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Original Research: Asthma |

Inhaled Corticosteroid Dose Response Using Domiciliary Exhaled Nitric Oxide in Persistent AsthmaThe Fenotype Trial: The Fenotype Trial

William J. Anderson, MBChB; Philip M. Short, MBChB; Peter A. Williamson, MBBCh; Brian J. Lipworth, MD
Author and Funding Information

From the Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, Ninewells Hospital and Medical School, The University of Dundee, Dundee, Scotland.

Correspondence to: Brian J. Lipworth, MD, Asthma and Allergy Research Group, Division of Cardiovascular and Diabetes Medicine, The University of Dundee, Dundee, DD1 9SY, Scotland; e-mail: brianlipworth@gmail.com


Funding/Support: This study was funded by a departmental grant from the University of Dundee as part of an unrestricted research grant from Teva Pharmaceuticals USA.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(6):1553-1561. doi:10.1378/chest.12-1310
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Background:  International guidelines advocate a standard approach to asthma management for all, despite its heterogeneity. “Personalized” treatment of inflammatory asthma phenotypes confers superior benefits. We wished to evaluate dose response to inhaled corticosteroids (ICSs) in patients with asthma with an elevated fractional exhaled nitric oxide (Feno) phenotype using domiciliary measurements.

Methods:  We performed a randomized, crossover trial in 21 patients with mild to moderate persistent asthma receiving ICSs with elevated Feno (>30 parts per billion [ppb]) that increased further (>10 ppb) after ICS washout. Patients were randomized to 2 weeks of either fluticasone propionate 50 μg bid (FP100) or 250 μg bid (FP500). The primary outcome was response in diurnal domiciliary Feno levels. Secondary outcomes included mannitol challenge, serum eosinophilic cationic protein (ECP), blood eosinophil count, and asthma control questionnaire.

Results:  We found significant dose-related reductions of diurnal Feno compared with baseline − morning Feno: baseline = 71 ppb (95% CI, 61-83 ppb); FP100 = 34 ppb (95% CI, 29-40 ppb), P < .001; FP500 = 27 ppb (95% CI, 22-33 ppb), P < .001; and significant dose separation for morning, P < .05, and evening, P < .001. Time-series Feno displayed exponential decay: FP100 R2 = 0.913, half-life = 69 h (95% CI, 50-114 h); FP500 R2 = 0.966, half-life = 55 h (95% CI, 45-69 h), as well as diurnal variation. The Asthma Control Questionnaire showed significant improvements exceeding the minimal important difference (>0.5) with values in keeping with controlled asthma (<0.75) after each dose: FP100 = 0.48 (95% CI, 0.24-0.71), P = .004; FP500 = 0.37 (95% CI, 0.18-0.57), P = .001. All other secondary inflammatory related outcomes (mannitol, ECP, and eosinophils) showed significant improvements from baseline but no dose separation.

Conclusions:  There is a significant dose response of diurnal Feno to ICS in patients with asthma with an elevated Feno phenotype, which translates into well-controlled asthma. Further interventional studies are warranted using domiciliary Feno in this specific phenotype.

Trial registry:  ClinicalTrials.gov; No.: NCT00995657; URL: clinicaltrials.gov

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