Biomedical subjects
Publications and source records attributed to U Wahn.
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A 10 yr old male with hypoxaemia, progressive infiltration on the chest radiograph and biopsy-proven desquamative interstitial pneumonia was treated with daily oral prednisolone for 6 months. Intravenous methylprednisolone pulses were concomitantly administered in doses averaging 10 mg x kg body weight(-1) on three consecutive days every 4-6 weeks. After 6 months improvement could be noted and oral steroids were stopped, while pulse therapy continued. Three months later, when seven pulses had been administered, a relapse occurred and the clinical status deteriorated. Instead of reinstating daily systemic steroids, the dose of methylprednisolone pulses was increased to 20 mg x kg body weight(-1) i.v. given on three consecutive days and repeat pulses every 4 weeks. This was followed by continuous improvement. After 24 months corticosteroid pulses were terminated. Normal lung function, serum lactate dehydrogenase, blood gases upon exertion and regular development was achieved. During the course of treatment, the child has grown 10 cm. It is concluded that the effect of corticosteroid pulse therapy on interstitial lung disease in childhood is dose-dependent and that the dose can be adjusted to the effect observed.
AIM: of our study was to investigate the effect of pre- and postnatal passive tobacco smoke exposure on the incidence of allergic sensitization. PATIENTS AND METHODS: Specific sensitization to food, outdoor and indoor allergens was determined in 342 children at the age of 1, 2 and 3 years. Parents were asked about their smoking habit at the birth of their children, at 18 months and 3 years of age. RESULTS: Multivariate regression analysis indicated, that during the first 3 years of life, pre- and postnatally exposed children had a significantly higher risk for sensitization to food allergens compared to children never exposed to tobacco smoke (OR 2.2, 95% CI 1.1-4.2; P = 0.02). With respect to inhalant allergens no significant influence of tobacco smoke exposure on specific sensitization could be demonstrated. CONCLUSION: During early childhood both pre- and postnatal tobacco smoke exposure has an adjuvant effect on allergic sensitization to food allergens.
METHODS: 14 patients with cystic fibrosis and chronic pulmonary pseudomonas infection received four courses of two-week intravenous antibiotic therapy at home and during hospitalisation over an 18-month period. Following a controlled, intra-individual cross-over design, two courses of home therapy were followed by two courses of hospital treatment or vice versa. Parameters for inflammation, lung function, and body mass index were obtained at the beginning and end of each intravenous antibiotic therapy. Health-related quality of life, i.e. physical, emotional, social and functional components as well as happiness and medical care, was assessed at the end of each course. RESULTS: There was a trend towards better reduction of infection (p = 0.20 for leukocyte reduction) and improvement of lung function (p = 0.20 for FEV1 improvement) with hospital intravenous antibiotic therapy, although the differences did not attain statistical significance. Quality of life during therapy was significantly higher with home therapy regarding social (p < 0.01), functional and emotional subscales and happiness (all p < 0.05). The necessity for professional help and support from family and/or partner was emphasised. Individual answers showed that home therapy has the advantage of self-determination and continuity of daily life. Parents and partners felt impaired by day and night intravenous therapy at home. CONCLUSION: From our data we conclude that home intravenous antibiotic therapy is a useful option for a selected subgroup of patients with cystic fibrosis, but professional support and family aid is important to gain an effect similar to hospital treatment.
Genetic studies of atopy-associated traits require unambiguous phenotypes to avoid both type 1 and 2 errors. The German Multicenter Allergy Study has provided a birth cohort with longitudinally well defined and stable phenotypes. We summarize data on candidate gene studies on chromosomes 12q, 5q, and 13q using high total IgE and atopic dermatitis (AD) as the most common atopy associated phenotypes in early childhood. We also present data on a functional RANTES promoter polymorphism that we recently identified. A significantly higher frequency of the mutant allele was seen in individuals of African descent compared to Caucasian subjects. In addition, an association of the polymorphism with AD could be demonstrated in the MAS cohort. Although the statistical approaches are limited, the MAS cohort has provided a valuable population for candidate gene studies in atopy.
