A phase II study on safety and efficacy of high-dose N-acetylcysteine in patients with cystic fibrosis

European Journal of Medical Research

Volumn 14, Issue 8, 2009, Pages 352-358

  Dauletbaev, N ^a   Fischer, P ^a   Aulbach, B ^a   Gross, J ^b   Kusche, W ^c   Thyroff Friesinger, U ^b   Wagner, T O F ^a   Bargon, Joachim ^a,d  

^a UNIVERSITY HOSPITAL FRANKFURT   (Germany)

^b Sandoz Biopharmaceuticals   (Germany)

^c ACRO Clinical Research Services GmbH   (Germany)

^d St Elisabeth Hospital   (Germany)

Author keywords

Cystic fibrosis; Glutathione; Induced sputum; Inflammation; N acetylcysteine

Indexed keywords

ACETYLCYSTEINE; GLUTATHIONE; INTERLEUKIN 8; PLACEBO; TUMOR NECROSIS FACTOR ALPHA;

ADULT; ANTIBIOTIC THERAPY; ARTICLE; CELL DIFFERENTIATION; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CYSTIC FIBROSIS; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; FORCED EXPIRATORY VOLUME; GASTROINTESTINAL HEMORRHAGE; HETEROZYGOSITY; HUMAN; LEUKOCYTE COUNT; LOW DRUG DOSE; MALE; PATIENT COMPLIANCE; PHASE 2 CLINICAL TRIAL; RANDOMIZED CONTROLLED TRIAL; TREATMENT DURATION; TREATMENT OUTCOME; UNSPECIFIED SIDE EFFECT;

EID: 69249175144     PISSN: 09492321     EISSN: None     Source Type: Journal    
DOI: 10.1186/2047-783x-14-8-352     Document Type: Article

References (23)

1. Eigen H, Rosenstein BJ, FitzSimmons S, Schidlow DV. A multicenter study of alternate-day prednisone therapy in patients with cystic fibrosis. Cystic Fibrosis Foundation Prednisone Trial Group. J Pediatr. 1995 Apr;126(4):515-23.
2. Auerbach HS, Williams M, Kirkpatrick JA, Colten HR. Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis. Lancet. 1985 Sep 28;2(8457):686-688
3. Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of high-dose ibuprofen in patients with cystic fibrosis. N Engl J Med. 1995 Mar 30;332 (13):848-854
4. Lands LC, Milner R, Cantin AM, Manson D, Corey M. High-dose ibuprofen in cystic fibrosis: Canadian safety and effectiveness trial. J Pediatr. 2007 Sep;151(3):249-254 (Pubitemid 47284135)
5. Lai HC, FitzSimmons SC, Allen DB et al. Risk of persistent growth impairment after alternate-day prednisone treatment in children with cystic fibrosis. N Engl J Med. 2000 Mar 23;342(12):851-859
6. Chmiel JF, Konstan MW. Inflammation and anti-inflammatory therapies for cystic fibrosis. Clin Chest Med. 2007 Jun;28(2):331-346
7. Schwarzer C, Fischer H, Kim EJ et al. Oxidative stress caused by pyocyanin impairs CFTR Cl(-) transport in human bronchial epithelial cells. Free Radic Biol Med. 2008 Dec 15;45(12):1653-1662
8. Rada B, Lekstrom K, Damian S, Dupuy C, Leto TL. The Pseudomonas toxin pyocyanin inhibits the dual oxidase-based antimicrobial system as it imposes oxidative stress on airway epithelial cells. J Immunol. 2008 Oct 1;181(7):4883-4893
9. Witko-Sarsat V, Delacourt C, Rabier D, Bardet J, Nguyen AT, Descamps-Latscha B. Neutrophil-derived long-lived oxidants in cystic fibrosis sputum. Am J Respir Crit Care Med. 1995 Dec;152(6 Pt 1):1910-1916
10. Tirouvanziam R, Conrad CK, Bottiglieri T, Herzenberg LA, Moss RB, Herzenberg LA. High-dose oral N-acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4628-4633
11. Dauletbaev N, Viel K, Buhl R, Wagner TO, Bargon J. Glutathione and glutathione peroxidase in sputum samples of adult patients with cystic fibrosis. J Cyst Fibros. 2004 Jun;3(2):119-124. (Pubitemid 38987022)
12. Dauletbaev N, Rickmann J, Viel K, Buhl R, Wagner TO, Bargon J. Glutathione in induced sputum of healthy individuals and patients with asthma. Thorax. 2001 Jan;56(1):13-18
13. Roum JH, Buhl R, McElvaney NG, Borok Z, Crystal RG. Systemic deficiency of glutathione in cystic fibrosis. J Appl Physiol. 1993 Dec;75(6):2419-2424 (Pubitemid 24008354)
14. Kogan I, Ramjeesingh M, Li C et al. CFTR directly mediates nucleotide-regulated glutathione flux. EMBO J. 2003 May 1;22(9):1981-1989
15. Gao L, Kim KJ, Yankaskas JR, Forman HJ. Abnormal glutathione transport in cystic fibrosis airway epithelia. Am J Physiol. 1999 Jul;277(1 Pt 1):L113-8. (Pubitemid 29356757)
16. Linsdell P, Hanrahan JW. Glutathione permeability of CFTR. Am J Physiol. 1998 Jul;275(1 Pt 1):C323-6.
17. Terheggen-Lagro SW, Rijkers GT, van der Ent CK. The role of airway epithelium and blood neutrophils in the inflammatory response in cystic fibrosis. J Cyst Fibros. 2005 Aug;4Suppl 2:15-23.
18. Jacquot J, Tabary O, Le RP, Clement A. Airway epithelial cell inflammatory signalling in cystic fibrosis. Int J Biochem Cell Biol. 2008;40(9):1703-1715
19. Ghibelli L, Coppola S, Rotilio G, Lafavia E, Maresca V, Ciriolo MR. Non-oxidative loss of glutathione in apoptosis via GSH extrusion. Biochem Biophys Res Commun. 1995 Nov 2;216(1):313-320
20. van den Dobbelsteen DJ, Nobel CS, Schlegel J, Cotgreave IA, Orrenius S, Slater AF. Rapid and specific efflux of reduced glutathione during apoptosis induced by anti-Fas/APO-1 antibody. J Biol Chem. 1996 Jun 28;271(1):15420-15427 (Pubitemid 26225311)
21. Hammond CL, Madejczyk MS, Ballatori N. Activation of plasma membrane reduced glutathione transport in death receptor apoptosis of HepG2 cells. Toxicol Appl Pharmacol. 2004 Feb 15;195(1):12-22.
22. Hammond CL, Marchan R, Krance SM, Ballatori N. Glutathione export during apoptosis requires functional multidrug resistance-associated proteins. J Biol Chem. 2007 May 11;282(19):14337-14347 (Pubitemid 47100459)
23. Marchan R, Hammond CL, Ballatori N. Multidrug resistance-associated protein 1 as a major mediator of basal and apoptotic glutathione release. Biochim Biophys Acta. 2008 Oct;1778(10):2413-2420