research and Education in Allergy and Airway Diseases) have presented international guidelines which in this article have been adapted to the clinical situation in Sweden. Visual analogue scale (VAS) is recommended for symptom evaluation, and the importance of correct allergen analysis and examination for coexisting asthma is emphasized. Treatment is recommended according to EUFOREA. Follow-up is important, and if VAS is ≥5 the disease is regarded as uncontrolled and must lead to a change of treatment. Since self-treatment is common in allergic rhinitis the importance of patient cooperation and information is underlined.

Climate change is one of the major public health emergencies with already unprecedented impacts on our planet, environment and health. Climate change has already resulted in substantial increases in temperatures globally and more frequent and extreme weather in terms of heatwaves, droughts, dust storms, wildfires, rainstorms and flooding, with prolonged and altered allergen and microbial exposure as well as the introduction of new allergens to certain areas. All these exposures may have a major burden on patients with respiratory conditions, which will pose increasing challenges for respiratory clinicians and other healthcare providers. In addition, complex interactions between these different factors, along with other major environmental risk factors ( e.g. air pollution), will exacerbate adverse health effects on the lung. For example, an increase in heat and sunlight in urban areas will lead to increases in ozone exposure among urban populations; effects of very high exposure to smoke and pollution from wildfires will be exacerbated by the accompanying heat and drought; and extreme precipitation events and flooding will increase exposure to humidity and mould indoors. This review aims to bring respiratory healthcare providers up to date with the newest research on the impacts of climate change on respiratory health. Respiratory clinicians and other healthcare providers need to be continually educated about the challenges of this emerging and growing public health problem and be equipped to be the key players in solutions to mitigate the impacts of climate change on patients with respiratory conditions., Educational Aims: To define climate change and describe major related environmental factors that pose a threat to patients with respiratory conditions.To provide an overview of the epidemiological evidence on climate change and respiratory diseases.To explain how climate change interacts with air pollution and other related environmental hazards to pose additional challenges for patients.To outline recommendations to protect the health of patients with respiratory conditions from climate-related environmental hazards in clinical practice.To outline recommendations to clinicians and patients with respiratory conditions on how to contribute to mitigating climate change., Competing Interests: Conflict of interest: Z.J. Andersen reports receiving support for attending meetings and/or travel from European Respiratory Society (ERS), outside the submitted work; and is Chair of the ERS Environment and Health Committee (EHC), and Executive Council member (councillor) of the International Society for Environmental Epidemiology (ISEE). A.M. Vicedo-Cabrera has nothing to disclose. B. Hoffmann has received honoraria for advisory board meetings from the Health Effects Institute, outside the submitted work; and is a member of the ERS Advocacy Council. E. Melén has received honoraria for lectures or advisory board meetings from ALK, AstraZeneca, Chiesi, Novartis and Sanofi outside the submitted work; and is a member of the ERS Environment and Health Committee (EHC)., (Copyright ©ERS 2023.)

Background: The COVID-19 pandemic has impacted on public health in several ways. The aim of the study was to investigate changes in lifestyle, adiposity, and cardiometabolic markers among young adults in Sweden during the COVID-19 pandemic and their determinants., Methods: The study included 1 004 participants from the population-based birth cohort BAMSE. Anthropometrics, body composition (bioelectric impedance analyses), pulse, and blood pressure were measured before (December 2016-May 2019; mean age 22.6 years) and during (October 2020-June 2021; mean age 25.7 years) the COVID-19 pandemic. Lifestyle changes during the pandemic were assessed through a questionnaire., Results: All measures of adiposity (weight, BMI, body fat percentage, trunk fat percentage) and cardiometabolic markers (blood pressure, pulse) increased during the study period (e.g., body fat percentage by a median of + 0.8% in females, p < 0.001, and + 1.5% in males, p < 0.001). Male sex, non-Scandinavian ethnicity, BMI status (underweight and obesity), and changes in lifestyle factors, e.g., decreased physical activity during the pandemic, were associated with higher increase in BMI and/or adiposity., Conclusion: Lifestyle factors, adiposity and cardiometabolic markers may have been adversely affected among young adults in Sweden during the COVID-19 pandemic compared with the preceding years. Targeted public health measures to reduce obesity and improve healthy lifestyle are important to prevent future non-communicable diseases., (© 2023. The Author(s).)

