A point-of-care neutrophil elastase activity assay identifies bronchiectasis severity, airway infection and risk of exacerbation.

Introduction: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick - NEATstik®) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk.
Methods: Sputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik®, which scores neutrophil elastase concentration from 0 (<8 µg·mL ^-1 elastase activity) to 10 (maximum detectable neutrophil elastase activity). High neutrophil elastase activity was regarded as a NEATstik® grade >6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy.
Measurements and Main Results: Patients had a median age of 69 years and forced expiratory volume in 1 s (FEV ₁ ) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV ₁ (p=0.02). A high NEATstik® grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63-4.64, p<0.001). The median time to next exacerbation for patients with a NEATstik® grade >6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71-3.94, p<0.001). Results were confirmed in the independent validation cohort.
Conclusions: A novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations.
Competing Interests: Conflict of interest: A. Shoemark has nothing to disclose. Conflict of interest: E. Cant has nothing to disclose. Conflict of interest: L. Carreto has nothing to disclose. Conflict of interest: A. Smith has nothing to disclose. Conflict of interest: M. Oriano has nothing to disclose. Conflict of interest: H.R. Keir has nothing to disclose. Conflict of interest: L. Perea has nothing to disclose. Conflict of interest: E. Canto has nothing to disclose. Conflict of interest: L. Terranova has nothing to disclose. Conflict of interest: S. Vidal has nothing to disclose. Conflict of interest: K. Moffitt was employed by Proaxsis, during the conduct of the study. Conflict of interest: S. Aliberti has nothing to disclose. Conflict of interest: O Sibila has nothing to disclose. Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Bayer Healthcare, Grifols and Insmed, grants from AstraZeneca, personal fees from Napp and Aradigm Corporation, outside the submitted work.
(Copyright ©ERS 2019.)