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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 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]

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]

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. Of the 62 probands with a neuropsychiatric 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.)

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.

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.