RESUMO
BACKGROUND: A genetic defect in the epidermal barrier protein filaggrin (FLG) plays a major role in the etiology of eczema and associated allergic airways diseases. However, it is still controversial to what extend loss-of-function (LOF) mutations in FLG contribute to the development and persistence of food allergies. OBJECTIVES: This study tested association of FLG LOF mutations with allergic reactions to diverse foods and investigated their potential effect on the persistence of early food allergies. METHODS: This study recruited 890 children with challenge-proven food allergy for the German Genetics of Food Allergy Study (GOFA). Longitudinal data were available for 684 children. All children were clinically characterized, including their allergic responses to specific foods, and genotyped for the 4 most common LOF mutations in FLG; R501X, 2282del4, R2447X, and S3247X. Associations between FLG mutations and food allergies were analyzed by logistic regression using the German Multicenter Allergy Study cohort as the control population. RESULTS: FLG mutations were associated with allergies to diverse foods including hen's egg (HE), cow's milk (CM), peanut, hazelnut, fish, soy, cashew, walnut, and sesame with similar risk estimates. Effects remained significant after adjusting for the eczema status. Interestingly, FLG mutations increased the risk of a persistent course of HE and CM allergy. CONCLUSIONS: Using the gold standard for food allergy diagnosis, this study demonstrates that FLG LOF mutations confer a risk of any food allergy independent of eczema. These mutations predispose to the persistence of HE and CM allergy and should be considered in the assessment of tolerance development.
Assuntos
Eczema , Hipersensibilidade a Ovo , Hipersensibilidade Alimentar , Hipersensibilidade a Leite , Bovinos , Feminino , Animais , Hipersensibilidade a Leite/genética , Proteínas Filagrinas , Galinhas , Eczema/genética , Alérgenos , Hipersensibilidade Alimentar/genética , Mutação , Proteínas de Filamentos Intermediários/genéticaRESUMO
BACKGROUND: The well-being of persons with overweight and obesity, in particular of children and adolescents, may be impaired. The present study investigates the health-related quality of life (HRQoL) of girls and boys with overweight and obesity living in Germany as compared to those of normal-weight, while taking a selection of relevant determinants of HRQoL into account. METHODS: The sample comprises 1771 children and adolescents aged 11 to 17 years that took part in the cross-sectional German Health Interview and Examination Survey for Children and Adolescents (KIGGS Wave 2, 2014-2017). Sex-and age-specific BMI (kg/m2) percentiles were utilized to classify overweight and obesity. HRQoL was measured with the KIDSCREEN-27 questionnaire, which gathers detailed information about the five dimensions physical and psychological well-being, well-being regarding peers (i.e., social acceptance), parents (i.e., autonomy) and within the school environment. Multiple regression analyses were performed with HRQoL dimensions as outcomes to test for differences between children and adolescents with normal-weight vs. those with overweight and vs. those with obesity, separately for girls and boys. In a next step, age, physical activity, media consumption, social support and self-efficacy were considered as potential confounders in the analyses. RESULTS: 18.7% of the children and adolescents under study were affected by overweight and among them 8.0% by obesity. After adjusting for potential confounders, overweight and obesity were associated with lower physical well-being as compared to normal weight in both sexes (boys with overweight: standardized beta [ß] = -.14, standard error [SE] = .03, p < .001, and obesity: ß = -.16, SE = .03, p < .001; girls with overweight: ß = -.09, SE = .04, p = .011, and obesity: ß = -.11, SE = .03, p = .003). Results moreover suggest lower levels of psychological (ß = -.10, SE = .04, p = .002) and parent-related well-being (ß = -.08, SE = .04, p = .036) of boys with obesity as compared to normal-weight peers. CONCLUSION: HRQoL of German children and adolescents with overweight and obesity is impaired according to physical well-being in general, while psychological and parent-related well-being is particularly affected in boys. Public health approaches should therefore promote children and adolescents with overweight and obesity by improving diverse facets of HRQoL as well as relevant associated factors (i.e., media consumption, self-efficacy) in general and in boys in particular.
