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BackgroundEvidence suggests that exposure to polycyclic aromatic hydrocarbons (PAHs) increases atopy; it is unclear how PAH exposure is linked to increased severity of atopic diseases.ObjectiveWe hypothesized that ambient PAH exposure is linked to impairment of immunity in atopic children (defined as children with asthma and/or allergic rhinitis) from Fresno, California, an area with elevated ambient PAHs.MethodsWe recruited 256 subjects from Fresno, CA. Ambient PAH concentrations (ng/m(3) ) were measured using a spatial-temporal regression model over multiple time periods. Asthma diagnosis was determined by current NHLBI criteria. Phenotyping and functional immune measurements were performed from isolated cells. For epigenetic measurements, DNA was isolated and pyrosequenced.ResultsWe show that higher average PAH exposure was significantly associated with impaired Treg function and increased methylation in the forkhead box protein 3 (FOXP3) locus (P < 0.05), conditional on atopic status. These epigenetic modifications were significantly linked to differential protein expression of FOXP3 (P < 0.001). Methylation was associated with cellular functional changes, specifically Treg dysfunction, and an increase in total plasma IgE levels. Protein expression of IL-10 decreased and IFN-γ increased as the extent of PAH exposure increased. The strength of the associations generally increased as the time window for average PAH exposure increased from 24 hr to 1 year, suggesting more of a chronic response. Significant associations with chronic PAH exposure and immune outcomes were also observed in subjects with allergic rhinitis.Conclusions and clinical relevanceCollectively, these results demonstrate that increased ambient PAH exposure is associated with impaired systemic immunity and epigenetic modifications in a key locus involved in atopy: FOXP3, with a higher impact on atopic children. The results suggest that increased atopic clinical symptoms in children could be linked to increased PAH exposure in air pollution.

Background: Parent's history of atopic traits increases the risk of the same traits in their children, but mother's history may confer an increased risk compared to father's history. Objective: To investigate parent‐specific effects on risk of developing allergic sensitization and asthma in childhood. Methods: We included 685 parent‐child trios from the Copenhagen Prospective Studies on Asthma in Childhood 2010 (COPSAC2010) cohort. Parent's asthma was assessed by structured interviews and child's asthma was diagnosed prospectively at regular visits to the COPSAC clinic until age 6. Specific IgE and total IgE levels were measured in parents and children by age 0.5, 1.5 and 6 years. Associations between parent and child disease traits were analyzed using general estimating equations model adjusted for breastfeeding and maternal smoking during 3rd trimester. Results: Maternal compared to paternal elevated specific IgE increased the child's risk of elevated specific IgE from 0‐6 years: adjusted odds ratio (aOR)mother = 1.49 [1.09‐2.03], P =.01 and aORfather = 1.32 [0.96‐1.82], P =.08. Maternal elevated total IgE also increased the child's risk of elevated total IgE: adjusted relative risk (aOR)mother = 4.32 [1.51‐10.8], P <.01, while a trend was observed for paternal total IgE: aORfather = 2.01 [0.76‐4.82], P =.13. Individual time point analyses showed that the maternal effect was strongest in early life, whereas the parental effects were comparable by age 6. A similar parent‐specific pattern was observed for the child's risk of asthma. Conclusions and Clinical Relevance: The effect of mother's history of atopic traits on the child's risk of developing the same traits in early childhood was stronger than the effect from father's history, which was not evident before age 6. This suggests that maternal non‐genetic factors seem to confer an added disease risk to the child, particularly in early life. [ABSTRACT FROM AUTHOR]

Background Reports about the increasing prevalence of atopy and atopic diseases are common, but recently they have been critically reviewed and the need for relevant research methods has been established. Objectives This study evaluated a 15-year trend in the prevalence of atopy markers [elevated total IgE, positive skin prick test (SPT) to common aeroallergens and positive atopic symptoms] in Croatian adults, separately for women and men. Methods The study included 721 subjects (445 men and 276 women), 18–45 years old, examined for allergies within a pre-employment preventive examination. All subjects underwent medical history, SPT with common inhalatory allergens and total serum IgE measurement. The trend analysis of atopy prevalence was performed after stratification of subjects into three consecutive 5-year periods from 1985 to1999. Results The prevalence of concurrently elevated total IgE and positive atopic symptoms significantly increased during the studied period in men [odds ratio (OR) 2.44, 95% confidence interval (CI) 1.39–4.29, P=0.002]. Women showed an increased prevalence of positive SPT only, with borderline significance (OR 1.65, 95% CI 1.00–2.71, P=0.050). In women, rural residence was found to be a predictor of elevated total IgE (OR 5.36, 95% CI 2.41–11.93, P=0.000) and smoking to be a predictor of concurrently elevated total IgE and positive SPT (OR 6.20, 95% CI 1.67–23.07, P=0.006). Conclusions An increasing trend in the prevalence of concurrently elevated total IgE and positive atopic symptoms was found in the Croatian adult male population between 1985 and 1999, but not in the female population. Sex differences responsible for the production and regulation of IgE were suggested. [ABSTRACT FROM AUTHOR]

