Asthma Sensitization Research Articles

Association between first‐degree familial predisposition of asthma and atopy (total IgE) in newborns

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

Corticosteroid Resistant (CR) Asthma Is Associated with Classical Activation Of Airway Macrophages and Exposure To Lipopolysaccharide (LPS)

RATIONALE: Microbial products like LPS affect the phenotype and function of airway macrophages and have been shown to cause severe asthma. We studied airway macrophages from CR and corticosteroid sensitive (CS) asthmatics for expression of pro-inflammatory cytokines, chemokines and exposure to LPS to further identify mechanisms of steroid resistance.

Consultation and referral guidelines citing the evidence: How the allergist-immunologist can help

Consultation and referral guidelines citing the evidence: How the allergist-immunologist can help

Cyclooxygenase-1 gene polymorphisms in patients with different asthma phenotypes and atopy

Cyclooxygenase-1 (COX-1) regulates the biosynthesis of prostaglandins, which are important mediators in asthma. The possible association of COX-1 gene polymorphisms with asthma has not been investigated. The allele frequencies of 20 COX-1 polymorphisms were determined in a random Australian Caucasian population using MassARRAY technology. Informative and potentially functional promoter (c.8592C > T, c.1676C > T) and coding region (c.22C > T, c.50C > T) polymorphisms were investigated in carefully phenotyped patients with mild (n = 316), moderate (n = 241), severe (n = 86) or aspirin-intolerant asthma (AIA) (n = 58), and in nonasthmatic subjects (n = 477). There were no allelic, genotypic or haplotypic associations between these four polymorphisms and asthma or asthma severity. Over-representation of the c.50TT genotype among AIA patients (3.4%) compared with aspirin-tolerant patients (0.8%), and a global haplotype association with AIA did not reach statistical significance. The c.22TT genotype was less frequent among atopic (0.1%) rather than nonatopic individuals (1.2%; odds ratio = 9.05, 95% confidence interval 1.01-81.29). In conclusion, the present investigation of cyclooxygenase-1 polymorphisms in asthma indicates that they do not appear to play a substantial role in genetic pre-disposition for asthma or asthma severity. However, the c.22TT genotype confers a small protective effect against atopy. Potential associations with aspirin-intolerant asthma were identified and warrant further investigation in a larger population of aspirin-intolerant asthma patients.

The primary prevention of asthma in children study: Design of a multifaceted prevention program

The PREVASC study addresses the primary prevention of asthma in infants and small children. The objective of this study is to investigate whether a multifaceted prenatally started intervention strategy in high-risk infants leads to a decrease in the occurrence of (severe) asthma and whether a refinement of the prevention strategy leads to an increase in the adherence to the prevention program. The primary prevention program includes house dust mite impermeable bed coverings, education on breast feeding, hypoallergenic feeding, timing of introduction of solid food and smoking cessation. A total of 888 infants were prenatally included. By the time of inclusion the mothers were 3-7 months pregnant. About 27 infants were excluded from the study and 18 dropped out. Of the remaining 843 infants 535 had a first-degree familial predisposition of asthma (high-risk group), whereas a reference group of 308 (162 boys) infants was not predisposed for asthma in the first-degree (low-risk group). To evaluate the (cost-)effectiveness of the preventive intervention, 222 (118 boys) infants of the high-risk group allocated to the intervention group and 221 (112 boys) allocated to a control group are followed up. The low-risk infants served as controls to evaluate the predictive value of high risk (first-degree familial predisposition of asthma). The infants are followed from the prenatal stage until they reach the age of 6 yr. The remaining 92 high-risk infants were included in an optimized randomized-clinical adherence trial (RCAT). Of these 92 infants, 45 (20 boys) were allocated to an intervention group and 47 (24 boys) to a control group. Until now all infants have been followed for at least 1 yr.

