Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D04296 (Asthma)
 25,733 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is evidence from epidemiologic studies, supported by more intensive study of selected groups of subjects, for the importance of allergy in initiating and contributing to the severity of bronchial asthma. Furthermore, removal of allergen exposure is followed by improvement in both symptoms and evidence of airway inflammation. Allergen immunotherapy reduces the sensitivity of the respiratory tract to allergens, blocks the influx of eosinophils and mucosal mast cells in response to allergen exposure, and alters the pattern of cytokine release by T-lymphocytes, generally decreasing Th2-related cytokines (IL-4) and increasing those related to the Th1 response (interferon-gamma, IL-2, IL-12). It would be remarkable, given these alterations in responsiveness produced by allergen immunotherapy, if this treatment were not effective in bronchial asthma. Indeed, an analysis of controlled studies of allergen immunotherapy does indicate that it is clinically effective in carefully selected, allergic asthmatics.
Allergy Asthma Proc
PMID:Does allergen immunotherapy have a role in the treatment of bronchial asthma? 919 42

We determined the effect of inhaled corticosteroid, budesonide, on the release of the anti-inflammatory cytokine, interleukin-10 (IL-10), and of pro-inflammatory cytokines, macrophage inflammatory protein-1alpha (MIP-1alpha), interferon-gamma (IFN-gamma), and granulocyte-macrophage colony-stimulating factor (GM-CSF), from blood monocytes and alveolar macrophages of mild asthmatic subjects in a double-blind, cross-over, placebo-controlled study. Budesonide reduced bronchial hyperresponsiveness and improved baseline FEV1. Alveolar macrophages were obtained by bronchoalveolar lavage performed at the end of each treatment phase. IL-10 from blood monocytes was not altered, but both IL-10 mRNA and protein expression from alveolar macrophages stimulated by lipopolysaccharide and IL-1beta were increased after corticosteroid therapy. By contrast, alveolar macrophages released significantly less MIP-1alpha, IFN-gamma, and GM-CSF after steroid treatment. In comparison to alveolar macrophages from normal nonasthmatic volunteers, those from asthmatic patients released more MIP-1alpha, IFN-gamma, and GM-CSF but lower amounts of IL-10 particularly at baseline and after IL-1beta stimulation. The ability of steroids to inhibit pro-inflammatory cytokines but to enhance the anti-inflammatory cytokine such as IL-10 may contribute to their beneficial actions in asthma. Asthma is characterized by alveolar macrophages exhibiting both an enhanced capacity to release pro-inflammatory cytokines and a reduced capacity to produce IL-10.
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PMID:Inhaled corticosteroids increase interleukin-10 but reduce macrophage inflammatory protein-1alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma release from alveolar macrophages in asthma. 944 7

Inflammatory airway disorders, such as asthma and chronic bronchitis, are characterized by overexpression of adhesion molecules on airway epithelial and endothelial cells. This phenomenon is associated with increased adherence and activation of polymorphonuclear leukocytes (PMNs). With the knowledge that beta2-adrenoceptor agonists demonstrate some anti-inflammatory activity in vitro, the present study was designed to evaluate whether fenoterol could interfere with adhesion molecule expression on airway epithelium. Human bronchial epithelial cells (HBECs), obtained by protease digestion from surgically resected bronchi, were stimulated with human recombinant interferon-gamma (rh IFN-gamma) in the presence of (a) fenoterol (10(-12)-10(-5) M); (b) dexamethasone (10(-12)-10(-5) M); and (c) fenoterol and dexamethasone. Because desensitization after high-dose exposure to agonists has been described for many membrane-associated receptors, in additional sets of experiments HBECs were preexposed to fenoterol and, as control, to dexamethasone for 8 hr, then washed and stimulated with rh IFN-gamma in the presence of fresh drugs. The cells were harvested after 24-hr culture and stained by specific monoclonal antibodies. The intensity of intercellular adhesion molecule-1 (ICAM-1) expression was then measured by flow cytometry analysis and expressed as mean fluorescence channel (mfc). The significant increase in ICAM-1 expression on HBECs induced by rh IFN-gamma was inhibited, in a dose-dependent manner, by the two drugs, but fenoterol was more efficient than dexamethasone at all of the concentrations tested (p < 0.05, all comparisons). In addition, the inhibitory activity of fenoterol was not enhanced by the simultaneous presence of dexamethasone in rh IFN-gamma-stimulated HBEC cultures (p > 0.05, all comparisons). Finally, preexposure to fenoterol or to dexamethasone did not induce any modification of the inhibitory effect of the two drugs on ICAM-1 expression (p > 0.05, all comparisons). These results suggest that clinical efficacy of fenoterol in patients with obstructive lung disease may include downregulation of adhesion molecule expression on airway epithelial cells.
J Asthma 1998
PMID:Downregulation of the expression of intercellular adhesion molecule (ICAM)-1 on bronchial epithelial cells by fenoterol, a beta2-adrenoceptor agonist. 973 47

