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High levels of cord serum eosinophil cationic protein predict the risk of atopy.

BACKGROUND: Transient tachypnoea of the newborn is a transient respiratory disturbance characterized by tachypnoea shortly after birth, which resolves within 2 to 5 days. The basic pathogenetic mechanism is the delayed resorption of the alveolar fluid of which the exact triggering mechanism still remains unknown. An etiological link associated with parenteral history of atopy was proposed by several studies. Some laboratory studies also revealed that serum IgE, eosinophil cationic protein (ECP) and cord IgE were higher among infants with maternal history of atopy. OBJECTIVE: The purpose of this study was to investigate the possible association of parental history of atopy with cord blood ECP and IgE concentrations in infants with transient tachypnoea of the newborn. METHODS: ECP and IgE levels were quantified in cord blood samples of 30 infants who were diagnosed as having transient tachypnoea of the newborn. The control group (N=30) was selected among healthy newborns with similar birth weight and gestational age. RESULTS: Cord blood ECP concentrations were significantly higher in the study group (17.6 microg/L) than in healthy control subjects (7.89 microg/L). In addition, transient tachypnoea of the newborn was more frequent in infants with a family history of atopic disease (p<0.01). Cord blood IgE concentrations were also higher in the study group than the controls (4.1 versus 3.28 mg/L) but the difference was not statistically significant (p>0.05). CONCLUSION: Family history of atopy and elevated levels of cord blood ECP are risk factors for transient tachypnoea of the newborn. In addition cord blood ECP level is a useful marker for predicting the risk of atopy.

Biomarkers↗

Genes for atopy and asthma.

The genetic basis of atopic diseases is represented by a complex network of interacting genes or common genetic variants rather than a few disease-causing mutations. The individual risk of developing asthma or other atopic diseases is defined by the concert of interaction of these hereditary factors and environmental stimuli. The first decade of asthma genetics has been spent identifying those genetic regions through linkage analysis, which are likely to harbour asthma genes. At the same time, several candidate genes for asthma and atopy have been identified and their variants characterized, some of them even to a level of functional understanding. Rather than adding new candidate regions and genes to the pool of knowledge, the interest in the past year has moved to a more sophisticated statistical evaluation of the given linkage and association data and a more precise definition of so-called 'intermediate phenotypes'. Some of the results are quite surprising and have helped us to understand the underlying pathophysiology. For example, the distinct clinical traits of asthma, such as atopic sensitization or inflammation of the bronchial epithelium, seem to be defined by distinct subsets of predisposing genes. At the same time, the very same subsets of genes might underlie further clinical diseases with similar clinical features. Polymorphisms within IL-4R alpha, which had been shown to be associated with asthma and atopy, have also been shown to be associated with kidney allograft rejection, systemic lupus erythematosus and Crohn's disease. There might thus just be a few asthma and atopy genes. Finally, asthma and atopy genetics has now reached a point of practical application. The genetics of susceptibility to environmental stimuli, pharmacogenetic data, and the advent of new pharmaceutical targets will greatly influence the whole field of asthma and atopy.

Asthma↗

The role of genetics in the development of asthma and atopy.

PURPOSE OF REVIEW: The mapping of complex traits such as asthma and atopy is one of the most important and central areas of human genetics. This article will present an overview of the current status of genetic studies of asthma and atopy using genome screens and association studies that have occurred in the literature since January 2003. RECENT FINDINGS: Many regions of the genome have been found to have linkage with the phenotypes of asthma and atopy. Over 70 variants in candidate genes have been reported to be associated with these phenotypes. The main regions these variants have been found are on chromosomes 2q, 5q, 6p, 11q, 12q, 16q and 17q. Five potential asthma susceptibility genes or complexes have been identified using a positional approach. These are ADAM33, DPP10, PHF11 and SETDB2, GPRA and SPINK5. It is evident that environmental factors will influence the expression of genes and the ultimate clinical phenotype of asthma and atopy. SUMMARY: The development of asthma and atopy involves many genes and environmental factors. An understanding of their genetic basis has great implications for their management.

Asthma↗

Cord serum IgE: an insensitive method for prediction of atopy.

