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Biomedical subjects

U Wahn

Publications and source records attributed to U Wahn.

At least 55 records · Page 3Linked to original sources
PubMed2001

Early childhood infectious diseases and the development of asthma up to school age: a birth cohort study.

OBJECTIVE: To investigate the association between early childhood infections and subsequent development of asthma. DESIGN: Longitudinal birth cohort study. SETTING: Five children's hospitals in five German cities. PARTICIPANTS: 1314 children born in 1990 followed from birth to the age of 7 years. MAIN OUTCOME MEASURES: Asthma and asthmatic symptoms assessed longitudinally by parental questionnaires; atopic sensitisation assessed longitudinally by determination of IgE concentrations to various allergens; bronchial hyperreactivity assessed by bronchial histamine challenge at age 7 years. RESULTS: Compared with children with </=1 episode of runny nose before the age of 1 year, those with >/=2 episodes were less likely to have a doctor's diagnosis of asthma at 7 years old (odds ratio 0.52 (95% confidence interval 0.29 to 0.92)) or to have wheeze at 7 years old (0.60 (0.38 to 0.94)), and were less likely to be atopic before the age of 5 years. Similarly, having >/=1 viral infection of the herpes type in the first 3 years of life was inversely associated with asthma at age 7 (odds ratio 0.48 (0.26 to 0.89)). Repeated lower respiratory tract infections in the first 3 years of life showed a positive association with wheeze up to the age of 7 years (odds ratio 3.37 (1.92 to 5.92) for >/=4 infections v </=3 infections). CONCLUSION: Repeated viral infections other than lower respiratory tract infections early in life may reduce the risk of developing asthma up to school age.

Antibodies↗
PubMed2001

Familial dysautonomia: a diagnostic dilemma. chronic lung disease with signs of an autoimmune disease.

We present an 11-year-old girl with sensory and autonomic neurological dysfunction, and respiratory insufficiency caused by recurrent aspiration. The diagnosis of familial dysautonomia (FD) was confirmed by a missing axonal flare to histamine, miosis in response to conjunctival methacholine and homozygous polymorphic linked markers DS58(18) and DS159(7) on chromosome 9. Ashkenazi Jewish descent could not be ascertained by history. A variety of positive tests for autoantibodies were initially interpreted as evidence for systemic lupus erythematosus vs. overlap syndrome with pulmonary, cerebral, skin, and ocular involvement. The diagnosis of FD was delayed because of the rarity of this disorder in Germany (second case reported). We discuss possible explanations for the misleading immunological findings, including interference by antibodies binding to milk proteins used as blocking reagents in enzyme-linked immunoassays and circulating immune-complexes due to chronic aspiration pneumonitis.

Autoantibodies↗
PubMed2001

Late clinical manifestation of cerebral tuberculomas in two children with tuberculous meningoencephalitis.

UNLABELLED: We report on two children with cerebral tuberculomas leading to late dramatic clinical exacerbation after appropriate antituberculous chemotherapy and high-dose corticosteroids. A 6-year-old girl with tuberculous meningoencephalitis initially fully recovered. However, after 9 months of continuous therapy she presented with acute increased intracranial pressure caused by tuberculomas requiring rapid drainage of CSF. A 16-year-old boy with miliary pulmonary tuberculosis and severe meningoencephalitis had reached a stable condition for more than 10 months although still suffering from a left-dominant spasticity and motor dysphasia. Fifteen months after initiation of therapy he presented with an acute central paralysis of the left facial nerve, progressive hemiplegia, severe ataxia and increasing lethargy caused by a cerebral tuberculoma with a perifocal oedema. Prolonged treatment with antituberculous chemotherapy and high-dose corticosteroids led to complete recovery in the younger patient and marked improvement in the older patient who remains severely handicapped. CONCLUSION: Patients with initially successful treatment of central nervous system tuberculosis should undergo an alert follow-up for the development of late cerebral tuberculomas. Treatment should consist of prolonged courses of antituberculous chemotherapy and high-dose corticosteroids.

