Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q99581 (FEV)
 3,296 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To define the mechanisms by which inhaled glucocorticosteroid regulates allergen-induced airway inflammation, a double-blind, placebo-controlled, cross-over study with inhaled budesonide was conducted in 14 subjects with allergic asthma. After baseline bronchoscopy and bronchoalveolar lavage (BAL), subjects were randomized to budesonide (400 microgram, twice daily) or placebo treatment for 4 wk. At the end of each treatment phase, whole-lung allergen inhalation challenge was performed, followed by BAL 48 h later. Budesonide treatment improved the FEV(1), attenuated both the immediate- and late-phase response to allergen, and prevented the increase in bronchial hyperresponsiveness after allergen challenge. Budesonide treatment also decreased allergen-induced airway eosinophilia. To determine the effects of budesonide on airway cell function, BAL cells were stimulated ex vivo with the T cell mitogen PHA, and cytokine generation was measured by ELISA. Budesonide decreased ex vivo generation of IL-5 and IFN-gamma by BAL cells. Ex vivo IL-5 production was significantly correlated with the number of airway eosinophils (r(s) = 0.61), and levels of eosinophil-derived neurotoxin (EDN) (r(s) = 0.57) and IL-5 (r(s) = 0.52) in BAL fluid. Moreover, PHA-induced IL-5 generation correlated with FEV(1) fall during the late-phase response to allergen (r(s) = 0.60). Budesonide decreased circulating eosinophils and serum levels of IL-5, but did not reduce IL-5 generation by peripheral blood mononuclear cells. The reduction in circulating eosinophils correlated with the decrease in levels of EDN (r(s) = 0.61) in BAL fluid and late response to inhaled allergen (r(s) = 0.51). These findings suggest that long-term treatment with inhaled budesonide reduces airway cell generation of cytokines, specifically IL-5, which then decreases circulating eosinophils and their availability for recruitment to the airway after allergen exposure.
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PMID:Inhaled budesonide decreases airway inflammatory response to allergen. 1098

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

Nocturnal airway obstruction occurs frequently in childhood asthma and results from increased airway inflammation. Lymphocytes are believed to be key effector cells of airway wall inflammation, releasing pro-inflammatory mediators and cytokines. A previous study showed that hydrocortisone infusion, an effective anti-inflammatory treatment, improves nocturnal and daytime FEV(1) values. This study in 16 children with moderate asthma was designed to assess whether there exists day and night differences in IL-4, IL-5, IL-8, and IFN-gamma production of concanavaline A stimulated peripheral blood mononuclear cells. Furthermore, we investigated whether substitution of low serum cortisol levels with intravenous hydrocortisone would affect those parameters. Saline (as a placebo) or hydrocortisone (30 microg/m(2) body surface area/24 h) was intravenously administered in a randomized, double blind, cross-over design. Measurements under saline or hydrocortisone infusions were separated by 1 wk. At 04:00 and 16:00 hours 10 ml blood was taken for determination of peripheral blood mononuclear cell isolation and stimulation, and an eosinophil count. Hydrocortisone infusion significantly reduced the nocturnal fall in FEV(1). Median values of IFNgamma, IL-4, IL-5, and IL-8 produced by peripheral blood mononuclear cells did not significantly differ at 04:00 and 16:00 hours, both with saline and hydrocortisone infusion. Our results suggest that FEV(1) improvement is not due to suppression of circulating peripheral blood mononuclear cell activation. We hypothesize that it is rather due to its effect on local lung tissue epithelial and/or fibroblasts thereby reducing airway inflammation and vascular leakage.
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PMID:The influence of intravenous hydrocortisone on cytokine levels in children with asthma. 1594 92