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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 &lt;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&lt;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.

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