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PubMed1999

Nucleotide and polyamine levels in colostrum and mature milk in relation to maternal atopy and atopic development in the children.

The prophylactic benefit of breastfeeding against atopic disease is still controversial. It seems to be limited to infants with genetic propensities to allergy in combination with late solid food introduction. Lower levels of n-3 polyunsaturated fatty acids in human milk have been related to atopy in children, stressing a non-specific role of nutritional components in the development of atopy. Nucleotides and polyamines have been related to intestinal integrity and immune function in infancy. The main sources of these nutrients are human milk nucleotides and polyamines early in life. Our aim was to study the composition of nucleotides and polyamines in colostrum and mature milk from atopic and non-atopic mothers and the relationship to sensitization against egg, milk or cat in their children during the first year of life. The nucleotide/nucleoside and polyamine levels were measured by HPLC in colostrum and in milk at 3 mo of lactation from mothers of 21 atopic and 14 non-atopic children. Among the mothers, 10 were atopic and 25 non-atopic. The nucleotides cytidine monophosphate (CMP), uridine monophosphate (UMP), adenosine monophosphate (AMP) and guanosine monophosphate (GMP) and the nucleosides cytidine and uridine were detected in human milk. In colostrum, CMP dominated, and the levels increased in mature milk, while the levels of the other compounds remained constant. The nucleotide/nucleoside composition was similar in colostrum from all mothers independent of the development of sensitization in their babies, except for the higher cytidine levels in mature milk from atopic mothers of atopic babies, as compared to healthy mothers of atopic babies. The polyamine levels were similar in colostrum from atopic and non-atopic mothers. However, putrescine and spermine levels were lower in mature milk from atopic mothers than non-atopic mothers. No relationship was found between milk putrescine and spermine levels and development of atopy in the children. In conclusion, low levels of human milk putrescine and spermine seem to be related to maternal atopy.

Chromatography, High Pressure Liquid↗
PubMed2000

Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations.

After a genomewide screen in the Hutterites was completed, the IL4RA gene was examined as the 16p-linked susceptibility locus for asthma and atopy. Seven known variants and one novel variant, representing all nonsynonymous substitutions in the mature protein, were examined in the Hutterites; on the basis of studies in the Hutterites, outbred white, black, and Hispanic families were genotyped for selected markers. All population samples showed evidence of association to atopy or to asthma (P values.039-.0044 for atopy and. 029-.0000061 for asthma), but the alleles or haplotypes showing the strongest evidence differed between the groups. Overall, these data suggest that the IL4RA gene is an atopy- and asthma-susceptibility locus but that variation outside the coding region of the gene influences susceptibility.

Alleles↗
PubMed2005

The impact of stress on the development and expression of atopy.

PURPOSE OF REVIEW: Biological hypersensitivity to environmental stimuli is a fundamental feature of atopy predisposing to a number of clinically expressed disorders including allergic rhinitis, atopic dermatitis or eczema, and allergic asthma. There is provocative evidence that psychological stress constitutes an increased risk for atopy. This risk is thought to be mediated by the effects of stress on neuroimmunoregulation which in turn modulates the hypersensitivity response. The primary objective is to review recent evidence updating our understanding of the role for psychological stress in atopy. RECENT FINDINGS: The Th1-Th2 paradigm has been central to interpreting quantitative differences in cytokine expression in response to environmental stimuli like stress. Here we argue that examination of other mechanisms (e.g. oxidative stress pathways, glucocorticoid resistance, nerve-mast cell interactions, intestinal dysbiosis) and a broader range of cytokines and neuropeptides produced by cells both within and outside the immune system may better delineate the true complexity of the underlying mechanisms linking stress to allergic sensitization and asthma. The role of genetics and gene by environment interactions - based on evolving knowledge of candidate genes that may be relevant to both the stress response in general and pathways linked specifically to atopy - is also discussed. SUMMARY: Psychological stress may be conceptualized as a social pollutant that, when 'breathed' into the body, may disrupt biological systems related to inflammation through mechanisms potentially overlapping with those altered by physical pollutants and toxicants.

Asthma↗
PubMedDate not supplied

Association of IL-13, RANTES, and leukotriene C4 synthase gene promoter polymorphisms with asthma and/or atopy in African Americans.

