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AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
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BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: Viral detection were associated with upregulation of several Type 1 and regulatory immune mediators, including IFN-É£, 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. CONCLUSION: 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.
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BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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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 (COPSAC2000) 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: COPSAC2000 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/m2 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 COPSAC2000 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.
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Asma , Cohorte de Nacimiento , Humanos , Dinamarca/epidemiología , Femenino , Masculino , Asma/epidemiología , Estudios de Seguimiento , Adolescente , Estudios Prospectivos , Factores de Riesgo , Niño , Trastornos Mentales/epidemiología , Preescolar , Lactante , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , Proyectos de InvestigaciónRESUMEN
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.
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Exposición a Riesgos Ambientales , Hipersensibilidad Inmediata , Inmunoglobulina E , Humanos , Animales , Exposición a Riesgos Ambientales/efectos adversos , Hipersensibilidad Inmediata/diagnóstico , Hipersensibilidad Inmediata/epidemiología , Hipersensibilidad Inmediata/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Niño , Dermatitis Atópica/epidemiología , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/inmunología , Gatos , Alérgenos/inmunología , Perros , Lactancia Materna , Lactante , PreescolarRESUMEN
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 0-3â years and episodes of severe wheeze (IRR 1.30, 95% CI 1.06-1.60, pFDR=0.04) at age 0-6â 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 18â 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 18â 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.
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Asma , Índice de Masa Corporal , Predisposición Genética a la Enfermedad , Ruidos Respiratorios , Infecciones del Sistema Respiratorio , Humanos , Asma/genética , Asma/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/genética , Femenino , Masculino , Ruidos Respiratorios/genética , Preescolar , Niño , Dinamarca/epidemiología , Lactante , Factores de Riesgo , Estudios Prospectivos , Adulto , Recién Nacido , Herencia Multifactorial , Hospitalización , AdolescenteRESUMEN
BACKGROUND: Early life respiratory tract infections have been linked to the development of asthma, but studies on the burden and subtypes of common infections in asthma development are sparse. OBJECTIVE: To examine the association between burden of early life infections, including subtypes, with the risk of asthma from age 3 to 10 years and lung function at age 10 years. METHODS: We included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort, for whom infections such as colds, acute tonsillitis, acute otitis media, pneumonia, gastroenteritis, and fever were registered prospectively in daily diaries at age 0 to 3 years and asthma was diagnosed longitudinally from age 3 to 10 years. The association between the burden of infection and subtypes and risk of asthma was analyzed by generalized estimating equations. RESULTS: The children experienced a median of 16 infections (interquartile range, 12-23 infections) at age 0 to 3 years. Children with a high burden of infections (above the median) had an increased risk of asthma at age 3 to 10 years (adjusted odds ratio = 3.61; 95% CI, 2.39-5.45; P < .001), which was driven by colds, pneumonia, gastroenteritis, and fever episodes (P < .05) but not by acute otitis media and tonsillitis. Lower lung function measures at age 10 years were associated with the burden of pneumonia but not the overall infection burden. The association between colds and the risk of asthma was significantly higher in children with allergic rhinitis at age 6 years (P interaction = .032). CONCLUSION: A high burden of early life infections in terms of colds, pneumonia, gastroenteritis, and fever is associated with an increased risk of developing asthma, particularly in children with respiratory allergy. Strategies to diminish these early life infections may offer a path for the primary prevention of childhood asthma.
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Asma , Infecciones del Sistema Respiratorio , Humanos , Asma/epidemiología , Preescolar , Niño , Masculino , Femenino , Infecciones del Sistema Respiratorio/epidemiología , Dinamarca/epidemiología , Estudios Prospectivos , Lactante , Recién Nacido , Factores de Riesgo , RiesgoRESUMEN
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.
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Hipersensibilidad a los Alimentos , Calidad de Vida , Humanos , Técnica Delphi , Hipersensibilidad a los Alimentos/diagnóstico , Hipersensibilidad a los Alimentos/terapia , Inmunoglobulina E , Evaluación de Resultado en la Atención de Salud , Proyectos de Investigación , Resultado del Tratamiento , Ensayos Clínicos como Asunto , Estudios Observacionales como AsuntoRESUMEN
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.
