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Background: Anaphylaxis following influenza vaccination is a rare but serious problem. The underlying immune responses are not well understood. This study elucidated the IgE and IgG antibody responses in healthy children and adolescents following inactivated influenza vaccines (IIVs). Methods: The efficacy and safety of quadrivalent IIV (QIV) and trivalent IIV (TIV) were compared in healthy subjects aged 0–18 years. Serum IIV‐specific IgE, IgG, and IgG4 levels (sIgE, sIgG, and sIgG4) were measured with ImmunoCAP. Hemagglutination inhibition (HI) assay was performed for each influenza virus subtype. Sera from earlier patients who developed anaphylaxis to different IIVs were similarly tested. Results: A total of 393 subjects were enrolled: 96 were 6 months−2 years old, 100 were 3–5 years old, 100 were 6–12 years old, and 97 were 13–18 years old. No anaphylaxis was observed. Generally, QIV and TIV induced similar antibody responses. IIV‐sIgE levels rose significantly after vaccination in the 6 months–2 years old and 3–5 years old groups, did not change in the 6–12 years old group, and decreased in the 13–18 years old group. In contrast, the IIV‐sIgG4/sIgE ratio increased significantly after vaccination in all age groups. Sensitized subjects had significantly higher HI titers and IIV‐sIgG levels in the youngest age group and higher IIV‐sIgG4 levels in all age groups compared with the non‐sensitized. The IIV‐sIgG4/sIgE ratio in five patients with anaphylaxis was significantly lower than in age‐matched healthy subjects. Conclusion: IIVs induce IgE sensitization in healthy children but also robust IgG4 responses that may protect them from anaphylaxis. [ABSTRACT FROM AUTHOR]

This is the English version of the Clinical Practice Guidelines for the Management of Atopic Dermatitis 2021. Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. In Japan, from the perspective of evidence‐based medicine, the current strategies for the treatment of AD consist of three primary measures: (i) use of topical corticosteroids, tacrolimus ointment, and delgocitinib ointment as the main treatment of the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling, and advice about daily life. In the present revised guidelines, descriptions of three new drugs, namely, dupilumab, delgocitinib, and baricitinib, have been added. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity‐related patient outcomes with respect to several important points requiring decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Safely liberalizing the diet to include an allergenic food may accelerate resolution of food allergy. The outcome of liberalization, however, varies among patients. Methods: We conducted a prospective observational study to identify factors associated with outcome for egg allergy 1 year after oral food challenge (OFC). We enrolled children <72 months old who had egg allergy and underwent OFC for determination of the safe intake quantity of egg allergen. Each child's baseline clinical background was recorded. Caregivers used the Food Allergy Quality of Life Questionnaire‐Parent Form (FAQLQ‐PF) to assess their children's QoL. Dietary advice based on the OFC result was provided to support safe egg consumption. At 1 year after OFC, the quantity of egg each child safely consumed in daily life was surveyed. We classified the outcome as Successful (Group S) if the quantity increased during the 1 year, or as Unsuccessful (Group U) if it did not. Factors associated with the outcome were investigated by multivariate logistic regression analysis. Results: A total of 93 children were enrolled, and after 1 year, 57 finished in Group S and 36 in Group U. The mean FAQLQ‐PF score at baseline was significantly lower (ie, a better QoL) in Group S than in Group U. Multivariate logistic regression analysis identified a good QoL and absence of comorbid asthma or atopic dermatitis as factors predicting a favorable outcome. Conclusion: QoL may affect food allergy outcome. Intervention focusing on the QoL may promote outgrowing of food allergies. [ABSTRACT FROM AUTHOR]

