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Epidemiological data suggest that atopic diseases begin in early life and that most cases present clinically during early childhood. The diseases are highly prevalent and increase as communities adopt western lifestyles. Disentangling the pathophysiological mechanisms leading to disease debut is necessary to identify beneficial/harmful exposures so that successful prevention and treatment can be generated. The objective of this review is to explore the definition of atopy and mechanisms of atopic diseases, and to investigate the importance of environmental factors in early life, prior to disease development. First, the distribution of sIgE levels in children is investigated, as this is one of the main criteria for the definition of atopy. Thereafter, it is explored how studies of parental atopic status, sensitization patterns, and early debut and severity of atopic dermatitis have substantiated the theory of an early‐life window of opportunity for intervention that precedes the development of atopic diseases in childhood. Then, it is examined whether early‐life exposures such as breastfeeding, dogs, cats, and house dust mites in the home perinatally constitute important influencers in this crucial time of life. Finally, it is discussed how these findings could be validated in randomized controlled trials, which might prepare the ground for improved diagnostics and prevention strategies to mitigate the current atopic pandemic. [ABSTRACT FROM AUTHOR]

Background: Fraction of exhaled nitric oxide (FeNO) is used for diagnosing and monitoring asthma in children, but the influence of allergic sensitization is still poorly understood. Here, we investigate how asthma and allergic sensitization influence FeNO levels during childhood. Methods: We investigated the associations between asthma, aeroallergen sensitization, and FeNO measured from age 5–18 years in the COPSAC2000 birth cohort of 411 children using repeated measurement mixed models adjusted for gestational age, sex, concurrent airway infection, inhaled corticosteroids, and tobacco exposure. Replication was sought in the similarly designed COPSAC2010 cohort of 700 children. Results: In the COPSAC2000 cohort, 133 had asthma between age 5 and 18 years, and in the COPSAC2010 cohort, 112 had asthma between age 5 and 10 years. In the COPSAC2000 cohort, asthma and aeroallergen sensitization were both associated with higher FeNO from age 5 to 18 years: adjusted geometric mean ratio (aGMR), 1.22 (1.08–1.35), p <.01, and 1.41 (1.21–1.65), p < 0.001, respectively. However, asthma was associated with increased FeNO among children with aeroallergen sensitization: 1.44 (1.23–1.69), p <.0001, whereas asthma was associated with decreased FeNO among nonsensitized children: 0.80 (0.65–0.99), p =.05 (p‐interaction<.0001 for asthma x sensitization). Replication in the COPSAC2010 cohort showed similar results (p‐interaction <.01). Further, blood eosinophil count, total‐IgE, bronchodilator response, and bronchial hyperreactivity were all associated with increased FeNO among children sensitized to aeroallergens, but not among nonsensitized children. Conclusion: Fraction of exhaled nitric oxide is elevated through childhood in children with asthma and is correlated with asthma‐associated traits depending on the presence of aeroallergen sensitization. These findings indicate that FeNO is only a valid asthma biomarker in children with concurrent aeroallergen sensitization, which is important for guideline recommendations on the clinical use of FeNO. [ABSTRACT FROM AUTHOR]

Background: Dental caries and enamel defects are the main causes of poor dental health in children, with a substantial impact on their well‐being. Use of inhaled asthma medication is a suspected risk factor, but there is a lack of prospective studies investigating this and other prenatal and early life risk factors. Methods: Copenhagen Prospective Studies on Asthma in Childhood 2010 mother–child cohort (COPSAC2010) consists of 700 women who were recruited at 24 weeks of pregnancy. 588 of their children participated in a dental examination at 6 years of age (84%) at the COPSAC2010 research unit. Caries was defined as decayed, missing, or filled surfaces. Enamel defect was defined as demarcated opacity, post‐eruptive enamel breakdown, and/or atypical restoration on at least one molar. Caries and enamel defects were assessed in both deciduous and permanent dentitions. Results: We found no associations between inhaled corticosteroids or β2‐agonists or asthma symptoms in early childhood and the risk of caries or enamel defects by 6 years of age. Furthermore, we found no strong pre‐, peri‐, or postnatal risk factors for dental diseases at 6 years, except from nominally significant associations between antibiotic use in pregnancy (OR = 1.25, [1.01–1.54]), maternal education level (OR = 1.57, [1.01–2.45]), having a dog at home (OR = 0.50, [0.27–0.93]), and risk of enamel defects. Conclusions: Use of inhaled corticosteroids, β2‐agonists, or asthma symptoms in the first 6 years of life were not associated with the development of caries or enamel defects. This finding is reassuring for parents and physicians prescribing asthma medication for young children. [ABSTRACT FROM AUTHOR]

The Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts have provided a foundation of 25 years of research on the origins, prevention, and natural history of childhood asthma and related disorders. COPSAC's approach is characterized by clinical translational research with longitudinal deep phenotyping and exposure assessments from pregnancy, in combination with multi-omic data layers and embedded randomized controlled trials. One trial showed that fish oil supplementation during pregnancy prevented childhood asthma and identified pregnant women with the highest benefits from supplementation, thereby creating the potential for personalized prevention. COPSAC revealed that airway colonization with pathogenic bacteria in early life is associated with an increased risk of asthma. Further, airway bacteria were shown to be a trigger of acute asthma-like symptoms, with benefit from antibiotic treatment. COPSAC identified an immature gut microbiome in early life as a risk factor for asthma and allergy and further demonstrated that asthma can be predicted by infant lung function. At a molecular level, COPSAC has identified novel susceptibility genes, early immune deviations, and metabolomic alterations associated with childhood asthma. Thus, the COPSAC research program has enhanced our understanding of the processes causing childhood asthma and has suggested means of personalized prevention and treatment. [ABSTRACT FROM AUTHOR]

Background We hypothesized that insufficient intake of fish oil–derived omega-3 long-chain polyunsaturated fatty acids (n-3 LCPUFAs) during pregnancy is a contributing factor to gastroenteritis in early childhood. We examined the effect of n-3 LCPUFA supplementation on gastroenteritis symptoms in the offspring's first 3 years of life. Methods This was a double-blinded, randomized controlled trial whereby 736 mothers were administered n-3 LCPUFA or control from pregnancy week 24 until 1 week after birth. We measured the number of days with gastroenteritis, number of episodes with gastroenteritis, and the risk of having a gastroenteritis episode in the first 3 years of life. Results A median reduction of 2.5 days with gastroenteritis (P  = .018) was shown, corresponding to a 14% reduction in the n-3 LCPUFA group compared with controls in the first 3 years of life (P  = .037). A reduction in the number of gastroenteritis episodes (P  = .027) and a reduced risk of having an episode (hazard ratio, 0.80 [95% confidence interval,.66–.97]; P  = .023) were also shown. Conclusions Fish oil supplementation from the 24th week of pregnancy led to a reduction in the number of days and episodes with gastroenteritis symptoms in the first 3 years of life. The findings suggest n-3 LCPUFA supplementation as a preventive measure against gastrointestinal infections in early childhood. Clinical Trials Registration NCT00798226. [ABSTRACT FROM AUTHOR]

Background: Early exposure to allergens through a defect skin barrier has been proposed as a mechanism for inducing sensitization and development of allergic diseases. We hypothesized that early‐onset, severe atopic dermatitis (AD) is associated with development of aeroallergen sensitization and allergic rhinitis. Methods: We included 368 children from the Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) at‐risk mother‐child cohort. AD was diagnosed prospectively based on Hanifin&Rajka's criteria and severity assessed using the Scoring Atopic Dermatitis (SCORAD) index. Early‐onset AD was defined as debut ≤1 year, late‐onset as debut from 1–6 years. Aeroallergen sensitization and allergic rhinitis were diagnosed at ages 6–7 and 12 years. Associations between early‐onset and late‐onset AD and allergy endpoints were calculated using general estimating equations (GEE) models to compute the overall odds ratios (OR) for both time points. Results: Early‐onset AD (yes/no) and severity (SCORAD) were associated with development of aeroallergen sensitization during childhood; GEE OR = 1.68 [1.08; 2.62], p =.02 and 1.08 [1.03; 1.12], p <.001, whereas late‐onset AD showed a borderline significant association and late‐onset severity showed no association; GEE OR = 1.65 [0.92; 2.94], p =.08 and 1.01 [0.97; 1.06], p =.55. The same trend was seen for allergic rhinitis with significant association between early‐onset AD and allergic rhinitis; GEE OR = 1.56 [1.01; 2.41], p =.04 and severity; GEE OR = 1.09 [1.05; 1.13], p <.001, whereas late‐onset AD showed no association. The effects on sensitization and rhinitis of early‐onset versus late‐onset AD severity were significantly different: p‐interactionsensitization =.03 and p‐interactionrhinitis <.01. Conclusion: Increasing severity of early‐onset AD, but not late‐onset AD, associates with aeroallergen sensitization and allergic rhinitis later in childhood. [ABSTRACT FROM AUTHOR]