Cord total serum IgE has been advocated as a screening test to detect infants at high risk of allergy who would be suitable for preventive measures. In a population based prospective study to look at the predictive capacity of cord IgE and family history of atopy 1111 one-year-old infants were followed-up. Cord IgE was measured using the EIA ultra technique (Pharmacia, Uppsala, Sweden). Atopic symptoms developed in 255 (23%) at one year, 183 (16.5%) had probable atopy (clinical disorder but negative skin prick test (SPT)) and 72 (6.5%) had definite atopy (clinical disorder with positive SPT). There was no difference in the mean cord IgE levels in infants with or without atopic manifestations. The cut-off for IgE was taken at 0.6 ku/1. The specificity of the test was 92% but the sensitivity was only 8.5%. The positive and negative predictive values were 24% and 78% respectively. Family history of atopy is far more sensitive in detecting infants at risk of atopy and little is added by knowledge of cord IgE.

Asthma↗

Asthma, allergy and atopy in southern Chinese school students.

In order to determine the prevalence of asthma, allergy and atopy in southern China and the relative importance of atopy and parental history in predicting asthma and allergic diseases, we carried out a cross-sectional study on 737 secondary school students aged 12-20 (492 boys, 245 girls; mean age = 16.4 years, SD = 1.8 years) in the city of San Bu, Guangdong, China. Standard questionnaires on respiratory and allergic symptoms were distributed for completion by parents with an overall response of 98.6%. Skinprick tests to common aeroallergens were performed on 647 subjects (87.8%) to determine atopic status. The prevalence (and 95% CI) of a history of hay fever, eczema, wheeze or asthma ever and wheeze in past 12 months were 1.6% (0.7-2.5), 10.4% (8.2-12.6), 1.9% (0.9-1.9) and 1.1% (0.3-1.9) respectively. Forty-nine per cent (45.2-52.9) of students had one or more positive skin tests to common aeroallergens. Amongst atopic subjects, 87.3% reacted to house dust mite (Dermatophagoides pteronyssinus) and 73.3% to cockroach. There was a close association between the degree of atopy and the prevalence of a history of wheeze (P < 0.05) but not with hay fever or eczema. After adjusting for age and sex, parental histories of hay fever, eczema and wheeze were strongly associated with the respective symptoms in the subjects (OR = 17.4 (3.2-93.9) for hay fever, 27.4 (12.7-59.0) for eczema, 79.4 (21.9-288.4) for wheeze). It is concluded that respiratory and allergic symptoms were uncommon in Chinese school students despite a high prevalence of atopy, and that parental history is more important in predicting asthma and allergy than atopy.

Adolescent↗

Maternal breast milk long-chain n-3 fatty acids are associated with increased risk of atopy in breastfed infants.

BACKGROUND: Australia has one of the highest prevalence rates internationally of allergic conditions, such as asthma and eczema. Atopy is one hallmark for the development of allergic disease and predisposes to allergic inflammation in the target organs. omega-3 (n-3) fatty acids (FAs) are thought to act as precursors to the formation of less active inflammatory mediators, with the potential to reduce inflammation. OBJECTIVE: To investigate whether increased n-3 FA levels in maternal breast milk are associated with a lower risk of developing atopy in infancy. METHODS: Subjects were part of the prospective Melbourne atopy cohort study, which involved 620 children born into families where at least one first-degree relative had an atopic disease. Some 224 women (mean age 31.4+/-4.2 (SD) years, with 73.2% (n=164) having self-reported atopy) provided either a colostrum (n=194) or 3-month expressed breast milk (EBM) sample (n=118). Maternal colostrum and 3-month EBM samples were analysed for FA content by gas chromatography. Skin prick tests (SPTs) to six common allergens were performed on infants at 6, 12 and 24 months of age and on mothers who agreed at study entry. RESULTS: For infants sensitized to foods at 6 months (n=29), the total n-3 FA level in the colostrum was significantly higher (P=0.004) as were levels of individual long-chain n-3 FAs, docosoapentaenoic acid (DPA, C22:5, P=0.001) and docosahexaenoic acid (DHA, C22:6, P=0.002) than in non-sensitized infants. Infants with aero-allergen sensitization at 24 months (n=30) had higher levels of the n-3 FA, DPA (P=0.002) and DHA (P=0.007), and similarly higher total n-3 FA (P=0.009) in maternal colostrum than those infants who were not sensitized. CONCLUSION: Higher n-3 FA levels in the colostrum do not appear to confer protection against, but may be a risk factor for, the eventual development of atopy in high-risk breastfed infants.