Adolescent↗
PubMed2001

Comparison of quantitative ELISA and semiquantitative Dustscreen for determination of Der p 1, Der f 1, and Fel d 1 in domestic dust samples.

BACKGROUND: Quantitative ELISA kits used for the measurement of indoor allergens are time-consuming. Therefore, an immunodot assay (Dustscreen) has been introduced, so that results can be obtained within 4 h. In order to assess the potential applications of the new method, we compared quantitative ELISA methods and Dustscreen. METHODS: We compared the measurements of the mite allergens Der p 1 and Der f 1, and Fel d 1 by both Dustscreen and one brand of ELISA in 82 dust samples, and we also compared the measurement of the cat allergen Fel d 1 by Dustscreen and a different brand of ELISA in 77 dust samples. Optimum dilutions of dust extracts were compared between the ELISA and the immunodot assay. The nonparametric coefficient of correlation (Spearman's rank) was calculated for each allergen. RESULTS: The immunodot assay was easy to perform. There was a good correlation between the results of the ELISA and Dustscreen (Der p 1: r=0.98, Der f 1: r=0.93, and Fel d 1: r=0.98). However, the coefficient of variation varied between 50% and 100% for Fel d 1 above 100 000 ng/g in Dustscreen. No cockroach allergen (Bla g 2) was detected in domestic dust samples in Berlin, and lower concentrations of group 2 allergen of mite (from not detectable to 19 500 ng/gm; median concentration 2000 ng/g) were found than mite group 1 allergens (sum of Der p 1 plus Der f 1: median 12 350 ng/g, minimum n.d., maximum 153 120 ng/g). CONCLUSION: Our results indicate that quantification of indoor allergens in house-dust samples can be performed easily with Dustscreen, and both the technology and methodology are satisfactory.

Allergens↗
PubMed2001

Low-dose cyclosporin A microemulsion in children with severe atopic dermatitis: clinical and immunological effects.

Cyclosporin A (CsA) is an effective and well-tolerated treatment for severe childhood atopic dermatitis (AD). By starting at a low dose, the therapeutic safety should be further increased. The aim of this study was to evaluate low-dose CsA in childhood AD with respect to clinical outcome and modulation of T-cell dysregulation. In an open prospective study, 10 children (age: 22-106 months) with severe AD (mean objective SCORAD score > 40 on two baseline measurements at a minimum interval of 2 weeks) were treated with CsA solution for 8 weeks. All patients received a starting dose of 2.5 mg/kg/day, which was increased stepwise in non-responders to a maximum of dose of 5 mg/kg/day. Disease activity was monitored using the SCORAD index. The frequency of cytokine-producing peripheral blood T lymphocytes was analyzed by intracellular cytokine staining, and T-cell numbers were measured by fluorescence-activated cell sorter (FACS) analysis. Twenty healthy age-matched children were included as controls for the immunological data. Nine of the 10 patients had a SCORAD reduction of at least 35%. In seven patients this was achieved with low-dose CsA at 2.5 mg/kg/day (n = 4) and 3.5 mg kg/day (n = 3). Seven of the nine responders experienced no relapse within the 4-week follow-up period. At baseline the percentage of interleukin-4 (IL-4), IL-13, and human leucocyte antigen (HLA)-DR-positive CD3(+) cells was higher in the patient group than in the controls. After CsA treatment there was a significant reduction in interferon-gamma (IFN-gamma), IL-2, IL-4, IL-13, and HLA-DR-positive CD3(+) cells. Hence, in severe pediatric AD, CsA microemulsion, when started at a low dose (2.5 mg/kg/day), improves clinical measures of disease, reduces T-lymphocyte cytokine production, and regulates T-cell activation.

Adolescent↗
PubMed2001

[Preventive monotherapy with montelukast versus DNCG in children with mild asthma. Results of and exploratory pilot study].

