{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T11:25:24Z","timestamp":1790162724689,"version":"4.1.0"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T00:00:00Z","timestamp":1556236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006501","name":"Cystic Fibrosis Foundation Therapeutics","doi-asserted-by":"publisher","award":["LIOU13A0, LIOU14Y4"],"award-info":[{"award-number":["LIOU13A0, LIOU14Y4"]}],"id":[{"id":"10.13039\/100006501","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL125520"],"award-info":[{"award-number":["HL125520"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006415","name":"Ben B. and Iris M. Margolis Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006415","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Claudia Ruth Goodrich Stevens Family Endowment Fund","award":["None"],"award-info":[{"award-number":["None"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Med Res Methodol"],"published-print":{"date-parts":[[2019,12]]},"DOI":"10.1186\/s12874-019-0705-0","type":"journal-article","created":{"date-parts":[[2019,4,26]],"date-time":"2019-04-26T12:05:13Z","timestamp":1556280313000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Prospective multicenter randomized patient recruitment and sample collection to enable future measurements of sputum biomarkers of inflammation in an observational study of cystic fibrosis"],"prefix":"10.1186","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0121-4847","authenticated-orcid":false,"given":"Theodore G.","family":"Liou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederick R.","family":"Adler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Argel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fadi","family":"Asfour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry S.","family":"Brown","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara A.","family":"Chatfield","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cori L.","family":"Daines","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dixie","family":"Durham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica A.","family":"Francis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Glover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Heynekamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Hoidal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judy L.","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Keogh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol M.","family":"Kopecky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noah","family":"Lechtzin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanping","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerimiah","family":"Lysinger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osmara","family":"Molina","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristyn A.","family":"Packer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie R.","family":"Poch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra L.","family":"Quittner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peggy","family":"Radford","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abby J.","family":"Redway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott D.","family":"Sagel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shawna","family":"Sprandel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Taylor-Cousar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane B.","family":"Vroom","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Yoshikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John P.","family":"Clancy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Stuart","family":"Elborn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth N.","family":"Olivier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David R.