Search PubMed⌕ Search

Biomedical subjects

M Wjst

Publications and source records attributed to M Wjst.

At least 37 records · Page 2Linked to original sources
PubMed2001

Early antibiotic treatment and later asthma.

The reasons for the asthma epidemic are poorly understood. As the asthma prevalence follows the geographical and temporal trend of antibiotic use into clinical medicine, we examined a possible association in a population-based study of 2,512 children age 5-14 in East Germany. Wheezing was associated with increasing number of antibiotic courses (never versus one time odds ratio 1.9, P = 0.012, 2 to 5 times odds ratio 3.0, P<0.001 and more than 5 times, odds ratio 6.9, P<0.001) which was also seen for asthma diagnosis. The risk increased with earlier administration (never versus second year odds ratio 4.6, month 7-12 odds ratio 5.4 and birth until month 6 odds ratio 7.9, all P<0.001). Also non pulmonary treatment indication was associated with later wheezing (odds ratio 3.9, P<0.001). The most likely possible explanation is reverse causation indicating that frequent upper respiratory infections, an early symptom of asthma, are treated with antibiotics. Antibiotic therapy could also be a proxy of another closely associated genetic or environmental factor. The high dose effect, the time dependency of the administration and the effect by non-pulmonary indications raises the possibility that early antibiotic treatment could itself be related to later asthma.

Adolescent↗
PubMed2001

Multipoint analysis using affected sib pairs: incorporating linkage evidence from unlinked regions.

In this paper, we proposed a multipoint method to assess evidence of linkage to one region by incorporating linkage evidence from another region. This approach uses affected sib pairs in which the number of alleles shared identical by descent (IBD) is the primary statistic. This generalized estimating equation (GEE) approach is robust in that no assumption about the mode of inheritance is required, other than assuming the two regions being considered are unlinked and that there is no more than one susceptibility gene in each region. The method proposed here uses data from all available families to simultaneously test the hypothesis of statistical interaction between regions and to estimate the location of the susceptibility gene in the target region. As an illustration, we have applied this GEE method to an asthma sib pair study (Wjst et al. [1999] Genomics 58:1-8), which earlier reported evidence of linkage to chromosome 6 but showed no evidence for chromosome 20. Our results yield strong evidence to chromosome 20 (P value = 0.0001) after incorporating linkage information from chromosome 6. Furthermore, it estimates with 95% certainty that the map location of the susceptibility gene is flanked by markers D20S186 and D20S101, which are approximately 16.3 cM apart.

Asthma↗
PubMed2001

Description of three data sets: Collaborative Study on the Genetics of Asthma (CSGA), the German Affected-Sib-Pair Study, and the Hutterites of South Dakota.

Three different data sets with clinical data and markers from genome-wide screens were submitted for analysis at Genetic Analysis Workshop 12. In each study, participants were carefully characterized for asthma and related phenotypes. Testing for bronchial hyper-responsiveness using methacholine and standardized protocols was performed. Total serum IgE levels were measured using standardized techniques. In addition, similar questionnaire data on symptoms and relevant environmental exposures were obtained. Relevant clinical data and genotypes for the polymorphic markers used for each genome-wide screen were submitted. The data set from the United States Collaborative Study on the Genetics of Asthma represents a heterogeneous population consisting of both Caucasian and African American families ascertained through two siblings with clinical asthma from multiple centers. Likewise, the families from the German Asthma Genetics Group were also ascertained through two siblings with asthma at multiple centers. In a contrast to these data sets, Dr. Carole Ober and her collaborators submitted data from the inbred Hutterite population in South Dakota.

Adolescent↗
PubMed2001

Fine mapping and single nucleotide polymorphism association results of candidate genes for asthma and related phenotypes.