BACKGROUND: Montelukast is used as an add-on medication with inhaled steroids in the therapy of childhood asthma. The aim was to determine the clinical effect of montelukast as a prophylactic therapy in mild asthma in comparison with inhaled sodium cromoglycate. METHOD: 20 children aged 6-14 years were treated in a 20-week open-labelled randomized cross-over design, starting after a 2-week run-in period with either montelukast or cromolyn for 16 weeks with a 2-week wash-out period between treatments. RESULTS: Children treated with cromoglycate showed a significant increase of FEV1 (100.6 vs. 96.5%, p < 0.01) and MEF25 (70.6 vs. 59.1%, p < 0.05) in base line lung function and after cold air challenge (FEV1 97.2 vs. 91.2%, p < 0.05; MEF25 62.9 vs. 54.4%, p < 0.01). Treatment with montelukast effected a significant increase (p < 0.05) in MEF25 from 59.1 to 67.8% in base line lung function alone. Both medications resulted in significant decreases (p < 0.05) in daytime asthma symptoms and evening peak flow variability. Comparing the two treatment substances no statistically significant differences could be registered in any endpoints including beta-agonist use. CONCLUSIONS: Both cromolyn and montelukast showed effective control of mild asthma in children; however, montelukast is more convenient in its application. Further studies are needed to determine the role of leukotriene receptor antagonists in childhood asthma.

Acetates↗
PubMed2001

Atopy patch tests, together with determination of specific IgE levels, reduce the need for oral food challenges in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is commonly associated with food allergy. In addition to skin prick tests (SPTs) and measurements of specific IgE levels, the atopy patch test (APT) has recently been introduced into the diagnostic procedure for food allergy. OBJECTIVE: Our aim was to evaluate whether a combination of allergologic tests could improve the prognostic value of the individual tests for positive food challenge results. We hypothesized that the combination of a positive APT result plus proof of specific IgE, a positive SPT result, or both would render double-blind, placebo-controlled, food challenges unnecessary. METHODS: One hundred seventy-three double-blind, placebo-controlled, food challenges were performed in 98 children (median age, 13 months) with atopic dermatitis. All children were subjected to SPTs, APTs, and determination of specific IgE. Sensitivity, specificity, and positive and negative predictive values were calculated. RESULTS: Ninety-five (55%) of 173 oral provocations were assessed as positive. For evaluating suspected cow's milk (CM) allergy, the APT was the best single predictive test (positive predictive value [PPV], 95%), and the combination of a positive APT result with evidence of specific IgE or an APT result together with a positive skin prick test response optimized the PPV to 100%. For hen's egg (HE) allergy, the APT was also the best single predictive test (PPV, 94%). The combination of 2 or more tests did not exceed the APT's predictive value. In both CM and HE challenges, the predictability of oral challenges depended on the level of specific IgE. For wheat allergy, the APT proved to be the most reliable test, and the PPV of 94% could not be improved by a combination with other allergologic tests. CONCLUSION: The combination of positive APT results and measurement of levels of specific IgE (CM, > or = 0.35 kU/L; HE, > or = 17.5 kU/L) makes double-blind, placebo-controlled, food challenges superfluous for suspected CM and HE allergy.

Administration, Oral↗
PubMed2001

Childhood risk factors for atopy and the importance of early intervention.

The increasing prevalence of atopic diseases, particularly atopy-associated asthma, has become a major challenge for allergists and public health authorities in many countries. The understanding of the natural history of the atopic march, including the determinants that are modifiable and might become candidates for preventive intervention, is still very limited. Information provided by cross-sectional studies can only generate hypotheses, which need to be supported by prospective, longitudinal, cohort studies. Ultimately, it will depend on the results of well-controlled intervention studies to identify which nutritional, environmental, or lifestyle-related factors should be considered for early intervention and might be useful to reverse the epidemiologic trend.

Biomarkers↗
PubMed2001

The pattern of atopic sensitization is associated with the development of asthma in childhood.