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,26]]},"reference":[{"issue":"8","key":"705_CR1","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1164\/rccm.200304-505SO","volume":"168","author":"RL Gibson","year":"2003","unstructured":"Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med. 2003;168(8):918\u201351.","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"705_CR2","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1513\/pats.200703-044BR","volume":"4","author":"SD Sagel","year":"2007","unstructured":"Sagel SD, Chmiel JF, Konstan MW. Sputum biomarkers of inflammation in cystic fibrosis lung disease. Proc Am Thorac Soc. 2007;4(4):406\u201317.","journal-title":"Proc Am Thorac Soc"},{"issue":"8","key":"705_CR3","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1164\/rccm.200609-1354OC","volume":"175","author":"N Mayer-Hamblett","year":"2007","unstructured":"Mayer-Hamblett N, Aitken ML, Accurso FJ, et al. Association between pulmonary function and sputum biomarkers in cystic fibrosis. Am J Respir Crit Care Med. 2007;175(8):822\u20138.","journal-title":"Am J Respir Crit Care Med"},{"issue":"6","key":"705_CR4","doi-asserted-by":"publisher","first-page":"2111","DOI":"10.1164\/ajrccm.152.6.8520783","volume":"152","author":"TL Bonfield","year":"1995","unstructured":"Bonfield TL, Panuska JR, Konstan MW, et al. Inflammatory cytokines in cystic fibrosis lungs. Am J Respir Crit Care Med. 1995;152(6 Pt 1):2111\u20138.","journal-title":"Am J Respir Crit Care Med"},{"key":"705_CR5","doi-asserted-by":"crossref","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;186:857\u201365.","DOI":"10.1164\/rccm.201203-0507OC"},{"issue":"8","key":"705_CR6","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1164\/rccm.201111-2068WS","volume":"185","author":"BW Ramsey","year":"2012","unstructured":"Ramsey BW, Banks-Schlegel S, Accurso FJ, et al. Future directions in early cystic fibrosis lung disease research: an NHLBI workshop report. Am J Respir Crit Care Med. 2012;185(8):887\u201392.","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"705_CR7","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1002\/ppul.20563","volume":"42","author":"H Levy","year":"2007","unstructured":"Levy H, Kalish LA, Huntington I, et al. Inflammatory markers of lung disease in adult patients with cystic fibrosis. Pediatr Pulmonol. 2007;42(3):256\u201362.","journal-title":"Pediatr Pulmonol"},{"issue":"9","key":"705_CR8","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1164\/rccm.200803-387OC","volume":"178","author":"M Saavedra","year":"2008","unstructured":"Saavedra M, Hughes G, Sanders L, et al. Circulating RNA transcripts identify therapeutic response in cystic fibrosis lung disease. Am J Respir Crit Care Med. 2008;178(9):929\u201338.","journal-title":"Am J Respir Crit Care Med"},{"issue":"4","key":"705_CR9","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1093\/aje\/153.4.345","volume":"153","author":"TG Liou","year":"2001","unstructured":"Liou TG, Adler FR, Fitzsimmons SC, Cahill BC, Hibbs JR, Marshall BC. Predictive 5-year survivorship model of cystic fibrosis. Am J Epidemiol. 2001;153(4):345\u201352.","journal-title":"Am J Epidemiol"},{"issue":"1","key":"705_CR10","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1016\/j.jcf.2011.08.007","volume":"11","author":"R Buzzetti","year":"2012","unstructured":"Buzzetti R, Alicandro G, Minicucci L, et al. Validation of a predictive survival model in Italian patients with cystic fibrosis. J Cyst Fibros Off J Eur Cyst Fibros Soc. 2012;11(1):24\u20139.","journal-title":"J Cyst Fibros Off J Eur Cyst Fibros Soc"},{"issue":"10","key":"705_CR11","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1056\/NEJM199409083311003","volume":"331","author":"HJ Fuchs","year":"1994","unstructured":"Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. N Engl J Med. 1994;331(10):637\u201342.","journal-title":"N Engl J Med"},{"issue":"1","key":"705_CR12","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1056\/NEJM199901073400104","volume":"340","author":"BW Ramsey","year":"1999","unstructured":"Ramsey BW, Pepe MS, Quan JM, et al. Intermittent Administration of Inhaled Tobramycin in patients with cystic fibrosis. N Engl J Med. 1999;340(1):23\u201330.","journal-title":"N Engl J Med"},{"issue":"13","key":"705_CR13","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1001\/jama.290.13.1749","volume":"290","author":"L Saiman","year":"2003","unstructured":"Saiman L, Marshall BC, Mayer-Hamblett N, et al. