Biomedical subjects

M Wjst

Publications and source records attributed to M Wjst.

At least 19 recordsLinked to original sources

PubMed2006

Cytokine gene polymorphisms and atopic disease in two European cohorts. (ECRHS-Basel and SAPALDIA).

BACKGROUND: Atopy and allergic phenotypes are biologically characterized by an imbalanced T helper cell response skewed towards a type 2 (TH2) immune response associated with elevated serum immunoglobulin E (IgE) levels. Polymorphisms in cytokine genes might modulate regulation of the TH1/TH2 balance. We thus aimed at reproducing our previous findings from a European study population on the association of various cytokine polymorphisms with self-reported hay fever as well as increased total and specific IgE levels in two comparable study populations. METHODS: Two prospective Caucasian cohorts were used. In the Basel center of the European Community Respiratory Health Survey (ECRHS, n = 418) ten distinct cytokine polymorphisms of putative functional relevance were genotyped. In the Swiss cohort Study on Air Pollution And Lung Disease In Adults (SAPALDIA, n = 6003) two cytokine polymorphisms were genotyped. The associations of these polymorphisms with atopy were estimated by covariance and logistic regression analysis. RESULTS: We confirmed IL4, IL10, IL6 and IL18 as candidate genes for atopic health outcomes. In the large, well-characterized SAPALDIA cohort the IL6(-174G>C) and IL18(-137G>C) polymorphisms were associated with circulating total IgE concentrations in subjects with hay fever. The IL18(-137G>C) polymorphism was also associated with the prevalence of hay fever. CONCLUSION: Comprehensive characterization of genetic variation in extended cytokine candidate gene regions is now needed. Large study networks must follow to investigate the association of risk patterns defined by genetic predisposing and environmental risk factors with specific atopic phenotypes.

Journal Article↗

PubMed2006

Inhalation of ultrafine carbon particles triggers biphasic pro-inflammatory response in the mouse lung.

High levels of particulate matter in ambient air are associated with increased respiratory and cardiovascular health problems. It has been hypothesised that it is the ultrafine particle fraction (diameter <100 nm) that is largely responsible for these effects. To evaluate the associated mechanisms on a molecular level, the current authors applied an expression profiling approach. Healthy mice were exposed to either ultrafine carbon particles (UFCPs; mass concentration 380 microg x m(-3)) or filtered air for 4 and 24 h. Histology of the lungs did not indicate any pathomorphological changes after inhalation. Examination of the bronchoalveolar lavage fluid revealed a small increase in polymorphonuclear cell number (ranging 0.6-1%) after UFCP inhalation, compared with clean air controls, suggesting a minor inflammatory response. However, DNA microarray profile analysis revealed a clearly biphasic response to particle exposure. After 4 h of inhalation, mainly heat shock proteins were induced, whereas after 24 h, different immunomodulatory proteins (osteopontin, galectin-3 and lipocalin-2) were upregulated in alveolar macrophages and septal cells. In conclusion, these data indicate that inhalation of ultrafine carbon particles triggers a biphasic pro-inflammatory process in the lung, involving the activation of macrophages and the upregulation of immunomodulatory proteins.

Air Pollutants↗

PubMed2006

Association between interleukin-1 receptor antagonist gene and asthma-related traits in a German adult population.

BACKGROUND: A recent study in German and Italian families associated variants in the interleukin-1 receptor antagonist (IL1RA) gene with asthma. The aim of the present study was to further investigate the role of single nucleotide polymorphisms (SNPs) in the IL1RA gene in the development of atopy and lifelong asthma in a population-based study. METHODS: DNA samples from the German centres of the European Community Respiratory Health Survey were analysed for genetic variants in the IL1RA gene and the development of asthma, atopy and bronchial hyperreactivity. RESULTS: Carriers of the rare G allele of SNP rs447713 had a significantly increased risk of developing asthma (P = 0.0013) and allergic sensitization (P = 0.0119). Carriers of the rare C allele of SNP rs3087271 had an increased risk of asthma (P = 0.0227) and high immunoglobulin E (IgE) levels (P = 0.0232). A haplotype built from eight SNPs in the IL1RA gene (A-C-A-G-A-C-G-A) was associated with a higher prevalence of asthma (P = 0.007) and high total IgE (P = 0.02). Bronchial hyperreactivity was positively associated with the haplotype A-C-G-G-A-C-G-C (P = 0.02) and negatively with the A-C-G-G-A-C-T-C (P = 0.03). CONCLUSION: A previously described association between IL1RA and asthma in families could be reproduced in a population-based sample. The genetic variants of IL1RA gene do not to seem to affect asthma alone, but to act as modulators of asthma-related traits as well, where different haplotypes drive the development of different phenotypes.

