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The present study investigated the association between pre- and postnatal maternal hair dye use and the risk of wheeze and asthma in Japanese children aged 5 years. Study participants were 1199 mother-child pairs. Information on the variables under study was obtained using repeated questionnaires completed by parents. Prenatal maternal hair dye use was associated with an increased risk of current wheeze and ever doctor-diagnosed asthma; the adjusted odds ratios (ORs) (95% confidence intervals [CIs]) were 1.44 (1.02-2.02) and 1.51 (1.00-2.25), respectively. Postnatal maternal hair dye use was related to the risk of doctor-diagnosed asthma; the adjusted OR (95% CI) was 1.58 (1.03-2.40). Children who were exposed to maternal hair dye use both prenatally and postnatally had an increased risk of childhood current wheeze and ever doctor-diagnosed asthma; the adjusted ORs (95% CIs) were 1.59 (1.03-2.42) and 1.76 (1.06-2.88), respectively. Our findings suggest that perinatal maternal hair dye use is associated with the risk of wheeze and asthma in children.

Objective: We examined independent and joint associations between prenatal and postnatal smoking exposure and the prevalence of wheeze and asthma among 3-year-old Japanese children. Sex differences were also investigated., Methods: Smoking exposure, allergic symptoms, and potential confounding factor data were collected using a self-administered questionnaire. Wheeze was defined on the basis of the International Study of Asthma and Allergies in Childhood criteria. Physician-diagnosed asthma was considered to be present if a physician had diagnosed the child with asthma any time before the survey was administered., Results: There were 6402 pediatric participants in this study. Maternal smoking throughout pregnancy and household smoking exposure during the first year of life were associated with an increased prevalence of wheeze among girls but not boys (adjusted odds ratio (OR) [95% CI] = 2.00 [1.13-3.42] and 1.34 [1.07-1.68], respectively). Girls exposed to both prenatal maternal smoking and postnatal household smoking exposure had a significantly higher prevalence of wheeze and physician-diagnosed asthma compared with girls without these exposures (adjusted OR [95% CI] = 2.06 [1.39-3.01] and 1.86 [1.01-3.26], respectively). No association was observed between perinatal smoking exposure and the prevalence of wheeze or asthma among boys. Significant interactions between sex and smoking exposure affecting wheeze and asthma were also found ( p for interaction = 0.0003 and 0.01, respectively)., Conclusion: We found a positive association between perinatal smoking exposure and the prevalence of wheeze and asthma only among girls. Effects of perinatal smoking exposure on wheeze and asthma might be sex specific. Further research is required.