Asthma is a complex disorder characterized by airway hyperreactivity and inflammation. To analyze cellular interactions required for the secretion of cytokines by the bronchial mucosa, we have evaluated the ex vivo response of tissue explants to allergen. Endobronchial mucosal biopsy tissue from mild atopic asthmatic subjects and normal control subjects were maintained in culture for 24 h. To detect reactivity to allergen, the explants were stimulated with dust mite extract Dermatophagoides pteronyssinus (Der p). Our analysis revealed that without any overt stimulation, mRNA transcripts for interleukin (IL)-5 and IL-13 were expressed by asthmatic but not normal bronchial tissue. In contrast, the expression of interferon-gamma was observed in a higher proportion of cultured bronchial biopsies from the normal control subjects than in those from asthmatic subjects. Addition of Der p allergen did not change the cytokine profile of the explants from control volunteers but augmented the expression of IL-5 mRNA and induced secretion of the protein by the asthmatic bronchial tissue. In most cases, allergen also increased the production of IL-13 by bronchial tissue from asthmatic subjects. The allergen-induced secretion of IL-5 and IL-13 was inhibited by the fusion protein CTLA-4Ig, reflecting a requirement for CD80 (B7-1) and/or CD86 (B7-2) costimulation for the expression of the Th2 cytokines. This requirement for B7/CD28 costimulation is consistent with the hypothesis that IL-5 and IL-13 are produced by allergen-specific T cells resident in the asthmatic bronchial mucosa.
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PMID:B7 costimulation is required for IL-5 and IL-13 secretion by bronchial biopsy tissue of atopic asthmatic subjects in response to allergen stimulation. 987 Sep 29

Previous studies on the effect of seasonal exposure to the sensitizing antigen on T-cell cytokine pattern from atopic subjects evaluated T-cell cytokine production by titration in the serum or culture supernatants. The purpose of this study was to determine the seasonal variations of T-cell cytokine pattern from atopic subjects at the single-cell level. We examined the interleukin-4 (IL-4) and interferon-gamma expression in peripheral blood CD4 + and CD8 + T cells from 11 subjects with grass-pollen-sensitive allergy before and during the 1999 grass pollen season using a flow cytometric method of intracellular cytokine detection. Eight healthy volunteers served as the control group. Flow cytometric analysis of peripheral blood lymphocytes showed no seasonal variations of IL-4- and interferon-gamma-producing T cells in atopic subjects. However, there was a decreased percentage of IL-4-producing cells among peripheral blood CD4+ and CD8+ T cells from the atopic subjects both during and outside the pollen season in comparison to the controLs. We did not find seasonal variations of T-cell cytokine pattern in peripheral blood from atopic subjects. However, we observed a decreased percentage of IL-4-producing T cells in peripheral blood from these subjects in comparison to healthy controls. These data add to the view of a continuous migration of T helper 2 (TH2) cells from the blood to the tissues of primary allergen exposure.
J Asthma 2001 Sep
PMID:Seasonal variations of T-cell cytokine pattern in peripheral blood from atopic subjects. 1164 13

A 46-year-old woman had been treated with 1,600-2,000 micrograms/day of beclomethasone dipropionate (BDP) and oral theophylline on the basis of a diagnosis of bronchial asthma in 1993. Eosinophilic pneumonia was diagnosed in June 1999, and she was then treated with 40 mg/day of oral prednisolone (PSL), which was gradually tapered off, and then stopped in October 1999. She was referred to our hospital because acid-fast bacilli were found in the sputum on January 18, 2000. Her chest radiographs and CT scans showed partial atelectasis of the right upper lobe, and fiberoptic bronchoscopy revealed bronchial inflammatory changes and whitish mucosal nodular lesions in the walls of the lower trachea, the right main bronchus and the orifice of the right upper lobe bronchus. She was found to have endobronchial tuberculosis. Anti-tuberculosis treatment with isoniazid, rifampicin, streptomycin and pyrazinamide was started. Serum levels of interferon-gamma were markedly elevated on admission. Asthma symptoms improved for a period of one month after the beginning of anti-tuberculosis treatment, despite the termination of inhaled corticosteroid. However, as the tuberculosis improved, the frequency and severity of the asthma increased and so corticosteroid inhalation was started again. Four months after administration of the anti-tuberculosis drug, fiberoptic bronchoscopy revealed that the endobronchial lesions had improved without any stenosis or constrictive changes. It was speculated that high doses of inhaled corticosteroid may have the potential to cause endobronchial tuberculosis whilst, ironically, at the same time preventing bronchial stenosis by endobronchial tuberculosis. This is an interesting case in which the asthma symptoms first decreased during the acute phase of endobronchial tuberculosis and then increased again after the tuberculosis improved.
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PMID:[A case of endobronchial tuberculosis associated with bronchial asthma treated with high doses of inhaled corticosteroid]. 1172 92