Background Cough variant asthma is a phenotype of asthma solely presenting with coughing. It involves airway inflammation and remodelling as does classic asthma with wheezing, and a subset of patients may progress to classic asthma. The atopic features of cough variant asthma remain unclear. Objective To compare atopic features between patients with cough variant asthma and those with classic asthma, and to examine the possible correlation of these features with the future development of wheezing in the former group. Methods Total and specific IgE levels of seven common aeroallergens [house dust mite (HDM), Gramineae/Japanese cedar/weed pollens, moulds, cat/dog dander] were examined in 74 cough variant asthma patients and in 115 classic asthma patients of varying severity. Forty of the former patients were prospectively observed for 2 years to determine whether cough variant asthma progressed to classic asthma despite inhaled corticosteroid treatment. Results Patients with classic asthma had higher total IgE ( P<0.0001), larger numbers of sensitized allergens ( P=0.03), and higher rates of sensitization to dog dander (24% vs. 3%, P<0.0001), HDM (46% vs. 28%, P=0.02), and moulds (17% vs. 7%, P=0.047) than did patients with cough variant asthma. Wheezing developed in six (15%) patients with cough variant asthma, who were sensitized to larger numbers of allergens ( P=0.02) and had higher rates of sensitization to HDM ( P=0.01) and dog dander ( P=0.02) than the 34 patients in whom wheezing did not develop. Among the patients with classic asthma, total and specific IgE variables were similar in the subgroup with mild disease ( n=60) and the subgroup with moderate-to-severe disease ( n=55), as reported previously. Conclusions Atopy may be related to the development of wheezing in patients with cough variant asthma. To prevent the progression of cough variant asthma to classic asthma, avoidance of relevant allergens may be essential. [ABSTRACT FROM AUTHOR]

Background It is generally thought that infants with a first-degree familial predisposition of asthma are at higher risk of developing asthma than infants without predisposition. Objective To investigate whether there is an association between being at high risk for developing asthma and increased level of total IgE in newborns and whether total IgE is influenced by gender, family size, birth season, maternal smoking, birth weight, gestational age, and maternal diet. Methods Two hundred and twenty-one high risk and 308 low-risk infants were prenatally selected in a 5-year-period. Three to 5 days after birth, the total IgE was measured in capillary heel blood. Results Data on total IgE and first-degree familial predisposition were available for 170 high-risk and 300 low-risk infants. There was a statistically significant relationship between being at high-risk (maternal asthma) and increased levels of total IgE in newborns (total IgE cut-off levels: 0.6–0.9 IU/mL (odds ratio (OR)=2.1, 95% confidence interval (CI): 1.2–3.7 to 3.0, 95% CI: 1.5–5.9)), between being born in autumn and increased levels of total IgE in newborns [total IgE cut-off levels: 0.5–0.6 IU/mL (OR=2.5, 95% CI: 1.2–5.1 to 2.5, 95% CI: 1.2–5.4)] and between maternal vitamin supplements intake and decreased levels of total IgE in newborns (total IgE cut-off level: 0.9 IU/mL (OR=0.5, 95% CI:0.3–1.0)). There was no interaction between the effects of maternal asthma and birth season on total IgE, as well as between the effects of maternal asthma and maternal vitamin supplements intake. Gender, family size, maternal smoking, birth weight, and gestational age did not influence the associations. Conclusion Being at high-risk of asthma (maternal asthma) and birth season are positively associated with the presence of increased levels of total IgE at birth, whereas maternal vitamin supplements intake is negatively associated with the presence of total IgE at birth. [ABSTRACT FROM AUTHOR]

