Background -Viscoelastic secretions in cystic fibrosis cause impaired mucus clearance and persistence of bacteria within the lung. The abnormal rheology is partly due to the presence of high molecular weight deoxyribonucleic acid (DNA). Recombinant human DNase I (rhDNase) has been shown to depolymerise DNA and thereby reduce the in vitro viscoelasticity of sputum in patients with cystic fibrosis. A phase II double blind placebo controlled study showed that rhDNase improved pulmonary function in patients with cystic fibrosis. The object of the present study was to evaluate the in vivo effects of rhDNase on sputum rheology and to determine whether these were correlated with changes in pulmonary function. Methods -Patients were randomised to receive either placebo or rhDNase 2-5 mg twice daily for 10 days. Sputum samples were collected in sterile containers during screening and during treatment with the study drug. Pulmonary function and rheological analysis were the primary outcomes evaluated. Other parameters assessed were quantitative sputum bacteriology, sputum DNA concentration, and change in molecular mass of DNA polymers.Results -The viscoelasticity of the sputum in untreated patients with cystic fibrosis was high and treatment with rhDNase reduced all the rheological parameters measured: dynamic storage modulus (a measure of elasticity), dynamic loss modulus (a measure ofviscosity), and log complex modulus (a measure of mucus rigidity). The calculated cough clearance index was also improved following treatment with rhDNase. These rheological parameters showed a correlation with forced expiratory volume in one second (FEV1) which was improved by a mean (SE) of 13'3 (5-6)% on day 10 of treatment with rhDNase compared with a change of 0-2 (3.1)% in the placebo group. There was no change in bacterial colony counts or sputum DNA concentrations following treatment with rhDNase, but a small decrease in high molecular weight DNA was observed. Conclusions -Patients with cystic fibrosis treated with rhDNase show an improvement in rheological properties and pulmonary function, one of the mechanisms being a reduction in the proportion of high molecular weight DNA.
Background: Chronic endobronchial sepsis and profuse airway secretions dominate pulmonary disease in cystic fibrosis. Recombinant human DNase I (dornase alfa) reduces the viscoelasticity of airway secretions and hence may improve clearance of airway secretions. Objectives: To evaluate the long-term influence of dornase alfa on disease progression by performing a case-controlled study with dornase alfa over a period of 4 years. Methods: A cohort of patients with cystic fibrosis who have been treated with dornase alfa were matched with a control group of patients with cystic fibrosis who had not received treatment with dornase alfa. The patients were matched by pulmonary function, age, and then sex. All available measurements of forced expiratory volume in one second (FEV1), height, weight and sputum bacteriology were collected for periods when the patients were free from respiratory exacerbations. Results: Thirty-eight patients were matched. Slopes of median changes in FEV1 were –2.19 (–3.32, –1.06) in the control group and –0.75 (–1.87, 0.36) in the dornase alfa-treated group (p = 0.076). There were more infective exacerbations per patient year in the control group [3.13 (1.25–4.25)] in comparison to the dornase alfa group [1.25 (0.63–3.0), p = 0.035] over the 4-year treatment period. Antibiotic requirements were also greater with a median 43.75 (17.5–60.0) days of intravenous antibiotic use per patient year in the control group and 16.25 (8.5–44.0) days in the dornase alfa group (p = 0.034). Conclusions: The trends suggest that dornase alfa may have some influence on disease progression but in view of the limitations of the current study the need for further long-term studies in larger cohorts of patients is emphasised.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.