Background: The beneficial effect of improving air quality on lung function development remains understudied. We assessed associations of changes in ambient air pollution levels with lung function growth from childhood until young adulthood in a Swedish cohort study., Methods: In the prospective birth cohort BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology (in Swedish)), spirometry was conducted at the 8-year (2002-2004), 16-year (2011-2013) and 24-year (2016-2019) follow-ups. Participants with spirometry data at 8 years and at least one other measurement in subsequent follow-ups were included (1509 participants with 3837 spirometry measurements). Ambient air pollution levels (particulate matter with diameter ≤2.5 μm (PM 2.5 ), particulate matter with diameter ≤10 μm (PM 10 ), black carbon (BC) and nitrogen oxides (NO x )) at residential addresses were estimated using dispersion modelling. Linear mixed effect models were used to estimate associations between air pollution exposure change and lung function development., Results: Overall, air pollution levels decreased progressively during the study period. For example, the median (interquartile range (IQR)) level of PM 2.5 decreased from 8.24 (0.92) μg·m -3 during 2002-2004 to 5.21 (0.67) μg·m -3 during 2016-2019. At the individual level, for each IQR reduction of PM 2.5 the lung function growth rate increased by 4.63 (95% CI 1.64-7.61) mL per year (p<0.001) for forced expiratory volume in 1 s and 9.38 (95% CI 4.76-14.00) mL per year (p<0.001) for forced vital capacity. Similar associations were also observed for reductions of BC and NO x . Associations persisted after adjustment for potential confounders and were not modified by asthma, allergic sensitisation, overweight, early-life air pollution exposure or dietary antioxidant intake., Conclusions: Long-term reduction of air pollution is associated with positive lung function development from childhood to young adulthood., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2023.)

Background: Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma., Methods: We searched four bibliographic databases from inception to 15 March 2021 . Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken., Results: 13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated "very low" to "low" for quality of measurement properties and none met all quality standards., Conclusions: This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics., Competing Interests: Conflict of interests: E. Khaleva and A. Rattu declare funding for the present manuscript from the 3TR European Union Innovative Medicines Initiative 2 paid to the university. C. Brightling declares grants from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic and 4DPharma, consulting fees from GlaxoSmithKline, AstraZeneca, Novartis, Chiesi, Boehringer Ingelheim, Genentech, Roche, Sanofi, Mologic, 4DPharma and Teva, and support from the 3TR project. A. Bourdin reports being an investigator for clinical trials promoted by AstraZeneca, Chieisi, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Regeneron and Sanofi; having received fees for lectures, attendance of meeting and consultancy from AstraZeneca, Chieisi, GlaxoSmithKline, Boehringer Ingelheim, Novartis, Regeneron and Sanofi; having received research grants from AstraZeneca and Boehringer Ingelheim; and participation on a data safety monitoring or advisory board of AB Science. A. Bossios has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva and Novartis; honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Novartis and Sanofi; and received support for attending meetings from AstraZeneca and Novartis, all outside the present work; reports being a member of the Steering Committee of SHARP, Secretary of Assembly 5 (Airway Diseases, Asthma, COPD and Chronic Cough) of the European Respiratory Society and Vice-chair of the Nordic Severe Asthma Network (NSAN). K.F. Chung has received honoraria for participating in advisory board meetings of GlaxoSmithKline, AstraZeneca, Roche, Novartis, Merck and Shionogi regarding treatments for asthma, COPD and chronic cough, and has also been renumerated for speaking engagements for Novartis and AstraZeneca. R. Chaudhuri has received lecture fees from GlaxoSmithKline, AstraZeneca, Teva, Chiesi, Sanofi and Novartis; honoraria for advisory board meetings from GlaxoSmithKline, AstraZeneca, Teva, Chiesi and Novartis; sponsorship to attend international scientific meetings from Chiesi, Napp, Sanofi, Boehringer, GlaxoSmithKline and AstraZeneca, and a research grant to her Institute from AstraZeneca for a UK multicentre study. C. Coleman declares funding received to support this work by the European Lung Foundation (ELF) from the European Commission's Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement number 831434 (3TR), and is an employee of the ELF. R. Djukanovic declares funding from European Respiratory Society, Teva, GlaxoSmithKline, Novartis, Sanofi and Chiesi for the SHARP CRC, consulting fees for Synairgen; honorarium for a lecture from GlaxoSmithKline, participation on a data safety monitoring board or advisory board for Kymab (Cambridge) and shares in Synairgen, outside the submitted work. S-E. Dahlen declares funding from 3TR IMI Grant; consulting fees from AstraZeneca, Cayman Co., GlaxoSmithKline, Novartis, Regeneron, Sanofi and Teva; honoraria for lectures from AstraZeneca and Sanofi. A. Exley declares being a minority shareholder in GlaxoSmithKline PLC. L. Fleming declares participation in advisory boards and honoraria for lectures from Sanofi, Respiri UK, AstraZeneca, Novartis and Teva, outside the scope of this publication. All payments were made to her institution. A. Gupta received speaker and advisory board fees from GlaxoSmithKline, Novartis, AstraZeneca and Boehringer Ingelheim. A. Gupta's institution had received research grants from GlaxoSmithKline, Novartis, AstraZeneca and Boehringer Ingelheim. E. Hamelmann declares support from the German Ministry of Education and Research (BMBF) and German Asthma Net (GAN) e.V.; funding for research in severe asthma in children (CHAMP-01GL1742D) and for Severe Asthma Register. G.H. Koppelman reports receiving research grants from the Lung Foundation of the Netherlands, Ubbo Emmius Foundation, H2020 European Union, Teva, GlaxoSmithKline and Vertex, outside this work (money to institution); he reports memberships of advisory boards to GlaxoSmithKline and PURE-IMS, outside this work (money to institution). E. Melen has received consulting fees from AstraZeneca, Chiesi, Novartis and Sanofi outside the submitted work. V. Mahler has no conflict of interest but declares that the views expressed in this review are the personal views of the author and may not be understood or quoted as being made on behalf of or reflecting the position of the respective national competent authority, the European Medicines Agency, or one of its committees or working parties. F. Singer reports being an investigator for clinical trials promoted by Vertex and having received fees for lectures from Vertex and Novartis, outside the submitted work. C. Porsbjerg declares grants, consulting fees and honoraria from AstraZeneca, GlaxoSmithKline, Novartis, Teva, Sanofi, Chiesi and ALK (paid to institution and personal honoraria); participation in the advisory board for AstraZeneca, Novartis, Teva, Sanofi and ALK, outside the submitted work. V. Ramiconi reports grants paid to EFA from Pfizer, Novartis, AstraZeneca, Sanofi, Chiesi Farmaceutici, Regeneron, DBV Technologies, MSD, GlaxoSmithKline, Aimmune, LeoPharma, AbbVie, Boehringer Ingelheim, OM Pharma and Roche; payment for expert testimony from Novartis Global Respiratory Patient Council 2021 and Novartis EPIS Steering Committee to EFA. G. Roberts declares EU IMI funding and consulting fees from AstraZeneca paid to his institution. No other author has any conflict of interest to declare., (Copyright ©The authors 2023.)