Adult↗

PubMed2006

Changes in active and passive smoking in the European Community Respiratory Health Survey.

The aim of the present investigation was to study changes and determinants for changes in active and passive smoking. The present study included 9,053 adults from 14 countries that participated in the European Community Respiratory Health Survey II. The mean follow-up period was 8.8 yrs. Change in the prevalence of active and passive smoking was expressed as absolute net change (95% confidence interval) standardised to a 10-yr period. Determinants of change were analysed and the results expressed as adjusted hazard risk ratio (HRR) or odds ratio (OR). The prevalence of active smoking declined by 5.9% (5.1-6.8) and exposure to passive smoking in nonsmokers declined by 18.4% (16.8-20.0). Subjects with a lower educational level (HRR: 0.73 (0.54-0.98) and subjects living with a smoker (HRR: 0.45 (0.34-0.59)) or with workplace smoking (HRR: 0.69 (0.50-0.95)) were less likely to quit. Low socio-economic groups were more likely to become exposed (OR: 2.21 (1.61-3.03)) and less likely to cease being exposed to passive smoking (OR: 0.48 (0.37-0.61)). In conclusion, the quitting rate was lower and the risk of exposure to passive smoking higher among subjects with lower socio-economic status. Exposure to other peoples smoking decreased quitting rates and increased the risk of starting to smoke.

Adult↗

PubMed2005

Maternal atopy and changes in parity.

BACKGROUND: Atopic women tend to have fewer children, although atopy may favour conception. OBJECTIVE: To assess whether atopy is associated with the number of new births and whether changes in parity are associated with a change in atopy in a cohort of young women. METHODS: Women had atopy (defined as the presence of serum-specific IgE against common aeroallergens) measured in the European Community Respiratory Health Study during the years 1991--92 (n=4580). About 9 years later, 2844 (62.1%) were recontacted and 2414 (52.7%) had atopy measured again. RESULTS: Atopic women had fewer children at baseline than non-atopic women but the association disappeared at the end of the follow-up. Atopy tended to increase parity during the follow-up, but in a non-statistically significant way (relative risk=1.08; 0.86-1.35, after adjusting for number of children at baseline, age, length of follow-up, education or social class). Prevalence of atopy during the follow-up changed by the same magnitude whatever the birth cohort and the change in the number of children (P for interaction >0.7). CONCLUSION: Atopic women did not have a significantly higher fertility rate but they may postpone having their first child compared with non-atopic women. We are unable to confirm the hypothesis that atopy in women may decrease with successive pregnancies.

Adult↗

PubMed2004

Is the increase in allergic asthma associated with an inborn Th1 maturation or with an environmental Th1 trigger defect?

The main reason for the asthma epidemic in industrialized countries is unknown. While childhood mortality from acute respiratory infection is still high in developing countries where asthma prevalence is low, there might be a suppressed natural selection in industrialized countries with a high asthma prevalence. Children with an inborn Th1 maturation defect might survive by better health care and antibiotic use at the cost of higher asthma and allergy rates. Another distinct group of children maybe represented by those having an environmental Th1 trigger deficit where the immune systems is not being sufficiently exposed in early life. Both, a Th1 maturation and a Th1 trigger defect may contribute to a dual Th1 allergy theory.

Asthma↗

PubMed2004

Asthma is associated with single-nucleotide polymorphisms in ADAM33.