IgE-mediated food allergies are caused by adverse immunologic responses to food proteins. Allergic reactions may present locally in different tissues such as skin, gastrointestinal and respiratory tract and may result is systemic life-threatening reactions. During the last decades, the prevalence of food allergies has significantly increased throughout the world, and considerable efforts have been made to develop curative therapies. Food allergen immunotherapy is a promising therapeutic approach for food allergies that is based on the administration of increasing doses of culprit food extracts, or purified, and sometime modified food allergens. Different routes of administration for food allergen immunotherapy including oral, sublingual, epicutaneous and subcutaneous regimens are being evaluated. Although a wealth of data from clinical food allergen immunotherapy trials has been obtained, a lack of consistency in assessed clinical and immunological outcome measures presents a major hurdle for evaluating these new treatments. Coordinated efforts are needed to establish standardized outcome measures to be applied in food allergy immunotherapy studies, allowing for better harmonization of data and setting the standards for the future research. Several immunological parameters have been measured in food allergen immunotherapy, including allergen-specific immunoglobulin levels, basophil activation, cytokines, and other soluble biomarkers, T cell and B cell responses and skin prick tests. In this review we discuss different immunological parameters and assess their applicability as potential outcome measures for food allergen immunotherapy that may be included in such a standardized set of outcome measures. [ABSTRACT FROM AUTHOR]

Allergic sensitization is associated with severe asthma, but assessment of sensitization is not recommended by most guidelines. We hypothesized that patterns of IgE responses to multiple allergenic proteins differ between sensitized participants with mild/moderate and severe asthma. IgE to 112 allergenic molecules (components, c-sIgE) was measured using multiplex array among 509 adults and 140 school-age and 131 preschool children with asthma/wheeze from the Unbiased BIOmarkers for the PREDiction of respiratory diseases outcomes cohort, of whom 595 had severe disease. We applied clustering methods to identify co-occurrence patterns of components (component clusters) and patterns of sensitization among participants (sensitization clusters). Network analysis techniques explored the connectivity structure of c-sIgE, and differential network analysis looked for differences in c-sIgE interactions between severe and mild/moderate asthma. Four sensitization clusters were identified, but with no difference between disease severity groups. Similarly, component clusters were not associated with asthma severity. None of the c-sIgE were identified as associates of severe asthma. The key difference between school children and adults with mild/moderate compared with those with severe asthma was in the network of connections between c-sIgE. Participants with severe asthma had higher connectivity among components, but these connections were weaker. The mild/moderate network had fewer connections, but the connections were stronger. Connectivity between components with no structural homology tended to co-occur among participants with severe asthma. Results were independent from the different sample sizes of mild/moderate and severe groups. The patterns of interactions between IgE to multiple allergenic proteins are predictors of asthma severity among school children and adults with allergic asthma. [ABSTRACT FROM AUTHOR]

Background: Parent's history of atopic traits increases the risk of the same traits in their children, but mother's history may confer an increased risk compared to father's history. Objective: To investigate parent‐specific effects on risk of developing allergic sensitization and asthma in childhood. Methods: We included 685 parent‐child trios from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort. Parent's asthma was assessed by structured interviews and child's asthma was diagnosed prospectively at regular visits to the COPSAC clinic until age 6. Specific IgE and total IgE levels were measured in parents and children by age 0.5, 1.5 and 6 years. Associations between parent and child disease traits were analyzed using general estimating equations model adjusted for breastfeeding and maternal smoking during 3rd trimester. Results: Maternal compared to paternal elevated specific IgE increased the child's risk of elevated specific IgE from 0‐6 years: adjusted odds ratio (aOR)mother = 1.49 [1.09‐2.03], P =.01 and aORfather = 1.32 [0.96‐1.82], P =.08. Maternal elevated total IgE also increased the child's risk of elevated total IgE: adjusted relative risk (aOR)mother = 4.32 [1.51‐10.8], P <.01, while a trend was observed for paternal total IgE: aORfather = 2.01 [0.76‐4.82], P =.13. Individual time point analyses showed that the maternal effect was strongest in early life, whereas the parental effects were comparable by age 6. A similar parent‐specific pattern was observed for the child's risk of asthma. Conclusions and Clinical Relevance: The effect of mother's history of atopic traits on the child's risk of developing the same traits in early childhood was stronger than the effect from father's history, which was not evident before age 6. This suggests that maternal non‐genetic factors seem to confer an added disease risk to the child, particularly in early life. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Infantile colic is a common condition with limited knowledge about later clinical manifestations. We evaluated the role of the early life gut microbiome in infantile colic and later development of atopic and gastrointestinal disorders.Copenhagen Prospective Studies on Asthma in Childhood2010 cohort was followed with 6 years of extensive clinical phenotyping. The 1‐month gut microbiome was analyzed by 16S rRNA sequencing. Infantile colic was evaluated at age 3 months by interviews. Clinical endpoints included constipation to age 3 years and prospectively diagnosed asthma and atopic dermatitis in the first 6 years of life, and allergic sensitization from skin prick tests, specific Immunoglobulin E, and component analyses.Of 695 children, 55 children (7.9%) had infantile colic. Several factors were associated with colic including race, breastfeeding, and pets. The 1‐month gut microbiome composition and taxa abundances were not associated with colic, however a sparse Partial Least Squares model including combined abundances of nine species was moderately predictive of colic: median, cross‐validated AUC = 0.627, p = .003. Children with infantile colic had an increased risk of developing constipation (aOR, 2.88 [1.51–5.35], p = .001) later in life, but also asthma (aHR, 1.69 [1.02–2.79], p = .040), atopic dermatitis (aHR, 1.84 [1.20–2.81], p = .005) and had a higher number of positive allergic components (adjusted difference, 116% [14%–280%], p = .012) in the first 6 years. These associations were not mediated by gut microbiome differences.We link infantile colic with risk of developing constipation and atopic disorders in the first 6 years of life, which was not mediated through an altered gut microbiome at age 1‐month. These results suggest infantile colic to involve gastrointestinal and/or atopic mechanisms. [ABSTRACT FROM AUTHOR]

