{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T15:34:28Z","timestamp":1791646468655,"version":"4.3.4"},"reference-count":82,"publisher":"Springer Science and Business Media LLC","issue":"1","content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Respir Res"],"published-print":{"date-parts":[[2017,12]]},"DOI":"10.1186\/s12931-017-0691-x","type":"journal-article","created":{"date-parts":[[2017,12,19]],"date-time":"2017-12-19T09:40:15Z","timestamp":1513676415000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":113,"title":["Neutrophil elastase in bronchiectasis"],"prefix":"10.1186","volume":"18","author":[{"given":"Andrea","family":"Gramegna","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Amati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Terranova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Sotgiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Tarsia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Miglietta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Adelaide","family":"Calderazzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Aliberti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Blasi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,19]]},"reference":[{"issue":"8","key":"691_CR1","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1038\/nri3024","volume":"11","author":"A Mantovani","year":"2011","unstructured":"Mantovani A, Cassatella MA, Costantini C, Jaillon S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat Rev Immunol. 2011 Jul 25;11(8):519\u201331.","journal-title":"Nat Rev Immunol"},{"issue":"18","key":"691_CR2","doi-asserted-by":"crossref","first-page":"2173","DOI":"10.1182\/blood-2016-01-688887","volume":"127","author":"C Silvestre-Roig","year":"2016","unstructured":"Silvestre-Roig C, Hidalgo A, Soehnlein O. Neutrophil heterogeneity: implications for homeostasis and pathogenesis. Blood. 2016 May 5;127(18):2173\u201381.","journal-title":"Blood"},{"key":"691_CR3","doi-asserted-by":"crossref","unstructured":"Weiss SJ. Tissue destruction by neutrophils. N Engl J Med. 1989 Feb9;320(6):365\u2013376.","DOI":"10.1056\/NEJM198902093200606"},{"issue":"1","key":"691_CR4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1056\/NEJM198007033030109","volume":"303","author":"G Weissmann","year":"1980","unstructured":"Weissmann G, Smolen JE, Korchak HM. Release of inflammatory mediators from stimulated neutrophils. N Engl J Med. 1980 Jul 3;303(1):27\u201334.","journal-title":"N Engl J Med"},{"issue":"1","key":"691_CR5","doi-asserted-by":"crossref","first-page":"300","DOI":"10.1172\/JCI114699","volume":"86","author":"MF Tosi","year":"1990","unstructured":"Tosi MF, Zakem H, Berger M. Neutrophil elastase cleaves C3bi on opsonised pseudomonas as well as CR1 on neutrophils to create a functionally important opsonin receptor mismatch. J Clin Invest. 1990 Jul;86(1):300\u20138.","journal-title":"J Clin Invest"},{"issue":"9","key":"691_CR6","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1136\/thx.39.9.663","volume":"39","author":"LA Smallman","year":"1984","unstructured":"Smallman LA, Hill SL, Stockley RA. Reduction of ciliary beat frequency in vitro by sputum from patients with bronchiectasis: a serine proteinase effect. Thorax. 1984 Sep;39(9):663\u20137.","journal-title":"Thorax"},{"issue":"1","key":"691_CR7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1165\/ajrcmb\/4.1.26","volume":"4","author":"R Amitani","year":"1991","unstructured":"Amitani R, Wilson R, Rutman A, Read R, Ward C, Burnett D, Stockley RA, Cole PJ. Effects of human neutrophil elastase and Pseudomonas Aeruginosa proteinases on human respiratory epithelium. Am J Respir Cell Mol Biol. 1991 Jan;4(1):26\u201332.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"1","key":"691_CR8","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1182\/blood.V63.1.88.88","volume":"63","author":"P Cech","year":"1984","unstructured":"Cech P, Lehrer RI. Phagolysosomal pH of human neutrophils. Blood. 