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA J Am Med Assoc. 2003;290(13):1749\u201356.","journal-title":"JAMA J Am Med Assoc"},{"issue":"3","key":"705_CR14","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1056\/NEJMoa043900","volume":"354","author":"MR Elkins","year":"2006","unstructured":"Elkins MR, Robinson M, Rose BR, et al. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006;354(3):229\u201340.","journal-title":"N Engl J Med"},{"issue":"5","key":"705_CR15","doi-asserted-by":"publisher","first-page":"1223","DOI":"10.1378\/chest.08-1421","volume":"135","author":"GZ Retsch-Bogart","year":"2009","unstructured":"Retsch-Bogart GZ, Quittner AL, Gibson RL, et al. Efficacy and safety of inhaled aztreonam lysine for airway pseudomonas in cystic fibrosis. Chest. 2009;135(5):1223\u201332.","journal-title":"Chest"},{"issue":"18","key":"705_CR16","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1056\/NEJMoa1105185","volume":"365","author":"BW Ramsey","year":"2011","unstructured":"Ramsey BW, Davies J, McElvaney NG, et al. A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011;365(18):1663\u201372.","journal-title":"N Engl J Med"},{"issue":"7","key":"705_CR17","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/S2213-2600(14)70132-8","volume":"2","author":"MP Boyle","year":"2014","unstructured":"Boyle MP, Bell SC, Konstan MW, et al. A CFTR corrector (lumacaftor) and a CFTR potentiator (ivacaftor) for treatment of patients with cystic fibrosis who have a phe508del CFTR mutation: a phase 2 randomised controlled trial. Lancet Respir Med. 2014;2(7):527\u201338.","journal-title":"Lancet Respir Med"},{"issue":"17","key":"705_CR18","doi-asserted-by":"publisher","first-page":"1707","DOI":"10.1001\/jama.2010.563","volume":"303","author":"L Saiman","year":"2010","unstructured":"Saiman L, Anstead M, Mayer-Hamblett N, et al. Effect of azithromycin on pulmonary function in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2010;303(17):1707\u201315.","journal-title":"JAMA"},{"issue":"2","key":"705_CR19","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1136\/thx.2008.100073","volume":"64","author":"KJ Fidler","year":"2009","unstructured":"Fidler KJ, Hilliard TN, Bush A, et al. Mannose-binding lectin is present in the infected airway: a possible pulmonary defence mechanism. Thorax. 2009;64(2):150\u20135.","journal-title":"Thorax"},{"issue":"3","key":"705_CR20","doi-asserted-by":"publisher","first-page":"528","DOI":"10.1111\/j.1365-2249.2003.02385.x","volume":"135","author":"C Hubeau","year":"2004","unstructured":"Hubeau C, Le Naour R, Ab\u00e9ly M, et al. Dysregulation of IL-2 and IL-8 production in circulating T lymphocytes from young cystic fibrosis patients. Clin Exp Immunol. 2004;135(3):528\u201334.","journal-title":"Clin Exp Immunol"},{"issue":"3","key":"705_CR21","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1164\/ajrccm.155.3.9116985","volume":"155","author":"DY Koller","year":"1997","unstructured":"Koller DY, Nething I, Otto J, Urbanek R, Eichler I. Cytokine concentrations in sputum from patients with cystic fibrosis and their relation to eosinophil activity. Am J Respir Crit Care Med. 1997;155(3):1050\u20134.","journal-title":"Am J Respir Crit Care Med"},{"issue":"25","key":"705_CR22","doi-asserted-by":"crossref","first-page":"16722","DOI":"10.1016\/S0021-9258(18)55361-8","volume":"266","author":"J Merenmies","year":"1991","unstructured":"Merenmies J, Pihlaskari R, Laitinen J, Wartiovaara J, Rauvala H. 30-kDa heparin-binding protein of brain (amphoterin) involved in neurite outgrowth. Amino acid sequence and localization in the filopodia of the advancing plasma membrane. J Biol Chem. 1991;266(25):16722\u20139.","journal-title":"J Biol Chem"},{"issue":"5425","key":"705_CR23","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1126\/science.285.5425.248","volume":"285","author":"H Wang","year":"1999","unstructured":"Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science. 