***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: Excessive Na+ absorption1,2 and defective regulation of apical membrane Cl- secretion3–6 likely leads to dehydration and abnormal rheology of CF airway secretions7 . These abnormalities contribute to poor clearance of airway secretions , and chronic bacterial infection in CF . Because amiloride inhibits the absorption of Na+ ( and liquid ) across airway mucosa1,8,9 when applied to the apical surface of CF airway epithelia , we hypo-thesized that inhalation of amiloride may improve rheology and clearance of airway secretions9,10 This hypothesis was tested in a doubleblind crossover study to explore the safety and efficacy of long-term amiloride aerosol in the treatment of cystic fibrosis lung disease11 OBJECTIVE --To assess the benefit of nebulised amiloride added to the st and ard inpatient treatment of a respiratory exacerbation in cystic fibrosis . DESIGN -- Prospect i ve , r and omised , double blind , placebo controlled trial . SUBJECTS--27 cystic fibrosis patients ( mean age 12.8 years ) . SETTING --Two hospitals in Leeds , UK . RESULTS --Both forced expiratory volume in one second ( FEV1 ) and forced vital capacity ( FVC ) showed improvements over the course of treatment , although there was no difference in respiratory function between the two groups at any of three time periods during the study . The time to reach peak FVC was significantly reduced in the amiloride group ( 4.2 v 7.6 days ; 95 % CI 0.4 to 6.4 days ) , but not in the time to reach peak FEV1 ( 5.7 v 7.9 days ; 95 % CI -1.2 to 5.6 days ) . CONCLUSIONS --Amiloride did not result in a greater overall improvement in respiratory function . There was a suggestion that it may have an effect on the rate of improvement , and thus may possibly influence the duration of treatment . This hypothesis deserves further evaluation BACKGROUND Abnormal homeostasis of the volume of airway surface liquid in patients with cystic fibrosis is thought to produce defects in mucus clearance and airway defense . Through osmotic forces , hypertonic saline may increase the volume of airway surface liquid , restore mucus clearance , and improve lung function . METHODS A total of 24 patients with cystic fibrosis were r and omly assigned to receive treatment with inhaled hypertonic saline ( 5 ml of 7 percent sodium chloride ) four times daily with or without pretreatment with amiloride .  Mucus clearance and lung function were measured during 14-day baseline and treatment periods . RESULTS Long-term inhalation of hypertonic saline without pretreatment with amiloride ( i.e. , with placebo pretreatment ) result ed in a sustained ( > or = 8 hours ) increase in 1-hour rates of mucus clearance , as compared with those with amiloride pretreatment ( 14.0+/-2.0 vs. 7.0+/-1.5 percent , respectively ; P=0.02 ) and increased 24-hour rates of mucus clearance over baseline . Furthermore , inhalation of hypertonic saline with placebo improved the forced expiratory volume in one second ( FEV1 ) between the baseline period and the treatment period ( mean difference , 6.62 percent ; 95 percent confidence interval , 1.6 to 11.7 ; P=0.02 ) , whereas hypertonic saline with amiloride did not improve FEV1 ( mean difference , 2.9 percent ; 95 percent confidence interval , -2.2 to 8.0 ; P=0.23 ) . Forced vital capacity ( FVC ) , the forced expiratory flow between 25 and 75 percent of FVC ( FEF25 - 75 ) , and respiratory symptoms also significantly improved in patients treated with hypertonic saline and placebo , whereas the residual volume as a proportion of total lung capacity ( RV : TLC ) did not change in either group . A comparison of the changes in lung function in the two groups showed no significant difference . In vitro data suggested that sustained hydration of airway surfaces was responsible for the sustained improvement in mucus clearance , whereas inhibition of osmotically driven water transport by amiloride accounted for the observed loss of clinical benefit . CONCLUSIONS In patients with cystic fibrosis , inhalation of hypertonic saline produced a sustained acceleration of mucus clearance and improved lung function . This treatment may protect the lung from insults that reduce mucus clearance and produce lung disease In order to evaluate the degree and type of gas