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Biomedical subjects

Ulrich Wahn

Publications and source records attributed to Ulrich Wahn.

At least 55 records · Page 3Linked to original sources

Body image in cystic fibrosis--development of a brief diagnostic scale.

For a number of reasons, body image is an important concept in behavioral medicine. First, it is known to be related to clinical phenomena such as poor self-esteem, depression, and anxiety. Second, body image has the potential to influence the patients' self-management and compliance motivation. Finally, body image can be improved through psychological and educative interventions. This study presents the development and validation of a brief, 8-item scale assessing attitudinal body image in patients with cystic fibrosis. A principal component analysis supported three domains represented by the items: evaluation/satisfaction, importance, and trust in physical functioning/health. The test-retest correlations ranged from 0.83 to 0.88, internal consistencies were above 0.70, except for the domain "importance" (alpha = 0.44). The scale scores differentiated between patients with mild and severe symptoms of the disease. Regression analyses identified body image as an important predictor of the patients' health-related quality of life. In summary, our results provide preliminary evidence for the reliability and construct, concurrent, and clinical validity of the instrument.

Activities of Daily Living↗

The revised German Cystic Fibrosis Questionnaire: validation of a disease-specific health-related quality of life instrument.

BACKGROUND: The assessment of health related quality of life (HRQOL) has increasingly been recognized as an important adjunct to medical outcome parameters in the monitoring of cystic fibrosis (CF) patients and in clinical studies. The Cystic Fibrosis Questionnaire (CFQ) is a disease-specific HRQOL instrument for CF patients developed in France. Translations are currently being validated in four different countries. The aim of the present study was to validate the German adaptation of the CFQ-14+. METHOD: On the basis of results from a first dataset (n = 197 CF adolescent and adult patients), revisions were made and retested in a second sample of 103 patients. RESULTS: The final revised version showed good construct validity. The same nine HRQOL domains as in the French original CFQ-14+ emerged from the analyses as structurally robust scales. The internal consistencies of the HRQOL scales ranged from 0.71 to 0.94. The instrument's clinical validity was supported by severely ill patients reporting lower HRQOL than less severely ill patients on most scales. CONCLUSION: We conclude that the evidence supports the validity and reliability of the instrument. An important future area of application is the use in comparative multi-center international studies.

Adolescent↗

Minimal inflammation, acute phase response and avoidance of misclassification of vitamin A and iron status in infants--importance of a high-sensitivity C-reactive protein (CRP) assay.

The acute phase response is known to affect many biological parameters used to assess the iron and vitamin A status. Usually, C-reactive protein (CRP) values higher than 5 to 10 mg/L are taken as indicative of this response. Here we report changes occurring at much lower CRP values. A range of parameters (clinical chemistry, retinol, vitamin E, carotenoids, thyroid status, blood count, immunology) were measured in 101 healthy one-year-old children with no or only minimal symptoms of airway infection and CRP values below 6 mg/L on routine testing. Additionally, CRP values were measured by a high-sensitivity assay (detection limit 0.2 mg/L). When determined by a more sensitive assay, CRP values (median, 0.26 mg/L) revealed highly significant associations with parameters known to be influenced by the acute phase response. Using a limit of 0.6 mg/L (75th percentile), significantly lower levels were observed for transthyretin, iron, retinol, and beta-carotene in the group with the higher CRP levels. This relationship was confirmed intra-individually in a subgroup of 21 children who underwent a second blood draw about four weeks after the first one. The acute phase response is triggered at very low inflammatory levels with CRP values considerably lower than 5 to 10 mg/L, and can occur in apparently healthy children. A high-sensitivity CRP assay is necessary to detect this low level, and in the case of iron or vitamin A, it can help to avoid misclassification of the nutritional status.

Acute-Phase Reaction↗

Urinary leukotriene E4 levels in children with allergic rhinitis treated with specific immunotherapy and anti-IgE (Omalizumab).