1999;285(5425):248\u201351.","journal-title":"Science"},{"issue":"8","key":"705_CR24","doi-asserted-by":"publisher","first-page":"822","DOI":"10.1164\/rccm.200712-1894OC","volume":"178","author":"SM Rowe","year":"2008","unstructured":"Rowe SM, Jackson PL, Liu G, et al. Potential role of high-mobility group box 1 in cystic fibrosis airway disease. Am J Respir Crit Care Med. 2008;178(8):822\u201331.","journal-title":"Am J Respir Crit Care Med"},{"issue":"8","key":"705_CR25","doi-asserted-by":"publisher","first-page":"e42748","DOI":"10.1371\/journal.pone.0042748","volume":"7","author":"TG Liou","year":"2012","unstructured":"Liou TG, Adler FR, Keogh RH, et al. Sputum biomarkers and the prediction of clinical outcomes in patients with cystic fibrosis. PLoS One. 2012;7(8):e42748.","journal-title":"PLoS One"},{"issue":"5","key":"705_CR26","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1164\/rccm.200703-409OC","volume":"178","author":"RD Gray","year":"2008","unstructured":"Gray RD, MacGregor G, Noble D, et al. Sputum proteomics in inflammatory and suppurative respiratory diseases. Am J Respir Crit Care Med. 2008;178(5):444\u201352.","journal-title":"Am J Respir Crit Care Med"},{"issue":"3","key":"705_CR27","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jcf.2010.01.005","volume":"9","author":"RD Gray","year":"2010","unstructured":"Gray RD, Imrie M, Boyd AC, Porteous D, Innes JA, Greening AP. Sputum and serum calprotectin are useful biomarkers during CF exacerbation. J Cyst Fibros Off J Eur Cyst Fibros Soc. 2010;9(3):193\u20138.","journal-title":"J Cyst Fibros Off J Eur Cyst Fibros Soc"},{"issue":"1","key":"705_CR28","first-page":"49","volume":"134","author":"W Goldstein","year":"1986","unstructured":"Goldstein W, D\u00f6ring G. Lysosomal enzymes from polymorphonuclear leukocytes and proteinase inhibitors in patients with cystic fibrosis. Am Rev Respir Dis. 1986;134(1):49\u201356.","journal-title":"Am Rev Respir Dis"},{"issue":"5","key":"705_CR29","doi-asserted-by":"publisher","first-page":"1478","DOI":"10.1172\/JCI115738","volume":"89","author":"H Nakamura","year":"1992","unstructured":"Nakamura H, Yoshimura K, McElvaney NG, Crystal RG. Neutrophil elastase in respiratory epithelial lining fluid of individuals with cystic fibrosis induces interleukin-8 gene expression in a human bronchial epithelial cell line. J Clin Invest. 1992;89(5):1478\u201384.","journal-title":"J Clin Invest"},{"issue":"1","key":"705_CR30","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1164\/ajrccm.159.1.9712108","volume":"159","author":"JL Hankinson","year":"1999","unstructured":"Hankinson JL, Odencrantz JR, Fedan KB. Spirometric reference values from a sample of the general U.S. population. Am J Respir Crit Care Med. 1999;159(1):179\u201387.","journal-title":"Am J Respir Crit Care Med"},{"key":"705_CR31","volume-title":"Planning of experiments","author":"DR Cox","year":"1958","unstructured":"Cox DR. Planning of experiments. New York: Wiley; 1958."},{"key":"705_CR32","doi-asserted-by":"publisher","DOI":"10.1017\/CBO9781139005036","volume-title":"Principles of Applied Statistics","author":"DR Cox","year":"2011","unstructured":"Cox DR, Donnelly CA. Principles of Applied Statistics. 1st ed. Cambridge: Cambridge University Press; 2011.","edition":"1"},{"issue":"7","key":"705_CR33","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1513\/AnnalsATS.201511-781OC","volume":"13","author":"EA Knapp","year":"2016","unstructured":"Knapp EA, Fink AK, Goss CH, et al. The Cystic Fibrosis Foundation patient registry. Design and methods of a National Observational Disease Registry. Ann Am Thorac Soc. 2016;13(7):1173\u20139.","journal-title":"Ann Am Thorac Soc"},{"key":"705_CR34","unstructured":"Cystic Fibrosis Foundation Patient Registry 2016 Annual Data Report [Internet]. Bethesda, Maryland: Cystic Fibrosis Foundation; 2017. Available from: https:\/\/www.cfsmartreports.com\/pages\/prelogin\/about . Accessed 27 Mar 2019."