exchange impairment in cystic fibrosis , ventilation/perfusion relationships in ten patients ( mean age 26 yrs , mean Shwachman score 86 ) were examined . Pulmonary gas exchange was studied using the multiple inert gas elimination technique . High-resolution computed tomography ( H RCT ) and spirometry , including diffusing capacity , were performed after each gas exchange study for comparison . Examinations were done before and after home i.v . antibiotic treatment ( HIVAT , 14 days ) and after inhaled amiloride and placebo ( 14 days ) , in crossover fashion , clinical status after HIVAT serving as the baseline for the crossover study . Before HIVAT , the mean residual volume was 182 % of the predicted value , the mean vital capacity 72 % pred and the mean forced expiratory volume in one second 53 % pred ( p<0.001 ) . The dispersion of pulmonary blood flow at different ventilation/perfusion ratios ( V'/Q ' ) ( ( logarithmic SD of the perfusion distribution ( log SDQ ) ) , used as an index for gas exchange impairment , was increased to a mean of 0.72 . No linear correlation was seen between ventilation/perfusion ine quality , spirometry and H RCT ( p>0.05 ) . After HIVAT , log SDQ was significantly improved to 0.66 ( p<0.05 ) . After placebo , but not after amiloride , log SDQ , arterial oxygen tension , alveolar-arterial oxygen tension difference and maximal expiratory flows when 50 % and 25 % of the forced vital capacity tension remain to be exhaled were significantly worse ( p<0.05 , respectively ) . Areas with a low V'/Q ' were significantly lower after amiloride compared to after the placebo period ( p<0.05 ) . Moderate ventilation/perfusion ine quality was present in the majority of the studied cystic fibrosis patients . The degree of ventilation/perfusion ine quality can not be estimated from spirometry or high-resolution computed tomography . The low proportion of low ventilation/perfusion ratios indicates that the regular treatment directed towards mucus plugging of small airways is beneficial . An improvement in the ventilation/perfusion relationship was seen after home i.v . antibiotic treatment and inhaled amiloride may possibly have a further positive effect on gas exchange In cystic fibrosis ( CF ) airway epithelial sodium absorption is increased 2 - 3 fold . Since sodium absorption is inhibited by the sodium channel blocker amiloride , our aim was to assess its therapeutic benefit in cystic fibrosis . A r and omized , double-blind , placebo-controlled , cross-over trial of nebulized amiloride was performed in 23 patients with cystic fibrosis .  Amiloride or placebo was administered four times daily for two six month periods . Existing treatment was continued , and any infective exacerbations treated in the usual way . Fourteen patients completed the study . No significant changes occurred in forced expiratory volume in one second , forced vital capacity , oxygen saturation , body weight , sputum volume , culture and rheology , serum urea , and electrolytes , white cell count and erythrocyte sedimentation rate during either treatment period . The frequency of infective exacerbations was also not different in either treatment period . We were thus unable to confirm the benefit shown in the only other clinical trial of nebulized amiloride in cystic fibrosis and conclude that , in the presence of established treatment for cystic fibrosis lung disease , nebulized amiloride offers no additional clinical benefit Aerosolized amiloride normalizes the excessive sodium absorption cystic fibrosis ( CF ) respiratory epithelium . The aims of this study were to assess the dose-effect relationship and the duration for which amiloride inhibits Na+ transport , to determine acute and chronic pharmacokinetics , and to test the effect of acute aerosolized amiloride on the amount of sputum expectorated . The effect of inhaled amiloride was assessed principally by nasal potential difference ( PD ) measurements . Amiloride serum levels were measured in 23 patients after inhalation of different doses of aerosolized amiloride .  Twenty CF patients inhaled amiloride ( 10(-3)M ) or a placebo in a double-blinded , r and omized order , and sputum production was quantitated . The results of this study showed that maximal initial PD inhibition was achieved by 6 x 10(-3)M of amiloride . The duration of inhibition of PD ( effective time until return to 50 % delta PD [ ET50 ] after nasal administration ) was dose dependent ( 10(-3)M , 39 + /- 0.8 minutes ; 10(-2)M ; 133 + /- 14 minutes ) .  