***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: The goal of this study was to evaluate the safety and efficacy of recombinant human DNase ( rhDNase ) in hospitalized patients with cystic fibrosis ( CF ) experiencing acute pulmonary exacerbations . Eighty patients with documented CF were enrolled at 11 CF centers when admitted for antibiotic therapy . Patients were at least 5 yr old with a forced vital capacity ( FVC ) > or = 35 % of predicted and an oxygen saturation > or = 90 % on a fraction of inspired oxygen ( FIO2 ) < 0.5 . Patients were r and omized to receive rhDNase 2.5 mg in 2.5 ml excipient twice a day ( n = 43 ) or 2.5 ml excipient alone twice daily ( n = 37 ) along with conventional treatment for exacerbations . Administration of rhDNase was not associated with acute adverse events or deaths , and no patients experienced allergic or anaphylactic reactions . Although forced expiratory volume in one second ( FEV1 ) and FVC improved in both treatment groups during the double-blind period , there were no statistically significant differences in the mean change from baseline in FEV1 or FVC between the two groups . rhDNase therapy is safe and well tolerated in CF patients with acute exacerbations requiring hospitalization , but the study did not demonstrate a statistically significant therapeutic effect of rhDNase when added to a regimen of antibiotics and chest physical therapy OBJECTIVE To assess the feasibility of measuring short-term effects of inhaled recombinant human deoxyribonuclease ( rhDNase , Pulmozyme on lung function , pulse oximetry and symptom scores in infants and toddlers with stable cystic fibrosis . DESIGN open-label r and omized placebo controlled cross-over pilot study . PATIENTS AND METHODS We treated nine CF patients ( 0.7 - 1.9 years ) with nebulised rhDNase ( 2.5 mg ) and NaCl 0.9 % ( 10 ml ) via jet nebulizer cross-over once daily during 2-week treatment blocks . Measurements were performed at baseline and after treatment blocks and consisted of lung function tests ( plethysmography and tidal rapid thoraco-abdominal compression technique ) , overnight pulse oximetry , and daily symptom scores . RESULTS DNase treatment and the different assessment s were well tolerated by all children and their parents . Lung function showed increased airway patency after treatment with rhDNase ( P < 0.001 ) , but not after NaCl 0.9 % . Overnight pulse oximetry and daily symptom scores did not change during the study period . CONCLUSIONS This pilot study indicates that objective assessment of the effects of rhDNase is feasible in infants with CF who have little or no respiratory symptoms . Our results warrant a larger r and omized placebo-controlled trial Economic evaluations of pharmaceuticals are increasingly being conducted in conjunction with r and omized phase III clinical trials to meet the dem and for pharmacoeconomic data when new products are launched . While the need for such data is often global , the trials in which relevant information may be collected are often conducted in only one or a limited number of countries . A critical issue is how data from pivotal clinical trials in one setting can serve as the basis for pharmacoeconomic evaluations in others . We address this issue and report on four economic evaluations that we undertook in conjunction with a recent U.S. phase III clinical trial of recombinant human deoxyribonuclease ( rhDNase ) , which is used to improve pulmonary function in patients with cystic fibrosis ( CF ) . The objective of these evaluations was to estimate the potential impact of  rhDNase therapy in France , Germany , Italy , and the United Kingdom on the direct costs of medical care for the treatment of respiratory tract infections ( RTIs ) in patients with CF . Analyses of economic impact were undertaken both with and without adjustment for differences in practice patterns between the United States and the countries of interest . Our findings suggest that rhDNase therapy may reduce the cost of RTI-related care by between US$ 600 and US$ 1,100 over a 24-week period ; the cost of rhDNase is not included in these figures , as a price was unavailable when our analyses were undertaken . Despite method ologic challenges , economic evaluations that meet the information needs of decision makers in diverse countries can nonetheless be undertaken in conjunction with phase III clinical trials Accumulation of viscous sputum enhances lung damage in patients with cystic fibrosis . High contents of DNA , released by leucocytes , are the major cause of the high viscosity of this sputum . Recombinant human DNase I ( rhDNase ) decreases viscoelastic properties of sputum in cystic fibrosis and improves lung function . We have investigated the effect of rhDNase over a period of 6 weeks , 2.5 mg once daily , on lung function and quality of life in 12 adult patients with cystic fibrosis . Significant improvements in FEV1 , IVC and daily peak flow values were measured . Airway resistance and FVC did not improve significantly . The cause of the improvements found is probably due to recruitment of previously , due to mucus plugging , unventilated lung areas . In addition , the awareness of symptoms related to sputum retention improved , although subjective parameters on general well-being and physical condition remained unchanged Cystic fibrosis ( CF ) is the most frequent lethal autosomal recessive disease among Caucasians . In more than 90 % of all patients the pulmonary involvement is the life-limiting factor . In the lung , the production of viscous sputum is a main and early clinical feature of CF . To help clear the lungs from this material mucolytic active drugs were used . Recombinant human DNase ( rhDNase ) w1x and hypertonic ( 5.85 % ) saline ( HS ) w2x both were mucolytic active and improved FEV1 in the same range in patients with CF . Besides this similarity there are differences such as the modulation of rheological parameters and costs . To determine whether these treatments can replace each other , we compared effect and acceptance in the same group of patients Recombinant human deoxyribonuclease ( rhDNase ) has been shown to improve lung function and reduce the number of pulmonary exacerbations in patients with cystic fibrosis ( CF ) , but its long-term effect on airway inflammation remains unknown . In this study , we used bronchoalveolar lavage ( BAL ) to investigate the long-term effect of rhDNase on inflammation in patients with CF having mild lung disease . A total of 105 patients with CF ( > or = 5 years of age ) having normal lung function were r and omized to receive rhDNase ( 2.5 mg/day ) or no rhDNase .  