BACKGROUND: The ADAM33 gene has recently been associated with asthma and bronchial hyper-reactivity. It codes for a disintegrin and metalloproteinase that triggers intra- and extracellular signalling by protein shedding. OBJECTIVE: We examined whether polymorphisms in ADAM33 are associated with asthma and related traits in two German populations. METHODS: We genotyped 15 intragenic single-nucleotide polymorphisms (SNPs) by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry of allele-specific primer extension products. The transmission disequilibrium test was used for association analysis in the German asthma family study. Additionally, we tested for association of these SNPs in a case-control sample from the European Community Respiratory Health Study using Armitage's trend test. RESULTS: In both studies, we found SNPs that were significantly associated with asthma and related traits. In the family study, significant associations were observed for the SNPs F+1, ST+4 and ST+5 (with the lowest P-value for F+1, P=0.005). Remarkably, this association is seen even in the absence of linkage with two microsatellite markers from a previous genome scan either 3.1 million bases (Mb) up- or 5.6 Mb downstream. In the case-control study, SNP ST+7 (P=0.008) was significantly associated with asthma. Some of these SNPs overlapped with those found to be associated with elevated total IgE levels and bronchial hyper-responsiveness. CONCLUSION: This study replicates the recently published association between asthma and ADAM33 gene variants. However, most of the associated SNPs were at non-identical positions in the German, UK and US samples. As linkage disequilibrium is high among the tested SNPs, and there is no known functional polymorphism, either not-tested variants in ADAM33, unknown regulatory elements or a gene in close proximity is responsible for this association.

ADAM Proteins↗

PubMed2004

Single nucleotide polymorphism screening and association analysis--exclusion of integrin beta 7 and vitamin D receptor (chromosome 12q) as candidate genes for asthma.

BACKGROUND: The human genes coding for integrin beta 7 (ITGB7) and vitamin D receptor (VDR) are two of the several candidate genes for asthma and related phenotypes found in a promising candidate region on chromosome 12q that has been identified in multiple genomewide screens and candidate gene approaches. METHODS: All exons, including parts of the neighbouring introns, and the predicted promoter region of the ITGB7 gene were screened for common polymorphisms in 32 independent asthmatic and healthy probands, resulting in the detection of two single nucleotide polymorphisms (SNPs) unknown so far. In addition to these SNPs, five already described SNPs of the ITGB7 and one in the human VDR gene were analysed in a Caucasian sib pair study of 176 families with at least two affected children, using matrix assisted laser desorption/ionization time of flight mass spectrometry. All confirmed SNPs were tested for linkage/association with asthma and related traits (total serum IgE level, eosinophil cell count and slope of the dose-response curve after bronchial challenge). RESULTS: Two new variations in the ITGB7 gene were identified. The coding SNP in exon 4 causes a substitution of the amino acid GLU by VAL, whereas the other variation is non-coding (intron 3). None of the eight analysed SNPs, of either the ITGB7 or the VDR genes, showed significant linkage/association with asthma or related phenotypes in the family study. CONCLUSIONS: These findings indicate that neither the human ITGB7 nor the VDR gene seem to be associated with the pathogenesis of asthma or the expression of related allergic phenotypes such as eosinophilia and changes in total IgE level.

Adolescent↗

PubMed2004

Increase in diagnosed asthma but not in symptoms in the European Community Respiratory Health Survey.

BACKGROUND: Information on the epidemiology of asthma in relation to age is limited and hampered by reporting error. To determine the change in the prevalence of asthma with age in young adults we analysed longitudinal data from the European Community Respiratory Health Survey. METHODS: A self-administered questionnaire was completed by 11 168 randomly selected subjects in 14 countries in 1991-3 when they were aged 20-44 years and 5-11 years later from 1998 to 2003. Generalised estimating equations were used to estimate net change in wheeze, nocturnal tightness in chest, shortness of breath, coughing, asthma attacks in the last 12 months, current medication, "diagnosed" asthma, and nasal allergies. RESULTS: Expressed as change in status per 10 years of follow up, subjects reporting asthma attacks in the previous 12 months increased by 0.8% of the population (95% CI 0.2 to 1.4) and asthma medication by 2.1% (95% CI 1.6 to 2.6), while no statistically significant net change was found in reported symptoms. Reported nasal allergies increased, especially in the youngest age group. CONCLUSIONS: As this cohort of young adults has aged, there has been an increase in the proportion treated for asthma but not in the proportion of those reporting symptoms suggestive of asthma. Either increased use of effective treatments has led to decreased morbidity among asthmatic subjects or those with mild disease have become more likely to label themselves as asthmatic.

