***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: Mucus hypersecretion is a hallmark of chronic obstructive pulmonary disease ( COPD ) and is regarded as contributing to airflow limitation in these patients . The value of mucolytic therapy is still a matter for debate . We investigated the short-term influence of an inhalative mucolytic drug mercapto-ethane sulfonate ( Mesna ) on the lung function , respiratory mechanics and viscous respiratory load in patients with COPD in a r and omized , placebo controlled , double-blind , cross-over study in 10 patients with moderate , stable COPD .  Resistance , static compliance and frequency dependent dynamic compliance and viscous respiratory work , FVC , FEV(1 ) , PEFR , MEF(75 ) , MEF(50 ) , MEF(25 ) , TLC and RV were measured . These lung function parameters did not show any significant differences between the treatment groups . In conclusion , an inhalative treatment with an active mucolytic drug of patients with mild COPD does not improve respiratory mechanics and respiratory load BACKGROUND AND AIMS Inhalation of hypertonic saline ( HTS ) has short term positive effects on airways clearance in non-cystic fibrosis ( CF ) bronchiectasis , however its long term effects are unknown . The aim of this study was to determine the effect of HTS 6 % on exacerbations , quality of life ( QOL ) and respiratory function over 12 months in non-CF bronchiectasis . METHODS Forty patients were r and omised to inhale isotonic saline ( IS ) 0.9 % or HTS 6 % daily for 12 months . Participants recorded their symptoms in a daily diary . Quality of life and respiratory function were measured after three , six and 12 months . Number of exacerbations and changes in sputum colonisation were recorded at 12 months . Participants , assessors and clinicians were blinded to group allocation . RESULTS The exacerbation rate at 12 months was similar in the two groups and similar clinical ly significant improvements in QOL were seen in both groups . The FEV(1 ) increased in both groups after six months ( mean 90 ml , 95 % confidence interval 11 - 169 ml ) with no difference between groups ( p = 0.394 ) . The FEF(25 - 75 % ) significantly improved at all time points ( mean increase at 12 months 187 ml , 69 - 304 ml ) with no difference between groups ( p = 0.705 ) . There was a reduction in sputum colonisation in both groups ( p = 0.046 ) . CONCLUSIONS Inhalation of HTS or IS has similar effects on exacerbations , QOL , sputum colonisation and respiratory function over 12 months in non-CF bronchiectasis . The trial was registered with both Clinical Trials.gov - NCT00484263 and Australian New Zeal and Clinical Trials Registry - ACTRN12607000367448 BACKGROUND Inhaled dry powder mannitol enhanced mucus clearance and improved quality of life over 2 weeks in non-cystic fibrosis bronchiectasis . This study 's objective was to investigate the efficacy and safety of dry powder mannitol over 12 weeks . METHODS Patients with bronchiectasis confirmed by high-resolution CT ( H RCT ) scan , aged 15 to 80 years , with FEV1≥50 % predicted and ≥1 L participated in a r and omized , placebo-controlled , double-blind study . Patients with a negative mannitol provocation test were r and omized to inhale 320 mg mannitol ( n=231 ) or placebo ( n=112 ) bid for 12 weeks . To further assess safety , the same mannitol dose/frequency was administered to a patient subset in an open-label extension over 52 weeks . Primary end points were changes from baseline at 12 weeks in 24-h sputum weight and St. George 's Respiratory Question naire ( SGRQ ) score . RESULTS There was a significant difference of 4.3 g in terms of change in sputum weight over 12 weeks ( 95 % CI , 1.64 - 7.00 ; P=.002 ) between mannitol and placebo ; however , this was largely driven by a decrease in sputum weight in the placebo group . This was associated , in turn , with more antibiotic use in the placebo group ( 50 of 112 [ 45 % ] ) than in the inhaled mannitol group ( 85 of 231 [ 37 % ] ) . There was no statistical difference between the groups ( P=.304 ) in total SGRQ score  ( mannitol , -3.4 points [ 95 % CI , -4.81 to -1.94 ] vs placebo , -2.1 points [ 95 % CI , -4.12 to -0.09 ] ) . In a subgroup study ( n=82 ) , patients receiving mannitol  showed less small airway mucus plugging on H RCT scan at 12 weeks compared with patients receiving placebo ( P=.048 ) . Compliance rates were high , and mannitol was well tolerated with adverse events similar to those of placebo . CONCLUSION Because the difference in sputum weights appears to be associated with increased antibiotic use in the placebo group , a larger controlled study is now required to investigate the long-term mannitol effect on pulmonary exacerbations and antibiotic use . