***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: Although long-term azithromycin decreases exacerbation frequency in bronchiectasis , increased macrolide resistance is concerning . We investigated macrolide resistance determinants in a secondary analysis of a multicenter r and omized controlled trial . Indigenous Australian children living in remote regions and urban New Zeal and Māori and Pacific Isl and er children with bronchiectasis were r and omized to weekly azithromycin ( 30 mg/kg ) or placebo for up to 24 months and followed post-intervention for up to 12 months . Nurses administered and recorded medications given and collected nasopharyngeal swabs 3–6 monthly for culture and antimicrobial susceptibility testing . Nasopharyngeal carriage of Haemophilus influenzae and Moraxella catarrhalis was significantly lower in azithromycin compared to placebo groups , while macrolide-resistant Streptococcus pneumoniae and Staphylococcus aureus carriage was significantly higher . Australian children , compared to New Zeal and children , had higher carriage overall , significantly higher carriage of macrolide-resistant bacteria at baseline ( 16/38 versus 2/40 children ) and during the intervention ( 69/152 versus 22/239 swabs ) , and lower mean adherence to study medication ( 63 % versus 92 % ) . Adherence ≥70 % ( versus < 70 % ) in the Australian azithromycin group was associated with lower carriage of any pathogen [ odds ratio ( OR ) 0.19 , 95 % confidence interval ( CI ) 0.07–0.53 ] and fewer macrolide-resistant pathogens ( OR 0.34 , 95 % CI 0.14–0.81 ) . Post-intervention ( median 6 months ) , macrolide resistance in S. pneumoniae declined significantly in the azithromycin group , from 79 % ( 11/14 ) to 7 % ( 1/14 ) of positive swabs , but S. aureus strains remained 100 % macrolide resistant . Azithromycin treatment , the Australian remote setting , and adherence < 70 % were significant independent determinants of macrolide resistance in children with bronchiectasis . Adherence to treatment may limit macrolide resistance by suppressing carriage 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 ) 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 the placebo group . CONCLUSIONS AND RELEVANCE Among adults with non-CF bronchiectasis , the daily use of azithromycin for 12 months compared with placebo result ed in a lower rate of infectious exacerbations . This could result in better quality of life and might influence survival , although effects on antibiotic resistance need to be considered . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00415350 RATIONALE There are no risk stratification tools for morbidity and mortality in bronchiectasis . Identifying patients at risk of exacerbations , hospital admissions , and mortality is vital for future research . OBJECTIVES This study describes the derivation and validation of the Bronchiectasis Severity Index ( BSI ) . METHODS Derivation of the BSI used data from a prospect i ve cohort study ( Edinburgh , UK , 2008 - 2012 ) enrolling 608 patients .  Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up . The score was vali date d in independent cohorts from Dundee , UK ( n = 218 ) ; Leuven , Belgium ( n = 253 ) ; Monza , Italy ( n = 105 ) ; and Newcastle , UK ( n = 126 ) . MEASUREMENTS AND MAIN RESULTS Independent predictors of future hospitalization were prior hospital admissions , Medical Research Council dyspnea score greater than or equal to 4 , FEV1 < 30 % predicted , Pseudomonas aeruginosa colonization , colonization with other pathogenic organisms , and three or more lobes involved on high-resolution computed tomography . Independent predictors of mortality were older age , low FEV1 , lower body mass index , prior hospitalization , and three or more exacerbations in the year before the study . The derived BSI predicted mortality and hospitalization : area under the receiver operator characteristic curve ( AUC ) 0.80 ( 95 % confidence interval , 0.74 - 0.86 ) for mortality and AUC 0.88 ( 95 % confidence interval , 0.84 - 0.91 ) for hospitalization , respectively . There was a clear difference in exacerbation frequency and quality of life using the St. George 's Respiratory Question naire between patients classified as low , intermediate , and high risk by the score ( P < 0.0001 for all comparisons ) . In the validation cohorts , the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88 . CONCLUSIONS The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality , hospitalization , and exacerbations across healthcare systems Background Given the advantages of the r and omised controlled trial ( RCT ) design for the evaluation of therapeutic interventions , it is tempting to assume that the same approach must be the gold st and ard for the evaluation of testing strategies . Such trials present considerable challenges , due to the complex nature of the decision – making process . To interpret how changes in testing strategies create observed effects , trials must pre – specify how test results should inform diagnostic and management decisions and treatment plans Increased airway responsiveness ( AR ) is frequently associated with bronchiectasis .  