PURPOSE: IL-13, RANTES (Regulated on Activation, Normal T cells Expressed and Secreted), and cysteinyl leukotrienes are asthma and atopy mediators. Two RANTES -403(G to A) and -28(C to G), an -1055 IL-13(C to T), and a -444(A to C) leukotriene C4 synthase (LTC4S) single nucleotide polymorphisms (SNPs) have been shown in Caucasians and Asians as asthma and atopy risk factors. We studied these SNPs in African Americans with asthma and/or atopy. METHODS: We studied 61 patients with asthma and/or atopy and 129 to 157 newborn controls for the -403 RANTES, -28 RANTES, and -1055 IL-13 SNPs, as well as 47 patients and 60 newborn controls for the -444 LTC4S SNP. RESULTS: The two groups did not significantly differ at the genotypes of the -403 and -28 RANTES SNP. On the other hand, the mutant TT genotype for the -1055 IL-13 SNP was detected in 19.7% of patients versus 12.7% in controls (P < 0.04, OR 2.9, 95% CI 1.0-8.0), and the mutant T allele in 58.3% versus 36.6% in controls (P < 0.02, OR 2.4, 95% CI 1.1-5.2). In a similar fashion, for the -444 LTC4S SNP, the mutant AC genotype was detected in 19.1% versus 10.0% in controls (P > 0.28); mutant C allele had an OR of 2.1 (95% CI 0.7-6.3). CONCLUSION: African American asthmatics/atopics had higher frequency of the TT mutant gene for the -1055 IL-13 SNP and of its mutant T allele. Regarding the -444 LTC4S SNP, there was a definite difference, although not statistically significant, with an OR of 2.1 for the mutant AC genotype in patients. If these findings become reproduced by larger studies, it may suggest that IL-13 and LTC4S SNPs can be used as predictive markers for asthma/atopy in African Americans.

Adolescent↗
PubMed1985

Atopy and rheumatoid arthritis.

The prevalence of rheumatoid arthritis (RA) was studied among 266 atopic patients attending an allergy clinic. Two patients had definite RA, a prevalence similar to that seen in the general population. We also studied the prevalence of atopy (positive skin-prick tests) and diseases associated with atopy among forty patients with RA and forty age- and sex-matched controls. The two groups had a similar prevalence of atopy (5 RA patients, nine controls) and atopic diseases (fourteen RA patients, fourteen controls) and they did not differ with respect to blood eosinophil counts or total serum IgE. Positive RAST tests to inhaled allergens were found in three RA patients and five controls and all patients had negative RAST tests to milk and egg. It was concluded that patients with rheumatoid arthritis have a normal prevalence of atopy and atopic diseases and we found no evidence that allergic factors contributed to the arthritis of the forty RA patients in the study.

Adult↗
PubMed1991

Reliability of respiratory symptoms to diagnose atopy.

As reliance of responses to epidemiological questionnaires on atopic symptoms is doubtful, we studied the predictive value of these questions relative to atopy, defined by the presence of serum specific IgE, taking into account some extraneous variables such as age and sex. The study population included 2067 adults, 20-60 years old. The protocol consisted of a standardized questionnaire and an evaluation of serum specific IgE using the Phadiatop (Pharmacia Diagnostics, Uppsala, Sweden) test. The predictive value of each symptom suggestive of atopy was quite low, but was much dependent on age and sex. Women more often than men reported atopic symptoms in the absence of atopy. Similarly, the predictive value of each symptom decreased with age. Thus atopic symptoms do not have the same value as predictors of atopy. These findings have both clinical and epidemiological important implications.

Adult↗
PubMed1992

Genetic analysis of the linkage between chromosome 11q and atopy.

Previous work has suggested that there is a genetic predisposition for the development of both asthma and atopy. A recent study has also shown that there is a striking link between chromosome 11q and the IgE response underlying asthma and rhinitis. To further assess the linkage between chromosome 11q and atopy, we have studied nine families of two and, in many instances, three generations with the index case having asthma and/or atopy. Using two restriction fragment length polymorphism probes associated with the regions 11q12-q13.2, namely PYGM and INT2, we have been unable to confirm a significant link between this region of chromosome 11q and atopy as defined by a positive skin-prick test and/or a raised specific IgE and/or a raised total IgE.