Adult↗

Risk factors for atopy among school children in a rural area of Latin America.

BACKGROUND: Infection with common childhood infectious diseases including geohelminth infections may provide protection against the development of atopy and allergic disease. Few studies have investigated risk factors for atopy among children living in rural areas of Latin America. OBJECTIVE: To identify risk factors associated with atopy among school-age children in a rural area of Latin America. METHODS: Analytic cross-sectional study of school-age children conducted in seven rural schools in Pichincha Province in Ecuador. Detailed risk factor information was obtained by questionnaire, stool samples were collected for identification of geohelminth parasites, and Mantoux testing was performed to determine tuberculin sensitization. RESULTS: A total of 1002 children from seven rural schools were recruited. The prevalence of geohelminth infections was high (70.1% were infected with at least one geohelminth parasite) and the prevalence of allergic sensitization was high (20.0% had evidence of aeroallergen sensitization). Factors associated with significant protection against atopy in multivariate analyses were the presence of overcrowding in the child's home, low socio-economic level, and infection with geohelminth parasites, and the protective effects of the three factors were statistically independent. CONCLUSION: Low socio-economic level, overcrowding and geohelminth infection, are independently protective against atopy among school-age children living in a rural area of Latin America.

Adolescent↗

Mannose-binding lectin 2 (MBL2) gene polymorphism in asthma and atopy among adults.

Mannose-binding lectin (MBL) insufficiency due to polymorphisms in the MBL2 gene causes an opsonization defect, which has been connected to infections and atopy. We investigated the significance of MBL2 genotypes with regard to persistent asthma and atopy among adults. The genotypes were determined in 243 adults with persistent asthma and 400 controls. Atopy was determined by skin-prick test. As a result, the carriage of -221 base pairs (bp) promoter region variant allele X (nucleotide change G-->C; alleles Y-->X, respectively) causing low MBL expression proved to be a significant risk factor for asthma in non-atopic males [odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23-5.15; P = 0.01]. Furthermore, the X-allele carriage was associated with the decrease in lung function (forced expiratory volume at 1 s, FEV(1)) during follow-up in the patients with asthma (P = 0.033), the effect being strongest for non-atopic asthmatics (P = 0.042). The MBL2 genotype had no clear effect on the occurrence of atopy in adults. In conclusion, our results abrogate the previously suggested predisposing effect of MBL insufficiency on atopy at least in adults. However, as MBL is a complement component participating in immune defence against microbes, and as in the pathogenesis of non-atopic asthma infectious agents are probably involved, the gene-environment interactions between MBL and infections should be assessed further with regard to asthma.

Adult↗

Clinical atopy and associated factors in primary-school pupils.

To investigate potential risk factors for clinical atopy in childhood, we obtained cross-sectional data from a cohort of 1376 8-year-old pupils. Parental atopy (hay fever, asthma, eczema), gestational age, maternal smoking habits, and the child's history of asthma, hay fever, and eczema were ascertained by questionnaire. Combining the history and the result of a skin prick test using seven aeroallergens, we defined the child's atopic diseases. Of the population evaluated, 25.4% were categorized as atopic (10.2% allergic asthma, 17.3% eczema, 6.9% hay fever). As compared with the clear nonatopics (40.2%), parental atopic diseases were more prevalent in each of the atopic groups. Significant associations of the parents' and child's disease were obvious for eczema and hay fever. Low gestational age (LGA) was more frequent in children with any atopy or with an allergic asthma (odds ratio (OR) 1.7; 95% confidence interval (CI) 1.02-2.97; OR 2.8; 95% CI 1.5-5.4). Hay fever and allergic asthma occurred less frequently in girls (OR 0.5; 95% confidence interval 0.3-0.8; OR 0.6; 95% CI 0.4-0.9). In conclusion, our data underline the importance of parental atopy for the clinical outcome in the offspring. In addition, LGA appears to be a risk factor for allergic asthma and for general atopy in later life.

