Pharmacology, clinical efficacy and safety of recombinant human DNase in cystic fibrosis

Expert Review of Respiratory Medicine

Volumn 1, Issue 3, 2007, Pages 317-329

  Bakker, e M ^a   Tiddens, Hawm ^a  

^a SOPHIA CHILDREN S HOSPITAL   (Netherlands)

Author keywords

chemistry; cystic fibrosis; dornase ; efficacy; Pulmozyme ; rhDNase; safety

Indexed keywords

EID: 84858173182     PISSN: 17476348     EISSN: 17476356     Source Type: Journal    
DOI: 10.1586/17476348.1.3.317     Document Type: Article

References (80)

1. Slieker MG, Uiterwaal CS, Sinaasappel M, Heijerman HG, van der Laag J, van der Ent CK. Birth prevalence and survival in cystic fibrosis. A national cohort study in the Netherlands. Chest 128 (4), 2309–2315 (2005).
2. Dupuis A, Hamilton D, Cole DE, Corey M. Cystic fibrosis birth rates in Canada: a decreasing trend since the onset of genetic testing. J. Pediatr. 147 (3), 312–315 (2005).
3. Riordan JR, Rommens JM, Kerem B et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245 (4922), 1066–1073 (1989).
4. Accurso FJ. Update in cystic fibrosis 2006. Am. J. Respir. Crit. Care Med. 175 (8), 754–757 (2007).
5. Rogers DF. Pulmonary mucus: pediatric perspective. Pediatr. Pulmonol. 36 (3), 178–188 (2003).
6. Ratjen F. Restoring airway surface liquid in cystic fibrosis. N. Engl. J. Med. 354 (3), 291–293 (2006).
7. 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. The Pulmozyme Study Group. N. Engl. J. Med. 331 (10), 637–642 (1994).
8. 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. 354 (3), 229–240 (2006).
9. Hodson ME. Aerosolized dornase α (rhDNase) for therapy of cystic fibrosis. Am. J. Respir. Crit. Care Med. 151 (3 Pt 2), S70 –S74 (1995).
10. Shah PL, Scott SF, Fuchs HJ, Geddes DM, Hodson ME. Medium term treatment of stable stage cystic fibrosis with recombinant human DNase I. Thorax 50 (4), 333–338 (1995).
11. Quan JM, Tiddens HA, Sy JP et al. A two-year randomized, placebo-controlled trial of dornase α in young patients with cystic fibrosis with mild lung function abnormalities. J. Pediatr. 139 (6), 813–820 (2001).
12. Duijvestijn YC, Brand PL. Systematic review of N-acetylcysteine in cystic fibrosis. Acta Paediatr. 88 (1), 38–41 (1999).
13. Decramer M, Rutten-van Molken M, Dekhuijzen PN et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet 365 (9470), 1552–1560 (2005).
14. Shak S, Capon DJ, Hellmiss R, Marsters SA, Baker CL. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Proc. Natl Acad. Sci. USA 87 (23), 9188–9192 (1990).
15. Henke MO, Ratjen F. Mucolytics in cystic fibrosis. Paediatr. Respir. Rev. 8 (1), 24–29 (2007).
16. Bye PT, Elkins MR. Other mucoactive agents for cystic fibrosis. Paediatr. Respir. Rev. 8 (1), 30–39 (2007).
17. Suri R, Metcalfe C, Lees B et al. Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial. Lancet 358 (9290), 1316–1321 (2001).
18. Vasconcellos CA, Allen PG, Wohl ME et al. Reduction in viscosity of cystic fibrosis sputum in vitro by gelsolin. Science 263 (5149), 969–971 (1994).
19. Sheils CA, Kas J, Travassos W et al. Actin filaments mediate DNA fiber formation in chronic inflammatory airway disease. Am. J. Pathol. 148 (3), 919–927 (1996).
20. Sanders MC, Goldstein AL, Wang YL. Thymosin β 4 (Fx peptide) is a potent regulator of actin polymerization in living cells. Proc. Natl Acad. Sci. USA 89 (10), 4678–4682 (1992).
