Fractional Exhaled Nitric Oxide (FeNO) in Patients with Stable Chronic Obstructive Pulmonary Disease: Short-Term Variability and Potential Clinical Implications

Background: The use of fractional exhaled nitric oxide (FeNO) has been proposed for identifying and monitoring eosinophilic airway inflammation in chronic obstructive pulmonary disease (COPD). To explore the clinical utility of FeNO in COPD, we aimed to assess its short-term variability in a clinically stable COPD cohort. Methods: Consecutive COPD patients, formerly smokers, underwent FeNO assessment at the baseline and six time-points through serial sampling spaced 3 days apart. Results: A total of 41 patients (mean age 72.9, 87.8% males) showed a median baseline value of FeNO of 11.7 (8.0–16.8) ppb. A weak linear relationship was documented between baseline FeNO values and both eosinophil counts (r = 0.341, p = 0.029) and the percentage of eosinophils (r = 0.331, p = 0.034), confirmed in multiple linear regressions after adjusting for steroid use. The overall individual variability of FeNO between time-points was 3.90 (2.53–7.29) ppb, with no significant difference in the distribution of FeNO values measured at different time-points (p = 0.204). A total of 28 (68.3%) patients exhibited FeNO always below the 25 ppb cut-off at all determinations, while the remining 13 (31.7%) had at least one value above the established limit. Interestingly, none of these 13 participants had FeNO stably above 25 ppb, all showing at least one normal value during serial sampling. Compared to these patients with more fluctuating values, the 28 with stably normal FeNO only exhibited a significantly higher body weight (80.0 ± 18.2 kg vs. 69.0 ± 8.8 kg, p = 0.013) and body mass index (29.7 ± 6.5 kg/m2 vs. 25.9 ± 3.7 kg/m2, p = 0.026), confirmed in multiple logistic regressions after adjusting for major potential confounders. Conclusions: A certain degree of FeNO variability, apparently unrelated to eosinophil counts but somehow influenced by body weight, must be considered in COPD patients. Further studies are needed to clarify whether this biomarker may be effectively used to plan more personalized pharmacological and rehabilitation strategies in this clinical setting