Austria↗

Coincidence of atopy profile in terms of monosensitization and polysensitization in children and their parents.

BACKGROUND: Results from epidemiologic studies have shown that childhood atopy is probably a hereditary disorder, because the offspring of affected parents have a higher risk of developing atopy. Among the atopic population, some subjects are sensitized to only one class of allergens (monosensitized), while other subjects are sensitized to more than one class of allergens (polysensitized). The aim of this study was to investigate whether atopy profile (monosensitization/polysensitization) in children is linked to the same conditions in their parents. METHODS: We evaluated sensitization to five classes of aeroallergens (house dust mites, animal danders, pollens, molds, and cockroach) by skin prick testing in a group of 494 children with suspicious allergic symptoms and in their parents. RESULTS: The frequency of parental atopy was highest (51.6%) in polysensitized children (n = 189), intermediate (37.1%) in monosensitized children (n = 178), and was lowest (22.4%) in nonsensitized children (n = 127). The proportion of polysensitized subjects among atopic parents was significantly higher for polysensitized children (45.6%) than for monosensitized children (31.1%). Polysensitized children were found to more frequently have one or both parents polysensitized (32.3%, 7.4%) than monosensitized children (18.5%, 2.2%) with odds ratios of 2.09 (95% CI: 1.29-3.40) and 3.48 (1.12-10.78), respectively, whereas the likelihood of having one or two monosensitized parents was not increased for polysensitized children. CONCLUSION: Our data suggest a familial coincidence of atopy profile in terms of monosensitization and polysensitization, although the relative importance of genetic or environmental influence should be studied further.

Allergens↗

In search for predictive factors for atopy in human cord blood.

Since early prevention is regarded as an important corner stone in the management of atopic diseases, the identification of reliable markers detecting individuals at risk are of major interest. Therefore, many efforts have been made to unravel reliable predictors for atopy which might identify children at risk and allow the initiation of preventive strategies at an early stage. In the past, much scientific energy has been forced in particular on the development of as noninvasive methods as possible to reach this goal. It is obvious that the identification of markers for atopy at the earliest time of life - namely immediately after birth - represents one of the most attractive attempts. In consequence various studies have been initiated to address this issue investigating markers for atopy in cord blood. Most of them have been geared to our current knowledge about cellular and soluble factors which are dysregulated in adolescent atopic individuals. Although the findings of these studies will improve our knowledge about the initial evolution of atopy, several parameters evaluated did not show any association or have led to almost conflicting results. In order to provide an up-date about the current developments in this field, recent research findings on predictive factors for atopy in cord blood are summarized in the following synopsis.

Antigen-Presenting Cells↗

Hospitalization for RSV bronchiolitis before 12 months of age and subsequent asthma, atopy and wheeze: a longitudinal birth cohort study.

Several epidemiological studies have reported recurrent wheezing and asthma in children after respiratory syncytial virus (RSV) bronchiolitis in infancy. The relationship with allergic sensitization is less clear and recent evidence suggests an interaction between atopy and RSV infection in the development of asthma. Data from a large, population-based, birth-cohort (Avon Longitudinal Study of Parents and Children) were used to compare outcomes of children according to whether or not they had been admitted to hospital in the first 12 months with RSV-proven bronchiolitis. Outcomes considered were 12-month prevalence of wheeze at two ages (between 30-42 and 69-81 months), cumulative prevalence of doctor-diagnosed asthma at 91 months and skin prick test defined atopy at 7 yr. Multivariable logistic regression models were used to calculate odds ratios for outcomes adjusted for potential confounders. A total of 150 infants (1.1% of the cohort) were admitted to hospital within 12 months of birth with RSV bronchiolitis. The prevalence of wheezing was 28.1% in the RSV group and 13.1% in controls at 30-42 months and 22.6% vs. 9.6% at 69-81 months. The cumulative prevalence of asthma was 38.4% in the RSV group and 20.1% in controls at 91 months. Atopy was found in 14.6% of the RSV group and in 20.7% of controls at 7 yr. RSV bronchiolitis was associated with subsequent wheezing between 30-42 (Odds ratio [95% CI] 2.3 [1.3, 3.9]) and 69-81 months (OR 3.5 [1.8, 6.6]) and with the cumulative prevalence of asthma at 91 months (OR 2.5 [1.4, 4.3]) but not with atopy (OR 0.7 [0.2, 1.7]). In a population-based birth cohort, RSV bronchiolitis was associated with subsequent wheezing and asthma but not with the development of atopy by age 7 yr.

