RT Journal Article SR Electronic T1 Phagocyte extracellular traps in children with neutrophilic airway inflammation JF ERJ Open Research JO erjor FD European Respiratory Society SP 00883-2020 DO 10.1183/23120541.00883-2020 VO 7 IS 2 A1 Paul T. King A1 Lovisa Dousha A1 Nadeene Clarke A1 Jennifer Schaefer A1 Rosemary Carzino A1 Roleen Sharma A1 Ken L. Wan A1 Aveena Anantharajah A1 Kim O'Sullivan A1 Zhong X. Lu A1 Stephen R. Holdsworth A1 Sarath Ranganathan A1 Philip G. Bardin A1 David S. Armstrong YR 2021 UL http://openres.ersjournals.com/content/7/2/00883-2020.abstract 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 α1-antitrypsin (AAT) on this process.We studied 76 children (median age of 4.0 years) with cystic fibrosis or chronic cough who underwent investigational bronchoscopy. NETs, METs and neutrophil elastase 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 neutrophil elastase activity were examined in vitro.Both subject groups had airway neutrophilia with prominent BAL production of NETs with neutrophil elastase co-expression; the mean %±standard error of the mean of neutrophils expressing NETs in the cystic fibrosis group was 23.3±2.8% and in the non-cystic fibrosis group was 28.4±3.9%. NET expression was higher in subjects who had detectable neutrophil elastase activity (p≤0.0074). The percentage of macrophages expressing METs in the cystic fibrosis group was 10.7±1.2% and in the non-cystic fibrosis group was 13.2±1.9%. DNase 1 decreased NET/MET expression (p<0.0001), but increased neutrophil elastase activity (p≤0.0137). The combination of AAT and DNase 1 reduced neutrophil elastase activity (p≤0.0049).We observed prominent extracellular trap formation in symptomatic children with and without cystic fibrosis. This innate inflammatory response was down-regulated by a combination of currently available therapeutics.Prominent extracellular trap formation may be observed in young children with airway inflammation, with and without cystic fibrosis. This innate inflammatory response is down-regulated by a combination of currently available therapeutics. https://bit.ly/3bDaWyC