Background: There is limited evidence on the association between prenatal smoking exposure and the risk of asthma in children. The aim of this prebirth cohort study was to investigate the association between prenatal and postnatal tobacco smoke exposure and the risk of asthma in Japanese children., Methods: Study subjects were 1304 mother-child pairs. Information on the variables under study was obtained using repeated questionnaires that were completed by mothers, first prior to delivery, then shortly after birth and subsequently around 4, 12, 24, and 36 months after delivery. Ever asthma was defined as a maternal report of physician-diagnosed asthma at any time since birth. Current asthma was defined as the use of asthma medication at the time of the sixth survey., Results: Logistic regression models revealed that maternal active smoking, either before pregnancy or during pregnancy, was not associated with the risk of ever asthma or current asthma. Further, no association was observed between postnatally living with at least one household smoker and the risk of asthma. Among children whose mothers are never smokers, maternal second-hand smoke (SHS) exposure at work and/or at home during pregnancy increased the risk of ever asthma and current asthma in children; adjusted odds ratio (95% confidence intervals) for ever asthma and current asthma were 2.41 (1.13-5.05) and 4.82 (1.68-13.43), respectively., Conclusions: Our findings suggest that maternal SHS exposure during pregnancy might be associated with an increased risk of ever asthma and current asthma in young children whose mothers have never smoked., (Copyright © 2020 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Some recent studies suggest that maternal prenatal stress (MPS) increases allergic diseases in the children. However, knowledge on this issue in Asian children are lacking. We investigated the association between MPS and the risks of wheeze and asthma in Japanese infants aged 16-24 months., Methods: The present subjects were 763 Japanese mother-child pairs. The first, second, and third surveys based on self-administered questionnaires were performed during pregnancy, between 2 and 9 months postpartum, and from 16 to 24 months postpartum, respectively. Data on MPS was obtained in the first survey, using the Stress Inventory (SI), which constructs 12 specific behavioral patterns as response styles to stressors. Data on wheeze and asthma was obtained in the third survey, where wheeze was based on the International Study of Asthma and Allergies in Childhood criteria and asthma was based on doctors' diagnosis., Results: There were 169 infants with wheeze (22.1%) and 33 infants with asthma (4.3%), at the time of the third survey. Multiple logistic regression analyses found that a maternal behavioral pattern characterized by chronic irritation and anger was associated with the risk of childhood asthma (adjusted odds ratio [OR] = 1.56, 95% confidence interval [CI]: 1.11 to 2.22), but not wheeze (adjusted OR = 1.02, 95%CI: 0.88 to 1.19), while there was no appreciable association between the other SI scales and the risk of childhood wheeze or asthma., Conclusions: The results partly supported the hypothesis that MPS might increase the risk of asthma in their infants in Japanese., Competing Interests: Declaration of Competing Interest The authors report no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The present cross-sectional study investigated the associations between low birthweight (LBW), high birthweight, preterm birth (PTB), postterm birth, small for gestational age (SGA), and large for gestational age (LGA) and the prevalence of wheeze and asthma in Japanese children aged three years (age range, 33-54 months; mean age, 38.7 months)., Methods: Study subjects were 6364 children. A questionnaire was used to collect all data. Wheeze and asthma were defined according to the criteria of the International Study of Asthma and Allergies in Childhood., Results: The prevalence values of wheeze and asthma were 19.5% and 7.7%, respectively. Of the 6364 subjects, 8.8% were classified as LBW (<2500g), 90.4% as normal birthweight, 0.8% as high birthweight (≥4000g), 4.8% as PTB (<37 weeks), 94.8% as term birth, 0.4% as postterm birth (≥42 weeks), 7.8% as SGA (<10th percentile), 82.5% as appropriate for gestational age, and 9.7% as LGA (>90th percentile). Compared with term birth, PTB was independently positively associated with wheeze and asthma: the adjusted ORs (95% CI) were 1.47 (1.11-1.92) and 1.52 (1.02-2.20), respectively. An independent positive association was shown between PTB and wheeze only in boys; the interaction between PTB and sex was significant. Such an interaction between PTB and sex was not seen for asthma. No evident associations were observed between LBW, high birthweight, postterm birth, SGA, or LGA and wheeze or asthma., Conclusions: This is the first study in Japan to show that PTB, but not LBW or SGA, was significantly positively associated with childhood wheeze and asthma., (Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: Recent meta-analyses found an inverse relationship between breastfeeding duration and asthma in children. The present cross-sectional study investigated the associations between breastfeeding duration and the prevalence of wheeze and asthma in Japanese children aged 3 years., Methods: Subjects were 6412 children who participated in the Kyushu Okinawa Child Health Study. Data were collected using a self-administered questionnaire. Wheeze was defined according to the criteria of the International Study of Asthma and Allergies in Childhood. Asthma was considered present if the child had been diagnosed by a physician as having asthma. Associations of breastfeeding duration with wheeze and asthma were estimated using multivariate generalized estimating equation methods adjusted for maternal, family, and health characteristics., Results: The prevalence values of wheeze and asthma were 19.5% and 7.0%, respectively. Compared with <4 months of exclusive breastfeeding, exclusive breastfeeding for ≥4 months was not significantly associated with wheeze or asthma. Compared with <10 months of breastfeeding duration regardless of exclusivity, 10 to <14 months, 14 to <19 months, and 19 months or more of breastfeeding duration regardless of exclusivity were independently inversely related to asthma: the adjusted odds ratios [ORs; 95% confidence intervals (CIs)] were 0.69 (0.52-0.91, p = 0.01), 0.73 (0.56-0.97, p = 0.03), and 0.67 (0.51-0.88, p = 0.004), respectively. No association was found between breastfeeding duration regardless of exclusivity and wheeze., Conclusions: We confirmed an inverse association between breastfeeding duration regardless of exclusivity and asthma.

Epidemiological evidence on the relationship between single-nucleotide polymorphisms (SNPs) rs7216389 and rs11650680 on chromosome 17q12-21 and asthma is inconsistent. We examined this issue in young adult Japanese women. Case subjects were 202 women who had been diagnosed with asthma by a doctor, while 1290 women without doctor-diagnosed asthma served as control subjects. Adjustments were made for age and the presence of older siblings. There were no significant associations between SNP rs7216389 and asthma. Compared with the CC genotype of SNP rs11650680, the CT genotype, but not the TT genotype, was significantly inversely associated with asthma: the adjusted odds ratio for the CT genotype was 0.67 (95% confidence interval: 0.46-0.96). This inverse relationship was significant in women with late-onset asthma, but not in those with early-onset asthma. Under the dominant model, a significant inverse association was found between rs11650680 and asthma in women without older siblings, but not in those with older siblings; the interaction, however, was not significant. This is the first study to show that the CT genotype of SNP rs11650680 was significantly inversely associated with asthma, especially adult-onset asthma. We could not find evidence for interactions between rs11650680 and older siblings affecting asthma.