Adolescent↗
PubMed2004

Farming exposure in childhood, exposure to markers of infections and the development of atopy in rural subjects.

BACKGROUND: Within the context of the hygiene hypothesis, we aimed to study the potential association between farming-related risk factors and Toxoplasma gondii (T. gondii) as well as Helicobacter pylori (H. pylori) seropositivity. METHODS: The study included questionnaire data and serum samples of 321 young adults living in a rural environment. Serum samples were analysed for specific IgE to a common panel of aeroallergens (SX1) as well as IgG against T. gondii and H. pylori. RESULTS: Regular contact with animal stables before the age of 3 years (odds ratio (OR) (95% confidence interval): 2.0 [1.0; 4.0]) and unpasteurized milk consumption at age 6 years (1.8 [1.0; 3.3]) were the strongest risk factors for T. gondii infection. None of the farming-related factors were significantly associated with H. pylori infection. Current consumption of raw farm milk was not significantly associated with H. pylori infection (2.1 [0.8; 5.3]). Regular contact with animal houses before the age of 7 years was the strongest predictor for atopy (0.49 [0.26-0.96]). The reduction in risk could not be further decreased by any other factor under consideration. After adjustment for animal house contact, the OR for atopy was decreased by raw milk consumption and H. pylori infection in an additive manner. CONCLUSION: Exposure to farming environments in childhood might predict T. gondii seropositivity in rural subjects. Nevertheless, the strongest predictor for atopy in rural subjects seems to be regular contact with farm animals. Whether T. gondii infection is an intermediate factor in the association between farm contact and atopy needs to be confirmed in larger studies.

Adult↗
PubMed2004

Mothers of very low birth weight infants have less atopy than mothers of full-term infants.

BACKGROUND: Studies on the pregnancy outcome of asthmatic mothers have suggested an increased rate of preterm deliveries. In contrast, our earlier study suggests that mothers of very low birth weight (VLBW) (<1500 g) infants less frequently had atopy than did mothers of full-term infants. METHODS: We inquired about symptoms of atopy and doctor-diagnosed atopy in parents of 370 infants of VLBW (<1500 g) and 544 parents of full-term infants. Odds ratios for atopic symptoms and diagnosed atopy were calculated, and groups were compared with a trend test. RESULTS: Mothers of preterm infants of birth weight (BW) <1000 g significantly less often had physician-diagnosed allergic rhinitis (AR) (P=0.02). Among all the mothers, a trend test showed that maternal AR was significantly (P=0.03) higher in parallel with a higher infant BW. Fathers of infants with different BWs showed no differences in prevalence of atopic symptoms. CONCLUSION: We thus infer that maternal balance between T-helper type 1 (Th1) and Th2 cells, shifted towards Th2 in those with AR, may have a favourable effect on maintenance of pregnancy before gestational week 30.

Adult↗
PubMed2004

A novel promoter polymorphism in the gene encoding complement component 5 receptor 1 on chromosome 19q13.3 is not associated with asthma and atopy in three independent populations.

BACKGROUND: The inflammatory functions of complement component 5 (C5) are mediated by its receptor, C5R1, which is expressed on bronchial, epithelial, vascular endothelial and smooth muscle cells. A susceptibility locus for murine allergen-induced airway hyper-responsiveness was identified in a region syntenic to human chromosome 19q13, where linkage to asthma has been demonstrated and where the gene encoding C5R1 is localized. OBJECTIVE: The aim of this study was to screen for novel polymorphisms in the C5R1 gene and to determine whether any identified polymorphisms are associated with asthma and/or atopy and whether they are functional. METHODS: Single-nucleotide polymorphism (SNP) detection in the gene encoding C5R1 was performed by direct sequencing. Genotyping was performed in three populations characterized for asthma and/or atopy: (1) 823 German children from The Multicenter Allergy Study; (2) 146 individuals from Tangier Island, Virginia, a Caucasian isolate; and (3) asthma case-parent trios selected from 134 families (N=783) in Barbados. Functional studies were performed to evaluate differences between the wild-type and the variant alleles. RESULTS: We identified a novel SNP in the promoter region of C5R1 at position -245 (T/C). Frequency of the -245C allele was similar in the German (31.5%) and Tangier Island (36.3%) populations, but higher in the Afro-Caribbean population (53.0%; P=0.0039 to <0.0001). We observed no significant associations between the -245 polymorphism and asthma or atopy phenotypes. Upon examination of the functional consequences of the -245T/C polymorphism, we did not observe any change in promoter activity. CONCLUSION: This new marker may provide a valuable tool to assess the risk for C5a-associated disorders, but it does not appear to be associated with asthma and/or atopy.