BACKGROUND: Even though atopic sensitization has been shown to be strongly associated with childhood asthma, asthma eventually develops in only one third of atopic children. OBJECTIVE: The aim of this study was to prospectively investigate the pattern of atopic sensitization typically associated with the development of asthma in childhood. METHODS: The German Multicenter Allergy Study followed 1314 children from birth to the age of 7 years. Parental questionnaires on asthma and asthmatic symptoms were completed 6 times up to the age of 2 years and from then on yearly. Determination of specific IgE to 9 food and inhalant allergens was performed yearly, and at the age of 7 years, a bronchial histamine challenge was conducted. RESULTS: Onset of atopic sensitization in atopic children with current asthma at the age of 7 years was significantly earlier than in atopic children without current asthma (39.4% before age 1 year vs 21.0%, P =.015). Early atopic sensitization without any sensitization to inhalant allergens at the age of 7 years conferred no increased risk for asthma at this age. Only those children sensitized to any allergen early in life and sensitized to inhalant allergens by the age of 7 years were at a significantly increased risk of being asthmatic at this age (odds ratio, 10.12; 95% CI, 3.81-26.88). However, even in this group of persistently sensitized children, the risk of being asthmatic at the age of 7 years was only increased if a positive parental history of asthma or atopy was present (odds ratio, 15.56; 95% CI, 5.78-41.83), with the effect being strongest for maternal asthma. CONCLUSION: Our results indicate that an underlying factor pertaining to asthma and maternal transmission may determine both a certain pattern of sensitization and the expression of asthma.

Age Factors↗
PubMed2001

Predictors of positive food challenge outcome in non-IgE-mediated reactions to food in children with atopic dermatitis.

BACKGROUND: Atopic dermatitis is frequently associated with food allergy. In general, clinically manifested food allergy is regarded as IgE mediated. However, there are some children with food allergy for whom IgE hypersensitivity cannot be proven. OBJECTIVE: The aim was to evaluate the percentage of children with positive double-blind, placebo-controlled food challenge (DBPCFC) results but without any proof of IgE sensitization and to characterize this subgroup of children. METHODS: Two hundred eight DBPCFCs were performed in 139 children (median age, 13 months) with atopic dermatitis and suspected food-related clinical symptoms. All children were subjected to skin prick tests (SPTs), determination of specific IgE, and atopy patch tests. RESULTS: One hundred eleven (53%) of 208 oral food challenge results were assessed as positive. Positive challenge results were separated into 2 groups according to IgE positivity: negative SPT and negative specific IgE results in serum (group A, n = 12) and positive SPT, specific IgE, or both results in serum (group B, n = 99). The atopy patch test results; the distribution of early, late, or both clinical reactions; the age of the children; and the total IgE levels all showed no significant differences between the 2 groups. However, wheat challenge results were more often positive among the apparently non-IgE-sensitized children, and hen's egg challenge results were more often positive in the sensitized group (P < .05). CONCLUSION: Around 10% of positive DBPCFC results are not IgE mediated. Therefore not the proof of specific IgE but the suspicion of food-related symptoms should be the indication to perform oral food challenges, especially in the case of wheat. Otherwise, some children will not receive diagnoses for food allergy and be denied the benefits of a specific diet.

Allergens↗
PubMed2001

Sensitizing capacity and residual allergenicity of hydrolyzed cow's milk formulae: results from a murine model.