Three previous genetic association studies conducted in Korea and China investigated the relationship between IL3 single nucleotide polymorphism (SNP) rs40401 and asthma, but their results were inconsistent. We examined this relationship and the possibility of an interaction between IL3 SNP rs40401 and smoking in young adult Japanese women. Included were 89 women who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma. Control subjects were 700 women without asthma according to the ECRHS criteria who had not been diagnosed with asthma and/or allergic rhinitis by a doctor and/or who had not met the criteria of the International Study of Asthma and Allergies in Childhood for rhinoconjunctivitis. A significant positive association was found between SNP rs40401 and the risk of asthma, with the TT genotype as the reference under the additive model: the adjusted odds ratio was 1.39 (95% CI: 1.004-1.93). The positive association was not statistically significant in any other genetic model. Compared with subjects with the TT or TC genotype of SNP rs40401 who had never smoked, those with the CC genotype who had ever smoked had a significantly increased risk of asthma: the adjusted OR was 2.67 (95% CI: 1.23-5.79); the additive interaction, but not the multiplicative interaction, was significant. This study suggests that IL3 SNP rs40401 is significantly associated with the risk of asthma in young adult Japanese women and reveals that the combination of ever smoking and having the CC genotype of IL3 SNP rs40401 is significantly positively associated with asthma., (© 2014 John Wiley & Sons Ltd.)

Purpose: This cohort study examined the relationship between maternal intake of individual fatty acids, meat, and fish during pregnancy and the risk of wheeze and eczema in children aged 23-29 months because epidemiologic evidence on this topic is inconclusive., Methods: Subjects were 1354 Japanese mother-child pairs. Data on maternal intake during pregnancy were assessed with a validated diet history questionnaire. Data on symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood., Results: Significant inverse exposure-response relationships were observed between maternal intake of eicosapentaenoic acid (EPA) and EPA plus docosahexaenoic acid (DHA) during pregnancy and infantile wheeze although the adjusted odds ratios between extreme quartiles fell just short of the significance level. No such inverse relationships were detected for infantile eczema. Maternal intake of total fat, saturated fatty acids, monounsaturated fatty acids, total n-3 polyunsaturated fatty acids (PUFA), α-linolenic acid, DHA, total n-6 PUFA, linoleic acid, arachidonic acid, cholesterol, fish, and meat and the ratio of n-3 to n-6 PUFA consumption were not significantly related to infantile wheeze or eczema., Conclusions: Higher maternal intake of EPA and EPA plus DHA during pregnancy may reduce the risk of infantile wheeze., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: Apart from its role in the coagulation system, thrombin plays an important role in the inflammatory response through its protease-activated receptors (PARs). However, the role of thrombin in the immune response is not clear., Objective: To evaluate whether thrombin has a modulatory role in allergic bronchial asthma., Methods: Bronchial asthma was induced in mice by intraperitoneal sensitization and inhalation challenge with ovalbumin. Thrombin or its inhibitors were administered by inhalation before each allergen challenge., Results: Mice with low but sustained coagulation activation had reduced allergic inflammation, and allergic asthma was inhibited by low doses of thrombin but worsened by high doses. Allergic asthma was worsened by antithrombin, argatroban, hirudin, and anti-thrombomodulin antibody. Mice with a higher level of an inhibitor of both thrombin and activated protein C had worse disease. Heterozygous PAR-1 mice had less allergic inflammation, but PAR-1 agonist worsened it. Allergic bronchial inflammation was worsened in mice that received adoptive transfer of PAR-1 agonist-treated Th2 cells as compared with controls. Low levels of thrombin suppressed the maturation and secretion of cytokines in dendritic cells, but high levels enhanced this., Conclusions: The effects of thrombin on allergic asthma are dose-dependent, with detrimental effects at high doses and protective effects at low doses. These data demonstrate that thrombin modulates the outcome in allergic bronchial asthma., (© 2013 International Society on Thrombosis and Haemostasis.)

Background: The current cross-sectional study examined the associations between low birth weight (LBW), preterm birth, and small-for-gestational-age (SGA) and the prevalence of wheeze, asthma, and eczema in Japanese children aged 3 years., Methods: Study subjects were 2004 children. All data were obtained using a questionnaire. Outcomes were defined according to the criteria of the International Study of Asthma and Allergies in Childhood. Adjustment was made for sex, number of siblings, breastfeeding duration, paternal and maternal educational level, paternal and maternal history of allergic disorders, maternal smoking during pregnancy, secondhand smoke exposure at home, and gestational age at birth., Results: The prevalence of wheeze, asthma, and eczema in the previous 12 months were 22.1%, 9.0%, and 17.5%, respectively, and 8.4% were classified as LBW (<2500 g), 4.7% as preterm birth (<37 weeks), and 7.1% as SGA (<10th percentile). There were no significant associations between LBW, preterm birth, or SGA and the prevalence of wheeze, asthma, or eczema. A positive relationship between preterm birth and asthma was of borderline significance in children whose mothers had smoked during pregnancy (adjusted OR: 4.71 [95% CI: 0.97-21.39]), but not in those whose mothers had never smoked during pregnancy; the multiplicative interaction between preterm birth and maternal smoking during pregnancy with respect to asthma was significant (p = .04)., Conclusions: The current study failed to detect significant associations between birth conditions and allergic disorders. Nevertheless, we did find evidence for an interaction between preterm birth and maternal smoking during pregnancy affecting asthma.