Reduced activation by systemic glucocorticoid of the AP-1 component c-jun in bronchial mucosal cells of GC sensitive, but not resistant asthmatics

Component c-jun in Bronchial Mucosal Cells of GC Sensitive, but Not Resistant Asthmatics C. J. Corrigan, K. Mallett, T. Loke, J. Ratoff, B. O’Connor, T. Lee; Asthma, Allergy & Respiratory Science, Guy’s. King’s and St. Thomas’ School of Medicine, London, UNITED KINGDOM. RATIONALE: Our previous studies implicate the transcriptional regulatory factor AP-1, composed of c-fos and c-jun, in the regulation of the clinical response of asthmatics to systemic GC therapy. We hypothesised that c-fos expression and c-jun phosphorylation are increased in the bronchial mucosa of GC resistant, as compared with sensitive asthmatics and differentially regulated by systemic GC. METHODS: We used immunohistochemistry with validated antibodies and digital image analysis to measure the expression of c-fos and total and phosphorylated c-jun (c-junP) in mucosal inflammatory cells in endobronchial biopsies from 9 GC sensitive (∆FEV1>25%, age 35-67 yr) and 20 GC resistant (∆FEV1 3 visits were analyzed at baseline and after 3 visits for asthma severity, medication use, urgent care visits, and missed school days. RESULTS: From 3/01-1/04, 440 children were evaluated with a mean age of 8 yrs (range 3-18), 46.4% female, 91.6% African American, >60% Medicaid and 70% with persistent asthma. At baseline, 20.9% were on albuterol alone and 9.8% on no medications. Baseline data (mean, range) included annual lost school days (7.4, 0-100), lifetime ED visits (6.9, 0-100), hospitalizations (1.6, 0-35) and oral steroid courses (4.4, 0-60). Skin testing revealed 83.6% with at least one positive test (54.3% + cockroach and > 40% + to mouse, tree and dust mite). For the 114 children seen for > 3 visits the # of school days missed decreased to an average of 2.6/year. Mean annual ED visits for this group were 0.58 (range 0-8), hospitalizations 0.07 (range 0-3) and oral steroids 0.72 (0-11). Asthma severity decreased from > 50% moderate/severe at baseline to 71.8% mild after >3 visits with 89% on controller medications. CONCLUSIONS: During the first 2 years of the program, the Baltimore Breathmobile has seen increased use of controller medications, decreased missed school days and decreased asthma morbidity. Funding: Maryland Tobacco Restitution Fund

Expression of CD163 on peripheral blood monocytes in allergic asthma patients during specific immunotherapy (SIT)

RATIONALE: CD163 is expressed on alternatively activated mononuclear phagocytes. The aim of this study was to evaluate the expression of CD163 and CD36 on peripheral blood monocytes of allergic asthma patients during SIT with house dust mite allergen extracts.METHODS: 25 mild allergic asthma (AA) patients with positive skin prick tests and a positive bronchial provocation test with Dermatophagoides pteronyssinus extract were selected for the study. 10 nonatopic healthy persons (HP) were used as a control group. SIT was performed on 20 (AA-IT) patients using Novo Helisen Depot. 5 patients (AA) who declined SIT were considered a control group. Blood was collected before, 3 months and 12 months after initiation of SIT. FACS analysis was performed on whole blood samples using labeled monoclonal antibodies against CD14, CD36 and CD163 (Pharmingen, USA).RESULTS: Before SIT more CD14 cells co-expressing CD163 (CD14+/CD163+) were found in AA-IT (47.4 +/- 19.6%) and AA (43.2 +/- 16%) than in HP (25.6 +/- 8.5; p< 0.01). In AA-IT patterns during SIT the number of CD14+/CD163+ cells increased reaching 54.8 +/- 11.6 % at 3 months and 49.1 +/- 8.9% at 12 months (p<0.01). The maximum increase in CD14+/CD163+ cells was associated with maximum improvement in FEV1. No change was found in the number of CD14+/CD163+ cells in AA during 12 month period. The number of CD14+/CD36+ monocytes decreased in AA-IT but did not change in AA.CONCLUSIONS: In house dust mite sensitive asthmatics, SIT is associated with alternative activation of peripheral blood monocytes. RATIONALE: CD163 is expressed on alternatively activated mononuclear phagocytes. The aim of this study was to evaluate the expression of CD163 and CD36 on peripheral blood monocytes of allergic asthma patients during SIT with house dust mite allergen extracts. METHODS: 25 mild allergic asthma (AA) patients with positive skin prick tests and a positive bronchial provocation test with Dermatophagoides pteronyssinus extract were selected for the study. 10 nonatopic healthy persons (HP) were used as a control group. SIT was performed on 20 (AA-IT) patients using Novo Helisen Depot. 5 patients (AA) who declined SIT were considered a control group. Blood was collected before, 3 months and 12 months after initiation of SIT. FACS analysis was performed on whole blood samples using labeled monoclonal antibodies against CD14, CD36 and CD163 (Pharmingen, USA). RESULTS: Before SIT more CD14 cells co-expressing CD163 (CD14+/CD163+) were found in AA-IT (47.4 +/- 19.6%) and AA (43.2 +/- 16%) than in HP (25.6 +/- 8.5; p< 0.01). In AA-IT patterns during SIT the number of CD14+/CD163+ cells increased reaching 54.8 +/- 11.6 % at 3 months and 49.1 +/- 8.9% at 12 months (p<0.01). The maximum increase in CD14+/CD163+ cells was associated with maximum improvement in FEV1. No change was found in the number of CD14+/CD163+ cells in AA during 12 month period. The number of CD14+/CD36+ monocytes decreased in AA-IT but did not change in AA. CONCLUSIONS: In house dust mite sensitive asthmatics, SIT is associated with alternative activation of peripheral blood monocytes.

