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PubMed2002

Fever episodes in early life and the development of atopy in children with asthma.

The hygiene hypothesis proposes that declining exposure to infections may contribute to the allergy and asthma "epidemic", but studies to identify the infections involved have so far provided conflicting data. An alternative approach could be based on an attempt to identify the mechanisms common to several different infections, which may exert an atopy "protective" effect. One of these mechanisms may be fever, which is frequently associated with infections and may stimulate the synthesis of interferon-gamma. The aim of this study was to test whether the frequency of fever episodes in the first years of life are related to the development of atopy. Asthmatic (cases, n=317) and nonasthmatic children (controls, n=304) attending the outpatients' allergy clinic were enrolled. The number of fever episodes in the first 2 yrs of life was retrospectively assessed by parental report via a questionnaire completed by interview. Atopy was determined by skin-prick tests to 10 prevalent inhalant allergens at the time of examination. Fever episodes in the first or in the second year of life were significantly more frequent among children with asthma. However, this difference was totally accounted for by a subgroup of children who started wheezing in the first 12 months of life. A significant inverse association between fever episodes in the first 12 months of life and atopy was found among cases, but not in controls. The association persisted after adjusting for age, sex, daycare attendance and family history of atopic disease and this was totally accounted for by asthmatic children who started wheezing after the first 12 months of life. No significant association was found between fever episodes in the second year of life and atopy for cases and controls. The data presented here suggests that fever episodes early in life may affect the natural history of asthma by preventing the development of atopy and highlights the need to monitor fever episodes of any kind in longitudinal studies aimed at investigating the hygiene hypothesis prospectively.

Adolescent↗
PubMed2005

IgA antibodies, TGF-beta1 and -beta2, and soluble CD14 in the colostrum and development of atopy by age 4.

Specific defense factors in breast milk together with length of breast-feeding and genetic predisposition may modulate the development of allergy. We studied whether IgA, soluble CD14 (sCD14), or transforming growth factor (TGF)-beta in colostrum could affect the development of atopy in children up to age 4. From a cohort of 4676, we selected four groups of children with either long or short exclusive breast-feeding (>3.5 or <0.5 mo); these groups further differed in the presence or absence of atopic heredity. In colostrum from mothers, we measured total IgA, IgA antibodies to cow's milk (CM) and casein, sCD14, and TGF-beta1 and -beta2. The children were divided into three groups: those with no atopic symptoms or IgE, those with allergic symptoms, and those with both outcomes. Mothers of infants later showing atopic symptoms or, in addition, having IgE sensitization (verified atopy) had a lower concentration of IgA casein antibodies in their colostrum than did mothers of infants with no indication of atopy at age 4. Low concentration of IgA casein antibodies was a significant risk for verified atopy. sCD14 levels were lower in colostrum of mothers with infants developing atopic symptoms and IgE sensitization than of those of infants with no atopy. Specific IgA antibodies to CM antigens and sCD14 in colostrum significantly associated with the appearance of both symptomatic and verified atopy by age 4.

Animals↗
PubMed2000

Impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic teenagers.

AIM: To investigate the impact of airway lability, atopy, and tobacco smoking on the development of asthma-like symptoms in asymptomatic subjects. METHODS: In this prospective, community-based study, 271 asymptomatic adolescents with an average age at inclusion of 13.9 years were followed for 6.4 years. Airway lability was assessed at baseline by three tests, including exercise challenge, airway provocation with methacholine, and monitoring of peak expiratory flow. Atopy was defined by one or more positive reactions (> or = 3-mm weal) to 10 common aeroallergens by skin prick testing. The influence of airway lability, atopy, and smoking on the development of asthma-like symptoms was assessed by logistic regression. RESULTS: During the 6-year study period, 68 of the previously asymptomatic teenagers (25%) developed asthma-like symptoms. Among those, 50% reported cough only, 29% reported wheezing only, and 21% reported both wheezing and coughing. Hyperresponsiveness to methacholine (odds ratio [OR], 3.5; 95% confidence interval [CI], 1.1 to 11.6), smoking (OR, 2.1; 95% CI, 1. 2 to 3.8), and atopy (OR, 3.5; 95% CI, 1.8 to 6.8) each contributed independently to explain symptom development (wheezing and cough together). Girls, but not boys, with airway lability were less likely to take up smoking, compared with subjects of that set with no airway lability (32% vs 51%; p < 0.05). No effect of airway lability on the likelihood of giving up smoking could be demonstrated, nor did the presence of atopy have any significant impact on smoking behavior. CONCLUSION: Hyperresponsiveness to methacholine, atopy, and smoking were independent risk factors for the development of asthma-like symptoms during adolescence. The presence of airway lability may prevent girls from taking up smoking.

