Biomedical subjects
B Niggemann
Publications and source records attributed to B Niggemann.
On relationship between exposure to dust mite allergen and bronchial response to exercise in schoolchildren sensitized to dust mites.
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The role of eosinophils and eosinophil cationic protein in monitoring oral challenge tests in children with food-sensitive atopic dermatitis.
To investigate the role of peripheral blood eosinophils and eosinophil cationic protein as parameters in monitoring oral food challenges, we monitored 25 infants and children with atopic dermatitis for up to 48 hours after 47 placebo-controlled oral food challenges with cow's milk, hen's egg, cow's milk and hen's egg, or placebo for up to 48 hours. Six healthy young nonatopic adult volunteers served as control subjects. Compared with baseline values, peripheral blood eosinophils decreased significantly immediately after clinical reaction in positive challenges (p < 0.0004), independent of the kind of reaction. Eosinophil cationic protein increased significantly 8 hours after provocation, with a maximum at 24 hours (p < 0.03). This increase was predominantly related to eczematous reactions (p < 0.005). Blood sampling immediately after clinical reaction (for eosinophils) and at 24 hours (for eosinophil cationic protein) seems to be useful in monitoring oral food challenges in children with atopic dermatitis.
Discrepancies between in vitro and in vivo tests for house dust mite allergy: in domestic exposure a better predictor than sensitization?
We subjected seven asthmatic children to two bronchial allergen challenges, first with an extract from the house dust mite Dermatophagoides pteronyssinus (Der p) and then Dermatophagoides farinae (Der f), or vice versa. All children had elevated specific serum IgE to both species as well as reactions by crossed radioimmuno/electrophoresis (CRIE) to both group I and II allergens from both species. Immunoabsorption and subsequent analysis by CRIE showed a considerable concentration of serum IgE with specificity for epitopes common to the two species of house dust mite. Home dust sampling established that all children were exposed to Der f and only two to Der p. On bronchial provocation tests, all responded to Der f with an immediate reaction and five with a late reaction, only three of seven showed an immediate response to Der p, with four of the seven showing a late reaction. Our data could indicate that the local allergic immune reaction in the respiratory tract is sustained by ongoing exposure, and may thus have a different species specificity than the response reflected in the serum. In conclusion, our data indicates a lack of association between in vitro and in vivo tests for house dust mite allergy, which supports the continuing need for monitoring current clinical sensitization by allergen provocation tests and by measuring domestic exposure to the corresponding allergen. Extended studies are needed to support our findings.
Twenty-four-hour time course of eosinophil granule proteins ECP and EPX during bronchial allergen challenges in serum of asthmatic children.
To study in vivo monitoring variables for bronchial allergen challenges, we investigated the time course of the eosinophil granule proteins, eosinophil cationic protein (ECP) and eosinophil protein X (EPX) after allergen provocation in serum. Thirty-two asthmatic children sensitive to house-dust mites and six healthy young adult controls were challenged by bronchial allergen provocations with Dermatophagoides pteronyssinus and D. farinae. Blood samples were taken at regular intervals up to 24 h. Base-line concentrations of ECP (P < 0.004), EPX (P < 0.002), and eosinophils (P < 0.001) were found to be increased in asthmatic children, as compared with healthy controls. ECP and EPX concentrations showed a uniform pattern with two characteristic features: 1) a rapid increase for both mediators up to 30 min after provocation over base-line values (P < 0.0001 and P < 0.001), followed by a rapid decrease nearly to base-line values in the next 30 min; and 2) a steady increase for ECP and EPX up to 10 h (P < 0.02 and P < 0.01), and even higher levels at 24 h, after challenge (P < 0.002 and P < 0.003). We conclude that although eosinophils are activated in asthmatic children after bronchial allergen challenge, ECP and EPX concentrations are not suitable monitoring variables. Base-line eosinophils seem to predict the occurrence of a late-phase asthmatic reaction after allergen provocation.
Serum levels of sCD23 and sCD25 in children with asthma and in healthy controls.
