Background
Having a better understanding of the risk factors of severe anaphylaxis is a crucial challenge for physicians.
Methods
To retrospectively analyse fatal/near‐fatal anaphylaxis cases ...recorded by the Allergy‐Vigilance® Network (2002–2020) and evaluate the characteristics associated with survival, age and allergens.
Results
Among the 3510 anaphylaxis cases documented in the network, 70 (2%) patients (males: 57%; mean age: 35.4 y) presented grade 4 (Ring‐Messmer) anaphylaxis and 25 died (19 food‐related); 33% had a history of asthma. The main allergens were food (60%; peanut, 20%; milks, 11%) involved in 25/26 cases in children and in 17/44 (39%) cases in adults. Non‐food anaphylaxis was related to drugs/latex (24%; neuromuscular blocking agents, 10%; betalactamins, 6%), Hymenoptera (16%). Three food‐related cases (one death) occurred during oral food challenge in children. Patients with a food allergy were younger (22.2 years vs. 55 years, p < .001), had more likely a history of asthma (50% vs. 7%; p < .001), a pre‐existing allergy (62% vs. 18%; p < .001) compared with other allergies. A cofactor was identified in 35 cases (50%) but predominantly in adults as opposed to children (64% vs. 27%; p = .01). The patients who died were younger (25.6 vs. 40.8 years; p = .01) than the survivors and mostly presented bronchospasm (56% vs. 29%; p = .05). Gaps in the prevention and management of anaphylaxis were noted in 15 cases (21%).
Conclusions
Severe food anaphylaxis has specific features compared with other causes such as young age, asthma history and exercise. Food is also involved in severe anaphylaxis in adults that should not be underestimated.
This study retrospectively analysed fatal/near‐fatal anaphylaxis and evaluated the characteristics associated with survival, age and allergens. The major eliciting factors included: food (60%), drug/latex (24%) and insect venom (16%). A history of asthma was identified in more than one‐third of cases mainly involving food anaphylaxis and children, whereas bronchospasm was documented in the half of the food anaphylaxis cases. The patients who died were younger than the survivors and mostly presented bronchospasm.
Background
Allergies are a serious public health issue, and prevalences are rising worldwide. The role of antibiotics in the development of allergies has repeatedly been discussed, as results remain ...inconsistent. The aim of this study was to investigate the association between pre‐ and post‐natal antibiotic exposure and subsequent development of allergies (atopic dermatitis, food allergy, asthma, atopic sensitization and allergic rhinitis).
Methods
A total of 1080 children who participated in a European birth cohort study (PASTURE) were included in this analysis. Data on antibiotic exposure during pregnancy and/or first year of life and allergic diseases were collected by questionnaires from pregnancy up to 6 years of age and analysed by performing logistic regressions. To take into account reverse causation, we included models, where children with diagnosis or symptoms of the respective disease in the first year of life were excluded.
Results
Antibiotic exposure in utero was significantly and positively associated with atopic dermatitis and food allergy. The strongest effect was on diseases with onset within the first year of life (for atopic dermatitis: aOR 1.66, 95% CI 1.11‐2.48 and for food allergy: aOR 3.01, 95% CI 1.22‐7.47). Antibiotics in the first year of life were positively associated with atopic dermatitis up to 4 years (aOR 2.73, 95% CI 1.66‐4.49) and also suggested a dose‐response relationship. A tendency was observed with asthma between 3 and 6 years (aOR 1.65, 95% CI 0.95‐2.86).
Conclusions
Our findings show positive associations between exposure to antibiotics and allergies, mainly atopic dermatitis and food allergy within the first year of life, after prenatal exposure, and atopic dermatitis and asthma after post‐natal exposure to antibiotics in children born in rural settings.
Background
The new European regulations require the enrichment of formulas with docosahexaenoic acid (DHA) because of the positive effects of long‐chain polyunsaturated fatty acids (LCPUFAs) on ...neurodevelopment and visual acuity. In this observational study, we aimed to evaluate whether the consumption of LCPUFA‐enriched formula was associated with the risk of infection and allergy in early childhood.
Methods
Analyses involved data from 8389 formula‐fed infants from the ELFE birth cohort. Formula enrichment was identified from the list of ingredients of the formula consumed at 2 months. Infections (gastrointestinal, lower respiratory tract LRTI, upper respiratory tract) and allergies (wheezing, itchy rash, asthma medication, food allergy) from age 2 months to 5.5 years were reported by parents during follow‐up surveys. Multivariable logistic regression models were used to assess associations between the consumption of LCPUFA‐enriched formula and the risk of infection and allergy.
