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PubMed2003

Polymorphisms in the interleukin-4 and interleukin-4 receptor alpha chain genes confer susceptibility to asthma and atopy in a Caucasian population.

BACKGROUND: IL-4 by binding to its receptor (IL-4R) is essential for the development of airway inflammation present in asthma, through the induction of IgE synthesis in B cells and differentiation of T cells to a Th2 phenotype. OBJECTIVE: To investigate the role of four common polymorphisms in the IL-4 (IL4-34CT and IL4-589CT) and IL-4Ralpha chain (IL4RAI50V and IL4RAQ576R) genes in conferring susceptibility to the development of atopy and/or asthma. METHODS: Two polymorphisms in the IL-4 gene promoter, IL4-34CT and IL4-589CT, and two polymorphisms in the IL-4Ralpha chain gene, IL4RAI50V and IL4RAQ576R, have been genotyped using PCR-based methods in 341 asthmatic families and in 184 non-asthmatic adults recruited from the south of England. RESULTS: Case-control analysis did not reveal differences in the distribution of the four polymorphisms between asthmatics and controls. However, the transmission disequilibrium test showed that the IL4-589 T allele was preferentially transmitted to asthmatic children (P=0.036) and that the IL4RAQ576 was preferentially transmitted to children with atopic asthma (P=0.018). Haplotype analysis showed a strong association between the IL4-34T/-589T haplotype and asthma per se (P=0.041), and a strong association between the IL4RA I50/Q576 haplotype and atopic asthma (P=0.006). CONCLUSION: Our data suggest that polymorphisms in the IL-4 and IL-4Ralpha chain genes might play a role both conferring susceptibility to and modulating severity of atopy and asthma.

Adolescent↗
PubMed2003

Intake of unsaturated fatty acids and HDL cholesterol levels are associated with manifestations of atopy in adults.

BACKGROUND: The increase in allergic diseases is still unexplained. It was hypothesized that the intake of unsaturated fatty acids is a contributing cause of this development. We investigated the relationship between serum cholesterol levels, intake of polyunsaturated fatty acids (PUFA) and manifestations of atopy in a population-based setting. METHODS: A nested case-control study was performed within the population of the 3rd MONICA survey in Augsburg (Germany). The serum levels of total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol of 1537 adults (aged 28-78 years, response 61.4%) and the estimated intake of PUFA in a subset of 139 men were compared with the frequency of a doctor's diagnosis of asthma, allergic rhinoconjunctivitis (AR), atopic eczema (AE) and allergic sensitization as measured by skin prick and Radio Allergo Sorbent Test. FINDINGS: In bivariate analyses, we obtained a negative linear association between total and LDL cholesterol levels and the frequency of AR and sensitization, which was no longer significant after adjustment for important confounders. In contrast, positive linear associations were found between HDL cholesterol levels and AR and AE and, furthermore, between the intake of PUFA and allergic sensitization in men (P<0.01). After adjustment, an increasing risk for atopic diseases with increasing levels of HDL cholesterol and an increasing risk for allergic sensitization with increasing intakes of PUFA remained statistically significant. INTERPRETATION: There is indication that HDL cholesterol also plays a role in the complex interaction of fat intake, metabolism and the manifestation of atopy in adults. These findings may contribute to the understanding of time trends and regional differences of allergies.

Adult↗
PubMed2003

Levels of soluble CD30 in cord blood and peripheral blood during childhood are not correlated with the development of atopic disease or a family history of atopy.

BACKGROUND: The CD30 molecule has been linked to Th2 responses. Furthermore, elevated levels of the soluble form of CD30 (sCD30) in blood as well as of the expression of CD30 on the plasma membrane of T cells are associated with atopic disease. OBJECTIVE: To assess the potential usefulness of sCD30 levels as a prognostic indicator of and/or diagnostic marker for the development of atopic disease in children. METHODS: sCD30 levels in cord blood and peripheral blood from 36 2-year-old (10 atopic and 26 non-atopic) and 74 7-year-old (35 atopic and 39 non-atopic) children were determined employing an ELISA procedure. Atopy was diagnosed on the basis of clinical evaluation in combination with a positive skin prick test. RESULTS: No significant correlation between sCD30 levels in cord blood and the development of atopic disease at 2 or 7 years of age was observed. At 7 years of age, the circulating sCD30 levels in children with atopic disease (median 41 U/mL, range 6-503 U/mL) did not differ from the corresponding values for non-atopic subjects (median 41 U/mL, range 8-402 U/mL). The same was true for children at 2 years of age. Furthermore, the sCD30 levels of children who had developed atopic eczema/dermatitis syndrome by the age of 7 years (median 49 U/mL, range 14-503 U/mL) were not significantly elevated in comparison with those of the non-atopic children. Finally, neither sCD30 levels in cord blood nor peripheral blood at 2 or 7 years of age could be linked to a family history of atopy. CONCLUSION: These findings indicate that the sCD30 concentration in cord blood is not a reliable prognostic indicator of, nor a useful diagnostic marker for, atopic disease in children up to 7 years of age. If such correlations do exist, they might be masked by age-dependent variations in the circulating levels of sCD30, which may reflect individual differences in the maturation of children's immunological responses.