Adolescent↗
PubMed2001

Results of intradermal tests in horses without atopy and horses with atopic dermatitis or recurrent urticaria.

OBJECTIVE: To compare results of intradermal tests (IDT) for environmental allergens at 30 minutes and 4, 6, and 24 hours after injection in horses without atopy and horses with atopic dermatitis (AD) or recurrent urticaria (RU). ANIMALS: 22 horses without atopy, 10 horses with RU, and 7 horses with AD. PROCEDURE: In all horses, medical history was obtained, and results of physical examination, hematologic examination, serum biochemical analyses, examination of bronchoalveolar lavage fluid, and IDT with 73 allergens were examined. RESULTS: Horses with AD or RU had a significantly greater mean number of positive reactions for IDT, compared with horses without atopy. Horses with AD had a significantly greater number of positive reactions than horses without atopy in every allergen group at all time periods, except for molds at 4 and 24 hours. Horses with RU had a significantly greater number of positive reactions than horses without atopy in every allergen group, except for molds at 30 minutes and 4 and 6 hours, trees at 4 and 6 hours, and grasses at 4 hours. CONCLUSIONS AND CLINICAL RELEVANCE: A significantly greater number of positive reactions for IDT in horses with AD or RU, compared with horses without atopy, provides evidence of type-I IgE-mediated hypersensitivity for these diseases. Evaluation of results of IDT performed in horses with AD or RU is useful in determining specific allergens for the formulation of immunotherapy along with providing identification of allergens that could be useful when creating avoidance strategies.

Allergens↗
PubMedDate not supplied

Atopy in childhood and diet in infancy. A nine-year follow-up study. I. Clinical manifestations.

A national program for the prevention of atopy in children has been in progress in Finland since 1979. Its aim is to prevent or at least to reduce atopic symptoms in childhood. Since the start of the program we have followed a group of 119 children with and without a family history of atopy. Half the atopy-prone children kept to the diet intended to prevent atopy, i.e., breast-feeding prolonged up to age 3 months and introduction of solid food and formulae based on cow's milk after age 3 months. All children were examined at ages 5 and 10 years. In addition to clinical examination and interview, skin-prick tests using eight common inhalant allergens were performed. At age 9 to 10 years, 38 of the 119 children (32%) exhibited at least one atopic illness (bronchial asthma, allergic rhinitis, allergic conjunctivitis, atopic eczema or food allergy). Forty percent of children with family histories of atopy had atopic illness, independent of diet in infancy. The occurrence of atopic manifestations in the children of nonatopic families was 21%. Only half the children who had atopic symptoms at age 12 months had symptoms 9 years later. Asthma, allergic rhinitis, and positive skin-prick test results at age 5 years, however, correlated well with the subsequent occurrence of respiratory allergy. Our observations indicate that the preventive measures in early infancy intended to reduce the risk of atopy had no influence on atopic manifestations 9 years later.

Child↗
PubMed1999

[Atopy and interleukin-4 receptor].

Both IL-4 and IL-13 induce IgE synthesis in B cells by binding to their functional receptors on target cells. These receptors are considered to be composed of heterodimers and both share the IL-4R alpha chain (IL-4R alpha) as a component. Atopy is an inherited tendency, underlying asthma, rhinitis and eczema, and generating high nonspecific IgE and/or high specific IgE against common antigens. Based on findings concerning the molecular mechanism of the signal transduction of IL-4 and IL-13, IL-4R alpha was considered a gene that gave rise to atopy. One polymorphism in the IL-4R alpha gene, Ile50Val, has been correlated with atopy by both genetic and functional assessment. The strategy used in these studies should lead to identification of other genes involved in atopy. Furthermore, these studies should be useful for gene diagnosis of atopy and development of new therapies for atopy in the future.