21. Safer D, Nachmias VT. β thymosins as actin binding peptides. Bioessays 16 (7), 473–479 (1994).
22. Rubin BK. The role of DNA and actin polymers on the polymer structure and rheology of cystic fibrosis sputum and depolymerization by gelsolin or thymosin β 4. Ann. NY Acad. Sci. 1112, 140–153 (2007).
23. Deterding R, Retsch-Bogart G, Milgram L et al. Safety and tolerability of denufosol tetrasodium inhalation solution, a novel P2Y2 receptor agonist: results of a Phase 1/Phase 2 multicenter study in mild to moderate cystic fibrosis. Pediatr. Pulmonol. 39 (4), 339–348 (2005).
24. Deterding RR, Lavange LM, Engels JM et al. Phase 2 randomized safety and efficacy trial of nebulized denufosol tetrasodium in cystic fibrosis. Am. J. Respir. Crit. Care Med. 176 (4), 362–369 (2007).
25. Lethem MI, James SL, Marriott C. The role of mucous glycoproteins in the rheologic properties of cystic fibrosis sputum. Am. Rev. Respir. Dis. 142 (5), 1053–1058 (1990).
26. Picot R, Das I, Reid L. Pus, deoxyribonucleic acid, and sputum viscosity. Thorax 33 (2), 235–242 (1978).
27. Kirchner KK, Wagener JS, Khan TZ, Copenhaver SC, Accurso FJ. Increased DNA levels in bronchoalveolar lavage fluid obtained from infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 154 (5), 1426–1429 (1996).
28. Wagener JS, Rock MJ, McCubbin MM, Hamilton SD, Johnson CA, Ahrens RC. Aerosol delivery and safety of recombinant human deoxyribonuclease in young children with cystic fibrosis: a bronchoscopic study. Pulmozyme Pediatric Bronchoscopy Study Group. J. Pediatr. 133 (4), 486–491 (1998).
29. McCarty M. Purification and properties of deoxyribonuclease isolated from beef pancreas. J. Gen. Physiol. 29, 123–139 (1946).
30. Armstrong JB, White JC. Liquefaction of viscous purulent exudates by deoxyribonuclease. Lancet 2, 739–742 (1950).
31. Chernick WS, Barbero GJ. Eichel HJ. In-vitro evaluation of effect of enzymes on tracheobronchial secretions from patients with cystic fibrosis. Pediatrics 27, 589–596 (1961).
32. Elmes PC, White JC. Deoxyribonuclease in the treatment of purulent bronchitis. Thorax 8 (4), 295–300 (1953).
33. Salomon A, Herchfus JA, Segal MS. Aerosols of pancreatic dornase in bronchopulmonary disease. Ann. Allergy 12 (1), 71–77 (1954).
34. Lieberman J. Dornase aerosol effect on sputum viscosity in cases of cystic fibrosis. JAMA 205 (5), 312–313 (1968).
35. Raskin P. Bronchospasm after inhalation of pancreatic dornase. Am. Rev. Respir. Dis. 98 (4), 697–698 (1968).
36. Lieberman J. Enzymatic dissolution of pulmonary secretions. An in vitro study of sputum from patients with cystic fibrosis of pancreas. Am. J. Dis. Child. 104, 342–348 (1962).
37. Liao TH, Salnikow J, Moore S, Stein WH. Bovine pancreatic deoxyribonuclease A. Isolation of cyanogen bromide peptides; complete covalent structure of the polypeptide chain. J. Biol. Chem. 248 (4), 1489–1495 (1973).
38. Suck D, Oefner C, Kabsch W. Three-dimensional structure of bovine pancreatic DNase I at 2.5 A resolution. EMBO J. 3 (10), 2423–2430 (1984).
39. Oefner C, Suck D. Crystallographic refinement and structure of DNase I at 2 A resolution. J. Mol. Biol. 192 (3), 605–632 (1986).
40. Pulmozyme – Summary of Product Characteristics. Roche Products Limited, Auckland, New Zealand (2004).
41. Zahm JM, Girod de Bentzmann S, Deneuville E et al. Dose-dependent in vitro effect of recombinant human DNase on rheological and transport properties of cystic fibrosis respiratory mucus. Eur. Respir. J. 8 (3), 381–386 (1995).
