Effects of Low-Dose Fluticasone Propionate/Salmeterol Combination Therapy on Exhaled Nitric Oxide and Nitrite/Nitrate in Breath Condensates from Patients with Mild Persistent Asthma

Abstract

Objective. The long-acting β2-agonist salmeterol in combination with the corticosteroid fluticasone propionate is used in clinical practice for the treatment of mild persistent asthma. Although the effect of fluticasone propionate alone in asthmatic patients is well documented, the effect of fluticasone propionate/salmeterol (FSC) combination therapy on airway inflammation and airway hyperresponsiveness (AHR) is not well characterized. Thus, we evaluated AHR, exhaled nitric oxide (FE_NO), and nitrite and nitrate in exhaled breath condensates (EBCs) from mild persistent asthmatic patients treated with a low-dose FSC (100/50). Methods. In this open label study, 18 mild persistent, steroid-naïve asthmatics (age, 22–62 years, forced expiratory volume in 1 s (FEV₁) > 70% predicted, provocative dose resulting in 20% reduction (PD₂₀) < 10 mg/mL) were treated with FSC 100/50 for 4 weeks. PD₂₀ to methacholine, FEV₁, FE_NO, and EBC nitrite and nitrate was measured before and after treatment. Results. After 4 weeks of therapy with FSC 100/50, FE_NO decreased from 74 ppb (SD = 37) to 34 ppb (SD = 15) (p < .001). FEV₁ (% predicted) increased from 89.4 (SD = 10.7) to 93.3 (SD = 9.5) (p < .01). The PD₂₀ for methacholine increased from 3.0 (±3.2) to 10.3 (±8.4) mg/mL (p < .01) in 3 of 18 patients reaching the maximum allowable dose (25 mg/mL). FE_NO correlated with the log of the methacholine dose. There was no statistically significant change in EBC nitrite and nitrate before and after treatment. Conclusions. Treatment of mild persistent, steroid-naïve asthmatics with low-dose combination therapy is effective in rapidly reducing airway inflammation and AHR. Our results suggest different metabolic origins for nitrite, nitrate, and FE_NO in this group of patients.

• airway hyperresponsiveness
• asthma
• combination therapy
• exhaled breath condensate
• exhaled nitric oxide
• fluticasone propionate
• nitrate
• nitrite
• salmeterol
• surrogate markers

Acknowledments

The authors thank Frances L. Jourd’heuil, Paula Malone, Theresa Evans, and Dr. Seema Patel for their help in the collection of the data. The authors thank Dr. Townley and Dr. Hopp (Creighton University, School of Medicine, Omaha, NE) for the critical review of the article.

Declaration of Interest

Funding/Financial support: GlaxoSmithKline study number 101550.

Disclosures: M. Asghar Pasha and David Jourd’heuil have received funding from Novartis Pharmaceutical Corp.

The study protocol was approved by the Albany Medical College Institutional Review Board.