Adult↗

PubMed2003

Maternal oral contraceptive use and atopic diseases in the offspring.

BACKGROUND: This study examined the association of maternal oral contraceptive (OC) use - before and after birth - and atopic manifestations in the offspring. METHODS: A total of 2754 East German children aged 5-14 years participated in a cross-sectional survey in 1998-99. The standardized parental questionnaire in 1998-99 included data on atopic diseases, socio-economic factors, parental atopy and maternal OC use. Specific immunoglobulin E against common inhalant allergens was measured by radioallergosorbent test (RAST). RESULTS: Maternal OC use before birth was associated with a higher risk of atopic diseases in the offspring compared with children of mothers who had never taken OC [asthma: odds ratio (OR) 1.6; 95% confidence interval (CI): 0.9-3.0; allergic rhinitis: OR 1.5; CI: 0.96-2.2; atopic eczema: OR 2.6; CI: 1.6-4.3; atopic sensitization: OR 1.5; CI: 0.97-2.2]. However, the effect estimates for maternal OC use after birth compared with the never users showed quite similar effects for these atopic conditions. No relations were observed between the prevalences of atopic diseases and maternal age at beginning of OC use, the duration of OC use, the type of contraceptive or maternal age at birth. CONCLUSION: This study raises doubts in a true biological association between OC use and atopic diseases.

Adolescent↗

PubMed2002

Asthma and IL-4 receptor alpha gene variants.

Linkage of allergy to chromosome 16 has been described in several studies, together with a positive association with interleukin 4 receptor alpha gene variants. Our aim was to replicate these findings in a sample of German and Swedish families recruited through sib-pairs affected by bronchial asthma. None of the markers showed linkage with the main phenotype of asthma or with total serum IgE. Seropositivity to D. pteronyssinus showed borderline significance in a region flanking the IL4Ralpha location. Single nucleotide polymorphisms (SNPs) leading to the protein exchanges I50V, E375A, C406R, S478P and Q551R in the IL-4 receptor alpha were examined for allele sharing in sibs with asthma. Multiple regression analysis was performed for association with total serum IgE and specific IgE. Allele sharing of IL4Ralpha SNPs in asthmatic children was not significantly increased for any of the examined SNPs except for the intracytoplasmatic polymorphism 551R (0.79 vs. 0.84 expected, P = 0.044). The variants 50V, 478P and 551R were associated with slightly increased, and 375A and 406R with decreased total IgE levels, all at a non-significant level. None of the examined IL4Ralpha variants were correlated to asthma severity. In summary, a single gene effect of IL4Ralpha variants or any other gene on chromosome 16 could not be shown in this selected population of children with asthma. As there could be interactions with multiple genetic and environmental factors, IL4Ralpha could still be involved in asthma pathogenesis.

Asthma↗

PubMed2002

Further support for the association of CCR5 allelic variants with asthma susceptibility.

English and German nuclear families containing multiple asthmatic children and asthmatic parents were analysed to retest a recently reported association between resistance to asthma and the delta32 allele of chemokine receptor 5 (CCR5). Analysis of the families by the transmission-disequilibrium test (TDT) revealed a non-significant trend in the English families that provided marginal confirmation of the association (P < 0.125), but no similar trend was observed in the German families. Case-control comparison of delta32 allele and genotype frequencies in asthmatic vs. non-asthmatic parents revealed a significantly lower frequency of delta32 in asthmatic English parents (P < 0.009) and a similar but non-significant trend in German parents (P < 0.265). Taken together, the pattern of results provides confirmation for the previously observed delta32-asthma association and indicates that susceptibility to asthma may be influenced by CCR5 or another gene in chromosomal region 3p21.