UNLABELLED: Encasings for mattresses, blankets and pillows in combination with mite allergen reduction on the floor have proved effective in reducing bronchial hyperreactivity of mite-allergic children. We studied the effect of combining the use of encasings with specific immunotherapy in comparison to the use of encasings alone (control group). Twenty mite-allergic children (Skin Prick Test, RAST, mean age 10 years) with asthma and high domestic mite allergen exposure ( > 2 microg Der p 1 + f 1/g mattress dust) were included in our study. The concentration of these major allergens as well as specific and nonspecific bronchial hyperreactivity (PC20 FEV1 histamine) were assessed before, 6 months after and 1 year after start of treatment. All children received elongated polytetrafluorethylene (ePTFE; Goretex/Intervent Allergy Bedding System) encasings. A subgroup of eight children were treated additionally by specific immunotherapy with a partially purified mite extract (ALK Scherax) and a maximum dose of 100000 SQ-U Der p + f. Initially both groups were comparable with respect to the parameters assessed. In 80% of children, encasings reduced Der p 1 and Der f 1 concentrations on the mattress to below 3% of the initial values (P < 0.01). The median reduction was 99%. PC20 FEV1 histamine increased from 0.4 to 1.4 mg/dl (median) in the combined group with immunotherapy and encasings (P < 0.05) and remained essentially unchanged in the control group. PC20 FEV1 Der p did not increase significantly in either group. CONCLUSION: Specific immunotherapy with allergen extracts is an effective adjunct to encasings. Encasings, a key factor for reducing Der p 1 and Der f 1 on the mattress, should be used in combination with other avoidance measures (e.g. removal of carpets) in order to improve allergen-induced bronchial hyperreactivity.
BACKGROUND: Epidemiologic studies suggest an inverse correlation between infections and development of atopy. The purpose of this study was to test the hypothesis whether a preexisting Th1-type immune response elicited by BCG immunization could suppress allergic sensitization and airway hyperreactivity in an animal model. METHODS: BALB/c mice were immunized with BCG and/or sensitized to ovalbumin. RESULTS: BCG immunization alone resulted in cutaneous type-IV hypersensitivity reactions to tuberculin and granulomatous lesions in the liver. Splenic mononuclear cells (MNCs) produced increased levels of IFN-gamma after activation by Concanavalin A (ConA). Ovalbumin sensitization alone resulted in increased production of IL-4 after activation by ConA. Ovalbumin-sensitized animals also demonstrated markedly elevated anti-ovalbumin IgE/IgG1 serum antibody titers and increased airway reactivity after allergen challenges by means of the airways. BCG immunization 14 days before the start of ovalbumin sensitization markedly hindered the development of allergic responses as indicated by (1) increased IFN-gamma and normalized IL-4 and IL-10 production by splenic MNCs after activation with ConA, (2) a reduced proliferation rate of splenic MNCs after ovalbumin restimulation, (3) partial prevention of ovalbumin-specific IgE/IgG1 serum antibody titers but elevated (nonallergic) anti-ovalbumin IgG2a serum antibody titers, (4) prevention of airway responsiveness, (5) reduced eosinophilic influx into the airway lumen, and (6) reduced levels of IL-4 and IL-5 in broncho alveolar lavage fluids. CONCLUSION: In this model BCG immunization established a Th1-type immune response that hinders allergic sensitization and the development of increased airway reactivity.