Abstracts

Abstracts

Immunotherapy Attenuates Eosinophil Transendothelial Migration Induced by the Supernatants of Antigen-Stimulated Mononuclear Cells from Atopic Asthmatics

Background: Eosinophil transendothelilal migration across vascular endothelial cells is an initial step of eosinophil accumulation in allergic inflammation. There is increasing evidence that specific immunotherapy (SIT) modulates the production of inflammatory molecules from mononuclear cells. Objective: The present study was undertaken to examine whether SIT modifies eosinophil transendothelial migration induced by the supernatants of antigen-stimulated mononuclear cells from atopic asthmatics. Methods:Dermatophagoides farinae(Df)-sensitive mild persistent asthmatics were divided into a SIT-treated group and a control group. Peripheral blood mononuclear cells (PBMC) were isolated before and after SIT using the rush protocol, and cultured for 96 h at 37°C in the presence or absence of Df antigen. Eosinophils were isolated from the blood of healthy subjects, and put on transwell filters coated with pulmonary microvascular endothelial cell monolayers stimulated with IL-4 plus TNF-α. The supernatants of PBMC were applied to the lower compartment and the transmigration of eosinophils was examined. Results:Df stimulation of PBMC resulted in an augmentation of eosinophil transendothelial migration. This enhancement was abrogated following SIT. In the control group, the antigen-induced effect on eosinophil transmigration did not show an interval change. Conclusion: SIT attenuates eosinophil transendothelial migration induced by antigen-stimulated mononuclear cells.

Influence of early life exposures on incidence and remission of asthma throughout life

Background Knowledge of the effects of early environmental and congenital factors on the natural history of asthma may provide important clues to the pathogenesis of asthma. Objective We assessed associations between potential, early determinants and the incidence and remission of asthma throughout life, and tested whether the strength and direction of these associations varied in childhood, adolescence, and adulthood. Methods The data pertaining to the individual asthma history of 18,156 subjects, age 0 to 44 years, who attended the clinical stage of the European Community Respiratory Health Survey were analyzed retrospectively by life-event methods. Onset of asthma was defined as age at the first attack, and asthmatic patients were considered to be in remission if they had not been under treatment or had an attack of asthma in the past 24 months. Onset and remission were evaluated in 3 time windows: <10, 10 to 20, and ≥20 years of age. The associations of asthma with early determinants were estimated by hazard ratios (HRs). Results A family history of asthma or allergy was associated with a higher risk of developing asthma (HR, 1.89; 95% CI, 1.67-2.13) and a lower chance of remission (HR, 0.79; 95% CI, 0.64-0.99) throughout life. No matter what one's genetic predisposition was, early, acute respiratory infections were associated with an increased lifelong risk of asthma onset (pooled HR, 3.19; 95% CI, 2.75-3.69), whereas early contact with older children, which is a marker of prolonged, intermittent exposure to infectious agents, conferred permanent protection against asthma (HR, 0.84; 95% CI, 0.74-0.96) and increased the chance of remission in childhood asthma (HR, 1.50; 95% CI, 1.10-2.04). Pet ownership had a protective effect only in childhood (HR, 0.78; 95% CI, 0.74-0.96), whereas maternal smoking did not show a significant association with asthma. Female sex was negatively associated with the onset of asthma in childhood (HR, 0.62; 95% CI, 0.52-0.75) and positively in adulthood (HR, 2.01; 95% CI, 1.61-2.51). The pattern of associations was similar in sensitized (positive assay to specific IgE) and nonsensitized asthmatic patients. Conclusion Genetic predisposition and exposure to infectious agents are major early determinants that influence a subsequent history of asthma. The length and type of exposure to infectious agents seem able either to promote or to suppress an anti-inflammatory process, unrelated to IgE, which can partially interfere with an acquired predisposition for asthma.