Results
Among formula‐fed infants at 2 months, 36% consumed formula enriched with DHA and arachidonic acid (ARA), and 11% consumed formula additionally enriched with eicosapentaenoic acid (EPA). Enriched formula consumption was not associated with infection or allergy, except for an association between consumption of DHA/ARA/EPA‐enriched formula and lower use of asthma medications. Furthermore, as compared with non‐DHA/ARA/EPA‐enriched formula, consumption of formula with high EPA content (≥3.2 mg/100 kcal) was related to lower risk of LRTI and lower use of asthma medications.
Conclusion
This study suggests that consumption of DHA/ARA/EPA‐enriched formula (especially those with high EPA content) is associated with a lower risk of LRTI and lower use of asthma medications.
Among formula‐fed infants at 2 months, 36% consumed DHA/ARA‐enriched formula, and 11% consumed formula additionally enriched with EPA. DHA/ARA/EPA‐enriched formula consumption (especially with high EPA content) was associated with a lower risk of LRTI and lower use of asthma medications up to 5.5 years. DHA/ARA/EPA‐enriched formula consumption was not associated with gastrointestinal infection, wheezing, itchy rash, and food allergy.Abbreviations: ARA, arachidonic acid; DHA, docosahexaenoic acid; ELFE, birth cohort (Étude longitudinale française depuis l’enfance); EPA, eicosapentaenoic acid; LCPUFA, long‐chain polyunsaturated fatty acids; LRTI, lower respiratory tract infection; OR, odds ratio.
Background
Legume consumption has increased during the two past decades. In France, legumes are responsible for 14.6% of food‐related anaphylaxis in children, with peanut as the main allergen ...(77.5%). Few studies have demonstrated cross‐reactivities between peanut and other legumes. The aim of this study was to determine prevalence and relevance of sensitization to legumes in peanut‐allergic children.
Methods
All children, aged of 1–17 years, admitted to the Pediatric Allergy Department of the University Hospital of Nancy between January 1, 2017 and February 29, 2020 with a confirmed peanut allergy (PA) and a documented consumption or sensitization to at least one other legume were included. Data were retrospectively collected regarding history of consumption, skin prick tests, specific immunoglobulin E (IgE), prior allergic reactions, and oral food challenges for each legume.
Results
Among the 195 included children with PA, 122 were sensitized to at least one other legume (63.9%). Main sensitizations were for fenugreek (N = 61, 66.3%), lentil (N = 38, 42.2%), soy (N = 61, 39.9%), and lupine (N = 63, 34.2%). Among the 122 sensitized children, allergy to at least one legume was confirmed for 34 children (27.9%), including six children who had multiple legume allergies (4.9%). Lentil, lupine, and pea were the main responsible allergens. Half of allergic reactions to legumes other than peanut were severe.
Conclusion
The high prevalence of legume sensitization and the frequent severe reactions reported in children with PA highlight that tolerated legume consumption should be explored for each legume in the case of PA, and sensitization should be investigated if not.
Background
Childhood asthma is a result of a complex interaction of genetic and environmental components causing epigenetic and immune dysregulation, airway inflammation and impaired lung function. ...Although different microarray based EWAS studies have been conducted, the impact of epigenetic regulation in asthma development is still widely unknown. We have therefore applied unbiased whole genome bisulfite sequencing (WGBS) to characterize global DNA‐methylation profiles of asthmatic children compared to healthy controls.
Methods
Peripheral blood samples of 40 asthmatic and 42 control children aged 5–15 years from three birth cohorts were sequenced together with paired cord blood samples. Identified differentially methylated regions (DMRs) were categorized in genotype‐associated, cell‐type‐dependent, or prenatally primed. Network analysis and subsequent natural language processing of DMR‐associated genes was complemented by targeted analysis of functional translation of epigenetic regulation on the transcriptional and protein level.
Results
In total, 158 DMRs were identified in asthmatic children compared to controls of which 37% were related to the eosinophil content. A global hypomethylation was identified affecting predominantly enhancer regions and regulating key immune genes such as IL4, IL5RA, and EPX. These DMRs were confirmed in n = 267 samples and could be linked to aberrant gene expression. Out of the 158 DMRs identified in the established phenotype, 56 were perturbed already at birth and linked, at least in part, to prenatal influences such as tobacco smoke exposure or phthalate exposure.
Conclusion
This is the first epigenetic study based on whole genome sequencing to identify marked dysregulation of enhancer regions as a hallmark of childhood asthma.
