Association of blood eosinophils and exhaled nitric oxide with exacerbations in patients with asthma, COPD and asthma+COPD: the NOVELTY study

Background: Blood eosinophils (EOS) and fractional exhaled nitric oxide (FeNO) are potential biomarkers for disease progression and treatment response in asthma and chronic obstructive pulmonary disease (COPD). We investigated their association with exacerbations in asthma, COPD and asthma+COPD. Methods: NOVEL observational longiTudinal studY is a multicountry prospective study of patients with physician-assigned asthma, COPD and asthma+COPD. Negative binomial and logistic regression analyses were performed for baseline EOS/FeNO (separately and combined), by diagnosis, and for different exacerbation subtypes (all, antibiotics-only, oral corticosteroids (OCS)-only). Results: Higher baseline EOS was significantly associated with increased risk of all exacerbations in asthma (incidence rate ratio (IRR) 1.09, 95% CI 1.01 to 1.18, p=0.033), with a trend increase with COPD (IRR 1.09, 95% CI 1.00 to 1.19, p=0.069) but not asthma+COPD. Higher baseline FeNO was significantly associated with decreased risk of all exacerbations in COPD (IRR 0.91, 95% CI 0.84 to 0.99, p=0.025) and increased risk of OCS-only exacerbations in asthma (OR 1.16, 95% CI 1.04 to 1.29, p=0.006) and asthma+COPD (OR 1.55, 95% CI 1.22 to 1.97, p<0.001). In exacerbation risk in asthma (IRR 1.14, 95% CI 1.05 to 1.24, p=0.003), while in COPD, both higher EOS (IRR 1.12, 95% CI 1.02 to 1.24, p=0.033) and lower FeNO (IRR 0.87, 95% CI 0.78 to 0.96, p=0.009) were independently associated with exacerbation risk. Conclusions: Higher EOS predicted exacerbations in asthma and COPD, while FeNO showed heterogeneous associations, particularly for OCS-only treated exacerbations. Assessment of exacerbation subtype might improve personalised management. Interpretation is limited by physician-assigned diagnoses, potential ICS confounding and recall bias.