BACKGROUND: Cow's milk allergy is the most common cause of clinically relevant adverse reactions to food in infants and children. Partially and extensively hydrolyzed formulae are used for the therapy and prevention of cow's milk allergy. However, the immunogenic potency of hydrolyzed cow's milk formulae to induce and/or enhance the allergic phenotype in vivo is still under debate. The aim of this study was to assess the sensitizing capacity and residual allergenicity of various partially and extensively hydrolyzed cow's milk formulae in a murine model of cow's milk allergy. METHODS: BALB/c mice were immunized with either a cow's milk formula or various partially and extensively hydrolyzed formulae. Immediate cutaneous hypersensitivity reactions and allergen-specific antibody production were assessed. RESULTS: Although immunization with cow's milk resulted in 12/13 cases in a positive skin test response to intradermal injection of cow's milk formulae, only 1 mouse showed a positive skin test to one of the partially hydrolyzed formulae, and none showed positive reactions to other partially hydrolyzed formulae, any of the extensively hydrolyzed formulae, phosphate-buffered saline or the amino acid formula. However, 6 of 8 mice showed positive skin tests when immunized with partially hydrolyzed formulae and with one of the extensively hydrolyzed formulae. CONCLUSIONS: The residual allergenic potential is markedly reduced in many hydrolyzed formulae, but most of the formulae investigated could induce an allergic immune response in BALB/c mice. Our murine model seems to be suitable to investigate the sensitizing capacity of hydrolyzed formulae and to differentiate even between extensively hydrolyzed formulae.

Animals↗
PubMed2001

Effect of low-dose cyclosporin a microemulsion on disease severity, interleukin-6, interleukin-8 and tumor necrosis factor alpha production in severe pediatric atopic dermatitis.

BACKGROUND: The release of cytokines [interleukin-6 (IL-6), IL-8 and tumor necrosis factor-alpha (TNF-alpha)] by skin cells is involved in the pathogenesis of atopic dermatitis (AD). OBJECTIVE: To evaluate the effect of low-dose cyclosporin A (CyA) on clinical symptoms and cytokine secretion in severe pediatric AD. METHODS: Ten children with severe AD (SCORAD index >50) were treated for 8 weeks with CyA. The initial dose of 2.5 mg/kg/day was titrated to a maximum of 5 mg/kg/day until a SCORAD reduction of >or =35% was achieved ("treatment response"). After stopping CyA all patients entered a 4-week follow-up period. Cytokine secretion (IL-6, IL-8 and TNF-alpha) from patients' PBMC was assessed by ELISA before and after CyA treatment and was compared with 18 healthy nonatopic controls. Only the data of patients, who responded to CyA and did not experience a relapse during the follow-up period, were evaluated for this paper. RESULTS: Seven patients responded to CyA without relapse during the follow-up period. The median SCORAD index in these patients improved from 71 at baseline to 22 after CyA treatment (p < 0.001). AD patients' PBMC produced more IL-6, IL-8 and TNF-alpha than PBMC of controls. Suppression of IL-6 (p < 0.05) and IL-8 (p < 0.05) production was observed after CyA treatment. TNF-alpha levels were unchanged by CyA in all patients. CONCLUSIONS: The reduction in severity of pediatric AD with CyA is associated with decreased production of IL-6 and IL-8, but not TNF-alpha by PBMC.

Adolescent↗
PubMed2001

Histamine challenges discriminate between symptomatic and asymptomatic children. MAS-Study Group. Multicentre Allergy Study.

The aims of this study were to investigate a threshold value for bronchial responsiveness in children aged 7 yrs, which discriminates between symptomatic and asymptomatic children, and to identify determinants of this responsiveness. Titrated bronchial histamine challenges using the reservoir method were performed in 645 children aged 7 yrs, from the birth cohort Multicentre Allergy Study (MAS). When defining a reference population of healthy children within the MAS cohort, the 95th percentile of the provocative concentration causing a 20% fall in forced expired volume in one second PC20 among these asymptomatic study subjects amounted to 0.60 mg x mL(-1). This resulted in a specificity of 93.0% and a sensitivity of 45.9%, for discriminating between "current wheezers" and "non-current wheezers". Determinants of airway responsiveness at this age were pulmonary function, sensitization to indoor allergens, total immunoglobulin E and current wheeze. The results indicate that a very low cut-off provocative concentration causing a 20% fall in forced expired volume in one second (<1.0 mg x mL(-1)) defines airway hyperresponsiveness in children aged 7 yrs using the reservoir method. Provocation protocols for histamine challenges in this age group should therefore start with concentrations markedly below 1.0 mg x mL(-1).

