***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: UNLABELLED Neutrophil elastase ( NE ) activity is increased in bronchiectasis and may play a role in this condition . We wished to determine the effect of AZD9668 , a selective oral inhibitor of NE . Efficacy and safety of AZD9668 60 mg twice daily over 4 weeks were evaluated in a r and omised , double-blind , placebo-controlled , parallel-group , Phase II , signal- search ing study in patients with bronchiectasis . Outcome measures included : waking and post-waking sputum neutrophil counts ; lung function tests ; 24-h sputum weight ; BronkoTest ( ® ) diary card data ; St George 's Respiratory Question naire for COPD patients ( SGRQ-C ) ; sputum NE activity ; inflammatory biomarker levels ; desmosine levels ; adverse events , safety haematology and biochemistry . AZD9668 levels in plasma and sputum were measured to confirm exposure . Thirty-eight patients were r and omised : 16 to placebo and 22 to AZD9668 . There was no change in sputum neutrophils with AZD9668 . Forced expiratory volume in 1 s improved by 100 mL in the AZD9668 group compared with placebo ( p = 0.006 ) . Significant changes ( defined a priori as p < 0.1 ) in favour of AZD9668 were also seen in slow vital capacity , plasma interleukin-8 , and post-waking sputum interleukin-6 and Regulated on Activation , Normal T-cell Expressed and Secreted levels . Non-significant changes in favour of AZD9668 were seen in other lung function tests , sputum weight and the SGRQ-C.  AZD9668 was well tolerated . In this small signal- search ing study , 4 weeks ' treatment with AZD9668  improved lung function  in patients with bronchiectasis and there were trends for reductions in sputum inflammatory biomarkers . Larger studies of longer duration would be needed to confirm the potential benefits of this agent in bronchiectasis . REGISTRATION NCT00769119 BACKGROUND AND OBJECTIVE We evaluated the efficacy of a 12-week oral treatment with azithromycin in adult patients with bronchiectasis . The objectives were to demonstrate that this treatment reduces sputum volume , improves quality of life and to assess the lengths of effects after cessation of therapy . METHODS Seventy-eight patients with bronchiectasis confirmed by high-resolution computed tomography were included in this study . Subjects received oral azithromycin or placebo in a r and omized manner for 12 weeks followed by placebo for another 12 weeks . Sputum volume , St George 's Respiratory Question naire ( SGRQ ) score and spirometry were recorded at baseline , 12 weeks and 24 weeks , respectively . End-point measurements were compared from baseline to the end of each study phase . RESULTS Sixty-eight subjects were included in the analysis . Mean 24-h sputum volume significantly decreased ( P < 0.01 ) during the active treatment phase and remained low during the control phase ( P < 0.01 ) . The mean SGRQ total score with azithromycin decreased ( i.e. improved health status ) from baseline by more than the 4 points at the end of 12 and 24 weeks . Lung functions remained stable during oral azithromycin therapy and the subsequent control phase . CONCLUSIONS Twelve weeks administration of azithromycin in bronchiectasis produces significant reductions in mean sputum volume , health status and stabilization of lung function values . Sputum volume reduction and the improvement of quality of life were sustained for 12 weeks after cessation of azithromycin . ( Clinical trials.gov number NCT02107274 ) RATIONALE Bronchiectasis is a chronic debilitating disease with few evidence -based long-term treatments . OBJECTIVES A r and omized controlled trial assessing the efficacy of nebulized gentamicin therapy over 1 year in patients with non-cystic fibrosis bronchiectasis . METHODS Sixty-five patients were r and omized to either twice-daily nebulized gentamicin , 80 mg , or nebulized 0.9 % saline , for 12 months . All were review ed at three-monthly intervals during treatment and at 3 months ' follow-up . MEASUREMENTS AND MAIN RESULTS At each review the following were assessed : quantitative and qualitative sputum bacteriology ; sputum purulence and 24-hour volume ; FEV(1 ) , FVC , and forced expiratory flow , midexpiratory phase ; exercise capacity ; Leicester Cough Question naire and St. George 's Respiratory Question naire ; and exacerbation frequency .  