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder caused by functional impairment of cilia throughout the body. The involvement of copy number variation (CNV) in the development of PCD is largely unknown. Methods: We examined 93 Japanese patients with clinically suspected PCD from 84 unrelated families. CNV was examined either by exome sequencing of a PCD gene panel or by whole‐exome sequencing (WES). The identified alterations were validated by PCR and Sanger sequencing. Nasal ciliary ultrastructure was examined by electron microscopy. Results: Analysis of CNV by the panel or WES revealed a biallelic deletion in the dynein regulatory complex subunit 1 (DRC1) gene in 21 patients, which accounted for 49% of the PCD patients in whom a disease‐causing gene was found. Sanger sequencing of the PCR product revealed a 27,748‐bp biallelic deletion including exons 1–4 of DRC1 with identical breakpoints in all 21 patients. The ciliary ultrastructure of the patients with this CNV showed axonemal disorganization and the loss or gain of central microtubules. Conclusion: The deletion of DRC1 is the major cause of PCD in Japan and this alteration can cause various ciliary ultrastructural abnormalities. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. The current strategies to treat AD in Japan from the perspective of evidence‐based medicine consist of three primary measures: (i) the use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation; (ii) topical application of emollients to treat the cutaneous barrier dysfunction; and (iii) avoidance of apparent exacerbating factors, psychological counseling and advice about daily life. The guidelines present recommendations to review clinical research articles, evaluate the balance between the advantages and disadvantages of medical activities, and optimize medical activity‐related patient outcomes with respect to several important points requiring decision‐making in clinical practice. [ABSTRACT FROM AUTHOR]

Human adenoviruses (HAdVs) cause severe inflammatory respiratory infections, but previous epidemiological studies lacked analysis of the characteristics of the inflammation. Consecutive patients <13 years old with acute febrile illness during a 2‐year period were tested. HAdV strains were isolated from nasopharyngeal swabs, and molecular identification was performed by hexon, fiber, and species‐specific PCR methods. Blood inflammatory markers, including the white blood cell (WBC) count, CRP, and 29 cytokines, were measured. A total of 187 patients were enrolled, and HAdV types were identified from 175 patients (93.5%). Species C (types 2, 1, 5, and 6, in order of frequency) was most common at 37.1%, followed by B (type 3) at 30.9% and E (type 4) at 26.9%. Species C was detected predominantly in 1‐year‐old, whereas B and E were in older ages. Species C and B had seasonal circulation patterns, but E was found in only one season during the 2‐year study period. The WBC count was highest in patients with species C. Eleven of the 29 tested serum cytokines were detected. Seven kinds, including G‐CSF, IL‐6, and TNF‐α, were elevated in species C infections, whereas IL‐10 was lowest in species C. Species differences in inflammatory responses, especially regarding serum cytokines were described in common pediatric HAdV infections. Species C causes the strongest inflammatory responses in young children. [ABSTRACT FROM AUTHOR]

Background Several patient-/caregiver-completed questionnaires have been utilized for the assessment of asthma control. However, due to the diversity in medical/social circumstances, they may not be optimal for use in all countries. The Japanese pediatric asthma guideline ( JPGL) aims at higher levels of control compared with other international guidelines, based on a strong social demand for best care. We developed a new control test to help meet that demand. Methods A 34-item working questionnaire was developed based on input from pediatric asthma specialists and the caregivers of preschool children with asthma. The questionnaire was administered to caregivers of 565 patients aged <6 years who had physician-diagnosed asthma or β2-agonist-responsive recurrent wheeze. Then, 6 questions for assessing JPGL-defined control levels were selected from the 34 questions by stepwise logistic regression methods using randomly selected questionnaires completed by two-thirds of the caregivers. We named that set of questions the Best Asthma Control Test for Preschoolers (Best ACT-P). Validation of Best ACT-P was performed using the remaining completed questionnaires. Results The 6 questions asked about the frequency/severity of cold-induced wheeze, nighttime awakening, exercise-induced symptoms, and disruption of family life due to asthma in the past 4 weeks and hospitalization in the past 12 months. The 6-item logistic model showed good statistical fit, and the scores for the physicians' ratings of the asthma control differed significantly in the hypothetical direction. Conclusions Best ACT-P is a valid caregiver-completed questionnaire of asthma control in preschoolers in whom total control needs to be achieved. [ABSTRACT FROM AUTHOR]

