Exhaled nitric oxide to predict corticosteroid responsiveness and reduce asthma exacerbation rates

Abstract

Until recently, no point-of-care tool was available for assessing the underlying airway inflammation associated with asthma. Fractional exhaled nitric oxide (FeNO) emerged in the last decade as an important biomarker for asthma assessment and management. Evidence also indicates that FeNO is most accurately classified as a marker of T-helper cell type 2 (Th2)-mediated airway inflammation with a high positive and negative predictive value for identifying corticosteroid-responsive airway inflammation. This manuscript evaluates the evidence for FeNO as a predictor of Th2-mediated corticosteroid-responsive airway inflammation and presents the results of a meta-analysis of three adult studies comparing asthma exacerbation rates with FeNO-based versus clinically-based asthma management algorithms, one of which was not included in a 2012 Cochrane meta-analysis. The primary purpose of the updated meta-analysis was to evaluate asthma exacerbation rates. The results demonstrate that the rate of exacerbations was significantly reduced in favor of FeNO-based asthma management (mean treatment difference = -0.27; 95% CI [-0.42, -0.12] as was the relative rate of asthma exacerbations (relative rate = 0.57; 95% CI [0.41, 0.80]). In summary, FeNO has value for identifying patients with airway inflammation who will and will not respond to corticosteroids. Importantly, the use of FeNO in conjunction with clinical parameters is associated with significantly lower asthma exacerbation rates compared with asthma managed using clinical parameters alone. Together these data indicate that FeNO testing has an important role in the assessment and management of adult asthma. Further studies will continue to define the exact role of FeNO testing in adult asthma.

Cost-effectiveness and Budget Impact of Routine Use of Fractional Exhaled Nitric Oxide Monitoring for the Management of Adult Asthma Patients in Spain

“…Two of these studies [10,11] had been included in systematic reviews of asthma treatment and FeNO monitoring [7,8]; the third study [15] was a FeNO-driven randomized controlled trial of anti-inflammatory treatment of atopic asthma. A study by Powell et al [16] conducted on a population of pregnant women was not used because its outcomes may have been influenced by pregnancy [16].…”

“…The analysis found a -0.23 (95%CI, -0.36 to -0.09) difference between the exacerbation rates observed in the FeNO monitoring arm and in the control arm. The results were subsequently adjusted to account for the prevalence of smoking in Spain (Spanish National Institute of Statistics, www.ine.es) under the assumption that FeNO monitoring might not improve outcomes in patients who are tobacco smokers [8]. An average exacerbation rate of 0.78 personyears was calculated by multiplying the average number of exacerbations per year in poorly controlled asthmatic patients by the probability for an asthmatic patient of being poorly controlled using parameters derived from expert opinion and from data reported by Borderias-Clau et al [22] and MartinezMoragon et al [23].…”

“…The estimated average reduction in the rate of exacerbations was 22.7%. The evidence on the usage of inhaled corticosteroids (ICS) is based on a systematic review [8] that found an approximately 27% average reduction in use of ICS when FeNO monitoring was applied in adult patients. This estimate was then adjusted to account for the prevalence of smoking in Spain.…”

“…FeNO testing has shown its value in identifying individuals who respond to inhaled corticosteroids [7][8] and biologic therapy [9] and has acted as a complement to conventional monitoring of asthma in children and adults in several randomized controlled clinical trials [10][11][12][13][14][15][16]. Moreover, in 2014, the National Institute for Health and Care Excellence (NICE) recommended FeNO testing to help diagnose asthma in adults and children when diagnosis is unclear.…”

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“…Exhaled NO is thought to be a useful marker of airway inflammation because asthmatic patients exhibit higher levels of exhaled NO than normal subjects [1][2][3] and because treatment with corticosteroids blunts such elevation in exhaled NO [3,4]. The level of nitric oxide in exhaled gas in patients with asthma has been the subject of many studies designed to elucidate its significance in relation to airway inflammation and severity of the symptoms [2,5,6].…”