Fifty-seven patients completed the study . At the end of 12 months ' treatment , compared with the saline group , in the gentamicin group there was reduced sputum bacterial density with 30.8 % eradication in those infected with Pseudomonas aeruginosa and 92.8 % eradication in those infected with other pathogens ; less sputum purulence ( 8.7 % vs. 38.5 % ; P < 0.0001 ) ; greater exercise capacity ( 510 [ 350 - 690 ] m vs. 415 [ 267.5 - 530 ] m ; P = 0.03 ) ; and fewer exacerbations ( 0 [ 0 - 1 ] vs. 1.5 [ 1 - 2 ] ; P < 0.0001 ) with increased time to first exacerbation ( 120 [ 87 - 161.5 ] d vs. 61.5 [ 20.7 - 122.7 ] d ; P = 0.02 ) . The gentamicin group had greater improvements in Leicester Cough Question naire ( 81.4 % vs. 20 % ; P < 0.01 ) and St. George 's Respiratory Question naire ( 87.5 % vs. 19.2 % ; P < 0.004 ) score . No differences were seen in 24-hour sputum volume , FEV(1 ) , FVC , or forced expiratory flow , midexpiratory phase . No P. aeruginosa isolates developed resistance to gentamicin . At follow-up , all outcome measures were similar to baseline . CONCLUSIONS Regular , long-term nebulized gentamicin is of significant benefit in non-cystic fibrosis bronchiectasis but treatment needs to be continuous for its ongoing efficacy . Clinical trial registered with www . clinical trials.gov ( NCT 00749866 ) Objective The therapeutic benefit of inhaled corticoids in bronchiectasis not due to cystic fibrosis is still not well documented . The aim of the present study was to assess the efficacy and safety of inhaled corticoids in this disease . Setting This study was conducted at a tertiary university hospital in the city of Barcelona , Catalonia , ( Spain ) . Method A prospect i ve , double-blind , parallel , placebo-masked study was conducted . Seventy-seven patients ( 40 women ; mean age : 68 years ) were r and omly assigned to receive either 400 mcg budesonide twice daily or placebo and were regularly review ed for six months . Results Differences in forced vital capacity and forced expiratory volume in the first second between the beginning and end of the study were not significantly lower in the budesonide group than in the placebo group , either in absolute values [ −17.4 ( 386.9 ) versus −21.4 ( 375.5 ) ] or in percentages [ −1.9(9.5 ) versus −2.8 ( 11.6 ) ] . Microbiological criteria applied to evaluate changes between the beginning and end of the study showed no worsening in the budesonide group compared with the control group , whereas a non-significant improvement was obtained in 8.1 % of cases in the budesonide group compared to 3 % in the placebo group . Although significance was only achieved for sputum eosinophils ( p = 0.021 ) , a consistent tendency towards improvement was also observed in secondary end-points ( symptoms , number and duration of exacerbations , quality of life , sputum cytology and interleukin-8 ) in the budesonide group . Conclusion Although further studies are required , inhaled corticoid treatment may be efficacious and safe in bronchiectasis not due to cystic fibrosis RATIONALE Chronic infection with Pseudomonas aeruginosa is associated with an increased exacerbation frequency , a more rapid decline in lung function , and increased mortality in patients with bronchiectasis . OBJECTIVES To perform a r and omized placebo-controlled study assessing the efficacy and safety of inhaled colistin in patients with bronchiectasis and chronic P. aeruginosa infection . METHODS Patients with bronchiectasis and chronic P. aeruginosa infection were enrolled within 21 days of completing a course of antipseudomonal antibiotics for an exacerbation . Participants were r and omized to receive colistin ( 1 million IU ; n = 73 ) or placebo ( 0.45 % saline ; n = 71 ) via the I-neb twice a day , for up to 6 months . MEASUREMENTS AND MAIN RESULTS The primary endpoint was time to exacerbation . Secondary endpoints included time to exacerbation based on adherence recorded by the I-neb , P. aeruginosa bacterial density , quality of life , and safety parameters . All analyses were on the intention-to-treat population . Median time ( 25 % quartile ) to exacerbation was 165 ( 42 ) versus 111 ( 52 ) days in the colistin and placebo groups , respectively ( P = 0.11 ) . In adherent patients ( adherence quartiles 2 - 4 ) , the median time to exacerbation was 168 ( 65 ) versus 103 ( 37 ) days in the colistin and placebo groups , respectively ( P = 0.038 ) . P. aeruginosa density was reduced after 4 ( P = 0.001 ) and 12 weeks ( P = 0.008 ) and the St. George 's Respiratory Question naire total score was improved after 26 weeks ( P = 0.006 ) in the colistin versus placebo patients , respectively . There were no safety concerns . CONCLUSIONS Although the primary endpoint was not reached , this study shows that inhaled colistin is a safe and effective treatment in adherent patients with bronchiectasis and chronic P. aeruginosa infection . Clinical trial registered with http://www.is rct n.org/ ( IS RCT N49790596 ) IMPORTANCE Macrolide antibiotics have been shown beneficial in cystic fibrosis ( CF ) and diffuse panbronchiolitis , and earlier findings also suggest a benefit in non-CF bronchiectasis . OBJECTIVE To determine the efficacy of macrolide maintenance treatment for adults with non-CF bronchiectasis . DESIGN , SETTING , AND PARTICIPANTS The BAT ( Bronchiectasis and Long-term Azithromycin Treatment ) study , a r and omized , double-blind , placebo-controlled trial conducted between April 2008 and September 2010 in 14 hospitals in The Netherl and s among 83 out patients with non-CF bronchiectasis and 3 or more lower respiratory tract infections in the preceding year . INTERVENTIONS Azithromycin ( 250 mg daily ) or placebo for 12 months . MAIN OUTCOME MEASURES Number of infectious exacerbations during 12 months of treatment . Secondary end points included lung function , sputum bacteriology , inflammatory markers , adverse effects , symptom scores , and quality of life . RESULTS Forty-three participants ( 52 % ) received azithromycin and 40 ( 48 % ) received  placebo and were included in the modified intention-to-treat analysis . At end of study , the median number of exacerbations in the azithromycin group was 0 ( interquartile range [ IQR ] , 0 - 1 ) , compared with 2 ( IQR , 1 - 3 ) in the placebo group ( P < .001 ) . Thirty-two ( 80 % ) placebo-treated vs 20 ( 46 % ) azithromycin-treated individuals had at least 1 exacerbation ( hazard ratio , 0.29 [ 95 % CI , 0.16 - 0.51 ] ) . In a mixed-model analysis , change in forced expiratory volume in the first second of expiration ( percent of predicted ) over time differed between groups ( F1,78.8 = 4.085 , P = .047 ) , with an increase of 1.03 % per 3 months in the azithromycin group and a decrease of 0.10 % per 3 months in the placebo group . Gastrointestinal adverse effects occurred in 40 % of patients in the azithromycin group and in 5 % in the placebo group ( relative risk , 7.44 [ 95 % CI , 0.97 - 56.88 ] for abdominal pain and 8.36 [ 95 % CI , 1.10 - 63.15 ] for diarrhea ) but without need for discontinuation of study treatment . A macrolide resistance rate of 88 % was noted in azithromycin-treated individuals , compared with 26 % in 
    Output:
    
There was inconclusive evidence on the use of long-term antibiotics and nebulised hypertonic saline for reducing exacerbation frequency and evidence that human deoxyribonuclease ( RhDNase ) increases exacerbation frequency .
Improvements in lung function were reported for inhaled corticosteroids ( ICS ) though this was small and not clinical ly relevant .
Evidence of benefit for hyperosmolar agents and mucolytics was inconclusive .
There was limited evidence of improvements in quality of life with airway clearance techniques and physical therapy but evidence of benefit for hyperosmolar agents was inconclusive .
Reduction in sputum production was reported for long-term antibiotics and airway clearance techniques but evidence of benefit for hyperosmolar agents was inconclusive .
The review s of short-term courses of antibiotics and inhaled hyperosmolar agents reported no significant differences in occurrence of adverse events .
We have highlighted important endpoints for studies ( particularly exacerbations , quality of life and lung function ) , and areas of clinical practice that are in most urgent need of evidence -based support ( including long-term antibiotics , ICSs and mucolytics).As the evidence is confined to small trials of short duration , it is not currently possible to assess the balance between the benefits and potential harms of treatments for bronchiectasis