Combination of IL-2 and IL-4 inhibits glucocorticoid receptor alpha (GCR-alpha) nuclear translocation in peripheral blood mononuclear cells (PBMC) and this effect is reversed by gamma interferon

Rationale Steroid resistant asthma is associated with increased IL-2 and IL-4 gene expression. IL-2/IL-4 combination is known to induce corticosteroid resistance. However the mechanism for steroid resistance is unknown. Methods PBMC from 6 healthy donors were grown in the presence of 50U/ml IL-2/IL-4 with or without 100U/ml gammaIFN, or in the media alone for 48h. The GCRalpha nuclear translocation was assessed in response to steroids (10-6M dexamethasone (DEX) 1h) by immunocytochemistry. PBMC from 5 steroid resistant (SR) and 3 steroid sensitive (SS) asthmatics were examined as well. Results In the absence of DEX, GCRalpha was mostly in the cell cytoplasm of PBMC. The cells that were grown in the media alone translocated GCRalpha in response to DEX. However, after IL-2/IL-4 treatment GCRalpha failed to translocate (p<0.001 as compared to media+DEX). Incubation with IL-2/IL-4 significantly reduced media levels of gammaIFN (36.2 ± 5.6%, p<0.001 as compared to IL-2 alone). We examined whether presence of gammaIFN is required to sustain proper steroid response. Addition of gammaIFN to IL-2/IL-4 combination restored GCRalpha nuclear translocation (p<0.0001). Reduced nuclear translocation of GCRalpha was also observed in PBMC from 4 of 5 SR asthmatics, while PBMC from 3 of 3 SS asthmatics underwent translocation of GCRalpha in response to DEX. The one SR asthmatic, with normal GCRalpha translocation in PBMC, had no GCRalpha nuclear translocation in BAL cells suggesting that the defect was localized to the lungs. Conclusions Steroid resistance of human PBMC may be associated with reduced GCRalpha nuclear translocation and this is defined by the cytokine environment.

Parental asthma as a risk factor for the development of early skin test sensitization in children

Background Recent epidemiologic evidence has challenged the paradigm suggesting a direct causal relationship between allergic sensitization and asthma. Objective We sought to investigate the role of a familial predisposition for asthma in the development of atopy in children. Methods Subjects were participants in the Tucson Children's Respiratory Study. Skin tests to aeroallergens were performed in parents and in children at ages 6, 11, and 16 years. Parents were considered asthmatic if they reported physician-confirmed asthma. Parents were divided into 4 phenotypes on the basis of skin sensitization (Skt+ or Skt−) and asthma status (As+ or As−): Skt−/As−, Skt−/As+, Skt+/As−, and Skt+/As+. Results Children's allergic sensitization differed among parental phenotypes at all ages ( P < .0001). Children in the Skt+/As− and Skt+/As+ groups were significantly more likely to be allergic than children in the Skt−/As− group at all ages. Among children with allergic parents, those with at least one parent with asthma were significantly more likely to have positive skin test responses than those with nonasthmatic parents at age 6 years (52.4% vs 37.4%, P < .005) and 11 years (70.1% vs 55.6%, P < .005) but not at age 16 years (82.3% vs 75.1%, P = .180). Results were independent of wheezing in the child and of the characteristics of atopy in parents. The Skt−/As+ group had too few subjects for meaningful comparisons. Conclusion Among children of atopic parents, parental asthma is a risk factor for allergic sensitization in early childhood. The strong association between allergic sensitization and asthma is at least in part explained by an increased susceptibility to allergen sensitization in subjects predisposed to asthma.