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT0027753 ; URL : www . clinical trials.gov INTRODUCTION Mucous plugging is associated with fatal asthma and may have a causative role for non-fatal cases of severe acute asthma . However , mucolytic agents have not been found effective in reversing the obstruction of acute asthma . We test the hypothesis that rhDNAse , an agent that reduces viscoelasticity of sputum in patients with cystic fibrosis , has a therapeutic role in acute asthma . METHODS Symptomatic asthmatics aged 18 - 55 years presenting to an Emergency Department with an FEV(1 ) < 60 % predicted after 2 nebulized albuterol and ipratropium treatments were included . Patients were r and omized into one of three nebulized rhDNAse treatment groups of 2.5 , 5.0 or 7.5 mg , or placebo . St and ardized bronchodilator therapy was continued throughout the protocol and the FEV(1 ) at 6 h was the primary study endpoint . RESULTS 50 patients were enrolled . There were no significant differences in FEV(1)% predicted between the rhDNAse and placebo patients at any of the post-r and omization time points . The dose of rhDNAse administered did not influence response . In a post-hoc stratification , patients with the lowest pre-r and omization FEV(1 ) tended to improve more from rhDNAse , particularly at times 60 and 120 min post-r and omization . CONCLUSION In this pilot study rhDNAse did not cause clinical improvement among severely ill adults refractory to st and ardized care . The observed trend to higher FEV(1 ) among the most severely obstructed patients is an exploratory finding that may warrant further study . This clinical trial was registered as NCT00169962 under the name " Study of Pulmozyme to Treat Severe Asthma Episodes " RATIONALE New treatment strategies are needed to improve airway clearance and reduce the morbidity and the time burden associated with cystic fibrosis ( CF ) . OBJECTIVES To determine whether long-term treatment with inhaled mannitol , an osmotic agent , improves lung function and morbidity . METHODS Double-blind , r and omized , controlled trial of inhaled mannitol , 400 mg twice a day ( n = 192 , " treated " group ) or 50 mg twice a day ( n = 126 , " control " group ) for 26 weeks , followed by 26 weeks of open-label treatment . MEASUREMENTS AND MAIN RESULTS The primary endpoint was absolute change in FEV(1 ) from baseline in treated versus control groups , averaged over the study period . Secondary endpoints included other spirometric measurements , pulmonary exacerbations , and hospitalization . Clinical , microbiologic , and laboratory safety were assessed . The treated group had a mean improvement in FEV(1 ) of 105 ml ( 8.2 % above baseline ) . The treated group had a relative improvement in FEV(1 ) of 3.75 % ( P = 0.029 ) versus the control group . Adverse events and sputum microbiology were similar in both treatment groups . Exacerbation rates were low , but there were fewer in the treated group ( hazard ratio , 0.74 ; 95 % confidence interval , 0.42 - 1.32 ; P = 0.31 ) , although this was not statistically significant . In the 26-week open-label extension study , FEV(1 ) was maintained in the original treated group , and improved in the original control group to the same degree . CONCLUSIONS Inhaled mannitol , 400 mg twice a day , result ed in improved lung function over 26 weeks , which was sustained after an additional 26 weeks of treatment . The safety profile was also acceptable , demonstrating the potential role for this chronic therapy for CF . Clinical trial registered with www . clinical trials.gov ( NCT 00630812 ) Background Many trials of nebulized therapy have used nebulized