Background: Interleukin (IL) 4 plays a critical role in immune responses by acting as a growth factor for type 2 helper T cells and inducing immunoglobulin (Ig) class switching to IgE. Epidemiological evidence of the relationship between single-nucleotide polymorphisms (SNPs) in IL4 and asthma is inconsistent., Objectives: We examined the association between the IL4 SNPs rs2243250, rs2070874, rs2227284, and rs2243290 and asthma in young adult Japanese women., Methods: The study population comprised 89 women who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma. The control group comprised 1281 nonasthmatic women (ECRHS criteria) who had not been diagnosed with asthma by a physician. Adjustment was made for age, region of residence, presence of older siblings, smoking, and education., Results: Compared with the AA genotype of rs2243290, the AC genotype, but not the CC genotype, was significantly associated with a reduced risk of asthma: the adjusted odds ratio for the AC genotype was 0.62 (95% CI, 0.39-0.996). No evident relationships were found between rs2243250, rs2070874, or rs2227284 and asthma. None of the haplotypes were significantly associated with asthma. No significant interactions were found between the 4 SNPs under study and smoking with respect to the risk of asthma., Conclusions: Ours is the first study in a non-Western population to show that the IL4 SNP rs2243290 was significantly associated with the risk of asthma. Smoking did not significantly modify the gene-disease associations under study.

Setting: Multiple A disintegrin and metalloprotease 33 (ADAM33) single nucleotide polymorphisms (SNPs) have been shown to be associated with asthma, but results have been inconsistent., Objectives: To examine the association between ADAM33 SNPs rs2787094, rs628977, rs2280089, rs2280090, rs2280091, rs2853209, rs528557 and rs612709 and asthma in young adult Japanese women, and to perform haplotype analyses and assess interactions between SNPs and smoking., Design: A total of 89 cases who met the criteria of the European Community Respiratory Health Survey (ECRHS) for asthma were included in the study. Control subjects were 1281 women without asthma, as per ECRHS criteria, who had not been diagnosed with asthma by a doctor. Adjustment was made for age, region of residence, presence of older siblings, smoking and education., Results: Under a co-dominant model, the AA genotype of the rs612709 SNP was significantly positively associated with asthma compared with the GG genotype: the adjusted OR was 4.27 (95%CI 1.49-12.25). A significant positive relationship was found between the CCGGAAGA haplotype and asthma. Interactions between SNPs rs628977 and rs528557 and smoking were marginally significant (P = 0.09 and 0.095, respectively)., Conclusions: ADAM33 SNP rs612709 and the CCGGAAGA haplotype may be associated with asthma. Smoking may modify the associations between SNPs rs628977 and rs528557 and asthma.

Setting: Epidemiological evidence on the relationship between socio-economic status and allergic disorders has been inconsistent., Objectives: We examined the associations between maternal employment, maternal job type, household income, and paternal and maternal educational levels and the risk of allergic disorders in Japanese children aged 4.5 years., Design: Subjects were 480 mother-child pairs. Definitions of wheeze and eczema symptoms were based on criteria of the International Study of Asthma and Allergies in Childhood. Data on self-reported doctor-diagnosed asthma and atopic eczema were available., Results: Compared with children whose mothers had received less than 13 years of education, those with mothers with ≥15 years of education had a significantly increased risk of wheeze and doctor-diagnosed asthma: the adjusted ORs were respectively 2.41 (95%CI 1.18-5.17) and 2.70 (95%CI 1.03-8.08). Fifteen years or more of paternal education was independently associated with an increased risk of eczema, but not of doctor-diagnosed atopic eczema (adjusted OR 1.89, 95%CI 1.07-3.42). Mother's employment, mother's job type and household income were not related to any of the outcomes., Conclusions: Higher maternal educational level may increase the risk of wheeze and asthma, while higher paternal educational level may increase the risk of eczema.

Background: Bronchial asthma is an inflammatory disease of the airways. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase that besides inhibiting fibrinolysis, also regulates inflammatory processes. The only validated substrate known for TAFI is fibrin. In the present study we evaluated the role of TAFI in bronchial asthma by comparing the development of allergic bronchial asthma between wild-type (WT) and TAFI-deficient mice (KO)., Methods: Asthmatic inflammation was induced by sensitization and challenge with ovalbumin in WT (WT/OVA) and TAFI KO (KO/OVA) mice. WT mice (WT/SAL) and TAFI KO (KO/SAL) were used as controls. Cytokines, markers of inflammation, and coagulation were measured in bronchoalveolar lavage fluid (BALF)., Results: Airway hyperresponsiveness was worse in KO/OVA mice than in WT/OVA mice or control mice. Markers of lung injury were significantly increased in BALF from KO/OVA mice compared to WT/OVA mice. Airway hyperresponsiveness and the BALF concentrations of IL-5 and osteopontin were significantly increased in KO/OVA mice compared to WT/OVA mice. Treatment of WT/OVA and KO/OVA mice with a C5a receptor antagonist significantly decreased hyperresponsiveness along with the BALF concentrations of total protein and C5a compared to untreated asthmatic mice., Conclusion: The results of this study suggest that TAFI plays a protective role in the pathogenesis of allergic inflammation probably by inhibiting the complement system.