},{"key":"705_CR35","unstructured":"Geography UCB. Geography Reference [Internet]. Available from: https:\/\/www.census.gov\/geo\/reference\/state-area.html . Accessed 27 Mar 2019."},{"issue":"3","key":"705_CR36","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1067\/mpd.2001.117288","volume":"139","author":"M Rosenfeld","year":"2001","unstructured":"Rosenfeld M, Emerson J, Williams-Warren J, et al. Defining a pulmonary exacerbation in cystic fibrosis. J Pediatr. 2001;139(3):359\u201365.","journal-title":"J Pediatr"},{"key":"705_CR37","unstructured":"Davison AC. Bootstrap Methods And Their Application. 1 edition. Cambridge; New York, NY, USA: Cambridge University Press; 1997."},{"issue":"3","key":"705_CR38","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1189\/jlb.1008662","volume":"86","author":"SH Dav\u00e9","year":"2009","unstructured":"Dav\u00e9 SH, Tilstra JS, Matsuoka K, et al. Ethyl pyruvate decreases HMGB1 release and ameliorates murine colitis. J Leukoc Biol. 2009;86(3):633\u201343.","journal-title":"J Leukoc Biol"},{"issue":"7","key":"705_CR39","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1164\/rccm.201207-1160OE","volume":"187","author":"PJ Mogayzel","year":"2013","unstructured":"Mogayzel PJ, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013;187(7):680\u20139.","journal-title":"Am J Respir Crit Care Med"},{"key":"705_CR40","first-page":"409","volume":"70","author":"JB Hilliard","year":"2002","unstructured":"Hilliard JB, Konstan MW, Davis PB. Inflammatory mediators in CF patients. Methods Mol Med. 2002;70:409\u201331.","journal-title":"Methods Mol Med"},{"issue":"5","key":"705_CR41","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1249\/00005768-198205000-00012","volume":"14","author":"GA Borg","year":"1982","unstructured":"Borg GA. Psychophysical bases of perceived exertion. Med Sci Sports Exerc. 1982;14(5):377\u201381.","journal-title":"Med Sci Sports Exerc"},{"issue":"10","key":"705_CR42","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.1001\/archinte.166.10.1092","volume":"166","author":"RL Spitzer","year":"2006","unstructured":"Spitzer RL, Kroenke K, Williams JBW, L\u00f6we B. A brief measure for assessing generalized anxiety disorder: the GAD-7. Arch Intern Med. 2006;166(10):1092\u20137.","journal-title":"Arch Intern Med"},{"issue":"12","key":"705_CR43","doi-asserted-by":"publisher","first-page":"1090","DOI":"10.1136\/thoraxjnl-2014-205983","volume":"69","author":"AL Quittner","year":"2014","unstructured":"Quittner AL, Goldbeck L, Abbott J, et al. Prevalence of depression and anxiety in patients with cystic fibrosis and parent caregivers: results of the international depression epidemiological study across nine countries. Thorax. 2014;69(12):1090\u20137.","journal-title":"Thorax"},{"issue":"9","key":"705_CR44","doi-asserted-by":"publisher","first-page":"606","DOI":"10.1046\/j.1525-1497.2001.016009606.x","volume":"16","author":"K Kroenke","year":"2001","unstructured":"Kroenke K, Spitzer RL, Williams JBW. The PHQ-9. J Gen Intern Med. 2001;16(9):606\u201313.","journal-title":"J Gen Intern Med"},{"issue":"6","key":"705_CR45","doi-asserted-by":"publisher","first-page":"1598","DOI":"10.1378\/chest.11-0132","volume":"140","author":"M Hayes","year":"2011","unstructured":"Hayes M, Yaster M, Haythornthwaite JA, et al. Pain is a common problem affecting clinical outcomes in adults with cystic fibrosis. Chest. 2011;140(6):1598\u2013603.","journal-title":"Chest"},{"issue":"1","key":"705_CR46","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1177\/0748730402239679","volume":"18","author":"T Roenneberg","year":"2003","unstructured":"Roenneberg T, Wirz-Justice A, Merrow M. Life between clocks: daily temporal patterns of human Chronotypes. J Biol Rhythm. 