Food Allergens and Essential Oils in Moisturizers Marketed for Children in Japan.

Introduction Personal skincare leave-on products increase the risk of food allergies. Parents must be imparted with an elevated degree of cognizance regarding the allergenic nature of pediatric skincare products. Material and methods We aimed to examine the data inferred from the promotional material on labeling these products about their proclivity to elicit skin sensitization. This study investigated the relationship between food allergens and essential oil ingredients and highlighted marketing terms, product prices, and ratings of moisturizers for children that are sold on Amazon, Japan. We searched and recorded the product labels and website marketing terms, price (per gram or milliliter), the number of reviews, and allergens and investigated the relationship between the percentage of food allergens in those products and marketing terms, price, and the number of Amazon reviews. Results Among the 164 pediatric skincare products we included, 144 (87.8%) that were manufactured in Japan were the most common; 7 (4.3%), 15 (9.1%), 23 (14.0%), 24 (14.6%), and 54 (32.9%) contained the eight regulated food allergens, grain, nut, fruit, and essential oils, respectively. Marketing terms emphasizing "natural/organic" were more likely to contain grain allergens and essential oils and were more expensive with and without "organic" labeling, respectively, whereas those labeled with marketing terms emphasizing "hypoallergenic" were less likely to contain fruit allergens or essential oils. Products with fewer Amazon reviews were more likely to use the marketing term "natural/organic" and had a higher grain allergen content. Conclusion In Japan, 4.3% of children's skincare products sold on Amazon contain eight food allergens that should obligatorily be labeled when included in food products. In addition, more than 10% of these children's skin care products contain ingredients derived from nuts, while more than 30% contain fruit extracts or essential oils.

House dust mite SLIT-tablet is well tolerated in pediatric patients with controlled asthma.

BACKGROUND: : Despite the reported clinical effectiveness of house dust mite (HDM) sublingual immunotherapy (SLIT) in pediatric patients, the risk of treatment remains unclear in pediatric patients with allergic asthma. OBJECTIVE: To show a risk of adverse drug reactions (ADRs) in pediatric patient with allergic asthma during the initiation period of HDM SLIT. METHODS: We retrospectively analyzed the clinical data of pediatric patients aged ≤ 15 years who initiated allergen immunotherapy (AIT) with the SQ HDM SLIT-tablet for allergic rhinitis between February 2017 and September 2019. Asthma severity at baseline and ADRs during the first 4 weeks of the treatment were determined for each subject. RESULTS: In our study population (n = 217; median age, 8.4 years), 99 patients (45.6%) were classified as having asthma. One hundred and one patients (46.5%) in the whole cohort experienced ADRs during the first 4 weeks of therapy, but a major gap in the frequency of ADRs was not observed between an asthma group and a non-asthma group. CONCLUSIONS: The SQ HDM SLIT-tablet was well tolerated in pediatric patients with controlled HDM-driven allergic asthma. HDM-SLIT is an option to treat their allergic rhinitis without excessive concern for its ADRs.

Differential activation of eosinophils by bacteria associated with asthma.

BACKGROUND: It has been suggested that there is a complex interaction between microbiota and various human diseases. Some bacteria have been reported to be involved in the inception and progression of asthma, and others in the protection against asthma. We know very little about the mechanisms by which bacteria do harm or good with regard to asthma. This study investigated whether bacteria exert differential effects on the functions of eosinophils, major effector cells in airway inflammation in asthma. METHODS: Eosinophils were purified from healthy adult volunteers by Percoll density gradient centrifugation and negative immunomagnetic bead selection using anti-CD16 microbeads. Three kinds of heat-killed bacteria that have been implicated in asthma, namely Staphylococcus aureus (SA), Haemophilus influenzae (HI) and a Prevotella sp. (PS), were tested for their effects on the secretion of eosinophil-derived neurotoxin (EDN), the generation of superoxides and the production of cytokines/chemokines. RESULTS: SA, but not HI or PS, induced significant EDN release in a dose-dependent manner. Superoxide generation was significantly enhanced by each of the bacterial species, but most strongly by SA, which induced significantly greater TNF-α production by eosinophils than either HI or PS. Conversely, interleukin 10, an anti-inflammatory cytokine, was more strongly induced by HI and PS than by SA. CONCLUSIONS: Bacteria exert differential effects on eosinophils. Based on these results, SA may be involved in the exacerbation of, and HI and PS in the inhibition of, eosinophilic inflammation in asthma.

Staphylococcus aureus directly activates eosinophils via platelet-activating factor receptor.

Colonization by SA is associated with exacerbation of AD. Eosinophilic inflammation is a cardinal pathological feature of AD, but little is known about possible direct interaction between SA and eosinophils. PAFR appears to be involved in phagocytosis of Gram-positive bacteria by leukocytes. The objective of this study was to investigate whether SA directly induces eosinophil effector functions via PAFR in the context of AD pathogenesis. Peripheral blood eosinophils were cultured with heat-killed SA, and EDN release, superoxide generation, and adhesion to fibronectin-coated plates were measured. Cytokines, released in the supernatants, were quantified by multiplex bead immunoassays. FISH-labeled SA was incubated with eosinophils and visualized by confocal laser-scanning microscopy. PAFR-blocking peptide and PAFR antagonists were tested for inhibitory effects on SA-induced reactions. SA induced EDN release and superoxide generation by eosinophils in a dose-dependent manner. IL-5 significantly enhanced SA-induced EDN release. IL-5 and IL-17A significantly enhanced SA-induced superoxide generation. SA enhanced eosinophil adhesion to fibronectin, which was blocked by anti-CD49d, and induced eosinophil secretion of various cytokines/chemokines (IL-2R, IL-9, TNFR, IL-1 ß, IL-17A, IP-10, TNF-α, PDGF-bb, VEGF, and FGF-basic). After incubation of eosinophils with SA, FISH-labeled SA was visualized in the eosinophils' cytoplasm, indicating phagocytosis. A PAFR-blocking peptide and two PAFR antagonists completely inhibited those reactions. In conclusion, SA directly induced eosinophil activation via PAFR. Blockade of PAFR may be a novel, therapeutic approach for AD colonized by SA.