Humans↗
PubMed2000

Ethnic differences in genetic susceptibility to atopy and asthma in Singapore.

INTRODUCTION: Asthma and atopy are complex traits, the phenotypes being influenced by the interaction of both genetic and environmental factors. In view of the growing evidence for inter-ethnic differences in genetic susceptibility to complex diseases such as asthma and atopy, we have assessed genetic factors for these diseases in the local population. METHODS: The genetic analysis of asthma and atopy is being approached by candidate gene analysis as well as linkage studies for mapping of susceptibility loci. We reviewed published studies, which include data from our population on some candidate genes, as well as our preliminary data on susceptibility locus mapping for linkage to chromosome 5q31-33. RESULTS: In local studies of the interleukin-4 receptor and tumour necrosis factor polymorphisms, we failed to find associations with genetic variants previously implicated to be associated with asthma and atopy. Evaluation of markers on chromosome 5q31-32 identified novel loci for susceptibility to asthma and atopy in addition to loci already described by others. CONCLUSION: Both the published literature and our own findings indicate that there are inter-ethnic differences in genetic susceptibility to asthma and atopy.

Asian People↗
PubMed1991

Asthma symptoms, bronchial hyperresponsiveness and atopy in a Maori and European adolescent population.

In 1989 a survey of 543 New Zealand rural adolescents of largely Maori descent was undertaken to determine the prevalence of asthma symptoms, bronchial hyperresponsiveness (BHR) and atopy. The overall prevalence of asthma was estimated at 13.7%, BHR at 13.4% and atopy at 31.1%. These rates were similar across the age range 13 to 18 years. The prevalence of BHR among those without asthma symptoms was 3%. Both current asthma symptoms and BHR were more common among females, but there was no difference between the sexes in the proportion with atopy. The prevalence of asthma symptoms was higher among Maoris than nonMaoris, but this difference disappeared when allowance was made for current smoking. There was a similar prevalence of BHR and atopy between these two ethnic groups. There was a similar prevalence of asthma but lower prevalence of BHR than was reported among 7-10 year olds in an urban Auckland survey. The low prevalence of BHR among those without asthma symptoms, and the uniform frequency of asthma symptoms, BHR and atopy over the age range suggest that adolescents would be a particularly useful population for national or international comparisons of the prevalence of asthma, BHR and atopy.

Adolescent↗
PubMedDate not supplied

Is the breast best for children with a family history of atopy? The relation between way of feeding and early childhood morbidity.

BACKGROUND: Previous studies reported that breast-feeding protects children against a variety of diseases, but these studies were generally conducted on "high-risk" or hospitalized children. This paper describes the results of our study on the effects of breast-feeding on rate of illness in normal children with a family history of atopy. METHODS: A historic cohort approach of 794 children with a family history of atopy was used to assess the effects of breast-feeding on illness rates. Family history of atopy was based on allergic diseases in family members as registered by the family physician. Illness data from birth onwards were available from the Continuous Morbidity Registration of the Department of Family Medicine. Information on breast-feeding was collected by postal questionnaire. We then compared rates of illness between children with a family history of atopy who were and who were not breast-fed. RESULTS: Breast-feeding was related to lower levels of childhood illness both in the first and the first three years of life. In the first year of life they had fewer episodes of gastroenteritis, lower respiratory tract infections, and digestive tract disorders. Over the next three years of life they had fewer respiratory tract infections and skin infections. CONCLUSIONS: Our results suggest a protective effect of breast-feeding among children with a family history of atopy that is not confined to the period of breast-feeding but continues during the first three years of life. Breast-feeding should be promoted in children with a family history of atopy.

Breast Feeding↗
PubMed1996

[Atopy score in infancy and the severity of asthma at 7 years of age].

Due to limitations in early diagnosis of atopy at wheezy infants in 1982 the authors introduced a special scoring system called "atopy-score". This evaluates the skin prick tests' results, serum IgE level, the presence of other allergic symptoms, and atopy in the family history. The relationship between atopy-score in early childhood and severity of atopic asthma at age 7 was investigated in 30 children (15 mild, and 15 severe asthmatics). It was proved, that atopy-score during infancy was high in those children who had severe atopic asthma at seven, and low in those who developed mild disease: 9.2 vs. 5.9. The findings indicate that wheezy infants with high atopy-score are candidates for preventive measures and early protective treatment.

