title: Effect of dornase alfa on inflammation and lung function: potential role in the early treatment of cystic fibrosis.
abstract: Dornase alfa has been shown to reduce markers of inflammation and neutrophil-associated metalloproteinases in cystic fibrosis (CF), suggesting a potential benefit from use of this therapy early in the disease. However, observational studies indicate that dornase alfa is often reserved for "sicker" patients. A 2-year, early intervention study of dornase alfa in CF patients with early lung disease demonstrated significant improvements in lung function and risk of exacerbation compared to placebo. A more recent analysis, using the database of the large observational Epidemiologic Study of Cystic Fibrosis (ESCF), found that initiation of dornase alfa has the potential to alter the course of CF by decreasing the rate of lung function decline in children and adults. These encouraging results, possibly linked to indirect effects on inflammation, suggest a greater role for dornase alfa therapy in the early treatment of CF, where it may help preserve lung function and potentially extend survival.
authors.affiliation: Case Western Reserve University School of Medicine and Rainbow Babies and Children's Hospital, 11100 Euclid Avenue, Cleveland, OH 44106, USA.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Konstan
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
mesh_terms: D003550:Cystic Fibrosis / Q000188:drug therapy* / Q000503:physiopathology; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D018450:Disease Progression; D005541:Forced Expiratory Volume; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D008168:Lung / Q000187:drug effects / Q000503:physiopathology; D020780:Matrix Metalloproteinase 9 / Q000032:analysis
chemical_list: C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I; D020780:Matrix Metalloproteinase 9
references.citation: Am J Respir Crit Care Med. 1994 Aug;150(2):448-54
references.pmid: 8049828
references.citation: J Infect Dis. 1997 Mar;175(3):638-47
references.pmid: 9041336
references.citation: N Engl J Med. 1994 Sep 8;331(10):637-42
references.pmid: 7503821
references.citation: J Cyst Fibros. 2009 Jun;8 Suppl 1:S15-9
references.pmid: 19460682
references.citation: Pediatr Pulmonol. 1999 Oct;28(4):231-41
references.pmid: 10497371
references.citation: J Pediatr. 1999 Jun;134(6):734-9
references.pmid: 10356143
references.citation: Pediatr Res. 1997 Feb;41(2):161-5
references.pmid: 9029632
references.citation: J Pediatr. 2007 Aug;151(2):134-9, 139.e1
references.pmid: 17643762
references.citation: Pediatr Pulmonol. 2005 Jan;39(1):1-4
references.pmid: 15532079
references.citation: Am J Respir Crit Care Med. 2007 Dec 1;176(11):1084-9
references.pmid: 17872492
references.citation: Pediatr Pulmonol. 1997 Aug;24(2):137-42; discussion 159-61
references.pmid: 9292910
references.citation: Am J Respir Crit Care Med. 2004 Mar 15;169(6):719-25
references.pmid: 14684561
references.citation: Thorax. 2002 Nov;57(11):930-4
references.pmid: 12403873
references.citation: Pediatr Pulmonol. 1999 Oct;28(4):248-54
references.pmid: 10497373
references.citation: Pediatr Pulmonol. 2011 Jun;46(6):545-53
references.pmid: 21438174
references.citation: Eur Respir J. 2011 May;37(5):1091-5
references.pmid: 21071470
references.citation: Acta Paediatr. 2006 Sep;95(9):1070-4
references.pmid: 16938752
references.citation: Pediatr Pulmonol. 1995 Aug;20(2):63-70
references.pmid: 8570304
references.citation: Am J Respir Crit Care Med. 1995 Apr;151(4):1075-82
references.pmid: 7697234
references.citation: Am J Respir Crit Care Med. 1996 Nov;154(5):1426-9
references.pmid: 8912759
references.citation: Am J Respir Crit Care Med. 1999 Jul;160(1):186-91
references.pmid: 10390398
references.citation: Chest. 1996 Oct;110(4):889-95
references.pmid: 8874241
references.citation: Lancet. 2003 Feb 22;361(9358):681-9
references.pmid: 12606185
references.citation: J Pediatr. 2008 Dec;153(6):746-51
references.pmid: 18760805
references.citation: Am J Respir Crit Care Med. 2007 Nov 15;176(10):957-69
references.pmid: 17761616
references.citation: Eur Respir J. 2007 Apr;29(4):624-32
references.pmid: 17215317
references.citation: N Engl J Med. 1995 Mar 30;332(13):848-54
references.pmid: 7503838
references.citation: J Pediatr. 1997 Dec;131(6):809-14
references.pmid: 9427882
references.citation: Paediatr Respir Rev. 2006;7 Suppl 1:S70-2
references.pmid: 16798601
references.citation: Proc Natl Acad Sci U S A. 1990 Dec;87(23):9188-92
references.pmid: 2251263
references.citation: J Pediatr. 2001 Dec;139(6):813-20
references.pmid: 11743506
references.citation: Stat Med. 2002 May 15;21(9):1271-87
references.pmid: 12111878
references.citation: J Cyst Fibros. 2008 Sep;7(5):385-90
references.pmid: 18342580
references.citation: J Immunol. 2010 Jun 1;184(11):6386-95
references.pmid: 20421641
references.citation: BMJ. 2011 Feb 28;342:d1008
references.pmid: 21357627
references.citation: J Cyst Fibros. 2010 Sep;9(5):332-8
references.pmid: 20646968
references.citation: Clin Chest Med. 2007 Jun;28(2):331-46
references.pmid: 17467552
references.citation: Pediatr Pulmonol. 1998 Aug;26(2):97-100
references.pmid: 9727759