Abstract：
BACKGROUND:Combination therapy with inhaled corticosteroids (ICS) and long-acting β(2)-adrenergic agonists (LABA) is reported to have superior effects on controlling asthma symptoms to ICS alone; however, there is no molecular-based evidence to explain the clinical effects. Here, the effect of the ICS/LABA combination was compared with ICS on glucocorticoid receptor (GR) activation in sputum macrophages. METHODS:In a randomised, double-blind cross-over placebo-controlled 6-visit study, 10 patients with mild asthma were given placebo, formoterol (Oxis(®) 12 μg), budesonide (Pulmicort(®) 200 μg :BUD200, or 800 μg :BUD800), or budesonide/formoterol combination (Symbicort(®)) as a single 100/6 μg (SYM100) or double 200/12 μg (SYM200) dose. Sputum macrophages were separated by plate adhesion from induced sputum. GR binding to the glucocorticoid-response elements on oligonucleotides (GR-GRE binding) was evaluated by ELISA. mRNA expression of MAP-kinase phosphatase (MKP)-1 and IL-8 were measured by quantitative RT-PCR. RESULTS:GR-GRE binding was significantly increased after treatment with SYM100 (3.5 OD/10 μg protein, median, p < 0.05) versus placebo (1.3) and BUD200 (1.6), and the induction was higher than that of BUD800 (2.4). MKP-1 mRNA was increased and IL-8 mRNA was significantly inhibited by BUD800, SYM100 and SYM200 versus placebo. CONCLUSIONS:The effects of SYM100 and SYM200 on GR activation were not different from that of BUD800 and superior to BUD200. Thus, it has been confirmed at a molecular level that inhaled combination therapy with a lower dose of budesonide has an equivalent effect to a high dose of budesonide alone. In addition, GR-GRE binding is found to be a valuable pharmacodynamic marker for steroid efficacy in clinical studies.
journal_name
Respir Medjournal_title
Respiratory medicineauthors
Essilfie-Quaye S,Ito K,Ito M,Kharitonov SA,Barnes PJdoi
10.1016/j.rmed.2011.08.020subject
Has Abstractpub_date
2011-12-01 00:00:00pages
1784-9issue
12eissn
0954-6111issn
1532-3064pii
S0954-6111(11)00298-8journal_volume
105pub_type
杂志文章,随机对照试验abstract：:Chronic obstructive pulmonary disease (COPD) is a condition characterized by progressive airflow limitation, with symptoms of dyspnoea, cough, and sputum production. Aside from information on prevalence, mortality and hospital resource utilization arising from COPD in Canada, there is a lack of data on the impact of t...
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pub_type： 临床试验,杂志文章,随机对照试验
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更新日期：2018-12-01 00:00:00
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pub_type： 杂志文章
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更新日期：2010-04-01 00:00:00
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pub_type： 杂志文章
doi：10.1053/rmed.2000.0817
更新日期：2000-08-01 00:00:00
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journal_title：Respiratory medicine
pub_type： 杂志文章
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更新日期：2003-11-01 00:00:00
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journal_title：Respiratory medicine
pub_type： 杂志文章
doi：10.1016/j.rmed.2008.07.015
更新日期：2009-01-01 00:00:00
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journal_title：Respiratory medicine
pub_type： 杂志文章,随机对照试验
doi：10.1016/j.rmed.2006.11.010
更新日期：2007-06-01 00:00:00
abstract：OBJECTIVES:To determine the efficacy of oral theophylline compared with placebo in people with stable chronic obstructive pulmonary disease (COPD). METHODS:Systematic review of randomized-controlled trials comparing oral theophylline with placebo for a minimum of 7 days in people with stable COPD. RESULTS:Twenty rand...
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pub_type： 杂志文章,meta分析,评审
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更新日期：2005-02-01 00:00:00