1984 Jan;63(1):88\u201395.","journal-title":"Blood"},{"issue":"3","key":"691_CR9","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1083\/jcb.131.3.775","volume":"131","author":"CA Owen","year":"1995","unstructured":"Owen CA, Campbell MA, Sannes PL, Boukedes SS, Campbell EJ. Cell surface-bound elastase and cathepsin G on human neutrophils: a novel, non-oxidative mechanism by which neutrophils focus and preserve catalytic activity of serine proteinases. J Cell Biol. 1995 Nov;131(3):775\u201389.","journal-title":"J Cell Biol"},{"issue":"5663","key":"691_CR10","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.1126\/science.1092385","volume":"303","author":"V Brinkmann","year":"2004","unstructured":"Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004 Mar 5;303(5663):1532\u20135.","journal-title":"Science"},{"issue":"Suppl 1","key":"691_CR11","doi-asserted-by":"crossref","first-page":"60","DOI":"10.3109\/15412555.2013.764403","volume":"10","author":"RA Sandhaus","year":"2013","unstructured":"Sandhaus RA, Turino G. Neutrophil elastase-mediated lung disease. COPD. 2013 Mar;10(Suppl 1):60\u20133.","journal-title":"COPD."},{"key":"691_CR12","doi-asserted-by":"crossref","unstructured":"Chan SC, Shum DK, Ip MS. Sputum sol neutrophil elastase activity in bronchiectasis: differential modulation by syndecan-1. Am J Respir Crit Care Med 2003 Jul 15;168(2):192-8. Epub 2003 Apr 17.","DOI":"10.1164\/rccm.200208-829OC"},{"key":"691_CR13","doi-asserted-by":"crossref","unstructured":"Korkmaz B, Moreau T, Gauthier F. Neutrophil elastase, proteinase 3 and cathepsin G: physicochemical properties, activity and physiopathological functions. Biochimie 2008 Feb;90(2):227-42. Epub 2007 Oct 25.","DOI":"10.1016\/j.biochi.2007.10.009"},{"key":"691_CR14","first-page":"708608","volume":"2014","author":"J Liu","year":"2014","unstructured":"Liu J, Zhong X, He Z, Wei L, Zheng X, Zhang J, Bai J, Zhong W, Zhong D. Effect of low-dose, long-term roxithromycin on airway inflammation and remodeling of stable noncystic fibrosis bronchiectasis. Mediat Inflamm. 2014;2014:708608.","journal-title":"Mediat Inflamm"},{"issue":"9","key":"691_CR15","doi-asserted-by":"crossref","first-page":"1479","DOI":"10.1183\/09031936.95.08091479","volume":"8","author":"CG Llewellyn-Jones","year":"1995","unstructured":"Llewellyn-Jones CG, Johnson MM, Mitchell JL, Pye A, Okafor VC, Hill SL, Stockley RA. In vivo study of indomethacin in bronchiectasis: effect on neutrophil function and lung secretion. Eur Respir J. 1995 Sep;8(9):1479\u201387.","journal-title":"Eur Respir J"},{"issue":"4","key":"691_CR16","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0002-9343(00)00507-6","volume":"109","author":"AT Hill","year":"2000","unstructured":"Hill AT, Campbell EJ, Hill SL, Bayley DL, Stockley RA. Association between airway bacterial load and markers of airway inflammation in patients with stable chronic bronchitis. Am J Med. 2000 Sep;109(4):288\u201395.","journal-title":"Am J Med"},{"issue":"10","key":"691_CR17","doi-asserted-by":"crossref","first-page":"1384","DOI":"10.1164\/rccm.201605-1027OC","volume":"195","author":"JD Chalmers","year":"2017","unstructured":"Chalmers JD, Moffitt KL, Suarez-Cuartin G, Sibila O, Finch S, Furrie E, Dicker A, Wrobel K, Elborn JS, Walker B, Martin SL, Marshall SE, Huang JT, Fardon TC. Neutrophil Elastase activity is associated with exacerbations and lung function decline in Bronchiectasis. Am J Respir Crit Care Med. 2017 May 15;195(10):1384\u201393.","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"691_CR18","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1136\/thx.39.6.408","volume":"39","author":"RA Stockley","year":"1984","unstructured":"Stockley RA, Hill SL, Morrison HM, Starkie CM. Elastolytic activity of sputum and its relation to purulence and to lung function in patients with bronchiectasis. Thorax. 1984 Jun;39(6):408\u201313.","journal-title":"Thorax"},{"issue":"Pt 1","key":"691_CR19","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1177\/000456329202900111","volume":"29","author":"B Starcher","year":"1992","unstructured":"Starcher B, Scott M. Fractionation of urine to allow desmosine analysis by radioimmunoassay. Ann Clin Biochem. 1992 Jan;29(Pt 1):72\u20138.","journal-title":"Ann Clin Biochem"},{"issue":"16","key":"691_CR20","doi-asserted-by":"crossref","first-page":"1991","DOI":"10.4155\/bio.13.164","volume":"5","author":"O Albarbarawi","year":"2013","unstructured":"Albarbarawi O, Barton A, Miller D, McSharry C, Chaudhuri R, Thomson NC, Palmer CN, Devereux G, Huang JT. Characterization and validation of an isotope-dilution LC-MS\/MS method for quantification of total desmosine and isodesmosine in plasma and serum. Bioanalysis. 2013 Aug;5(16):1991\u20132001.","journal-title":"Bioanalysis"},{"issue":"12","key":"691_CR21","doi-asserted-by":"crossref","first-page":"2400","DOI":"10.1002\/(SICI)1522-2683(19990801)20:12<2400::AID-ELPS2400>3.0.CO;2-T","volume":"20","author":"S Viglio","year":"1999","unstructured":"Viglio S, Valentini G, Chiarelli L, Zanaboni G, Cetta G, Iadarola P. Micellar electrokinetic chromatography as a complementary method to sodium dodecyl sulfate-polyacrylamide gel electrophoresis for studying limited proteolysis of proteins. Electrophoresis. 