PURPOSE: Endothelin-1 (ET-1) is a highly potent bronchoconstrictor, 100 times more so than methacholine. In asthmatics, BAL and circulating ET-1 levels are elevated, and are further elevated during acute exacerbations. This pilot study was performed to assess the effect of bosentan on patients with poorly controlled asthma.
METHODS: This was a 17 week, double-blind, placebo-controlled crossover pilot study. Subjects were between the ages of 21-70, maintained on anti-inflammatory and long acting B-agonist therapy, and had poorly controlled asthma, with a baseline FEV1 of 40-70%. Exclusions included hepatic disease, renal disease, active cardiac disease, pulmonary disease other than asthma, > 10 pack year tobacco history, and exacerbation within 30 days. After placebo run-in, subjects were randomized to receive bosentan (4 weeks at 62.5 mg BID then 4 weeks of 125 mg BID), or placebo. Thereafter, subjects crossed over to the alternate therapy. FEV1, Asthma Control Test (ACT) scores, and Asthma Symptom Scores were measured at baseline and during the last week of bosentan and placebo therapy. During the first day of 125 mg bosentan or placebo, acute changes in FEV1 were measured at 1, 2, and 4 hours.
RESULTS: Ten subjects were enrolled from March 2009 to April 2010. Seven subjects completed the protocol. Mean baseline FEV1 was 1.49±0.47 L (59%) before bosentan phase and 1.40±0.40 (56%) before placebo phase p=0.393. There was no difference in FEV1 after bosentan and placebo phases (1.53±0.42 versus 1.63±0.48 p= 0.525). ACT scores were similar during the bosentan and placebo phases (14±5.6 and 17±3.2 p=0.162) as was Asthma Symptom Score (19±8.2 versus 18±5.6 p= 0.932). Acute FEV1 changes were similar after both bosentan and placebo at baseline at 1, 2, and 4 hours.
CONCLUSIONS: In this pilot study, 4 weeks of bosentan did not improve FEV1, Asthma Symptom Score or ACT score in poorly controlled asthma compared with placebo.
CLINICAL IMPLICATIONS: In this pilot study there was no evidence of response to bosentan in patients with poorly controlled asthma.
DISCLOSURE: Mark Metersky: Grant monies (from industry related sources): Grant received for this study only
The following authors have nothing to disclose: Timothy Coyle
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