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Notizen: The hypothesis that repeated exposure to a specific allergen will further increase bronchial responsiveness to that allergen is supported by indirect evidence. However, it has not been tested as intensely in the laboratory setting, and in some cases, conflicting results are presented. In order to test the hypothesis in the atopic subjects, allergen inhalation challenge tests were performed in 29 house dust mite (Dermatophagoides pternyssinus) sensitive subjects with allergic rhinitis. Nine subjects displayed early asthmatic responses (EARs) to the first challenge (Group 1). Twenty subjects with no significant airway response were submitted to the second challenge 24 h later. Thirteen subjects showed EARs (Group FI) and two of these showed late asthmatic responses (LARs)aswell. In Group II, there were significant changes between the first and second challenge in post-allergen early phase FEV1, (88.1 ± 4.2 vs 71.7 ± 4.2%, baseline, P 〈 0.05) and in post-allergen late phase FEV1, (93.1 ± 3.4 vs 86.6 ± 7.8. P 〈 0.05). After the second challenge. PD20 (provocative dose of methacholine required to produce a 20% fall in FEV1) decreased significantly from the baseline values. When challenged separately with twofold dose of allergen, only three and one of the Group II showed EAR and LAR respectively. PD20 did not change significantly after this challenge. These results indicated that two repeated exposure to allergen dose, which is not enough to cause significant airway responses at a time, may provoke asthmatic airway responses in the subjects with allergic rhinitis and that this effect of priming is not attributed to the cumulative dose but to the consequent effect of repeated allergen exposure.

Notizen: Several candidate genes have been reported to be linked to intermediate phenotypes of asthma in Caucasian populations.To evaluate linkage between phenotypes of asthma and gene markers of high affinity IgE receptor-β gene (D11S97), IL-4 cytokine gene cluster (IL-4R1), and T-cell receptor α/δ gene complex (D14S50) in Korean nuclear families.Nuclear families (127 probands and their 130 siblings) for the linkage analysis were ascertained through asthmatic children. Linkages between total serum IgE response, skin responses to common aeroallergens, and bronchial responsiveness to methacholine were performed using a sib-pair approach.The square difference of the slope of the dose–response curve (DRS) between sib-pairs with two IL-4R1 identical alleles was smaller than with one or with neither IL-4R1 identical allele (P = 0.004). As for D14S50, the differences of DRS between sib-pairs with two identical alleles and with one identical allele were smaller than with neither identical alleles (P = 0.01). As for D11S97, no significant differences were observed among the groups with identical alleles of two, one or zero. With regard to total serum IgE levels, no significant linkage was found between this phenotype and the above three gene markers. As for skin responses to common aeroallergens, significant evidence was obtained to establish a linkage between this phenotype and the marker IL-4R1 (P = 0.01). However, no significant linkage was found between this phenotype and the markers D11S97 and D14S50.The expression of bronchial responsiveness to methacholine may be influenced by genetic factors in the IL-4 cytokine gene cluster and/or T-cell receptor α/δ gene complex, but the genetic influence of the FcεRI-β gene may be minimal in the expression of bronchial responsiveness in Korean nuclear families.

Notizen: Cough variant asthma is an occult form of asthma in which the only sign or symptom is chronic cough. It is a common problem amongst all ages that frequently goes unrecognized, leading to under diagnosis and under treatment. To characterize the pathophysiological abnormalities in these patients, we performed bronchial provocation tests with methacholine using the stepwise doubling concentration technique, and measured the concentration of methacholine and the severity of airway obstruction when wheezing was first detected. Airway hyper responsiveness, defined as PC20 in the cough variant asthma group was not significantly different from that of classic asthma. There was a good correlation between the PCW (the concentration of methacholine causing wheezing) and the PC20 with the PCW values higher than PC20 values in both groups. However, in the cough variant asthma group, the PCW: PC20 ratio was greater than that of the classic asthma group. Furthermore, the mean % fall in FEV1 at which wheezing was first detected in the former group was significantly larger than that of the latter group. The results indicated that the mechanism for the manifestation of cough without wheeze in the cough variant asthma may be a higher wheezing threshold, i.e. wheezing becomes audible at the greater degree of airway obstruction than classic asthma. They suggested that patients with cough variant asthma may represent a subset of asthmatic subjects whose airways are less able to produce a wheeze.

