Asthma and lower airway diseaseStatins enhance the anti-inflammatory effects of inhaled corticosteroids in asthmatic patients through increased induction of indoleamine 2, 3-dioxygenase
Section snippets
Patients
Nonsmoking patients with stable asthma were defined according to American Thoracic Society criteria and were treated with less than 1,000 μg/d beclomethasone dipropionate or an equivalent ICS. None of the patients had received oral corticosteroids within 3 months before the study. Subjects had a baseline FEV1 of 60% or greater of predicted value and demonstrated 12% or greater reversibility of FEV1 after therapy with nebulized salbutamol (2.5 mg) and a provocative concentration of methacholine
Patients
Of a total of 63 screened patients, 50 fulfilled the entry requirements and were randomized into either the simvastatin tablet group (n = 25) or the placebo group (n = 25; Fig 1, B, and Table I). Forty-seven patients completed the treatment phase, and 3 patients discontinued the study before completion, 3 in the simvastatin arm (2 were unable to provide adequate sputum and 1 had missing final lung function test data).
Simvastatin increases the anti-inflammatory effect of ICSs on eosinophilic airway inflammation in asthmatic patients
During the run-in off-treatment period, all patients had eosinophilic airway
Discussion
We conceived this randomized controlled study to verify whether a statin enhances the anti-inflammatory effects of an ICS in asthma. Here we have demonstrated that simvastatin increases the anti-inflammatory effect of inhaled budesonide in suppressing eosinophilic airway inflammation in asthmatic patients and that this is mediated through the activation of IDO through 2 distinct but interacting molecular pathways. First, corticosteroids induce IDO activation through the GITRL-associated
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Supported by the Siriraj Grant for Research Development and Medical Education of the Faculty of Medicine Siriraj Hospital, Mahidol University.
Disclosure of potential conflict of interest: P. J. Barnes has received research support from GlaxoSmithKline, AstraZeneca, and Novartis. The rest of the authors have declared that they have no conflict of interest.