Recently, we were able to demonstrate that Omalizumab, a humanized monoclonal anti-IgE antibody, reduces in vitro leukotriene (LT) release of peripheral leukocytes stimulated with allergen in children with allergic rhinitis undergoing allergen immunotherapy. The aim of this study was to investigate the effect of anti-IgE in combination with specific immunotherapy (SIT) on urinary leukotriene E4 (LTE4) levels. Children and adolescents with sensitization to birch and grass pollens and suffering from seasonal allergic rhinitis were included in a phase III, placebo-controlled, multicenter clinical study. Within the four-arm study, patients were randomized to receive SIT for either birch or grass pollen and to receive either subcutaneous anti-IgE or placebo for 24 weeks during the pollen season. From a total population of 225 children, we collected three urine samples in a subgroup of 19 children [n = 12 boys (63%); mean age 11.8 years; range 7.2-17.5 years; Group A (n = 10): SIT (grass or birch) + anti-IgE; Group B (n = 9): SIT (grass or birch) + placebo]. Urine samples were collected before, during and at the end of treatment. Endogenous urinary LTE4 was separated by high-performance liquid chromatography (HPLC) and determined by enzyme immunoassay with a specific antibody. No differences in urinary LTE4 concentrations were observed between the anti-IgE and the placebo groups before (A: 35.2; B: 36.5 nmol/mol creatinine), during (A: 27.0; B: 29.3) and after treatment (A: 28.9; B: 26.5 nmol/mol creatinine). We conclude that urinary LTE4 levels are not helpful in monitoring patients treated with anti-IgE and SIT.

Adolescent↗

Treatment of allergic alveolitis with methylprednisolone pulse therapy.

We report on a 13-year-old-boy who had been admitted to our hospital for dyspnea, hypoxia, and pulmonary infiltrates. The diagnosis of allergic alveolitis was based on history (provocation by exposure), lung function tests, bronchoalveolar lavage, and transbronchial lung biopsy. No specific allergen could be identified. Five courses of methylprednisolone pulse therapy (15 mg/kg on three consecutive days) stabilized the patient with normalization of lung function and blood gas analysis. Between pulses the boy returned to his home on a farm without relapse. It is estimated that the effect of a single pulse lasted for at least 2-4 weeks. We conclude that pulse therapy can be used instead of continuous therapy in this rare disease in childhood.

Adolescent↗

The costs of atopy and asthma in children: assessment of direct costs and their determinants in a birth cohort.

The aim of this study was to estimate costs accrued by the health care of children with asthma in comparison to children with atopic eczema and seasonal rhinitis and to investigate cost determinants. From the multicenter cohort study (MAS-90), we selected children with an asthma, atopic eczema and/or seasonal rhinitis diagnosis during the first 8 years of life, and overall 8-year health care utilization was estimated retrospectively by reviewing medical records. Asthma treatment (n = 76) incurs an average cost of 627 US dollars per year, 44% due to hospital stays. Atopic eczema treatment (n = 91) cost on average 219 US dollars and seasonal rhinitis (n = 69) 57 US dollars per year. In asthma and atopic eczema, costs increase significantly with disease severity. Allergy diagnostics use accounts for only 1% of total costs. Costs for asthma and atopic eczema treatment are highest in those years when topical steroids are used for the first time, but decrease with every further year of steroid use. A remarkable 25% of asthmatic children with severe symptoms were not treated according to national guidelines, so that most steroid treatment was initiated during the first hospital stay. In the case of asthma, total direct costs increased until the 3rd year of the disease, and then decreased with further years of diagnosis, while steroid use continued to increase. These results indicate a 'learning effect' in the treatment of asthma and atopic eczema for each patient as well as considerable cost-saving potential by preventing severe asthma. Moreover, the importance of considering cost-driving factors and using cohort or longitudinal designs in cost-of-illness approaches is emphasized.

Anti-Asthmatic Agents↗

Effect of oral cyclosporin A in children with Staphylococcus aureus-colonized vs S aureus-infected severe atopic dermatitis.