Background: Studies on the associations between smoking and allergic diseases have mostly focused on asthma. Epidemiological studies in adults on the effects of smoking on allergic diseases other than asthma, such as eczema and rhinoconjunctivitis, have been limited, and the information that is available has been inconsistent. The aim of this study was to investigate the association between smoking status and environmental tobacco smoke (ETS) exposure and the prevalence of allergic diseases., Methods: Study subjects were 1743 pregnant Japanese women. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age; region of residence; family history of asthma, atopic eczema, and allergic rhinitis; household income; and education., Results: Compared with never smoking, current smoking and ≥ 4 pack-years of smoking were independently positively associated with the prevalence of wheeze. There were no associations between smoking status and the prevalence of asthma, eczema, or rhinoconjunctivitis. When subjects who had never smoked were classified into four categories based on the source of ETS exposure (never, only at home, only at work, and both), exposure occurring both at home and at work was independently associated with an increased prevalence of two outcomes: wheeze and rhinoconjunctivitis. No relationships were observed between exposure to ETS and the prevalence of asthma or eczema., Conclusions: Our results provide evidence that current smoking and ETS exposure may increase the likelihood of wheeze. The possibility of a positive association between ETS exposure and rhinoconjunctivitis was also suggested.

Background: Studies reporting on the association between obesity and allergies have mostly focused on asthma. Little is known about the relationship of obesity to other allergic diseases, and the information that is available has been inconsistent. We examined the association between body mass index (BMI) and the prevalence of wheeze, asthma, eczema, and rhinoconjunctivitis in Japanese schoolchildren., Methods: Study subjects were 24,399 children aged 6-15 years in Okinawa, Japan. Outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. BMI was categorized into five groups; <5th, 5th to 35th, >35th to 65th, >65th to 95th, and >95th percentile groups. Adjustment was made for sex, age, region of residence, number of siblings, smoking in the household, physical activity, paternal and maternal history of allergic disorders, and paternal and maternal educational levels., Results: The prevalence values of wheeze, asthma, eczema, and rhinoconjunctivitis in the previous 12 months were 10.8%, 7.6%, 6.9%, and 7.6%, respectively. Compared with the referent category (>35th to 65th percentile group), higher percentile categories were positively associated with the prevalence of wheeze. A U-shaped relationship between BMI and asthma was observed. No material associations between BMI percentile categories and the prevalence of eczema or rhinoconjunctivitis were found., Conclusion: These findings suggested that being either underweight or overweight might increase the likelihood of asthma among Japanese schoolchildren.

Rationale: bronchial asthma is caused by inappropriate acquired immune responses to environmental allergens. It is a major health problem, with a prevalence that is rapidly increasing. Curative therapy is not currently available., Objectives: to test the hypothesis that thrombomodulin (TM) inhibits allergic bronchial asthma by inducing tolerogenic dendritic cells (DCs)., Methods: the protective effect of TM was evaluated using a murine asthma model. Asthma was induced in mice by exposure to chicken egg ovalbumin, and the effects of inhaled TM or TM-treated DCs were assessed by administering before ovalbumin exposure., Measurements and Main Results: treatment with TM protects against bronchial asthma measured as improved lung function and reduced IgE and cells in alveolar lavage fluid by inducing tolerogenic dendritic dells. These are characterized by high expression of surface TM (CD141/TM(+)) and low expression of maturation markers and possess reduced T-cell costimulatory activity. The CD141/TM(+) DCs migrate less toward chemokines, and after TM treatment there are fewer DCs in the draining lymph node and more in the lungs. The TM effect is independent of its role in coagulation. Rather, it is mediated via the TM lectin domain directly interacting with the DCs., Conclusions: the results of this study show that TM is a modulator of DC immunostimulatory properties and a novel candidate drug for the prevention of bronchial asthma in atopic patients.

The present prospective study examined the association between maternal consumption of dairy products, calcium, and vitamin D during pregnancy and the risk of wheeze and eczema in the infants aged 16-24 months. Subjects were 763 Japanese mother-child pairs. Data on maternal intake during pregnancy were assessed with a diet history questionnaire. Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood. Higher maternal intake of total dairy products, milk, cheese and calcium during pregnancy was significantly related to a decreased risk of infantile wheeze, but not eczema (adjusted ORs (95% CI) between extreme quartiles were 0.45 (0.25-0.79), 0.50 (0.28-0.87), 0.51 (0.31-0.85), and 0.57 (0.32-0.99), respectively). When maternal vitamin D consumption during pregnancy was categorised into two groups using a cut-off point at the 25th percentile, children whose mothers had consumed > or =4.309 microg x day(-1) had a significantly reduced risk of wheeze and eczema (adjusted ORs (95% CI) were 0.64 (0.43-0.97) and 0.63 (0.41-0.98), respectively). Higher consumption of calcium and dairy foods other than yoghurt during pregnancy may reduce the risk of infantile wheeze. Higher vitamin D intake during pregnancy may be protective against childhood wheeze and eczema.

