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The Use of Exhaled Nitric Oxide to Guide Asthma Management

A Randomized Controlled Trial

¹ Institute for Lung Health, Department of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital, Leicester, United Kingdom; and ² Department of General Practice, University of Aberdeen, Aberdeen, United Kingdom

Correspondence and requests for reprints should be addressed to Ian D. Pavord, D.M., F.R.C.P., Consultant Physician and Honorary Professor of Medicine, Institute for Lung Health, Department of Respiratory Medicine and Thoracic Surgery, Glenfield Hospital, Leicester LE3 9QP, United Kingdom. E-mail: ian.pavord{at}uhl-tr.nhs.uk

Rationale: Current asthma guidelines recommend adjusting antiinflammatory treatment on the basis of the results of lung function tests and symptom assessment, neither of which are closely associated with airway inflammation.

Objectives: We tested the hypothesis that titrating corticosteroid dose using the concentration of exhaled nitric oxide in exhaled breath (FE_NO) results in fewer asthma exacerbations and more efficient use of corticosteroids, when compared with traditional management.

Methods: One hundred eighteen participants with a primary care diagnosis of asthma were randomized to a single-blind trial of corticosteroid therapy based on either FE_NO measurements (n = 58) or British Thoracic Society guidelines (n = 60). Participants were assessed monthly for 4 months and then every 2 months for a further 8 months. The primary outcome was the number of severe asthma exacerbations. Analyses were by intention to treat.

Measurements and Main Results: The estimated mean (SD) exacerbation frequency was 0.33 per patient per year (0.69) in the FE_NO group and 0.42 (0.79) in the control group (mean difference, –21%; 95% confidence interval [CI], –57 to 43%; p = 0.43). Overall the FE_NO group used 11% more inhaled corticosteroid (95% CI, –17 to 42%; p = 0.40), although the final daily dose of inhaled corticosteroid was lower in the FE_NO group (557 vs. 895 µg; mean difference, 338 µg; 95% CI, –640 to –37; p = 0.028).

Conclusions: An asthma treatment strategy based on the measurement of exhaled nitric oxide did not result in a large reduction in asthma exacerbations or in the total amount of inhaled corticosteroid therapy used over 12 mo, when compared with current asthma guidelines.

Clinical trial registered with www.controlled-trials.com (ISRCTN08067387).

Key Words: asthma management • exhaled nitric oxide • controlled trial

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Current evidence suggests that exhaled nitric oxide, a noninvasive surrogate marker of airway inflammation, can be used in asthma to reduce treatment and predict preventable asthma exacerbations. What This Study Adds to the Field Using exhaled nitric oxide–driven asthma management did not result in fewer asthma exacerbations, or in the use of less treatment, when compared with traditional management, in the largest study of its kind to date.

 

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