A variety of genes are related to allergic disorders in different ethnic populations. The genetic basis for the gender discrepancy of allergic diseases remains to be determined. This study was conducted to investigate whether IL-4 promoter (−590 C/T) and cytotoxic T lymphocyte antigen 4 (CTLA-4) (+49 A/G) polymorphisms were correlated with a gender discrepancy of total IgE levels and allergic diseases in a Chinese population. A total of 1333 participants aged 19–49 years were enrolled in this study. Allergic diseases were recognized by the presence of asthma, rhinitis or atopic dermatitis in conjunction with detectable specific IgE in the blood. Polymorphisms of IL-4 promoter (−590) and CTLA-4 (+49) were determined by restriction fragment length polymorphism. Males or females with allergic diseases had higher total IgE levels than those without ( P=0.000). Females with the A/A genotype in the CTLA-4 (+49) position had significantly higher total IgE levels than those with A/G, and those with the G/G genotype had the lowest IgE levels (154.9 vs. 107.1 vs. 79.8 KU/L; mean log values: 1.79 vs. 1.65 vs. 1.54, P< 0.001). However, males with different genotypes in the CTLA-4 (+49) position exhibited no difference in the total IgE levels. Females with allergic rhinitis had a significantly higher frequency of the A/A genotype in the CTLA-4 (+49) polymorphism than those without atopic diseases ( P=0.016). In contrast, males with and without allergic disorders exhibited no significant difference in the CTLA-4 (+49) polymorphisms ( P>0.05). The IL-4 promoter (–590) polymorphisms, however, had no correlation with the total IgE levels or allergic diseases in either females or males. In females only, the CTLA-4 (+49), but not the IL-4 promoter (−590), polymorphism was significantly associated with elevation of total IgE levels and allergic rhinitis. Here, we have, for the first time, demonstrated a gender-linked genetic relationship with allergic disease. [ABSTRACT FROM AUTHOR]

Summary Background Several studies in patient populations have reported a positive association between alcohol consumption and serum total IgE. Furthermore, we have previously reported a positive association between alcohol consumption and the prevalence of skin prick test (SPT positivity) to inhalant allergens in a population-based cross-sectional study. Objective To investigate the relationship of alcohol consumption to levels of serum total IgE and the development of IgE sensitization to inhalant allergens. Methods In 1990, self-reported consumption of alcohol, serum total IgE, SPT positivity and specific IgE positivity to inhalant allergens were assessed in 1112 subjects, aged 15–69 years, participating in a population-based cross-sectional study in Copenhagen, Denmark. In 1998, they were invited to a follow-up and 734 were re-examined (participation rate 69.0%). Adjustment for potential confounders was performed by using multivariable regression analyses. Results In non-atopic (specific IgE negative) subjects there was a positive association between alcohol consumption and the concentration of total IgE (P = 0.001). During the follow-up period, 45 and 33 subjects developed SPT positivity and specific IgE positivity, respectively. There was no significant association between alcohol consumption and the development of SPT positivity or specific IgE positivity. However, the risk of developing SPT positivity tended to increase with increasing consumption of alcohol (P = 0.055). Conclusions This epidemiological study confirms that alcohol consumption has an influence on levels of serum total IgE. A significant association between alcohol consumption and the development of IgE sensitization was not established. However, there seems to be a lack epidemiological data on this issue. [ABSTRACT FROM AUTHOR]

Several candidate genes have been reported to be linked to intermediate phenotypes of asthma in Caucasian populations. To evaluate linkage between phenotypes of asthma and gene markers of high affinity IgE receptor-β gene (D11S97), IL-4 cytokine gene cluster (IL-4R1), and T-cell receptor α/δ gene complex (D14S50) in Korean nuclear families. Nuclear families (127 probands and their 130 siblings) for the linkage analysis were ascertained through asthmatic children. Linkages between total serum IgE response, skin responses to common aeroallergens, and bronchial responsiveness to methacholine were performed using a sib-pair approach. The square difference of the slope of the dose–response curve (DRS) between sib-pairs with two IL-4R1 identical alleles was smaller than with one or with neither IL-4R1 identical allele (P = 0.004). As for D14S50, the differences of DRS between sib-pairs with two identical alleles and with one identical allele were smaller than with neither identical alleles (P = 0.01). As for D11S97, no significant differences were observed among the groups with identical alleles of two, one or zero. With regard to total serum IgE levels, no significant linkage was found between this phenotype and the above three gene markers. As for skin responses to common aeroallergens, significant evidence was obtained to establish a linkage between this phenotype and the marker IL-4R1 (P = 0.01). However, no significant linkage was found between this phenotype and the markers D11S97 and D14S50. The expression of bronchial responsiveness to methacholine may be influenced by genetic factors in the IL-4 cytokine gene cluster and/or T-cell receptor α/δ gene complex, but the genetic influence of the FcεRI-β gene may be minimal in the expression of bronchial responsiveness in Korean nuclear families. [ABSTRACT FROM AUTHOR]

