Management of asthma based on exhaled nitric oxide in addition to guideline-based treatment for inner-city adolescents and young adults: a randomised controlled trial

Abstract

Background: Preliminary evidence is equivocal about the role of exhaled nitric oxide (NO) in clinical asthma management. We aimed to assess whether measurement of exhaled NO, as a biomarker of airway inflammation, could increase the effectiveness of asthma treatment, when used as an adjunct to clinical care based on asthma guidelines for inner-city adolescents and young adults.

Methods: We did a randomised, double-blind, parallel-group trial at ten centres in the USA. We screened 780 inner-city patients, aged 12-20 years, who had persistent asthma. All patients completed a run-in period of 3 weeks on a regimen based on standard treatment. 546 eligible participants who adhered to treatment during this run-in period were then randomly assigned to 46 weeks of either standard treatment, based on the guidelines of the National Asthma Education and Prevention Program (NAEPP), or standard treatment modified on the basis of measurements of fraction of exhaled NO. The primary outcome was the number of days with asthma symptoms. We analysed patients on an intention-to-treat basis. This trial is registered with clinicaltrials.gov, number NCT00114413.

Findings: During the 46-week treatment period, the mean number of days with asthma symptoms did not differ between the treatment groups (1.93 [95% CI 1.74 to 2.11] in the NO monitoring group vs 1.89 [1.71 to 2.07] in the control group; difference 0.04 [-0.22 to 0.29], p=0.780). Other symptoms, pulmonary function, and asthma exacerbations did not differ between groups. Patients in the NO monitoring group received higher doses of inhaled corticosteroids (difference 119 mug per day, 95% CI 49 to 189, p=0.001) than controls. Adverse events did not differ between treatment groups (p>0.1 for all adverse events).

Interpretation: Conventional asthma management resulted in good control of symptoms in most participants. The addition of fraction of exhaled NO as an indicator of control of asthma resulted in higher doses of inhaled corticosteroids, without clinically important improvements in symptomatic asthma control.

Figures

Figure 1. Consort Diagram

Consort Diagram showing the flow of participants from enrollment to completion of study.

Figure 2. Asthma Outcomes and Medications by Study Visit*

Mean values and 95% confidence intervals for asthma outcomes, pulmonary function and medications burden through the course of the study with maximum symptom days (Panel A), FEV1 % predicted (Panel B), exhaled nitric oxide levels (Panel C), adherence by percent of doses taken (Panel D), inhaled corticosteroid dose in mcg/day (Panel E), and long-acting ß2-agonist therapy in mcg/day (Panel F). The first three weeks constitute the run-in period. * Data for treatment related variables (Panels D,E and F) is presented through the final treatment assessment at week 41, whereas follow-up data panels (Panels A,B and C) continue through week 49, the end of the study period