Assuntos
Obesidade Infantil/epidemiologia , Qualidade de Vida , Adolescente , Criança , Estudos Transversais , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Children with sensitization against foods have to be orally food-challenged before eating these foods for the first time. However, the waiting time for an oral food challenge (OFC) in Germany is about 3-6 months. In contrast, there are hints that an early introduction of allergenic foods might be protective regarding the development of food allergy. The aim of this clinical trial is therefore to investigate, whether an introduction and regular consumption of small amounts of food allergens is safe and will result in an increase of tolerance in children with sensitization against food allergens with unknown clinical relevance. METHODS: In this randomized, placebo-controlled, double-blind, single-center trial, 138 children (8 months to 4 years of age) sensitized to the target allergen(s) hen's egg, cow's milk, peanuts, and/or hazelnuts with unknown clinical relevance will be randomized in a 1:1 ratio to either an active or a placebo group, daily receiving a rusk-like biscuit powder with or without the target allergen(s) for 3-6 months until an OFC will be performed in routine diagnostics. The primary endpoint is an IgE-mediated food allergy to the primary target allergen, after the interventional period. DISCUSSION: Children with sensitization against food allergens with unknown clinical relevance often have to avoid the corresponding foods for several months until an OFC is performed. Therefore, the "window of opportunity" for an early preventive introduction of allergenic foods might be missed. This trial will assess whether an introduction of small allergen amounts will favor tolerance development in these children. TRIAL REGISTRATION: German Clinical Trials Register DRKS00032769. Registered on 02 October 2023.
Assuntos
Galinhas , Hipersensibilidade Alimentar , Criança , Lactente , Bovinos , Humanos , Feminino , Animais , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/prevenção & controle , Leite/efeitos adversos , Alérgenos/efeitos adversos , Tolerância ImunológicaRESUMO
BACKGROUND: It has been reported that sometimes children fall asleep and can barely be woken up during allergic reactions on food ingestion. Nevertheless, to date, there is scarce data on narcolepsy-like sleepiness as a symptom of allergic reactions. OBJECTIVE: To investigate the frequency of narcolepsy-like sleepiness during oral food challenges and characterize this symptom regarding comorbidities, eliciting allergens, and severity of reactions. METHODS: Children with immediate-type allergic reactions during oral food challenges (89% were double-blind, placebo-controlled) have been analyzed in this study. Narcolepsy-like sleepiness was defined as a somnolent condition during which patients could barely be woken up again, occurring within 2 hours of food intake and which was not due to drug side effects. Logistic generalized estimating equations were used to explore the effect of age, severity of reactions, and eliciting allergens on the occurrence of narcolepsy-like sleepiness. RESULTS: In 106 (12.5%) of all 848 food-allergic children, narcolepsy-like sleepiness was observed during oral food challenges. Children with eczema had a higher risk of developing narcolepsy-like sleepiness (P = .006). Narcolepsy-like sleepiness occurred most often due to an allergic reaction to hazelnut (P = .009) or other tree nuts (P = .003). Moderate to severe reactions occurred more often than mild reactions (P = .026; odds ratio, 1.521; 95% CI, 1.051-2.202) in children with narcolepsy-like sleepiness. CONCLUSIONS: We were able to show for the first time that narcolepsy-like sleepiness is a frequently occurring clinical manifestation of immediate-type allergic reactions on food ingestion in childhood. Further research is needed to unravel the underlying mechanisms to gain a deeper insight into this underestimated symptom.
