title: Effects of recombinant human DNase and hypertonic saline on airway inflammation in children with cystic fibrosis.
abstract: Recombinant human DNase (rhDNase) is an established treatment in cystic fibrosis (CF), but it may liberate cationic mediators bound to DNA in the airways. An alternative mucolytic therapy is hypertonic saline (HS); however, HS may potentiate neutrophilic inflammation. We compared the effect of rhDNase and HS on cationic proinflammatory mediators in CF sputum. In a randomized, crossover trial, 48 children with CF were allocated consecutively to 12 weeks of once-daily 2.5 mg rhDNase, alternate-day 2.5 mg rhDNase, and twice-daily 7% HS. Sputum levels of total interleukin-8 (IL-8), free IL-8, myeloperoxidase, eosinophil cationic protein, and neutrophil elastase (NE) activity were measured before and after each treatment. The change in mediator levels from baseline with daily rhDNase and HS was not significant; however, with alternate-day rhDNase, there was an increase in free IL-8. When changes in mediator levels with daily rhDNase were compared with alternate-day rhDNase and HS, no significant differences were detected. Only changes in NE activity were associated with changes in lung function. In summary, we were unable to show that rhDNase or HS promote airway inflammation in CF.
authors.affiliation: MRCPCH, Department of Respiratory Paediatrics, Royal Brompton and Harefield NHS Trust, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK. suriranjan@hotmail.com
authors.forename: Ranjan
authors.initials: R
authors.lastname: Suri
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Marshall
authors.forename: Colin
authors.initials: C
authors.lastname: Wallis
authors.forename: Christopher
authors.initials: C
authors.lastname: Metcalfe
authors.forename: Andrew
authors.initials: A
authors.lastname: Bush
authors.forename: Janis K
authors.initials: JK
authors.lastname: Shute
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018592:Cross-Over Studies; D003550:Cystic Fibrosis / Q000150:complications*; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005100:Expectorants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000032:analysis*; D008297:Male; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012140:Respiratory Tract Diseases / Q000150:complications* / Q000188:drug therapy*; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D013183:Sputum / Q000737:chemistry
chemical_list: D005100:Expectorants; D018836:Inflammation Mediators; D011994:Recombinant Proteins; D012462:Saline Solution, Hypertonic; C085693:DNASE1 protein, human; D003850:Deoxyribonuclease I