The burden of pediatric asthma remains high with one-third of patients being under- or overtreated because of the unique challenges in the assessment and management of childhood asthma. Until recently, there has been no point of care tool for assessing the underlying airway inflammation (i.e., inflammometry) in asthma. Recently, fractional exhaled nitric oxide (FeNO) has emerged as an important biomarker for the assessment and management of asthma. Recent evidence indicates that FeNO identifies T-helper cell type 2 (Th2)–mediated airway inflammation with a high positive and negative predictive value for identifying corticosteroid responsive airway inflammation. This article examines the evidence for FeNO as a predictor of Th2-mediated inhaled corticosteroid (ICS) responsive airway inflammation and reviews recent studies evaluating the role of FeNO, whether helpful or not, in the assessment and management of pediatric asthma. FeNO is a reliable adjunct to traditional tests in the assessment of suspected asthma. Importantly, it is useful for identifying and for excluding ICS-responsive airway inflammation. Although individual study results have varied, collectively, asthma managed using FeNO is associated with lower exacerbation rates compared with clinical algorithms alone. Finally, FeNO may be useful in identifying patients at risk for future impairment or loss of asthma control during reduction/cessation of ICS treatment. FeNO testing has an important role in the assessment of pediatric patients with suspected asthma and in the management of pediatric patients with established asthma. Additional studies will continue to define the exact role of FeNO testing in pediatric asthma.

Background Predictors of improvement in asthma control and lung function to STEP-3 therapy in children with persistent asthma have not been identified despite reported heterogeneity in responsiveness. Objective To evaluate potential predictors of asthma control and lung function responsiveness to STEP-3 therapy. Methods A post-hoc analysis from the Best Add-On Giving Effective Response (BADGER) study tested the association between baseline biological, asthma control, pulmonary function and demographic markers and responsiveness to step-up to higher dose inhaled corticosteroids (ICS step-up), or addition of leukotriene receptor antagonist (LTRA step-up) or long acting beta-2 (LABA step-up) therapy. Results In multivariate analyses, higher impulse oscillometry (IOS) AX levels were associated (p=0.047) with a differential forced expiratory volume in 1-second (FEV1) response favoring LABA over ICS step-up while higher levels of urinary leukotriene E4 (uLTE4) were marginally (p=0.053) related to a differential FEV1 response favoring LTRA over LABA step-up therapy. Predictors of differential responses comparing ICS to LTRA step-up therapy were not apparent probably due to suppression of allergic markers with low-dose ICS treatment. Minimal overlap was seen across FEV1 and asthma control day (ACD) predictors suggesting distinct mechanisms related to lung function and ACD responses. Conclusion Levels of IOS AX indicating peripheral airway obstruction and uLTE4 indicating cysteinyl leukotriene inflammation can differentiate LABA step-up responses from responses to LTRA or ICS step-up. Further studies with physiological, genetic and biological markers related to these phenotypes will be needed to predict individual responses to LABA step-up therapy.

Disclosure of potential conflict of interest: J. Malka has received payment for lectures and travel support from Aerocrine and Mead Johnson. S. J. Szefler has consultant arrangements with Roche, AstraZeneca, Aerocrine, Daiichi Sankyo, Boehringer Ingelheim, Merck, Genentech, and Novartis and has received grants from GlaxoSmithKline. J. D. Spahn declares that he has no relevant conflicts of interest.

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