1999 Sep;20(12):2400\u20136.","journal-title":"Electrophoresis"},{"issue":"4","key":"691_CR22","first-page":"1075","volume":"151","author":"TZ Khan","year":"1995","unstructured":"Khan TZ, Wagener JS, Bost T, Martinez J, Accurso FJ, Riches DW. Early pulmonary inflammation in infants with cystic fibrosis. Am J Respir Crit Care Med. 1995 Apr;151(4):1075\u201382.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"691_CR23","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1164\/rccm.200901-0069OC","volume":"180","author":"PD Sly","year":"2009","unstructured":"Sly PD, Brennan S, Gangell C, de Klerk N, Murray C, Mott L, Stick SM, Robinson PJ, Robertson CF, Ranganathan SC. Australian respiratory early surveillance team for cystic fibrosis (AREST-CF). Lung disease at diagnosis in infants with cystic fibrosis detected by newborn screening. Am J Respir Crit Care Med. 2009 Jul 15;180(2):146\u201352.","journal-title":"Am J Respir Crit Care Med"},{"issue":"9","key":"691_CR24","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1164\/rccm.201203-0507OC","volume":"186","author":"SD Sagel","year":"2012","unstructured":"Sagel SD, Wagner BD, Anthony MM, Emmett P, Zemanick ET. Sputum biomarkers of inflammation and lung function decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2012;186(9):857\u201365.","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"691_CR25","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/S0002-9440(10)62040-8","volume":"167","author":"JA Park","year":"2005","unstructured":"Park JA, He F, Martin LD, Li Y, Chorley BN, Adler KB. Human neutrophil elastase induces hypersecretion of mucin from well-differentiated human bronchial epithelial cells in vitro via a protein kinase C{delta}-mediated mechanism. Am J Pathol. 2005 Sep;167(3):651\u201361.","journal-title":"Am J Pathol"},{"issue":"4","key":"691_CR26","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1136\/thx.2003.014902","volume":"59","author":"F Rubio","year":"2004","unstructured":"Rubio F, Cooley J, Accurso FJ, Remold-O'Donnell E. Linkage of neutrophil serine proteases and decreased surfactant protein-a (SP-A) levels in inflammatory lung disease. Thorax. 2004 Apr;59(4):318\u201323.","journal-title":"Thorax"},{"issue":"8","key":"691_CR27","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1182\/blood.V96.8.2673","volume":"96","author":"PE Van den Steen","year":"2000","unstructured":"Van den Steen PE, Proost P, Wuyts A, Van Damme J, Opdenakker G. Neutrophil gelatinase B potentiates interleukin-8 tenfold by aminoterminal processing,whereas it degrades CTAP-III, PF-4, and GRO-alpha and leaves RANTES and MCP-2 intact. Blood. 2000 Oct 15;96(8):2673\u201381.","journal-title":"Blood"},{"issue":"7","key":"691_CR28","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1086\/423821","volume":"190","author":"MP Rogan","year":"2004","unstructured":"Rogan MP, Taggart CC, Greene CM, Murphy PG, O'Neill SJ, McElvaney NG. Loss of microbicidal activity and increased formation of biofilm due to decreased lactoferrin activity in patients with cystic fibrosis. J Infect Dis. 2004 Oct 1;190(7):1245\u201353.","journal-title":"J Infect Dis"},{"issue":"47","key":"691_CR29","doi-asserted-by":"crossref","first-page":"32377","DOI":"10.1074\/jbc.M803707200","volume":"283","author":"N Guyot","year":"2008","unstructured":"Guyot N, Butler MW, McNally P, Weldon S, Greene CM, Levine RL, O\u2019Neill SJ, Taggart CC, McElvaney NG. Elafin, an elastase-specific inhibitor, is cleaved by its cognate enzyme neutrophil elastase in sputum from individuals with cystic fibrosis. J Biol Chem. 2008 Nov 21;283(47):32377\u201385.","journal-title":"J Biol Chem"},{"issue":"9","key":"691_CR30","doi-asserted-by":"crossref","first-page":"4842","DOI":"10.4049\/jimmunol.154.9.4842","volume":"154","author":"G D\u00f6ring","year":"1995","unstructured":"D\u00f6ring G, Frank F, Boudier C, Herbert S, Fleischer B, Bellon G. Cleavage of lymphocyte surface antigens CD2, CD4, and CD8 by polymorphonuclear leukocyte elastase and cathepsin G in patients with cystic fibrosis. J Immunol. 1995 May 1;154(9):4842\u201350.","journal-title":"J Immunol"},{"issue":"12","key":"691_CR31","doi-asserted-by":"crossref","first-page":"1423","DOI":"10.1038\/nm1690","volume":"13","author":"D Hartl","year":"2007","unstructured":"Hartl D, Latzin P, Hordijk P, Marcos V, Rudolph C, Woischnik M, Krauss-Etschmann S, Koller B, Reinhardt D, Roscher AA, Roos D, Griese M. Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis in lung disease. Nat Med. 2007 Dec;13(12):1423\u201330.","journal-title":"Nat Med"},{"issue":"42","key":"691_CR32","doi-asserted-by":"crossref","first-page":"32227","DOI":"10.1074\/jbc.M110.155259","volume":"285","author":"M Gentzsch","year":"2010","unstructured":"Gentzsch M, Dang H, Dang Y, Garcia-Caballero A, Suchindran H, Boucher RC, Stutts MJ. The cystic fibrosis transmembrane conductance regulator impende proteolytic stimulation of the epithelial Na+ channel. J Biol Chem. 2010 Oct 15;285(42):32227\u201332.","journal-title":"J Biol Chem"},{"issue":"2","key":"691_CR33","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1164\/rccm.201205-0875OC","volume":"187","author":"M Le Gars","year":"2013","unstructured":"Le Gars M, Descamps D, Roussel D, Saussereau E, Guillot L, Ruffin M, Tabary O, Hong SS, Boulanger P, Paulais M, Malleret L, Belaaouaj A, Edelman A, Huerre M, Chignard M, Sallenave JM. Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo. Am J Respir Crit Care Med. 2013 Jan 15;187(2):170\u20139.","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"691_CR34","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1183\/09031936.00194611","volume":"40","author":"JS Elborn","year":"2012","unstructured":"Elborn JS, Perrett J, Forsman-Semb K, Marks-Konczalik J, Gunawardena K, Entwistle N. Efficacy, safety and effect on biomarkers of AZD9668 in cystic fibrosis. Eur Respir J. 2012 Oct;40(4):969\u201376.","journal-title":"Eur Respir J"},{"issue":"2","key":"691_CR35","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1183\/09031936.00047306","volume":"29","author":"M Griese","year":"2007","unstructured":"Griese M, Latzin P, Kappler M, Weckerle K, Heinzlmaier T, Bernhardt T, Hartl D. alpha1-antitrypsin inhalation reduces airway inflammation in cystic fibrosis patients. Eur Respir J. 2007 Feb;29(2):240\u201350.","journal-title":"Eur Respir J"},{"issue":"3","key":"691_CR36","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1136\/thx.51.3.267","volume":"51","author":"D St\u0103nescu","year":"1996","unstructured":"St\u0103nescu D, Sanna A, Veriter C, Kostianev S, Calcagni PG, Fabbri LM, Maestrelli P. Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. Thorax. 1996 Mar;51(3):267\u201371.","journal-title":"Thorax"},{"issue":"6","key":"691_CR37","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1165\/rcmb.2009-0220TR","volume":"41","author":"PJ Barnes","year":"2009","unstructured":"Barnes PJ. The cytokine network in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol. 2009 Dec;41(6):631\u20138.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"11","key":"691_CR38","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1164\/rccm.200807-1148OC","volume":"179","author":"TR Richens","year":"2009","unstructured":"Richens TR, Linderman DJ, Horstmann SA, Lambert C, Xiao YQ, Keith RL, Bo\u00e9 DM, Morimoto K, Bowler RP, Day BJ, Janssen WJ, Henson PM, Vandivier RW. Cigarette smoke impairs clearance of apoptotic cells through oxidant-dependent activation of RhoA. Am J Respir Crit Care Med. 2009 Jun 1;179(11):1011\u201321.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"691_CR39","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1172\/JCI112600","volume":"78","author":"VV Damiano","year":"1986","unstructured":"Damiano VV, Tsang A, Kucich U, Abrams WR, Rosenbloom J, Kimbel P, Fallahnejad M, Weinbaum G. Immunolocalization of elastase in human emphysematous lungs. J Clin Invest. 1986 Aug;78(2):482\u201393.","journal-title":"J Clin Invest"},{"issue":"6\u20137","key":"691_CR40","doi-asserted-by":"crossref","first-page":"1287","DOI":"10.1016\/j.biocel.2007.12.008","volume":"40","author":"G Lungarella","year":"2008","unstructured":"Lungarella G, Cavarra E, Lucattelli M, Martorana PA. The dual role of neutrophil elastase in lung destruction and repair. Int J Biochem Cell Biol. 2008;40(6\u20137):1287\u201396.","journal-title":"Int J Biochem Cell Biol"},{"issue":"6","key":"691_CR41","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1016\/S0002-9440(10)63589-4","volume":"163","author":"SD Shapiro","year":"2003","unstructured":"Shapiro SD, Goldstein NM, Houghton AM, Kobayashi DK, Kelley D, Belaaouaj A. Neutrophil elastase contributes to cigarette smoke-induced emphysema in mice. Am J Pathol. 