Roxithromycin is a new semisynthetic macrolide antibiotic that also has anti-inflammatory activities . This study was design ed to see whether roxithromycin could favourably alter the degree of AR in patients with bronchiectasis and increased AR . Twenty five children with bronchiectasis , who had an increased AR ( defined as a provocative concentration of methacholine causing a 20 % fall in forced expiratory volume in one second ( FEV1 ) ( PC20 ) < 25 mg x mL(-1 ) evaluated by the dosimeter method ) , were r and omized , double-blind into two parallel groups . Thirteen of the children were treated with roxithromycin ( 4 mg x kg(-1 ) b.i.d . ) for 12 weeks and 12 received placebo .  FEV1 , sputum purulence and leucocyte scores were assessed every 3 weeks . To estimate AR , high-dose methacholine challenge tests were performed before and after treatment . On the dose-response curve to methacholine , PD20 and maximal response ( two indices of AR ) were measured . Changes in FEV1 were not observed during the course of the study in both groups . A significant improvement in sputum features was noted after 6 weeks of treatment in the roxithromycin group . After 12 weeks of roxithromycin therapy , the geometric mean ( range of 1 SD ) of provocative cumulative dose producing a 20 % fall in FEV1 ( PD20 ) increased significantly ( p<0.01 ) to 169.2 ( 83.2 - 344.2 ) breath units ( BU ) ( 1 BU denotes one inhalation of 1 mg x mL(-1 ) methacholine ) and the mean+/-SD of maximal response decreased significantly ( p<0.01 ) to 32.5+/-6.8 % , as compared with the initial values ( PD20 87.1 ( 47.3 - 160.4 ) BU ; maximal response 40.9+/-7.4 % ) . No significant changes in either parameter were observed in the placebo group . Our results indicate that roxithromycin may decrease the degree of airway responsiveness in patients with bronchiectasis and increased airway responsiveness . Further study is necessary to determine the mechanism by which roxithromycin reduces airway responsiveness in bronchiectasis and its clinical impact CONTEXT Treatment strategies for cystic fibrosis ( CF ) lung disease include antibiotics , mucolytics , and anti-inflammatory therapies . Increasing evidence suggests that macrolide antibiotics might be beneficial in patients with CF . OBJECTIVE To determine if an association between azithromycin use and pulmonary function exists in patients with CF . DESIGN AND SETTING A multicenter , r and omized , double-blind , placebo-controlled trial conducted from December 15 , 2000 , to May 2 , 2002 , at 23 CF care centers in the United States . PARTICIPANTS Of the 251 screened participants with a diagnosis of CF , 185 ( 74 % ) were r and omized . Eligibility criteria included age 6 years or older , infection with Pseudomonas aeruginosa for 1 or more years , and a forced expiratory volume in 1 second ( FEV1 ) of 30 % or more . Participants were stratified by FEV1 ( > or = 60 % predicted vs < 60 % predicted ) , weight of less than 40 kg vs 40 kg or more , and CF center . INTERVENTION The active group ( n = 87 ) received 250 mg ( weight < 40 kg ) or 500 mg ( weight > or = 40 kg ) of oral azithromycin 3 days a week for 168 days ; placebo group ( n = 98 ) received identically packaged tablets . MA 
    Output:
    
Long-term macrolide therapy may reduce the frequency of exacerbations and improve quality of life , although supporting evidence is derived mainly from studies of azithromycin , rather than other macrolides , and predominantly among adults rather than children .
However , macrolides should be used with caution , as limited data indicate an associated increase in microbial resistance .
Macrolides are associated with increased risk of cardiovascular death and other serious adverse events in other population s , and available data can not exclude a similar risk among patients with bronchiectasis