HTR4 gene structure and altered expression in the developing lung

Background: Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT4R) gene (HTR4) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach

Overweight in relation to allergic disease in childhood and adolescence

The prevalences of childhood overweight and allergic diseases have increased in parallel during the last decades. The overall aim of this thesis was to investigate the associations between overweight (maternal and childhood) and allergic diseases, as well as lung function, throughout childhood up to adolescence. In addition, we investigated the validity of self-reported height, weight and corresponding body mass index (BMI) among Swedish adolescents. All studies were based on the BAMSE study, a population-based birth cohort of 4,089 children followed until age 16 years. Maternal BMI was obtained from the Swedish medical birth register, while childhood BMI was measured at clinical investigations, collected from child and school health care records and self-reported. Allergic diseases were assessed by repeated questionnaires regarding symptoms and medications, while allergic sensitization to inhalant allergens was defined by the presence of specific immunoglobulin E (IgE)-antibodies in blood. Lung function was measured by spirometry at 8 and 16 years and by impulse oscillometry (IOS) at 16 years. The results of Study I showed that maternal BMI in early pregnancy was associated with asthma, but not rhinitis, eczema or allergic sensitization in the offspring up to 16 years. The association was strongest for persistent asthma, while no increased risk was observed for transient asthma. Categorization of maternal BMI showed that maternal obesity, but not overweight, was significantly associated with childhood asthma. However, the child’s own weight status could partly explain the observed association between maternal BMI and asthma in the offspring. In Study II, we found that girls with persistent asthma had a higher BMI and an increased risk of overweight throughout childhood, compared to girls without asthma. Girls with transient asthma had an increased risk of overweight at ages 4-7.9 years, whereas girls with late-onset asthma had a tendency towards an increased risk of overweight at age ≥15 years. In boys, the difference in BMI between children with and without asthma was smaller, and no consistent association was observed between asthma phenotypes and overweight. In Study III, we observed that overweight and obesity at age 8 years were associated with increased forced vital capacity (FVC) and to some extent forced expiratory volume in one second (FEV1), but reduced FEV1/FVC ratios at 8 and 16 years. The strongest association with FEV1/FVC was observed for persistent overweight at both 8 and 16 years, whereas no significant association was found for transient overweight. Cross-sectional analyses of IOS showed that overweight and obesity were associated with higher peripheral airway resistance and reactance at 16 years. The result of Study IV showed that self-reported and measured height and weight were highly correlated at 16 years (r=0.98 for height, r=0.96 for weight). On average, self-reported weight was underreported by 1.1 kg and height was overreported by 0.5 cm, leading to an underestimation of BMI by 0.5 kg/m2. The accuracy of self-reported BMI was somewhat lower among girls and among overweight and obese participants, compared to normal weight participants. Our results suggest that maternal and childhood overweight and obesity are associated with asthma and evidence of airway obstruction in children and adolescents. The association between maternal BMI and asthma may, to some extent, be mediated through childhood overweight and seems to be explained by non-allergic mechanisms. In addition, we conclude that web-based self-reported BMI can be used as a valid, quick and cost-effective alternative to measured BMI among Swedish adolescents. The accuracy however declines with increasing BMI, and is somewhat lower among girls compared to boys

Optimizing care for children with difficult-to-treat and severe asthma through specialist paediatric asthma centres:expert practical experience and advice

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.</p

Rule-Based Models of the Interplay between Genetic and Environmental Factors in Childhood Allergy

Peer reviewe

Clean air in europe for all: taking stock of the proposed revision to the ambient air quality directives. A Joint ERS, HEI, and ISEE Workshop Report

Ambient air pollution is a major public health concern and comprehensive new legislation is currently being considered to improve air quality in Europe. The European Respiratory Society (ERS), Health Effects Institute (HEI), and International Society for Environmental Epidemiology (ISEE) organised a joint meeting on May 24, 2023 in Brussels, Belgium, to review and critically evaluate the latest evidence on the health effects of air pollution and discuss ongoing revisions of the European Ambient Air Quality Directives (AAQDs). A multi-disciplinary expert group of air pollution and health researchers, patient and medical societies, and policy representatives participated. This report summarises key discussions at the meeting

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Current state and future of pediatric allergology in Europe: A road map

The history of pediatric allergology (PA) in Europe is relatively youthful, dating back to 1984, when a small group of pediatricians founded the European Working Group on Pediatric Allergy and Immunology—later giving rise to ESPACI (European Society on Pediatric Allergology and Clinical Immunology). In 1990, the first dedicated journal, Pediatric Allergy and Immunology (PAI), was founded. There are striking differences across Europe, and even within European countries, in relation to the training pathways for doctors seeing children with allergic disease(s). In 2016, the EAACIClemens von Pirquet Foundation (CvP) organized and sponsored a workshop with the European Academy of Allergy and Clinical Immunology (EAACI) Pediatric Section. This collaboration focussed on the future of PA and specifically on education, research, and networking/ advocacy. The delegates representing many countries across Europe have endorsed the concept that optimal care of children with allergic diseases is delivered by pediatricians who have received dedicated training in allergy, or allergists who have received dedicated training in pediatrics. In order to meet the needs of children and families with allergic disease(s), the pediatric allergist is highly encouraged to develop several networks. Our challenge is to reinforce a clear strategic approach to scientific excellence to across our member base and to ensure and enhance the relevance of European pediatric research in allergy. With research opportunities in basic, translational, clinical, and epidemiologic trials, more trainees and trained specialists are needed and it is an exciting time to be a pediatric allergologist