Maternal Dietary Vitamin D Intake during Pregnancy Is Associated with Allergic Disease Symptoms in Children at 3 Years Old: The Japan Environment and Children's Study.

INTRODUCTION: Vitamin D plays an important role in the immune system, and postnatal vitamin D insufficiency is one of the risk factors for the development of allergic disease. However, the effects of women's vitamin D intake during pregnancy on the prevalence of allergic disease in their children remain controversial. METHODS: From the Japan Environment and Children's Study, an ongoing nationwide birth cohort study, we obtained information on maternal dietary vitamin D intake determined using a food frequency questionnaire and parent-reported allergic disease symptoms based on the ISAAC questionnaire in children at 3 years of age. RESULTS: From the full dataset of 103,060 pregnancies, we analyzed complete data for 73,309 mother-child pairs. The prevalence of current wheeze, current rhinitis, current rhino-conjunctivitis, current eczema, ever asthma, ever pollinosis, and ever atopic dermatitis in the children was 17.2%, 29.7%, 3.8%, 15.2%, 9.6%, 3.7%, and 11.0%, respectively. The ORs for current rhinitis were significantly lower in the 3rd, 4th, and 5th quintiles than in the 1st quintile after adjustment for various covariates and showed a linear association. The ORs for ever pollinosis were significantly lower in the 2nd, 3rd, and 4th quintiles than in the 1st quintile, showing a U-shaped curve. There was no clear association between mothers' dietary vitamin D intake and symptoms of asthma or atopic dermatitis in their 3-year-old children. CONCLUSION: Maternal dietary vitamin D intake during pregnancy is associated with the ORs for nasal allergies in children at the age of 3 years. Further studies are warranted to evaluate the appropriate intake dose of vitamin D for pregnant women to prevent the development of nasal allergies in their children.

Association of soap use when bathing 18-month-old infants with the prevalence of allergic diseases at age 3 years: The Japan Environment and Children's Study.

BACKGROUND: Atopic march is defined as the progression from atopic dermatitis (AD) during early life to other allergic diseases in later childhood. In a nationwide birth cohort study, the Japan Environment and Children's Study, we investigated the association of bathing habits, which are known to affect skin conditions, for infants with their later development of allergic diseases. METHODS: Pregnant women who lived in 15 designated regional centers throughout Japan were recruited. We obtained information on bathing habits for their 18-month-old infants and the prevalence of allergic diseases when they were aged 3 years. RESULTS: Data for 74,349 children were analyzed. Most 18-month-old infants were bathed or showered almost every day. When they were divided into four groups according to the frequency of soap use during bathing (every time, most of the time, sometimes, and seldom), the risk of AD later at age 3 was shown to increase in association with a decreasing frequency of soap use [most of the time: adjusted odds ratio (aOR) 1.18, 95% confidence interval (CI) 1.05-1.34; sometimes: aOR 1.72, 95% CI 1.46-2.03; seldom: aOR 1.99, 95% CI 1.58-2.50], compared with soap use every time during bathing at 18 months of age. Similar results were obtained for food allergy but not for bronchial asthma. CONCLUSIONS: Frequent soap use when bathing 18-month-old infants was associated with a decreased risk of them developing allergic diseases at age 3. Further well-designed clinical studies are warranted to determine an effective bathing regimen for preventing the development of allergic diseases.

Association between Maternal Vitamin D Intake and Infant Allergies: The Japan Environment and Children's Study.

Maternal nutrition during pregnancy is one of the factors affecting the health of offspring. There are conflicting findings about the association between maternal vitamin D status and the development of allergic diseases in offspring. The purpose of this study is to evaluate the association between maternal vitamin D intake and the development of allergic diseases in offspring at 1 y of age. From an ongoing nationwide birth cohort study (the Japan Environment and Children's Study), we obtained information on maternal vitamin D intake, determined by a food frequency questionnaire, and parent-reported physician-diagnosed allergic diseases in offspring at 1 y of age. From the full dataset of 103,062 pregnancies, we analyzed complete data for 82,592 mother-offspring pairs. The prevalence of physician-diagnosed asthma, food allergy, and atopic dermatitis in the children was 2.5%, 6.6%, and 4.3%, respectively. The mean (± standard deviation) maternal vitamin D intake was 4.7±4.7 µg/d, which is much lower than the recommended amount in Japan (7 µg/d). After adjustment for various covariates, the odds ratios were significantly higher for asthma in the 2nd quintile and for food allergies in the 3rd and 4th quintiles compared with the 1st quintile. However, there were no clear associations between maternal vitamin D intake and the development of allergic diseases in offspring at 1 y of age, even in a large nation-wide cohort study. Protective effects of vitamin D supplementation remain unclear.

An epidermal keratinocyte homogenate induced type 2 and proinflammatory cytokine expression in cultured dermal cells.