Aging↗
PubMed2000

Common polymorphisms and alternative splicing in the ILT3 gene are not associated with atopy.

Recently, a linkage of the chromosomal region 19q13.4 with bronchial asthma has been demonstrated. This region harbours the so-called leucocyte receptor cluster with the gene for immunoglobulin-like-transcript 3 (ILT3) as a member. ILT3 represents an inhibitory receptor bearing three immunoreceptor tyrosine inhibitory motifs (ITIM). The protein mediates downregulation of cell activation through recruitment of different SH2-containing protein tyrosine phosphatases. With regard to the negative immunoregulatory function particularly on B-cells, ILT3 represents a candidate gene for atopy and asthma. The aim of this study was to screen for common polymorphisms in the gene coding for ILT3 and to test for association with the atopic phenotype. Using single-stranded conformal polymorphism-analysis and direct genomic sequencing seven polymorphisms, three mutations, a common deletion of 7 bp in the third intron and evidence for further alternative splicing of the ILT3 gene were found. Although no association was found with atopy phenotypes, it might prove useful to test for association with bronchial asthma.

Adolescent↗
PubMed2002

Serum eosinophil cationic protein (S-ECP) in a population with low prevalence of atopy.

The study is a part of the European Community Respiratory Health Survey. A random sample (n = 351) of 20-44-year olds and persons of the same age with asthma-like symptoms or current asthma medication according to a postal questionnaire (n = 95) were studied. Interview was taken, methacholine challenge was done and ECP, total and specific IgE were measured from serum. The median S-ECP value was 8.0 micrograms/l in the random sample. The geometric mean of S-ECP was higher in subjects with, than without atopy (10.2 vs 8.9 micrograms/l, P < 0.01) and in subjects with bronchial hyperresponsiveness (BHR) than in subjects without BHR (9.9 vs 8.0 micrograms/l, P < 0.01). The levels correlated weakly to forced expiratory volume in one second (FEV1) (r = 0.13, P < 0.01) and were not independently correlated with respiratory symptoms, asthma or FEV1 after adjusting for BHR, IgE, sensitisation and smoking. Our results indicate that the level of eosinophil activation is low in a population with a low prevalence of atopy, even when BHR is common.

Adult↗
PubMed2003

Reversibility to a beta2-agonist in COPD: relationship to atopy and neutrophil activation.

Chronic obstructive pulmonary disease (COPD) is characterised by limited bronchial reversibility and chronic neutrophilic inflammation. However, in some cases of COPD, eosinophilic inflammation is present. We investigated the relationship between reversibility to beta2-agonist with atopy and neutrophil activation in patients with stable COPD. For this purpose, 38 outpatients with COPD (mean age: 64 years) 12 with asthma (mean age: 51 years) and 13 healthy controls (mean age: 49 years) were tested using increasing doses of inhaled salbutamol (up to 3100 microg). According to their reversibility, COPD patients were divided into two groups: reversible COPD (deltaFEV1 > or = 12% pred, n = 16) and non-reversible COPD (deltaFEV1 < 12% pred, n = 22). Atopy, assessed by skin prick, was found at similar frequencies in both COPD groups. Total serum IgE was higher in COPD patients vs. controls, but did not differ significantly between the COPD groups. The blood eosinophil count was significantly higher in the reversible COPD group than in the non-reversible COPD, and correlated with deltaFEV % pred (Rs = 0.54, P < 0.05), as well as in asthmatics. The non-reversible COPD group had a higher level of spontaneous neutrophil activation (by reduction of nitroblue tetrazolium) versus controls. We conclude that airway reversibility in COPD patients is associated with the degree of blood eosinophilia, but not with the degree of blood neutrophil activation.

Adrenergic beta-Agonists↗
PubMed2004

Prevalence of asthma and atopy in Italian Olympic athletes.

