Effect of dampness at home in childhood on bronchial hyperreactivity in adolescence.
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BACKGROUND: Relatively little is known about risk factors for the persistence of asthma and respiratory symptoms from childhood into adolescence, and few studies have included objective measurements to assess outcomes and exposure. METHODS: From a large cross sectional study of all 4th grade school children in Munich (mean age 10.2 years), 234 children (5%) with active asthma were identified. Of these, 155 (66%) were reinvestigated with lung function measurements and bronchial provocation three years later (mean age 13.5 years). RESULTS: At follow up 35.5% still had active asthma. Risk factors for persisting asthma symptoms in adolescence were more severe asthma (OR 4.94; CI 1.65 to 14.76; p = 0.004) or allergic triggers (OR 3.54; CI 1.41 to 8.92; p = 0.007) in childhood. Dampness was associated with increased night time wheeze and shortness of breath but not with persisting asthma. Risk factors for bronchial hyperreactivity in adolescence were bronchial hyperreactivity in childhood (p = 0.004), symptoms triggered by allergen exposure (OR 5.47; CI 1.91 to 25.20; p = 0.029), and damp housing conditions (OR 16.14; CI 3.53 to 73.73; p < 0.001). In a subgroup in whom house dust mite antigen levels in the bed were measured (70% of the sample), higher mite antigen levels were associated with bronchial hyperreactivity (OR per quartile of mite antigen 2.30; CI 1.03 to 5.12; p = 0.042). Mite antigen levels were also significantly correlated with dampness (p = 0.05). However, the effect of dampness on bronchial hyperreactivity remained significant when adjusting for mite allergen levels (OR 5.77; CI 1.17 to 28.44; p = 0.031). CONCLUSION: Dampness at home is a significant risk factor for the persistence of bronchial hyperreactivity and respiratory symptoms in children with asthma. This risk is only partly explained by exposure to house dust mite antigen. (+info)
Production of recombinant Der fI (a major mite allergen) by Aspergillus oryzae.
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Der fI is a major mite allergen. To produce Der fI by Aspergillus oryzae, we placed a DNA fragment encoding precursor-type recombinant Der fI E(-1)K (reDer fI E(-1) K), which had the C-terminal amino acid of the pro-sequence (Glu) changed to Lys, downstream of the glaA gene promoter and introduced it into Aspergillus oryzae. In liquid culture, most of the reDer fI E(-1)K produced by the transformants was degraded when culture was shaken vigorously. However, the degradation of reDer fI E(-1)K was suppressed when it was shaken gently. The processed reDer fI E(-1)K could be obtained after lysylendopeptidase and endoglycosidase Hf (Endo Hf) treatment. The yield of processed reDer fI E(-1)K was 8 mg/l. When the transformant was grown on a wheat bran culture, the yield of processed reDer fI E(-1)K reached 48 mg/kg. Because processed reDer fI E(-1)Ks obtained from both cultures had almost the same IgE-binding activity and elicited the same skin reaction as native Der fI, they could be very useful for diagnostic purposes or immunotherapy. (+info)
Cloning and expression of Der f 6, a serine protease allergen from the house dust mite, Dermatophagoides farinae.
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House dust mite allergen is thought to be a major cause of asthma. Characterization of these allergen molecules is therefore an important step for the development of effective diagnostic and therapeutic agents against mite-associated allergic disorders. Here we report molecular cloning and expression of the group 6 (chymotrypsin-like) allergen from the house dust mite, Dermatophagoides farinae. Sequencing analysis indicates that cloned cDNA, designated Der f 6, encodes a 279 amino acid polypeptide which conserves a primary structure characteristic for chymotrypsin-like serine proteases found in mammals. Recombinant Der f 6 expressed in Escherichia coli bound IgE in a pool made of 20 sera, and induced histamine release from patients' peripheral blood cells. (+info)
Der p 1 facilitates transepithelial allergen delivery by disruption of tight junctions.
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House dust mite (HDM) allergens are important factors in the increasing prevalence of asthma. The lung epithelium forms a barrier that allergens must cross before they can cause sensitization. However, the mechanisms involved are unknown. Here we show that the cysteine proteinase allergen Der p 1 from fecal pellets of the HDM Dermatophagoides pteronyssinus causes disruption of intercellular tight junctions (TJs), which are the principal components of the epithelial paracellular permeability barrier. In confluent airway epithelial cells, Der p 1 led to cleavage of the TJ adhesion protein occludin. Cleavage was attenuated by antipain, but not by inhibitors of serine, aspartic, or matrix metalloproteinases. Putative Der p 1 cleavage sites were found in peptides from an extracellular domain of occludin and in the TJ adhesion protein claudin-1. TJ breakdown nonspecifically increased epithelial permeability, allowing Der p 1 to cross the epithelial barrier. Thus, transepithelial movement of Der p 1 to dendritic antigen-presenting cells via the paracellular pathway may be promoted by the allergen's own proteolytic activity. These results suggest that opening of TJs by environmental proteinases may be the initial step in the development of asthma to a variety of allergens. (+info)
Highly Th2-skewed cytokine profile of beta-lactam-specific T cells from nonatopic subjects with adverse drug reactions.
