PT - JOURNAL ARTICLE AU - Paul T. King AU - Lovisa Dousha AU - Nadeene Clarke AU - Jennifer Schaefer AU - Rosemary Carzino AU - Roleen Sharma AU - Ken L. Wan AU - Aveena Anantharajah AU - Kim O'Sullivan AU - Zhong X. Lu AU - Stephen R. Holdsworth AU - Sarath Ranganathan AU - Philip G. Bardin AU - David S. Armstrong TI - Phagocyte extracellular traps in children with neutrophilic airway inflammation AID - 10.1183/23120541.00883-2020 DP - 2021 Jan 01 TA - ERJ Open Research PG - 00883-2020 4099 - http://openres.ersjournals.com/content/early/2021/02/18/23120541.00883-2020.short 4100 - http://openres.ersjournals.com/content/early/2021/02/18/23120541.00883-2020.full AB - Childhood lung infection is often associated with prominent neutrophilic airway inflammation and excess production of proteases such as neutrophil elastase (NE). The mechanisms responsible for this inflammation are not well understood. One potentially relevant pathway is the production of extracellular traps by neutrophils (NETs) and macrophages (METs). The aim of this study was to measure NET and MET expression in children and the effect of deoxyribonculease (DNase) 1 and alpha-1 antitrypsin (AAT) on this process.We studied 76 children (median age of 4.0 years) with cystic fibrosis (CF) or chronic cough who underwent investigational bronchoscopy. NETs, METs and NE activity in bronchoalveolar lavage (BAL) samples were measured using confocal microscopy and functional assays. The effects of DNase 1 and AAT on NET/MET expression and NE activity were examined in vitro.Both subject groups had airway neutrophilia with prominent BAL production of NETs with NE co-expression; the mean %±standard error of the mean of neutrophils expressing NETs in the CF group was 23.3±2.8% and in the non-CF group was 28.4±3.9%. NET expression was higher in subjects who had detectable NE activity (p≤0.0074). The percentage of macrophages expressing METs in the CF group was 10.7±1.2% and in the non-CF group was 13.2±1.9%. DNase 1 decreased NET/MET expression (p<0.0001), but increased NE activity (p≤0.0137). The combination of AAT and DNase 1 reduced NE activity (p≤0.0049).We observed prominent extracellular trap formation in symptomatic children with and without CF. This innate inflammatory response was down-regulated by a combination of currently available therapeutics.FootnotesThis manuscript has recently been accepted for publication in the ERJ Open Research. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJOR online. Please open or download the PDF to view this article.Conflict of interest: Dr. King has nothing to disclose.Conflict of interest: Dr. Dousha has nothing to disclose.Conflict of interest: Dr. Clarke has nothing to disclose.Conflict of interest: Dr. Schaefer has nothing to disclose.Conflict of interest: Dr. Carzino has nothing to disclose.Conflict of interest: Dr. Sharma has nothing to disclose.Conflict of interest: Dr. Wan has nothing to disclose.Conflict of interest: Dr. Ananthrajah has nothing to disclose.Conflict of interest: Dr. O'Sullivan has nothing to disclose.Conflict of interest: Dr. Lu has nothing to disclose.Conflict of interest: Dr. Holdsworth has nothing to disclose.Conflict of interest: Dr. Ranganathan has nothing to disclose.Conflict of interest: Dr. Bardin has nothing to disclose.Conflict of interest: Dr. Armstrong has nothing to disclose.