Age Factors↗
PubMedDate not supplied

Prevalence of atopy in young healthy population, in Izmir, Turkey.

The aim of this study was to determine the prevalence of atopy especially in young aged group in which allergic diseases are frequently seen. We carried out this study in Izmir which is located on the west coast of Turkey and has all the characteristics of mediterranean climate. However, we evaluated whether geographical characteristics such as climate, dampness, kinds of plant might be affected on prevalence of atopy. Participants were randomly selected and detailed standard questionnaire about if they or their relatives had any allergic symptoms were applied. The skin prick tests (SPT) with standardzied allergen extracts were performed and serum total IgE levels were assayed. The study group consisted of 277 individuals, aged 15-25 years. Based on the questionnaire, 123 (44.4%) participants described positive history of atopy. In 127 of 277 subjects (46%) was found at least one positive skin-test response and the most frequent allergen was house-dust mites. SPT was positive in 68 (55.2%) of 123 subjects who had atopic history and in 59 (38%) of 154 subjects who had negative history of atopy. The subjects who had atopic history showed more frequently positive SPT prevalence than the others (p < 0.01). Geometric mean of total IgE level was 105.5 kU/L in SPT positive 127 subjects and 57.7 kU/L in SPT negative 150 subjects. There was a positive relationship between total IgE level and positive SPT (p < 0.01). History of atopy was correlated with total IgE levels in males (p < 0.01) but not in females. Women more often than men reported atopic history in the absence of true atopy.

Adolescent↗
PubMed1984

Keratosis punctata and atopy. Report of 31 cases with a prospective study of prevalence.

We report 31 cases of keratosis punctata palmaris et plantaris in blacks. Eleven of these were found in a prospective study of 573 consecutive black private dermatologic outpatients, a prevalence of 1.9%, and 20 cases were randomly encountered over a three-year period in the same office. Five of the 30 patients able to give a history were symptomatic, and they and ten others came to the office because of this disease, where as 15 came for other reasons, two of whom were unaware of the disease. Four of the 31 patients also had foot lesions. Four patients were aware of relatives with palmar keratoses. The mean duration of disease was 4.3 years, the median was three years, and the range was zero to 38 years. The mean age at onset was 30.3 years, the median was 29 years, and the range was 12 to 70 years, with one case beginning in infancy. Each patient in the prospective study was examined for personal atopy or for a family history of atopy. Nine (82%) of the 11 patients with keratosis punctata had atopy and/or a family history of atopy. Statistical analysis confirmed the association between keratosis punctata and atopy in the prospective study.

Adolescent↗
PubMed2001

Linkage analysis of asthma and atopy including models with genomic imprinting.

Asthma and atopy are two closely related, common complex traits in which a number of genetic and environmental factors are suspected to play a role. We have performed parametric and nonparametric multi-marker linkage analysis for the Busselton data set, which is part of problem 1 of Genetic Analysis Workshop 12. In particular, we have focused on the dichotomous trait atopy, as well as on dichotomized versions of the quantitative traits RASTI and loge slope. The lod score analysis with adequate modeling of a parent-of-origin effect, by use of the program GENEHUNTER-IMPRINTING, was a special interest. The most prominent findings are a multipoint mod score of 3.12 at D13S153 for RASTI, and a multipoint mod score of 4.32 at the same locus for atopy, both with four-penetrance imprinting models that point to a gene subject to maternal imprinting. In addition, there are marked differences between imprinting and non-imprinting mod scores. These results corroborate earlier findings of linkage between atopy and D13S153, but add the aspect of paternal gene expression. Furthermore, suggestive evidence for linkage to atopy is found near D6S291, D7S530, and D14S74. The best-fitting models for chromosome 6 and 14 may suggest that genomic imprinting takes plae at these two loci as well.

Adult↗
PubMed2007

Vaccines, antibiotics, and atopy.