Several genome-wide screens for asthma and related phenotypes have been published to date but data on fine-mapping are scarce. For higher resolution we performed a fine-mapping study with 2 cM average spacing in often discussed asthma candidate regions (2p, 5q, 6p, 7p, 9q, 11p, and 12q) to narrow down the regions of interest. All participants of a Caucasian family study (97 families with at least two affected sib pairs) were genotyped for 49 supplementary polymorphic dinucleotide markers. Our results indicate increased evidence for linkage on chromosome 6p, 9q, and 12q. These candidate regions were further analyzed with SNP polymorphisms in the endothelin 1 (EDN1), lymphotoxin alpha (LTA), and neuronal nitric oxide synthase (NOS1) genes. In addition, IL4 -590C>T and IL10 -592C>A, localized on chromosomes 5q and 1q, respectively, have been analyzed for SNP association. Of the six SNPs tested, four revealed weak association with the examined phenotypes. These are the IL10 -592C>A SNP in the interleukin 10 gene (p=0.036 for eosinophil cell counts), the 4124T>C SNP in EDN1 (p=0.044 for asthma), the 3391C>T SNP in NOS1 with eosinophil cell counts (p=0.0086), and the 5266C>T polymorphism, also in the NOS1 gene, for high IgE levels (p=0.022). In summary, fine mapping data enable us to confine asthma candidate regions, while variants of EDN1 and NOS1, or nearby genes, may play an important role in this context.

Asthma↗
PubMed2001

When air is rare: behind the scenes of an asthma web site.

OBJECTIVE: The number of medical Web sites has increased tremendously during the past 5 years. While the quality of the content has also been on the rise, some questions are still open: Where are users referredfrom, how large is the target audience, and how do they behave during their visit? METHODS: The Asthma Information Center is an independent Web site for physicians, patients, and other health care professionals providing information about asthma. Besides mirroring electronic documents of the Global InitiativeforAsthma, numerous interactive pages have been constructed. MAIN OUTCOME MEASURES: Logfiles of the Web server were analyzed for a 5-year interval for numbers of page views, visitors, visits, and external referring sites. RESULTS: The number of visitors has increased since 1995, up to 100,000 page views at the end of the observation interval. In February 2000 approximately 9000 visitors were recorded per month. 3.4 pages were retrieved per visit, which lasted on average 1:57 min. Users are referred primarily by portal sites and only to a lesser extent by search engines. CONCLUSIONS: The audience is large for a specialized medical Web site. Users are usually referred from nonmedical sites. They are seeking fast information, most probably as a second opinion after having consulted their physician.

Asthma↗
PubMed2001

Current concepts on the genetics of asthma.

Asthma is a complex genetic disorder with variable phenotype, largely attributed to the interactions of the environment and multiple genes, each potentially having small effects. Numerous asthma and atopy loci have been reported in studies demonstrating associations and/or linkage of the asthma-associated phenotypes, atopy, elevated IgE levels, and bronchial hyperresponsiveness to alleles of microsatellite markers and single nucleotide polymorphisms within specific cytokine/chemokine and IgE regulating genes. Although the studies reporting these observations are compelling, most of them lack statistical power. This review compiles the evidence that supports linkage and associations to the various genetic loci and candidate genes. Whereas significant progress has been made in the field of asthma genetics in the past decade, the roles of the genes and genetic variations within the numerous candidate asthma genes that have been found to associate with the expression of the asthmatic phenotype remain to be determined.

Animals↗
PubMed2001

Margarine consumption and allergy in children.

Dietary fat consumption is hypothesized to influence atopy development by modulation of IgE production. The aim of our study was to assess whether margarine consumption is associated with allergic sensitization and diseases in children. Data of a cross-sectional health survey in 1998-1999 comprising 2,348 children age 5 to 14 yr were analyzed. Information on type of fat used as spread during the past 12 mo, children's health, and sociodemographic factors were gathered by questionnaire. Allergic sensitization to common aeroallergens was assessed by specific serum IgE. Compared with butter consumption, margarine consumption was associated with allergic sensitization (adjusted odds ratio 1.30 [95% confidence interval: 1.01 to 1.67]) and with rhinitis symptoms during the past 12 mo (1.41 [1.01 to 1.97]). Sex-stratified analysis showed that these associations were limited to boys (boys: sensitization 1.57 [1.12 to 2.20], rhinitis symptoms 1.76 [1.12 to 2.78]; girls: sensitization 0.99 [0.67 to 1.46], rhinitis symptoms 1.03 [0.63 to 1.70]). No statistically significant relation was observed between exclusive margarine consumption and ever physician-diagnosed hay fever or asthma in all children. In conclusion, the sex difference in the association of margarine consumption with allergic sensitization was in accordance with the higher IgE concentrations and atopy prevalence in boys compared with girls. Increased intake of certain polyunsaturated fatty acids might further stimulate IgE production in boys.

