Alveolar nitric oxide (CA(NO) ) is a potential biomarker of small airway inflammation. We investigated effects on CA(NO) of the addition of coarse and fine particle inhaled corticosteroids to standard therapy in severe asthma.
Methods: Severe asthmatics taking ≥1600µg/day budesonide or equivalent performed a randomised open-label crossover study. Subjects with FEV(1) <80%, gas trapping and CA(NO) ≥2ppb entered a 6week dose-ramp run-in of Fluticasone/Salmeterol(FPSM) 250/50µg BID for 3weeks, then 500/50µg BID for 3weeks. Patients then received additional HFA-BDP 200µg BID or FP 250µg BID for 3wks in a cross-over. Participants then received prednisolone(PRED) 25mg/day for 1week. Nitric oxide, lung function, mannitol challenge, systemic inflammatory markers and urinary cortisol were measured.
Results: 15 completed per protocol: mean(SD) age, 51(12)yr; FEV(1,) 58(13)% predicted; residual volume, 193(100)% predicted; mannitol(PD10) , 177(2.8)mcg. There was no significant difference between FPSM and add-on therapy for CA(NO) . FPSM/BDP and FPSM/PRED suppressed Jaw(NO) and FE(NO) compared to FPSM alone, but there was no significant difference between FPSM/BDP and FPSM/FP. ECP, e-selectin and ICAM-1 were suppressed by FPSM/PRED compared to FPSM and FPSM/FP but not FPSM/BDP. Plasma cortisol was significantly suppressed by FPSM/PRED.
Conclusion: In severe asthma, CA(NO) is insensitive to changes in dose and delivery of inhaled corticosteroids and is not suppressed by systemic corticosteroids. Additional inhaled HFA-BDP reducted FE(NO) and Jaw(NO) without adrenal suppression. There was a trend to reduction in FE(NO) and Jaw(NO) with additional FP but this did not reach statistical significance. Prednisolone reduced FE(NO) and Jaw(NO) with suppression of systemic inflammatory markers and urinary cortisol. © 2012 The Authors. British Journal of Clinical Pharmacology © 2012 The British Pharmacological Society.
Authors: Williamson PA, Short PM, Vaidyanathan S, Lipworth BJ
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