To investigate whether markers of lymphocyte activation are useful markers of disease activity in childhood asthma, we studied serum levels of soluble CD25 (receptor for IL-2) and soluble CD23 (low-affinity receptor for IgE) in 178 children (aged 2-18 years) suffering from mild to moderate asthma (mean asthma severity score: 2, range: 1-4), and in 175 healthy age-matched controls. Levels of sCD23 and sCD25 were inversely related to age. sCD23 was lower in patients with asthma (means per age group: 4.93-2.29 micrograms/l; controls: 6.92-4.11 micrograms/l, P < 0.05), while sCD25 tended to be higher (1601-597 kU/ml, controls: 1350-661 kU/ml, P = NS). sCD25 correlated significantly with asthma severity score (r = 0.41; P < 0.01) and MEF25 (maximum expiratory flow at 25% of vital capacity, r = -0.43; P < 0.05) in children < 10 years, while sCD23 correlated with asthma severity (r = 0.28; P < 0.05) in children > 10 years. On follow-up, levels of sCD25 normalized with clinical improvement. In children with nonatopic asthma, levels of sCD25 were significantly higher than in atopic patients. Our observations provide further evidence of the role of T-cell activation in asthma. Monitoring of lymphocyte activation markers, particularly levels of sCD25, may be useful in the follow-up of asthmatic children.
Proposals for standardization of oral food challenge tests in infants and children.
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Age related IgG subclass concentrations in asthma.
The prevalence of IgG subclass deficiency in asthma is still controversial. Earlier studies often included patients receiving treatment with systemic steroids which can induce hypogammaglobulinaemia. Concentrations of IgG subclasses were studies in 200 children (aged 2-17 years) with asthma (mean asthma severity score (ASS) 2, range 1-4) who had not received systemic steroids for at least six weeks before investigation, and in 226 healthy age matched controls. The mean concentrations of IgG subclasses in children with asthma were within the 1SD range of those of the control group. In the group with asthma there was a trend towards higher levels of IgG1 and IgG4, whereas the number of children with low concentrations of IgG2 (< 2 SD of control serum samples; absolute concentrations 0.08-1.25 g/l) was slightly greater than in the group who did not have asthma (4.5 v 2.2%). Patients with subnormal concentrations of IgG2 could not be distinguished clinically or on the basis of case history and additional immunological studies did not show further abnormalities. Patients with severe asthma (ASS 3-4) had significantly higher concentrations of IgG4 (mean (SE) 0.53 (0.09) v 0.26 (0.04) g/l) than patients with mild asthma (ASS 1). No significant difference in subclass concentration was found between patients with atopic and those with non-atopic asthma. It is concluded that in an unselected group of children with asthma the mean IgG subclass concentrations do not differ significantly from a group of healthy age matched controls.
Asymptomatic pulmonary involvement in 2 children with Niemann-Pick disease type B.
We present 2 cases of children with Niemann-Pick disease type B, and surprisingly with reticular lung infiltrations, although otherwise healthy in terms of pulmonary manifestation. Finding such reticular infiltrations should lead one to think of the possibility of metabolic storage disease.
Serum tryptase and urinary 1-methylhistamine as parameters for monitoring oral food challenges in children.
To study the usefulness of urinary 1-methylhistamine and serum tryptase concentration as monitoring parameters in clinical settings, we investigated 32 children with atopic dermatitis and suspected food allergy during oral food challenges with eggs and cow's milk. Urinary 1-methylhistamine (MH) excretion increased significantly within 1 h after positive oral food challenges (p < 0.006), but showed considerable variation in negative challenges. MH seems to be a sensitive parameter (92.8%), but its specificity is insufficient (37.7%). In the group of 16 positive oral food challenges serum tryptase concentration increased significantly (p < 0.02) directly after provocation and remained elevated up to 2 h after provocation. No variation was observed in negative challenges or nonatopic controls. Serum tryptase concentration seems to be specific for marked clinical reactions after oral food challenges (100%), but its sensitivity was low (25%) and not superior to evaluation by clinical means. We conclude that, despite positive results for the group of children, MH and serum tryptase concentrations are not useful parameters for monitoring oral food challenges in an individual child due to insufficient sensitivity and specificity.