Background: The relationship between allergic sensitization during childhood and risk of developing asthma remains unclear. Objective: To analyze single time‐point and temporal patterns of sensitization in childhood in relation to asthma at age 13. Methods: Specific IgE (sIgE) level and skin prick test (SPT) toward 22 food allergens and aeroallergens were assessed at 6, 18 months, 4, 6, and 13 years in children from the high‐risk Copenhagen Prospective Studies on Asthma in Childhood2000 (COPSAC2000) mother‐child cohort. We analyzed the association between single time‐point monosensitization, polysensitization, and quantitative assessment of sensitization, that is, sum of all sIgE levels and SPT wheal sizes, against asthma at age 13. In addition, we analyzed the association between three temporal patterns of sensitization: (a) early‐transient, (b) late‐onset, and (c) persistent sensitization and asthma. Results: Polysensitization status measured by SPT or sIgE was at all single time‐points associated with increased risk of asthma at age 13: OR range, SPT = 3.0‐15.7, and sIgE = 2.6‐15.7, respectively, whereas monosensitization status was inconsistently associated with asthma. Quantitative assessment of both sIgE and SPT results was associated with asthma at all single time‐points: OR range, SPT = 1.3‐3.6, and sIgE = 1.1‐1.7. Persistent sensitization, but not early‐transient or late‐onset sensitization was associated with asthma by age 13: OR [95% CI], SPT = 8.9 [2.8‐28.23], and sIgE = 2.9 [1.1‐7.6], respectively. Conclusion: Sensitization to multiple allergens at single time‐points, increasing sIgE levels and SPT wheal sizes, and persistent sensitization during childhood were associated with increased risk of asthma at age 13, suggesting the use of quantitative and repetitive sensitization measurements when assessing risk of developing asthma. [ABSTRACT FROM AUTHOR]

