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Effects of a short course of inhaled corticosteroids in noneosinophilic asthmatic subjects.

ABSTRACT: Noneosinophilic asthma has been regarded as a distinct phenotype characterized by a poor response to inhaled corticosteroids (ICS).To determine whether noneosinophilic, steroid-naive asthmatic subjects show an improvement in asthma control, asthma symptoms and spirometry after four weeks of treatment with ICS, and whether they further benefit from the addition of a long-acting beta-2 agonists to ICS.A randomized, double-blind, placebo-controlled, multicentre study comparing the efficacy of placebo versus inhaled fluticasone propionate 250 mcg twice daily for four weeks in mildly uncontrolled, steroid-naive asthmatic subjects with a sputum eosinophil count of 2% or less. This was followed by an open-label, four-week treatment period with fluticasone propionate 250 mcg?salmeterol 50 mcg, twice daily for all subjects.After four weeks of double-blind treatment, there was a statistically significant and clinically relevant improvement in the mean (± SD) Asthma Control Questionnaire score in the ICS-treated group (n = 6) (decrease of 1.0 ± 0.5) compared with the placebo group (n = 6) (decrease of 0.09 ± 0.4) (P = 0.008). Forced expiratory volume in 1 s declined in the placebo group (-0.2 ± 0.2 L) and did not change in the ICS group (0.04 ± 0.1 L) after four weeks of treatment (P = 0.02). The open-label treatment with fluticasone propionate 250 mcg?salmeterol 50 mcg did not produce additional improvements in those who were previously treated for four weeks with inhaled fluticasone alone.A clinically important and statistically significant response to ICS was observed in mildly uncontrolled noneosinophilic asthmatic subjects.

SUBMITTER: Lemiere C

PROVIDER: S-EPMC3267606 | biostudies-literature | 2011 Sep-Oct

REPOSITORIES: biostudies-literature

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Effects of a short course of inhaled corticosteroids in noneosinophilic asthmatic subjects.

Lemière Catherine C Tremblay Caroline C FitzGerald Mark M Aaron Shawn D SD Leigh Richard R Boulet Louis-Philippe LP Martin James G JG Nair Parameswaran P Olivenstein Ronald R Chaboillez Simone S

Canadian respiratory journal 20110901 5

<h4>Background</h4>Noneosinophilic asthma has been regarded as a distinct phenotype characterized by a poor response to inhaled corticosteroids (ICS).<h4>Objective</h4>To determine whether noneosinophilic, steroid-naive asthmatic subjects show an improvement in asthma control, asthma symptoms and spirometry after four weeks of treatment with ICS, and whether they further benefit from the addition of a long-acting beta-2 agonists to ICS.<h4>Methods</h4>A randomized, double-blind, placebo-controll ...[more]

PMID: 21969930

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Project description:Background and purposeInhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma.Experimental approachBronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.Key resultsCompared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.Conclusions and implicationsExpression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy.

Dataset Information

Effects of a short course of inhaled corticosteroids in noneosinophilic asthmatic subjects.

Publications

Effects of a short course of inhaled corticosteroids in noneosinophilic asthmatic subjects.

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