Atopic dermatitis (AD) is frequently associated with skin colonization or infection with Staphylococcus aureus strains producing exotoxins. The aim of this investigation was to evaluate the effect of oral cyclosporin A (CsA) on disease severity and bacterial counts in colonized and infected patients. Eleven children with severe AD (SCORAD index >50, mean objective SCORAD score >40) were treated for 8 weeks with 2.5-5 mg/kg CsA. In five patients, the skin was only colonized with S. aureus whereas the remaining six patients presented clinically relevant suppurative S. aureus skin infections characterized by small pustules, crustings, pus and increased pruritus in the presence of S. aureus as determined by contact sampling and culture which regularly resulted in the indication for antibiotic treatment. Clinical and microbiological investigations were performed before and after CsA therapy. Clinical signs and symptoms of AD improved in all patients with a reduction in mean SCORAD index from 74 to 29 (p < 0.001). However, disease severity and bacterial counts were more reduced by CsA in the colonized patients compared with the patients with clinical overt infections. In conclusion, treatment with CsA resulted in an improvement of clinical symptoms in children suffering from severe AD. However, anti-infective treatment administered before immunomodulatory therapy is likely to be decisive for the long-term therapeutic effect.

Administration, Oral↗

Fexofenadine is efficacious and safe in children (aged 6-11 years) with seasonal allergic rhinitis.

BACKGROUND: This is the first prospective, randomized, double-blind, placebo-controlled study showing statistical improvement of an H(1)-antihistamine in children with seasonal allergic rhinitis in all symptoms throughout the entire treatment period. OBJECTIVE: This randomized, placebo-controlled, parallel-group, double-blind study was performed to assess the efficacy and safety of fexofenadine in children with seasonal allergic rhinitis. METHODS: This study was conducted at 148 centers in 15 countries. Nine hundred thirty-five children (aged 6-11 years) were randomized and treated with either fexofenadine HCl 30 mg (n = 464) or placebo (n = 471) tablets twice a day for 14 days. Individual symptoms (sneezing; rhinorrhea; itchy nose, mouth, throat, and/or ears; itchy, watery, and/or red eyes; and nasal congestion) were assessed at baseline and then daily at 7:00 AM and 7:00 PM (+/-1 hour) during the double-blind treatment period. Each total symptom score was the sum of all symptoms, excluding nasal congestion. The primary efficacy variable was the change from baseline in the average of the daily 12-hour evening reflective total symptom scores throughout the double-blind treatment. Safety was evaluated from adverse-event reporting, vital signs, physical examinations, and clinical laboratory data at screening and study end point. RESULTS: Fexofenadine was significantly superior to placebo in the primary efficacy analysis (P </=.0001). Individual symptom scores showed statistically significant superiority compared with placebo (P <.05), including nasal congestion in the evening reflective assessment (P <.05). There was no significant difference in adverse events between fexofenadine and placebo, either overall or by causality. CONCLUSION: The efficacy and safety of the H(1)-antihistamine fexofenadine has been confirmed in this multicenter, multinational study of children aged 6 to 11 years with seasonal allergic rhinitis.

Anti-Allergic Agents↗

Down-regulation of vasoactive intestinal polypeptide receptor expression in atopic dermatitis.

BACKGROUND: Receptors for vasoactive intestinal polypeptide (VIP) have recently been suggested to play a key role in immunomodulation with genetically modified mice. However, it is not known whether changes in receptor gene regulation are involved in the pathogenesis of human immune disorders. OBJECTIVE: We studied the expression of VPAC(2) in acute lesions of the human immune disease atopic dermatitis. METHODS: By using nonradioactive in situ hybridization, quantitative immunohistochemistry, RT-PCR, and gene array studies, the expression status of VPAC(2) was assessed in atopic dermatitis and control tissues and in the human mast cell line HMC-1. RESULTS: In situ hybridization and immunohistochemistry demonstrated VPAC(2) mRNA and protein expression in human mast cells surrounded by VIP positive nerve fibers. Gene array experiments and RT-PCR studies showed high levels of VPAC(2) mRNA expression in mast cells that were increased compared to other receptors such as VPAC(1) or VIP in the human mast cell line HMC-1. Stimulation of HMC-1 cells led to a downregulation of VPAC(2). Similarly, quantitative immunohistochemistry for VPAC(2) in acute atopic dermatitis lesions showed a significantly decreased VPAC(2) immunoreactivity in mast cells. CONCLUSION: The downregulation of VPAC(2) in human mast cells in acute lesions of atopic dermatitis suggests a role of this G-protein;coupled receptor in the pathophysiology of the disease.