42. Hubbard RC, McElvaney NG, Birrer P et al. A preliminary study of aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis. N. Engl. J. Med. 326 (12), 812–815 (1992).
43. Green JD. Pharmaco–toxicological expert report Pulmozyme rhDNase Genentech, Inc. Hum. Exp. Toxicol. 13 (Suppl. 1), S1 –S42 (1994).
44. Aitken ML, Burke W, McDonald G et al. Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis. A Phase 1 study. JAMA 267 (14), 1947–1951 (1992).
45. Ranasinha C, Assoufi B, Shak S et al. Efficacy and safety of short-term administration of aerosolised recombinant human DNase I in adults with stable stage cystic fibrosis. Lancet 342 (8865), 199–202 (1993).
46. Ramsey BW, Astley SJ, Aitken ML et al. Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis. Am. Rev. Respir. Dis. 148 (1), 145–151 (1993).
47. Laube BL, Auci RM, Shields DE et al. Effect of rhDNase on airflow obstruction and mucociliary clearance in cystic fibrosis. Am. J. Respir. Crit. Care Med. 153 (2), 752–760 (1996).
48. Tiddens HA. Detecting early structural lung damage in cystic fibrosis. Pediatr. Pulmonol. 34 (3), 228–231 (2002).
49. Shah PI, Bush A, Canny GJ et al. Recombinant human DNase I in cystic fibrosis patients with severe pulmonary disease: a short-term, double-blind study followed by six months open-label treatment. Eur. Respir. J. 8 (6), 954–958 (1995).
50. McCoy K, Hamilton S, Johnson C. Effects of 12-week administration of dornase α in patients with advanced cystic fibrosis lung disease. Pulmozyme Study Group. Chest 110 (4), 889–895 (1996).
51. Jones AP, Wallis CE. Recombinant human deoxyribonuclease for cystic fibrosis. Cochrane Database Syst. Rev. 3, CD001127 (2003).
52. Hodson ME, McKenzie S, Harms HK et al. Dornase α in the treatment of cystic fibrosis in Europe: a report from the Epidemiologic Registry of Cystic Fibrosis. Pediatr. Pulmonol. 36 (5), 427–432 (2003).
53. Armstrong DS, Grimwood K, Carzino R et al. Lower respiratory infection and inflammation in infants with newly diagnosed cystic fibrosis. BMJ 310 (6994), 1571–1572 (1995).
54. Khan TZ, Wagener JS, Bost T et al. Early pulmonary inflammation in infants with cystic fibrosis. Am. J. Respir. Crit. Care Med. 151 (4), 1075–1082 (1995).
55. Shah PL, Scott SF, Geddes DM, Hodson ME. Two years experience with recombinant Human DNase I in the treatment of pulmonary disease in cystic fibrosis. Respir. Med. 89, 499–502 (1995).
56. Harms HK, Matouk E, Tournier G et al. Multicenter, open-label study of recombinant human DNase in cystic fibrosis patients with moderate lung disease. DNase International Study Group. Pediatr. Pulmonol. 26 (3), 155–161 (1998).
57. Christopher F, Chase D, Stein K, Milne R. rhDNase therapy for the treatment of cystic fibrosis patients with mild to moderate lung disease. J. Clin. Pharm. Ther. 24 (6), 415–426 (1999).
58. Sanders NN, Franckx H, De Boeck K et al. Role of magnesium in the failure of rhDNase therapy in patients with cystic fibrosis. Thorax 61 (11), 962–968 (2006).
59. Paul K, Rietschel E, Ballmann M et al. Effect of treatment with dornase α on airway inflammation in patients with cystic fibrosis. Am. J. Respir. Crit. Care Med. 169 (6), 719–725 (2004).
60. Suri R, Marshall LJ, Wallis C et al. Effects of recombinant human DNase and hypertonic saline on airway inflammation in children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 166 (3), 352–355 (2002).
