Clinical aspects of using exhaled NO in asthma diagnosis and management

Abstract

Background: Current guidelines recommend tailoring of asthma management according to disease control, which is largely defined by increased symptoms and deterioration in lung function. These features do not reflect the severity nor the type of the asthmatic airway inflammation. Fractional exhaled nitric oxide (FENO) is a simple, non-invasive and cost-effective online test applicable in both adults and children. In addition to symptoms and lung function measurements, FENO reflects airway eosinophilia and hence allows online assessment of the corticosteroidsensitive T helper 2 type airway inflammation in asthmatic patients. FENO can thus be applied to aid asthma diagnosis and treatment monitoring both in clinical practice and for research purposes. Objectives: The scope of this review is to provide an overview of the most important clinical studies using FENO in asthma management and to summarise the implications of FENO measurements in clinical practice. Results and Conclusion:In several studies, FENO measurements provided additional information on aspects of asthma including phenotyping, corticosteroidresponsiveness and disease control. Thus, if correctly applied and interpreted, FENO can aid asthma diagnosis, identify patients at risk of exacerbation and support customized treatment decisions. A simple and reliable tool to quantify peripheral nitric oxide will further aid to identify patients with small airways inflammation.Please cite this paper as: Ludviksdottir D, Diamant Z, Alving K, Bjermer L and Malinovschi A. Clinical aspects of using exhaled NO in asthma diagnosis and management. Clin Respir J 2012; 6: 193-207.

Exhaled Nitric Oxide and Airway Hyperresponsiveness to Adenosine 5′-monophosphate and Methacholine in Children with Asthma

“…NO is synthesized by various cells through the oxidation of L-arginine by NO synthase. In asthma, inducible NO synthase expression is upregulated by activating STAT-6 through interleukins 4 and 13 produced by T helper 2 cells, mast cells and eosinophils [4,21]. Thus, eNO directly signals the proinflammatory cytokine mechanisms of central importance in the pathophysiology of asthma.…”

“…In recent years, fractional eNO (FeNO) has become a valuable tool for the diagnosis and monitoring of asthma in childhood [4]. Previous studies investigating relationships between FeNO and AHR have shown inconsistent results and the correlations were generally low [5,6,7].…”

Childhood asthma biomarkers: present knowledge and future steps

“…It can be performed using different techniques, including chemiluminescence, electrochemical detection, and laser spectroscopy [20]. Online and offline methods are available for collecting and analyzing FE NO , but only the single breath online method (SBOL) has been fully standardized and it is now the gold standard for FE NO measurement in children who are able to cooperate [21].…”

“…In particular, IL-4 and IL-13 induce an upregulated epithelial iNOS expression. Exhaled NO directly reflects Th2-mediated proinflammatory cytokine mechanisms [20,29].…”

Validation of a New Portable Exhaled Nitric Oxide Analyzer, NIOX VERO®: Randomized Studies in Asthma

“…NO is an excellent surrogate marker of inhaled corticosteroid (ICS)-sensitive local type-2 cytokine-driven inflammatory mechanisms, which are of central importance in allergic airway inflammation [1][2][3][4].…”