Adolescent↗
PubMed2001

Increasing prevalence of bronchial hyperresponsiveness in three selected areas in East Germany. Bitterfeld Study Group.

The prevalence of asthma, bronchial hyperresponsiveness (BHR) and allergic rhinitis in children was lower in East Germany compared to West Germany. The reasons for this difference are still not understood. This study tested the hypothesis that prevalence of BHR increased in East German children after reunification. Two consecutive cross-sectional surveys of schoolchildren aged 8-14 yrs from three communities in East Germany were carried out in 1992-1993 and 1995-1996. A subsample of 530 and 790 children with complete lung function and cold air challenge data was analysed. The prevalence of BHR increased from 6.4%, in 1992-1993 to 11.6% in 1995-1996 (odds ratio (OR): 2.0, 95% confidence interval (CI): 1.3-3.0, adjusted for age, sex, season, community and parental education). No changes were found for asthma, allergic rhinitis or allergic sensitization. In contrast, physician diagnosed bronchitis, pneumonia and frequent colds decreased significantly. The observed increase in the prevalence of BHR was reduced (OR: 1.5, 95% CI: 0.95-2.3) after adjustment for several indoor factors. In conclusion, while the prevalence of nonallergic respiratory diseases seems to decrease, the prevalence of bronchial hyperresponsiveness might be a first indicator of the suspected increase of asthma prevalence in East Germany. The present results give indirect evidence, that less respiratory infections may be associated with higher bronchial hyperresponsiveness.

Asthma↗
PubMed2001

The European Community Respiratory Health Survey: what are the main results so far? European Community Respiratory Health Survey II.

The European Community Respiratory Health Survey (ECRHS) was the first study to assess the geographical variation in asthma and allergy in adults using the same instruments and definitions. The database of the ECRHS includes information from approximately 140,000 individuals from 22 countries. The aim of this review is to summarize the results of the ECRHS to date. The ECRHS has shown that there are large geographical differences in the prevalence of asthma, atopy and bronchial responsiveness, with high prevalence rates in English speaking countries and low prevalence rates in the Mediterranean region and Eastern Europe. Analyses of risk factors have highlighted the importance of occupational exposure for asthma in adulthood. The association between sensitization to individual allergens and bronchial responsiveness was strongest for indoor allergens (mite and cat). Analysis of treatment practices has confirmed that the treatment of asthma varies widely between countries and that asthma is often undertreated. In conclusion, the European Community Respiratory Health Survey 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 most likely due to environmental factors.

Asthma↗
PubMed2000

A first trial of retrospective collaboration for positional cloning in complex inheritance: assay of the cytokine region on chromosome 5 by the consortium on asthma genetics (COAG).

The central problem of complex inheritance is to map oligogenes for disease susceptibility, integrating linkage and association over samples that differ in several ways. Combination of evidence over multiple samples with 1,037 families supports loci contributing to asthma susceptibility in the cytokine region on 5q [maximum logarithm of odds (lod) = 2.61 near IL-4], but no evidence for atopy. The principal problems with retrospective collaboration on linkage appear to have been solved, providing far more information than a single study. A multipoint lod table evaluated at commonly agreed reference loci is required for both collaboration and metaanalysis, but variations in ascertainment, pedigree structure, phenotype definition, and marker selection are tolerated. These methods are invariant with statistical methods that increase the power of lods and are applicable to all diseases, motivating collaboration rather than competition. In contrast to linkage, positional cloning by allelic association has yet to be extended to multiple samples, a prerequisite for efficient combination with linkage and the greatest current challenge to genetic epidemiology.

Asthma↗
PubMed2000

Association of beta(2)-adrenoreceptor variants with bronchial hyperresponsiveness.

