Home-based up-dosing of wheat oral immunotherapy: Real-world effectiveness and predictive factor analysis.

BACKGROUND: Wheat allergy is one of the most prevalent allergens in Korea, decreasing quality of life and causing nutritional repercussions. OBJECTIVE: We aimed to investigate the efficacy and safety of the home-based wheat oral immunotherapy (OIT) using wheat noodles in children with a wheat allergy. METHODS: We conducted a retrospective study involving 72 children aged 3 to 17 years diagnosed with a wheat allergy. Patients received wheat OIT using wheat noodles (n = 50) and were compared with a historical control group (n = 22). Baseline characteristics, adverse events, and immunological changes were assessed. Predictors of successful desensitization were identified using logistic regression analysis. RESULTS: Among 50 patients completing the up-dosing phase, 82.0% achieved desensitization to 2,400 mg of wheat protein, compared to 4.5% in the control group (p < 0.001). During the up-dosing period, the median number of adverse reactions per person was 2, and anaphylaxis occurred in 30.0% (15/50). However, there were no life-threatening adverse events. In multivariable analysis, the presence of asthma (adjusted odds ratio [aOR], 8.88; 95% confidence interval [CI], 1.10-71.97; p = 0.041) and a higher ratio of specific IgE (sIgE) to ω-5-gliadin and total IgE (aOR 19.09, 95%CI 1.21-300.80, p = 0.036) were significantly associated with treatment outcomes of wheat OIT. CONCLUSION: Our study showed the safety and efficacy of home-based wheat OIT using boiled noodles in Korean children with wheat allergies. Careful consideration is warranted for patients with elevated baseline sIgE to ω-5-gliadin to total IgE ratio and a history of asthma.

NLRP3 inhibition attenuates the allergic rhinitis symptoms in a mouse model.

BACKGROUND: Recent human and animal studies have demonstrated that Nod-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome is closely involved in the development of allergic diseases. OBJECTIVE: To identify the mechanism underlying the activation of NLRP3 inflammasome signaling pathway in an ovalbumin (OVA)-induced allergic rhinitis (AR) mice model and to validate the effect of a specific inhibitor of the NLRP3, MCC950. METHODS: Mice were divided into three groups and each group consisted of ten mice (saline group, the negative control group; OVA group, the OVA-induced AR model group; and OVA+MCC group, treated with 10 mg/kg MCC950). MCC950 was administered intraperitoneally every second day. Multiple parameters of AR, including NLRP3, caspase-1, interleukin (IL)-1ß, and IL-18 were evaluated by using ELISA, RT-qPCR, histopathology, and immunohistochemistry. RESULTS: The mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 were upregulated in the OVA group compared with those of the saline group. MCC950 significantly inhibited the mRNA and protein levels of NLRP3, caspase-1, IL-1ß and IL-18 in nasal tissue. Further, AR symptoms and eosinophil count were normalized after MCC950 treatment. However, OVA-specific IgE was not restored in the OVA+MCC group. CONCLUSION: NLRP3 inflammasome signaling pathway may be an alternative pathway to induce AR symptoms in OVA-induced AR model. MCC950 is a specific inhibitor of NLRP3 cascade, which attenuates AR symptoms regardless of IgE.

Potential Effects of Low-Level Toluene Exposure on the Nervous System of Mothers and Infants.

In day-to-day living, individuals are exposed to various environmentally hazardous substances that have been associated with diverse diseases. Exposure to air pollutants can occur during breathing, posing a considerable risk to those with environmental health vulnerabilities. Among vulnerable individuals, maternal exposure can negatively impact the mother and child in utero. The developing fetus is particularly vulnerable to environmentally hazardous substances, with potentially greater implications. Among air pollutants, toluene is neurotoxic, and its effects have been widely explored. However, the impact of low-level toluene exposure in daily life remains unclear. Herein, we evaluated 194 mothers and infants from the Growing children's health and Evaluation of Environment (GREEN) cohort to determine the possible effects of early-life toluene exposure on the nervous system. Using Omics experiments, the effects of toluene were confirmed based on epigenetic changes and altered mRNA expression. Various epigenetic changes were identified, with upregulated expression potentially contributing to diseases such as glioblastoma and Alzheimer's, and downregulated expression being associated with structural neuronal abnormalities. These findings were detected in both maternal and infant groups, suggesting that maternal exposure to environmental hazardous substances can negatively impact the fetus. Our findings will facilitate the establishment of environmental health policies, including the management of environmentally hazardous substances for vulnerable groups.

Prevalence of Severe Atopic Dermatitis and Comorbid Chronic Systemic Diseases Is Increasing in Korean Children and Adolescents.