saline as a " placebo " . However , nebulized isotonic saline is sometimes used to assist sputum expectoration and relieve breathlessness in COPD patients . We design ed this study to establish if nebulized saline had a placebo effect or a clinical effect . Methods 40 patients were studied following hospital admission for exacerbated COPD ( mean FEV1 30 % predicted ) . Patients were r and omised to single-blind administration of either 4 mls of nebulized isotonic saline using an efficient nebulizer ( active group n = 20 ) or an inefficient nebulizer ( placebo group n = 20 ) . Spirometry and subjective breathlessness scores ( Modified Likert Scale ) were measured before nebulized treatment and 10 minutes after treatment . Results There was no significant change in FEV1 after active or placebo nebulized saline treatment . Patients reported a 4 % improvement in mean breathlessness score following placebo ( Wilcoxon test ; p = 0.37 ) compared with 23 % improvement following active nebulized saline ( p = 0.0001 ) . 65 % of patients given active nebulized saline but only 5 % of the placebo group reported that mucus expectoration was easier after the treatment . Conclusions This study lends support to the current use of nebulized saline to relieve breathlessness ( possibly by facilitating sputum clearance ) in COPD patients . Lung function was not affected . Nebulized saline can therefore be used as a placebo in bronchodilator studies involving COPD patients but it can not be used as a placebo in trials assessing symptom relief BACKGROUND Inhaled hypertonic saline is used for bronchial challenge and sputum induction in patients with chronic obstructive pulmonary disease ( COPD ) . We studied the effects of saline aerosol inhalation before each exercise session in an 8-week pulmonary rehabilitation program . METHODS This was a double-blind r and omized parallel controlled trial , conducted at an out-patient clinic . Sixty-eight subjects with COPD ( mean age 67 + /- 6.5 y , percent of predicted FEV(1 ) 47 + /- 21 ) were r and omized to inhale either 3 % hypertonic saline ( 34 subjects ) or normal saline ( 34 subjects ) before each exercise session in an 8-week exercise program that had 3 sessions per week . We measured 6-min walk distance , dyspnea , and quality of life ( with the Medical Outcomes Study 36-item short-form health survey ) . RESULTS After the 8-week exercise program , both groups ' mean 6-min walk distance had significantly increased : from 195 + /- 92 m to 251 + /- 97 m ( P < .001 ) in the hypertonic-saline group , and from 237 + /- 93 m to 441 + /- 121 m in the normal-saline group ( P < .001 ) . The normal-saline group had greater improvement than the hypertonic-saline group ( P < .001 ) . Dyspnea score improved from 3.1 + /- 0.9 to 2.3 + /- 0.8 ( P < .01 ) in the hypertonic-saline group , and from 3.5 + /- 0.2 to 2.3 + /- 1.0 ( P < .01 ) in the normal-saline group . Quality of life also significantly improved , except for the physical-functioning and social aspect domains in the hypertonic-saline group . Adverse effects ( cough or bronchospasm ) occurred in 4 patients ( 12 % ) in the hypertonic-saline group . CONCLUSIONS The improvement in 6-min walk distance was greater with normal saline than with hypertonic saline . Hypertonic saline was associated with adverse effects . It is unclear whether the only predictor of improved functional exercise capacity was exercise training . ( Clinical Trials.gov number , NCT00639236 . ) Bronchiectasis is characterised by hypersecretion and impaired clearance of mucus . A 400-mg dose of inhaled mannitol improves mucus clearance however , the effect of other doses is unknown . A total 
    Output:
    
Most AEs were mild and transient , including bronchospasm , cough and breathlessness .
NS eased symptomatic burden in COPD , while NS and HS improved spirometry , HRQOL and sputum burden in non-CF bronchiectasis .
Mannitol  improved mucociliary clearance in asthma and bronchiectasis , while the effects of N-acetylcysteine were unclear .
In chronic lung diseases outside CF , there are small benefits of mannitol , NS and HS  .
Adverse effects of rhDNase suggest this should not be administered in non-CF bronchiectasis