Fractional Exhaled Nitric Oxide Falls Progressively During Treated Exacerbations of COPD and Is Discordant with Blood Eosinophil Counts

Background: The behavior of fractional exhaled nitric oxide (FeNO) during treated COPD exacerbations and its agreement with blood eosinophil counts are poorly characterized. Aims: To describe serial FeNO trajectories across hospitalized COPD exacerbations (AECOPDs), assess concordance between FeNO and blood eosinophils, and test whether these can predict length of stay (LOS). Methods: Prospective cohort of patients hospitalized for AECOPD. FeNO was measured on admission, on day 2 and at discharge; blood eosinophils and post-bronchodilator spirometry on admission and before discharge; and arterial blood gases on admission and on day 2. The admission measurements preceded the first dose of corticosteroid. All patients received guideline-directed treatment, including systemic corticosteroids. Results: Most patients were male (94.7%), with a mean age of 71.7 ± 8.3 years. FeNO fell from 16 (IQR 10–25) ppb on admission to 13.5 (7–20) ppb on day 2 and 9 (6–18) ppb at discharge (p < 0.001). Blood eosinophils fell from 60 (20–150) to 0 (0–40) cells/µL (p < 0.001), and FEV1 increased from 38% to 45% predicted (p < 0.001). Agreement between biomarkers on admission was poor (ρ = 0.21, p = 0.07; κ = 0.08, 95% CI −0.15 to +0.30), and 31 patients (40.8%) were classified differently by the two markers. Admission FeNO (ρ = 0.03, p = 0.79), ΔFeNO (ρ = −0.12, p = 0.31), and admission eosinophils (ρ = −0.08, p = 0.49) were not associated with LOS. Of the patients who were type-2-high on admission (FeNO ≥ 20 ppb), 57% had fallen below that threshold by day 2 and 62% by discharge (71% and 71%, respectively, at ≥25 ppb). Over the admission-to-discharge interval, the changes in the two markers were unrelated once each was adjusted for its own admission value (partial ρ = 0.05, p = 0.73), and there was no agreement on the direction of change (κ = 0.03). Conclusions: FeNO progressively declines during treated AECOPD, alongside a fall in the blood eosinophil count, so that the type-2 label assigned on admission is no longer valid for most patients 48 h later. FeNO and blood eosinophils identified largely non-overlapping patients, and no biomarker predicted length of stay.