Notizen: Background With β-agonists being the most widely used agents in the treatment of asthma, in vitro studies reported that β2-adrenergic receptor (ADRB2) polymorphisms are associated with agonist-promoted down-regulation.Objective The present population-based study aimed to evaluate the association between bronchodilating response to inhaled short-acting β-agonist and two non-synonymous single-nucleotide polymorphisms (SNPs) of ADRB2 (ADRB2-16 and ADRB2-27).Methods Two hundred and nine children with reduction in forced expiratory volume in 1 s of more than 20% on methacholine bronchial challenge underwent bronchodilating response testing 5 min after the inhalation of 200 μg of albuterol. Of these 209, 195 gave peripheral blood for genotyping of ADRB2 polymorphisms.Results The bronchodilating response was significantly higher in subjects with the homozygous Arg16 than in those with the homozygous Gly16. It was further demonstrated that haplotype pairs of the homozygous Arg16Gln27 and of the heterozygous Arg16Gln27/Gly16Glu27 showed the highest bronchodilating responses, and the haplotype pairs of the homozygous Gly16Gln27 the lowest response. As a whole, the bronchodilating response was more positively associated with the combined quantity of Arg16 and Glu27 polymorphisms than with that of Arg16 alone.Conclusion Non-synonymous SNPs of ADRB2 at codons 16 and 27 is significantly associated with bronchodilating response to inhaled short acting β-agonists.

Notizen: Background Recent investigations have demonstrated that spider mites are important allergens in the development of asthma in fruit-cultivating farmers.Objective The aim of this study was to evaluate the sensitization rate to the citrus red mite (Panonychus citri) in children living in rural areas, and to determine the allergenic cross-reactivity with other mites.Methods A total of 7254 children (ages 7–15 years) living in rural areas were enrolled, and each subject was evaluated by a questionnaire and a skin prick test. Allergenic cross-reactivity was evaluated by ELISA inhibition tests.Results The most common sensitizing allergens were house dust mites, followed by citrus red mite and cockroach. High serum-specific IgE bindings to the citrus red mite were detected in 21 of 100 randomly selected subjects. The prevalence of asthma was higher among those with positive skin responses to the citrus red mite than with negative skin responses to this mite. ELISA inhibition tests showed that IgE bindings to this mite were minimally inhibited with additions of domestic mites.Conclusion Spider mites such as the citrus red mite may be important outdoor allergens among children living in rural areas, and spider mite-derived allergens have unique allergenic determinants compared with domestic mites.

Notizen: Background There have been many studies concerning pathological changes in bronchial mucosa from asthmatics; however, few studies has been carried out to evaluate pathological changes according to the severity of asthma.Objective This study was designed to evaluate the cellular components in bronchoalveolar lavage fluid (BALF) and histologicai abnormalities in asthmatics according to the severity ot asthma.Methods Bronchoalveolar lavages, bronchoscopic biopsies and ultrastructural examinations were performed in 13 asthmatics and 11 (BAL) or four (biopsies) non-asthmatic controls. The proportions of epithelial cells and eosinophils in BALF were significantly increased in asthmatics and showed significant correlations with PC20Meth which reflects bronchial hyperresponsiveness. Light microscopic examination revealed loss of epithelium, inllammatory cell infiltrations and thickening of the basement membrane which also showed significant correlation with PC20Meth. Hypertrophy of airway smooth muscles and hyperplasia of mucous glands were prominent in asthmatics but there was no difference according to the severity of asthma. Ultra-structural examination revealed that basement membrane thickening on light microscopic examination is due to the increased subepithelial collagen deposition with normal thickeness of basal lamina.Conclusion These data suggest that loss of epithelial cells, infiltration of inflammatory cells, especially eosinophils, and increased deposition of subepithelial collagen play major roles in determining the severity of asthma and non-specific bronchial hyperresponsiveness.