2003 Dec;163(6):2329\u201335.","journal-title":"Am J Pathol"},{"issue":"2","key":"691_CR42","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1155\/2011\/139493","volume":"31","author":"G Paone","year":"2011","unstructured":"Paone G, Conti V, Vestri A, Leone A, Puglisi G, Benassi F, Brunetti G, Schmid G, Cammarella I, Terzano C. Analysis of sputum markers in the evaluation of lung inflammation and functional impairment in symptomatic smokers and COPD patients. Dis Markers. 2011;31(2):91\u2013100.","journal-title":"Dis Markers"},{"issue":"1","key":"691_CR43","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1124\/jpet.111.182139","volume":"339","author":"T Stevens","year":"2011","unstructured":"Stevens T, Ekholm K, Gr\u00e4nse M, Lindahl M, Kozma V, Jungar C, Ottosson T, Falk-H\u00e5kansson H, Churg A, Wright JL, Lal H, Sanfridson A. AZD9668: pharmacological characterization of a novel oral inhibitor of neutrophil elastase. J Pharmacol Exp Ther. 2011 Oct;339(1):313\u201320.","journal-title":"J Pharmacol Exp Ther"},{"issue":"4","key":"691_CR44","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1016\/j.rmed.2011.10.020","volume":"106","author":"P Kuna","year":"2012","unstructured":"Kuna P, Jenkins M, O'Brien CD, Fahy WA. AZD9668, a neutrophil elastase inhibitor, plus ongoing budesonide\/formoterol in patients with COPD. Respir Med. 2012 Apr;106(4):531\u20139.","journal-title":"Respir Med"},{"issue":"2","key":"691_CR45","doi-asserted-by":"crossref","first-page":"111","DOI":"10.3109\/15412555.2011.641803","volume":"9","author":"C Vogelmeier","year":"2012","unstructured":"Vogelmeier C, Aquino TO, O'Brien CD, Perrett J, Gunawardena KA. A randomised, placebo-controlled, dose-finding study of AZD9668, an oral inhibitor of neutrophil elastase, in patients with chronic obstructive pulmonary disease treated with tiotropium. COPD. 2012 Apr;9(2):111\u201320.","journal-title":"COPD"},{"issue":"9991","key":"691_CR46","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/S0140-6736(15)60860-1","volume":"386","author":"KR Chapman","year":"2015","unstructured":"Chapman KR, Burdon JG, Piitulainen E, Sandhaus RA, Seersholm N, Stocks JM, Stoel BC, Huang L, Yao Z, Edelman JM, NG ME. RAPID trial study group. Intravenous augmentation treatment and lung density in severe \u03b11 antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet. 2015 Jul 25;386(9991):360\u20138.","journal-title":"Lancet"},{"issue":"5","key":"691_CR47","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1378\/chest.119.5.1329","volume":"119","author":"PG Gibson","year":"2001","unstructured":"Gibson PG, Simpson JL, Saltos N. Heterogeneity of airway inflammation in persistent asthma: evidence of neutrophilic inflammation and increased sputum interleukin-8. Chest. 2001 May;119(5):1329\u201336.","journal-title":"Chest"},{"issue":"5","key":"691_CR48","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1111\/j.1365-2222.2006.02493.x","volume":"36","author":"R Louis","year":"2006","unstructured":"Louis R, Djukanovic R. Is the neutrophil a worthy target in severe asthma and chronic obstructive pulmonary disease? Clin Exp Allergy. 2006 May;36(5):563\u20137.","journal-title":"Clin Exp Allergy"},{"issue":"5","key":"691_CR49","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1164\/rccm.200503-369OC","volume":"172","author":"JL Simpson","year":"2005","unstructured":"Simpson JL, Scott RJ, Boyle MJ, Gibson PG. Differential proteolytic enzyme activity in eosinophilic and neutrophilic asthma. Am J Respir Crit Care Med. 2005 Sep 1;172(5):559\u201365.","journal-title":"Am J Respir Crit Care Med"},{"issue":"5","key":"691_CR50","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1183\/09031936.00119114","volume":"45","author":"JD Chalmers","year":"2015","unstructured":"Chalmers JD, Aliberti S, Blasi F. Management of bronchiectasis in adults. Eur Respir J. 2015 May;45(5):1446\u201362.","journal-title":"Eur Respir J"},{"issue":"3","key":"691_CR51","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1183\/13993003.01888-2015","volume":"48","author":"S Aliberti","year":"2016","unstructured":"Aliberti S, Masefield S, Polverino E, De Soyza A, Loebinger MR, Menendez R, Ringshausen FC, Vendrell M, Powell P, Chalmers JD, EMBARC Study Group. Research priorities in bronchiectasis: a consensus statement from the EMBARC clinical research collaboration. Eur Respir J. 2016 Sep;48(3):632\u201347.","journal-title":"Eur Respir J"},{"issue":"3","key":"691_CR52","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1159\/000455880","volume":"93","author":"F Amati","year":"2017","unstructured":"Amati F, Franceschi E, Gramegna A, Chalmers JD, Aliberti S. Investigating the etiology of Bronchiectasis: you do not find what you do not look for. Respiration. 