| Treatment with a peroxisomal proliferator activated receptor gamma agonist has a modest effect in the allergen challenge model in asthma: a randomised controlled trial. | |
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MedLine Citation:
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PMID: 19944580 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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PURPOSE: A considerable body of non clinical evidence has accumulated to support peroxisomal proliferator-activated receptor gamma agonists as candidate anti-inflammatory drugs in asthma. We utilized rosiglitazone as a tool compound in the inhaled allergen challenge model of asthma. METHODS: A single centre, double-blind, randomised, placebo controlled, two period cross-over study. Subjects received rosiglitazone 4mg and placebo twice daily for 28 days in random order. On day 28, inhaled allergen challenge was performed 1 hour post-dose. A methacholine challenge was performed on day 29 and an adenosine monophosphate challenge on day 14. Exhaled nitric oxide was measured on days 1, 14, 28, 29. Blood was collected pre dose on days 1, 14 and 28 and analysed for markers associated with PPAR activity and systemic markers of inflammation. RESULTS: The late asthmatic reaction (LAR) change from post saline FEV(1) from 4-10 hrs post allergen on day 28 was statistically significant for the weighted mean LAR. The difference in weighted mean was 0.06 L (95% CI 0.01 to 0.11) which equates to a 15% attenuation of the response during placebo treatment. This was accompanied by trends in other markers of efficacy and anti-inflammatory activity but none were considered major effects. DISCUSSION: Treatment with a PPARgamma agonist (rosiglitazone) was associated with a modest (15%) reduction in the late asthmatic reaction in the allergen challenge model of asthma. Based on the results of this study, PPARgamma agonist monotherapy is unlikely to represent a clinically useful intervention in human asthma. Registered with www.clinicaltrials.gov (NCT00318630). |
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Authors:
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Duncan B Richards; Philippe Bareille; Emma L Lindo; Dean Quinn; Stuart N Farrow |
Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2009-11-26 |
Journal Detail:
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Title: Respiratory medicine Volume: 104 ISSN: 1532-3064 ISO Abbreviation: Respir Med Publication Date: 2010 May |
Date Detail:
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Created Date: 2010-05-03 Completed Date: 2010-10-07 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8908438 Medline TA: Respir Med Country: England |
Other Details:
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Languages: eng Pagination: 668-74 Citation Subset: IM |
Affiliation:
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Drug Discovery, GlaxoSmithKline, Stevenage, UK. duncan.b.richards@gsk.com |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adiponectin
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blood Adolescent Adult Allergens / diagnostic use Anti-Inflammatory Agents / adverse effects, therapeutic use* Asthma / drug therapy*, immunology, physiopathology Biological Markers / blood Breath Tests Bronchial Provocation Tests Bronchoconstrictor Agents / diagnostic use Cross-Over Studies Double-Blind Method Female Forced Expiratory Volume Humans Male Methacholine Chloride / diagnostic use Middle Aged Nitric Oxide / analysis PPAR gamma / agonists* Thiazolidinediones / adverse effects, therapeutic use* Young Adult |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Allergens; 0/Anti-Inflammatory Agents; 0/Biological Markers; 0/Bronchoconstrictor Agents; 0/PPAR gamma; 0/Thiazolidinediones; 10102-43-9/Nitric Oxide; 122320-73-4/rosiglitazone; 62-51-1/Methacholine Chloride |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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