Notizen: Background Allergen-specific immunotherapy has proven to be clinically effective in the treatment of patients with atopic asthma; however, the mechanisms are still unclear. Several noted immunological changes include an increase of the allergen-specific IgG antibody, a reduction in the allergen-specific IgE antibody subsequent to transient increase, an allergen-specific T cell shift in cytokine production from Th2 to Th1, and a decrease in quantity and activity of basophils and mast cells.Objective To analyse the changes of basophil histamine release in response to IgE-mediated and non-IgE-mediated stimuli before and after conventional house-dust mite immunotherapy in children who suffer from atopic asthma.Methods Fourteen Dermatophagoides farinae (Df) sensitive asthmatic children with conventional immunotherapy were examined. Basophil histamine releasability was measured 0 months (just before immunotherapy), 4 months and 9 months after immunotherapy. Basophils were stimulated with Df and goat anti-human IgE antibody as IgE-mediated stimuli; and formyl-Met-Leu-Phe (fMLP) and calcium ionophore A23187 as non-IgE-mediated stimuli. Accordingly, the asthma symptom score was used to assess clinical outcome and the skin test reactivity to Df was measured.Results In contrast to pre-immunotherapy activity, 4 and 9 months after immunotherapy there were significant decreases in histamine release by Df and by anti-IgE antibody. The histamine release by fMLP and by calcium ionophore showed no significant changes after immunotherapy. Histamine release by Df demonstrated significant correlation to that by anti-IgE antibody and by fMLP, yet there was no observable correlation between histamine release by Df and by calcium ionophore. The asthma symptom score decreased significantly 4 and 9 months after immunotherapy and showed significant correlation with histamine release by Df. The skin test reactivity (allergen/histamine ratio) remained constant 4 months after immunotherapy, but decreased significantly 9 months after immunotherapy.Conclusion Basophils have the potential to play an important role in the early clinical improvement of conventional immunotherapy in children with atopic asthma, which may be a result of the decreased IgE-mediated histamine releasability during immunotherapy.

Notizen: Background Spider mites such as the citrus red mite and the two-spotted spider mite have been demonstrated to be important allergens for fruit cultivating farmers.Objective To evaluate the role of environmental exposure to spider mites in the sensitization and the clinical manifestations of asthma and rhinitis in children and adolescents living in urban and rural areas.Methods A total of 16 624 subjects (aged 7 to 18 years) living in urban (metropolitan and non-metropolitan) and rural areas (apple orchards and citrus orchards) in Korea were evaluated by questionnaire and skin prick test for 11 common aeroallergens, including citrus red mite (CRM) and two-spotted spider mite (TSM).Results The positive skin response rates to TSM were 4.2% of 1563 metropolitan subjects, 3.8% of 5568 non-metropolitan subjects and 6.5% of 1464 subjects living nearby apple farms, and that to CRM 15.6% of 8029 living nearby citrus farms. The prevalence of current wheeze and rhinitis as reported on a questionnaire was higher among those with a history of visiting fruit farms once or more per year than among those without it (10% vs. 7.1%, 32.8% vs. 26.7%, for wheezing and rhinitis, respectively). Among those with wheezing or rhinitis, the positive skin responses to TSM or CRM were also higher among those with a history of visiting fruit farms than among those without one (11.2% vs. 6.6%, 13.0% vs. 6.6%, respectively), although the positive skin responses to house dust mites were similar in the both groups.Conclusion Spider mites are common sensitizing allergens in children and adolescents exposed to them, and environmental exposure to these mites may represent an important risk factor in the sensitization and the clinical manifestations of asthma and rhinitis in children and adolescents living in rural and urban areas.

Notizen: Background  Our previous work on linkage analysis showed that histamine release from basophils to anti-IgE stimuli was linked to the gene marker of chromosome 11q13, where the β chain of the high-affinity receptor for IgE (FcεRI-β) is located.Objective  To evaluate the association between FcεRI-mediated histamine release from basophils and four bi-allelic single nucleotide polymorphisms of the FcεRI-β gene.Methods  Phenotypes of asthma, such as maximal histamine release from basophils and atopy, were measured from 80 randomly recruited asthmatic children. Polymorphisms of the FcεRI-β gene were determined by PCR-based methods.Results  The polymorphism in exon 7, resulting in Glu to Gly substitution, was significantly associated with histamine release from basophils to anti-IgE stimuli, but not with total IgE levels and skin test responses to aeroallergens.Conclusion This study supports a role for the FcεRI-β gene in the expression of high affinity IgE receptor-mediated histamine release from basophils.