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BMC Medicine
Published in: BMC Medicine 1/2012

Open Access 01-12-2012 | Review

State of progress in treating cystic fibrosis respiratory disease

Authors: Patrick A Flume, Donald R Van Devanter

Published in: BMC Medicine | Issue 1/2012

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Abstract

Since the discovery of the gene associated with cystic fibrosis (CF), there has been tremendous progress in the care of patients with this disease. New therapies have entered the market and are part of the standard treatment of patients with CF, and have been associated with marked improvement in survival. Now there are even more promising therapies directed at different components of the pathophysiology of this disease. In this review, our current knowledge of the pathophysiology of lung disease in patients with CF is described, along with the current treatment of CF lung disease, and the therapies in development that offer great promise to our patients.
Appendix
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Literature
1.
Cystic Fibrosis Foundation Patient Registry: 2010 Annual Data Report. Bethesda, MD. 2011
2.
Rommens JM, Iannuzzi MC, Kerem B, Drumm ML, Melmer G, Dean M, Rozmahel R, Cole JL, Kennedy D, Hidaka N, Zsiga M, Buchwald M, Riordan JR, Tsui LC, Collins FS: Identification of the cystic fibrosis gene: chromosome walking and jumping. Science. 1989, 245 (4922): 1059-1065. 10.1126/science.2772657.PubMed
3.
Riordan JR, Rommens JM, Kerem B, Alon N, Rozmahel R, Grzelczak Z, Zielenski J, Lok S, Plavsic N, Chou JL, Drumm ML, Iannuzzi MC, Collins FS, Tsui LC: Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science. 1989, 245 (4922): 1066-1073. 10.1126/science.2475911.PubMed
4.
Kerem B, Rommens JM, Buchanan JA, Markiewicz D, Cox TK, Chakravarti A, Buchwald M, Tsui LC: Identification of the cystic fibrosis gene: genetic analysis. Science. 1989, 245 (4922): 1073-1080. 10.1126/science.2570460.PubMed
5.
Collins FS: Cystic fibrosis: molecular biology and therapeutic implications. Science. 1992, 256 (5058): 774-779. 10.1126/science.1375392.PubMed
6.
Davis PB, Drumm M, Konstan MW: Cystic fibrosis. Am J Respir Crit Care Med. 1996, 154 (5): 1229-1256.PubMed
7.
Quinton PM: Role of epithelial HCO3- transport in mucin secretion: lessons from cystic fibrosis. Am J Physiol Cell Physiol. 2010, 299 (6): C1222-1233. 10.1152/ajpcell.00362.2010.PubMedPubMedCentral
8.
Farrell PM, Rosenstein BJ, White TB, Accurso FJ, Castellani C, Cutting GR, Durie PR, Legrys VA, Massie J, Parad RB, Rock MJ, Campbell PW: Cystic Fibrosis Foundation Guidelines for diagnosis of cystic fibrosis in newborns through older adults: Cystic Fibrosis Foundation consensus report. J Pediatr. 2008, 153 (2): S4-S14. 10.1016/j.jpeds.2008.05.005.PubMedPubMedCentral
9.
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, 151 (4): 1075-1082.PubMed
10.
Armstrong DS, Grimwood K, Carzino R, Carlin JB, Olinsky A, Phelan PD: Lower respiratory infection and inflammation in infants with newly diagnosed cystic fibrosis. BMJ. 1995, 310: 1571-1572. 10.1136/bmj.310.6994.1571.PubMedPubMedCentral
11.
Burns JL, Gibson RL, McNamara S, Yim D, Emerson J, Rosenfeld M, Hiatt P, McCoy K, Castile R, Smith AL, Ramsey BW: Longitudinal assessment of Pseudomonas aeruginosa in young children with cystic fibrosis. J Infect Dis. 2001, 183 (3): 444-452. 10.1086/318075.PubMed
12.
Rosenfeld M, Gibson RL, McNamara S, Emerson J, Burns JL, Castile R, Hiatt P, McCoy K, Wilson CB, Inglis A, Smith A, Martin TR, Ramsey BW: Early pulmonary infection, inflammation, and clinical outcomes in infants with cystic fibrosis. Pediatr Pulmonol. 2001, 32 (5): 356-366. 10.1002/ppul.1144.PubMed
13.
Mott LS, Gangell CL, Murray CP, Stick SM, Sly PD, AREST CF: Bronchiectasis in an asymptomatic infant with cystic fibrosis diagnosed following newborn screening. J Cyst Fibros. 2009, 8 (4): 285-287. 10.1016/j.jcf.2009.04.009.PubMed
14.
Stick SM, Brennan S, Murray C, Douglas T, von Ungern-Sternberg BS, Garratt LW, Gangell CL, De Klerk N, Linnane B, Ranganathan S, Robinson P, Robertson C, Sly PD, Australian Respiratory Early Surveillance Team for Cystic Fibrosis (AREST CF): Bronchiectasis in infants and preschool children diagnosed with cystic fibrosis after newborn screening. J Pediatr. 2009, 155 (5): 623-628e1. 10.1016/j.jpeds.2009.05.005.PubMed
15.
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, 180 (2): 146-152. 10.1164/rccm.200901-0069OC.PubMed
16.
Pillarisetti N, Linnane B, Ranganathan S, AREST CF: Early bronchiectasis in cystic fibrosis detected by surveillance CT. Respirology. 2010, 15 (6): 1009-1011. 10.1111/j.1440-1843.2010.01765.x.PubMed
17.
Boucher RC: Evidence for airway surface dehydration as the initiating event in CF airway disease. J Intern Med. 2007, 261: 5-16. 10.1111/j.1365-2796.2006.01744.x.PubMed
18.