Abstract Background Early life factors are associated with allergic respiratory diseases, but the role of high grass pollen concentrations during pregnancy and shortly after birth is not known. Objective To assess outdoor levels of grass pollen during the intrauterine period and at birth during peak pollen season on cord blood IgE in birth cohorts. Methods Three birth cohorts were included: MACS (n = 429), Australia; COPSAC 2000 (n = 200), Denmark; and LISA (n = 1968), Germany. Cord blood IgE was categorized (<0.5 kU/L, 0.5–1 kU/L, >1 kU/L) and dichotomized (high IgE ≥ 0.5 kU/L). Birth during the grass pollen season months and cumulative exposure to outdoor grass pollen counts during pregnancy with cord blood IgE were analysed using multinomial regression and analysed in meta-analysis using binomial regression adjusted for potential confounders. Results Birth during the grass pollen season had higher pooled odds of cord blood IgE >0.5 kU/L 1.37 (95% CI 1.06, 1.77) in a meta-analysis with little heterogeneity between the three cohorts. Cumulative exposure to outdoor grass pollen counts during the entire pregnancy was associated with slightly lower pooled odds but significant (OR = 0.98, 95% CI: 0.96 to 0.99). Conclusions Birth during grass pollen seasons were associated with increased risk of high cord blood IgE in cities from both hemispheres, but high pollen loads in the environment during the entire pregnancy appeared protective. As IgE responses develop during the first months of life, our study findings provide new insights into the mechanisms of grass pollen exposure at birth and shortly after on possible allergic respiratory diseases. Highlights • Grass pollen roles on intrauterine environment and subsequent development of respiratory allergic disease is not known. • A pooled estimates of birth in grass pollen seasons is associated with higher risk of high cord blood IgE in 3 cities. • New insights on the mechanisms of early environment exposures and cord blood IgE to subsequent possible allergic diseases. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion The COVID‐19 pandemic altered the pattern of many paediatric infections. We aimed to assess the incidence and characteristics of children hospitalised with gastroenteritis during the early and the late pandemic, relative to previous years.In a retrospective study, we collected data from patient files of children aged 1 month to 5 years, admitted with gastroenteritis to a paediatric department in Denmark during January–June, of 2017 to 2021, comparing incidence rates and clinical features in the early pandemic (March to June 2020), and late pandemic period (January to June 2021), to similar pre‐pandemic months.In the early pandemic, admission rates per 1000 children/month declined to 0.5 (95% CI: 0.3–0.6) from pre‐pandemic rates of 1.6 (95% CI: 1.4–1.7) (p < 0.0001) and increased in the late pandemic to 2.2 (95% CI: 1.9–2.6) (p = 0.006). Children admitted in the late pandemic period were older than those admitted previously.A resurgence of gastroenteritis in children occurred in the spring of 2021, with higher hospital admission rates of children, who were older, but not more severely ill than previously. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results Conclusion Viral infection is a common trigger of severe respiratory illnesses in early life and a risk factor for later asthma development. The mechanism leading to asthma could involve an aberrant airway immune response to viral infections, but this has rarely been studied in a human setting.To investigate in situ virus‐specific differences in upper airway immune mediator levels during viral episodes of respiratory illnesses and the association with later asthma.We included 493 episodes of acute respiratory illnesses in 277 children aged 0–3 years from the COPSAC2010 mother–child cohort. Levels of 18 different immune mediators were assessed in nasal epithelial lining fluid using high‐sensitivity MesoScale Discovery kits and compared between children with and without viral PCR‐identification in nasopharyngeal samples. Finally, we investigated whether the virus‐specific immune response was associated with asthma by age 6 years.Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN‐ɣ, TNF‐α, CCL4, CXCL10 and IL‐10 and downregulation of Type 2 and Type 17 immune mediators, including CCL13, and CXCL8 (FDR <0.05). Children developing asthma had decreased levels of IL‐10 (FDR <0.05) during viral episodes compared to children not developing asthma.We described the airway immune mediator profile during viral respiratory illnesses in early life and showed that children developing asthma by age 6 years have a reduced regulatory (IL‐10) immune mediator level. This provides insight into the interplay between early‐life viral infections, airway immunity and asthma development. [ABSTRACT FROM AUTHOR]