Alleles↗

PubMed2002

[Biological markers in epidemiology: concepts, applications, perspectives (part I)].

The inclusion of biomarkers in epidemiological research provides new possibilities for exposure assessment and the study of early structural or functional changes and pre-clinical stages of diseases. At the same time issues of validity, reliability, and quality control as well as logistics require special attention. Usually epidemiological studies become more expensive with regard to time and cost. Interdisciplinary collaboration between epidemiology, basic research, and laboratory research is crucial. A prerequisite for this collaboration are agreements on definitions, methods and procedures. The definition of "biomarker" and a description of previous uses of biomarkers in epidemiological studies are presented in the first part of this paper. The second part addresses genetic markers and markers of individual sensitivity and susceptibility. We will end with a discussion about the possible future of biomarkers in epidemiology.

Biomarkers↗

PubMed2002

[Biological Markers in Epidemiology: Concepts, applications, Perspectives (Part II)].

The first part of this paper outlined terms and definitions in the context of the application of biological markers in epidemiological studies. Cardiovascular epidemiology served as an example for their historical development. The second part focusses on DNA-based biomarkers, practical and methodological dimensions of the use of biomarkers in analytic epidemiological studies as well as requirements in respect of validity and quality assurance. Most genetic polymorphisms have no impact on health. However, some can be used as biomarkers for individual sensitvity to exposures and susceptibility for specific diseases. The Human Genome Project has brought about a quantum leap in the development of genetic markers. The practical implications cannot presently be assessed with certainty. However, present and future research programmes of gene-environment interactions depend on "traditional" epidemiological study designs, methods, and concepts. Ethical principles and data protection requirements apply equally to genetic and molecular epidemiology as do the "Guidelines for Good Epidemiological Practice".

Biomarkers↗

PubMed2002

[European Community Respiratory Health Survey in Adults (ECRHS)].

The European Community Respiratory Health Survey (ECRHS) was the first study to assess the geographical variation in asthma, allergy, and allergic sensitization in adults using the same instruments and definitions. The database of the ECRHS includes information from approximately 140 000 individuals aged 20 - 44 years from 22 countries. The aim of this review is to summarize the results of the ECRHS and to present the specific contribution of the German centers in Hamburg and Erfurt. The prevalence ranged from 2.0 - 11.9 % for asthma, 9.5 - 40.9 % for allergic rhinitis, 4.0 - 32.0 % for wheeze, 3.4 - 27.9 % for bronchial hyperreactivity, and 16.2 - 44.5 % for allergic sensitisation against common aeroallergens. Although the prevalence of these atopic disorders were found to be consistently higher for the Hamburg center compared to the Erfurt center, strong regional differences in the prevalences were also found within several other European countries. Overall Europe, the lowest prevalences were seen in the Eastern and Middle European countries with the center Erfurt, followed by the Mediterranean region. The highest prevalences were reported for all English speaking centers. Strong geographic variation was reported for medication for asthma. Asthma seems to be undertreated in several countries. Environmental exposures and in particular indoor factors, and exposures at the workplace are playing a major role for asthma in adulthood. Furthermore, protective effects on atopy were found for exposures to pets (dogs) and a large number of siblings in early childhood. In conclusion, the ECRHS has shown that the prevalence of asthma varies widely. The fact that the geographical pattern is consistent with the distribution of atopy and bronchial responsiveness supports the conclusion that the geographical variations in the prevalence of asthma are true and likely due to environmental factors.

Adult↗

PubMed2002

[Environmental surveys in the areas of Bitterfeld, Hettstedt and a comparative area in 1992-2000].