Chmiel JF, Berger M, Konstan MW: The role of inflammation in the pathophysiology of cystic fibrosis lung disease. Clin Rev Allergy Immunol. 2002, 23: 5-27. 10.1385/CRIAI:23:1:005.PubMed
19.
Linnane BM, Hall GL, Nolan G, Brennan S, Stick SM, Sly PD, Robertson CF, Robinson PJ, Franklin PJ, Turner SW, Ranganathan SC, AREST-CF: Lung function in infants with cystic fibrosis diagnosed by newborn screening. Am J Respir Crit Care Med. 2008, 178 (12): 1238-1244. 10.1164/rccm.200804-551OC.PubMed
20.
Cystic Fibrosis Foundation, Borowitz D, Robinson KA, Rosenfeld M, Davis SD, Sabadosa KA, Spear SL, Michel SH, Parad RB, White TB, Farrell PM, Marshall BC, Accurso FJ: Cystic Fibrosis Foundation evidence-based guidelines for management of infants with cystic fibrosis. J Pediatr. 2009, 155 (6 Suppl): S73-93.
21.
Robertson JM, Friedman EM, Rubin BK: Nasal and sinus disease in cystic fibrosis. Paediatr Respir Rev. 2008, 9 (3): 213-219. 10.1016/j.prrv.2008.04.003.PubMed
22.
Flume PA, Mogayzel PJ, Robinson KA, Rosenblatt RL, Quittell L, Marshall BC, Cystic Fibrosis Foundation Pulmonary Therapies Committee: Cystic fibrosis pulmonary guidelines: pulmonary complications: hemoptysis and pneumothorax. Am J Respir Crit Care Med. 2010, 182 (3): 298-306. 10.1164/rccm.201002-0157OC.PubMed
23.
Braun AT, Merlo CA: Cystic fibrosis lung transplantation. Curr Opin Pulm Med. 2011, 17 (6): 467-472.PubMed
24.
Flume PA, Robinson KA, O'Sullivan BP, Finder JD, Vender RL, Willey-Courand DB, White TB, Marshall BC, Clinical Practice Guidelines for Pulmonary Therapies Committee: Cystic fibrosis pulmonary guidelines: airway clearance therapies. Respir Care. 2009, 54 (4): 522-537.PubMed
25.
Ferkol T, Rosenfeld M, Milla CE: Cystic fibrosis pulmonary exacerbations. J Pediatr. 2006, 148 (2): 259-264. 10.1016/j.jpeds.2005.10.019.PubMed
26.
Goss CH, Burns JL: Exacerbations in cystic fibrosis 1: epidemiology and pathogenesis. Thorax. 2007, 62 (4): 360-367. 10.1136/thx.2006.060889.PubMedPubMedCentral
27.
Konstan MW, Morgan WJ, Butler SM, Pasta DJ, Craib ML, Silva SJ, Stokes DC, Wohl ME, Wagener JS, Regelmann WE, Johnson CA, Scientific Advisory Group and the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis: Risk factors for rate of decline in forced expiratory volume in one second in children and adolescents with cystic fibrosis. J Pediatr. 2007, 151 (2): 134-139. 10.1016/j.jpeds.2007.03.006. 139e1PubMed
28.
VanDevanter DR, Wagener JS, Pasta DJ, Elkin E, Jacobs JR, Morgan WJ, Konstan MW: Pulmonary outcome prediction (POP) tools for cystic fibrosis patients. Pediatr Pulmonol. 2010, 45: 1156-1166. 10.1002/ppul.21311.PubMedPubMedCentral
29.
VanDevanter DR, O'Riordan MA, Blumer JL, Konstan MW: Assessing time to pulmonary function benefit following antibiotic treatment of acute cystic fibrosis exacerbations. Respir Res. 2010, 11: 137-10.1186/1465-9921-11-137.PubMedPubMedCentral
30.
Sanders DB, Bittner RC, Rosenfeld M, Hoffman LR, Redding GJ, Goss CH: Failure to recover to baseline pulmonary function after cystic fibrosis pulmonary exacerbation. Am J Respir Crit Care Med. 2010, 182 (5): 627-632. 10.1164/rccm.200909-1421OC.PubMed
31.
Collaco JM, Green DM, Cutting GR, Naughton KM, Mogayzel PJ: Location and duration of treatment of cystic fibrosis respiratory exacerbations do not affect outcomes. Am J Respir Crit Care Med. 2010, 182 (9): 1137-1143. 10.1164/rccm.201001-0057OC.PubMedPubMedCentral
32.
Sanders DB, Bittner RC, Rosenfeld M, Redding GJ, Goss CH: Pulmonary exacerbations are associated with subsequent FEV1 decline in both adults and children with cystic fibrosis. Pediatr Pulmonol. 2011, 46 (4): 393-400. 10.1002/ppul.21374.PubMed
33.
Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, Rosenstein BJ, Smith AL, Wohl ME: 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): 637-642. 10.1056/NEJM199409083311003.PubMed
34.
Ramsey BW, Pepe MS, Quan JM, Otto KL, Montgomery AB, Williams-Warren J, Vasiljev-K M, Borowitz D, Bowman CM, Marshall BC, Marshall S, Smith AL: Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med. 1999, 340 (1): 23-30. 10.1056/NEJM199901073400104.PubMed
35.
Quan JM, Tiddens HA, Sy JP, McKenzie SG, Montgomery MD, Robinson PJ, Wohl ME, Konstan MW, Pulmozyme Early Intervention Trial Study Group: A two-year randomized, placebo controlled trial of dornase alfa in young patients with cystic fibrosis with mild lung function abnormalities. J Pediatr. 2001, 139 (6): 813-820. 10.1067/mpd.2001.118570.PubMed
36.
Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT, National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group: A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006, 354 (3): 229-240. 10.1056/NEJMoa043900.PubMed
37.
McCoy KS, Quittner AL, Oermann CM, Gibson RL, Retsch-Bogart GZ, Montgomery AB: Inhaled aztreonam lysine for chronic airway Pseudomonas aeruginosa in cystic fibrosis. Am J Respir Crit Care Med. 2008, 178 (9): 921-928. 10.1164/rccm.200712-1804OC.PubMedPubMedCentral
38.
Wagener J, Rasouliyan L, Past D, Mabie J, Morgan W, Konstan M: Practice patterns for treating respiratory exacerbations in cystic fibrosis. Pediatr Pulmonol. 2008, 359-Supplement 31
39.
Orenstein DM, Pattishall EN, Nixon PA, Ross EA, Kaplan RM: Quality of well-being before and after antibiotic treatment of pulmonary exacerbation in patients with cystic fibrosis. Chest. 1990, 98: 1081-1084. 10.1378/chest.98.5.1081.PubMed
40.
Bradley J, McAlister O, Elborn S: Pulmonary function, inflammation, exercise capacity and quality of life in cystic fibrosis. Eur Respir J. 2001, 17: 712-715. 10.1183/09031936.01.17407120.PubMed
41.
Britto MT, Kotagal UR, Hornung RW, Atherton HD, Tsevat J, Wilmott RW: Impact of recent pulmonary exacerbations on quality of life in patients with cystic fibrosis. Chest. 2002, 121: 64-72. 10.1378/chest.121.1.64.PubMed
42.
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: 345-352. 10.1093/aje/153.4.345.PubMedPubMedCentral
43.
Mayer-Hamblett N, Rosenfeld M, Emerson J, Goss CH, Aitken ML: Developing cystic fibrosis lung transplant referral criteria using predictors of 2-year mortality. Am J Respir Crit Care Med. 2002, 166: 1550-1555. 10.1164/rccm.200202-087OC.PubMed
44.
Emerson J, Rosenfeld M, McNamara S, Ramsey BW, Gibson RL: Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosis. Pediatr Pulmonol. 2002, 34: 91-100. 10.1002/ppul.10127.PubMed
45.
Ellaffi M, Vinsonneau C, Coste J, Hubert D, Burgel PR, Dhainaut JF, Dusser D: One-year outcome after severe pulmonary exacerbation in adults with cystic fibrosis. Am J Respir Crit Care Med. 2005, 171: 158-164.PubMed
46.
Flume PA, Mogayzel PJ, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, Marshall BC, Clinical Practice Guidelines for Pulmonary Therapies Committee: Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009, 180 (9): 802-808. 10.1164/rccm.200812-1845PP.PubMed
47.
Konstan MW, VanDevanter DR, Rasouliyan L, Pasta DJ, Yegin A, Morgan WJ, Wagener JS: Trends in the use of routine therapies in cystic fibrosis: 1995-2005. Pediatr Pulmonol. 2010, 45: 1167-1172. 10.1002/ppul.21315.PubMedPubMedCentral
48.
Griesenbach U, Alton EW: Progress in gene and cell therapy for cystic fibrosis lung disease. Curr Pharm Des. 2012, 18 (5): 642-662. 10.2174/138161212799315993.PubMed
49.
Zielenski J, Tsui LC: Cystic fibrosis: genotypic and phenotypic variations. Annu Rev Genet. 1995, 29: 777-807. 10.1146/annurev.ge.29.120195.004021.PubMed
50.
Rowntree RK, Harris A: The phenotypic consequences of CFTR mutations. Ann Hum Genet. 2003, 67 (Pt 5): 471-485.PubMed
51.
Van Goor F, Hadida S, Grootenhuis PD, Burton B, Cao D, Neuberger T, Turnbull A, Singh A, Joubran J, Hazlewood A, Zhou J, McCartney J, Arumugam V, Decker C, Yang J, Young C, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu P: Rescue of CF airway epithelial cell function in vitro by a CFTR potentiator, VX-770. Proc Natl Acad Sci USA. 2009, 106 (44): 18825-18830. 10.1073/pnas.0904709106.PubMedPubMedCentral
52.
Ramsey BW, Davies J, McElvaney NG, Tullis E, Bell SC, Dřevínek P, Griese M, McKone EF, Wainwright CE, Konstan MW, Moss R, Ratjen F, Sermet-Gaudelus I, Rowe SM, Dong Q, Rodriguez S, Yen K, Ordoñez C, Elborn JS: A CFTR potentiator in patients with cystic fibrosis and the G551D mutation. N Engl J Med. 2011, 365: 1663-1672. 10.1056/NEJMoa1105185.PubMedPubMedCentral
53.
Flume PA, Liou TG, Borowitz DS, Li H, Yen K, Ordoñez CL, Geller DE: Ivacaftor in subjects with cystic fibrosis who are homozygous for the F508del-CFTR mutation. Chest. 2012.
54.
Denning GM, Anderson MP, Amara JF, Marshall J, Smith AE, Welsh MJ: Processing of mutant cystic fibrosis transmembrane conductance regulator is temperature-sensitive. Nature. 1992, 358 (6389): 761-764. 10.1038/358761a0.PubMed
55.
Kartner N, Augustinas O, Jensen TJ, Naismith AL, Riordan JR: Mislocalization of delta F508 CFTR in cystic fibrosis sweat gland. Nat Genet. 1992, 1 (5): 321-327. 10.1038/ng0892-321.PubMed
56.
