Neutrophil elastase is correlated with disease severity in a cohort from Southern Europe

Active neutrophil elastase (aNE) has emerged as promising biomarker correlated to disease severity and progression in bronchiectasis. Current evidence derives mainly from Northern Europe, while bronchiectasis has demonstrated to be a heterogeneous disease across countries. The present study aims to determine the prevalence of patients with high levels of aNE in sputum in a Southern European country and to explore its association with clinical outcomes. This was a prospective, observational study enrolling consecutive stable adults (≥18 years) with significant bronchiectasis at the Policlinico Hospital, Milan, Italy, between March 2017 and March 2019. A priori three groups of patients were identified based on the median and tertile concentrations of aNE on sputum. Among the 200 patients (75% females; median [IQR] age: 62 [50-71] years, 60% with P. aeruginosa infection) enrolled, the median (IQR) aNE was 15.52 (5.8-29.6). All but 5 patients had aNE higher than 0.016 ug/ml. aNE correlated with both BSI (r =0.19; P=0.009) and E-FACED (r =0.26; P=0.0005). Median levels of aNE significantly increased across BSI (p =0.03) and E-FACED risk classes (p =0.004). Median levels of aNE were higher in patients with vs. without chronic P. aeruginosa infection (25.7 [13.3-40.5] VS. 10.8 [4.8-23-2] ug/ml ug/ml, P<0.0001). Group with high aNE levels included 69 (34.5%) patients. The three aNE groups had different disease severity with both BSI and E-FACED progressively increasing from low to high aNE group (BSI: 6 [4-10] vs 7 [4.5-9.5] vs 8 [5-13], p =0.04; E-FACED: 1 [1-3] vs 2 [1-3] vs 3 [1-4], p =0.002). aNE is a significant biomarker also in Southern Europe where a high presence of chronic P. aeruginosa infection is present.