***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: The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis . Such a model could help research ers and clinicians to evaluate therapies , improve the design of prospect i ve studies , monitor practice patterns , counsel individual patients , and determine the best c and i date s for lung transplantation . The authors used information from the Cystic Fibrosis Foundation Patient Registry ( CFFPR ) , which has collected longitudinal data on approximately 90 % of cystic fibrosis patients diagnosed in the United States since 1986 . They developed multivariate logistic regression models by using data on 5,820 patients r and omly selected from 11,630 in the CFFPR in 1993 . Models were tested for goodness of fit and were vali date d for the remaining 5,810 patients for 1993 . The vali date d 5-year survivorship model included age , forced expiratory volume in 1 second as a percentage of predicted normal , gender , weight-for-age z score , pancreatic sufficiency , diabetes mellitus , Staphylococcus aureus infection , Burkerholderia cepacia infection , and annual number of acute pulmonary exacerbations . The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research Background : Osmotic agents , such as inhaled dry powder mannitol , may increase mucociliary clearance by rehydrating the airway surface liquid and thus act as disease-modifying treatments in cystic fibrosis ( CF ) . This is the first therapeutic trial of inhaled mannitol in children with CF ; it was compared with recombinant human deoxyribonuclease ( rhDNase ) , the current best established mucolytic treatment . Methods : 38 children were recruited to an open crossover study . Subjects underwent an initial bronchial provocation challenge with dry powder mannitol . Those children with a negative challenge were r and omly allocated to one of three consecutive 12-week treatment blocks ( inhaled mannitol alone , nebulised rhDNase alone and mannitol + rhDNase ) . The primary outcome was forced expiratory volume in 1 s ( FEV1 ) . A number of secondary outcome measures were also studied . Results : Twenty children completed the study .  Bronchoconstriction and cough associated with mannitol administration contributed to the high attrition rate . The mean increase in FEV1 following 12 weeks of treatment was 0.11 litres ( 6.7 % ) ( p = 0.055 ) for mannitol alone , 0.12 litres ( 7.2 % ) ( p = 0.03 ) for rhDNase alone and 0.03 litres ( 1.88 % ) ( p = 0.67 ) for rhDNase and mannitol . None of the secondary clinical outcomes was statistically significantly different between treatments . Conclusions : Inhaled mannitol was at least as effective as rhDNase after 3 months treatment . There was a marked individual variation in tolerance to mannitol and in response to treatment however . Children who do not respond to rhDNase many benefit from a trial of inhaled mannitol . The combination of mannitol and rhDNase was not useful . Trial registration number : 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 β2-agonists and osmotic agents  stimulate mucociliary clearance ( MCC ) via different mechanisms which could potentially interact . The effects of inhaling terbutaline in combination with mannitol on MCC were investigated in nine healthy ( aged 19±1 yrs ) and 11 mild ( aged 21±4 yrs ) asthmatic subjects . Using 99mTc-sulphur colloid radioaerosol and a gamma camera , MCC was studied on four separate days with each of the following interventions : 1 ) terbutaline or its placebo inhaled 10 min before mannitol ( in r and om , double blind ) ; 2 ) terbutaline inhaled 5 min after mannitol ; and 3 ) terbutaline inhaled 10 min before the control for mannitol . Lung images were collected over a period of 120 min postintervention and over 150 min in total . The mannitol-induced increase in clearance was transiently inhibited by terbutaline pretreatment and transiently enhanced when terbutaline was administered after mannitol both in asthmatic and healthy subjects . The order of administration of mannitol and terbutaline did not affect the total clearance of radioactive mucus over 140 min from the start of intervention in both groups . The pathways through which terbutaline and mannitol  increase mucociliary clearance may transiently interact in an inhibitory or synergistic way , depending on the order of administration . However , this did not affect the overall increase in mucociliary clearance over 140 min It has been postulated that hypertonic saline ( HS ) might impair the antimicrobial effects of defensins within the airways . Alternative non-ionic osmotic agents such as mannitol may thus be preferable to HS in promoting bronchial mucus clearance ( BMC ) in patients with cystic fibrosis ( CF ) . This study reports the effect of inhalation of another osmotic agent , dry powder Mannitol ( 300 mg ) , compared with its control ( empty capsules plus matched voluntary cough ) and a 6 % solution of HS on BMC in 12 patients with cystic fibrosis ( CF ) .  