Review of exhaled nitric oxide in chronic obstructive pulmonary disease.

The up-regulation of nitric oxide (NO) by inflammatory cytokines and mediators in central and peripheral airway sites can be easily monitored in exhaled air (F(E)NO). It is now possible to estimate the predominant airway site of increased F(E)NO i.e. large versus peripheral airway/alveoli, and its potential pathologic and physiologic role in obstructive lung disease. In asthma, six double-blind, randomized, controlled algorithm trials have reported only equivocal benefits of add-on measurements of F(E)NO to usual clinical guideline management including spirometry. Significant design issues, as emphasized by Gibson, may exist. However, meta-analysis of these six studies (Petsky et al 2012 Thorax 67 199-208) concluded that routine serial measurements of F(E)NO for clinical asthma management does not appear warranted. In COPD including chronic bronchitis and emphysema, despite significant expiratory airflow limitation, when clinically stable as well as during exacerbation, F(E)NO, j'(awNO) and C(ANO) may all be normal or increased. Furthermore, the role of add-on monitoring of exhaled NO to GOLD management guidelines is less clear because of the absence of conclusive doubleblind, randomized, control trial studies concerning potential clinical benefits in the management of COPD.