Background: High body mass index (BMI) is an established risk factor for asthma, but the underlying mechanisms remain unclear., Objective: To increase understanding of the BMI-asthma relationship by studying the association between genetic predisposition to higher BMI and asthma, infections and other asthma traits during childhood., Methods: Data were obtained from the two ongoing Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) mother-child cohorts. Polygenic risk scores for adult BMI were calculated for each child. Replication was done in the large-scale register-based Integrative Psychiatric Research (iPSYCH) cohort using data on hospitalisation for asthma and infections., Results: In the COPSAC cohorts (n=974), the adult BMI polygenic risk score was significantly associated with lower respiratory tract infections (incidence rate ratio (IRR) 1.20, 95% CI 1.08-1.33, false discovery rate p-value (pFDR)=0.005) at age 0-3 years and episodes of severe wheeze (IRR 1.30, 95% CI 1.06-1.60, pFDR=0.04) at age 0-6 years. Lower respiratory tract infections partly mediated the association between the adult BMI polygenic risk score and severe wheeze (proportion mediated: 0.59, 95% CI 0.28-2.24, p-value associated with the average causal mediation effect (pACME)=2e -16 ). In contrast, these associations were not mediated through the child's current BMI and the polygenic risk score was not associated with an asthma diagnosis or reduced lung function up to age 18 years. The associations were replicated in iPSYCH (n=114 283), where the adult BMI polygenic risk score significantly increased the risk of hospitalisations for lower respiratory tract infections and wheeze or asthma throughout childhood to age 18 years., Conclusion: Children with genetic predisposition to higher BMI had increased risk of lower respiratory tract infections and severe wheeze, independent of the child's current BMI. These results shed further light on the complex relationship between body mass BMI and asthma., Competing Interests: Conflict of interest: The authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Background: Atopic diseases, obesity and neuropsychiatric disorders are lifestyle-related and environmental-related chronic inflammatory disorders, and the incidences have increased in the last years., Objective: To outline the design of the 18-year follow-up of the Copenhagen Prospective Study on Asthma in Childhood (COPSAC 2000 ) birth cohort, where risk factors of atopic diseases, obesity and neuropsychiatric disorders are identified through extensive characterisation of the environment, along with deep clinical phenotyping and biosampling for omics profiling., Methods: COPSAC 2000 is a Danish prospective clinical birth cohort study of 411 children born to mothers with asthma who were enrolled at 1 month of age and closely followed at the COPSAC clinical research unit through childhood for the development of atopic diseases. At the 18-year follow-up visit, biomaterial (hair, blood, urine, faeces, throat, and skin swabs, nasal lining fluid and scraping, and hypopharyngeal aspirates) and extensive information on environmental exposures and risk behaviours were collected along with deep metabolic characterisation and multiorgan investigations including anthropometrics, heart, lungs, kidneys, intestines, bones, muscles and skin. Neuropsychiatric diagnoses were captured from medical records and registers accompanied by electronic questionnaires on behavioural traits and psychopathology., Results: A total of 370 (90%) of the 411 cohort participants completed the 18-year visit. Of these, 25.1% had asthma, 23.4% had a body mass index >25 kg/m 2 and 16.8% had a psychiatric diagnosis in childhood. A total of 68.7% drank alcohol monthly, and when drinking, 22.2% drank >10 units. Of the participants, 31.4% were currently smoking, and of these, 24.1% smoked daily. A total of 23.8% had tried taking drugs, and 19.7% reported having done self-destructive behaviour. The mean screen time per day was 6.0 hours., Conclusion: This huge dataset on health and habits, exposures, metabolism, multiorgan assessments and biosamples from COPSAC 2000 by age 18 provides a unique opportunity to explore risk factors and underlying mechanisms of atopic disease and other lifestyle-related, non-communicable diseases such as obesity and neuropsychiatric disorders, which are highly prevalent in the community and our cohort., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: IgE-mediated food allergy (FA) is a global health concern with substantial individual and societal implications. While diverse intervention strategies have been researched, inconsistencies in reported outcomes limit evaluations of FA treatments. To streamline evaluations and promote consistent reporting, the Core Outcome Measures for Food Allergy (COMFA) initiative aimed to establish a Core Outcome Set (COS) for FA clinical trials and observational studies of interventions., Methods: The project involved a review of published clinical trials, trial protocols and qualitative literature. Outcomes found as a result of review were categorized and classified, informing a two-round online-modified Delphi process followed by hybrid consensus meeting to finalize the COS., Results: The literature review, taxonomy mapping and iterative discussions with diverse COMFA group yielded an initial list of 39 outcomes. The iterative online and in-person meetings reduced the list to 13 outcomes for voting in the formal Delphi process. One more outcome was added based on participant suggestions after the first Delphi round. A total of 778 participants from 52 countries participated, with 442 participating in both Delphi rounds. No outcome met a priori criteria for inclusion, and one was excluded as a result of the Delphi. Thirteen outcomes were brought to the hybrid consensus meeting as a result of Delphi and two outcomes, 'allergic symptoms' and 'quality of life' achieved consensus for inclusion as 'core' outcomes., Conclusion: In addition to the mandatory reporting of adverse events for FA clinical trials or observational studies of interventions, allergic symptoms and quality of life should be measured as core outcomes. Future work by COMFA will define how best to measure these core outcomes., (© 2024 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Background: We previously showed an association between neonatal bacterial airway colonisation and increased risk of persistent wheeze/asthma until age 5 years. Here, we study the association with persistent wheeze/asthma and allergy-related traits until age 18 years., Methods: We investigated the association between airway colonisation with Streptococcus pneumoniae , Moraxella catarrhalis and/or Haemophilus influenzae in 1-month-old neonates from the COPSAC 2000 mother-child cohort and the development of persistent wheeze/asthma and allergy-related traits longitudinally until age 18 years using generalised estimating equations. Replication was sought in the similarly designed COPSAC 2010 cohort of 700 children., Results: Neonatal airway colonisation was present in 66 (21%) out of 319 children and was associated with a 4-fold increased risk of persistent wheeze/asthma (adjusted OR 4.01 (95% CI 1.76-9.12); p<0.001) until age 7 years, but not from age 7 to 18 years. Replication in the COPSAC 2010 cohort showed similar results using 16S data. Colonisation was associated with an increased number of exacerbations (adjusted incidence rate ratio 3.20 (95% CI 1.38-7.44); p<0.01) until age 7 years, but not from age 7 to 18 years. Colonisation was associated with increased levels of blood eosinophils (adjusted geometric mean ratio 1.24 (95% CI 1.06-1.44); p<0.01) and tumour necrosis factor (TNF)-α (adjusted geometric mean ratio 1.09 (95% CI 1.02-1.16); p=0.01) until age 12 years. There were no associations with lung function, bronchial reactivity, fractional exhaled nitric oxide, allergic sensitisation, total IgE or atopic dermatitis up to age 18 years., Conclusions: Neonatal airway colonisation was associated with early-onset persistent wheeze/asthma, exacerbations, elevated blood eosinophils and elevated TNF-α in blood, most prominent in early childhood, thereafter diminishing and no longer evident by age 18 years., Competing Interests: Conflict of interest: J. Thorsen reports lecture honoraria from AstraZeneca, outside the submitted work. A-M.M. Schoos reports lecture honoraria from Thermo Fisher Scientific, and advisory board participation with ALK, outside the submitted work. J. Stokholm reports support for the present work from the Lundbeck Foundation (grant number R16-A1694), the Ministry of Health (grant number 903516), the Danish Council for Strategic Research (grant number 0603-00280B) and the Capital Region Research Foundation; outside the submitted work, J. Stokholm reports grants from Novo Nordisk Foundation, TANDEM grant and DFF (Starting Grant – Research Leader and Danish ERC programme). K. Bønnelykke reports consulting fees from Sanofi and AstraZeneca, lecture honoraria from Boehringer Ingelheim, and advisory board participation with ALK-Abelló Nordic, outside the submitted work. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024. For reproduction rights and permissions contact permissions@ersnet.org.)

