Different Relationships between FENO and COPD Characteristics in Smokers and Ex-Smokers

Exhaled nitric oxide (FENO) is a marker of type-2 inflammation in asthma and is used in its management. However, smokers and ex-smokers have lower FENO values, and the clinical use of FENO values in COPD patients is unclear. Therefore, we investigated if FENO had a relationship to different COPD characteristics in smoking and ex-smoking subjects. Patients with COPD (n = 533, 58% females) were investigated while in stable condition. Measurements of FENO50, blood cell counts, IgE sensitisation and lung function were performed. Medication reconciliation was used to establish medication usage. Smokers (n = 150) had lower FENO50 9 (8, 10) ppb (geometric mean, 95% confidence interval) than ex-smokers did (n = 383) 15 (14, 16) ppb, p < 0.001. FENO50 was not associated with blood eosinophil or neutrophil levels in smokers, but in ex-smokers significant associations were found (r = 0.23, p < 0.001) and (r = -0.18, p = 0.001), respectively. Lower FENO values were associated with lower FEV1% predicted in both smokers (r = 0.17, p = 0.040) and ex-smokers (r = 0.20, p < 0.001). Neither the smokers nor ex-smokers with reported asthma or IgE sensitisation were linked to an increase in FENO50. Ex-smokers treated with inhaled corticosteroids (ICS) had lower FENO50 14 (13, 15) ppb than non-treated ex-smokers 17 (15, 19) ppb, p = 0.024. This was not found in smokers (p = 0.325). FENO is associated with eosinophil inflammation and the use of ICS in ex-smoking COPD subjects, but not in smoking subjects suggesting that the value of FENO as an inflammatory marker is more limited in smoking subjects. The association found between low FENO values and low lung function requires further investigation.