Van Goor F, Straley KS, Cao D, González J, Hadida S, Hazlewood A, Joubran J, Knapp T, Makings LR, Miller M, Neuberger T, Olson E, Panchenko V, Rader J, Singh A, Stack JH, Tung R, Grootenhuis PD, Negulescu P: Rescue of DeltaF508-CFTR trafficking and gating in human cystic fibrosis airway primary cultures by small molecules. Am J Physiol Lung Cell Mol Physiol. 2006, 290 (6): L1117-1130. 10.1152/ajplung.00169.2005.PubMed
57.
Van Goor F, Hadida S, Grootenhuis PD, Burton B, Stack JH, Straley KS, Decker CJ, Miller M, McCartney J, Olson ER, Wine JJ, Frizzell RA, Ashlock M, Negulescu PA: Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc Natl Acad Sci USA. 2011, 108 (46): 18843-18848. 10.1073/pnas.1105787108.PubMedPubMedCentral
58.
Cain C: Cystic fibrosis two-step. SciBX. 2012, 5 (8): doi:101038/scibx2012192
59.
60.
61.
62.
The Cystic Fibrosis Genetic Analysis Consortium: Population variation of common cystic fibrosis mutations. Hum Mutat. 1994, 4 (3): 167-177.
63.
Du M, Liu X, Welch EM, Hirawat S, Peltz SW, Bedwell DM: PTC124 is an orally bioavailable compound that promotes suppression of the human CFTR-G542X nonsense allele in a CF mouse model. Proc Natl Acad Sci USA. 2008, 105: 2064-2069. 10.1073/pnas.0711795105.PubMedPubMedCentral
64.
Sermet-Gaudelus I, Boeck KD, Casimir GJ, Vermeulen F, Leal T, Mogenet A, Roussel D, Fritsch J, Hanssens L, Hirawat S, Miller NL, Constantine S, Reha A, Ajayi T, Elfring GL, Miller LL: Ataluren (PTC124) induces cystic fibrosis transmembrane conductance regulator protein expression and activity in children with nonsense mutation cystic fibrosis. Am J Respir Crit Care Med. 2010, 182 (10): 1262-1272. 10.1164/rccm.201001-0137OC.PubMed
65.
Kerem E, Hirawat S, Armoni S, Yaakov Y, Shoseyov D, Cohen M, Nissim-Rafinia M, Blau H, Rivlin J, Aviram M, Elfring GL, Northcutt VJ, Miller LL, Kerem B, Wilschanski M: Effectiveness of PTC124 treatment of cystic fibrosis caused by nonsense mutations: a prospective phase II trial. Lancet. 2008, 372 (9640): 719-727. 10.1016/S0140-6736(08)61168-X.PubMed
66.
67.
Chan HC, Goldstein J, Nelson DJ: Alternate pathways for chloride conductance activation in normal and cystic fibrosis airway epithelial cells. Am J Physiol. 1992, 262 (5 Pt 1): C1273-C1283.PubMed
68.
Erlinge D: P2Y receptors in health and disease. Adv Pharmacol. 2011, 61: 417-439.PubMed
69.
Knowles MR, Clarke LL, Boucher RC: Activation by extracellular nucleotides of chloride secretion in the airway epithelia of patients with cystic fibrosis. N Engl J Med. 1991, 325 (8): 533-538. 10.1056/NEJM199108223250802.PubMed
70.
Accurso FJ, Moss RB, Wilmott RW, Anbar RD, Schaberg AE, Durham TA, Ramsey BW, TIGER-1 Investigator Study Group: Denufosol tetrasodium in patients with cystic fibrosis and normal to mildly impaired lung function. Am J Respir Crit Care Med. 2011, 183 (5): 627-634. 10.1164/rccm.201008-1267OC.PubMed
71.
Ratjen F, Durham T, Navratil T, Schaberg A, Accurso FJ, Wainwright C, Barnes M, Moss RB, the TIGER-2 Study Investigator Group: Long term effects of denufosol tetrasodium in patients with cystic fibrosis. J Cyst Fibros. 2012.
72.
Yerxa BR, Sabater JR, Davis CW, Stutts MJ, Lang-Furr M, Picher M, Jones AC, Cowlen M, Dougherty R, Boyer J, Abraham WM, Boucher RC: Pharmacology of INS37217 P(1)-(uridine 5')-P(4)- (2'-deoxycytidine 5') tetraphosphate, tetrasodium salt, a next-generation P2Y(2) receptor agonist for the treatment of cystic fibrosis. J Pharmacol Exp Ther. 2002, 302 (3): 871-880. 10.1124/jpet.102.035485.PubMed
73.
Pettit RS, Johnson CE: Airway-rehydrating agents for the treatment of cystic fibrosis: past, present, and future. Ann Pharmacother. 2011, 45 (1): 49-59. 10.1345/aph.1P428.PubMed
74.
Zeitlin P, Boyle M, Guggino W, Molina L: A phase I trial of intranasal Moli1901 for cystic fibrosis. Chest. 2004, 125 (1): 143-149. 10.1378/chest.125.1.143.PubMed
75.
Grasemann H, Stehling F, Brunar H, Widmann R, Laliberte T, Molina L, Döring G, Ratjen F: Inhalation of moli1901 in patients with cystic fibrosis. Chest. 2007, 131 (5): 1461-1466. 10.1378/chest.06-2085.PubMed
76.
Matsui H, Randell SH, Peretti SW, Davis CW, Boucher RC: Coordinated clearance of periciliary liquid and mucus from airway surfaces. J Clin Invest. 1998, 102 (6): 1125-1131. 10.1172/JCI2687.PubMedPubMedCentral
77.
Burrows E, Southern K, Noone P: Sodium channel blockers for cystic fibrosis. Cochrane Database Syst Rev. 2006, 3: CD005087.PubMed
78.
Donaldson SH, Bennett WD, Zeman KL, Knowles MR, Tarran R, Boucher RC: Mucus clearance and lung function in cystic fibrosis with hypertonic saline. N Engl J Med. 2006, 354 (3): 241-250. 10.1056/NEJMoa043891.PubMed
79.