61. Henry RL, Gibson PG, Carty K, Cai Y, Francis JL. Airway inflammation after treatment with aerosolized deoxyribonuclease in cystic fibrosis. Pediatr. Pulmonol. 26 (2), 97–100 (1998).
62. Que C, Cullinan P, Geddes D. Improving rates of decline in FEV1 in young adults with cystic fibrosis. Thorax 61 (2), 155–157 (2006).
63. de Jong PA, Lindblad A, Rubin L et al. Progression of lung disease on computed tomography and pulmonary function tests in children and adults with cystic fibrosis. Thorax 61 (1), 80–85 (2006).
64. Brody AS, Tiddens HA, Castile RG et al. Computed tomography in the evaluation of cystic fibrosis lung disease. Am. J. Respir. Crit. Care Med. 172 (10), 1246–1252 (2005).
65. de Jong PA, Tiddens HA. Cystic fibrosis specific computed tomography scoring. Proc. Am. Thorac. Soc. 4 (4), 338–342 (2007).
66. Robinson TE, Goris ML, Zhu HJ et al. Dornase α reduces air trapping in children with mild cystic fibrosis lung disease. Chest 128 (4), 2327–2335 (2005).
67. Nasr SZ, Kuhns LR, Brown RW et al. Use of computerized tomography and chest x-rays in evaluating efficacy of aerosolized recombinant human DNase in cystic fibrosis patients younger than age 5 years: a preliminary study. Pediatr. Pulmonol. 31 (5), 377–382 (2001).
68. Brody AS, Sucharew H, Campbell JD et al. Computed tomography correlates with pulmonary exacerbations in children with cystic fibrosis. Am. J. Respir. Crit. Care Med. 172 (9), 1128–1132 (2005).
69. Tiddens HA, Brody AS. Monitoring cystic fibrosis lung disease in clinical trials: is it time for a change? Proc. Am. Thorac. Soc. 4 (4), 297–298 (2007).
70. Brody AS. Computed tomography scanning in cystic fibrosis research trials: practical lessons from three clinical trials in the United States. Proc. Am. Thorac. Soc. 4 (4), 350–354 (2007).
71. Boe J, Dennis JH, O’Driscoll BR et al. European Respiratory Society Guidelines on the use of nebulizers. Eur. Respir. J. 18 (1), 228–242 (2001).
72. Fiel SB, Fuchs HJ, Johnson C, Gonda I, Clark AR. Comparison of three jet nebulizer aerosol delivery systems used to administer recombinant human DNase I to patients with cystic fibrosis. The Pulmozyme rhDNase Study Group. Chest 108 (1), 153–156 (1995).
73. Shah PL, Scott SF, Geddes DM et al. An evaluation of two aerosol delivery systems for rhDNase. Eur. Respir. J. 10 (6), 1261–1266 (1997).
74. Geller DE, Eigen H, Fiel SB et al. Effect of smaller droplet size of dornase α on lung function in mild cystic fibrosis. Dornase α Nebulizer Group. Pediatr. Pulmonol. 25 (2), 83–87 (1998).
75. Vecellio L. The mesh nebulizer: a recent technical innovation for aerosol delivery. Breathe 2 (3), 253–260 (2006).
76. Berge MT, Wiel E, Tiddens HA et al. DNase in stable cystic fibrosis infants: a pilot study. J. Cyst. Fibros. 2 (4), 183–188 (2003).
77. Brandt T, Breitenstein S, von der Hardt H, Tummler B. DNA concentration and length in sputum of patients with cystic fibrosis during inhalation with recombinant human DNase. Thorax 50 (8), 880–882 (1995).
78. Puchelle E, Zahm JM, de Bentzmann S et al. Effects of rhDNase on purulent airway secretions in chronic bronchitis. Eur. Respir. J. 9 (4), 765–769 (1996).
79. Rubin BK. The pharmacologic approach to airway clearance: mucoactive agents. Paediatr. Respir. Rev. 7 (Suppl. 1), S215 –S219 (2006).
80. US FDA www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm