***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: Objective We conducted a single-centre , r and omised , double-blinded , placebo-controlled phase II clinical study to test safety and efficacy of a 12-week therapy with low-dose ( 700 mg/daily ) or high-dose ( 2800 mg/daily ) of NAC . Methods Twenty-one patients ( ΔF508 homo/heterozygous , FEV1 > 40 % pred . ) were included in the study . After a 3-weeks placebo run-in phase , 11 patients received low-dose NAC , and 10 patients received high-dose NAC . Outcomes included safety and clinical parameters , inflammatory ( total leukocyte numbers , cell differentials , TNF-α , IL-8 ) measures in induced sputum , and concentrations of extracellular glutathione in induced sputum and blood . Results High-dose NAC was a well-tolerated and safe medication . High-dose NAC did not alter clinical or inflammatory parameters . However , extracellular glutathione in induced sputum tended to increase on high-dose NAC . Conclusions High-dose NAC is a well-tolerated and safe medication for a prolonged therapy of patients with CF with a potential to increase extracellular glutathione in CF airways BACKGROUND Inhaled hypertonic saline acutely increases mucociliary clearance and , in short-term trials , improves lung function in people with cystic fibrosis . We tested the safety and efficacy of inhaled hypertonic saline in a long-term trial . METHODS In this double-blind , parallel-group trial , 164 patients with stable cystic fibrosis who were at least six years old were r and omly assigned to inhale 4 ml of either 7 percent hypertonic saline or 0.9 percent ( control ) saline twice daily for 48 weeks , with quinine sulfate ( 0.25 mg per milliliter ) added to each solution to mask the taste . A bronchodilator was given before each dose , and other st and ard therapies were continued during the trial . RESULTS The primary outcome measure , the rate of change ( slope ) in lung function ( reflected by the forced vital capacity [ FVC ] , forced expiratory volume in one second [ FEV1 ] , and forced expiratory flow at 25 to 75 percent of FVC [ FEF25 - 75 ] ) during the 48 weeks of treatment , did not differ significantly between groups ( P=0.79 ) . However , the absolute difference in lung function between groups was significant ( P=0.03 ) when averaged across all post-r and omization visits in the 48-week treatment period . As compared with the control group , the hypertonic-saline group had significantly higher FVC ( by 82 ml ; 95 percent confidence interval , 12 to 153 ) and FEV1 ( by 68 ml ; 95 percent confidence interval , 3 to 132 ) values , but similar FEF25 - 75 values . The hypertonic-saline group also had significantly fewer pulmonary exacerbations ( relative reduction , 56 percent ; P=0.02 ) and a significantly higher percentage of patients without exacerbations ( 76 percent , as compared with 62 percent in the control group ; P=0.03 ) . Hypertonic saline was not associated with worsening bacterial infection or inflammation . CONCLUSIONS Hypertonic saline preceded by a bronchodilator is an inexpensive , safe , and effective additional therapy for patients with cystic fibrosis . ( Clinical Trials.gov number , NCT00271310 . Neutrophilic airway inflammation is a hallmark of cystic fibrosis ( CF ) . As high oxidant producers , airway neutrophils contribute largely to the systemic redox imbalance seen in CF . In turn , this chronic and profound imbalance can impact circulating neutrophils before their migration into airways . Indeed , in 18 CF patients with stable disease , blood neutrophils were readily deficient in the pivotal antioxidant glutathione ( P = 0.003 , compared with 9 healthy controls ) . In a phase 1 study , this deficiency was improved ( P = 0.025 ) by the glutathione prodrug N-acetylcysteine , given orally in high doses ( 0.6 to 1.0 g three times daily , for 4 weeks ) . This treatment was safe and markedly decreased sputum elastase activity ( P = 0.006 ) , the strongest predictor of CF pulmonary function . Consistently , neutrophil burden in CF airways was decreased upon treatment ( P = 0.003 ) , as was the number of airway neutrophils actively releasing elastase-rich granules ( P = 0.005 ) , as measured by flow cytometry . Pulmonary function measures were not improved , as expected with short-term treatment . After excluding data from subjects without baseline airway inflammation , positive treatment effects were more pronounced and included decreased sputum IL-8 levels ( P = 0.032 ) . Thus , high-dose oral N-acetylcysteine has the potential to counter the intertwined redox and inflammatory imbalances in CF S-nitrosoglutathione ( GSNO ) , a naturally occurring constituent of airway lining fluid , enhances ciliary motility , relaxes airway smooth muscle , inhibits airway epithelial amiloride-sensitive sodium transport , and prevents pathogen replication . Remarkably , airway levels of GSNO are low in patients with cystic fibrosis ( CF ) . We hypothesized that replacement of airway GSNO would improve gas exchange in CF . In a double-blind , placebo controlled study , we administered 0.05 ml/kg of 10 mM GSNO or phosphate buffered saline by aerosol to patients with CF and followed oxygen saturation , spirometry , respiratory rate , blood pressure , heart rate , and expired nitric oxide ( NO ) .  Nine patients received GSNO and 11 placebo . GSNO inhalation was associated with a modest but sustained increase in oxygen saturation at all time points . Expired NO increased in the low ppb range with GSNO treatment , peaking at 5 minutes but remaining above baseline at 30 minutes . There were no adverse effects . We conclude that GSNO is well tolerated in patients with CF and improves oxygenation through a mechanism that may be independent of free NO . Further , GSNO breakdown increases expired NO . We suggest that therapy aim ed at restoring endogenous GSNO levels in the CF airway may merit study The aim of the present studies was to investigate the tolerability and activity of a novel mucolytic drug , Nacystelyn ( NAL ) , for the treatment of cystic fibrosis ( CF ) lung disease . In study 1 , involving 10 CF patients , the main objective was to determine the tolerability and potential efficacy of a range of single doses of NAL in comparison to a placebo , in order to establish an optimal dose for further testing . On five consecutive scheduled treatment days , patients inhaled either from two ( 4 mg ) to eight puffs ( 16 mg ) of a single dose of NAL from the range , administered in an open-label fashion , or 12 puffs of active NAL ( 24 mg ) versus 12 puffs of placebo , administered in a r and omized double-blind fashion . Pulmonary function data were unaffected and clinical ly-adverse effects were limited to wheezing in some patients that inhaled 12 puffs of either placebo or active drug . Subsequent rheological analysis of their sputum showed a dose-dependent decrease in sputum viscoelasticity , accompanied by a decrease in sputum solids content and an increase in chloride and sodium concentrations . In study 2 , involving 12 CF patients , the clinical safety and mucolytic activity of a single dose of NAL was monitored over 24 h. On different scheduled treatment days , 7 days apart , patients inhaled a single dose of 12 puffs of active NAL ( 24 mg ) or 12 puffs of placebo drug in a r and omized , double-blind sequence , with sputum sample s taken at intervals before and after inhalation . Mucus rigidity decreased following NAL inhalation , with the maximum effect observed at 4 h ; the 1- , 2- and 4-h NAL rheology results were significantly different from placebo . No adverse effects were observed . The drug was well tolerated in both studies . Sputum results were predictive of improved clearability by ciliary and cough transport mechanisms Twenty-seven patients with cystic fibrosis completed a controlled trial comparing the effects of an inhaled mucolytic drug , sodium-2-mercaptoethane sulphonate ( Mistabron , UCB Pharmaceutical Division , Brussels , Belgium ) , with inhaled iso-osmolar hypertonic saline . As a group the 22 patients with chronic sputum production showed small but statistically significant improvement in pulmonary function tests after Mistabron therapy , both when compared with a control period , and with iso-osmolar saline results . Subjective measurements by diary card failed to show any changes . No significant changes were found in five patients with no measurable sputum production . The inhalations were given after physiotherapy and were well tolerated . There were no significant side effects . The results suggest that Mistabron has a beneficial therapeutic effect unrelated to its high osmolality , and the intermittent inhalation of Mistabron may have a role in the treatment of selected patients with cystic fibrosis The effect of peroral N-acetylcysteine ( NAC ) in patients with cystic fibrosis ( CF ) and primary ciliary dyskinesia ( PCD ) was investigated . 