Amiloride serum levels were below 2.5 ng/ml in 20 of 28 patients ; levels were above 5 ng/ml only within 4 hours after high dose inhalation ( 10(-2)M ) . In the double-blinded , crossover study , more sputum was expectorated after amiloride inhalation as compared with that after a placebo ( P < 0.05 ) . In conclusion , the bioelectric effects of amiloride and serum levels after inhalation are dose dependent , and amiloride is effective at inducing sputum expectoration in CF STUDY OBJECTIVE To compare the pharmacokinetics and systemic exposure of nebulized and oral amiloride in adolescents and adults with mild to moderate cystic fibrosis ( CF ) . DESIGN Open-label , r and omized , two-way crossover , single-dose pharmacokinetic study . SETTING University hospital clinical research unit . PATIENTS Nine adolescents and 10 adults with mild to moderate CF ( forced expiratory volume in 1 sec > or = 50 % predicted , Brasfield score > or = 15 ) . INTERVENTIONS Patients received amiloride solution orally ( 10 mg of amiloride 1-mg/ml solution ) and by inhalation [ 4.5 ml amiloride of 1-mg/ml solution in 12 % saline ( approximately 3.8 mmol/L ) by DeVilbiss 646 nebulizer ] during two study phases separated by a 7- to 28-day washout period . Serial blood and urine sample s were collected for 48 and 72 hours , respectively . MEASUREMENTS AND MAIN RESULTS After oral dosing , the mean + /- SD maximum peak concentration ( Cmax ) was 20.6 + /- 10.0 ng/ml at 3.2 + /- 1.2 hours in adults and 21.7 + /- 4.88 at 2.9 + /- 0.6 hours in the adolescents . Mean area under the concentration-time curve ( AUC ) from time zero to infinity hours was 275 + /- 115 and 254 + /- 60 ng.hr/ml in the adult and adolescent groups ; half-life was 16.0 + /- 0.7 and 13.4 + /- 1.4 hours , respectively . After nebulization , 14 of 19 subjects exhibited two concentration peaks ( Cmax1 and Cmax2 ) with mean values of 1.57 + /- 1.67 ng/ml at 0.5 + /- 0.2 hours and 1.37 + /- 1.21 ng/ml at 4.0 + /- 1.0 hours for adults , and 1.49 + /- 0.99 ng/ml at 0.5 + /- 0.1 hours and 1.52 + /- 0.81 ng/ml at 3.3 + /- 0.5 hours for adolescents . Estimated mean + /- SD dose nebulized was 1.91 + /- 0.66 and 2.28 + /- 0.30 mg in the adult and adolescent groups , respectively . Mean + /- SD AUC from time zero to the last measurable plasma amiloride concentration after inhalation was 14.4 + /- 17.6 and 15.4 + /- 10.1 ng.hr/ml in the adults and adolescents . No significant adverse events occurred during the study . Pharmacokinetic parameters were not statistically different between the adolescent and adult groups by route of administration . However significant differences in peak amiloride concentration , AUC , and urinary amiloride excretion were evident when comparing oral versus inhalation administration within each group . CONCLUSIONS Mean amiloride plasma concentration peaks and AUC after inhalation were significantly lower than after oral dosing . In addition , the second amiloride plasma concentration peak may be due to oral ingestion of the nebulized amiloride , whereas the earlier Cmax1 after inhalation may be due to pulmonary absorption of amiloride . These results suggest that single-dose amiloride inhalation in patients with mild to moderate CF results in minimal systemic exposure compared with oral dosing , and that drug disposition is similar in adolescents and adults with CF Lithium is known to affect several aspects of cellular regulation which may be related to ion channel function in epithelial cells . To determine whether the ion transport abnormality in cyst 
    Output:
    
A two-week study demonstrated that hypertonic saline with amiloride pre-treatment did not result in a significant improvement in respiratory function or mucus clearance , in contrast to pre-treatment with placebo .
There were no significant differences identified in other clinical ly relevant outcomes .
We found no evidence that the topical administration of a short-acting sodium channel blocker improves respiratory condition in people with cystic fibrosis and some limited evidence of deterioration in lung function