This study aimed to assess the prevalence of asthma and atopy in the Italian athletes who were trying for a position on the Italian Olympic team for the 2000 Sydney Olympic Games. Overall, 1060 athletes (mean age 24 years, range 15 - 69 years, 729 males) were recruited and divided into three groups of sport activities: 1) anaerobic, 2) aerobic-anaerobic, 3) aerobic. Asthmatic and atopic athletes were identified by a self-administered, standardized questionnaire modified from the ISAAC questionnaire. Spirometry was performed in the athletes who reported wheezing or asthma and in an equal number of randomly selected controls. Athletes reporting wheezing or asthma were 15 %. However, only a minority of asthmatics had moderate or severe disease: indeed, 2.5 % reported more than 4 attacks in the last year. The prevalence of atopy was 18 %. Asthma was more common in athletes engaged in aerobic sport activities than in the other groups. Asthmatic athletes had a significantly lower value of some spirometric parameters in comparison with the control group. In conclusion, the prevalence of wheezing or asthma in a large sample of Italian competitive athletes was found higher than in general population; respiratory symptoms were more prevalent in athletes engaged in aerobic sport activities; a significant impairment of lung function was found in athletes suffering from mild and rarely symptomatic asthma.

Adolescent↗
PubMed2001

Factor analysis of asthma and atopy traits shows 2 major components, one of which is linked to markers on chromosome 5q.

BACKGROUND: A variety of definitions of asthma and atopy traits have been used in genetic studies. The variables used may be correlated, increasing the likelihood of type I error. OBJECTIVE: We sought to clarify and quantify phenotypes that may be characterized by related traits. Principal components and factor analysis were applied to the correlation matrix of asthma and atopy traits before linkage analysis. METHODS: Factor analysis was performed on 468 Hispanic and non-Hispanic white children enrolled in the Tucson Children's Respiratory Study, with complete information on 24 items, including skin test response to 7 allergens, total serum IgE levels, presence or absence of asthma attacks, wheezing episodes, hay fever, and cough. Factor score coefficients were then applied to all siblings (n = 877), and quantitative factor scores were derived. Single-point and multipoint nonparametric sib-pair analyses were performed to assess linkage to markers on chromosome 5q31-33. Analyses were also performed for individual items. RESULTS: Two main factors were identified: Factor I had high loadings on atopic items, including skin test responses, IgE, and hay fever, and Factor II had high loadings that included asthma diagnosis, wheezing, cough, and Alternaria species skin test response. Factors I and II were correlated at an r value of 0.19. For the quantitative factor scores, significant single-point linkage (P < .0001) was demonstrated only for atopic Factor I, and a peak multipoint LOD score of 2.7 was seen for marker D5S479. Multipoint LOD scores for individual items were 1.1 or less. CONCLUSION: These analyses suggest evidence for a locus or loci mapping to chromosome 5q31-33 associated with this composite atopic phenotype.

Asthma↗
PubMed2002

Array-based diagnostic gene-expression score for atopy and asthma.

Whether gene expression is useful in discriminating different atopic phenotypes is unclear. The aim of the study was to evaluate a gene-expression score for the diagnosis of atopy and asthma and to assess disease activity as a guide for therapeutic decisions. Purified mRNA from PBMCs of 18 atopic asthmatic subjects, 8 atopic nonasthmatic subjects, and 14 healthy control subjects was hybridized to cDNA membranes. A composite atopy gene expression (CAGE) score was determined by using 10 genes dysregulated in atopic individuals according to a specific algorithm. The CAGE score was better than total IgE in differentiating atopic from nonatopic subjects (sensitivity, 96%; specificity, 92%). Correlation between the CAGE score and total IgE (P <.001) was found, and there was a trend for correlation with asthma severity (P =.051). The CAGE score was able to quantify phenotype-specific alteration in gene expression of atopic individuals. The CAGE score might be used as a diagnostic tool or to monitor the effects and side effects of therapy.

Adolescent↗
PubMed2002

Maternal stress and T-cell differentiation of the developing immune system: possible implications for the development of asthma and atopy.

The constant increase in asthma and atopy prevalences--despite improved treatment and knowledge of many aspects of the diseases--has raised growing concern. Accumulating evidence suggests that these increases in atopic diseases are largely attributable to environmental and lifestyle factors, and the lack of systemic childhood infections has in many studies emerged as a major factor. In addition to current high standards of hygiene and the lack or scarcity of such infections, another factor characteristic of our present-day lives could be involved. This review briefly outlines the possibility that prolonged maternal stress associated with sustained excessive cortisol secretion could affect the developing immune system--especially T(H)1/T(H)2 cell differentiation--and further increase the susceptibility to asthma and atopy in genetically predisposed individuals. This hypothesis is critically evaluated in the light of current knowledge.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2002

Importance of chamber size for the outcome of atopy patch testing in children with atopic dermatitis and food allergy.