Because of its involvement in the regulation of airway tone, the beta(2)-adrenoreceptor is considered a candidate for bronchial hyperresponsiveness (BHR) associated with asthma. This notion is supported by several reports that have implicated the chromosomal region 5q31-q33 harboring the gene for the beta(2)-adrenoreceptor in the genetics of asthma and related phenotypes. We performed a population-based association study focusing on BHR as a qualitative trait and omitting other asthma-related phenotypes. From a German population sample of 1,150 individuals we extracted all 152 bronchohyperreactive probands, who were compared with 295 bronchonormoreactive control subjects. All individuals were genotyped for three single nucleotide polymorphisms of the beta(2)-adrenoreceptor gene resulting in variants at the amino acid positions 16, 27, and 164. The genotyping protocol used allowed the determination of haplotypes of these polymorphisms. Whereas no individual polymorphism was associated with BHR, the Gly16/Gln27/Th164 haplotype was significantly underrepresented in the case group indicating a protective effect of this haplotype with regard to BHR. Upon reanalysis by sex a significant association persisted only for female probands.

Airway Resistance↗
PubMed2000

A nationwide survey in Germany on fatal asthma and near-fatal asthma in children: different entities?

In adults fatal and near-fatal asthma have similar clinical characteristics. Therefore, near-fatal asthma in adults can be used as a model for fatal asthma. A nationwide study on fatal and near-fatal asthma in children <16 yrs was performed in order to assess whether, as in adults, near-fatal asthma can be used as a model for fatal asthma. From 1996 to 1998, all paediatric hospitals and paediatric pulmonologists in Germany were asked to report cases of fatal asthma and near-fatal asthma to a central survey unit (Erhebungseinheit für seltene pädiatrische Erkrankungen in Deutschland (ESPED)) on a monthly basis. All reports were followed by detailed questionnaires. Sixteen fatal and 45 near-fatal asthma cases were analysed. Fatal asthma patients were older than near-fatal asthma patients. Respiratory tract infections were frequently reported only in near-fatal asthma (47 versus 0%). The proportion of cases with rapid-type onset (duration of symptoms < or =1 h) was higher in fatal asthma (53 versus 14%). Long-term regular treatment with short acting beta2-agonists was common in both groups, but the use of concomitant inhaled corticosteroids was significantly lower in fatal asthma cases. A high proportion of poor compliance was observed in both groups. As fatal and near-fatal asthma differ significantly in important clinical aspects, analysis of near-fatal asthma might be of limited value in elucidating the causes of fatal asthma in children.

Administration, Inhalation↗
PubMed1999

A genome-wide search for linkage to asthma. German Asthma Genetics Group.

Asthma is among the most frequent chronic diseases in childhood. Although numerous environmental risk factors have already been identified, the basis for familial occurrence of asthma remains unclear. Previous genome screens for atopy in British/Australian families and for asthma in different American populations showed inconsistent results. We report a sib pair study of a sample of 97 families, including 415 persons and 156 sib pairs. Following an extensive clinical evaluation, all participants were genotyped for 351 polymorphic dinucleotide markers. Linkage analysis for asthma identified four chromosomal regions that could to be linked to asthma: chromosome 2 (at marker D2S2298, P = 0.007), chromosome 6 (around D6S291, lowest P = 0.008), chromosome 9 (proximal to D9S1784, P = 0.007), and chromosome 12 (D12S351, P = 0.010). These linkage regions could be reproduced for all loci by analysis of total or specific immunoglobulin E (minimum P values at these regions were 0. 003, 0.001, 0.010, and 0.015, respectively).

Asthma↗
PubMed1999

Trends in allergies among children in a region of former East Germany between 1992-1993 and 1995-1996.

A lower prevalence of asthma and allergies has been reported among children and adults living in the area of former East Germany compared with those living in West Germany. After German reunification in 1990, the East German population rapidly adopted a western lifestyle. Therefore, this study examined if the prevalence rates of allergic diseases, symptoms, and sensitisation and asthma have increased among East German children since German reunification. - Children aged 5 to 7 years living in the region of Sachsen-Anhalt, East Germany were examined in two cross-sectional studies during 1992-93 (n = 769, response rate 84.0%) and 1995-96 (n = 725, response rate 74.6%). Sensitisation was assessed by specific immunoglobulin E measurements against five common aeroallergens using the CAP-FEIA technique. After adjustment for sex, parental education, season of examination, day care attendance, breast feeding, environmental tobacco smoke exposure, cat dander exposure, and several indoor factors, an increase in the prevalence of self-reported, physician-diagnosed allergies (OR 1.44, 95% CI 1.01-2. 06), but not in allergic sensitisation (OR 0.85, 95% CI 0.62-1.16) was found. The only evidence of an increase in allergies of the self-reported increase in the prevalence of physician-diagnosed allergies is likely due to changes in physician diagnostic patterns and the heightened public awareness of allergic diseases. - In conclusion, there were no significant changes in the prevalence of asthma, allergic rhinitis, or self-reported symptoms of allergic diseases.