Introduction: Bronchiolitis is one of the most common reasons for hospital admissions in early childhood. As supportive treatment, some treatment guidelines suggest using nasal irrigation with normal saline (NS) to facilitate clearance of mucus from the airways. In addition, most paediatric departments in Denmark use nebulised NS for the same purpose, which can mainly be administered as inpatient care. However, no studies have ever directly tested the effect of saline in children with bronchiolitis., Methods and Analysis: The study is an investigator-initiated, multicentre, open-label, randomised, controlled non-inferiority trial and will be performed at six paediatric departments in eastern Denmark. We plan to include 300 children aged 0-12 months admitted to hospital with bronchiolitis. Participating children are randomised 1:1:1 to nebulised NS, nasal irrigation with NS or no saline therapy. All other treatment will be given according to standard guidelines.The primary outcome is duration of hospitalisation, analysed according to intention-to-treat analysis using linear regression and Cox regression analysis. By including at least 249 children, we can prove non-inferiority with a limit of 12 hours admission, alpha 2.5% and a power of 80%. Secondary outcomes are need for respiratory support with nasal continuous positive airway pressure or high-flow oxygen therapy and requirement of fluid supplements (either by nasogastric tube or intravenous)., Ethics and Dissemination: This study may inform current practice for supportive treatment of children with bronchiolitis. First, if NS is found to be helpful, it may be implemented into global guidelines. If no effect of NS is found, we can stop spending resources on an ineffective treatment. Second, if NS is effective, but nasal irrigation is non-inferior to nebulisation, it may reduce the workload of nurses, and possible duration of hospitalisation because the treatment can be delivered by the parents at home., Trial Registration Number: NCT05902702., Competing Interests: Competing interests: The authors declare no potential, perceived or real conflict of interest regarding the content of this manuscript., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: We recently conducted a double-blinded randomised controlled trial showing that fish-oil supplementation during pregnancy reduced the risk of persistent wheeze or asthma in the child by 30%. Here, we explore the mechanisms of the intervention., Methods: 736 pregnant women were given either placebo or n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the third trimester in a randomised controlled trial. Deep clinical follow-up of the 695 children in the trial was done at 12 visits until age 6 years, including assessment of genotype at the fatty acid desaturase (FADS) locus, plasma fatty acids, airway DNA methylation, gene expression, microbiome and metabolomics., Results: Supplementation with n-3 LCPUFA reduced the overall risk of non-atopic asthma by 73% at age 6 (relative risk (RR) 0.27 (95% CI 0.06 to 0.85), p=0.042). In contrast, there was no overall effect on asthma with atopic traits (RR 1.42 (95% CI 0.63 to 3.38), p=0.40), but this was significantly modified by maternal FADS genotype and LCPUFA blood levels (interaction p<0.05), and supplementation did reduce the risk of atopic asthma in the subgroup of mothers with FADS risk variants and/or low blood levels of n-3 LCPUFA before the intervention (RR 0.31 (95% CI 0.11 to 0.75), p=0.016). Furthermore, n-3 LCPUFA significantly reduced the number of infections (croup, gastroenteritis, tonsillitis, otitis media and pneumonia) by 16% (incidence rate ratio 0.84 (95% CI 0.74 to 0.96), p=0.009)., Conclusions: n-3 LCPUFA supplementation in pregnancy showed protective effects on non-atopic asthma and infections. Protective effects on atopic asthma depended on maternal FADS genotype and n-3 LCPUFA levels. This indicates that the fatty acid pathway is involved in multiple mechanisms affecting the risk of asthma subtypes and infections., Trial Registration Number: NCT00798226., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Spontaneous pneumomediastinum is a rare but maybe also underdiagnosed condition in the paediatric population. Symptoms are often mild, and the disease course is often benign, but more serious differential diagnosis must be excluded. This case report is about a four-year-old boy admitted to the children's department with a suspected allergic reaction because off swelling of his chin after taking NSAID. He had pain from the throat and neck and crepitation on the left side of his thorax. X-ray showed pneumomediastinum and subcutaneous emphysema.