Allergens↗
PubMed2001

Effect of glucocorticoid therapy on glucocorticoid receptors in children with autoimmune diseases.

Low-dose glucocorticoids (GC) achieve their action completely by classical genomic effects, mediated by the glucocorticoid receptor (GCR). In high doses of GC, nongenomic effects have also been found, but it is still unclear to what extent they contribute to a beneficial outcome. In this study, we present a determination of the number of lymphocyte GCR sites and the binding affinity in healthy children and children with autoimmune diseases. We further assess the effect of GC administration, especially of high-dose pulse therapy on the number of binding sites. The number of GCR sites per cell was analyzed with [(3)H]-dexamethasone radioligand binding assay and binding affinity (Kd given in nM) in peripheral blood mononuclear cells isolated from 48 healthy children and 35 patients. The patients were divided into three groups based on GC treatment: 0 mg/kg (group 1), 0.01-0.3 mg/kg orally (group 2), and 10-15 mg/kg i.v. pulse therapy (group 3) of prednisolone equivalent per day. Gender- and age-independent normal values of 4338 +/- 1687 sites/lymphocytes and Kd 6.7 +/- 2.2 nM were found. At 3463 +/- 1574, the number of receptor sites in patients without GC (group 1) was significantly lower than that of healthy volunteers (p < 0.05). In patients receiving GC treatment, this value was reduced to 2952 +/- 512 (group 2). Significant down-regulation to a minimum of 479 +/- 168 (group 3) was found after pulse therapy compared with untreated patients (p < 0.01). In pulse therapy, GC lead to a fast and dramatic receptor down-regulation. We suppose that the increase in therapeutic success of pulse-therapy may partly be mediated through additional nongenomic effects.

Adolescent↗
PubMed2001

Delayed hypersensitivity to tuberculin, total immunoglobulin E, specific sensitization, and atopic manifestation in longitudinally followed early Bacille Calmette-Guérin-vaccinated and nonvaccinated children.

BACKGROUND: Bacille Calmette-Guérin (BCG) is a strong T helper 1 incentive and, thus, may contribute to a decreased risk of T helper 2-dependent atopic disease. OBJECTIVE: To investigate the natural course of specific immunoglobulin E (IgE) responses and atopic disease in BCG-vaccinated and nonvaccinated children. PARTICIPANTS: Seven hundred seventy-four children from a prospectively followed birth cohort. OUTCOME MEASURES: Physical examination and case history were performed at 3, 6, 12, 18, 24, 36, 48, 60, 72, and 84 months of age. Total and specific serum IgE levels to 9 common inhalant and food allergens were determined (CAP; Pharmacia, Freiburg, Germany) at 12, 24, 36, 60, 72, and 84 months of age. Purified protein derivative (PPD) skin testing was performed at 84 months. RESULTS: Period and lifetime prevalences of atopic dermatitis and recurrent wheezing tended to be lower in the BCG-vaccinated group early in life, whereas no such trend was found after the second birthday or for allergic rhinitis. The proportion of children remaining free of clinical manifestations tended to be higher in the BCG-vaccinated group but differences decreased over time. No statistically significant differences were found for total IgE levels (median). Atopic sensitization tended to be lower among BCG-vaccinated children during the first 2 years of life. The diameter of the skin reaction to PPD did not correlate with total serum IgE. Clinical and serologic correlates of atopy were not significantly different between children with a skin test diameter of >/=5 mm and those with a smaller diameter. CONCLUSION: These results do not support the hypothesis that BCG vaccination in early infancy is associated with a subsequently markedly decreased risk of atopic sensitization or allergy. In addition, PPD skin test reactivity was not impaired in atopic individuals.

BCG Vaccine↗