2003;18(1):80\u201390.","journal-title":"J Biol Rhythm"},{"key":"705_CR47","unstructured":"Nord M. Assessing Potential Technical Enhancements to the U.S. Household Food Security Measures [Internet]. US Department of Agriculture, Economic Research Service; 2012 [cited 2016 Jul 19]. Available from: https:\/\/www.ers.usda.gov\/publications\/pub-details\/?pubid=47606 . Accessed 27 Mar 2019."},{"issue":"2","key":"705_CR48","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/j.jbi.2008.08.010","volume":"42","author":"PA Harris","year":"2009","unstructured":"Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform. 2009;42(2):377\u201381.","journal-title":"J Biomed Inform"},{"key":"705_CR49","unstructured":"R Core Team. R: A language and environment for statistical computing [Internet]. Vienna, Austria: R Foundation for Statistical Computing; 2015. Available from: https:\/\/www.r-project.org\/ . Accessed 27 Mar 2019."},{"key":"705_CR50","unstructured":"TNM Download [Internet]. [cited 2016 Jul 19];Available from: https:\/\/viewer.nationalmap.gov\/basic\/?basemap=b1&category=ned,nedsrc&title=3DEP%20View . Accessed 27 Mar 2019."},{"issue":"6","key":"705_CR51","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1183\/09031936.00080312","volume":"40","author":"PH Quanjer","year":"2012","unstructured":"Quanjer PH, Stanojevic S, Cole TJ, et al. Multi-ethnic reference values for spirometry for the 3\u201395-yr age range: the global lung function 2012 equations. Eur Respir J. 2012;40(6):1324\u201343.","journal-title":"Eur Respir J"},{"issue":"1","key":"705_CR52","doi-asserted-by":"publisher","first-page":"e000183","DOI":"10.1136\/bmjdrc-2015-000183","volume":"4","author":"TG Liou","year":"2016","unstructured":"Liou TG, Jensen JL, Allen SE, et al. Improving performance in the detection and management of cystic fibrosis-related diabetes in the mountain west cystic fibrosis consortium. BMJ Open Diabetes Res Care. 2016;4(1):e000183.","journal-title":"BMJ Open Diabetes Res Care"},{"key":"705_CR53","first-page":"24s","volume":"37","author":"MM Kelly","year":"2002","unstructured":"Kelly MM, Keatings V, Leigh R, et al. Analysis of fluid-phase mediators. Eur Respir J Suppl. 2002;37:24s\u201339s.","journal-title":"Eur Respir J Suppl"},{"issue":"11","key":"705_CR54","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/j.clinbiochem.2004.07.008","volume":"37","author":"AA Smountas","year":"2004","unstructured":"Smountas AA, Lands LC, Mohammed SR, Grey V. Induced sputum in cystic fibrosis: within-week reproducibility of inflammatory markers. Clin Biochem. 2004;37(11):1031\u20136.","journal-title":"Clin Biochem"},{"issue":"5","key":"705_CR55","first-page":"393","volume":"80","author":"A Hector","year":"2010","unstructured":"Hector A, Jonas F, Kappler M, Feilcke M, Hartl D, Griese M. Novel method to process cystic fibrosis sputum for determination of oxidative state. Respir Int Rev Thorac Dis. 2010;80(5):393\u2013400.","journal-title":"Respir Int Rev Thorac Dis"},{"issue":"4","key":"705_CR56","first-page":"685","volume":"18","author":"MM Kelly","year":"2001","unstructured":"Kelly MM, Leigh R, Carruthers S, et al. Increased detection of interleukin-5 in sputum by addition of protease inhibitors. Eur Respir J Off J Eur Soc Clin Respir Physiol. 2001;18(4):685\u201391.","journal-title":"Eur Respir J Off J Eur Soc Clin Respir Physiol"},{"issue":"2","key":"705_CR57","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.2517-6161.1958.tb00292.x","volume":"20","author":"DR Cox","year":"1958","unstructured":"Cox DR. The regression analysis of binary sequences. J R Stat Soc Ser B Methodol. 1958;20(2):215\u201342.","journal-title":"J R Stat Soc Ser B Methodol"},{"issue":"2","key":"705_CR58","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1111\/j.2517-6161.1972.tb00899.x","volume":"34","author":"DR Cox","year":"1972","unstructured":"Cox DR. Regression models and life-tables. J R Stat Soc Ser B Methodol. 