Predictive value of exhaled nitric oxide in the management of asthma: a systematic review

Abstract

The clinical value of measuring fractional exhaled nitric oxide (FeNO) in asthma is not clear. We aimed to assess whether FeNO can reliably predict clinical outcomes in asthma treated with inhaled corticosteroids (ICS). We also evaluated whether its predictive role is influenced by different inflammatory phenotypes of asthma.We conducted a systematic review focusing on five clinically relevant questions. Two authors independently screened search results, extracted data and assessed quality of the included studies. Data were synthesised by qualitative methods.12 prospective studies were included, answering partly three of the five questions. In steroid-naïve asthma, a high FeNO level probably predicts good response to ICS. In ICS-treated asthmatics, a low FeNO level probably predicts low risk of exacerbation, and the patient is unlikely to benefit from increasing ICS dose. There were scarce data to conclude whether FeNO predicts exacerbations when ICS treatment is stopped in well-controlled asthma. Only one study reported results separately in different asthma phenotypes.The current evidence on the predictive value of FeNO and its role in the management of asthma is incomplete. Future studies should focus on clinically meaningful questions and probably target only eosinophilic phenotypes where FeNO is best associated with the activity of airway inflammation.

Asthma and lung function in adulthood after a viral wheezing episode in early childhood

“…41 However, it is known that eosinophilic inflammation in the airways is most pronounced in atopic asthma, and the concentration of nitric oxide is related to eosinophilic inflammation in the airways. 41 However, it is known that eosinophilic inflammation in the airways is most pronounced in atopic asthma, and the concentration of nitric oxide is related to eosinophilic inflammation in the airways.…”

Spirometry‐adjusted fraction of exhaled nitric oxide increases accuracy for assessment of asthma control in children

“…Standardized procedures for its measurement and clinical use have already been published, with a strong level of evidence in the diagnosis of eosinophilic airway inflammation and for monitoring airway inflammation in patients with asthma . In fact, the expression of inducible nitric oxide synthetase mRNA has been shown to be increased in the airways of subjects with asthma and to be downregulated by the use of inhaled steroids …”

“…Furthermore, correlations between airway inflammation and symptoms, asthma control and asthma severity are weak or absent . In steroid‐naïve patients, high exhaled NO levels predict a good response to inhaled corticosteroids (ICS) treatment, and a low level of exhaled NO in adults in ICS treatment is associated with reduced likelihood ratio of exacerbation . Until now, it is not possible to provide clear recommendations for the utility of the exhaled NO in asthma management, as studies failed to show an overall benefit in the rate of exacerbations as well as in asthma control, lung function and use of oral corticosteroids during exacerbations .…”

“…1,[9][10][11] In steroid-naïve patients, high exhaled NO levels predict a good response to inhaled corticosteroids (ICS) treatment, and a low level of exhaled NO in adults in ICS treatment is associated with reduced likelihood ratio of exacerbation. 12 Until now, it is not possible to provide clear recommendations for the utility of the exhaled NO in asthma management, as studies failed to show an overall benefit in the rate of exacerbations as well as in asthma control, lung function and use of oral corticosteroids during exacerbations. 13 In a recent study, exhaled NO was used in relation to FEV 1 (exhaled NO/FEV 1 ) to distinguish patients with asthma from those without with promising results.…”

Do clinical investigations predict long‐term wheeze? A follow‐up of pediatric respiratory outpatients

“…To our knowledge, no studies assess the predictive value of FeNO on wheeze persistence at school age. Available publications assessed the predictive value of FeNO on asthma control, relapse or exacerbations in asthmatic children, but with a short follow‐up …”