2017;93(3):228\u20139.","journal-title":"Respiration"},{"key":"691_CR53","doi-asserted-by":"crossref","first-page":"642503","DOI":"10.1155\/2015\/642503","volume":"2015","author":"FL Dente","year":"2015","unstructured":"Dente FL, Bilotta M, Bartoli ML, et al. Neutrophilic bronchial inflammation correlates with clinical and functional findings in patients with noncystic fibrosis Bronchiectasis. Mediat Inflamm. 2015;2015:642503.","journal-title":"Mediat Inflamm"},{"key":"691_CR54","doi-asserted-by":"crossref","unstructured":"Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med 2009 Aug 18;151(4):264-9, W64.","DOI":"10.7326\/0003-4819-151-4-200908180-00135"},{"issue":"4","key":"691_CR55","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.rmed.2012.12.009","volume":"107","author":"R Stockley","year":"2013","unstructured":"Stockley R, De Soyza A, Gunawardena K, Perrett J, Forsman-Semb K, Entwistle N, Snell N. Phase II study of a neutrophil elastase inhibitor (AZD9668) in patients with bronchiectasis. Respir Med. 2013 Apr;107(4):524\u201333.","journal-title":"Respir Med"},{"issue":"4","key":"691_CR56","doi-asserted-by":"crossref","first-page":"1217","DOI":"10.1164\/ajrccm.155.4.9105057","volume":"155","author":"H Nakamura","year":"1997","unstructured":"Nakamura H, Abe S, Shibata Y, Yuki H, Suzuki H, Saito H, Sata M, Kato S, Tomoike H. Elevated levels of cytokeratin 19 in the bronchoalveolar lavage fluid of patients with chronic airway inflammatory diseases--a specific marker for bronchial epithelial injury. Am J Respir Crit Care Med. 1997 Apr;155(4):1217\u201321.","journal-title":"Am J Respir Crit Care Med"},{"issue":"8","key":"691_CR57","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1136\/thx.53.8.685","volume":"53","author":"M Gaga","year":"1998","unstructured":"Gaga M, Bentley AM, Humbert M, Barkans J, O'Brien F, Wathen CG, Kay AB, Durham SR. Increases in CD4+ T lymphocytes, macrophages, neutrophils and interleukin 8 positive cells in the airways of patients with bronchiectasis. Thorax. 1998 Aug;53(8):685\u201391.","journal-title":"Thorax"},{"issue":"5","key":"691_CR58","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1172\/JCI0213572","volume":"109","author":"RW Vandivier","year":"2002","unstructured":"Vandivier RW, Fadok VA, Hoffmann PR, Bratton DL, Penvari C, Brown KK, Brain JD, Accurso FJ, Henson PM. Elastase-mediated phosphatidylserine receptor cleavage impairs apoptotic cell clearance in cystic fibrosis and bronchiectasis. J Clin Invest. 2002 Mar;109(5):661\u201370.","journal-title":"J Clin Invest"},{"issue":"10","key":"691_CR59","doi-asserted-by":"crossref","first-page":"792","DOI":"10.1053\/rmed.2001.1155","volume":"95","author":"L Zheng","year":"2001","unstructured":"Zheng L, Shum H, Tipoe GL, Leung R, Lam WK, Ooi GC, Tsang KW. Macrophages, neutrophils and tumour necrosis factor-alpha expression in bronchiectatic airways in vivo. Respir Med. 2001 Oct;95(10):792\u20138.","journal-title":"Respir Med"},{"issue":"1","key":"691_CR60","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1378\/chest.102.1.129","volume":"102","author":"J Fujita","year":"1992","unstructured":"Fujita J, Nakamura H, Yamagishi Y, Yamaji Y, Shiotani T, Irino S. Elevation of plasma truncated elastase alpha 1-proteinase inhibitor complexes in patients with inflammatory lung diseases. Chest. 1992 Jul;102(1):129\u201334.","journal-title":"Chest"},{"issue":"5","key":"691_CR61","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1165\/rcmb.2008-0185OC","volume":"41","author":"SC Chan","year":"2009","unstructured":"Chan SC, Leung VO, Ip MS, Shum DK. Shed syndecan-1 restricts neutrophil elastase from alpha1-antitrypsin in neutrophilic airway inflammation. Am J Respir Cell Mol Biol. 2009 Nov;41(5):620\u20138.","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"9","key":"691_CR62","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1164\/ajrccm.164.9.2105083","volume":"164","author":"J Angrill","year":"2001","unstructured":"Angrill J, Agust\u00ed C, De Celis R, Filella X, Ra\u00f1\u00f3 A, Elena M, De La Bellacasa JP, Xaubet A, Torres A. Bronchial inflammation and colonization in patients with clinically stable bronchiectasis. Am J Respir Crit Care Med. 2001 Nov 1;164(9):1628\u201332.","journal-title":"Am J Respir Crit Care Med"},{"issue":"2","key":"691_CR63","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/thx.47.2.88","volume":"47","author":"P Lloberes","year":"1992","unstructured":"Lloberes P, Montserrat E, Montserrat JM, Picado C. Sputum sol phase proteins and elastase activity in patients with clinically stable bronchiectasis. Thorax. 