大矢 幸弘

BACKGROUND: The Prevention of Allergy via Cutaneous Intervention (PACI) randomized controlled trial (RCT) demonstrated that early enhanced topical corticosteroid (TCS) therapy modestly reduced food allergy (FA) at 28 weeks of age. The present prospective follow-up study (PACI-ON) evaluated whether these effects persisted to age 3 years. METHODS: Participants were randomized in infancy to early enhanced (proactive) or early conventional (reactive) TCS treatment (1:1) for atopic dermatitis (AD) until 28 weeks. A total of 590 (91%) children who completed the PACI RCT were followed to age 3 years. During follow-up, no protocolized interventions were given; all participants received usual care. Main outcomes included physician-diagnosed FA, AD severity (EASI, POEM), sensitization profiles, allergic comorbidities, and growth parameters as safety outcomes. RESULTS: At age 3 years, the prevalence of any FA remained lower in the early enhanced group than in the conventional group (47.4% vs. 58.8%, p = 0.006), mainly driven by a reduced prevalence of raw egg allergy (30.4% vs. 40.5%, p = 0.013). No between-group differences were observed for wheeze, asthma, or rhinitis. Japanese cedar sensitization at age 2 was lower in the enhanced group (6.1% vs. 12.2%, p = 0.02 6) but not at age 3. AD control and quality of life were well maintained and similar across groups, with > 90% achieving mild or less disease. Early growth suppression at 1 year resolved by age 3. CONCLUSION: Early enhanced AD intervention was associated with a sustained modest reduction in its planned primary follow-up outcome of FA and safety (growth) up to age 3. Although most differences were small and may reflect early diagnosis and good overall management in both groups, the findings support early AD treatment as a potential strategy to modify allergic disease trajectories.

INTRODUCTION: The atopic march describes the progression from early eczema to food allergies and asthma. In Japan, early-onset atopic dermatitis (AD) is linked to allergic diseases, but the role of peanut sensitization-a known asthma risk factor in Western populations-remains uncertain because of its lower prevalence. This study aimed to evaluate whether peanut sensitization predicts asthma development in Japanese children with AD and to compare its predictive value with other common allergens. METHODS: We conducted a retrospective cohort study of 203 children under age two with physician-diagnosed AD who underwent simultaneous measurement of specific immunoglobulin E to egg white, peanut, and house dust mite at a tertiary Allergy Center in Tokyo. Participants were followed until age six. Sensitization was categorized as none, mono (one allergen), or oligo (≥2 allergens). Associations with asthma development were evaluated using multivariate logistic regression and decision tree analysis. RESULTS: Asthma developed in 32.0% of participants. Peanut sensitization was significantly more common in the asthma group (53.8% vs. 29.7%, p = 0.001), as were oligo-sensitization and allergic rhinitis. Decision tree analysis identified peanut sensitization as the most influential predictor, with an 83% asthma incidence among children with both peanut sensitization and rhinitis. Logistic regression confirmed peanut sensitization as an independent risk factor (adjusted odds ratio: 2.74, 95% confidence interval: 1.44-5.24). CONCLUSIONS: Peanut sensitization in infancy strongly predicts asthma in Japanese children with AD. Early allergen-specific sensitization profiling may help identify high-risk children and support targeted asthma prevention strategies.

IMPORTANCE: Allergic diseases in children are influenced by gene-environment interactions. Although advanced parental age has been associated with genetic and epigenetic changes, its relationship with childhood allergy risk remains unclear. OBJECTIVE: To examine the association between parental age at childbirth and the risk of allergic diseases in early childhood. DESIGN, SETTING, AND PARTICIPANTS: This nationwide, multicenter, population-based, prospective birth cohort study used data from the Japan Environment and Children's Study (JECS). Participants were enrolled at 15 regional centers in Japan between January 2011 and March 2014, with follow-up data collected at child ages 1, 2, and 4 years. The present analysis was conducted from July 8, 2024, to February 4, 2025. Eligible participants were singleton live births with data on parental age and allergic outcomes. Physician-diagnosed allergy outcomes were collected via parental report. House dust mite (HDM) sensitization was assessed in a subcohort. MAIN OUTCOMES AND MEASURES: The primary outcomes were physician-diagnosed food allergy, wheeze, asthma, and eczema at ages 1, 2, and 4 years. The secondary outcome was HDM sensitization at ages 2 and 4 years. Adjusted odds ratios (ORs) were calculated using multivariable logistic regression after multiple imputation for missing values. RESULTS: A total of 34 942 mother-child pairs were included; the mean (SD) maternal age at entry was 31.0 (4.7) years, and 17 892 mothers (51.2%) had a medical allergy history. The prevalence of food allergy at age 1 year was 6.6% (95% CI, 6.4%-6.9%), decreasing with maternal age. Compared with children of mothers aged 25 to 29 years, those of mothers aged 35 to 39 years (OR, 0.79; 95% CI, 0.70-0.90) and aged 40 years and older (OR, 0.59; 95% CI, 0.44-0.79) had lower odds of food allergy. Children of parents both aged 35 years or older had lower odds of wheezing at age 4 years (OR, 0.89; 95% CI, 0.82-0.95). HDM was assessed in 1991 children at age 2 years and 1840 children at age 4 years, and children of older mothers also had lower odds of HDM sensitization (children of mothers aged 30-34 years, OR, 0.76; 95% CI, 0.59-0.98; children of mothers aged 35-39 years, OR, 0.68; 95% CI, 0.50-0.91). CONCLUSIONS AND RELEVANCE: In this cohort study of 34 942 mother-child pairs, children of older mothers had reduced odds of food allergy, wheezing, and HDM sensitization in early childhood, suggesting that advanced maternal age may be protective against the development of allergic diseases in early childhood.

BACKGROUND: Understanding factors influencing vaccine-induced immunity in adolescents is important for optimizing COVID-19 vaccination strategies. Allergic diseases have been hypothesized to alter immune responses through Th2-dominant inflammation, but data regarding their impact on SARS-CoV-2 mRNA vaccine antibody production remain limited in real-world adolescent populations. The purpose of this study is to identify factors affecting SARS-CoV-2 antibody titers after mRNA vaccination in a general population of 16- to 17-year-olds. METHODS: This study analyzed data from 233 participants in the T-CHILD Study, a Japanese general birth cohort, who received their 17-year medical checkup between July 2021 and October 2023. Individuals with a history of COVID-19 or serological evidence of prior infection (positive for both S- and N-antibodies) were excluded. Associations between SARS-CoV-2 S-antibody titers and vaccination history, allergic diseases, and other variables were examined. RESULTS: Multivariate analysis revealed that only a higher number of vaccine doses was independently associated with higher SARS-CoV-2 antibody titers. No significant associations were found between antibody titers and vaccine type, the interval since the last vaccination, allergic diseases such as asthma, atopic dermatitis (AD), or food allergy, or with total serum IgE levels. CONCLUSIONS: These findings suggest that adolescents with mild allergic diseases can mount sufficient immune responses to SARS-CoV-2 mRNA vaccines, supporting the safety and efficacy of vaccination in this population. (230 words).