Persistently elevated exhaled nitric oxide fraction is associated with increased risk of exacerbation in COPD

Preventing the occurrence of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) is a major therapeutic goal. We hypothesise that persistently increased levels of exhaled nitric oxide (F_eNO) during follow-up can identify a group of COPD patients at higher risk of AECOPD.To test this hypothesis, we measured F_eNO levels (HypAir F_eNO®, Medisoft; Sorinnes, Belgium) prospectively in 226 clinically stable COPD outpatients at recruitment and during follow-up (at 6 and 12 months). Patients were stratified according to the number of visits with F_eNO ≥20 ppb.F_eNO was <20 ppb in all three visits in 44.2% of patients, 29.6% in visit 1 and 26.1% in visit 2 or 3. These three groups suffered progressively higher AECOPD rates during follow-up (0.67, 0.91 and 1.42, respectively, p<0.001). After adjusting for potential confounding variables (log-rank test), the hazard ratio for AECOPD was higher in the latter group (1.579 (95% CI 1.049-2.378), p=0.029). Likewise, time to first moderate and severe AECOPD was shorter in these patients. Finally, there was no relationship between F_eNO levels and circulating eosinophils.Persistent F_eNO levels ≥20 ppb in clinically stable COPD outpatients are associated with a significantly higher risk of AECOPD.