Signal transducers and activators of transcription 6 (Stat6) variants in childhood and adult asthma

Signal transducers and activators of transcription 6 (Stat6) is a key transcription factor involved in interleukin (IL)-4 and IL-1 3-mediated biological responses. Recently, we reported the association between the dinucleotide (GT) repeat polymorphism in the first exon of Stat6 and allergic subjects in a Japanese population. The aim of the present study was to evaluate whether this GT repeat polymorphism is associated with bronchial asthma, including childhood asthma and atopic and non-atopic adult asthma. Stat6 gene polymorphisms were genotyped by polymerase chain reaction (PCR) fragment length polymorphism analysis. In the first exon of Stat6, polymorphic PCR products were classified into six alleles (12–17 GT repeats). A significant difference was found in the genotypic frequency of the GT repeat polymorphism between controls and child asthmatics (P = 0.015), but not atopic or non-atopic adult asthma. The frequency of the 15 repeat allele (wild type) was lower in child asthmatics than in controls (P = 0.0047; odds ratio (OR) 1.6, 95% confidence interval (CI) 1.16-2.23), whereas shorter repeat alleles (12, 13 and 14 GT repeat) were higher in child asthmatics than in controls (P = 0.0064; OR (95%CI) 1.66 (1.15-2.39)). Genetic variations in the Stat6 gene may be associated with a predisposition for childhood asthma.

Dust mites living in human lungs – the cause of asthma?

Asthma does not have a clear cause and may represent a cluster of diseases. We propose that asthma in house dust mite sensitive patients may be caused by recurrent inhalation of live dust mites which are able to live for some time in the bronchioles of the lung. To provide themselves with a food source, the mites may purposefully excrete proteolytic enzymes, including Der p1, which increase epithelial shedding by freeing cells from the basement membrane. The mites then feed on the shed respiratory epithelial cells. Consequent loss of an intact respiratory epithelium exposes underlying tissues to dust mite protein and other allergens triggering sensitisation to these proteins. Later, repeated infestation provokes an allergic response which manifests itself as asthma attacks. The evidence for this hypothesis was tested against the Bradford–Hill criteria for causation; consistency, strength, temporal association and dose response. Potential areas for further research were also identified. The association between asthmatic symptoms and pulmonary acariasis was consistent across a number of studies. Determining the strength of the association and any dose response requires more work which is dependent on the development of better tests for the detection of mites in sputum. There was tentative evidence of a temporal association in the published studies identified. Biological plausibility and experimental evidence was available for pulmonary acariasis in primates and arsenic treatment was effective in humans. Better tests for mites in sputum are needed, as is work to assess more modern anti-acaricidal drugs in dust mite sensitive asthmatics.

Distribution in allele frequencies of predisposition-to-atopy genotypes in Chinese children.

Asthma is one of the most common chronic diseases in childhood; it is caused by a complex interaction between genetic factors and exposure to environmental allergens and irritants. Previous studies using the candidate gene approach showed that asthma was linked to a number of susceptibility genetic loci in Caucasian subjects. There are, however, only a few studies on asthma predisposition genes in the Chinese population. We studied the distribution of allele frequencies of I50V for the interleukin-4 receptor, two polymorphisms in intron 2 and exon 7 for the high-affinity IgE receptor (Fc epsilon RI-beta), R16G and E27Q for the beta(2)-adrenoceptor,and R275Q (824G/A) for CC chemokine receptor 3 in Chinese children.Seventy-six patients, with a mean age of 10.6 years, and 70 age- and sex-matched controls, were studied. Significantly more subjects in the asthma group had specific IgE antibodies against environmental allergens (P < 0.0001; odds ratio, 9.82). Genotyping of the six genetic markers showed that none of the six polymorphisms was associated with asthma in this cohort. The allele frequencies of I50V, R16G, and E27Q in our population were similar to those published for Asian subjects but not Caucasians. The R275Q substitution was a rare finding in our study and in the published reports. Our results demonstrate ethnic differences in polymorphisms of atopy candidate genes. Additional studies involving larger samples are required to investigate the association between asthma or atopy and the genotypes studied to date in Chinese children.