Objective : Pathogenic airway bacteria colonizing the neonatal airway increase the risk of childhood asthma, but little is known about the determinants of the establishment and dynamics of the airway microbiota in early life. We studied associations between perinatal risk factors and bacterial richness of the commensal milieu in the neonatal respiratory tract. Methods : Three hundred and twenty-eight children from the Copenhagen Prospective Studies on Asthma in the Childhood2000 (COPSAC2000) at-risk birth cohort were included in this study. The bacterial richness in each of the nasopharynxes of the 1-month old, asymptomatic neonates was analyzed by use of a culture-independent technique (T-RFLP). Information on perinatal risk factors included predisposition to asthma, allergy and eczema; social status of family; maternal exposures during pregnancy; mode of delivery; and postnatal exposures. The risk factor analysis was done by conventional statistics and partial least square discriminant analysis (PLSDA). Results : The nasopharyngeal bacterial community at 1-month displayed an average of 35 (IQR: 14-55, range 1-161) phylogenetically different bacteria groups. Season of birth was associated with nasopharyngeal bacterial richness at 1-month of age with a higher bacterial richness (p = 0.003) and more abundant specific bacterial profiles representing Gram-negative alpha-proteobacteria and Gram-positive Bacilli in the nasopharynx of summer-born children. Conclusion: Early postnatal bacterial colonization of the upper airways is significantly affected by birth season, emphasizing a future focus on the seasonality aspect in modelling the impact of early dynamic changes in airway bacterial communities in relation to later disease development.

Vitamin D insufficiency has become a common health problem worldwide, particularly among pregnant women and young children. Therefore, we sought to identify environmental, dietary, and genetic determinants of serum 25(OH)-vitamin D (25(OH)D) levels during pregnancy and early childhood. 25(OH)D was measured in women at 24-weeks of gestation ( n = 738) and one-week postpartum ( n = 284) in the population-based Danish COPSAC 2010 mother-child cohort; and in cord blood ( n = 257) and age 4 years ( n = 298) in children from the at-risk COPSAC 2000 mother-child cohort. Environmental, dietary, and genetic variables were tested for association with 25(OH)D using linear regression analyses. After adjusting for season of blood sampling, determinants of lower 25(OH)D levels during pregnancy in the women were higher pre-pregnancy BMI, lower age at birth, lower genetic vitamin D score, lower dietary vitamin D intake, and lower social circumstances. In children, the determinants were lower maternal age at birth, higher pre-pregnancy BMI, lower genetic vitamin D score, older siblings, exposure to tobacco smoking, and female sex. Genetics was an important determinant at all time points, alone explaining 2%-11% of the variance in 25(OH)D. Important determinants of circulating 25(OH)D levels during pregnancy and early childhood include environmental factors, diet, and to a large extent genetics.

A six-year-old boy presented with fever, neck pain, and ear pain. Within days, the motility of his neck limited, his temperature rose, and blood samples showed signs of infection. On suspicion of cervical spondylodiscitis, a bone scintigraphy was performed, but gave negative results. A magnetic resonance imaging of the neck area showed results, which led to the diagnosis of a retropharyngeal abscess. This case is a reminder that retropharyngeal abscess poses a diagnostic challenge for the physician, and that the prognosis is potentially serious.

A 71-year-old man was referred to the lung department with pain in the right side of the chest through three months, especially when physically active. The patient presented with a tendency to shortness of breath, fatigue, low energy level and night sweats. The tentative diagnosis of pleural tumour/metastases was made. Chest x-ray showed pleural thickening and poorly defined ribs on the right side, consistent with bone destruction. Computed tomography showed a big mass in the 5th rib and universal bone lesions. Biopsy from the rib revealed the diagnosis of myelomatosis.