1992 Feb;47(2):88\u201392.","journal-title":"Thorax"},{"issue":"4","key":"691_CR64","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1046\/j.1440-1843.1999.00208.x","volume":"4","author":"W Ichikawa","year":"1999","unstructured":"Ichikawa W, Ogushi F, Tani K, Maniwa K, Kamada M, Ohmoto Y, Sakatani M, Sone S. Characterization of immunoglobulin binding factor in sputum from patients with chronic airway diseases. Respirology. 1999 Dec;4(4):375\u201381.","journal-title":"Respirology"},{"issue":"5","key":"691_CR65","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1136\/thorax.56.5.366","volume":"56","author":"RA Stockley","year":"2001","unstructured":"Stockley RA, Bayley D, Hill SL, Hill AT, Crooks S, Campbell EJ. Assessment of airway neutrophils by sputum colour: correlation with airways inflammation. Thorax. 2001 May;56(5):366\u201372.","journal-title":"Thorax"},{"issue":"2","key":"691_CR66","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1111\/resp.12219","volume":"19","author":"PC Goeminne","year":"2014","unstructured":"Goeminne PC, Vandooren J, Moelants EA, Decraene A, Rabaey E, Pauwels A, Seys S, Opdenakker G, Proost P, Dupont LJ. The sputum colour chart as a predictor of lung inflammation, proteolysis and damage in non-cystic fibrosis bronchiectasis: a case-control analysis. Respirology. 2014 Feb;19(2):203\u201310.","journal-title":"Respirology"},{"issue":"7","key":"691_CR67","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1164\/rccm.201203-0487OC","volume":"186","author":"JD Chalmers","year":"2012","unstructured":"Chalmers JD, Smith MP, McHugh BJ, Doherty C, Govan JR, Hill AT. Short- and long term antibiotic treatment reduces airway and systemic inflammation in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2012 Oct 1;186(7):657\u201365.","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"691_CR68","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1159\/000029463","volume":"67","author":"B Schaaf","year":"2000","unstructured":"Schaaf B, Wieghorst A, Aries SP, Dalhoff K, Braun J. Neutrophil inflammation and activation in bronchiectasis: comparison with pneumonia and idiopathic pulmonary fibrosis. Respiration. 2000;67(1):52\u20139.","journal-title":"Respiration"},{"issue":"1","key":"691_CR69","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1034\/j.1399-3003.2000.16a26.x","volume":"16","author":"L Zheng","year":"2000","unstructured":"Zheng L, Tipoe G, Lam WK, Ho JC, Shum I, Ooi GC, Leung R, Tsang KW. Endothelin-1 in stable bronchiectasis. Eur Respir J. 2000 Jul;16(1):146\u20139.","journal-title":"Eur Respir J"},{"issue":"4","key":"691_CR70","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1183\/13993003.01899-2015","volume":"47","author":"S Aliberti","year":"2016","unstructured":"Aliberti S, Lonni S, Dore S, McDonnell MJ, Goeminne PC, Dimakou K, Fardon TC, Rutherford R, Pesci A, Restrepo MI, Sotgiu G, Chalmers JD. Clinical phenotypes in adult patients with bronchiectasis. Eur Respir J. 2016 Apr;47(4):1113\u201322.","journal-title":"Eur Respir J"},{"issue":"6","key":"691_CR71","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/0954-6111(93)90072-8","volume":"87","author":"M Ip","year":"1993","unstructured":"Ip M, Shum D, Lauder I, Lam WK, So SY. Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis. Respir Med. 1993 Aug;87(6):449\u201354.","journal-title":"Respir Med"},{"issue":"3","key":"691_CR72","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1136\/thx.2003.008037","volume":"59","author":"AP Watt","year":"2004","unstructured":"Watt AP, Brown V, Courtney J, Kelly M, Garske L, Elborn JS, Ennis M. Neutrophil apoptosis, proinflammatory mediators and cell counts in bronchiectasis. Thorax. 2004 Mar;59(3):231\u20136.","journal-title":"Thorax"},{"issue":"7","key":"691_CR73","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1016\/j.rmed.2013.04.006","volume":"107","author":"P Mandal","year":"2013","unstructured":"Mandal P, Morice AH, Chalmers JD, Hill AT. Symptoms of airway reflux predict exacerbations and quality of life in bronchiectasis. Respir Med. 2013 Jul;107(7):1008\u201313.","journal-title":"Respir Med"},{"issue":"1","key":"691_CR74","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/BF01489487","volume":"15","author":"R Sepper","year":"1995","unstructured":"Sepper R, Konttinen YT, Ingman T, Sorsa T. Presence, activities, and molecular forms of cathepsin G, elastase, alpha 1-antitrypsin, and alpha 1-antichymotrypsin in bronchiectasis. J Clin Immunol. 