Setting: Data on the association between breastfeeding and allergies are conflicting., Objective: To investigate the relationship between the duration and exclusivity of breastfeeding and the prevalence of wheeze, asthma and eczema in young Japanese children., Design: Study subjects were 1957 children aged 3 years. Data on breastfeeding, allergic symptoms and potential confounders were collected using a questionnaire. Outcomes were defined according to the criteria of the International Study of Asthma and Allergies in Childhood. Adjustment was made for sex, number of siblings, household smoking, paternal and maternal history of asthma, atopic eczema and allergic rhinitis, and paternal and maternal educational levels., Results: The prevalence values of symptoms of wheeze, asthma and eczema in the previous 12 months were respectively 22.1%, 8.9% and 17.3%. Exclusive breastfeeding for > or =4 months vs. <4 months was associated with a lower prevalence of asthma. The duration of breastfeeding, regardless of exclusivity, for > or =6 months tended to be associated with a lower prevalence of asthma. There was no appreciable association between breastfeeding and wheeze or eczema., Conclusions: Data from this study indicate that breastfeeding may be associated with a lower prevalence of asthma among young Japanese children.

Background: It has been hypothesized that increased consumption of n-6 polyunsaturated fatty acids and decreased consumption of n-3 polyunsaturated fatty acids have contributed to the recent increased prevalence of asthma., Objectives: The present cross-sectional study examined the association of intake of specific types of fatty acids with the prevalence of asthma symptoms using data from the Ryukyus Child Health Study., Methods: Study subjects were 25,033 schoolchildren aged 6-15 years in Okinawa, Japan. Symptoms of wheeze and asthma were defined according to diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Information on dietary factors was collected using a self-administered brief diet history questionnaire for children. Adjustment was made for age, sex, number of siblings, smoking in the household, body mass index, paternal and maternal history of allergic diseases, and paternal and maternal educational level., Results: Intake of polyunsaturated fatty acids, n-3 and n-6 polyunsaturated fatty acids and linoleic acid (18:2 n-6) was independently associated with an increased prevalence of wheeze--the multivariate odds ratios for the highest quintile were 1.19 (95% confidence interval [CI], 1.05-1.35), 1.17 (95% CI, 1.03-1.34), 1.19 (95% CI, 1.04-1.35), and 1.20 (95% CI, 1.06-1.37), respectively. There was no measurable relationship of consumption of alpha-linolenic (18:3 n-3), eicosapentaenoic (20:5 n-3), docosahexaenoic (22:6 n-3) or arachidonic acid (20:4 n-6) or the ratio of n-3 to n-6 polyunsaturated fatty acids with the prevalence of wheeze. Consumption of total fat, saturated fatty acids, monounsaturated fatty acids and cholesterol were not evidently related to wheeze. No material dose-response association was found between the intake of any of the types of fatty acids considered and the prevalence of asthma., Conclusions: The findings suggest that consumption of both n-3 and n-6 polyunsaturated fatty acids, especially linoleic acid, may be associated with an increased prevalence of wheeze.

Epidemiological evidence for an effect of breastfeeding on asthma continues to be inconclusive. The present prospective study examined the relationship between breastfeeding and the risk of wheeze and asthma in Japanese infants. A birth cohort of 763 infants was followed. The first survey during pregnancy and the second survey between 2 and 9 months postpartum collected information on potential confounding factors. Data on breastfeeding, wheeze, and asthma were obtained from questionnaires in the third survey from 16 to 24 months postpartum. Adjustment was made for maternal age, maternal and paternal history of asthma, atopic eczema, and allergic rhinitis, indoor domestic pets (cats, dogs, birds, or hamsters), family income, maternal and paternal education, maternal smoking during pregnancy, baby's sex, baby's older siblings, household smoking in the same room as the infant, and time of delivery before the third survey. By the third survey, the cumulative incidence of wheeze and asthma was 22.1% and 4.3%, respectively. Neither exclusive breastfeeding for 4 months or more nor partial breastfeeding for 6 months or more were materially related to the risk of wheeze. No measurable association was observed between exclusive breastfeeding for 4 months or more and the risk of asthma. Partial breastfeeding for 6 months or more was inversely related to the risk of asthma although the adjusted odds ratio (OR) was not statistically significant. When infants were stratified according to whether there was a negative or positive allergic history in at least 1 parent, a nearly 40% and 60% decrease, respectively, in the ORs were found for exclusive and partial breastfeeding only in infants without a parental allergic history, although the ORs were not statistically significant. The present prospective study showed no statistically significant relationship between breastfeeding duration and the risk of wheeze or asthma in Japanese infants.

Purpose: Evidence remains inconclusive as to whether environmental tobacco smoke is a risk factor for allergic disorders in childhood. The present large-scale cross-sectional study examined the relationship between passive smoking at home and the prevalence of allergic disorders in Japanese schoolchildren., Methods: Study subjects were 23,044 children aged 6 to 15 years in Okinawa. Outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for sex, age, region of residence, number of siblings, paternal and maternal history of asthma, atopic eczema, or allergic rhinitis, as well as paternal and maternal educational level., Results: The prevalence of wheeze, asthma, atopic eczema, and allergic rhinoconjunctivitis in the previous 12 months was 10.7%, 7.6%, 6.8%, and 7.7%, respectively. Current heavy passive smoking and 7.0 or more pack-years of smoking in the household were independently related to an increased prevalence of wheeze and asthma, especially in children 6 to 10 years of age and children with a positive parental allergic history. There was no dose-response relationship between pack-years of smoking in the household and atopic eczema or allergic rhinoconjunctivitis., Conclusions: Our findings suggested that environmental tobacco smoke might be associated with an increased prevalence of wheeze and asthma in Japanese children.