Mucus clearance was measured using a radioaerosol/gamma camera technique . Post-intervention clearance was measured for 60 min , followed by cough clearance for 30 min . Neither mannitol nor HS improved BMC during the actual intervention period compared with their respective controls . However during the post-intervention measurement there was a significant improvement in BMC for both the mannitol ( 8.7+/-3.3 % versus 2.8+/-0.7 % ) and HS ( 10.0+/-2.3 % versus 3.5+/-0.8 % ) . There was also a significant improvement in cough clearance with the Mannitol ( 9.7+/-2.4 % ) compared with its control ( 2.5+/-0.8 % ) . Despite premedication with a bronchodilator , a small fall in forced expiratory volume in one second ( FEV1 ) was seen immediately after administration of both the mannitol ( 7.3+/-2.5 % ) and HS ( 5.8+/-1.2 % ) . Values of FEV1 returned to baseline by the end of the study . Inhaled mannitol is a potential mucoactive agent in cystic fibrosis patients . Further studies are required to establish the optimal dose and the long-term effectiveness of mannitol This international phase III study of inhaled dry powder mannitol was a r and omised , double-blind , 26-week study , followed by a further 26-week , open-label ( OL ) extension . 324 cystic fibrosis ( CF ) patients were r and omised , in a 3:2 ratio , to mannitol ( 400 mg b.i.d . ) and control groups . The primary efficacy end-point was to determine the change in forced expiratory volume in 1 s ( FEV1 ) over the double-blind phase . Secondary end-points included changes in forced vital capacity and pulmonary exacerbations . A significant improvement in FEV1 was seen over 26 weeks ( p<0.001 ) and was apparent by 6 weeks , irrespective of concomitant recombinant human deoxyribonuclease ( rhDNase ) use . At 26 weeks , there was a significant improvement in FEV1 of 92.9 mL for subjects receiving mannitol compared with controls ( change from baseline 118.9 mL ( 6.5 % ) versus 26.0 mL ( 2.4 % ) ; p<0.001 ) . Improvements in FEV1 were maintained up to 52 weeks in the OL part of the study . There was a 35.4 % reduction in the incidence of having an exacerbation on mannitol ( p=0.045 ) . The incidence of adverse events ( AEs ) was similar in both groups , although treatment-related AEs were higher in the mannitol compared with the control group . The most common mannitol-related AEs were cough , haemoptysis and pharyngolaryngeal pain .  Mannitol showed sustained , clinical ly meaningful benefit in airway function in CF , irrespective of concomitant rhDNase use . Mannitol appears to have an acceptable safety profile for patients with CF 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 ) Inhalation of hypertonic saline stimulates mucociliary clearance ( MCC ) in healthy subjects and those with obstructive lung disease . We investigated the effect of inhaling the osmotic agent mannitol on MCC . We used a dry-powder preparation of mannitol British Pharmacopea ( BP ) which was encapsulated and delivered using a Dinkihaler .  MCC was measured for 75 min in six asthmatic and six healthy subjects on two occasions before and after the mannitol inhalation or its control , using 99mTc-sulphur colloid and a gamma camera . The inhaled dose of man 
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For the comparison of mannitol and control , we found no consistent differences in health-related quality of life in any of the domains , except for burden of treatment , which was less for mannitol up to four months in the two pooled studies of a similar design ; this difference was not maintained at six months .
Up to and including six months , lung function in terms of forced expiratory volume at one second ( millilitres ) and per cent predicted were significantly improved in all three studies comparing mannitol to control .
Beneficial results were observed in these studies in adults and in both concomitant  dornase alfa users and non users .
A significant reduction was shown in the incidence of pulmonary exacerbations in favour of mannitol at six months ; however , the estimate of this effect was imprecise so it is unclear whether the effect is clinical ly meaningful .
Cough , haemoptysis , bronchospasm , pharyngolaryngeal pain and post-tussive vomiting were the most commonly reported side effects on both treatments .
Mannitol was not associated with any increase in isolation of bacteria over a six-month period .
In the 12-week cross-over study ( 28 participants ) , no significant differences were found in the recorded domains of health-related quality of life or measures of lung function between mannitol versus dornase alfa alone and versus mannitol plus dornase alfa .
There seemed to be a higher rate of pulmonary exacerbations in the mannitol plus dornase alfa arm compared with dornase alfa alone ; although not statistically significant , this was the most common reason for stopping treatment in this arm .
Cough was the most common side effect in the mannitol alone arm but there was no occurrence of cough in the dornase alfa alone arm and the most commonly reported reason of withdrawal from the mannitol plus dornase alfa arm was pulmonary exacerbations .
Mannitol ( with or without dornase alfa ) was not associated with any increase in isolation of bacteria over the 12-week period .
There is evidence to show that treatment with mannitol over a six-month period is associated with an improvement in some measures of lung function in people with cystic fibrosis compared to control .
There is no r and omised evidence of improvement in lung function or quality of life comparing mannitol to dornase alfa alone and to mannitol plus dornase alfa .