Abstract
BackgroundObese asthmatics tend to have poorly controlled asthma, and resistance to standard asthma controller medications. The purpose of this study was to determine the efficacy of pioglitazone, an anti-diabetic medication which can alter circulating adipokines and have direct effects on asthmatic inflammation, in the treatment of asthma in obesity.MethodsA two-center, 12-week, randomized, placebo-controlled, double-blinded trial. Treatments were randomly assigned with concealment of allocation. The primary outcome was difference in change in airway reactivity between participants assigned to pioglitazone versus placebo at 12 weeks.ResultsTwenty-three participants were randomized to treatment, 19 completed the study. Median airway reactivity, measured by PC20 to methacholine was 1.99 (IQR 3.08) and 1.60 (5.91) mg/ml in placebo and pioglitazone group at baseline, and 2.37 (15.22) and 5.08 (7.42) mg/ml after 12 weeks, p = 0.38. There was no difference in exhaled nitric oxide, asthma control or lung function between treatment groups over the 12 week trial. Participants assigned to pioglitazone gained a significant amount more weight than those assigned to placebo (pioglitazone group mean weight 113.6, CI 94.5-132.7 kg at randomization and 115.9, CI 96.9-135.1 at 12 weeks; placebo mean weight 127.5, CI 108.4 – 146.6 kg at randomization and 124.5, CI 105.4 – 143.6 kg at 12 weeks; p = 0.04).ConclusionsThis pilot study suggests limited efficacy for pioglitazone in the treatment of poorly controlled asthma in obesity, and also the potential for harm, given the weight gain in those assigned to active treatment, and the association between increased weight and worse outcomes in asthma.Trial RegistrationClinicaltrials.gov (NCT00634036)
Highlights
Obese asthmatics tend to have poorly controlled asthma, and resistance to standard asthma controller medications
We have shown that obese asthmatics have increased leptin and decreased adiponectin in visceral adipose tissue compared to obese non-asthmatics, and that visceral fat leptin expression correlates directly with airway reactivity in obese asthmatics [11]
Animal models of asthma have implicated PPARγ receptors in the airway in the pathogenesis of asthma, and suggested that pioglitazone might be efficacious in the treatment of allergic asthma in lean allergic animal models of asthma [19, 20] A recent single center crossover study showed that rosiglitazone had modest efficacy in reducing the late asthmatic response to allergen challenge in mild-allergic asthmatics [21], and Spears et al found a significant improvement in lung function in smoking asthmatics treated for 4 weeks with rosiglitazone compared with inhaled corticosteroids [22]
Summary
Obese asthmatics tend to have poorly controlled asthma, and resistance to standard asthma controller medications. One study suggested that obese asthmatics had a nearly five-fold increased risk of hospitalization for asthma compared with lean asthmatics [3]. One reason for this poor asthma control, is that they do not respond as well to standard asthma therapy [4, 5], and in vitro. In our earlier work we have shown that obese asthmatics have evidence of increased airway oxidative stress [7, 8], and decreased peripheral lung compliance [9].
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