***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 
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    Input: Five hundred and twenty-six patients suffering from chronic bronchitis were r and omized to receive either N-acetylcysteine ( NAC ) or placebo during a 6-month period . The aim was to compare the number of acute exacerbations in the two groups . General practitioners were asked to enter patients with a diagnosis of chronic bronchitis , based on the MRC criteria . We failed to find any statistically significant difference in the number of exacerbations between the two treatment groups although there was a slight trend towards improvement in the NAC group during the first 3 months of the trial . The tolerability was similar for both treatments . Patients taking NAC showed a reduction in number of days on which they were incapacitated and this result was statistically significant Background The clinical effects of mucolytics in patients with chronic obstructive pulmonary disease ( COPD ) are discussed controversially . Cineole is the main constituent of eucalyptus oil and mainly used in inflammatory airway diseases as a mucolytic agent . We hypothesised that its known mucolytic , bronchodilating and anti-inflammatory effects as concomitant therapy would reduce the exacerbation rate and show benefits on pulmonary function tests as well as quality of life in patients with COPD . Methods In this double-blind , placebo-controlled multi-center- study we r and omly assigned 242 patients with stable COPD to receive 200 mg of cineole or placebo 3 times daily as concomitant therapy for 6 months during winter-time . The frequency , duration and severity of exacerbations were combined as primary outcome measures for testing as multiple criteria . Secondary outcome measures included changes of lung function , respiratory symptoms and quality of life as well as the single parameters of the exacerbations . Results Baseline demographics , lung function and st and ard medication of both groups were comparable . During the treatment period of 6 months the multiple criteria frequency , severity and duration of exacerbations were significantly lower in the group treated with cineole in comparison to placebo . Secondary outcome measures vali date d these findings . Improvement of lung function , dyspnea and quality of life as multiple criteria were statistically significant relative to placebo . Adverse events were comparable in both groups . Conclusion Concomitant therapy with cineole reduces exacerbations as well as dyspnea and improves lung function and health status . This study further suggests cineole as an active controller of airway inflammation in COPD by intervening in the pathophysiology of airway inflammation of the mucus membrane . Trial registration IS RCT Seventy-four pulmonologists and one allergist were recruited to assess the efficacy and safety of iodinated glycerol ( Organidin ) , 60 mg qid , vs placebo in patients with stable chronic obstructive bronchitis in a r and omized , double-blind , placebo-controlled , parallel design . A total of 361 patients ( 180 to iodinated glycerol and 181 to placebo ) who complained of cough and difficulty bringing up sputum entered the eight-week study . Evaluations were based upon eight primary symptom efficacy parameters ( cough frequency , cough severity , chest discomfort , dyspnea , ease in bringing up sputum , patient and physician global assessment s , and a derived patients ' global assessment ) , and six secondary parameters ( frequency of aerosol bronchodilator use , incidence and duration of acute exacerbations , frequency of concomitant medication use , incidences of adverse experiences and dropouts ) . Cough frequency , cough severity , chest discomfort , patients ' ease in bringing up sputum , patients ' overall condition , and a derived subject global assessment were significantly ( p less than 0.05 ) improved by iodinated glycerol as compared with placebo within eight weeks of treatment . Dyspnea showed a trend toward improvement and the physicians ' global evaluation showed no significant difference between groups . Similar findings were noted in a subgroup analysis of moderately-to-severely affected patients . The mean duration ( days ) of acute exacerbations and number of dropouts attributable to adverse experiences were significantly less ( p less than 0.05 ) in the iodinated glycerol group . ( ABSTRACT TRUNCATED AT 250 WORDS STUDY OBJECTIVE It has been reported that therapy with iodinated glycerol ( IG ) can improve the quality of life for patients with chronic