Background Experience has shown some variation in the associations between IgE, atopy, and sensitization to platinum salts. Clarification of these associations, and the value of the parameters in predicting and diagnosing sensitization of workers at risk, required prospective investigation. Objectives Evaluation of total IgE and Phadiatop® status to establish baseline values, and changes during employment, predictive or associated with subsequent platinum salt sensitization. Methods A 24-month prospective study, in a South African primary platinum refinery, of a cohort of 78 healthy recruits without evidence of atopy (tested negative to skin prick test with common allergens). Subsequently they were categorized as 22 sensitized (positive skin prick test to platinum salts), 46 not sensitized (negative skin prick test and symptom free), and 10 symptomatic subjects not included in either category. Results (1) Pre-employment: four (18%) of the subsequently sensitized subjects and eight (17%) not sensitized were Phadiatop® positive. Levels of total IgE > 100 kU/L, present in 16 subjects were associated with positive Phadiatop® status and race. (2) During employment: Phadiatop® status converted from negative to positive in more sensitized (12/18) than unsensitized (6/38) subjects (P ≤ 0.0001). Total IgE levels at outcome had increased in more sensitized subjects, and median levels were higher than in unsensitized subjects (17 (77%) vs six (13%), and 92 vs 26 kU/L, P = 0.0015). Multivariate analysis showed the likelihood of an increase in total IgE was nine times greater in subjects sensitized to platinum salts, and five times greater with higher platinum salt exposure. Specific IgE was demonstrated, generally in only one sample of the series, in two sensitized and three unsensitized subjects. Positive responses to skin prick tests with common allergens occurred in five (23%) sensitized and 11 (24%)... [ABSTRACT FROM AUTHOR]

Background A recent study reported an association between a large head circumference at birth and adult total IgE. However, no study has yet looked at the relation between head circumference and cord blood IgE. Objectives To assess the relationship between child's cord blood total IgE and head circumference at birth taking parental allergy and smoking habits as well as placental calcifications into account. Methods Two samples of unselected newborns and their mothers with uncomplicated pregnancies were studied: 235 in study A with data on parental allergy and 99 in study B with data on placental calcifications. Results In both studies, cord blood IgE was significantly related to large head circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs ≥ 37 cm, respectively, P = 0.03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE significantly increased in mothers exposed to both active and passive smoking during pregnancy compared with other pregnant women. High cord blood IgE were associated with high maternal IgE (r = 0.38; P < 0.001). Multiple linear regression showed that large head circumference, maternal IgE and clinical manifestations of maternal, but not paternal, allergy were independently related to cord blood IgE (study A). Large head circumference and placental calcifications were independently related to a higher cord blood IgE level (study B). Conclusions Besides the role of genetic factors, results on the preferential role of maternal vs paternal allergy and associations to large head circumference and placental calcifications support the hypothesis of the role of environmental factors during pregnancy on the level of cord blood IgE. [ABSTRACT FROM AUTHOR]

BackgroundWe have started a large birth cohort study in which pregnant women with and without atopy are differentially included. In view of the large number of subjects to be screened (12 000), a simple questionnaire was developed for the assessment of atopy in pregnant women. ObjectiveThe objective of our study was to evaluate the efficacy of a questionnaire using serum IgE tests. MethodsDuring a antenatal visit to the midwife clinic, 175 expecting mothers completed a questionnaire and from each subject blood was obtained in which total and specific IgE against house dust mite, cat, dog, birch and grass was determined. ResultsWhen atopy was defined as the presence of a positive test for IgE against at least one allergen, seven questions from the questionnaire had a sensitivity and specificity of 55.0% and 88.7%, respectively. With the use of the questionnaire it was possible to select about 50% of the subjects with specific IgE to one or more common inhalant allergens. The positive predictive value of the screening questions was 71.7%. Taking total IgE into account did not change these results. ConclusionThe screening questionnaire is an efficient tool for differential inclusion of subjects with and without atopy in epidemiological studies. [ABSTRACT FROM AUTHOR]