Background Oral immunotherapy ( OIT) induces desensitization and/or tolerance in patients with persistent food allergy, but the biomarkers of clinical outcomes remain obscure. Although OIT-induced changes in serum allergen-specific IgE and IgG4 levels have been investigated, the response of other allergen-specific IgG subclasses and IgA during OIT remains obscure. Methods A pilot study was conducted to investigate egg OIT-induced changes in allergen-specific IgE, IgG subclasses, and IgA levels and search for possible prediction biomarkers of desensitization. We measured serum levels of egg white-, ovomucoid-, and ovalbumin-specific IgE, IgA, and IgG subclasses by high-sensitivity allergen microarray in 26 children with egg allergy who received rush OIT. Results Allergen-specific IgE gradually decreased while IgG4 increased during 12-month OIT. Serum levels of IgG1, IgG3, and IgA increased significantly after the rush phase, then decreased during the maintenance phase. IgG2 levels changed in a manner similar to that of IgG4. In particular, significantly high fold increases in egg white-specific IgG1, relative to baseline, after the rush phase and high IgA levels before OIT were observed in responders, compared with low-responders to OIT. Patients who could not keep desensitization showed relatively small changes in all immunoglobulin levels during OIT. Conclusion The response to OIT was associated with significant increases in serum allergen-specific IgG1 levels after rush phase and high baseline IgA levels, compared with small changes in immunoglobulin response in low-responders. The characteristic IgG1 changes and IgA levels in the responders could be potentially useful biomarkers for the prediction of positive clinical response to OIT. [ABSTRACT FROM AUTHOR]

Background Wheat protein derivatives are used in a variety of products worldwide. Gluten is commercially used 'as is' or with modifications such as hydrolysis, which is carried out to overcome its insolubility. Several cases of contact urticaria following exposure to hydrolysed wheat protein (HWP) in cosmetics or of anaphylaxis caused by deamidated gluten in food or non-food products have been described. Objectives To evaluate the types of HWP that have higher allergenicity for percutaneous sensitization. Methods We enrolled 7 patients with wheat-dependent exercise-induced anaphylaxis who had been sensitized to HWP primarily through the percutaneous and/or the rhinoconjunctival route by using facial soap containing HWP. Reaction to wheat proteins was confirmed by IgE immunoblotting and basophil CD203c expression with six HWP variants. Results The IgE of all the patients reacted to HWPs composed of large polypeptide aggregates. High molecular weight (MW) HWPs were also found to induce significant enhancement of basophil CD203c expression. Conclusions HWPs composed of large polypeptide aggregates possibly induce sensitization to a greater degree than lower-MW HWPs. Basophil surface CD203c expression is useful for evaluating the allergenicity of HWPs. [ABSTRACT FROM AUTHOR]

Elevated blood levels of thymus and activation-regulated chemokine (TARC)/CCL17 have been observed in atopic dermatitis (AD) and may serve as a new biomarker for AD. However, the normal levels, especially in children, have not been well determined. We sought to establish an efficient enzyme-linked immunosorbent assay (ELISA) with a wide range of detection that would be suitable for measurement of serum TARC/CCL17 and to determine the normal ranges of this chemokine in different age groups and its diagnostic usefulness for AD. A sensitive specific ELISA for TARC/CCL17, which we previously reported, was modified to accommodate the wide range of TARC/CCL17 values often found in sera. Twenty-seven children with AD under 6 yr of age and 25 age-matched normal non-atopic controls, and 18 patients with AD and 27 controls who were 6 yr and older were enrolled. The severity of AD was evaluated using the SCORAD index. The serum levels of TARC/CCL17 were measured with the ELISA, and the serum levels of IP-10/CXCL10 were also measured. With the novel ELISA system, the assayable range of TARC/CCL17 was 14–8000 pg/ml, and the coefficient of variation at various concentrations ranged from 2.3% to 5.0%. The serum levels of TARC/CCL17 in normal individuals were significantly higher in young children, especially in the age group of 0–1 yr. The cut-off values of TARC/CCL17 for the diagnosis of AD were 1431 pg/ml for 0–1 yr group, 803 pg/ml for 2–5 yr group and 510 pg/ml for the 6 yr and older group, with high sensitivity and specificity of 0.83 and 0.93, 0.83 and 0.92, 0.85 and 0.96, respectively. The magnitude of the decrease in the SCORAD index after treatment with topical steroids correlated significantly with the decrease in serum TARC/CCL17. There was no difference in the serum levels of IP-10/CXCL10 between AD and the controls. The TARC/CCL17:IP-10/CXCL10 ratio tended to be higher in the control children aged 0–1 yr than in those aged 2–5 yr. The serum level of TARC/CCL17 reflects the severity and therapeutic response in AD. The high normal levels in infants should be taken into account when assaying TARC/CCL17. [ABSTRACT FROM AUTHOR]