Because the small backs of young children offer little space for atopy patch testing, it would be helpful to use smaller chambers. We therefore compared 6-mm chambers with the 12-mm chambers used in previous studies. We performed 55 double-blind, placebo-controlled food challenges in 30 children (17 boys, 13 girls) aged 3 to 58 months (median, 13 months). Sensitivity, specificity, positive predictive value, negative predictive value, and efficiency results show that the 12-mm chamber size yields much better results than the 6-mm chamber size. Therefore, 12-mm cups should be used for atopy patch tests with food, even in infants and small children.

Allergens↗
PubMed2002

Atopy, asthma, and antibodies to Ascaris among rural and urban children in Kenya.

OBJECTIVE: The purpose of this study was to evaluate differences in the relationship between asthma and immune responses to allergens in children living in rural and urban areas of Kenya. STUDY DESIGN: Children (mean age, 11 years) from Kabati (n = 136), a rural village, and Thika (n = 129), a small town, were studied by skin testing and serum immunoglobulin E (IgE) and immunoglobulin G (IgG) antibody measurement. Asthma was evaluated by symptoms, as well as spirometry before and after vigorous exercise to test for exercised-induced bronchospasm (EIB). School children from a study performed in Atlanta, Georgia, were used for comparison of anthropometric and immunologic results. RESULTS: Compared with the urban area of Kenya, children living in the rural area had a lower percentage of body fat, smaller and fewer skin test responses to allergens, a higher prevalence of IgE antibodies to Ascaris (67% vs 26%) and 10-fold higher total IgE. In the urban area of Kenya, there was a strong correlation between EIB and atopy determined both by IgE antibodies (P =.02) and skin tests (P =.002). By contrast, in the rural area, none of the 13 children with EIB were skin-test positive (vs 13/109 of children without EIB). CONCLUSIONS: Among the rural children, there was no association between immune responses to allergens and airway-related symptoms or reactivity. The association between asthma and atopy seen in the town of Thika may represent an important step in the increase in asthma seen both in urban Africa and in the West.

Adolescent↗
PubMed2000

Effects of indoor painting and smoking on airway symptoms in atopy risk children in the first year of life results of the LARS-study. Leipzig Allergy High-Risk Children Study.

INTRODUCTION: The Leipzig Allergy High-Risk Children Study (LARS) is a prospective nested cohort control study about the influence of chemical indoor exposure in dwellings on the health outcome of atopy-risk children during the first years of life. DESIGN AND METHODS: 475 premature children and children with allergic risk factors have been selected out of the 1995/1996 birth cohort in the city of Leipzig. Twenty-five volatile organic compounds (VOC) were measured in the infant's bedrooms using passive sampling systems for 4 weeks after birth. The babies underwent a medical examination at the age of six weeks and 1 year. The parents answered a questionnaire. RESULTS: Correlations between VOC exposures and infections were calculated by multiple logistic regression. Selected VOC show a direct association to actually painted dwellings (OR = 2.4; 95% Cl 1.1-5.3). An increase of risk of pulmonary infections was observed in infants aged 6 weeks if restoration (painting OR 5.6; 95% Cl 1.3-24.0) or flooring connected with painting had occurred during the pregnancy period. Higher concentration of styrene (> 2.0 micrograms/m3, indicator for flooring) elevated the risk of pulmonary infections in six-week-old infants (OR = 2.1; 95% Cl 1.1-4.2). Environmental benzene > 5.6 micrograms/m3 increased the risk of airway infections in six-week-old babies (OR = 2.4; 95% Cl 1.28-4.48). Smoking in the dwelling (OR = 2.0; 95% Cl 1.1-3.5) as well as restoration (OR = 1.9; 95% Cl 1.1-3.5) are also risk factors of the development of wheezing in the one-year-old child. CONCLUSIONS: The data give indications in order to prevent allergies and chronic lung diseases in atopy risk children exposure to chemicals from indoor air should be minimised from birth on.

Air Pollution, Indoor↗
PubMed2003

Genetics of inflammation and atopy.

Multiple chromosomal regions and polymorphisms of several candidate genes have been linked to or associated with atopic diseases (hayfever, asthma, allergic eczema and rhinitis). In this mini-review, we present data demonstrating that the genetic regulation of the inflammatory response makes a major contribution to the risk of atopy. These data also suggest that the quantity (or quality) of the inflammation affects the priming phase of atopy, i.e., that induced by allergens or infectious agents in early childhood.

