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Targets for asthma therapy
S6 The FENOtype Trial: Inhaled Corticosteroid Dose-Response Using Domiciliary Exhaled Nitric Oxide in Persistent Asthma
  1. WJ Anderson,
  2. PM Short,
  3. PA Williamson,
  4. BJ Lipworth
  1. University of Dundee, Dundee, United Kingdom

Abstract

Background International guidelines advocate a standard approach to asthma management for all despite its heterogeneity. ‘Personalised’ treatment for inflammatory asthma phenotypes confers superior benefits. We wished to evaluate dose-response to inhaled corticosteroids (ICS) in asthmatics with an elevated exhaled nitric oxide (FeNO) phenotype using domiciliary measurements.

Methods We performed a randomised, cross-over trial in 21 mild-to-moderate persistent asthmatics receiving ICS with elevated FeNO (>30ppb) that increased further (>10ppb) after ICS washout. Patients were randomised to 2 weeks of either fluticasone propionate 50µg twice-daily (FP100) or 250µg twice-daily (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 (ACQ).

Results We found significant dose-related reductions of diurnal FeNO compared to baseline - morning FeNO: baseline=71ppb (95%CI:61–83ppb); FP100=34ppb (95%CI:29–40ppb), p<0.001; FP500=27ppb (95%CI:22–33ppb), p<0.001; and significant dose separation for morning, p<0.05, and evening, p<0.001. Time series FeNO displayed exponential decay (Figure 1): FP100 R2=0.913, half-life=69hrs (95%CI:50–114hrs); FP500 R2=0.966, half-life=55hrs (95%CI:45–69hrs); as well as diurnal variation. ACQ 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=0.004; FP500=0.37 (95%CI:0.18–0.57), p=0.001. 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 asthmatics with an elevated FeNO phenotype, which translates into well-controlled asthma. Further interventional studies are warranted using domiciliary FeNO in this specific phenotype.

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