1995 Jan;15(1):27\u201334.","journal-title":"J Clin Immunol"},{"issue":"2","key":"691_CR75","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1378\/chest.117.2.420","volume":"117","author":"KW Tsang","year":"2000","unstructured":"Tsang KW, Chan K, Ho P, Zheng L, Ooi GC, Ho JC, Lam W. Sputum elastase in steady-state bronchiectasis. Chest. 2000 Feb;117(2):420\u20136.","journal-title":"Chest"},{"issue":"11","key":"691_CR76","first-page":"1602","volume":"12","author":"S Finch","year":"2015","unstructured":"Finch S, McDonnell MJ, Abo-Leyah H, Aliberti S, Chalmers JD. A comprehensive analysis of the impact of Pseudomonas Aeruginosa colonization on prognosis in adult Bronchiectasis. Ann Am Thorac Soc. 2015 Nov;12(11):1602\u201311.","journal-title":"Ann Am Thorac Soc"},{"issue":"4","key":"691_CR77","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1164\/rccm.201005-0756OC","volume":"183","author":"MP Murray","year":"2011","unstructured":"Murray MP, Govan JR, Doherty CJ, Simpson AJ, Wilkinson TS, Chalmers JD, Greening AP, Haslett C, Hill AT. A randomized controlled trial of nebulized gentamicin in non-cystic fibrosis bronchiectasis. Am J Respir Crit Care Med. 2011 Feb 15;183(4):491\u20139.","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"691_CR78","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1183\/09031936.99.13613809","volume":"13","author":"H Nakamura","year":"1999","unstructured":"Nakamura H, Fujishima S, Inoue T, Ohkubo Y, Soejima K, Waki Y, Mori M, Urano T, Sakamaki F, Tasaka S, Ishizaka A, Kanazawa M, Yamaguchi K. Clinical and immunoregulatory effects of roxithromycin therapy for chronic respiratory tract infection. Eur Respir J. 1999 Jun;13(6):1371\u20139.","journal-title":"Eur Respir J"},{"issue":"4","key":"691_CR79","doi-asserted-by":"crossref","first-page":"288","DOI":"10.5414\/CP201674","volume":"51","author":"KA Gunawardena","year":"2013","unstructured":"Gunawardena KA, Gullstrand H, Perrett J. Pharmacokinetics and safety of AZD9668, an oral neutrophil elastase inhibitor, in healthy volunteers and patients with COPD. Int J Clin Pharmacol Ther. 2013 Apr;51(4):288\u2013304.","journal-title":"Int J Clin Pharmacol Ther"},{"issue":"7","key":"691_CR80","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1002\/cmdc.201500131","volume":"10","author":"F von Nussbaum","year":"2015","unstructured":"von Nussbaum F, Li VM, Allerheiligen S, Anlauf S, B\u00e4rfacker L, Bechem M, Delbeck M, Fitzgerald MF, Gerisch M, Gielen-Haertwig H, Haning H, Karthaus D, Lang D, Lustig K, Meibom D, Mittendorf J, Rosentreter U, Sch\u00e4fer M, Sch\u00e4fer S, Schamberger J, Telan LA, Tersteegen A. Freezing the bioactive conformation to boost potency: the identification of BAY 85-8501, a selective and potent inhibitor of human Neutrophil Elastase for pulmonary diseases. ChemMedChem. 2015 Jul;10(7):1163\u201373.","journal-title":"ChemMedChem"},{"key":"691_CR81","doi-asserted-by":"crossref","unstructured":"Watz H, Pedersen F, Kirsten A, Nagelschmitz J, Bandel TJ, Schwers S, Rabe K. Safety and tolerability of the NE inhibitor BAY 85-8501 in patients with non-CF bronchiectasis. ERS International Congress 2016.","DOI":"10.1183\/13993003.congress-2016.PA4088"},{"key":"691_CR82","doi-asserted-by":"crossref","unstructured":"Miglietta D, Carnini C, Puviani V, Finch H, Fox C, Fitzgerald M, Patacchini R, Civelli M, Villetti G. Pharmacological characterization of CHF6333, a novel potent inhaled inhibitor of neutrophil elastase. ERS International Congress 2016.","DOI":"10.1183\/13993003.congress-2016.OA4539"}],"container-title":["Respiratory Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12931-017-0691-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T01:41:30Z","timestamp":1693359690000},"score":1,"resource":{"primary":{"URL":"https:\/\/respiratory-research.biomedcentral.com\/articles\/10.1186\/s12931-017-0691-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,12]]},"references-count":82,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2017,12]]}},"alternative-id":["691"],"URL":"https:\/\/doi.org\/10.1186\/s12931-017-0691-x","relation":{},"ISSN":["1465-993X"],"issn-type":[{"value":"1465-993X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,12]]},"article-number":"211"}}