Abstract
BackgroundPeroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial.MethodsSixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis.ResultsThere was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02).ConclusionsWe found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma.Trial RegistrationClinicalTrials.gov NCT01134835
Highlights
Asthma is a common and chronic condition that affects 235 million people worldwide and is responsible for substantial healthcare expenditures [1]
There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [confidence intervals (CIs)] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the full analysis (FA)
The PP analysis replicated the FA, with the exception of a lower evening peak expiratory flow (PEF) in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02)
Summary
Asthma is a common and chronic condition that affects 235 million people worldwide and is responsible for substantial healthcare expenditures [1]. Inhaled corticosteroids and bronchodilators are the mainstay of asthma pharmacotherapy These treatments are highly effective, many patients fail to achieve optimal asthma control and are at risk of impaired quality of life, recurrent exacerbations, and even death. In some patients, these outcomes are due to poor concordance with medication, while others dislike or exhibit reduced responses to inhaled medications, creating a need to identify novel therapeutic targets if the burden of asthma is to be reduced. There is evidence that PPAR-γ is involved in inflammation and airway remodeling responses in asthma [4]. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial
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