Dermatitis, Atopic↗

Associations between total serum IgE levels and the 6 potentially functional variants within the genes IL4, IL13, and IL4RA in German children: the German Multicenter Atopy Study.

BACKGROUND: Increased total serum IgE levels are a common characteristic of atopic disorders. Six potentially functional variants, including C-590T in the IL4 gene, C-1055T and Arg130Gln in the IL13 gene, and Ile50Val, Ser478Pro, and Gln551Arg in the IL4RA gene, have been evaluated for their involvement in the control of total serum IgE levels and related atopic disorders, but the results of these studies have been inconsistent. OBJECTIVE: We examined whether these 6 variants had genotypic effects on total serum IgE levels in 823 unrelated German children from a large infant cohort, the German Multicenter Atopy Study. METHODS: Marginal effect models were used for the analyses of the repeated IgE measurements. Weighted linear regression and family-based tests of association were performed to minimize the possibility of spurious effects caused by selection bias or confounding on the basis of ethnic background. RESULTS: There are significant associations between increased total serum IgE levels and 2 variants in the IL13 gene (P <.005 and.0002 for Arg130Gln and C-1055T, respectively). These genetic effects are unlikely to be due to solely linkage disequilibrium between 2 polymorphisms, population stratification, or nonrepresentative samples. In addition, exposure to maternal smoking appears to modify the above effects on total serum IgE levels. However, no statistical association was observed between this quantitative phenotype and the other 4 variants examined. CONCLUSION: These findings suggest that variants C-1055T and Arg130Gln of the IL13 gene might play an important role on total serum IgE production in this study population.

Alleles↗

Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children.

BACKGROUND: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16) gene maps to this region. CC16 is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16 gene (A38G) was previously associated with asthma. OBJECTIVE: We evaluated the role of the CC16 SNP in pediatric asthma and asthma severity in 2 German study populations. METHODS: The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the present study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1 was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied. RESULTS: No association of the CC16*38A allele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC(20)FEV(1) values were significantly lower in individuals homozygous or heterozygous for the CC16*38A allele compared with those in subjects with the CC16*38GG genotype (P <.05 and P <.03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1 after exercise when homozygous for the CC16*38A allele compared with that seen in asthmatic patients with the *38AG or *38GG genotype (P <.04 and P =.006, respectively). CONCLUSION: We conclude that the CC16*A38G SNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children.

Adolescent↗

Is there a role for anti-IgE in combination with specific allergen immunotherapy?

PURPOSE OF REVIEW: A line of novel therapeutic approaches that try to interfere more specifically with the immunological mechanisms underlying allergen-induced pathology are currently undergoing clinical evaluation. The most advanced of these is anti-IgE, which directly targets IgE serum antibodies, thus inhibiting the central mechanism of immediate type hypersensitivity reactions. In addition, a lot of interest has recently been focused on allergen-specific immunotherapy due to its potential to cure allergic diseases. In the present review, state-of-the-art treatment of allergic diseases with anti-IgE and allergen-specific immunotherapy is summarized, and the potential of combination therapy with both treatment options is discussed. RECENT FINDINGS: Application of anti-IgE antibodies effectively reduces IgE serum levels regardless of allergen specificity. This treatment has been successfully tested in patients with allergic rhinitis, asthma and food allergy, showing significant efficacy in reducing symptom scores and rescue medication use. Anti-IgE therapy is limited by high costs and the necessity for permanent or every-season treatment. The strongest argument in favor of allergen-specific immunotherapy is the potential to cure allergic diseases, which has been demonstrated in patients with allergic rhinitis, insect venom allergy and, to a lesser degree, asthma. The broader application of allergen-specific immunotherapy is restricted by sometimes life-threatening side effects. A combination of anti-IgE and allergen-specific immunotherapy was shown to be superior to each single treatment protocol in children and adolescents with allergic rhinitis, as demonstrated by efficacy of symptom scores and rescue medication use. SUMMARY: There are strong arguments for a combination of anti-IgE plus allergen-specific immunotherapy for treatment of allergic diseases: improved efficacy, limited side effects, and potential curative effects.

Antibodies, Anti-Idiotypic↗

Transient suppression of atopy in early childhood is associated with high vaccination coverage.

