RT Journal Article
SR Electronic
T1 A double blind randomised placebo controlled trial of the PPAR-gamma agonist pioglitazone in mild asthma
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 4862
VO 42
IS Suppl 57
A1 John Anderson
A1 Kevin Mortimer
A1 Linhua Pang
A1 Katherine Smith
A1 Helen Bailey
A1 Alan Knox
A1 Tim Harrison
YR 2013
UL http://erj.ersjournals.com/content/42/Suppl_57/4862.abstract
AB IntroductionActivation of peroxisome proliferator-activated receptor gamma (PPAR-γ) modulates inflammatory gene transcription, and may be a novel therapeutic target for asthma (Nie et al. J Biol Chem 2005; 280(4):2550-61). To determine whether activating PPAR-γ results in measurable clinical effects in asthma, we performed a single centre randomised, parallel group, double blind, placebo controlled trial using the PPAR-γ agonist, pioglitazone (PIO).Methods68 non-smokers with asthma (taking as-required short-acting bronchodilators & 0-800mcg beclometasone) were randomised to PIO (n=34) or placebo (n=34). The primary outcome was the adjusted mean FEV1 at 12 weeks. Secondary outcomes were adjusted mean morning and evening peak expiratory flow (PEF), asthma control & quality of life questionnaires, exhaled nitric oxide, bronchial hyper-responsiveness, induced sputum cell counts & adverse events (AE) at 12 weeks. Outcomes were adjusted for baseline value and other covariates and compared with ANCOVA. The full analysis (FA) included 55 completed cases & the per-protocol analysis (PPA) 52.ResultsThere was no significant difference in the adjusted mean FEV1 (-0.014 L, 95 % CI -0.15 to 0.12, p=0.84) or any of the secondary outcomes at 12 weeks in the FA. The PPA replicated the FA, except for a significantly lowered adjusted evening PEF in the PIO group at 12 weeks (-21.33 L/min 95% CI -39.15 to -3.51 p=0.02). There were more reported AEs (40% vs. 32%) & a lower adjusted haemoglobin in the PIO group at 12 weeks (-0.53 g/dL 95% CI -0.96, -0.11, p=0.015).Conclusion PPAR-γ agonists are not promising treatments for mild asthma.