41 CF patients and 13 PCD patients completed the study which was a double-blind , placebo-controlled , cross-over trial . The patients received either NAC or placebo for two periods of three months followed by a three month follow-up period . Active treatment consisted of NAC , either 200 mg x 3 daily ( patients weighing less than 30 kg ) or 400 mg x 2 daily ( greater than 30 kg ) . The effect was evaluated in terms of a subjective clinical score , weight , sputum bacteriology , blood leucocyte count , sedimentation rate , titres of specific antimicrobial antibodies , lung function parameters and measurement of the ciliary function . No effect was seen in PCD patients , but in CF patients an improved lung function was seen in the period when the patients suffer most from lower airway infections Examined in this study are the immediate effects of bronchial drainage preceded by the inhalation of aerosol solutions of a mucolytic agent , a bronchodilator , and their combination upon four measures of pulmonary function in 20 patients with cystic fibrosis . On three separate occasions , pulmonary function was tested preceding and following treatments consisting of one of the above three aerosol solutions followed by bronchial drainage . The order of solutions used was r and om and each subject received one treatment with each solution . The greatest overall improvement in function was seen with the bronchodilator and bronchial drainage . The combination of the bronchodilator/mucolytic agents and bronchial drainage was the next most effective technique . The mucolytic agent , when used alone with bronchial drainage , decreased function . Comparison of the pulmonary function scores indicated a significant difference among the three treatments The therapeutic efficacy of oral N-acetylcysteine ( NAC ) and ambroxol as compared with the effect of placebos was studied in 36 cystic fibrosis ( CF ) patients with mild to moderate pulmonary disease . The patients were r and omly assigned to one of three regimens , matched on the basis of age and Chrispin-Norman scores . The trial was conducted over a period of 12 weeks . Patients were assessed clinical ly and by extensive pulmonary function techniques ( body-plethysmography , maximal expiratory flow-volume curves , trapped air determination ) . Although no clinical differences could be observed between the three groups , significant impairment in the placebo group was found for trapped air and FEV1 when compared to the active groups , suggesting a therapeutic effect of ambroxol and NAC in CF BACKGROUND Respiratory disease in patients with cystic fibrosis is characterized by airway obstruction caused by the accumulation of thick , purulent secretions , which results in recurrent , symptomatic exacerbations . The viscoelasticity of the secretions can be reduced in vitro by recombinant human deoxyribonuclease I ( rhDNase ) , a bioengineered copy of the human enzyme . METHODS We performed a r and omized , double-blind , placebo-controlled study to determine the effects of once-daily and twice-daily administration of rhDNase on exacerbations of respiratory symptoms requiring parenteral antibiotics and on pulmonary function . A total of 968 adults and children with cystic fibrosis were treated for 24 weeks as out patients . RESULTS One or more exacerbations occurred in 27 percent of the patients given placebo , 22 percent of those treated with rhDNase once daily , and 19 percent of those treated with rhDNase twice daily . As compared with placebo , the administration of rhDNase once daily and twice daily reduced the age-adjusted risk of respiratory exacerbations by 28 percent ( P = 0.04 ) and 37 percent ( P < 0.01 ) , respectively . The administration of rhDNase once daily and twice daily improved forced expiratory volume in one second during the study by a mean ( + /- SD ) of 5.8 + /- 0.7 and 5.6 + /- 0.7 percent , respectively . None of the patients had anaphylaxis . Voice alteration and lary 
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Although generally well-tolerated with no significant adverse effects , there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments .
Oral thiol derivatives were generally well-tolerated with no significant adverse effects , however there was no evidence of significant clinical benefit in our primary outcomes in participants receiving these treatments .
We found no evidence to recommend the use of either nebulized or oral thiol derivatives in people with cystic fibrosis .