OBJECTIVE: To analyze prevalences of allergic sensitization and atopic disease in relation to vaccination coverage. METHODS: A German atopy risk-enhanced birth cohort of 1314 neonates who were born in 1990 in 5 German cities was studied. A total of 943 children participated in the follow-up visit at 5 years of age. Atopic symptoms and diagnoses (derived from structured interviews), total serum immunoglobulin E, and specific immunoglobulin E against 9 common allergens (CAP Radio-Allergo-Sorbent Test Fluoro-Enzyme Immunoassay) were evaluated. Children were grouped into dose percentiles according to cumulative doses of any vaccine given up to 5 years of age (<10%, 0-11 doses; 10%-50%, 12-14 doses; 51%-90%, 15-20 doses; >90%, 21-27 doses). RESULTS: The cumulative vaccine dose was inversely related to atopic dermatitis prevalences at 6 months (13.8%, 5.2%, 5.1%, and 4.5%), 2 years (16.9%, 10.9%, 7.4%, and 3.7%), 3 years (27.6%, 16.4%, 13.5%, and 4.5%), and 5 years (28.3%, 16.0%, 9.3%, and 11.9%). Asthma followed a similar pattern at age 3 (22.4%, 8.6%, 6.7%, and 6.3%), age 4 (20.0%, 8.6%, 8.9%, and 8.1%), and age 5 (20.8%, 12.6%, 10.3%, and 5.5%). Allergic sensitization rates were inversely related to the cumulative vaccine dose at age 2 (37.5%, 29.1%, 23.8%, and 12.9%). CONCLUSION: Children with a higher vaccination coverage seemed to be transiently better protected against development of atopy in the first years of life.

Asthma↗

The development of childhood asthma: lessons from the German Multicentre Allergy Study (MAS).

Epidemiological surveys have indicated that there has been a notable increase in the prevalence of both asthma and other allergic symptoms in children and young adults. Since it seems unlikely that genetic factors would contribute to the rising trend, environmental factors might play a major part in the development of childhood asthma. In a prospective birth-cohort study, we assessed the relevance of different exposures such as mite and cat allergen exposure, environmental tobacco smoke (ETS) exposure, early infectious diseases and vaccinations for the development of childhood asthma up to the age of 10 years. Data up to 7 years of age have been evaluated. Of 1314 newborn infants enrolled in five German cities in 1990, follow-up data at age 7 years were available for 939 children (72%). Assessments included repeated measurements of specific IgE to food and inhalant allergens, measurement of indoor allergen exposure at 6 months, 18 months and 3 years of age and yearly interviews by a paediatrician. At age 7 years, pulmonary function was tested and bronchial responsiveness was determined in 645 children. At age 7, the prevalence of wheezing in the past 12 months was 10% (94 out of 938), and 6.1% (57 out of 939) parents reported a doctor's diagnosis of asthma in their children. Sensitisation to indoor allergens was associated with asthma, wheeze and increased bronchial responsiveness. However, no relationship between early indoor allergen exposure and the prevalence of asthma, wheeze and bronchial responsiveness was seen. During the first 3 years of life, intra-uterine tobacco and consistent ETS exposure have an adjuvant effect on allergic sensitisation that is transient and restricted to children with a genetic predisposition for allergy. Children sensitised to any allergen early in life and sensitised to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio (OR) = 10.12; 95% confidence interval (CI) = 3.81-26.88). Children with repeated episodes (> or =2) of runny nose before the age of 1 year were less likely to develop asthma by the age of 7 years (OR = 0.52; 95% CI = 0.29-0.92). Our data do not support the hypothesis that exposure to environmental allergens directly causes asthma in childhood but that induction of specific IgE responses and the development of childhood asthma are determined by independent factors. Indoor allergen avoidance is recommended as first line treatment in secondary and tertiary prevention; however, conclusions should be drawn with caution about the possible effect of primary preventative measures. Since allergic asthma seems to be a Th2-disease, immunomodulating factors such as early childhood infections, LPS-exposure or other factors influencing gene-environment interaction and individual susceptibility seem to be relevant for the development of childhood asthma.

Animals↗