Assuntos
Hipersensibilidade Imediata , Hipersensibilidade , Narcolepsia , Humanos , Criança , Sonolência , Alérgenos , Nozes , Narcolepsia/diagnóstico , Narcolepsia/epidemiologiaRESUMO
BACKGROUND: Up to 8% of all children in industrialized countries suffer from food allergies, whereas children with atopic eczema are affected considerably more frequently. In addition, the type and starting time of weaning foods seem to influence the development of food allergies. However, data from interventional studies on weaning are controversial. The aim of this randomized-controlled clinical trial is to investigate, whether an early introduction of hen's egg (HE), cow's milk (CM), peanut (PN), and hazelnut (HN) in children with atopic eczema can reduce the risk for developing food allergies in the first year of life. METHODS: This is a protocol for a randomized, placebo controlled, double blind, single-center clinical trial. One hundred fifty infants with atopic eczema at 4-8 months of age will be randomized in a 2:1 manner into an active group that will receive rusk-like biscuit powder with HE, CM, PN, and HN (initially approximately 2 mg of each food protein) for 6-8 months or a placebo group, whose participants will receive the same rusk-like biscuit powder without HE, CM, PN, and HN on a daily basis. During the interventional period, the amount of allergens in the study product will be increased three times, each after 6 weeks. All study participants who are sensitized to HE, CM, PN, or HN at the end of the interventional period will undergo an oral food challenge to the respective food in a further visit. Primary endpoint is IgE-mediated food allergy to at least one of the four foods (HE, CM, PN or HN) after 6-8 months of intervention (i.e., at around 1 year of age). Secondary endpoints include multiple food allergies, severity of eczema, wheezing, and sensitization levels against food allergens. DISCUSSION: This clinical trial will assess whether an early introduction of allergenic foods into the diet of children with atopic eczema can prevent the development of food allergies. This trial will contribute to update food allergy prevention guidelines. TRIAL REGISTRATION: German Clinical Trials Register DRKS00016770 . Registered on 09 January 2020.
Assuntos
Eczema , Hipersensibilidade Alimentar , Alérgenos , Animais , Bovinos , Galinhas , Feminino , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/prevenção & controle , Tolerância ImunológicaRESUMO
BACKGROUND: Peanuts (PN) and tree nuts (TN) are among the most frequent elicitors of food allergy and can lead to life-threatening reactions. The current advice for allergic patients is to strictly avoid the offending food independently of their individual threshold level, whereas sensitized patients without allergic symptoms should frequently consume the food to avoid (re-)development of food allergy. The aim of this trial is to investigate (I) whether the consumption of low allergen amounts below the individual threshold may support natural tolerance development and (II) to what extent regular allergen consumption in sensitized but tolerant subjects prevents the (re-)development of PN or TN allergy. METHODS: The TINA trial consisting of (part I) a randomized, controlled, open, parallel group, single-center, superiority trial (RCT), and (part II) a prospective observational exploratory cohort study. Children and adults (age 1-67 years) with suspected or known primary PN and/or TN allergy will undergo an oral food challenge (OFC) to determine their clinical reactivity and individual threshold. In the RCT, 120 PN or TN allergic patients who tolerate ≥100 mg of food protein will be randomized (1:1 ratio) to consumption of products with low amounts of PN or TN on a regular basis or strict avoidance for 1 year. The consumption group will start with 1/100 of their individual threshold, increasing the protein amount to 1/50 and 1/10 after 4 and 8 months, respectively. The primary endpoint is the clinical tolerance to PN or TN after 1 year assessed by OFC. In the cohort study, 120 subjects sensitized to PN and/or TN but tolerant are advised to regularly consume the food and observed for 1 year. The primary endpoint is the maintenance of clinical tolerance to PN and/or TN after 1 year assessed by challenging with the former tolerated cumulative dose. DISCUSSION: This clinical trial will help to determine the impact of allergen consumption versus avoidance on natural tolerance development and whether the current dietary advice for PN or TN allergic patients with higher threshold levels is still valid. TRIAL REGISTRATION: German Clinical Trials Register; ID: DRKS00016764 (RCT), DRKS00020467 (cohort study). Registered on 15 January 2020, http://www.drks.de .