Adult↗
PubMed1999

Age of entry to day nursery and allergy in later childhood.

BACKGROUND: Infections in early childhood may prevent allergies in later life. If this hypothesis is true, early exposure to childcare outside the home would protect against atopy by promotion of cross infections. We investigated whether children who attend a nursery at a young age have a lower rate of atopy and fewer allergies than children who attend from an older age. METHODS: In a cross-sectional study carried out in 1992-93, we examined 2471 children in three age-groups (5-7, 8-10, and 11-14 years) from the towns of Bitterfeld, Hettstedt, and Zerbst in eastern Germany. The children's parents answered a questionnaire about allergies and symptoms, attendance at day care, and related factors. Sensitisation was assessed by skin-prick tests and measurement of allergen-specific IgE antibodies in serum. FINDINGS: In 669 children from small families (up to three people), the prevalence of atopy was higher among children who started to attend day nursery at an older age than in those who started to attend at a younger age (p<0.05). Compared with children who first attended at age 6-11 months, the adjusted odds ratios for a positive skin-prick test were 1.99 (95% CI 1.08-3.66) for children who attended at age 12-23 months and 2.72 (1.37-5.40) for those who attended at age 24 months and older. In 1761 children from large families (more than three people), age of entry to day nursery had no effect on atopy. INTERPRETATION: Our findings accord with the hypothesis that early infection may protect against allergies in later life.

Adolescent↗
PubMed1999

Current status of the Asthma and Allergy Database.

The database provides an online resource for access to data on the genetics of asthma and allergy. This report describes the present status of the site. Currently, a detailed description of 88 linkage studies (7164 linkage positions) and 72 mutation studies are available. The results can be accessed in table form or graphically. The database also contains mouse asthma studies and human homology relationships, gene expression studies and links to relevant patents. Technical details about the server architecture, database installation, database construction, database structure and the user interface are explained elsewhere [Wjst and Immervoll (1998) Bioinformatics, 14, 827-828]. The URL is http://cooke.gsf.de

Animals↗
PubMed1999

Indoor risk factors for atopic eczema in school children from East Germany.

This study aimed to investigate the relation between environmental influences such as arsenic, cadmium, lead, and mercury, as well as environmental tobacco smoke, pet keeping, and heating systems on the prevalence of atopic eczema. Therefore, a multicenter cross-sectional study of school children aged 5-14 years, including a standardized questionnaire, blood and urine analyses, and a dermatological examination, was undertaken. A cases-control approach was chosen in order to identify relevant risk factors. A total of 2200 school children (response 79.1%) of two areas (Bitterfeld, Hettstedt) polluted by industrial activities and an agricultural control region (Zerbst) of the former German Democratic Republic were examined. Atopic eczema as identified by dermatological examination and history was the outcome variable of interest. Body burden of arsenic and heavy metals and questionnaire data on environmental tobacco smoke exposure, pet keeping, and heating system were investigated as potential risk factors. The overall prevalence of atopic eczema was 2.6%, with higher prevalences in the industrial areas (2.5 and 2.9%) compared to the control area (1.6%, not significant). Bivariate analyses did not reveal statistically significant associations between atopic eczema and tobacco smoke exposure or the body burden of arsenic and heavy metals. According to multiple logistic regression analysis, atopic eczema was significantly more frequent in predisposed families and those who reported keeping guinea pigs (OR=4.37, CI 2.15-8.91), but not other pets, like dogs, cats, and hamsters. In comparison to a distant heating system, a decreased risk was observed in households with central heating system (OR=0.30, CI 0.10-0.90), whereas the presence of a gas heater with an exhaust pipe connection to the wall was associated with a significantly elevated risk for eczema (OR=8.22, CI 2.44-27.66). The heating system and exposure to certain animal allergens are related to the manifestation of atopic eczema. Further studies are needed to clarify how far a causal relationship is reflected by these findings.

Adolescent↗