1972;34(2):187\u2013220.","journal-title":"J R Stat Soc Ser B Methodol"},{"issue":"4","key":"705_CR59","doi-asserted-by":"publisher","first-page":"2347","DOI":"10.1378\/chest.128.4.2347","volume":"128","author":"AL Quittner","year":"2005","unstructured":"Quittner AL, Buu A, Messer MA, Modi AC, Watrous M. Development and validation of the cystic fibrosis questionnaire in the United States: a health-related quality-of-life measure for cystic fibrosis. Chest. 2005;128(4):2347\u201354.","journal-title":"Chest"}],"container-title":["BMC Medical Research Methodology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-019-0705-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1186\/s12874-019-0705-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1186\/s12874-019-0705-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T09:54:14Z","timestamp":1721210054000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmcmedresmethodol.biomedcentral.com\/articles\/10.1186\/s12874-019-0705-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,26]]},"references-count":59,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,12]]}},"alternative-id":["705"],"URL":"https:\/\/doi.org\/10.1186\/s12874-019-0705-0","relation":{},"ISSN":["1471-2288"],"issn-type":[{"value":"1471-2288","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,26]]},"assertion":[{"value":"18 September 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"DRC is an Honorary Fellow at Nuffield College. His pioneering work in Statistics includes introduction of the current methods of logistic regression [] and proportional hazards models []. He was awarded the Guy Medal in both Silver and Gold from the Royal Statistical Society, the Kettering Prize and Gold Medal for Cancer Research, the Copley Medal from the Royal Society, and he recently won the first International Prize in Statistics awarded jointly by the American Statistical Association, the International Biometric Society, the Institute of Mathematical Statistics, the International Statistical Institute, and the Royal Statistical Society. His lifelong experience improving the design of experiments [,] was instrumental in the design of the current study.RK received her DPhil under the supervision of DRC from the University of Oxford. She is now Associate Professor in the Department of Medical Statistics at the London School of Hygiene and Tropical Medicine, is funded by a Medical Research Council Methodology Fellowship, and teaches Master\u2019s level courses in medical statistics. She helped the study greatly by participating in the teaching video (Additional files 1, 2 and 3) with DRC and with our initial study design.Our non-MWCFC collaborators brought skills and experience not found in the MWCFC. NL is Director of the Adult CF Program and Associate Professor in the Department of Medicine, Division of Pulmonary and Critical Care Medicine at the Johns Hopkins University. He has published in the area of assessment of pain in patients with CF [] and brings that expertise to our study. ALQ is a behavioral scientist and clinical psychologist at the Miami Children\u2019s Research Institute. She was awarded the inaugural Mattingly Leadership in Mental Health Care Award in 2016 by the US CF Foundation, and she contributed her expertise on quantitative measurements of depression, anxiety and quality of life [] to the study.The study benefited greatly from guidance by the external advisory committee. JPC is Professor and Research Director for the Division of Pulmonary Medicine, Department of Pediatrics, at the U of Cincinnati and has been a member or leader of multiple research organizations within the CF Foundation, the European CF Society and the National Institutes of Health in the US (NIH). KNO is Senior Clinician and Chief of the Pulmonary Branch of the National Heart, Lung and Blood Institute (NHLBI) of the NIH and leader of the Chronic Airway Infection Laboratory at the NHLBI. He has led multiple studies of bronchiectasis and infections, especially non-tuberculous <i>Mycobacteria<\/i>. JSE is Faculty