Worldwide asthma epidemic

Overall, an increasing trend has been reported in the prevalence of asthma in recent decades; however, large variations in the prevalence of childhood and adult asthma have been reported. Prevalences are generally higher in affluent countries than in poorer countries. Numerous hypotheses have been proposed to explain these trends. These theories most often relate to socioeconomic status, family size, early-childhood infections and hygiene, allergen exposure, diet and obesity, perinatal risk factors, and environmental pollution. Asthma is a complex syndrome rather than a single entity. Different phenotypes with varying prognosis and determinants have been described, particularly those that occur during the childhood years [1]. Transient early wheezing is characterized by the occurrence of wheezing symptoms in infants up to age 2 to 3 years, after which the symptoms disappear. The main predictor of these wheezing illnesses is premorbid, reduced lung function [2,3]. These impairments in pulmonary function in part are determined by passive smoke exposure in utero [4] and result in symptoms of airway obstruction in infants who are infected with respiratory viruses. Atopy and a family history do not influence the incidence and natural course of this wheezing phenotype. In contrast, wheeze among school-aged children most often is associated with atopic sensitization, airway hyperresponsiveness, and a familial predisposition for asthma [1]. The severity of symptoms and degree of atopic sensitization and airway responsiveness determine the prognosis of this wheezing phenotype [5]. It seems likely that a third wheezing phenotype exists among preschool children that mostly is related to viral infections [6]. These children have a better prognosis than atopic wheezers, and their symptoms often disappear around school age. Most epidemiologic studies have been cross-sectional surveys and do not enable examination the different wheezing phenotypes. Only prospective studies

Association between familiar predisposition of asthma and IgE in infants 5 days post-partum

In this study we investigated the relation between first degree familiar predisposition of asthma and IgE in infants five days postpartum. IgE was determined in blood collected with the heel prick making sure that the results are not disturbed by contamination with maternal IgE. The high risk group consists exclusively of infants with a first degree familiar predisposition of asthma, instead of a mix of asthma, hay fever, atopic eczema and food allergy as in other studies. Total IgE was determined using a modified RAST. A random sample of 301 infants was taken from a prospective birth cohort of 733. Infants in the high risk group (n=193) had at least one family member with asthma. In the control group (n=108) this predisposition was not present. We observed a statistically significant difference in total IgE (p=0.025) between the high risk group (75th percentile=0.32) and the control group (75th percentile=0.21) five days postpartum. This difference could not be attributed to sex. We assume that familiar predisposition of asthma is associated with IgE five days postpartum.

Expression of TGF-β1, TGF-β RII and EGFR in nasal polyp tissue: Comparison between ASA- and non-ASA sensitive asthmatics

Expression of TGF-β1, TGF-β RII and EGFR in nasal polyp tissue: Comparison between ASA- and non-ASA sensitive asthmatics

Role of sulfite additives in wine induced asthma: single dose and cumulative dose studies

BACKGROUNDWine appears to be a significant trigger for asthma. Although sulfite additives have been implicated as a major cause of wine induced asthma, direct evidence is limited. Two studies were...

Oligogenic approaches to the predisposition of asthma in ethnically diverse populations.

Using the genome-wide screening data of the Collaborative Study on the Genetics of Asthma (CSGA) (226 families, 1,461 genotyped subjects, 323 marker loci) and Hutterite studies (129 families, 690 genotyped subjects, 365 marker loci), we applied a genetic similarity function in order to quantify the inter-individual genetic distances d(xi,xj) between feature vectors xi, xj made up by the allelic patterns of subjects i,j with respect to loci li, l2,..., ln. Based on this similarity function, we structurally decomposed the genetic diversity of the CSGA population in order to address the question of ethnicity-related asthma vulnerability for genetically homogenous CSGA subgroups. The question of ethnicity-independent asthma vulnerability was investigated with all CSGA families as training and the Hutterite families as replication samples. We evaluated the between-sib similarities, which were expected to deviate from "0.5" in affected sib pairs if the region of interest contained markers close to disease-causing genes. The reference value 0.5 was derived by determining the parent-offspring similarities, which are always 0.5, irrespective of the affection status of parents and offspring. We found 18 vulnerability loci on chromosomes 1, 3, 4, 5, 6, 8, 12, 13, and 14, which were remarkably reproducible in the CSGA and the Hutterite data and constituted an ethnicity-independent oligogenic model.