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A positive lymphocyte transformation test to beta-lactams (beta-L) was found in 12 of 29 subjects with adverse drug reaction (ADR) to beta-L, irrespective of either the type of clinical manifestation or the presence of specific serum IgE. Short-term T cell lines specific for penicillin G, amoxicillin, and ampicillin could be generated only from subjects with ADR (eight with positive and one with negative lymphocyte transformation test), while streptokinase and Dermatophagoides pteronyssinus group 1 (Der p 1)-specific T cells were obtained from all these subjects, from 7 atopic Der p-sensitive donors without history of ADR and 17 healthy nonatopic donors. Streptokinase-specific T cells from all subjects showed intracellular expression of IFN-gamma with poor or no IL-4, whereas Der p 1-specific T cells exhibited IFN-gamma but low or no IL-4 expression in nonatopics, and remarkable IL-4 expression in atopic donors. By contrast, all penicillin G-, ampicillin-, and amoxicillin-specific short-term T cell lines showed high intracellular expression of IL-4, IL-5, and IL-13, but poor or no expression of IFN-gamma, thus exhibiting a clear-cut Th2 profile. Accordingly, most penicillin G-specific T cell clones derived from two subjects with ADR released high concentrations of IL-4 alone or IL-4 and IFN-gamma. These data suggest that cytokines produced by Th2 cells play an important role in all beta-L-induced ADR, even when late clinical manifestations occur and an IgE-mediated mechanism is apparently indemonstrable. (+info)
Prevalence of allergic sensitization to regional inhalants among allergic patients in Jakarta, Indonesia.
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Sensitization towards a panel of eight regional inhalant allergens was evaluated among 107 patients with allergic rhinitis and/or asthma. A total of 32 children (age 5-13 years, mean 9 years; 18 male, 14 female), 75 adolescents and adults (aged 14-66 years, mean 32 years; 21 male, 54 female) and 20 normal control volunteers (aged 16-46, mean 30 years; 4 male, 16 female) were evaluated via skin prick test. A weal response of 3 x 3 mm or greater was taken to be positive. The sensitization rates among individuals to these allergens were: house dust mites, Dermatophagoides pteronyssinus (77.57%), Blomia tropicalis (71.96%), Austroglycyphagus malaysiensis (33.64%), pollen, palm oil Elaeis guineensis (22.43%), Acacia auriculiformis (12.15%), fern spore, resam Dicranopteris spp (11.21%), fungal spores: Curvularia fallax (8.41%) and Exserohilum rostratum (13.08%). There were significantly higher frequencies of sensitization to these allergens among allergic individuals compared to normal controls, and among atopic individuals with two allergy manifestations (rhinitis and asthma) compared to those with only one. No difference was noted between children and adults in the allergic group. In conclusion, the allergic patients were highly sensitized to dust mites and sensitization to regional pollen and spores was also documented. They should be considered as relevant and be included in skin test batteries in Indonesia. (+info)
Role of allergy in nasal polyps of Thai patients.
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As distinct from many countries, allergy in Thailand is of the perennial type which may play a role in the formation of nasal polyps. Forty consecutive patients with nasal polyps and 30 normal subjects as control were studied at the Allergy Clinic, Department of Otolaryngology, Pramongkutklao Hospital. A positive clinical history and skin allergy testing are diagnostic criteria for allergy. In the nasal polyps group, these were 28 males and 12 females, aged between 12-65 years, with an average age of 38.5 years. In the control group, there were 18 males and 12 females, aged between 15-53 yeas, with an average age of 34 years. All had received prick skin testing with 6 common aeroallergens. The prick skin test was considered positive when the wheal was > or = 3 mm with surrounding erythema. Twenty-four of 40 patients (60%) with nasal polyps had a positive prick skin test, while 6 in the 30 control cases (20%) had a positive prick skin test. This difference was statistically significant (P = 0.0019), Odd's ratio = 6.0 which means allergic persons were 6 times more prone to have polyps form than normal persons. (+info)
Administration of interleukin-12 exerts a therapeutic instead of a long-term preventive effect on mite Der p I allergen-induced animal model of airway inflammation.
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Interleukin-12 (IL-12) is a key cytokine, which promotes T helper type 1 (Th1) cell-mediated immunity and inhibits Th2-type responses. It has been previously shown that IL-12 administration during active immunization following a single allergen exposure can prevent antigen-induced increases in immunoglobulin E (IgE) formation, Th2 cytokine production and bronchoalveolar lavage (BAL) eosinophils in a murine model of allergic airway inflammation. Thus, these studies have now been extended and two IL-12 treatment protocols on this murine model were evaluated. Administration of IL-12 during the active immunization strikingly increased Der p I-specific serum IgG2a and transiently decreased the levels of IgG1 and IgE antibodies following multiple allergen challenges. Such early treatment of IL-12 down-regulated IL-5 production and modestly up-regulated interferon-gamma production but did not effect BAL eosinophilia. These results suggest that repeated exposure to antigen and IL-12 is necessary to maintain a persistent Th1-recall response. Furthermore, administration of IL-12 to actively immunized mice, in which Th2-associated responses were established, had a significant effect on IgG2a synthesis and a modest effect on IgE levels, also down-regulation of IL-5 production, and markedly increased interferon-gamma production and abolished recruitment of eosinophils. Therefore, these data indicate that IL-12 can inhibit antigen-induced eosinophil infiltration into airways, despite the existence of a Th2-associated response. Taken together, these studies suggest that IL-12 may be useful as an immunotherapeutic agent in the treatment of such pulmonary allergic disorders as bronchial asthma. (+info)