Comparison of hypertonic saline and alternate-day or daily recombinant human deoxyribonuclease in children with cystic fibrosis: a randomised trial.
BACKGROUND
Daily recombinant human deoxyribonuclease (rhDNase) is an established but expensive treatment in cystic fibrosis. Alternate-day treatment, if equally effective, would reduce the drug cost. Hypertonic saline improved lung function to the same degree as rhDNase in short-term studies. We compared the effectiveness of daily rhDNase, hypertonic saline, and alternate-day rhDNase in children with cystic fibrosis.


METHODS
In an open cross-over trial, 48 children were allocated in random order to 12 weeks of once-daily rhDNase (2.5 mg), alternate-day rhDNase (2.5 mg), and twice-daily 5 mL 7% hypertonic saline. The primary outcome was forced expiratory volume in 1 s (FEV(1)). Secondary outcomes were forced vital capacity, number of pulmonary exacerbations, weight gain, quality of life, exercise tolerance, and the total costs of hospital and community care.


RESULTS
Mean FEV(1) increased by 16% (SD 25%), 14% (22%), and 3% (21%) with daily rhDNase, alternate-day rhDNase, and hypertonic saline, respectively. There was no difference between daily and alternate-day rhDNase (2% [95% CI -4 to 9], p=0.55). However, daily rhDNase showed a significantly greater increase in FEV(1) than hypertonic saline (8% [2 to 14], p=0.01). The average difference in 12-week cost between daily and alternate-day rhDNase was pound513 (95% CI -546 to 1510) and that between daily rhDNase and hypertonic saline was pound1409 (440 to 2318). None of the secondary clinical outcomes showed significant differences between treatments.


CONCLUSIONS
Hypertonic saline, delivered by jet nebuliser, is not as effective as daily rhDNase, although there is variation in individual response. There is no evidence of a difference between daily and alternate-day rhDNase.
Suri
R
R
Respiratory Unit, Great Ormond Street Hospital for Children NHS Trust, London, UK. suriranjan@hotmail.com
Metcalfe
C
C
Lees
B
B
Grieve
R
R
Flather
M
M
Normand
C
C
Thompson
S
S
Bush
A
A
Wallis
C
C
D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000188:drug therapy*; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D017079:Exercise Tolerance / Q000187:drug effects; D005100:Expectorants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D013147:Spirometry
D005100:Expectorants; D011994:Recombinant Proteins; D012462:Saline Solution, Hypertonic; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I