Robinson M, Hemming AL, Regnis JA, Wong AG, Bailey DL, Bautovich GJ, King M, Bye PT: Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis. Thorax. 1997, 52: 900-903. 10.1136/thx.52.10.900.PubMedPubMedCentral
80.
Amin R, Subbarao P, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F: Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax. 2010, 65 (5): 379-383. 10.1136/thx.2009.125831.PubMed
81.
Reeves EP, Williamson M, O'Neill SJ, Greally P, McElvaney NG: Nebulized hypertonic saline decreases IL-8 in sputum of patients with cystic fibrosis. Am J Respir Crit Care Med. 2011, 183 (11): 1517-1523. 10.1164/rccm.201101-0072OC.PubMed
82.
Dmello D, Nayak RP, Matuschak GM: Stratified assessment of the role of inhaled hypertonic saline in reducing cystic fibrosis pulmonary exacerbations: a retrospective analysis. BMJ Open. 2011, 1 (1): e000019-10.1136/bmjopen-2010-000019.PubMedPubMedCentral
83.
Wark P, McDonald VM: Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2009, 2: CD001506.PubMed
84.
85.
Rosenfeld M, Ratjen F, Brumback L, Daniel S, Rowbotham R, McNamara S, Johnson R, Kronmal R, Davis SD, ISIS Study Group: Inhaled hypertonic saline in infants and children younger than 6 years with cystic fibrosis: the ISIS randomized controlled trial. JAMA. 307 (21): 2269-2277.
86.
Daviskas E, Anderson SD, Eberl S, Chan HK, Bautovich G: Inhalation of dry powder mannitol improves clearance of mucus in patients with bronchiectasis. Am J Respir Crit Care Med. 1999, 159: 1843-1848.PubMed
87.
Aitken ML, Bellon G, De Boeck K, Flume PA, Fox HG, Geller DE, Haarman EG, Hebestreit HU, Lapey A, Schou IM, Zuckerman JB, Charlton B: Long-term inhaled dry powder mannitol in cystic fibrosis: an international randomized study. Am J Respir Crit Care Med. 2012, 185: 645-652. 10.1164/rccm.201109-1666OC.PubMed
88.
Zabner J, Seiler MP, Launspach JL, Karp PH, Kearney WR, Look DC, Smith JJ, Welsh MJ: The osmolyte xylitol reduces the salt concentration of airway surface liquid and may enhance bacterial killing. Proc Natl Acad Sci USA. 2000, 97 (21): 11614-11619. 10.1073/pnas.97.21.11614.PubMedPubMedCentral
89.
90.
Lester MK, Flume PA: Airway clearance therapy: guidelines and implementation. Respir Care. 2009, 54: 733-750. 10.4187/002013209790983205.PubMed
91.
Kellett F, Redfern J, Niven RM: Evaluation of nebulised hypertonic saline (7%) as an adjunct to physiotherapy in patients with stable bronchiectasis. Respir Med. 2005, 99 (1): 27-31. 10.1016/j.rmed.2004.05.006.PubMed
92.
Konstan MW, Ratjen F: Effect of dornase alfa on inflammation and lung function: potential role in the early treatment of cystic fibrosis. J Cyst Fibros. 2012, 11 (2): 78-83. 10.1016/j.jcf.2011.10.003.PubMed
93.
Robinson TE, Goris ML, Zhu HJ, Chen X, Bhise P, Sheikh F, Moss RB: Dornase alfa reduces air trapping in children with mild cystic fibrosis lung disease: a quantitative analysis. Chest. 2005, 128 (4): 2327-2335. 10.1378/chest.128.4.2327.PubMed
94.
Amin R, Subbarao P, Lou W, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F: The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis. Eur Respir J. 2011, 37 (4): 806-812. 10.1183/09031936.00072510.PubMed
95.
Ratjen F, Rietschel E, Griese M, Ballmann M, Kleinau I, Döring G, Reinhardt D, Paul K: Fractional analysis of bronchoalveolar lavage fluid cytology in cystic fibrosis patients with normal lung function. Bronchoalveolar lavage for the evaluation of anti-inflammatory treatment (BEAT) study group. Eur Respir J. 2000, 15 (1): 141-145. 10.1183/09031936.00.15114100.PubMed
96.
Konstan MW, Wagener JS, Pasta DJ, Millar SJ, Jacobs JR, Yegin A, Morgan WJ, Scientific Advisory Group and Investigators and Coordinators of Epidemiologic Study of Cystic Fibrosis: Clinical use of dornase alpha is associated with a slower rate of FEV1 decline in cystic fibrosis. Pediatr Pulmonol. 2011, 46 (6): 545-553. 10.1002/ppul.21388.PubMedPubMedCentral
97.
Sawicki GS, Signorovitch JE, Zhang J, Latremouille-Viau D, von Wartburg M, Wu EQ, Shi L: Reduced mortality in cystic fibrosis patients treated with tobramycin inhalation solution. Pediatr Pulmonol. 2012, 47 (1): 44-52. 10.1002/ppul.21521.PubMed
98.
Flume PA, O'Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ, Willey-Courand DB, Bujan J, Finder J, Lester M, Quittell L, Rosenblatt R, Vender RL, Hazle L, Sabadosa K, Marshall B, Cystic Fibrosis Foundation Pulmonary Therapies Committee: Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007, 176 (10): 957-969. 10.1164/rccm.200705-664OC.PubMed
99.
Weaver LT, Green MR, Nicholson K, Mills J, Heeley ME, Kuzemko JA, Austin S, Gregory GA, Dux AE, Davis JA: Prognosis in cystic fibrosis treated with continuous flucloxacillin from the neonatal period. Arch Dis Child. 1994, 70: 84-89. 10.1136/adc.70.2.84.PubMedPubMedCentral
100.