bronchitis . The purpose of this study was to determine the effects of IG therapy on the quality of life , pulmonary function , and on the properties of sputum collected from adults with stable chronic bronchitis . DESIGN Thirty-two week , double-blind , r and omized , placebo-controlled cross-over study . SETTING A university outpatient pulmonary clinic . PARTICIPANTS Twenty-six adults with stable chronic bronchitis completed the study ; 28 completed the first treatment arm . INTERVENTIONS Sixteen weeks each of placebo or IG 60 mg qid . MEASUREMENTS First , pulmonary function by spirometry and plethysmography . Second , symptom score measured using a question naire . Third , sputum bulk and surface rheology , spinnability , mucociliary transportability and cough transportability . RESULTS There were no significant changes in pulmonary function , clinical scores , or sputum properties related to therapy with IG . There was a significant improvement in the Global Petty score after both IG ( p = 0.01 ) and placebo ( p < 0.01 ) when compared with baseline , but there was no difference between treatment periods . There was a positive correlation between changes in the Global score during therapy and changes in sputum spinnability ( p < 0.01 , r = 0.38 ) . CONCLUSIONS This study clearly demonstrates that in chronic bronchitis , 16 weeks of therapy with IG does not produce any appreciable effect on pulmonary function , well being , or on sputum viscoelasticity or clearability BACKGROUND The aim of this double-blind , r and omised , controlled study vs placebo was to evaluate the efficacy and tolerability of neltenexine ( tablets ) versus placebo ( tablets ) , administered to smoking and non-smoking patients with chronic obstructive pulmonary disease ( COPD ) . METHODS Sixty patients with mild stable COPD were recruited . The exclusion criteria were lung cancer , pulmonary tuberculosis , asthma , cystic fibrosis , bronchiectasis , community-acquired pneumonia ( CAP ) , intercurrent infections , concomitant treatment with corticosteroids , antitussives , beta2 agonists , anticholinergic and other mucolytic agents . The patients were allocated r and omly to receive neltenexine ( 20 smokers and 20 non-smokers ) or a matching placebo ( 20 smokers ) , 1 tablet twice daily for 20 days . The efficacy criteria were sputum characteristics and volume , difficulty in expectorating , cough , dyspnoea , pulmonary auscultation , forced expiratory volume in one second ( FEV1 ) , vital capacity and arterial partial oxygen pressure ( PO2 ) . Tolerability was monitored and adverse events were reported . RESULTS At the study end , the improvement of patients treated with  neltenexine  ( smokers and non-smokers ) was greater and statistically significant as compared with the patients in the placebo group in terms of improvement of dyspnoea ( p<0.02 ) , cough ( p<0.02 ) , pulmonary auscultation ( p<0.02 ) , and difficulty in expectorating ( p<0.02 ) . Furthermore , a significant improvement of the sputum characteristics ( p<0.02 ) and volume ( p<0.01 ) was evidence d , as compared with patients treated with placebo , in non smoking patients treated with neltenexine and in smoking patients treated with neltenexine . CONCLUSIONS The study confirmed earlier clinical experiences showing that neltenexine is effective in the treatment of COPD patients and highlighted the correlation between abstention from smoking and the efficacy of mucoactive treatment The objective of this prospect i ve , r and omized , double-blind , placebo-controlled , multicenter parallel-group study was to evaluate the effect of long-term ambroxol treatment in preventing exacerbations of chronic obstructive pulmonary disease ( COPD ) . Two hundred and forty-two out patients with COPD defined by ATS criteria with value of FEV1 between > or = 60 and 80 % of predicted and history of one or more exacerbations in the previous year were recruited by 26 Respiratory Medicine Centers in Italy and treated for 1 year with one ambroxol retard capsule of 75 mg twice daily or placebo . The percentage of patients free from exacerbation at 6 months was 63 % with ambroxol and 60 % with placebo ( p=0.366 ) and at 12 months 56 % with ambroxol and 53 % with placebo ( p=0.363 ) . In a subset of 45 patients with more severe baseline symptoms , ambroxol therapy was associated with a significant higher percentage of patients free from exacerbation compared to placebo : 63 vs. 38 % ( p=0.038 ) . In conclusion , we did not find a significant difference between long-term ambroxol therapy and placebo , in preventing exacerbations