BACKGROUND: The "itch-scratch cycle" is a clinically well-known cause of exacerbation of atopic dermatitis (AD), but the underlying molecular mechanisms remain largely unknown. OBJECTIVE: To test our hypothesis that some molecules released from damaged epidermal keratinocytes by scratching inducetype 2 responses in intact skin dermal cells, leading to exacerbation of AD. METHODS: Normal human dermal fibroblasts (NHDF) and human dermal blood microvascular endothelial cells (HMVEC-dBl) were treated with an epidermal keratinocyte homogenate (EKH). We used qPCR and ELISA, respectively, to measure the mRNA expressions and protein concentrations of various cytokines, including IL-6, IL-8, thymic stromal lymphopoietin (TSLP), and IL-33. We analyzed IL-33 protein expression in the nuclear fractions of NHDF by Western blotting. We also investigated the effects of IL-1R1 gene-silencing and several AD therapeutic drugs on EKH induction of cytokine production by the dermal cells. RESULTS: EKH significantly induced IL-6 and IL-8 in NHDF and HMVEC-dBl. EKH also induced type 2 cytokines, TSLP and IL-33, in NHDF. IL-1R1 gene-silencing in NHDF partially attenuated the induction. Dexamethasone (a corticosteroid) significantly inhibited, while ABT494 (a JAK1 inhibitor) partially inhibited, EKH's induction of cytokines in fibroblasts. In contrast, ABT494 was more effective than dexamethasone in inhibiting the cytokine induction in HMVEC-dBl. CONCLUSION: This study showed that a homogenate of epidermal keratinocytes significantly induced AD-related cytokines in cultured dermal cells, and IL-1α, an alarmin, might be involved in that induction. Combined use of corticosteroids and JAK1 inhibitors is likely to block the itch-scratch cycle by targeting different types of dermal cells.

Maternal exposure to smoking and infant's wheeze and asthma: Japan Environment and Children's Study.

BACKGROUND: Evidence regarding independent effects of maternal smoking in different time frames of pregnancy and maternal exposure to secondhand smoke on the development of wheeze/asthma in her offspring is limited. We aimed to investigate the effect of maternal exposure to tobacco smoke on wheeze/asthma development at 1 year of age in her offspring using data from the nationwide birth cohort study in Japan. METHODS: Pregnant women who lived in the 15 designated regional centers throughout Japan were recruited. We obtained information about maternal smoking or secondhand smoke status and wheeze/asthma development in the offspring from a self-administered questionnaire. RESULTS: We analyzed 90,210 singleton births. Current maternal smoking during pregnancy increased the risks of wheeze/asthma in the offspring compared with no maternal smoking (wheeze: 1-10 cigarettes/day: adjusted odds ratio (aOR) 1.436, 95% CI 1.270-1.624; ≧11 cigarettes/day: aOR 1.669, 95% CI 1.341-2.078; asthma: 1-10 cigarettes/day: aOR 1.389, 95% CI 1.087-1.774; ≧11 cigarettes/day: aOR 1.565, 95% CI 1.045-2.344). Daily maternal exposure to secondhand smoke during pregnancy also increased the risks of wheeze/asthma in her offspring compared with no secondhand smoke exposure (wheeze: aOR 1.166, 95% CI 1.083-1.256; asthma: aOR 1.258, 95% CI 1.075-1.473). The combination of current maternal smoking during pregnancy and maternal history of allergy increased the risks of wheeze/asthma in her offspring (wheeze: aOR 2.007, 95% CI 1.739-2.317; asthma: aOR 1.995, 95% CI 1.528-2.605). CONCLUSIONS: We found that current maternal smoking and maternal secondhand smoke exposure during pregnancy increased the risks of wheeze and asthma in her offspring.

Functional benefits of corticosteroid and IVIG combination therapy in a coronary artery endothelial cell model of Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) is the most common pediatric systemic vasculitides of unknown etiology. Recent clinical studies led to reappraisal of the usefulness of initial combination therapy of intravenous immunoglobulin (IVIG) plus a corticosteroid for patients with severe KD. However, the molecular mechanisms underlying the clinical benefits of that combination therapy remain unclear. Here, we used cultured human coronary artery endothelial cells (HCAECs), as a mimic of KD, to study the possible mechanisms responsible for the clinical benefits of adding a corticosteroid to standard IVIG therapy for patients with severe KD. METHODS: HCAECs were stimulated with TNF-α, IL-1α or IL-1ß in the presence and absence of high-dose IgG and/or dexamethasone (DEX). The mRNA and protein concentrations for high-mobility group box-1 (HMGB1), IL-1α, IL-6 and granulocyte-colony stimulating factor (G-CSF) in the culture supernatants were measured by quantitative PCR (qPCR) and ELISA, respectively. Apoptosis was evaluated by the caspase 3/7 activities. RESULTS: DEX, but not IgG, significantly inhibited apoptosis caused by inflammatory stimuli, resulting in effective reduction of HMGB1 and IL-1α protein release by HCAECs. As previously reported, DEX or IgG alone significantly suppressed TNF-α-induced production of IL-6 and G-CSF and mRNA expression, but induction of those cytokines by IL-1 s (IL-1α and IL-1ß) was resistant to high-dose IgG. CONCLUSIONS: A corticosteroid can effectively inhibit the release of HMGB1 and IL-1α, which may be involved in IVIG resistance in KD. Since high-dose IgG does not have such beneficial anti-cytotoxic effects, adding a corticosteroid to standard IVIG therapy may help prevent the progression of IVIG resistance in KD.