PURPOSE: Early exposure to vaccines and antibiotics may increase the risk of developing atopy by protecting against infectious agents and reducing duration and severity of infections (the hygiene hypothesis). It may also shift the developing immune system towards a more allergic response. We assess possible associations in young allergy clinic patients. METHODS: We conducted a case-control study of 6- to 16-year-old new allergy clinic patients who were skin tested for inhalant allergens during 1987-2001 and enrolled in KPNW since birth (n = 1074). Atopic cases had positive tests for at least one inhalant allergen. Non-atopic controls had negative tests for all inhalant allergens. Using logistic regression analysis, we estimated atopy odds ratios for vaccine and antibiotic exposure variables and associations between vaccine and antibiotic exposures during the first 2 years of life and subsequent new allergy diagnoses. RESULTS: Atopy was not significantly associated with numbers of vaccine and antigen doses, or number of different antigens during the first 2 years of life. Number of antibiotic prescriptions was negatively associated with atopy risk. Neither exposure was significantly associated with risk of new allergy diagnoses in atopic children. CONCLUSIONS: Atopy development appears to be unrelated to early vaccine exposure. Frequency of antibiotic prescriptions during early life, a proxy for infection frequency, appears to protect against allergic sensitization. Neither vaccines nor antibiotics appear to induce subsequent allergic reactions in atopic children.

Adolescent↗
PubMed2000

Genetics of atopy in a mouse model: polymorphism of the IL-5 receptor alpha chain.

To study the genetics of atopy systematically we established a mouse model that provides the general phenotype of atopy: the early response characteristic of IgE-dependent eczema or atopic dermatitis, and the diagnostic test of atopy, the skin-prick test. Using an immediate cutaneous hypersensitivity test (ICHS) against birch pollen extract we could classify A/J and C57BL/6 (B6) inbred mouse strains respectively as high responder and low responders. The F1 hybrids were found to be high responders with incomplete penetrance. Backcrossing F1 mice to the low responder B6 strain yielded three classes of responders, high, intermediate, and low. A genome-wide microsatellite screen of the backcross progeny disclosed suggestive linkage to a microsatellite marker on chromosome 6 close to the locus of the IL-5 receptor alpha chain. Its allelic variation in A/J and B6 strains was investigated and two major differences were detected. Firstly, a nucleotide exchange in the 5' untranslated region of B6 mRNA resulted in increased transcription/translation of a reporter construct. Higher expression of the receptor on the cell surface would be expected to favor an allergic immune response. Secondly, the two alleles are differentially spliced so as to yield two soluble isoforms in A/J mice versus one in B6 mice. Higher expression of soluble IL-5R would be expected to reduce the level of allergy through capture of IL-5. Thus both findings conform to the expectation based on susceptibility to atopy and thus identify the IL-5R alpha chain as a likely contributor to the genetics of atopy.

Alternative Splicing↗
PubMed1994

Dietary linoleic acid-induced changes in respiratory beta-adrenergic receptor function and the form of arrhenius plots of isoprenaline- and prostaglandin E2-stimulated adenylate cyclase activity in a model for atopy.

Varying dietary linoleic acid altered lung membrane fatty acid composition with linoleic acid content increasing from approximately 6% total in those on 3 en% diet to approximately 14% total fatty acid in those on a 12 en% diet. Accompanying this were two- to three-fold increases in the levels of the elongation products of linoleic acid, namely 20:2 (n-6) and 22:5 (n-6) and a decrease in 18:1 oleic acid from approximately 26% to approximately 19% total. Administration of Haemophilus influenzae, to animals on 6 en% linoleic acid, serving as a model for atopy, effected a small increase in the levels of 22:5 (n-3) and doubled those of 22:6 (n-3). beta-Adrenergic-induced tracheal relaxation and stimulation of lung adenylate cyclase were elevated by increasing dietary linoleic acid from 3 to 6 en%, although such differences were abolished in the atopic model and when dietary linoleic acid was increased to 12 en%. Arrhenius plots of NaF-stimulated lung adenylate cyclase activities exhibited a break (t1) at approximately 26 degrees C in all dietary groups with unchanged activation energies and activity. In contrast, whilst both isoprenaline and PGE2-stimulated adenylate cyclase activities showed similar break-points in their Arrhenius plots, dietary linoleic acid manipulation markedly altered their form. As with NaF-stimulated activities then, irrespective of dietary manipulation and induction of atopy, these plots showed an invariant break occurring at approximately 26 degrees C. But, for animals on 3 and 6 en% diets, a second break was apparent at approximately 15 degrees C, which was slightly decreased to approximately 12 degrees C upon induction of atopy and completely abolished on increasing dietary linoleic acid to 12 en%. Accompanying such changes were marked alterations in activation energies. We suggest that profound changes in lung plasma membrane bilayer properties occur upon both altering dietary linoleic acid levels and in atopy. These selectively perturb adenylate cyclase activity when it is receptor-stimulated but not when it is activated by direct G-protein stimulation with NaF. We suggest that atopy and dietary challenge elicit an asymmetric perturbation of the plasma membrane that predominantly affects the outer half of the lipid bilayer.