Cystic pulmonary lesion in a 6 year old girl.
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Monitoring of inflammation during challenge tests in children.
From our data we conclude, that the determinations of ECP and EPX do not add any useful information as monitoring parameters for bronchial allergen challenge tests. In contrast, eosinophils and eosinophil cationic protein may deserve further study as potentially useful monitoring parameters for oral food challenges in patients with food related atopic eczema.
Lymphocyte subsets, sIL2-R and sICAM-1 in blood during allergen challenge tests in asthmatic children.
In order to study cell activation in peripheral blood on bronchial allergen provocation up to 24 h, we investigated 32 asthmatic children, sensitive to house-dust mites. Six healthy young adult volunteers served as controls. Lymphocyte subsets (CD3, CD19, CD4, CD8) and activation markers (CD25-T, HLADR-T, CD23) in peripheral blood as well as soluble IL2-R and soluble ICAM-1 in serum were evaluated. In terms of clinical reaction, 23 children exhibited a DAR, 6 an EAR, 6 a LAR and 3 children did not show a bronchoconstrictor response to allergen challenge with house-dust mite extract (NAR). In comparison to controls, asthmatic children showed a significantly higher expression of CD23 on B-lymphocytes (p < 0.05). Other subsets were in the same range in both groups. After provocation there was a significant increase of CD4/CD8-ratio only in asthmatic children. Serum levels of sIL2-R were significantly higher in asthmatic children compared to controls at baseline as well as at 12 and 24 h after provocation, without variation during observation period. No differences were noted for sICAM-1. Our results confirm the hypothesis that lymphocytes, as important cells in regulation of allergic immune response, are recruited into peripheral blood under allergen challenge conditions in sensitized asthmatic children.
Substitution of metered-dose inhalers for hand-held nebulizers.
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[Homozygous alpha 1-antitrypsin deficiency. Lung changes in children and adolescents].
Homozygous alpha 1-antitrypsin deficiency can lead to pan-lobular emphysema early in adulthood. Based on own studies and a review of the literature the article dates up the knowledge about risk factors (especially smoking), the variable clinical pattern (relationship to bronchial hyperreactivity) and pulmonary function (30% pulmonary hyperinflation) of children and adolescents with homozygous alpha 1-antitrypsin deficiency (PIZZ). It discusses diagnostic (selective screening, regular lung function tests) and therapeutic possibilities (substitution) as well as preventive aspects (passive and active smoking cessation).
[Adrenal cortex function in children with bronchial asthma in fluticasone therapy].
In order to study the adverse reaction of a new, inhaled steroid (Fluticasone) on the pituitary-adrenocortical axis in asthmatic children, we investigated 7 children (aged 7 to 15 years) before and during treatment with Fluticason (100-200 micrograms/day). For the dosage tested, we found no depression of adrenal function, neither in circadian cortisol secretion nor in hCRH-stimulation-test. Another 7 asthmatic children under treatment with Budesonide (800 micrograms/day) were examined by the same tests. They equally did not show an adrenocortical suppression. However, in 4 other children under therapy with oral prednisone (2.5 to 7.5 mg/day), there was a marked suppression on adrenocortical function, even with low doses of the steroid. We conclude that Fluticasone (as well as Budesonide) in the above dosages represent a safe therapy for bronchial asthma in children.
Abnormal length of cilia--a cause of primary ciliary dyskinesia--a case report.
A 7-year-old Turkish boy had suffered from chronic coughing from early childhood. Severe bronchiectasis in the right lung was confirmed by bronchography. Ciliary beat frequency determined in a bronchial mucosal biopsy was markedly decreased (5.7 Hz). Electron microscopy revealed cilia with a length of 15 microns. No structural abnormality was found. A possible link between the abnormally long, slow beating cilia and the clinical symptoms is discussed.