Whole‐genome bisulfite sequencing in whole blood identifies 158 DMRs related to childhood‐asthma predominantly affecting enhancer regions, including an enhancer for IL‐4. Global DNA‐hypomethylation in the asthma‐phenotype affects key immune genes such as IL5RA or EPX. 35% of the aberrant DNA‐methylation in asthma is already present in cord blood, which is partially related to adverse prenatal influences such as tobacco smoke exposure.Abbreviations: DMR, differentially methylated region, EPX, eosinophil peroxidase; IL5RA, interleukin 5 receptor subunit alpha; LINA, Lifestyle and environmental factors and their influence on newborns allergy risk; LISA, Lifestyle‐related factors on the immune system and the development of allergies in childhood; PASTURE, Protection against allergy: study in rural environments
Background and objectives
Partially hydrolyzed formulas (pHF) are recommended in non‐breastfed infants with familial history of allergy to prevent allergy development. However, recent meta‐analysis ...does not provide strong support for their protective effect. The present work assesses the links between 2‐month infant formula use and the incidence of eczema, respiratory symptoms, or food allergies (FA) up to 2 years of age.
Methods
The nationwide ELFE birth cohort is a population‐based study from mainland France. Infant feeding (breast milk only, partially hydrolyzed formula with pHF‐HA or without a hypoallergenic label pHF‐non‐HA, and non‐hydrolyzed formula Nhf) was reported at 2 months. Eczema, FA, and respiratory symptoms such as wheezing and asthma were reported at 2 months, 1 year, and 2 years. Infants with prior FA at 2 months were excluded from analyses.
Results
Among 11 720 infants, those who received only breast milk at 2 months were at lower risk of eczema at 1 year than those who received nHF (OR95% CI = 0.780.65‐0.94 in non‐at‐risk infants; 0.860.75‐0.98 in at‐risk infants). The use of pHF‐HA, compared with nHF, at 2 months was related to higher risk of wheezing at 1 year in at‐risk infants (1.681.24‐2.28) and higher risk of FA at 2 years both in non‐at‐risk infants (3.781.52‐9.41) and in at‐risk infants (2.311.36‐3.94).
Conclusions
In this nationwide study, pHF‐HA use was not associated with a lower risk of any of the studied outcomes. Quite the reverse, it was associated with a higher risk of wheezing and FA. This should be confirmed in further studies.
Background
Numerous children present with early wheeze symptoms, yet solely a subgroup develops childhood asthma. Early identification of children at risk is key for clinical monitoring, timely ...patient‐tailored treatment, and preventing chronic, severe sequelae. For early prediction of childhood asthma, we aimed to define an integrated risk score combining established risk factors with genome‐wide molecular markers at birth, complemented by subsequent clinical symptoms/diagnoses (wheezing, atopic dermatitis, food allergy).
Methods
Three longitudinal birth cohorts (PAULINA/PAULCHEN, n = 190 + 93 = 283, PASTURE, n = 1133) were used to predict childhood asthma (age 5–11) including epidemiological characteristics and molecular markers: genotype, DNA methylation and mRNA expression (RNASeq/NanoString). Apparent (ap) and optimism‐corrected (oc) performance (AUC/R2) was assessed leveraging evidence from independent studies (Naïve‐Bayes approach) combined with high‐dimensional logistic regression models (LASSO).
Results
Asthma prediction with epidemiological characteristics at birth (maternal asthma, sex, farm environment) yielded an ocAUC = 0.65. Inclusion of molecular markers as predictors resulted in an improvement in apparent prediction performance, however, for optimism‐corrected performance only a moderate increase was observed (upto ocAUC = 0.68). The greatest discriminate power was reached by adding the first symptoms/diagnosis (up to ocAUC = 0.76; increase of 0.08, p = .002). Longitudinal analysis of selected mRNA expression in PASTURE (cord blood, 1, 4.5, 6 years) showed that expression at age six had the strongest association with asthma and correlation of genes getting larger over time (r = .59, p < .001, 4.5–6 years).
Conclusion
Applying epidemiological predictors alone showed moderate predictive abilities. Molecular markers from birth modestly improved prediction. Allergic symptoms/diagnoses enhanced the power of prediction, which is important for clinical practice and for the design of future studies with molecular markers.
For early prediction of childhood asthma, an integrated risk score combining established risk‐factors with genome‐wide molecular markers (genotype, DNA methylation, mRNA expression) at birth was defined, complemented by subsequent clinical symptoms/diagnoses (wheeze, atopic dermatitis, food allergy). While epidemiological predictors have moderate predictive power, molecular markers from birth improve prediction to a modest extent. Including allergic symptoms/diagnoses significantly increased predictive efficiency.
Background
Although children can frequently experience a cough that affects their quality of life, few epidemiological studies have explored cough without a cold during childhood.
Objectives
The ...objective of the study was to describe the latent class trajectories of cough from one to 10 years old and analyse their association with wheezing, atopy and allergic diseases.