BACKGROUND: Although there is accepted information on the prevalence rates of sensitization to latex in patients with spina bifida, little is known about the clinical relevance of this sensitization. METHODS: We performed provocation tests with latex gloves in 159 patients with spina bifida (median age, 10 years). RESULTS: Eighty-eight patients (55.3%) were sensitized to latex in terms of a positive skin prick test response, specific IgE to latex in serum, or both. Fifty-five patients (34.6% of all patients or 62.5% of latex-sensitized patients) showed clinical symptoms on provocation. Specific IgE to latex was significantly higher in patients with a positive provocation test response (P <.0001). The total number of operations and degree of sensitization showed a significant correlation. More than 8 operations significantly increased the risk of sensitization (P <.0001), and more than 9 operations increased the risk of allergy to latex (P <.0001). One hundred seventeen (75%) patients had a ventricular shunt system. Specific IgE in these patients was significantly higher than in patients without (P <.0001), and the odds ratio for the existence of a shunt system in terms of a positive provocation was 3.9. Patients with a shunt system were significantly more often sensitized and had positive provocation results (P <.0001). Seventy-two patients (45.3%) were classified as atopic; they were significantly more often sensitized and clinically symptomatic (P <.0001), and the odds ratio for having a positive provocation response was 3.2 for atopic subjects. History of symptoms on contact with material containing latex had a sensitivity of 53.7% and specificity of 94.2%. CONCLUSIONS: Our results indicate that an atopic disposition, number of operations, and presence of a shunt system increase the risk of becoming not only sensitized but also allergic to latex. Our results strongly support the necessity that patients with spina bifida as a high-risk group for latex allergy should remain latex-free from the first day of life.
Asthma training programs for parents and children have been developed to increase both the self-management skills of asthmatic children and compliance with medical regimes. In order to evaluate two training programs for asthmatic children aged 7-14, 81 patients were randomly assigned to three groups. Group 1 consisted of 27 patients and their parents who participated in a five-day standardized family-oriented clinical asthma training program. They had monthly follow-up meetings with the training team for a period of six months. Group 2 (n = 29) had the same clinical training without follow-up interventions; a control group (n = 25) received regular medical treatment according to the international guidelines at the asthma clinics without a training program and served as control group. Questionnaires regarding self-management aspects, coping and anxiety were filled out by patients, parents, family doctors and the training team prior to as well as twelve months after the training. The results indicate that Training group 1 benefitted most with respect to active asthma self-management, Training group 2 to some degree while the control group showed no significant effects. The differences after one year between the three groups regarding physical parameters such as lung-function and days missed in school did not reach the level of significance. Our results indicate that the long-term efficacy of self management courses for asthmatic children is enhanced by regular follow-up training sessions.
OBJECTIVE: In order to study the effect of high-dose, intravenous immunoglobulin (i.v.IG) in severe childhood asthma, we investigated 31 children and adolescents (15 girls, 16 boys) aged 9-22 years (median age of 14 years) suffering from severe bronchial asthma. METHODS: In a prospective, double-blind fashion, patients received either four doses of i.v.IG (1 g/kg body weight) or identical doses of intravenous human serum albumin. The first two doses were given on two consecutive days, followed by two further doses at 4 week intervals. RESULTS: There was no statistical difference in the actively treated group when compared with the placebo group in symptom-score, bronchial hyperreactivity or peak-flow-variability. There was a trend for fewer total days of upper respiratory tract infections and also symptom-scores in the i.v.IG group but these did not reach statistical significance. CONCLUSION: Our data indicate that treatment with i.v.IG in asthmatic children did not show a significant reduction in the incidence of upper respiratory tract infections, but the patients who did have upper respiratory infections in the i.v.IG-group appear to have less protracted infections. Severity and bronchial hyperreactivity do not seem to be affected by the treatment as performed in our study.