Ratjen F, Comes G, Paul K, Posselt HG, Wagner TO, Harms K, German Board of the European Registry for Cystic Fibrosis (ERCF): Effect of continuous antistaphylococcal therapy on the rate of P aeruginosa acquisition in patients with cystic fibrosis. Pediatr Pulmonol. 2001, 31 (1): 13-16. 10.1002/1099-0496(200101)31:1<13::AID-PPUL1001>3.0.CO;2-N.PubMed
101.
Smyth A, Walters S: Prophylactic antibiotics for cystic fibrosis. Cochrane Database Syst Rev. 2003, 3: CD001912.PubMed
102.
Valerius NH, Koch C, Høiby N: Prevention of chronic Pseudomonas aeruginosa colonisation in cystic fibrosis by early treatment. Lancet. 1991, 338 (8769): 725-726. 10.1016/0140-6736(91)91446-2.PubMed
103.
Frederiksen B, Koch C, Høiby N: Antibiotic treatment of initial colonization with Pseudomonas aeruginosa postpones chronic infection and prevents deterioration of pulmonary function in cystic fibrosis. Pediatr Pulmonol. 1997, 23 (5): 330-335. 10.1002/(SICI)1099-0496(199705)23:5<330::AID-PPUL4>3.0.CO;2-O.PubMed
104.
Munck A, Bonacorsi S, Mariani-Kurkdjian P, Lebourgeois M, Gérardin M, Brahimi N, Navarro J, Bingen E: Genotypic characterization of Pseudomonas aeruginosa strains recovered from patients with cystic fibrosis after initial and subsequent colonization. Pediatr Pulmonol. 2001, 32 (4): 288-292. 10.1002/ppul.1121.PubMed
105.
Ratjen F, Döring G, Nikolaizik WH: Effect of inhaled tobramycin on early Pseudomonas aeruginosa colonisation in patients with cystic fibrosis. Lancet. 2001, 358 (9286): 983-984. 10.1016/S0140-6736(01)06124-4.PubMed
106.
Ratjen F, Munck A, Kho P, Angyalosi G, ELITE Study Group: Treatment of early Pseudomonas aeruginosa infection in patients with cystic fibrosis: the ELITE trial. Thorax. 2010, 65 (4): 286-291. 10.1136/thx.2009.121657.PubMed
107.
Treggiari MM, Retsch-Bogart G, Mayer-Hamblett N, Khan U, Kulich M, Kronmal R, Williams J, Hiatt P, Gibson RL, Spencer T, Orenstein D, Chatfield BA, Froh DK, Burns JL, Rosenfeld M, Ramsey BW, Early Pseudomonas Infection Control (EPIC) Investigators: Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis. Arch Pediatr Adolesc Med. 2011, 165 (9): 847-856. 10.1001/archpediatrics.2011.136.PubMedPubMedCentral
108.
Hansen CR, Pressler T, Høiby N: Early aggressive eradication therapy for intermittent Pseudomonas aeruginosa airway colonization in cystic fibrosis patients: 15 years experience. J Cyst Fibros. 2008, 7 (6): 523-530. 10.1016/j.jcf.2008.06.009.PubMed
109.
Langton Hewer SC, Smyth AR: Antibiotic strategies for eradicating Pseudomonas aeruginosa in people with cystic fibrosis. Cochrane Database Syst Rev. 2009, 4: CD004197.PubMed
110.
Quittner AL, Buu A: Effects of tobramycin solution for inhalation on global ratings of quality of life in patients with cystic fibrosis and Pseudomonas aeruginosa infection. Pediatr Pulmonol. 2002, 33 (4): 269-276. 10.1002/ppul.10074.PubMed
111.
Oermann CM, Retsch-Bogart GZ, Quittner AL, Gibson RL, McCoy KS, Montgomery AB, Cooper PJ: An 18-month study of the safety and efficacy of repeated courses of inhaled aztreonam lysine in cystic fibrosis. Pediatr Pulmonol. 2010, 45 (11): 1121-1134. 10.1002/ppul.21301.PubMed
112.
Murphy TD, Anbar RD, Lester LA, Nasr SZ, Nickerson B, VanDevanter DR, Colin AA: Treatment with tobramycin solution for inhalation reduces hospitalizations in young CF subjects with mild lung disease. Pediatr Pulmonol. 2004, 38: 314-320. 10.1002/ppul.20097.PubMed
113.
Szaff M, Høiby N, Flensborg EW: Frequent antibiotic therapy improves survival of cystic fibrosis patients with chronic Pseudomonas aeruginosa infection. Acta Paediatr Scand. 1983, 72 (5): 651-657. 10.1111/j.1651-2227.1983.tb09789.x.PubMed
114.
Pedersen SS, Jensen T, Høiby N, Koch C, Flensborg EW: Management of Pseudomonas aeruginosa lung infection in Danish cystic fibrosis patients. Acta Paediatr Scand. 1987, 76 (6): 955-961. 10.1111/j.1651-2227.1987.tb17271.x.PubMed
115.
Birrer P, McElvaney NG, Rudeberg A, Sommer CW, Liechti-Gallati S, Kraemer R, Hubbard R, Crystal RG: Protease-antiprotease imbalance in the lungs of children with cystic fibrosis. Am J Respir Crit Care Med. 1994, 150: 207-213.PubMed
116.
Eigen H, Rosenstein BJ, FitzSimmons S, Schidlow DV: A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. J Pediatr. 1995, 126 (4): 515-523. 10.1016/S0022-3476(95)70343-8.PubMed
117.