Methods
Questions about cough, wheeze and allergic diseases were asked at 1, 1.5, 2, 3, 4, 5, 6 and 10 years of age in the European prospective cohort of Protection against Allergy: STUdy in Rural Environment (PASTURE). Specific IgE assays were performed at 10 years of age. Questions regarding a cough without a cold were used to build a latent class model of cough over time.
Results
Among the 961 children included in the study, apart from the never/infrequent trajectory (59.9%), eight trajectories of cough without a cold were identified: five grouped acute transient classes (24.1%), moderate transient (6.8%), late persistent (4.8%) and early persistent (4.4%). Compared with the never/infrequent trajectory, the other trajectories were significantly associated with wheezing, asthma and allergic rhinitis. For asthma, the strongest association was with the early persistent trajectory (ORa = 31.00 14.03–68.51), which was inversely associated with farm environment (ORa = 0.39 0.19–0.77) and had a high prevalence of cough triggers and unremitting wheeze. Late and early persistent trajectories were also associated with food allergy. Atopic sensitization was only associated with the late persistent trajectory.
Conclusion
Late and early persistent coughs without a cold are positively associated with atopic respiratory diseases and food allergy. Children having recurrent cough without a cold with night cough and triggers would benefit from an asthma and allergy assessment. Growing up on a farm is associated with reduced early persistent cough.
Five different patterns of cough trajectories during early childhood have been highlighted. Recurrent cough without a cold, with night cough and triggers should lead to allergy and asthma assessment. Growing up on a farm seems to have a protective effect on acute transient cough and early persistent cough.
Growing up on a farm is associated with an asthma-protective effect, but the mechanisms underlying this effect are largely unknown. In the Protection against Allergy: Study in Rural Environments ...(PASTURE) birth cohort, we modeled maturation using 16S rRNA sequence data of the human gut microbiome in infants from 2 to 12 months of age. The estimated microbiome age (EMA) in 12-month-old infants was associated with previous farm exposure (β = 0.27 (0.12-0.43), P = 0.001, n = 618) and reduced risk of asthma at school age (odds ratio (OR) = 0.72 (0.56-0.93), P = 0.011). EMA mediated the protective farm effect by 19%. In a nested case-control sample (n = 138), we found inverse associations of asthma with the measured level of fecal butyrate (OR = 0.28 (0.09-0.91), P = 0.034), bacterial taxa that predict butyrate production (OR = 0.38 (0.17-0.84), P = 0.017) and the relative abundance of the gene encoding butyryl-coenzyme A (CoA):acetate-CoA-transferase, a major enzyme in butyrate metabolism (OR = 0.43 (0.19-0.97), P = 0.042). The gut microbiome may contribute to asthma protection through metabolites, supporting the concept of a gut-lung axis in humans.
Background
The effect of exposure to microorganisms on allergic diseases has been well studied. The protective effect of early food diversity against allergic diseases was previously shown in the ...PASTURE cohort study. The consumption of cheese, a food potentially rich in microbial diversity, deserves further examination. We aimed to evaluate whether cheese consumption is associated with allergic diseases.
Methods
In the PASTURE study (birth cohort in 5 European countries), data on feeding practices, environmental factors, and allergic diseases were collected by questionnaires from birth to 6 years (N = 931). Cheese consumption at 18 months of age was quantified in terms of frequency and diversity (ie, number of consumed types among 6 types: hard pressed, semipressed, soft, blue, fresh cheese, and cheese from the farm). Multiple logistic regressions were performed to evaluate the effect of cheese consumption on atopic dermatitis (AD), food allergy (FA), allergic rhinitis, asthma, and atopic sensitization at 6 years after adjustment for confounders of atopy.
Results
Cheese consumption (vs. nonconsumption) had a significant protective effect on AD (OR = 0.51 0.29‐0.90, P = 0.02) and FA (OR = 0.32, 0.15‐0.71, P = 0.004), but no effect on atopic sensitization, allergic rhinitis, and asthma at 6 years. This effect on AD and FA may be related to the diversity of consumed cheeses (OR = 0.64 0.48‐0.85 per cheese type, P = 0.002; OR = 0.55 0.33‐0.92, P = 0.02, respectively).
Conclusion
Although reverse causality cannot totally be ruled out, cheese diversity at 18 months had a protective effect against AD and FA at 6 years in addition to the protective effect of diversity of other foods.
Data from the PASTURE cohort were used to evaluate the effect of cheese consumption at 18 months of age against allergic diseases up to 6 years of age
Multivariate analyses adjusted for major confounders showed a protective effect of cheese consumption and variety against atopic dermatitis and food allergy, but not on allergic rhinitis, asthma, and sensitization to allergens. Reverse causality cannot be totally ruled out but is unlikely.
Hypothesis: The variety of cheese consumed in early life could influence the immune system, through microbial components and by anti‐inflammatory compounds (short‐chain fatty acids)
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