Antigen-Presenting Cells↗
PubMed2005

Elevated atopy in healthy obese women.

BACKGROUND: Allergic disorders, including asthma, have increased dramatically in the United States in the past 20 y. Epidemiologic studies have found body mass index (body weight in kg/height squared in m) to be a positive independent correlate of atopy in women but not in men. OBJECTIVE: We investigated the prevalence of atopy among healthy obese and nonobese women and its relation to fat mass (FM), insulin resistance, and plasma concentrations of 17beta-estradiol, interleukin 4 (IL-4), and leptin. DESIGN: A cross-sectional study of 21 obese (> or = 30% body fat) and 22 nonobese (< 30% body fat) women (18-41 y of age) was performed. The following measurements were taken: FM by plethysmography, total and specific immunoglobulin E (IgE) by automated immunosorbent analysis, and blood glucose, insulin, C-peptide, 17beta-estradiol, sex hormone-binding globulin, and IL-4. Insulin sensitivity was determined on the basis of the fasting insulin resistance index and with an oral-glucose-tolerance test. RESULTS: The frequency of specific IgE in the obese group was almost 3 times that in the nonobese group (P = 0.008). The total IgE concentration was not significantly different between groups. Plasma concentrations of 17beta-estradiol, the ratio of 17beta-estradiol to sex hormone-binding globulin, the fasting insulin resistance index, and C-peptide and leptin concentrations were higher in the obese than in the nonobese group (P < 0.05) after adjustment for oral contraceptive use. All factors correlated positively with FM. Logistic regression showed FM to be the only positive predictor of specific IgE (P = 0.01). CONCLUSION: The findings confirm a direct relation between obesity and a T helper 2 cell immune response in women.

Adipose Tissue↗
PubMed2003

Allergy, atopy, and cancer: a prospective study of the 1981 Busselton cohort.

The associations among certain allergic disorders, atopy upon skin-prick testing, and specific cancers were evaluated in a prospective study. Information regarding history of asthma and hay fever was collected by questionnaire from 3,308 cancer-free participants in the 1981 Busselton Health Survey. A subset of 1,005 participants also underwent skin-prick testing. The cohort was followed for a new diagnosis of cancer or death until the end of 1999. Cox proportional hazards regression analysis was used to estimate adjusted hazard ratios (relative risks) for breast, prostate, colorectal, lung, and hematologic cancers and melanoma. Having a skin reaction to house dust mites nearly tripled the risk of prostate cancer (relative risk = 2.90, 95% confidence interval: 1.26, 6.68). History of asthma and hay fever were associated with a trend toward a reduced risk of colorectal cancer and increased risk of leukemia, but these results were not statistically significant. Hay fever was associated with melanoma risk in men but not in women. No association was found between breast and lung cancers and allergic disorders or atopy.

Allergens↗
PubMed1978

Frequency of atopy and allergy in an anaesthetic patient population.

Ten thousand patients presenting for anaesthesia in the British Isles were questioned about a possible history of atopic or allergic disorders. The overall percentage frequency of atopy was 8.5, comprising eczema 2.4, hay fever 3.8 and asthma 3.5. The frequency of allergies was 13.5, of which penicillin was the most common (6.2). Females had a significantly greater frequency of atopy or allergy than males. Patients with a history of atopic disorders had a higher frequency of allergies than the non-atopic group (36.2% compared with 11.4%) and vice versa.

Adolescent↗
PubMed1994

A 2.8 Mb YAC contig in 11q12-q13 localizes candidate genes for atopy: Fc epsilon RI beta and CD20.

An important locus for Atopy (familial asthma, hay fever and eczema) has been localized to the 11q12-q13 region with the minimum recombination fraction around the CD20 gene. We have constructed a 2.8 megabase (Mb) Yeast Artificial Chromosome (YAC) contig of the candidate region using 15 STSs. A total of seven genes have been mapped within this interval in the order cen-OSBP-TCN1-GIF-Fc epsilon RI beta-CD20-CD5-PGA-q(ter) and can be covered by a minimum of eight YAC clones. Contig integrity was assayed with fluorescence in-situ hybridization (FISH) and the mapping of YAC ends on somatic cell and radiation hybrid panels. A long range restriction map of the contig has been constructed to establish the order of and distance between loci. Two promising candidates for the atopy locus, the beta subunit of the high affinity immunoglobulin E receptor (Fc epsilon RI beta) and CD20, a molecule involved in B cell differentiation, have been placed within the contig.

Antigens, CD↗