Asthma↗
PubMed2005

Mucosal symptoms elicited by fragrance products in a population-based sample in relation to atopy and bronchial hyper-reactivity.

BACKGROUND: Exposure to perfume and fragrance products may, in some individuals, cause symptoms from the eyes and airways. The localization, character and risk factors of such symptoms in the general population are unknown. OBJECTIVE: To investigate both the localization and character of symptoms from the eyes and airways elicited by fragrance products, and the associations between such symptoms and skin prick test reactivity (atopy), methacholine bronchial hyper-reactivity (BHR), allergic rhinitis and asthma. METHODS: A questionnaire on mucosal symptoms elicited by fragrance products was posted to 1189 persons who had participated in a Danish population-based study of allergic diseases in 1997/1998. The study included measurement of BHR, atopy, forced expiratory volume in 1 s (FEV1), and serum eosinophilic cationic protein (serum ECP). RESULTS: The response rate was 79.6%. Symptoms from the eyes or airways elicited by fragrance products were reported by 42%. BHR (adjusted odds ratio 2.3, 95% confidence interval 1.5-3.5) was independently associated with symptoms from the eyes and airways elicited by fragrance products. There were no significant associations between these symptoms and atopy, FEV1 or serum ECP. CONCLUSIONS: Mucosal symptoms from the eyes and airways were common in this population. BHR was a significant and independent predictor of these symptoms. The lack of association with atopy suggested that IgE-mediated allergic mechanisms do not play a major role in the development of these symptoms.

Asthma↗
PubMed1998

Determinants of bronchial responsiveness in the European Community Respiratory Health Survey in Italy: evidence of an independent role of atopy, total serum IgE levels, and asthma symptoms.

The aim of the analysis was to test whether total serum IgE levels, specific serum IgE levels, and asthma symptoms are independent predictors of bronchial hyperresponsiveness (BHR), after controlling for known risk factors or potential confounders. The study was carried out on a sample of 875 young adults, 20-44 years old, who took part in the European Community Respiratory Health Survey in Italy. The subjects underwent a dose-response methacholine challenge test. We also measured airway caliber as the baseline FEV1 in absolute terms and as percentage of forced vital capacity (FVC); skin wheal response to 11 common environmental allergens; and total and specific serum IgE levels to mites, molds, pets, and respiratory symptoms by means of a standardized questionnaire. Atopy (positive skin prick test and/or positive specific IgE assay), total IgE, asthma symptoms, airway caliber, and age appeared to be independent predictors of BHR. When all the other risk factors were taken into account, atopy and total IgE were associated with a threefold increase in BHR risk and thus emerged as the main determinants of BHR. The importance of symptom status as a determinant of BHR decreased remarkably after controlling for atopy and IgE: the odds ratio of current asthmatics to asymptomatic subjects decreased from 15.3 to 8.8. When controlling for symptoms and atopy, a family history of allergic diseases and early respiratory infections was not found to be associated with BHR. Both FEV1 and FEV1/FVC were strongly and inversely associated with BHR. When airway caliber was taken into account, older age was associated with decreased responsiveness, and the level of responsiveness did not differ significantly between males and females and between smokers and nonsmokers. The results from this analysis indicate that at any given age, irrespective of sex and smoking habits, total serum IgE, specific IgE, airway caliber, and asthma symptoms are the main independent factors influencing the occurrence of BHR in a young adult sample.

Adult↗
PubMed2004

Fatty acids in colostrum from mothers of children at high risk of atopy in relation to clinical and laboratory signs of allergy in the first year of life.