Severe atopic dermatitis (AD) is not a localized cutaneous disease, but a systemic disease that often accompanies comorbidities. In this nationwide population-based study, we aimed to analyze the prevalence of severe AD and chronic systemic diseases in Koreans aged ≤ 20 years between 2011 and 2019 using the data from the Korean Health Insurance Review and Assessment Service. Total AD and severe AD were defined according to the International Classification of Diseases-10 code L20. In children aged 6-20 years, the prevalence of severe AD significantly increased from 0.02% in 2011 to 0.04% in 2019 (P for trend < 0.001), with the ratio of severe AD to total AD increasing from 0.76% in 2011 to 1.10% in 2019 (P for trend < 0.001). The prevalence rates of severe AD significantly increased between 2011 and 2019 in children aged 6-12 years (P for trend < 0.05) and 13-18 years (P for trend < 0.001). Severe AD was more frequently found in males than in females each year (all P < 0.001, from 2011 to 2019). During the period from 2011 to 2019, the prevalence rate of chronic systemic diseases was higher in subjects with severe AD than in those without AD (P < 0.001) or with mild-to-moderate AD (P < 0.001). In conclusion, our results suggest that the prevalence of severe AD is increasing in Korean children and adolescents and is higher in males and older age groups. Moreover, severe AD is associated with chronic systemic diseases. Therefore, more attention should be paid to managing severe AD.

Advanced fructo-oligosaccharides improve itching and aberrant epidermal lipid composition in children with atopic dermatitis.

Introduction: The effects of fructo-oligosaccharides (FOS) on atopic dermatitis (AD) have not been determined. Methods: In a randomized, double-blind, placebo-controlled trial, children with AD aged 24 months to 17 years received either advanced FOS containing 4.25 g of 1-kestose or a placebo (maltose) for 12 weeks. Results: The SCORAD and itching scores were reduced in patients treated with both FOS (all p < 0.01) and maltose (p < 0.05 and p < 0.01). Sleep disturbance was improved only in the FOS group (p < 0.01). The FOS group revealed a decreased proportion of linoleic acid (18:2) esterified omega-hydroxy-ceramides (EOS-CERs) with amide-linked shorter chain fatty acids (C28 and C30, all p < 0.05), along with an increased proportion of EOS-CERs with longer chain fatty acids (C32, p < 0.01). Discussion: FOS may be beneficial in alleviating itching and sleep disturbance, as well as improving skin barrier function in children with AD.

Initial updosing phase of oral immunotherapy improves quality of life and psychological burden in parents of children with food allergy.

Background: Oral immunotherapy (OIT) can impose psychological burdens on patients and their parents due to the necessary preparations and repeated adverse reactions. Objective: To investigate changes in quality of life (QoL) and psychological burden in parents of children receiving OIT for food allergy (FA). Methods: Children aged 3-13 years with FA were enrolled. Parents were asked to fill out the Korean versions of the Food Allergy Quality of Life-Parental Burden (FAQL-PB), the Korean versions of the Food Allergy Quality of Life-Parental Form (K-FAQLQ-PF), the Korean versions of the Beck Anxiety Inventory (K-BAI), and the Korean version of the Patient Health Questionnaire-9 (PHQ-9) for depression before OIT (T1), after 2 months of updosing (T2), and after the end of the updosing phase (T3). Results: A total of 111 parents were enrolled. The total FAQL-PB scores were decreased at T2 and T3 compared with those at T1 (all p < 0.001). Greater improvement in the total FAQL-PB score at T2 was noted in parents with a higher parental burden (FAQL-PB score ≥ 74 points) at baseline than in those with a lower parental burden (p = 0.001). Among the K-FAQLQ-PF domains, "food anxiety" scores were decreased at T2 and T3 compared with those at T1 (p = 0.049 and p = 0.030, respectively), whereas there was no change in "social and dietary limitation" and "emotional impact" scores between T1 and T2 and between T1 and T3. However, no differences were observed in K-BAI and PHQ-9 scores between T1 and T2 and between T1 and T3. Conclusion: Our results suggest that OIT improves parental burden and QoL in parents of children with FA.

Skin biomarkers predict the development of food allergy in early life.

BACKGROUND: Food allergy (FA) often occurs in early childhood with and without atopic dermatitis (AD). FA can be severe and even fatal. For primary prevention, it is important to find early biomarkers to predict the future onset of FA before any clinical manifestations. OBJECTIVE: Our aim was to find early predictors of future onset of FA in the stratum corneum (SC). METHODS: Skin tape strips were collected from the forearm of newborns (n = 129) at age 2 months, before any signs of clinical FA or AD. Children were clinically monitored until they reached age 2 years to confirm the presence or absence of FA and AD. Skin tape strips were subjected to lipidomic analyses by liquid chromatography-tandem mass spectrometry and cytokine determination by Meso Scale Discovery U-Plex assay. RESULTS: Overall, 9 of 129 infants (7.0%) developed FA alone and 9 of 129 infants (7.0%) developed FA concomitantly with AD. In the stratum corneum of children with future FA and concomitant AD and FA, absolute amounts of unsaturated (N24:1)(C18-sphingosine)ceramide and (N26:1)(C18-sphingosine)ceramide and their relative percentages within the molecular group were increased compared with the amounts and percentages in healthy children, with P values ranging from less than .01 to less than .05 according to ANOVA. The children with future AD had normal levels of these molecules. IL-33 level was upregulated in those infants with future FA but not in those with future AD, whereas thymic stromal lymphopoietin was upregulated in those with future AD but not in those with future FA. Logistic regression analysis revealed strong FA predicting power for the combination of dysregulated lipids and cytokines, with an odds ratio reaching 101.4 (95% CI = 5.4-1910.6). CONCLUSION: Noninvasive skin tape strip analysis at age 2 months can identify infants at risk of FA in the future.