Asthma is a chronic inflammatory disease that persists even during adequate therapy and asymptomatic episodes. We questioned whether "silent" chronic allergen exposure can induce and maintain airway inflammation and whether this still occurs during regular treatment with inhaled steroids. Twenty-six patients with house dust mite allergy and mild asthma (dual responders) participated in a parallel, double-blind study. All patients inhaled a low-dose of allergen on 10 subsequent working days (Days 1-5, 8-12). They were treated with 400 micro g budesonide once daily (n = 13) or placebo (n = 13) from Days -3 to 19. At baseline (Day -6) and on Days 5, 12, and 19 we measured the provocative concentration of methacholine causing a 20% fall in FEV(1) (PC(20)), and percent eosinophils, interleukin (IL)-5/interferon-gamma messenger RNA ratio (in sputum cells by real-time reverse transcription-polymerase chain reaction [RT-PCR]), and eosinophilic cationic protein (ECP) in induced sputum. Symptoms, peak expiratory flow (PEF), FEV(1), and exhaled nitric oxide (NO) were recorded repeatedly during the study. In the placebo group, repeated low-dose allergen exposure resulted in a significant increase in sputum eosinophils (p = 0.043), ECP (p = 0.011), IL-5/IFN-gamma messenger RNA ratio (p = 0.04), and in exhaled NO (p = 0.001), without worsening of symptoms, PEF, or baseline FEV(1) (p > 0.07). In the budesonide group, the changes in PC(20), sputum ECP, and exhaled NO were significantly different as compared with the placebo group (p < 0.03). We conclude that repeated low-dose allergen exposure in asthma can lead to airway inflammation without worsening of symptoms, which can be prevented by inhaled steroid treatment. This suggests that antiinflammatory therapy is beneficial during allergen exposure, even during asymptomatic episodes.
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PMID:Asymptomatic worsening of airway inflammation during low-dose allergen exposure in asthma: protection by inhaled steroids. 1215 60

Nasal polyposis (NP) is a chronic inflammatory disease of the sinuses often associated with asthma. Although we have not yet achieved a full understanding of the precise mechanisms underlying the pathogenesis of NP, recent insights have been acquired into the regulation of eosinophil chemotaxis, activation, and survival, in addition to their possible link to gross histopathologic changes such as pseudocyst formation. Interleukin (IL)-5, transforming growth factor-beta(1), and eotaxin seem to be crucial players in the regulation of eosinophilic inflammation and extracellular matrix breakdown. The cytokine pattern in NP assumes neither a T helper 1 (Th1) nor Th2 type predominance, because IL-4, IL-5, IL-12, and interferon-gamma have all been shown to be upregulated in NP tissue, without influence of the atopic status. However, recent studies have demonstrated a strong local upregulation of the immunoglobulin E (IgE) synthesis with the formation of specific IgE to Staphylococcus aureus enterotoxins, suggesting a possible role of superantigens in these pathologic processes.
Curr Allergy Asthma Rep 2002 Nov
PMID:Mediators in nasal polyposis. 1235 19

Asthma and atopy are polygenic diseases with an hereditary and an environmental component. Improvement in statistical and molecular tools has enabled the localization of a dozen chromosome regions bearing susceptibility genes: 1p32-34, 3q21, 5q31-33, 6p21-23, 11p15, 11q13, 12q14-24, 13q14-qter, 14q11, 17q11-21, 19q13 and 20p13. There are many candidate genes, particular the cluster of interleukin-4 genes (5q31-33), the major histocompatibility complex genes HLA D and the TNFalpha gene (6p21-23), the gene of the receptor B chain with strong affinity for IgE (11q13), the interferon-gamma gene (12q15-24), the genes of the alpha/gamma chains of the T receptor (14q11), the IL4 receptor gene (16p12), and the metalloprotease gene ADAM33 (20p13). Research will continue to define these genes more precisely or to recognize others and to apply this knowledge to therapeutic and diagnostic applications.
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PMID:[Respiratory allergic disease genes]. 1284 91

Recurrent viral infections are frequently observed in children with atopic asthma. In this study we investigated the ability of the synthetic immunomodulator pidotimod to affect in vitro the phenotype and/or cytokine profile of blood cells in relation to atopic asthma. Peripheral blood mononuclear cells were isolated from 13 atopic asthmatic and 9 normal children and stimulated in culture with mitogen either in the presence or not of the drug. Expression of surface markers was evaluated by flow cytometry, and production of interleukin-4 and interferon-gamma was measured in supernatants. Pidotimod was able to down-regulate the expression of CD30 on cells from both atopic and normal subjects. Because CD30 has been associated with Th-2 cells, this observation supports the possibility of pidotimod being able to affect the Th-1/Th-2 balance in atopic asthma.
J Asthma 2004
PMID:Immune modulator pidotimod decreases the in vitro expression of CD30 in peripheral blood mononuclear cells of atopic asthmatic and normal children. 1526 Apr 61


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