BACKGROUND: It remains controversial whether fatty acid (FA) composition of breast milk relates to development of atopy in the infant. This study evaluates FA in colostrum from mothers of children at high risk of atopy in association with atopy at the age of 1 year. METHODS: The FA of colostrum were analyzed for 218 children (60 with low birth weight between 1500 and 2500 g, 84 with a history of maternal atopy, and 74 with an elevated cord blood immunoglobulin (Ig)E of >0.9 IU/ml). Total lipids were extracted, methylated and separated by gas-liquid chromatography. Laboratory screening for allergic sensitization and clinical examination took place within the Leipzig Allergy Risk Children's Study (LARS). RESULTS: Low birth weight was correlated with low percentage levels of 20:2n-6, 22:2n-6, and 22:3n-3 (r = 0.14, P < 0.05; r = 0.14, P < 0.05 and r = 0.20, P < 0.01, respectively) and low gestational age at birth was correlated with low 22:3n-3 (r = 0.15, P < 0.05). There was no association between FA and atopic eczema at the age of 1 year. However, high linoleic acid (LA, 18:2n-6) was linked to high specific IgE against cow's milk protein (P < 0.05), and low docosapentaenoic acid (DPA, 22:5n-3) was associated with elevated total serum IgE (P < 0.05) at the age of 1 year, respectively. CONCLUSIONS: The polyunsaturated fatty acid composition of colostrum in a high risk newborn population shows associations with atopic sensitization at the age of 1 year and may be predictive for later atopic disease.

Adult↗
PubMed1981

HLA-DR7 in children with idiopathic nephrotic syndrome. Correlation with atopy.

Idiopathic nephrotic syndrome (INS) of childhood is likely to be underlain by an immunopathological mechanism; we investigated the presence of immunogenetic HLA markers in this disease. Fifty-four unrelated INS-affected children, among them 20 with an allergic status, were studied for 33 HLA-A,B and 6 HLA-DR antigens. The results were compared to those obtained in 49 children with glomerulonephritis, 28 children with atopy but without nephropathy, and 91 healthy blood donors. The HLA-A and B antigen frequencies were not significantly different from normal frequencies. The incidence of HLA-DR7 was significantly increased in INS-affected patients as compared to the other groups (66.7% in patients vs 31.1% in healthy controls; corrected P value less than 0.001; relative risk = 4.4), and more so in those with atopy than in those without atopy (90% vs 46%; P = 0.002). The frequency of this antigen is not increased in atopic non-nephrotic children. No relationship between HLA-DR7, clinical outcome and steroid-responsiveness was found. We suggest that the pathogenesis of INS could be influenced by an HLA-linked immune response gene, especially in its atopy associated form.

Child↗
PubMed2005

Additive effect of eosinophilia and atopy on exhaled nitric oxide levels in children with or without a history of respiratory symptoms.

Although atopy and blood eosinophilia both influence exhaled nitric oxide (eNO) measurements, no study has quantified their single or combined effect. We assessed the combined effect of atopy and blood eosinophilia on eNO in unselected schoolchildren. In 356 schoolchildren (boys/girls: 168/188) aged 9.0-11.5 yr, we determined eNO, total serum IgE, blood eosinophil counts and did skin prick tests (SPT) and spirometry. Parents completed a questionnaire on their children's current or past respiratory symptoms. Atopy was defined by a SPT >3 mm and eosinophilia by a blood cell count above the 80th percentile (>310 cells/ml). eNO levels were about twofold higher in atopic-eosinophilic subjects than in atopic subjects with low blood eosinophils [24.3 p.p.b. (parts per billion) vs. 14.1 p.p.b.] and than non-atopic subjects with high or low blood eosinophils (24.3 p.p.b. vs. 12.2 p.p.b. and 10.9 p.p.b.) (p <0.001 for both comparisons). The additive effect of atopy and high eosinophil count on eNO levels remained unchanged when subjects were analyzed separately by sex or by a positive history of wheeze (n=60), respiratory symptoms other than wheeze (n=107) or without respiratory symptoms (n=189). The frequency of sensitization to Dermatophagoides (Dpt or Dpf) was similar in atopic children with and without eosinophilia (66.2% and 67.4%, respectively); eosinophilia significantly increased eNO levels in Dp-sensitized children as well in children sensitized to other allergens. In a multiple linear regression analysis, eNO levels were mainly explained by the sum of positive SPT wheals and a high blood eosinophil count (t=4.8 and 4.3, p=0.000), but also by the presence of respiratory symptoms (especially wheeze) and male sex (t=2.6 and 2.0, p=0.009 and 0.045, respectively). Measuring eNO could be a simple, non-invasive method for identifying subjects at risk of asthma in unselected school populations.