Pro-Vice Chancellor of the School of Medicine, Dentistry and Biomedical Sciences and Faculty in the Institute for Health Sciences and the Centre for Experimental Medicine, Queen's University Belfast, UK. He was President of the European CF Society for 8\u2009years and Trustee, Chair or Member of the Medical Advisory Committee of the CF Trust in the UK since 2002. He received knighthood in 2012 for his work in health care in Northern Ireland. He has been author and driving force for many studies that have improved knowledge and care of patients with CF.The authors from the Mountain West CF Consortium have been meeting and working collaboratively for over 20\u2009years including a recent publication []. The long-standing close relationships between these individuals and teams enhanced the ability to design and perform this complex multicenter study.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Authors\u2019 information"}},{"value":"Our project was reviewed and approved by the Investigational Review Board (IRB) of the University of Utah (IRB_00011571), the St. Luke\u2019s Health System IRB (IRB Protocol No.: 13\u20130547), the IRB of Billings (Study 14.07), the Western IRB (for the Las Vegas CF Center) (STUDY NUM 1146159, WIRB PRO NUM: 20140721, INVEST NUM: 112264, WO NUM: 1\u2013837046-1, Protocol Number 20130530), the National Jewish Health IRB (Study Number: HS-2797), Colorado Multiple IRB (for Children\u2019s Hospital Colorado) (COMIRB Protocol 13\u20133172), the Phoenix Children\u2019s Hospital IRB (PCH IRB #13\u2013087), the University of Arizona IRB (Protocol Number: 1407394040), and the Human Research Review Committee in the Human Research Protections Office at the University of New Mexico (Study ID 14\u2013085). No patients were enrolled prior to IRB approval. All patients younger than 18 provided assent with informed written consent provided by parents or other legal guardians. Each adult patient gave informed written consent on his or her own behalf.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"TGL, JAF, JLJ, YL, KAP and JBV received other support from the CFF (CC132-16\u2009AD, LIOU14Y0, LIOU14P0) and the National Heart Lung and Blood Institute (NHLBI) of the National Institutes of Health (NIH) (R01 HL125520) and received support during the current study for performing clinical trials from Abbvie, Gilead, Nivalis, Novartis, Proteostasis, Inc., Savara and Vertex. FRA received additional other support from the NHLBI\/NIH (R01 HL125520), the National Science Foundation (EMSW21-RTG) and the Margolis Foundation of Utah. PSB received other support from the CFF (Center and TDC grants) and the NHLBI\/NIH (U01 HL114623) and received support for a clinical trial from Alcresta. BAC received other support from the CFF (C112\u201312, C112-TDC09Y, 10063SUB, 41,339,154.s132P010379SUB) and received support for clinical trials from Genentech, Novartis and Vertex. CLD received other support from the CFF (C004\u201311, C004-TDC09Y, DAINES11Y3) and from the Health Resources and Services Administration (T72MC00012). TH received other support from the CFF (PACE, Center Grant) and received support for clinical trials from Celtaxsys and Vertex. JRH received other support from the NHLBI\/NIH (HHSN268200900018C) and the Veterans Administration Healthcare System (I01 BX001533). JL received other support from the CFF (C017-11AF). CN received other support from the CFF (C138\u201312). PR received other support from the CFF (C003\u201312, C003-TDC09Y). SDS received other support from the CFF (AQUADEK12K1, SAGEL11CS0, GOAL13K2, NICK13A0, SAGEL14K1, NICK15R0) and the NHLBI\/NIH (U54 HL096458) and the NCATS\/NIH (Colorado CTSA Grant Number UL1 TR002535). JLT-C received other support from the CFF (TDC) and the NHLBI\/NIH (HL103801) and received support for clinical trials from Vertex. KNO is funded by the intramural research program of the NHLBI, NIH.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Publisher\u2019s Note"}}],"article-number":"88"}}