Adenylyl Cyclases↗
PubMed2003

Prenatal prediction of infant atopy by maternal but not paternal total IgE levels.

BACKGROUND: The atopic history of parents has long been used to predict infant atopy. However, bias from questionnaires of allergic history are also frequently suspected, because a large number of vasomotor rhinitis, intrinsic asthma, and seborrheic dermatitis cases are probably misinterpreted to be atopic diseases. OBJECTIVE: We attempted to identify a risk factor other than parental atopic history to predict elevated infant IgE levels and infant atopy. METHODS: A total of 655 core families were prenatally recruited, and finally 545 families completed the study for the prospective analysis of infant atopy at 6 months of age. Atopic history and blood samples of parents were collected in the third trimester during pregnancy. Cord blood (CB) was collected immediately after birth. Infant blood samples and history of infant eczema were collected in the 6-month physical checkup clinic. Blood total IgE and specific IgE levels were determined by use of the Pharmacia CAP system. RESULTS: In univariate analysis, maternal, but not paternal, atopic history correlated with elevated CB IgE levels and the occurrence of infant eczema. Elevated maternal, but not paternal, total IgE levels (>150 KU/L) significantly correlated with increases of CB IgE levels (median, 0.54 vs 0.17 KU/L, P <.001), infant IgE levels (log-transformed mean values, 1.32 +/- 0.51 vs 1.13 +/- 0.51 KU/L, P <.001), and infant eczema (P =.008). Multivariate logistical regression analysis, however, showed that only maternal total IgE levels correlated with CB and infant IgE levels and the development of infant eczema. CONCLUSIONS: The maternal, but not paternal, total IgE level correlates with elevated infant IgE levels and infant atopy. This provides a high specificity (83%) and a sensitivity of 34% for prediction of infant atopy. This suggests that maternal factors, placental factors, or both have an impact on perinatal allergic sensitization.

Eczema↗
PubMed2005

Association of atopy and eczema with polymorphisms in T-cell immunoglobulin domain and mucin domain-IL-2-inducible T-cell kinase gene cluster in chromosome 5 q 33.

BACKGROUND: The T-cell immunoglobulin domain and mucin domain (TIM) gene family and the gene for IL-2-inducible T-cell kinase (ITK), located in chromosome 5 q 33 and potentially involved in the T-cell proliferation and differentiation, are good candidate genes for allergic diseases. OBJECTIVE: We assessed the role of polymorphisms in the TIM family genes and ITK in atopy, eczema, and asthma. METHODS: Twenty-one polymorphisms in the TIM-ITK gene cluster were genotyped in 564 children enrolled in the Tucson Children's Respiratory Study. Skin prick tests to common allergens were performed at age 6.1 years (n=508), age 10.8 years (n=539), and age 16.6 years (n=424). Asthma and eczema were assessed by questionnaire at these 3 points. Averaged relative risks were estimated. RESULTS: One 15-bp insertion/deletion in exon 4 of TIM 1 was significantly related to atopy and eczema (relative risk associated with carrying at least 1 rare allele=1.24 [1.07--1.45], P=.005; and 1.43 [1.01--2.01], P=.004, respectively). The 3 tested single nucleotide polymorphisms (SNPs) in TIM 3 were significantly related to atopy and eczema. One of them, at position +4259 calculated from the translation start site, predicts a putative change in the amino acid sequence of the protein, and was the most strongly related to atopy (relative risk=1.28 [1.12--1.47]; P=.0003). SNPs in the 5' genomic region in ITK, which show moderate linkage disequilibrium with those in TIM 3, had an independent effect on atopy. None of the polymorphisms studied was related to asthma. CONCLUSION: Our findings support a potential role for SNPs in TIM 1, TIM 3, and ITK, independent of each other, in allergic diseases.

Adolescent↗