Effect of Inhaled β(2)-Agonist on Exhaled Nitric Oxide in Chronic Obstructive Pulmonary Disease

The fractional exhaled nitric oxide measured at an expiratory flow of 50mL/s (FE(NO)50) is a marker of airway inflammation, and high levels are associated with greater response to steroid treatment. In asthma, FE(NO)50 increases with bronchodilation and decreases with bronchoconstriction, the latter potentially causing an underestimate of the degree of airway inflammation when asthma worsens. It is unknown whether the same effect occurs in chronic obstructive lung disease (COPD). Likewise, it is not known whether changes in airway calibre in COPD patients alter flow-independent parameters describing pulmonary nitric oxide exchange, such as the maximal flux of nitric oxide (NO) from the proximal airway compartment (J’aw(NO)) and the distal airway/alveolar concentration of NO (CA(NO)). We recruited 24 patients with COPD and performed FE(NO) analysis at multiple expiratory flows before and after treatment with inhaled β(2)-agonist bronchodilator therapy. For the 21 patients analysed, FE(NO)50 rose from 17.1 (1.4) ppb (geometric mean (geometric SD)) at baseline, to 19.3 (1.3) ppb after bronchodilator therapy, an increase of 2.2 ppb (95% CI, 0.7–3.6; P = 0.005). There were non-significant changes in flow-independent NO parameters. The change in FE(NO)50 correlated positively with the change in J’aw(NO) (r(s) = 0.67, P < 0.001; r(s) = 0.62, P = 0.002 before and after correction for axial back-diffusion respectively) following bronchodilation. Inhaled bronchodilator therapy can increase exhaled nitric oxide measurements in COPD. The standardisation of inhaled bronchodilator therapy before FE(NO) analysis in COPD patients should therefore be considered in both research and clinical settings.