Background: Post COVID-19 conditions, also known as long COVID, are of public health concern, but little is known about their underlying risk factors. We aimed to investigate associations of air pollution exposure with long COVID among Swedish young adults., Methods: We used data from the BAMSE (Children, Allergy, Environment, Stockholm, Epidemiology [in Swedish]) cohort. From October 2021 to February 2022 participants answered a web-questionnaire focusing on persistent symptoms following acute SARS-CoV-2 infection. Long COVID was defined as symptoms after confirmed infection with SARS-CoV-2 lasting for two months or longer. Ambient air pollution levels (particulate matter ≤2.5 μm [PM 2.5 ], ≤10 μm [PM 10 ], black carbon [BC] and nitrogen oxides [NO x ]) at individual-level addresses were estimated using dispersion modelling., Findings: A total of 753 participants with SARS-CoV-2 infection were included of whom 116 (15.4%) reported having long COVID. The most common symptoms were altered smell/taste (n = 80, 10.6%), dyspnea (n = 36, 4.8%) and fatigue (n = 34, 4.5%). Median annual PM 2.5 exposure in 2019 (pre-pandemic) was 6.39 (interquartile range [IQR] 6.06-6.71) μg/m 3 . Adjusted Odds Ratios (95% confidence intervals) of PM 2.5 per IQR increase were 1.28 (1.02-1.60) for long COVID, 1.65 (1.09-2.50) for dyspnea symptoms and 1.29 (0.97-1.70) for altered smell/taste. Positive associations were found for the other air pollutants and remained consistent across sensitivity analyses. Associations tended to be stronger among participants with asthma, and those having had COVID during 2020 (versus 2021)., Interpretation: Ambient long-term PM 2.5 exposure may affect the risk of long COVID in young adults, supporting efforts for continuously improving air quality., Funding: The study received funding from the Swedish Research Council (grant no. 2020-01886, 2022-06340), the Swedish Research Council for Health, Working life and Welfare (FORTE grant no. 2017-01146), the Swedish Heart-Lung Foundation, Karolinska Institute (no. 2022-01807) and Region Stockholm (ALF project for cohort and database maintenance)., Competing Interests: The authors have nothing to disclose., (© 2023 The Author(s).)