Objective: It remains controversial whether the intake of n-3 polyunsaturated fatty acids and fish is preventive against asthma. This cross-sectional study investigated the relationship between fat and fish intake and the prevalence of asthma using baseline data from a prospective study., Design: The subjects were 1002 pregnant Japanese females. A diet history questionnaire was used to assess dietary habits. Current asthma and asthma after age 18 were defined as present if subjects had been treated with medications at some time in the previous 12 months and after reaching the age of 18, respectively., Results: Fish consumption was independently associated with a decreased prevalence of asthma after age 18 and current asthma. A significant inverse relationship was observed between the ratio of n-3 to n-6 polyunsaturated fatty acid intake and the prevalence of current asthma, but not asthma after age 18. Intake of total fat, saturated, monounsaturated, n-3 polyunsaturated and n-6 polyunsaturated fatty acids, cholesterol, meat, eggs or dairy products was not evidently related to either outcome for asthma., Conclusion: Our results suggest that fish consumption and the high ratio of n-3 to n-6 polyunsaturated fatty acid intake may be associated with a reduced prevalence of asthma in young female Japanese adults.

Effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial hyperresponsiveness induced by subthreshold concentration of aerosolized thromboxane A2 analogue (STA2) were investigated in anesthetized, artificially ventilated guinea pigs in order to examine the role of the cyclooxygenase pathway in bronchial hyperresponsiveness. Pretreatment with aerosolized OKY-046 significantly inhibited the bronchial hyperresponsiveness to histamine, but pretreatment with intravenous indomethacin showed a tendency to potentiate bronchial hyperresponsiveness. These results suggest that subthreshold concentration of thromboxane A2 contributes to bronchial hyperresponsiveness through activating the cyclooxygenase pathway including thromboxane A2 synthesis, and that the released cyclooxygenase products have an inhibitory effect on the bronchial hyperresponsiveness in guinea pigs.

To evaluate the effect of chronic airway inflammation on cough sensitivity and bronchial responsiveness, we measured the cough threshold to tartaric acid and bronchial responsiveness to methacholine (PC20-FEV1) in 13 asthmatic, 13 bronchitic (sino-bronchial syndrome) and 49 healthy non-atopic subjects. All subjects were non-smokers. The geometric mean value of the cough threshold was 9.55, 5.62 and 12.3% in asthmatic, bronchitic and normal subjects, respectively. The value in bronchitic subjects was significantly (p less than 0.02) lower than that in normal subjects. The geometric mean value of PC20-FEV1 in asthmatic subjects (0.63 mg/ml) was significantly lower than those in bronchitic (8.7 mg/ml) (p less than 0.01) and normal subjects (21.4 mg/ml) (p less than 0.01). There was no correlation between cough threshold and PC20-FEV1 values [correlation coefficient (r) = 0.06, p greater than 0.1]. These results indicate that cough sensitivity is potentiated by chronic airway inflammation in bronchitis but not in asthma and suggest that cough sensitivity and bronchial responsiveness may be independently potentiated by different mechanisms resulting from chronic airway inflammation.

Many reports have been published about the late asthmatic response (LAR) of animal model. But most of the animals used were sensitized actively and it is considered generally that it is impossible to generate LAR in passively sensitized animals, especially in guinea pig. About the mechanism of LAR, most discussion are focused on airway hyperreactivity, inflammation and chemical mediators. But little is known about the direct initiator of the late phase bronchoconstriction. Instead of the circulating antibody which is generated by antibody producing cells in actively sensitized animals, anti-serum was administered to guinea pigs intravenously as passive sensitization fifteen minutes prior to antigen inhalation. Four to eight hours after antigen inhalation, we investigated bronchoconstriction. Eight hours after antigen challenge, bronchoalveolar lavage (BAL) were performed. In the BAL fluid, macrophages decreased and neutrophils increased significantly. These results suggest that LAR can occur without airway inflammation and the inflammation might be the result of antigen-antibody reaction at the airway wall, and that the direct initiator of late phase bronchoconstriction might be the recruitment of homocytotropic antibody from circulating blood to the airway wall.

Bronchial hyperresponsiveness (BHR) to various stimuli is one of the major clinical features of bronchial asthma. In this study, the effect of a thromboxane A2 (TXA2) receptor antagonist, AA-2414, on BHR to methacholine was evaluated in 15 patients with asthma. The methacholine inhalation test was performed before and after oral administration of AA-2414 for 4 days (20 or 40 mg/day). The provocative concentration of methacholine producing a 20% fall in FEV1 (PC20) was measured as an index of BHR. There was a significant increase in PC20 (p less than 0.01) from 0.43 (geometric SEM, 1.42) mg/ml to 0.93 (geometric SEM, 1.43) mg/ml after 40 mg/day of AA-2414, whereas baseline values of FVC and FEV1 were not changed by the treatment. Twenty milligrams per day of AA-2414 did not alter the PC20 value nor the parameter of baseline pulmonary functions. These findings might support our hypothesis that the subthreshold concentration of TXA2 in the bronchial tissues, which has no effect on bronchomotor tone per se, may be involved in BHR in asthma. Further studies with more potent and specific TXA2 receptor antagonists are needed to confirm the conclusion.