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Bronquiolitis , Solución Salina , Niño , Preescolar , Humanos , Bronquiolitis/terapia , Presión de las Vías Aéreas Positiva Contínua/métodos , Hospitalización , Terapia por Inhalación de Oxígeno/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto , Solución Salina/uso terapéutico , Estudios de Equivalencia como AsuntoRESUMEN
BACKGROUND: Risk factors of asthma-like symptoms in childhood may act through an increased infection burden because infections often trigger these symptoms. OBJECTIVE: We sought to investigate whether the effect of established risk factors of asthma-like episodes in early childhood is mediated through burden and subtypes of common infections. METHODS: The study included 662 children from the Copenhagen Prospective Studies on Asthma in Childhood 2010 mother-child cohort, in which infections were registered prospectively in daily diaries from age 0 to 3 years. The association between established risk factors of asthma-like episodes and infection burden was analyzed by quasi-Poisson regressions, and mediation analyses were performed for significant risk factors. RESULTS: In the first 3 years of life, the children experienced a median of 16 (interquartile range, 12-23) infectious episodes. We found that the infection burden significantly (PACME < .05) mediated the association of maternal asthma (36.6% mediated), antibiotics during pregnancy (47.3%), siblings at birth (57.7%), an asthma exacerbation polygenic risk score (30.6%), and a bacterial airway immune score (80.2%) with number of asthma-like episodes, whereas the higher number of episodes from male sex, low birth weight, low gestational age, and maternal antibiotic use after birth was not mediated through an increased infection burden. Subtypes of infections driving the mediation were primarily colds, pneumonia, gastroenteritis, and fever, but not acute otitis media or acute tonsillitis. CONCLUSIONS: Several risk factors of asthma-like symptoms in early childhood act through an increased infection burden in the first 3 years of life. Prevention of infectious episodes may therefore be beneficial to reduce the burden of asthma-like symptoms in early childhood.
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Asma , Neumonía , Recién Nacido , Femenino , Embarazo , Humanos , Masculino , Preescolar , Lactante , Estudios Prospectivos , Asma/etiología , Factores de Riesgo , Antibacterianos/uso terapéutico , Neumonía/tratamiento farmacológico , Ruidos RespiratoriosRESUMEN
BACKGROUND: We previously showed an association between neonatal bacterial airway colonisation and increased risk of persistent wheeze/asthma until age 5â years. Here, we study the association with persistent wheeze/asthma and allergy-related traits until age 18â 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 COPSAC2000 mother-child cohort and the development of persistent wheeze/asthma and allergy-related traits longitudinally until age 18â years using generalised estimating equations. Replication was sought in the similarly designed COPSAC2010 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 7â years, but not from age 7 to 18â years. Replication in the COPSAC2010 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 7â years, but not from age 7 to 18â 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 12â years. There were no associations with lung function, bronchial reactivity, fractional exhaled nitric oxide, allergic sensitisation, total IgE or atopic dermatitis up to age 18â 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 18â years.
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Asma , Dermatitis Atópica , Hipersensibilidad , Recién Nacido , Humanos , Preescolar , Adolescente , Niño , Lactante , Asma/etiología , Hipersensibilidad/complicaciones , Sistema Respiratorio , Dermatitis Atópica/complicaciones , Streptococcus pneumoniae , Ruidos Respiratorios/etiologíaRESUMEN
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.
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Asma , Óxido Nítrico , Humanos , Niño , Preescolar , Adolescente , Inmunoglobulina E , Asma/diagnóstico , Asma/epidemiología , Asma/complicaciones , Alérgenos , Espiración , Biomarcadores , Pruebas RespiratoriasRESUMEN
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 ß2 -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, ß2 -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.
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Asma , Caries Dental , Animales , Perros , Embarazo , Humanos , Preescolar , Femenino , Estudios Prospectivos , Antibacterianos , Asma/tratamiento farmacológico , Asma/epidemiología , CorticoesteroidesRESUMEN
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.
