Clinical Values of Nitric Oxide Parameters from the Respiratory System

Background: Fractional exhaled nitric oxide (FENO) concentration reliably reflects central airway inflammation, but it is not sensitive to changes in the NO dynamics in the lung periphery. By measuring FENO at several different flow rates one can estimate alveolar NO concentration (CANO), bronchial NO flux (J(aw)NO), bronchial wall NO concentration (CawNO) and the bronchial diffusivity of NO (DawNO). Objective: We aimed to describe the current knowledge and clinical relevance of NO parameters in different pulmonary diseases. Methods: We conducted a systematic literature search to identify publications reporting NO parameters in subjects with pulmonary or systemic diseases affecting the respiratory tract. A narrative review was created for those with clinical relevance. Results: Estimation of pulmonary NO parameters allows for differentiation between central and peripheral inflammation and a more precise analysis of central airway NO output. CANO seems to be a promising marker of parenchymal inflammation in interstitial lung diseases and also a marker of tissue damage and altered gas diffusion in chronic obstructive pulmonary disease and systemic diseases affecting the lung. In asthma, CANO can detect small airway involvement left undetected by ordinary FENO measurement. Additionally, CawNO and DawNO can be used in asthma to assess if FENO is increased due to enhanced inflammatory activity (increased CawNO) or tissue changes related to bronchial remodelling (altered DawNO). Conclusion: NO parameters may be useful for diagnosis, prediction of disease progression and prediction of treatment responses in different parenchymal lung and airway diseases. Formal trials to test the added clinical value of NO parameters are needed.