in patients with COPD . In patients with more severe respiratory symptoms at baseline , however , we observed a significant difference in the cumulative exacerbation-free persistence between ambroxol and placebo , suggesting that long-term muco-regulatory therapy with ambroxol could be useful in highly symptomatic patients with COPD The study was design ed to assess the safety and efficacy of orally-administered iodinated glycerol ( Organidin ) in the management of patients with stable , chronic obstructive bronchitis , who complained of cough and difficulty in raising sputum , and who would be c and i date s for mucolytic-expectorant The PARI-IS Study is a double-blind placebo-controlled r and omized clinical trial to study the effect of an immunostimulating agent to prevent acute respiratory exacerbation in patients with COPD . Three hundred eighty-one ambulatory patients ( 190 placebo and 191 immunostimulant )  were followed at home for 6 mo by experienced research nurses . The risk of having at least one episode of acute exacerbation ( primary outcome ) was similar in the two groups ( p = 0.872 ) . In contrast , the total number of days of hospitalization for a respiratory problem was 55 % less in the group treated with OM-85 BV ( 287 d ) than in the group treated with placebo ( 642 d ) . Patients treated with OM-85 BV spent an average of 1.5 d in hospital compared with 3.4 d for patients treated with placebo ( p = 0.037 ) . The risk of being hospitalized for a respiratory problem was 30 % lower in the treated group ( 16.2 % ) than in the placebo group ( 23.2 % ) ; p = 0.089 . Eight deaths were observed : two in patients treated with OM-85 BV and six in patients treated with placebo ( p = 0.153 ) . During the course of the study dyspnea improved slightly in patients treated with OM-85 BV , whereas it deteriorated slightly in patients receiving placebo ( p = 0.028 ) . These results suggest that this immunostimulating agent may be beneficial for patients with COPD by reducing the likelihood of severe respiratory events leading to hospitalization Patients with chronic obstructive pulmonary disease ( COPD ) exhale more hydrogen peroxide ( H2O2 ) and lipid peroxidation products than healthy subjects . This may reflect oxidative stress in the airways that plays important role in the development and progression of COPD . N-acetylcysteine ( NAC ) , a mucolytic drug , possesses antioxidant properties as it is a precursor of reduced glutathione that together with glutathione peroxidase may decompose H2O2 and lipid peroxides . We aim ed to determine the effect of NAC , 600 mg effervescent tablets ( Fluimucil ) , once a day for 12 months , and placebo on the concentration of H2O2 and thiobarbituric acid reactive substances ( TBARs ) in expired breath condensate and serum levels of two lipid peroxidation products ( TBARs , lipid peroxides ) in patients with COPD . The study was performed as a double-blind , double-dummy comparison between active drug and placebo in two parallel groups . Forty-four out patients with stable COPD ( 22 in the NAC group and 22 in the placebo group ) completed the study .  Specimens of expired breath condensate and serum were collected at the r and omization visit and then every 3 months over 1 year . The concentration of TBARs and H2O2 in expired breath condensate was measured spectrofluorimetrically by the thiobarbituric acid and homovanillic acid methods , respectively . Serum levels of lipid peroxides were determined spectrophotometrically after extraction with butanol and pyridine . Initially , H2O2 exhalation did not differ between the placebo and NAC groups up to 6 months of treatment . After this the significant differences were observed . After 9 and 12 months of treatment NAC group exhaled 2.3-fold ( 0.17+/-0.33 microM vs. 041+/-0.26 microM , P<0.04 ) [ median 0.01 microM , quartile range (qr)=0.22 vs. median 0.15 microM , qr = 0.43 ] and 2.6-fold ( 0.15+/-0.23 
    Output:
    
There was no clinical ly important improvement in lung function or consistent impact on quality of life with mucolytics .
AUTHORS ' CONCLUSIONS In participants with chronic bronchitis or COPD , treatment with a mucolytic may produce a small reduction in acute exacerbations , but may have little or no effect on the overall quality of life .
The effects on exacerbations shown in early trials were larger than those found in the more recent studies .
This may be because the earlier smaller trials were at higher risk of selection or publication bias , so the benefits of treatment may not be as large as suggested by the previous evidence