Slow-reacting substance of anaphylaxis (SRS-A) is an important factor mediating bronchoconstriction in asthma. We developed a guinea pig model for SRS-A mediated bronchoconstriction induced by antigen inhalation. Using this model, we investigated the effect of inhaled WP871, a new anti-allergic drug, on bronchoconstriction. Aerosol WP871 (0.01 and 0.033%) to some extent inhibited the antigen-induced bronchoconstriction in a dose-dependent fashion, but high-dose WP871 (0.1%) inhalation itself produced a non-specific bronchoconstriction. However, aerosol WP871 (0.033%) showed no inhibitory effect on bronchoconstriction caused by direct inhalation of leukotriene C4, a component of SRS-A. These findings indicate that aerosol WP871 does not antagonize SRS-A, but inhibits synthesis and/or release of SRS-A and has some non-specific bronchoconstrictive effect in high concentration.

To determine whether the involvement of thromboxane A2 in bronchial hyperresponsiveness is specific to asthma, we examined the effects of a selective thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (indomethacin) on bronchial responsiveness to methacholine in patients with bronchial asthma and chronic bronchitis. The provocative concentration of methacholine producing a 20% fall in forced expiratory volume in one second (PC20-FEV1) was measured before and after oral administration of OKY-046 and indomethacin in eight asthmatic and 10 bronchitic subjects. Baseline FEV1 value was not altered by OKY-046 or indomethacin. The geometric mean value of PC20-FEV1 increased significantly (p less than 0.005) from 1.78 to 4.27 mg/ml after OKY-046 in asthmatic subjects, but not in bronchitic subjects. On the other hand, PC20-FEV1 was not altered by indomethacin in all subjects. It was concluded that the involvement of thromboxane A2 in bronchial hyperresponsiveness may be specific to asthma.

The purpose of this study was to investigate whether procaterol (beta 2 agonist) inhibits the release of cyclooxygenase products in bronchoalveolar lavage fluid (BALF) during in vivo allergic bronchoconstriction in passively sensitized guinea pigs. Antigen-induced bronchoconstriction was significantly inhibited by pretreatment with procaterol. The concentrations of 6-keto-PGF1 alpha, PGF2 alpha and TXB2 in BALF significantly decreased in guinea pigs pretreated with inhaled procaterol. The concentration of TXB2, which is the stable metabolite of TXA2, a strong bronchoconstrictor, was especially markedly decreased compared with that in the control animals. These data indicate that procaterol (beta 2 agonist) may inhibit the release of chemical mediators during allergic reactions as well as directly decrease the contractility of airway smooth muscle. Consequently, regular inhalation of procaterol may be clinically useful for prophylaxis of bronchial asthma.

Background Bacillus Calmette-Guérin (BCG) vaccination triggers a T-helper type 1 response. Whether BCG vaccination and positive tuberculin reactivity are preventive against allergic disorders remains controversial. Objective The current cross-sectional study investigated the relationship of BCG vaccination and tuberculin reactivity with the prevalence of allergic disorders using data from the Ryukyus Child Health Study (RYUCHS). Methods Subjects were 5717 schoolchildren aged 8–11 years in Okinawa, Japan. The RYUCHS collected information on symptoms of allergic disorders and potential confounding factors. The outcomes were based on diagnostic criteria from the International Study of Asthma and Allergies in Childhood. Data on BCG vaccination and tuberculin tests were obtained from school records. Allowance was made for grade, sex, sibship size, smoking in the household, paternal and maternal history of asthma, atopic eczema, and allergic rhinitis, and paternal and maternal educational level. Results No measurable relationship was found between BCG vaccination in infants and the prevalence of allergic disorders. Among 5567 BCG-vaccinated children, positive tuberculin reactivity (induration ⩾10 mm) in the first grade was independently associated with a decreased prevalence of wheeze, asthma, and atopic eczema: the multivariate odds ratios for wheeze, asthma, and atopic eczema were 0.80 (95% confidence interval [CI], 0.67–0.94), 0.78 (95% CI, 0.64–0.95), and 0.77 (95% CI, 0.62–0.95), respectively. The inverse associations were more pronounced in children with a negative parental allergic history than in those with a positive parental allergic history. There was no significant relationship between tuberculin reactivity and allergic rhinoconjunctivitis. Conclusions The findings suggest that positive tuberculin reactivity may be inversely associated with the prevalence of wheeze, asthma, and atopic eczema, but not allergic rhinoconjunctivitis, especially among Japanese children without a parental allergic history. [ABSTRACT FROM AUTHOR]