Asthma↗

Relationship between exhaled nitric oxide and atopy in Asian young adults.

OBJECTIVES: The relationship between exhaled nitric oxide and atopy is controversial. The aim of this study was to determine the relationship between exhaled nitric oxide (FE(NO)) and atopy in Asian young adults. METHODOLOGY: Subjects were assessed by: (i) the International Study of Asthma and Allergies in Childhood questionnaire to differentiate asthmatic from nonasthmatic and rhinitis from non-rhinitis subjects; (ii) skin prick testing to 10 allergens; and (iii) FE(NO) measurements performed online at a flow rate of 50 mL/s. RESULTS: Complete results were available for 84 subjects. FE(NO) values were highest in atopic asthmatics (n = 34; median FE(NO), 59.8 p.p.b.; interquartile range, 30.4-85.5 p.p.b), followed by atopic nonasthmatics (n = 34; median, 38.4 p.p.b.; range, 16.7-49.3 p.p.b), nonatopic asthmatics (n = 5; median, 19.1 p.p.b.; range, 17.9-33.4 p.p.b), and lowest in nonatopic nonasthmatics (n = 11; median, 15.7 p.p.b.; range, 11.5-21.7 p.p.b). FE(NO) values were significantly higher in atopic (n = 68; median, 44.7 p.p.b.; range, 27.3-75.2 p.p.b) compared to nonatopic subjects (n = 16; median, 17.0 p.p.b.; range, 11.7-23.8 p.p.b.; P < 0.0001), regardless of asthma and rhinitis status. FE(NO) levels correlated with the severity of atopy (wheal size) for both asthmatic (r = 0.44, P = 0.005) and nonasthmatic subjects (r = 0.48, P = 0.001). There was no significant difference in FE(NO) levels between nonatopic asthmatics and nonatopic nonasthmatic subjects (P = 0.25). CONCLUSIONS: Increased FE(NO) levels are more reflective of atopy rather than asthma, and increased nitric oxide production may be predominantly a feature of atopy in asthmatics.

Adolescent↗

Atopy and coeliac disease: bias or true relation?

Several reports have suggested a relationship between atopy and coeliac disease and atopy has also been linked to the pathogenesis of the mucosal damage. Conclusive epidemiological evidence of the relationship has not been satisfactorily established. The case-control study reported here was undertaken to test the hypothesis that coeliac disease is linked to atopy. Eighty-two coeliac disease cases and a group of 180 age matched controls and all their first degree relatives were investigated for atopy. Siblings of cases reported an increased prevalence of food intolerance, compared to siblings of controls. No increase in asthma, eczema, rhinitis, conjunctivitis, cow's milk protein allergy (CMPA) were detected in relatives of cases, compared to those of controls. When each index case and each control were investigated no increased prevalence of atopic conditions was found. Skin prick testing to major allergens was positive in a similar proportion of cases and controls. Serum total IgE of a random sample of cases and controls showed no difference in mean values. This study supports the null hypothesis: there is no difference in the prevalence of atopy in cases affected by coeliac disease and their relatives, compared to controls and their relatives. The sources of possible bias in previous reports are discussed.

Case-Control Studies↗

Continued increase in the prevalence of asthma and atopy.