Patients with a normal percentage of neutrophils in BAL fluid at baseline were not r and omized and served as the control group . The percentage of neutrophils in the pooled BAL sample was similar in both r and omized groups at baseline . A significant increase in neutrophils was observed over the 3-year study period in both untreated patients and control subjects , whereas neutrophils remained unchanged in patients treated with rhDNase .  Elastase activities and interleukin-8 concentrations also increased in untreated patients and remained stable in patients on rhDNase . We conclude that in patients with CF , an increase in neutrophilic airway inflammation is found that is positively influenced by rhDNase treatment OBJECTIVES This study compared the relative cost-effectiveness of daily recombinant human deoxyribonuclease ( rhDNase ) , with alternate day rhDNase and hypertonic saline ( HS ) for treating children with cystic fibrosis ( CF ) . METHODS A r and omized controlled trial with a crossover design allocated 40 CF children consecutively to 12 weeks of daily rhDNase , alternate day rhDNase , or HS . The primary outcome measure was forced expiratory volume in 1 second ( FEV1 ) , a measure of lung function . All health re source use was prospect ively documented for each patient and multiplied by unit costs to give a total health service cost for each 12-week treatment period . The nonparametric bootstrap method was used to present cost-effectiveness acceptability curves and net benefit statistics for each treatment comparison , for various hypothetical levels of the decision maker 's ceiling ratio . RESULTS Compared with HS , there was a 14 % improvement in FEV1 for daily rhDNase ( 95 % Cl , 5 % to 23 % ) , and a 12 % improvement ( 95 % Cl , 2 % to 22 % ) for alternate day rhDNase . For a ceiling ratio of 200 pounds sterling per 1 % gain in FEV1 , the mean net benefits of daily and alternate day rhDNase compared with HS were 1,158 pounds sterling ( 95 % Cl , -621pounds sterling to 2,842 ) and 1,188 pounds sterling ( 95 % Cl , -847 to 3,343 ) , respectively ; the mean net benefit of daily compared with alternate day rhDNase was -30 pounds sterling ( 95 % Cl , -2,091 pounds sterling to 1,576 ) . CONCLUSIONS If decision makers are prepared to pay 200 pounds sterling for a 1 % gain in FEV1 over a 12-week period , then on average either rhDNase strategy is cost-effective OBJECTIVE Our objective was to determine whether long-term treatment of young patients with cystic fibrosis ( CF ) with dornase alfa maintains lung function and reduces respiratory tract exacerbations . STUDY DESIGN This was a 96-week , r and omized , double-blind , placebo-controlled trial involving 49 CF centers . Inclusion criteria were age 6 to 10 years and forced vital capacity > or = 85 % predicted . Patients were excluded for hospitalization for complications of CF within 2 months and use of dornase alfa within 6 months . Patients were treated with dornase alfa 2.5 mg or placebo once daily with a jet nebulizer and a compressor . RESULTS Patients were r and omized , 239 to dornase alfa and 235 to placebo . At baseline the mean age was 8.4 years , the mean forced expiratory volume in 1 second 95 % predicted , the mean forced expiratory flow , midexpiratory phase 85 % predicted , and the mean forced vital capacity 102 % predicted . At 96 weeks the treatment benefit for dornase alfa compared with placebo in percent predicted ( mean + /- SE ) was 3.2 + /- 1.2 for forced expiratory volume in 1 second ( P = .006 ) , 7.9 + /- 2.3 for forced expiratory flow between 25 % and 75 % of vital capacity ( P = .0008 ) , and 0.7 + /- 1.0 for forced vital capacity ( P = .51 ) . The risk of respiratory tract exacerbation was reduced by 34 % in patients who received dornase alfa ( relative risk 0.66 , P = .048 ) . There was no statistically significant difference between the groups in changes in weight-for-age percentile . Adverse event profiles for the treatment groups were similar . CONCLUSIONS Treatment of young patients with CF with dornase alfa maintains lung function and reduces the risk of exacerbations over a 96-week period Cystic fibrosis ( CF ) is caused by mutation in the gene for the CF transmembrane conductance regulator which leads to massive , abnormally viscous , purulent sputum , chronic destructive endobronchitis and early death . Purified recombinant human ( rh ) DNase can digest extracellular DNA and its inhalation in these patients significantly improves lung function . To evaluate the poorly understood mechanisms , saliva protected sputum from patients treated with and without rhDNase  were evaluated . Therapy with rhDNase result ed in a soluble sputum fraction that had a higher percentage of phosphatidylethanolamine , a phospholipid present mainly in cellular membranes , a much lower percentage of phosphatidylcholine , but a higher surface activity . The rigidity was significantly lower and the ratio of viscosity in proportion to elasticity increased . All these data are consistent with an increased clearability of the sputum by coughing , but not by mucociliary activity . Thus the interaction of inhaled rhDNase with the purulent mucus and the endobronchial inflammatory processes may induce changes that result in rheological properties favoring clearance of sputum by cough 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 r and om 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 . FINDINGS 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 
    Output:
    
The number of deaths was not significant between treatment groups .
Lung function improved in the treated groups , with significant differences at one month , three months , six months and two years .
Therapy over a two year period ( based on one trial ) significantly improved FEV1 in children and there was a non-significant reduction in the risk of infective exacerbations .
Voice alteration and rash appear to be the only adverse events reported with increased frequency in r and omised controlled trials