Sputum biomarkers of eosinophil degranulation in COPD; relationship with cell counts

Eosinophil counts can identify chronic obstructive pulmonary disease (COPD) patients with increased type 2 inflammation in the lungs. However, sputum counts may underestimate activation due to degranulation (reducing intact cells). We investigated free eosinophil granules (FEGs) and eosinophil derived neurotoxin (EDN) as sputum biomarkers of eosinophil activation in COPD and assessed the relationship with blood eosinophil counts (BECs). BECs, sputum cell counts and levels of FEGs and sputum EDN were quantified in patients with COPD. Blood and sputum eosinophil counts were dichotomized using ≥300 cells·µL −1 and ≥3% (eosinophil high ), respectively. Group median values identified EDN high or FEG high . Receiver operating characteristics (ROC) curve analysis determined the ability of BEC to predict elevated degranulation markers. EDN and FEGs were associated with sputum eosinophil counts; rho=0.38, p<0.01, and rho=0.65, p<0.0001, respectively. BECs were associated with EDN (rho=0.48, p<0.0001) and FEGs (rho=0.40, p<0.0001). BEC predicted elevated FEGs and EDN with an AUC of 0.69 and 0.70 (95%CI: 0.58–0.80 and 0.59–0.82, respectively). A cut-off of >0.3×10^9·L −1 BECs had a specificity of 100.0 and 95.0%, for FEGs and EDN, respectively. Discordance between cell counts and degranulation biomarkers were observed in patients with Eosinophil low /FEGs high , eosinophil low /EDN high and eosinophil high /EDN low comprising 31.5, 34.4 and 2.2% of the cohort, respectively. Markers of eosinophil degranulation may be present with low numbers of intact eosinophils in sputum. BECs were associated with elevated levels of degranulation markers in the lung.