AIMS: To describe the change in the prevalence of wheeze, diagnosed asthma, and atopy in Wagga Wagga, NSW, Australia, between 1992 and 1997, and to compare this to the increase in prevalence reported between 1982 and 1992. METHODS: A cross sectional study of the prevalence of respiratory symptoms and atopy in schoolchildren aged 8-11 years (n = 1016, response rate 71%) in 1997 compared with studies of similar design in 1992 (response rate 83%, n = 850) and 1982 (response rate 88%, n = 769). Main outcome measures were respiratory symptoms measured by parent completed questionnaire and atopy measured by skin prick tests. RESULTS: Between 1992 and 1997, the prevalence of wheeze increased by 5.1% (95% CI 1.2 to 9.0), asthma diagnosis by 8.1% (95% CI 3.8 to 12.4), and atopy by 6.7% (95% CI 2.2 to 11.2). Similar increases in prevalence had been found between 1982 and 1992. CONCLUSIONS: The prevalence of wheeze, asthma diagnosis, and atopy in Wagga Wagga has continued to increase.

Asthma↗

Atopy and keratoconus: a multivariate analysis.

BACKGROUND/AIMS: The primary goal of this study was to determine if atopy is a risk factor for keratoconus. Other potential risk factors were also studied and included age, sex, race, eye rubbing, mitral valve prolapse, handedness, collagen vascular disease, ocular trauma, pigmentary retinopathy, Marfan's syndrome, Down's syndrome, and a history of contact lens wear. METHODS: A case-control study was designed (n=120) with incident cases assembled from the years 1985-99. Controls were chosen from the same person-time experience as cases and were picked from a source population with multiple outcomes ensuring that none was knowingly related to any of the potential exposures being studied. Atopy was defined based on the UK working group 1994 definition (at least 4/6 criteria = complete, 3/6 criteria = incomplete, and at least 1/6 criteria = partial). Keratoconus was defined based on clinical criteria and previously published I-S values. Multiple logistic regression was used in the analysis to obtain the odds ratios as the measure of association. RESULTS: In the univariate associations, there was an association between keratoconus and atopy as well as eye rubbing and family history of keratoconus. However, in the multivariate analysis, only eye rubbing was still a significant predictor of keratoconus (odds ratio = 6.31 p = 0.001). CONCLUSIONS: This study supports the hypothesis that the most significant cause of keratoconus is eye rubbing. Atopy may contribute to keratoconus but most probably via eye rubbing associated with the itch of atopy. No other variable measured was significantly associated with the aetiology of keratoconus.

Adult↗

HLA antigens and atopy in children with coeliac disease.

HLA antigens and various aspects of atopy were studied in 42 Finnish children and adolescents with coeliac disease, and the results were compared with findings of recent population studies. The HLA associations were as expected: relative risks for coeliac disease in individuals with HLA-B8, DR3, and DR7 were 8 . 0, 18 . 6, and 15 . 0, respectively. Children with coeliac disease were significantly more often atopic than unselected schoolchildren. Atopy was significantly more frequent and the onset of coeliac disease later for B8/DR3- patients than B8/DR3+ patients. There was no obvious relation between DR7 and atopy. It is concluded that atopy predisposes to coeliac disease partly independently of the HLA-DR3 associated disease susceptibility gene(s), and that different mechanisms may operate in the pathogenesis in coeliac disease patients with and without atopy.

Adolescent↗

Atopy: a predisposing factor for chronic bronchitis in Finland.

STUDY OBJECTIVE: To investigate the predictive value of atopy, smoking, and living in a farm environment in the development of chronic bronchitis. DESIGN: This was a cross sectional and longitudinal study. SETTING: Postal surveys carried out in Finland in 1975 and 1981. PARTICIPANTS: The study was part of the Finnish twin cohort study, which included adult twin pairs born in Finland before 1958. The cross sectional sample consisted of 18,351 subjects, including 1025 prevalent cases, and the follow up sample comprised 17,134 subjects, 553 of whom were incident cases of chronic bronchitis. MAIN RESULTS: According to the cross sectional data, chronic bronchitis was associated with atopy (relative risk 1.41) and smoking (2.43). In the follow up data, chronic bronchitis was related to atopy (1.28), smoking (2.31), and farming (1.45). CONCLUSIONS: The results confirm the earlier finding in the Finnish farming population that, in addition to smoking, atopy predisposes the development of chronic bronchitis. A farm environment was also found to be a predisposing factor. The results give further support to the "Dutch hypothesis" on the etiology of chronic bronchitis, according to which atopy is a predisposing factor.

Adolescent↗