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Asma , Ácidos Grasos Omega-3 , Niño , Femenino , Humanos , Embarazo , Aceites de Pescado/uso terapéutico , Suplementos Dietéticos , Asma/prevención & control , Ácidos GrasosRESUMEN
BACKGROUND: Exposure to perfluoroalkyl substances may affect offspring immune development and thereby increase risk of childhood asthma, but the underlying mechanisms and asthma phenotype affected by such exposure is unknown. METHODS: In the Danish COPSAC2010 cohort of 738 unselected pregnant women and their children plasma PFOS and PFOA concentrations were semi-quantified by untargeted metabolomics analyses and calibrated using a targeted pipeline in mothers (gestation week 24 and 1 week postpartum) and children (age ½, 1½ and 6 years). We examined associations between pregnancy and childhood PFOS and PFOA exposure and childhood infections, asthma, allergic sensitization, atopic dermatitis, and lung function measures, and studied potential mechanisms by integrating data on systemic low-grade inflammation (hs-CRP), functional immune responses, and epigenetics. FINDINGS: Higher maternal PFOS and PFOA exposure during pregnancy showed association with a non-atopic asthma phenotype by age 6, a protection against sensitization, and no association with atopic asthma or lung function, or atopic dermatitis. The effect was primarily driven by prenatal exposure. There was no association with infection proneness, low-grade inflammation, altered immune responses or epigenetic changes. INTERPRETATIONS: Prenatal exposure to PFOS and PFOA, but not childhood exposure, specifically increased the risk of low prevalent non-atopic asthma, whereas there was no effect on atopic asthma, lung function, or atopic dermatitis. FUNDING: All funding received by COPSAC are listed on www.copsac.com. The Lundbeck Foundation (Grant no R16-A1694); The Novo Nordic Foundation (Grant nos NNF20OC0061029, NNF170C0025014, NNF180C0031764); The Ministry of Health (Grant no 903516); Danish Council for Strategic Research (Grant no 0603-00280B); and The Capital Region Research Foundation have provided core support to the COPSAC research center. COPSAC acknowledges the National Facility for Exposomics (SciLifeLab, Sweden) for supporting calibration of the untargeted metabolomics PFAS data. BC and AS has received funding for this project from the European Union's Horizon 2020 research and innovation programme (BC: grant agreement No. 946228 DEFEND; AS: grant agreement No. 864764 HEDIMED).
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Asma , Dermatitis Atópica , Fluorocarburos , Efectos Tardíos de la Exposición Prenatal , Femenino , Embarazo , Humanos , Asma/etiología , Madres , Fenotipo , Inflamación/complicaciones , Fluorocarburos/toxicidadRESUMEN
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.
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Asma , Hipersensibilidad , Femenino , Humanos , Embarazo , Estudios Prospectivos , Investigación Biomédica Traslacional , Asma/genética , Hipersensibilidad/diagnóstico , Factores de RiesgoRESUMEN
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 (Pâ =â .018) was shown, corresponding to a 14% reduction in the n-3 LCPUFA group compared with controls in the first 3 years of life (Pâ =â .037). A reduction in the number of gastroenteritis episodes (Pâ =â .027) and a reduced risk of having an episode (hazard ratio, 0.80 [95% confidence interval, .66-.97]; Pâ =â .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.
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Ácidos Grasos Omega-3 , Gastroenteritis , Embarazo , Femenino , Preescolar , Humanos , Aceites de Pescado/uso terapéutico , Suplementos Dietéticos , Ácidos Grasos Omega-3/uso terapéutico , Gastroenteritis/prevención & controlRESUMEN
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.
Asunto(s)
Anafilaxia , Enfisema Mediastínico , Enfisema Subcutáneo , Anafilaxia/diagnóstico , Anafilaxia/tratamiento farmacológico , Anafilaxia/etiología , Dolor en el Pecho/etiología , Niño , Preescolar , Humanos , Masculino , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/etiología , Enfisema Subcutáneo/diagnóstico por imagen , Enfisema Subcutáneo/etiología , Tomografía Computarizada por Rayos XRESUMEN
Asthma is the most common chronic disease in children and a cause of great distress for both the children and their families [...].
RESUMEN
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.