1,25-Dihydroxyvitamin D3 upregulates functional C-x-C chemokine receptor type 4 expression in human eosinophils.

BACKGROUND: Epidemiological studies suggest that vitamin D may be protective against the inception and exacerbation of allergic diseases. However, the direct effect of vitamin D on eosinophils, the major effector cells in allergic inflammation, is not known. It has been reported that C-X-C chemokine receptor type 4 (CXCR4) in eosinophils is induced in non-Th2 cytokine milieu or in response to glucocorticoids, recruiting the cell to noninflammatory sites. OBJECTIVES: To test whether 1,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3) or calcitriol], the active metabolite of vitamin D, acts directly on eosinophils to induce upregulation of CXCR4. METHODS: Peripheral blood eosinophils from normal volunteers were isolated by CD16 immunomagnetic beads. Vitamin D receptor (VDR) expression was detected by RT-PCR. Eosinophils were cultured with 1,25-(OH)(2)D(3) and the survival and expression of CXCR4 on eosinophils were measured by flowcytometry. Eosinophil migration by CXCL-12/SDF-1 in the presence of 1,25-(OH)(2)D(3) was also analyzed. RESULTS: Eosinophils expressed VDR. 1,25-(OH)(2)D(3) prolonged eosinophil survival and upregulated eosinophil surface expression of CXCR4 in a concentration-dependent manner. Interleukin (IL)-5 significantly reduced CXCR4 expression and migration induced by the ligand CXCL-12/SDF-1. 1,25-(OH)(2)D(3) reversed the negative effects of IL-5 on the CXCR4-CXCL12 pathway. CONCLUSION: 1,25-(OH)(2)D(3) regulates CXCR4 expression in eosinophils. The mechanism may be involved in eosinophil recruitment to noninflammatory sites where the ligand of CXCR4 is constitutively expressed.

[Prevalence of allergy in patients with severe motor and intellectual disabilities (SMID)].

BACKGROUND: Recent advances in medical care have drastically improved life prognosis of severe life-threatening diseases in newborns and young children. However, 'intact' survival without sequelae for all the children is still to be achieved and prevalence of severe motor and intellectual disabilities (SMID) secondary to central nervous system damages of any cause in childhood, especially in neonatal period, is increasing. Patients with SMID have complex problems involving multiple organs and multidisciplinary approach is mandatory. However, prevalence of allergic diseases in SMID patients is not known. METHODS: Forty one patients who were institutionalized and 26 outpatients at Mie National Hospital with SMID were enrolled. Diagnosis of allergic diseases was determined based on guidelines for the institutionalized patients and on a questionnaire asking if he/she had ever been diagnosed as the allergic diseases by any physician for outpatients. Serum total IgE, specific IgE to common allergens, eosinophil number, and exhaled nitric oxide by on-line tidal breathing method were measured. RESULTS: Lifetime prevalence of bronchial asthma, atopic dermatitis, food allergy, allergic rhinitis, allergic conjunctivitis, and drug allergy were 13.4%, 3.0%, 3.0%, 23.9%, 10.4%, and 6.0%, respectively. The sensitizations to Japanese cedar pollen, cypress, orchard grass, and ragweed were significantly more prevalent in outpatients compared with institutionalized patients. The prevalence of allergic rhinitis and allergic conjunctivitis are higher in outpatients compared with institutionalized patients (61.5% vs 0%, 23.1% vs 2.4%, respectively, p< 0.05). Exhaled nitric oxide levels in subjects who were diagnosed as asthma were significantly higher than in non-asthma. CONCLUSIONS: Allergic diseases are as common in SMID patients as general population. Further study is necessary to establish proper management for the patients.

Inhibition of eosinophil activation mediated by a Toll-like receptor 7 ligand with a combination of procaterol and budesonide.

BACKGROUND: Viral respiratory tract infections play an important role in the inception and exacerbation of asthma. Eosinophils, major effector cells in asthma, often accumulate in the airways during viral infections and are possibly activated by respiratory RNA viruses through Toll-like receptor (TLR) 7. We investigated the effect of a ß(2)-agonist, i.e. procaterol, and a corticosteroid, i.e. budesonide, that are commonly used for viral-induced asthma, on TLR7 ligand-induced activation of eosinophils in vitro. METHODS: Purified peripheral blood eosinophils were incubated with procaterol and/or budesonide and stimulated with a TLR7 ligand, i.e. R-837. Expression of CD11b was analyzed by flow cytometry. Superoxide generation was measured via the cytochrome C reduction method. IL-8 in the supernatants was assayed by ELISA. RESULTS: Although procaterol or budesonide alone did not inhibit R-837-induced CD11b expression, combinations of the 2 drugs significantly inhibited CD11b. Likewise, the combinations significantly inhibited O(2)(-) generation at low concentrations. Budesonide significantly inhibited R-837-induced IL-8 production in a concentration-dependent manner, and procaterol potentiated inhibition by budesonide although single-agent procaterol had no effect. CONCLUSION: A combination of procaterol and budesonide inhibits the TLR7-mediated effector function of eosinophils, indicating their possible anti-inflammatory effect for virus-induced asthma.