BACKGROUND: Cord blood-IgE as risk factor or predictor for atopic diseases in infants has been discussed in a large number of papers with contradictory results. Our aim was to evaluate cord blood-IgE as risk factor and predictor for atopic dermatitis, recurrent wheezing and sensitization with emphasis on a clear-cut distinction between risk factor and predictor. METHODS: A cohort of 1314 newborns was recruited in six German obstetric departments and followed-up for 5 years. Four hundred and ninety-nine infants (38%) were considered to be at high risk with at least two atopic family members and/or a cord blood-IgE value above the threshold of 0.9 kU/L. At follow-up visits, parents filled in a questionnaire, the infants were clinically examined, and blood samples were taken. RESULTS: With regard to early onset atopic dermatitis up to 12 months we found that the odds ratios at the cord blood-IgE cut-off points of 0.70 kU/L and 1.25 kU/L with values of 0.53 and 0.32, respectively, were smaller than one (i.e. protective factors) and highly statistically significant. No significant association was found between elevated cord blood-IgE and recurrent wheezing. There was a strong positive association between elevated cord blood-IgE levels and sensitization at 12 months, but even in this case the predictive performance was rather poor: a maximum positive predictive value of 42% was attained with a cut-off point of 3.0 kU/L, but the sensitivity was only 10%. CONCLUSION: We conclude that even when elevated cord blood-IgE levels are identified as a strong risk factor for sensitization, their poor predictive performance may make them useless as a basis for preventive measures.
BACKGROUND: Screening tests for atopy risk in newborns have a low predictive value. If early atopic symptoms and signs could be used as predictors for the next expected atopic disorder then secondary prevention could be employed. The aim of this study was to evaluate the capacity of early atopic dermatitis to predict aeroallergen sensitization and the manifestation of respiratory atopic disorders at 5 years of age. METHODS: 1314 children of a German prospective birth cohort study MAS-90 were followed from birth up to 5 years of age. Atopic dermatitis, asthma and rhinoconjunctivitis were diagnosed from symptoms and signs at physical examinations and by interviews of the parents. Blood was drawn at 1, 2, 3, and 5 years of age. Aeroallergen sensitization was diagnosed by a specific IgE value of at least 0.35 kU/L (CAP class > or = 1) against any of five respiratory allergens (mite, cat, dog, birch, grass). RESULTS: Atopic dermatitis in the first 3 months was a risk factor for aeroallergen sensitization at 5 years. The risk increased with a positive family history for atopic diseases. Seventy-seven per cent of children with two atopic parents and early atopic dermatitis were sensitized against aeroallergens at 5 years, i.e. could have been predicted in early infancy without any laboratory tests. Although these risk factors were also significantly associated with the manifestation of allergic airway disease, the positive predictive value for this outcome at age 5 years was not yet as high, i.e. 50%. CONCLUSION: Infants with very early signs of atopic dermatitis and a positive family history are candidates for early intervention measures against respiratory allergies.
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BACKGROUND: A family history of atopy is a poor predictor of sensitization to inhalant allergens and allergic disease during childhood. We recently identified early sensitization to food allergens, especially hen's egg, as a valuable predictor of subsequent sensitization to inhalant allergens. OBJECTIVE: (1) Whether prediction will be improved by in vitro allergy tests at 1 year of age in combination with family history and medical history data. (2) Comparison with the capacities of in vitro tests to predict sensitization to aeroallergens. METHODS: Of an observational birth cohort study (MAS) 49 children who were sensitized to inhalant allergens at 5 years of age and 116 non-sensitized controls were included in the present study. For the prediction of sensitization to inhalant allergens the following prognostic factors were evaluated: atopic family history (FH), atopic dermatitis (AD) during the first year of life, two in vitro allergy tests for specific IgE to common food allergens at 1 year of age (fx5 [Pharmacia] and single allergen specific tests (sIgE) for four allergens) and 'high' total serum IgE, defined by three different cut off points. RESULTS: The combination of medical history data and laboratory tests resulted in the best predictive discrimination. The positive predictive values (PPV) were higher if sensitization to food was detected by single allergen specific tests (PPV: 66%/75%/100% corresponding to the three evaluated risk groups) than by the qualitative fx5 (PPV: 46%/65%/100%). The negative predictive values were equal for both tests (69 and 92% for the two low risk groups). High total serum IgE had low predictive capacity. CONCLUSION: During infancy the prediction of sensitization to inhalant allergens should be based on medical history data and allergy tests determining sensitization to food allergens. The in vitro tests improve the predictive discrimination, but the individual risk profile of the child must be considered for a reliable and valid prediction.