Lai HC, FitzSimmons SC, Allen DB, Kosorok MR, Rosenstein BJ, Campbell PW, Farrell PM: Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis. N Engl J Med. 2000, 342 (12): 851-859. 10.1056/NEJM200003233421204.PubMed
118.
Balfour-Lynn IM, Lees B, Hall P, Phillips G, Khan M, Flather M, Elborn JS, CF WISE (Withdrawal of Inhaled Steroids Evaluation) Investigators: Multicenter randomized controlled trial of withdrawal of inhaled corticosteroids in cystic fibrosis. Am J Respir Crit Care Med. 2006, 173 (12): 1356-1362. 10.1164/rccm.200511-1808OC.PubMed
119.
Ren CL, Pasta DJ, Rasouliyan L, Wagener JS, Konstan MW, Morgan WJ, Scientific Advisory Group and the Investigators and Coordinators of the Epidemiologic Study of Cystic Fibrosis: Relationship between inhaled corticosteroid therapy and rate of lung function decline in children with cystic fibrosis. J Pediatr. 2008, 153 (6): 746-751. 10.1016/j.jpeds.2008.07.010.PubMed
120.
De Boeck K, Vermeulen F, Wanyama S, Thomas M, members of the Belgian CF Registry: Inhaled corticosteroids and lower lung function decline in young children with cystic fibrosis. Eur Respir J. 2011, 37 (5): 1091-1095. 10.1183/09031936.00077210.PubMed
121.
Brown KA, Collins AJ: Action of nonsteroidal, anti-inflammatory drugs on human and rat peripheral leucocyte migration in vitro. Ann Rheum Dis. 1977, 36: 239-243. 10.1136/ard.36.3.239.PubMedPubMedCentral
122.
Sordelli DO, Cerquetti MC, el-Tawil G, Ramwell PW, Hooke AM, Bellanti JA: Ibuprofen modifies the inflammatory response of the murine lung to Pseudomonas aeruginosa. Eur J Respir Dis. 1985, 67: 118-127.PubMed
123.
Kaplan HB, Edelson HS, Korchak HM, Given WP, Abramson S, Weissmann G: Effects of non-steroidal anti-inflammatory agents on human neutrophil functions in vitro and in vivo. Biochem Pharmacol. 1984, 33: 371-378. 10.1016/0006-2952(84)90228-4.PubMed
124.
Konstan MW, Byard PJ, Hoppel CL, Davis PB: Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995, 332 (13): 848-854. 10.1056/NEJM199503303321303.PubMed
125.
Lands LC, Milner R, Cantin AM, Manson D, Corey M: High-dose ibuprofen in cystic fibrosis: Canadian safety and effectiveness trial. J Pediatr. 2007, 151 (3): 249-254. 10.1016/j.jpeds.2007.04.009.PubMed
126.
Konstan MW, Schluchter MD, Xue W, Davis PB: Clinical use of ibuprofen is associated with slower FEV1 decline in children with cystic fibrosis. Am J Respir Crit Care Med. 2007, 176 (11): 1084-1089. 10.1164/rccm.200702-181OC.PubMedPubMedCentral
127.
Nelson S, Summer WR, Terry PB, Warr GA, Jakab GJ: Erythromycin-induced suppression of pulmonary antibacterial defenses. A potential mechanism of superinfection in the lung. Am Rev Respir Dis. 1987, 136 (5): 1207-1212. 10.1164/ajrccm/136.5.1207.PubMed
128.
Tsai WC, Rodriguez ML, Young KS, Deng JC, Thannickal VJ, Tateda K, Hershenson MB, Standiford TJ: Azithromycin blocks neutrophil recruitment in Pseudomonas endobronchial infection. Am J Respir Crit Care Med. 2004, 170 (12): 1331-1339. 10.1164/rccm.200402-200OC.PubMed
129.
Ichikawa Y, Ninomiya H, Koga H, Tanaka M, Kinoshita M, Tokunaga N, Yano T, Oizumi K: Erythromycin reduces neutrophils and neutrophil-derived elastolytic-like activity in the lower respiratory tract of bronchiolitis patients. Am Rev Respir Dis. 1992, 146 (1): 196-203.PubMed
130.
Oda H, Kadota J, Kohno S, Hara K: Erythromycin inhibits neutrophil chemotaxis in bronchoalveoli of diffuse panbronchiolitis. Chest. 1994, 106 (4): 1116-1123. 10.1378/chest.106.4.1116.PubMed
131.
Oishi K, Sonoda F, Kobayashi S, Iwagaki A, Nagatake T, Matsushima K, Matsumoto K: Role of interleukin-8 (IL-8) and an inhibitory effect of erythromycin on IL-8 release in the airways of patients with chronic airway diseases. Infect Immun. 1994, 62 (10): 4145-4152.PubMedPubMedCentral
132.
Cigana C, Nicolis E, Pasetto M, Assael BM, Melotti P: Anti-inflammatory effects of azithromycin in cystic fibrosis airway epithelial cells. Biochem Biophys Res Commun. 2006, 350 (4): 977-982. 10.1016/j.bbrc.2006.09.132.PubMed
133.
Yoshida K, Sunazuka T, Nagai K, Sugawara A, Cho A, Nagamitsu T, Harigaya Y, Otoguro K, Akagawa KS, Omura S: Macrolides with promotive activity of monocyte to macrophage differentiation. J Antibiot (Tokyo). 2005, 58 (1): 79-81. 10.1038/ja.2005.11.
134.
Li YJ, Azuma A, Usuki J, Abe S, Matsuda K, Sunazuka T, Shimizu T, Hirata Y, Inagaki H, Kawada T, Takahashi S, Kudoh S, Omura S: EM703 improves bleomycin-induced pulmonary fibrosis in mice by the inhibition of TGF-beta signaling in lung fibroblasts. Respir Res. 2006, 7: 16-10.1186/1465-9921-7-16.PubMedPubMedCentral
135.