The aim of the environmental epidemiological study was to determine possible adverse effects on the health of children in the environmentally polluted areas of Bitterfeld and Hettstedt compared to the less polluted area of Zerbst (Eastern Germany). The changes of the health parameters were recorded together with the environmental changes during the time period of 6 years. The study design consisted of three repeated regional cross-sectional studies in 1992/93, 1995/96 and 1998/99. In total, 7,611 questionnaires could be analysed (participation rate: 89%, 75% and 75%). Children living in the most polluted area of Hettstedt had a noticeable higher risk for non-allergic respiratory diseases and symptoms compared to children living in the control area of Zerbst. From 1992 to 1999 a statistically significant decrease in the prevalences of these health outcomes was found. Children without indoor pollutants in their homes had the greatest benefit by the improvement of ambient air quality. The increase in lung function (FVC, FEV1) also underlines the improvement of the respiratory health. Children living in the polluted areas reported allergies more often (physician's diagnosis, allergy specific antibodies). The prevalence of asthma, the bronchial hyperreactivity and atopic eczema was increased within the observational period of 6 years. An increased prevalence was also shown for more severe allergic sensitisation (RAST classes > 17.5 kU/l), while the prevalence of hay fever increased slightly on a non-significant level. The burden with lead and cadmium was higher in children living in polluted areas and decreased during the study period except for 1997 where the lead concentration in blood increased according to the higher lead concentration in settled dust in Hettstedt at that time.

Adolescent↗

PubMed2002

Trends in prevalence of atopic diseases and allergic sensitization in children in Eastern Germany.

Trends in prevalence of atopic diseases and allergic sensitization in children from Eastern Germany during the 1990s were analysed. The study consisted of three regional cross-sectional surveys of a total of 7,632 children (aged 5-14 yrs) in 1992-1993, 1995-1996, and 1998-1999. Information was gathered on atopic diseases and potential predictors by a parental questionnaire. Allergic sensitization for birch, grass, mite, cat, and cladosporium were assessed by radioallergosorbent test (RAST). After adjustment for age, sex and the study area of the participants, prevalence increased between the first and third survey for hay fever, for asthma and for atopic eczema. The adjusted prevalence of allergic sensitization (RAST > 0.35 kU x L(-1)) showed a decrease, whereas the prevalence of strong sensitization (RAST > or = 17.5 kU x L(-1)) increased significantly, specifically in cohorts born after 1989. Further adjustment for possible determinants of these atopic diseases did not change the trend estimates. A clear increase in the prevalence of atopic diseases, with the exception of hay fever, was observed as well as a shift towards a stronger allergic sensitization, which might affect the onset of clinical manifestations of atopic diseases. Differences in the epidemiology of respiratory symptoms, illnesses and allergies between populations living in the former East Germany and those living in the former West Germany have been reported. Among East German children, lower prevalence rates of asthma, and positive skin-prick tests were observed compared to West German children in the early 1990s. Similarly, among East German adults, lower specific immunoglobulin (Ig) E levels and lower prevalence rates of asthma, wheezing, positive methacholine-challenge tests, allergic rhinitis, and positive skin-prick tests have been reported compared to those of West German adults.

Adolescent↗

PubMed2001

Genomewide scans of complex human diseases: true linkage is hard to find.

Many "complex" human diseases, which involve multiple genetic and environmental determinants, have increased in incidence during the past 2 decades. During the same time period, considerable effort and expense have been expended in whole-genome screens aimed at detection of genetic loci contributing to the susceptibility to complex human diseases. However, the success of positional cloning attempts based on whole-genome screens has been limited, and many of the fundamental questions relating to the genetic epidemiology of complex human disease remain unanswered. Both to review the success of the positional cloning paradigm as applied to complex human disease and to investigate the characteristics of the whole-genome scans undertaken to date, we created a database of 101 studies of complex human disease, which were found by a systematic Medline search (current as of December 2000). We compared these studies, concerning 31 different human complex diseases, with regard to design, methods, and results. The "significance" categorizations proposed by Lander and Kruglyak were used as criteria for the "success" of a study. Most (66.3% [n=67]) of the studies did not show "significant" linkage when the criteria of Lander and Kruglyak (1995) were used, and the results of studies of the same disease were often inconsistent. Our analyses suggest that no single study design consistently produces more-significant results. Multivariate analysis suggests that the only factors independently associated with increased study success are (a) an increase in the number of individuals studied and (b) study of a sample drawn from only one ethnic group. Positional cloning based on whole-genome screens in complex human disease has proved more difficult than originally had been envisioned; detection of linkage and positional cloning of specific disease-susceptibility loci remains elusive.

Asthma↗