Since early intervention could modulate the natural course of atopic disease, the availability of predictive markers is of considerable interest. As long as specific genetic markers are not available, early IgE-responses (hen's egg) together with a positive family history of atopy can be proposed as highly specific and predictive markers, which could define subgroups as potential candidates for secondary prevention.
Chronic skin colonization with Staphylococcus aureus is a well-known feature in atopic dermatitis. The aim of this study was to develop a human-SCID mouse model to analyze the possible role of bacterial superantigens in human allergic immune responses under in vivo conditions. SCID mice were reconstituted with peripheral blood mononuclear cells (between 2 and 9 x 10(7) cells per mouse) from atopic dermatitis patients sensitized to house dust mite allergen (Der p). Total and Der p specific antibody production required the following conditions: (i) injection of Der p; (ii) presence of CD14+ antigen-presenting cells; and (iii) IL-4 as shown by the inhibitory effect of human soluble IL-4 receptor on immunoglobulin E production. This model was used to study the immunomodulatory effects of the superantigen staphylococcal enterotoxin B in comparison with Der p. In intraperitoneally reconstituted human-SCID mice, topical treatment was ineffective in inducing skin inflammation. Therefore, additionally to intraperitoneal transfer, peripheral blood mononuclear cells from atopic donors were also injected intradermally. Such reconstituted SCID mice were then exposed via the skin to either Der p, staphylococcal enterotoxin B, or a combination of both. Maximal effects on epidermal inflammation and dermal T cell infiltration were obtained with staphylococcal enterotoxin B and Der p. Staphylococcal enterotoxin B alone was less effective and Der p only stimulated dermal T cell infiltration. These findings support the hypothesis that bacterial superantigens can act as trigger factors in allergic skin inflammation.
The aim of the study was to investigate possible associations between the time course of early sensitization to latex and various life style factors. Of the 398 children from a prospective birth cohort study, 20 (5%) showed specific serum IgE to latex at the age of 5 years. Sensitization started beyond the first year of life and 19 out of 20 sensitized children showed increasing specific IgE-values over time. All 20 sensitized children were atopic (p < 0.00000). Total IgE was significantly higher in the sensitized group (median 394.5 kU/I) than in the non-sensitized group (median 39.2 kU/l) (p < 0.00001). Comparing the latex-sensitized group with the non-sensitized children, there were significantly more operations in the latex group (p < 0.05) during the first 5 years of life. Medical history, certain foods, the use of pacifiers, mattress composition and socio-economic data proved not to be significant risk factors. From our study we conclude that besides the number of operations and an atopic predisposition--no other definite risk factor for developing sensitization or allergy to latex (such as everyday household objects) can be identified in children up to 5 years of age.
The purpose of the study was to investigate whether the duration of sensitization to food allergens during early childhood is related to later development of IgE mediated hypersensitivity to inhalant allergens and of allergic rhinitis and asthma in 5-year-old children and whether long-lasting food-sensitization may be used to predict subsequent allergic airway diseases. Five hundred and eight children of a prospective birth cohort study with available serum samples at one and two years of age were included and followed up until five years of age. Specific sensitization to food and inhalant allergens and the occurrence of subsequent allergic airway diseases were determined. Children with a long-lasting sensitization to food allergens (persistently sensitized for more than one year) produced significantly higher total IgE and specific IgE levels than children who were only transiently food-sensitized by two years of age. Children persistently sensitized to food had a 3.4 fold higher risk of developing allergic rhinitis and a 5.5 fold higher risk of developing asthma than infants who were only transiently food sensitized. Persistent food sensitization in combination with a positive atopic family history was a strong predictor for the development of allergic rhinitis and asthma at five years of age. The risks for these children are up to 50%, and 67% respectively. Persistently detectable sensitization to food over more than one year in early childhood is a strong prognostic factor for subsequent allergic airway disease. Persistently food-sensitized children especially in atopic families have to be regarded as a high-risk group and should be considered for preventive measures against respiratory atopy.