Background Studies in children have shown that family size is negatively associated with atopy and atopic disease. Objective To describe the association of family size with atopy and atopic disease in young adults. Methods A randomly selected sample of 1159 men and women aged 20-44 years provided information on respiratory symptoms, hay fever and eczema. Blood samples were taken for assessment of total IgE and specific IgE to house dust mite, grass, cat, Cladosporium and birch. The association of family size and birth order with respiratory symptoms, atopy and total IgE was assessed by multiple logistic and linear regression. Results There was a negative association between family size and the reporting of 'wheeze with breathlessness' (adjusted odds ratio for an increase of one sibling 0.85; 95% confidence interval 0.75-0.98), 'wheeze without a cold' (adjusted odds ratio for an increase of one sibling 0.85; 95% confidence interval 0.75-0.98) and 'asthma attacks' in the last 12 months (adjusted odds ratio for an increase of one sibling 0.77; 95% confidence interval 0.61-0.97), current 'hayfever and nasal allergies' (adjusted odds ratio for an increase of one sibling 0.84; 95% confidence interval 0.75-0.94) and sensitization to grass (adjusted odds ratio for an increase of one sibling 0.87; 95% confidence interval 0.76-0.99). Birth order was negatively associated with 'hayfever and nasal allergies' only. A decreased risk of sensitization to grass in those from large families did not fully explain the negative association between family size and hayfever. No statistically significant (P > 0.05) association of family size or birth order with the reporting of other respiratory symptoms, eczema, sensitization to the other allergens or total IgE was observed. Conclusion There is a negative association between family size and some symptoms suggestive of asthma, 'hayfever and nasal allergies' and sensitization to grass in young adults. There is no consistent, significant association between family size and eczema, total IgE or sensitization to other allergens. [ABSTRACT FROM AUTHOR]

Background: Smoking has been identified as a risk factor for atopy but there are difficulties in interpreting many of the previous studies because the subjects who have been studied have not been representative of the entire population and because there is confounding between gender and smoking. Objective To investigate the association of age, gender and smoking with total IgE and specific IgE to house dust mite, grass and cat. Methods A stratified random sample of 20–44 year olds living in three centres in East Anglia and registered with a local general practitioner had blood taken for total immunoglobulin E (IgE) and specific IgE. A smoking history was obtained from a structured interviewer-led questionnaire. Results Among non-smokers geometric mean total IgE was higher in men than women but unrelated to age. Smoking explained less than 1% of the variation in total IgE. Smoking was associated with an increased risk of sensitization to house dust mite (odds ratio 1.59; 95% confidence interval 1.02–2.48) but a decreased risk of sensitization to grass (odds ratio 0.45; 95% confidence interval 0.28–0.71) and cat (odds ratio 0.47; 0.24–0.94). Conclusion: Men aged 20–44 years have higher total IgE levels than women of the same age. In young adults smoking explains little of the variation in total IgE and its association with sensitization to common allergens varies between allergens. [ABSTRACT FROM AUTHOR]

Summary Background Previous studies have shown that IgE levels vary according to factors such as age, gender and smoking but most studies have been small and none have been based on a nationally representative sample. Objectives To investigate the influence of epidemiological factors on serum total IgE and house dust mite-specific IgE levels. Methods An interviewer-led questionnaire was carried out and blood samples taken from 24 952 people aged 11 and over as part of the 1995 and 1996 Health Surveys for England. Serum total IgE and house dust mite-specific IgE were measured. Results Both total and house dust mite-specific IgE were more frequently raised in men and in younger age groups. After adjusting for age and sex, raised total IgE was more common in current smokers and non-white ethnic groups and was not related to social class. The higher levels in non-white ethnic groups was not explained by smoking, urban living or being born outside the UK. Whilst total IgE levels declined in older age groups in non-smokers, among smokers they increased across successive age groups from 50 years onwards. In contrast, following adjustment for age and sex, raised house dust mite IgE was more common in non-manual workers and in some non-white ethnic groups but was not related to smoking. Conclusions This large nationwide study provides further confirmation of differing epidemiological patterns for total serum IgE and allergen-specific sensitization. Indicative ranges for ‘usual’ values for a wide range of ages among men and women in England are given. [ABSTRACT FROM AUTHOR]