Jaffé A, Francis J, Rosenthal M, Bush A: Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet. 1998, 351 (9100): 420-10.1016/S0140-6736(05)78360-4.PubMed
136.
Saiman L, Marshall BC, Mayer-Hamblett N, Burns JL, Quittner AL, Cibene DA, Coquillette S, Fieberg AY, Accurso FJ, Campbell PW, Macrolide Study Group: Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003, 290 (13): 1749-1756. 10.1001/jama.290.13.1749.PubMed
137.
Tateda K, Ishii Y, Hirakata Y, Matsumoto T, Ohno A, Yamaguchi K: Profiles of outer membrane proteins and lipopolysaccharide of Pseudomonas aeruginosa grown in the presence of sub-MICs of macrolide antibiotics and their relation to enhanced serum sensitivity. J Antimicrob Chemother. 1994, 34 (6): 931-942. 10.1093/jac/34.6.931.PubMed
138.
Imamura Y, Higashiyama Y, Tomono K, Izumikawa K, Yanagihara K, Ohno H, Miyazaki Y, Hirakata Y, Mizuta Y, Kadota J, Iglewski BH, Kohno S: Azithromycin exhibits bactericidal effects on Pseudomonas aeruginosa through interaction with the outer membrane. Antimicrob Agents Chemother. 2005, 49 (4): 1377-1380. 10.1128/AAC.49.4.1377-1380.2005.PubMedPubMedCentral
139.
Ichimiya T, Takeoka K, Hiramatsu K, Hirai K, Yamasaki T, Nasu M: The influence of azithromycin on the biofilm formation of Pseudomonas aeruginosa in vitro. Chemotherapy. 1996, 42 (3): 186-191. 10.1159/000239440.PubMed
140.
Nagino K, Kobayashi H: Influence of macrolides on mucoid alginate biosynthetic enzyme from Pseudomonas aeruginosa. Clin Microbiol Infect. 1997, 3 (4): 432-439. 10.1111/j.1469-0691.1997.tb00279.x.PubMed
141.
Phaff SJ, Tiddens HA, Verbrugh HA, Ott A: Macrolide resistance of Staphylococcus aureus and Haemophilus species associated with long-term azithromycin use in cystic fibrosis. J Antimicrob Chemother. 2006, 57 (4): 741-746. 10.1093/jac/dkl014.PubMed
142.
McElvaney NG, Hubbard RC, Birrer P, Chernick MS, Caplan DB, Frank MM, Crystal RG: Aerosol alpha 1-antitrypsin treatment for cystic fibrosis. Lancet. 1991, 337 (8738): 392-394. 10.1016/0140-6736(91)91167-S.PubMed
143.
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, 29 (2): 240-250.PubMed
144.
Roum JH, Buhl R, McElvaney NG, Borok Z, Crystal RG: Systemic deficiency of glutathione in cystic fibrosis. J Appl Physiol. 1993, 75 (6): 2419-2424.PubMed
145.
Bishop C, Hudson VM, Hilton SC, Wilde C: A pilot study of the effect of inhaled buffered reduced glutathione on the clinical status of patients with cystic fibrosis. Chest. 2005, 127 (1): 308-317. 10.1378/chest.127.1.308.PubMed
146.
Dauletbaev N, Fischer P, Aulbach B, Gross J, Kusche W, Thyroff-Friesinger U, Wagner TO, Bargon J: A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis. Eur J Med Res. 2009, 14 (8): 352-358.PubMedPubMedCentral
147.
Rosenblatt RL: Lung transplantation in cystic fibrosis. Respir Care. 2009, 54 (6): 777-786. 10.4187/002013209790983197. discussion 786-787PubMed
148.
Iacono AT, Smaldone GC, Keenan RJ, Diot P, Dauber JH, Zeevi A, Burckart GJ, Griffith BP: Dose-related reversal of acute lung rejection by aerosolized cyclosporine. Am J Respir Crit Care Med. 1997, 155 (5): 1690-1698.PubMed
149.
Iacono AT, Johnson BA, Grgurich WF, Youssef JG, Corcoran TE, Seiler DA, Dauber JH, Smaldone GC, Zeevi A, Yousem SA, Fung JJ, Burckart GJ, McCurry KR, Griffith BP: A randomized trial of inhaled cyclosporine in lung-transplant recipients. N Engl J Med. 2006, 354 (2): 141-150. 10.1056/NEJMoa043204.PubMed
150.
Konstan MW, Flume PA, Kappler M, Chiron R, Higgins M, Brockhaus F, Zhang J, Angyalosi G, He E, Geller DE: Safety, efficacy and convenience of tobramycin inhalation powder in cystic fibrosis patients: The EAGER trial. J Cyst Fibros. 2011, 10 (1): 54-61. 10.1016/j.jcf.2010.10.003.PubMed
151.
Geller DE, Flume PA, Staab D, Fischer R, Loutit JS, Conrad DJ, Mpex 204 Study Group: Levofloxacin inhalation solution (MP-376) in patients with cystic fibrosis with Pseudomonas aeruginosa. Am J Respir Crit Care Med. 2011, 183 (11): 1510-1516. 10.1164/rccm.201008-1293OC.PubMed
152.
VanDevanter DR, Konstan MW: Outcome measures for clinical trials assessing treatment of cystic fibrosis lung disease. Clin Invest. 2012, 2 (2): 163-175. 10.4155/cli.11.174.
Metadata
Title
State of progress in treating cystic fibrosis respiratory disease
Authors
Patrick A Flume
Donald R Van Devanter
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2012
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/1741-7015-10-88

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