Analysis of Variance↗
PubMed2006

Atopy, eczema and breast milk fatty acids in a high-risk cohort of children followed from birth to 5 yr.

BACKGROUND: The incidence of atopic diseases such as eczema is increasing in westernized societies. The suggestion that there is a "protective" association between the unique fatty acid composition of breast milk, particularly the omega-3 (n-3) and omega-6 (n-6) essential polyunsaturated fatty acid content, and the development of atopic disease in children was investigated in a cohort study of 263 infants born into families with a history of allergy (one or both parents had asthma, hayfever, eczema). The objectives of this study were to determine the lipid profile [specifically in relation to long-chain polyunsaturated fatty acid (LC-PUFA) composition] in maternal breast milk samples collected at 6 wk and at 6 months following birth, and to investigate the potential role of these fatty acids in modulating the phenotype of children at high genetic risk of developing atopic disease. METHOD: Breast milk samples were available from 91 atopic mothers at their child's ages of 6 wk and 6 months. These samples were analysed for the fatty acid spectrum. Analysis of variance was used to detect differences between groups of outcomes (no atopy or eczema, non-atopic eczema, atopy, atopic eczema) at ages 6 months and 5 yr, and a multiple comparisons procedure was conducted to isolate the parameters producing the different results (F-test, LSD test). For the exposure variables, n-3 and n-6 fatty acids are expressed as weight percentage and as a ratio (at both time-points). RESULTS: The fatty acid profiles of maternal breast milk at 6 wk and 6 months were similar. An increased ratio of n-6: n-3 fatty acids in both 6 wk and 6 month milk samples was associated with non-atopic eczema (p < 0.005) but not atopy alone or atopic eczema. CONCLUSION: We found milk fatty acids were a significant modulator of non-atopic eczema but not atopy or atopic eczema in infants at 6 months. In mothers with a history of asthma, hayfever or eczema, their 6-month-old infants were more likely to develop non-atopic eczema if their milk had a higher ratio of n-6: n-3 LC-PUFA.

Child, Preschool↗
PubMed1995

Does a family history of atopy influence lung function at follow-up of infants born prematurely?

The aim of this study was to assess whether a family history of atopy influenced lung function at follow-up of infants born prematurely. Analysis was made of thoracic gas volume and airways resistance measurements performed at 1 year of age in 86 infants born at a median gestational age of 29 weeks. These measurements had been made during a prospective follow-up study. The 30 infants with a family history of atopy were found to have a higher airways resistance (median 35 cmH2O/l/s) than the 56 infants without such a family history (median 30 cmH2O/l/s) (p < 0.05). However, when the results from 18 infants with a family history of atopy were compared with 18 controls who were matched for requirement for neonatal ventilation, parental smoking and were within at least 1 week of gestational age, no significant difference in airways resistance was found between the two groups. Multiple regression analysis demonstrated that gestational age and birth weight explained the apparent relationship between a family history of atopy and an elevated airways resistance at follow-up.

Adult↗
PubMed2003

Therapeutic implications of sex differences in asthma and atopy.

Clear sex differences exist in asthma and atopy with a preponderance of boys before puberty. There is a reversal of this sex ratio during puberty with girls having more asthma and atopy throughout the reproductive years. Elucidating the reasons for the switch in the sex ratio should provide fresh insights into asthma and atopy with a real prospect of novel therapies for these troublesome diseases. The challenge is to match the epidemiology and physiology with the accumulating scientific knowledge on gender differences in immune responses. Hormonal changes have been implicated in the reversal of the sex ratio. Testosterone is an immunosuppressant and is likely to be protective, while female sex steroids are proinflammatory and will increase the susceptibility to atopy. Modified so as to be non-virilising/feminising, sex steroids could therefore play a useful part in modulating the immunological and inflammatory processes that underlie asthma and other allergic disorders, complementing the currently used glucocorticoid derived steroids.

Anti-Allergic Agents↗