***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 Treating symptoms and preventing exacerbations are key components of chronic obstructive pulmonary disease ( COPD ) long-term management . Recently , a more tailored treatment approach has been proposed , in particular for two well-established clinical phenotypes , frequent exacerbators and chronic bronchitis-dominant COPD . ELOM-080 has demonstrated clinical efficacy in treating symptoms and preventing exacerbations in subjects with chronic bronchitis . However , little is known about the potential effects of ELOM-080 in COPD patients . Aim To evaluate the effect on exacerbation , cough sputum , and general state of health of long-term treatment with ELOM-080 in COPD patients with an exacerbation history and chronic bronchitis . Methods We performed a post-hoc analysis of a r and omized , double-blinded , placebo-controlled parallel-group clinical trial of a 6-month treatment with ELOM-080 ( 3 × 300 mg ) in patients with chronic bronchitis and concomitant COPD . The primary outcome was the proportion of subjects with at least one exacerbation over the 6-month study period . Secondary outcomes included the total number of exacerbations ( ie , cumulative occurrence of exacerbations during the study period ) and the proportion of acute exacerbations necessitating an antibiotic treatment , monthly evaluations of sputum and cough symptoms , and the general state of health and a safety analysis . Results Of 260 r and omized subjects , 64 patients fulfilled the inclusion criteria for COPD ( ELOM-080 : 35 , placebo : 29 ) . Compared to placebo , ELOM-080 reduced the percentage of subjects with at least one exacerbation ( 29 % versus 55 % , P=0.031 ) and a reduction in the overall occurrence of exacerbations ( ELOM-080 : 10 , placebo : 21 , P=0.012 ) during the winter season . The percentage of asymptomatic or mildly symptomatic patients ( sputum/expectoration and cough ) was consistently higher in the ELOM-080 group compared to placebo , with statistical significant differences after 2 and 3 months of treatment ( 2 months : ELOM-080 25 % , placebo 11 % , P<0.005 ; 3 months : ELOM-080 26 % , placebo 14 % , P<0.05 ) . Likewise the subjective rating of general health status was better in the ELOM-080 group with statistically significant superiority after 2 and 3 months of treatment ( 2-month treatment : P=0.015 ; 3-month treatment : P=0.024 ) . Tolerability results were comparable between ELOM-080 and placebo . Conclusion ELOM-080 is efficacious in patients with COPD and a chronic bronchitis phenotype . Prophylactic use reduces the rate of exacerbations and improves the key symptoms of sputum and cough with a favorable long-term tolerability profile 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 BACKGROUND The mucolytic and antioxidant effects of N-acetylcysteine ( NAC ) may have great value in COPD treatment . However , beneficial effects have not been confirmed in clinical studies , possibly due to insufficient NAC doses and /or inadequate outcome parameters used . The objective of this study was to investigate high-dose NAC plus usual therapy in Chinese patients with stable COPD . METHODS The 1-year HIACE ( The Effect of High Dose N-acetylcysteine on Air Trapping and Airway Resistance of Chronic Obstructive Pulmonary Disease-a Double-blinded , R and omized , Placebo-controlled Trial ) double-blind trial conducted in Kwong Wah Hospital , Hong Kong , r and omized eligible patients aged 50 to 80 years with stable COPD to NAC 600 mg bid or placebo after 4-week run-in . Lung function parameters , symptoms , modified Medical Research Council ( mMRC ) dyspnea and St. George 's Respiratory Question naire ( SGRQ ) scores , 6-min walking distance ( 6MWD ) , and exacerbation and admission rates were measured at baseline and every 16 weeks for 1 year . RESULTS Of 133 patients screened , 120 were eligible ( 93.2 % men ; mean age , 70.8±0.74 years ; % FEV1 53.9±2.0 % ) . Baseline characteristics were similar in the two groups . At 1 year , there was a significant improvement in forced expiratory flow 25 % to 75 % ( P=.037 ) and forced oscillation technique , a significant reduction in exacerbation frequency ( 0.96 times/y vs 1.71 times/y , P=.019 ) , and a tendency toward reduction in admission rate ( 0.5 times/y vs 0.8 times/y , P=.196 ) with NAC vs placebo . There were no significant between-group differences in mMRC dypsnea score , SGRQ score , and 6MWD . No major adverse effects were reported . CONCLUSION In this study , 1-year treatment with high-dose NAC result ed in significantly improved small airways function and decreased exacerbation frequency in patients with stable COPD . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01136239 ; URL : www . clinical trials.gov Antioxidant therapy has a potential to be introduced as therapeutic modality for chronic obstructive pulmonary disease ( COPD ) patients . This study aim ed to determine the effect of antioxidant supplementation [ ascorbic acid and N-Acetylcysteine ( NAC ) ] on nutritional and antioxidant status in male COPD patients . A parallel and single blind r and omised controlled clinical trial ( RCT ) was conducted at two medical centers in Kuala Lumpur , Malaysia . Seventy-nine subjects were recruited and r and omly divided into four trial arms ( i.e. , NAC , vitamin C , NAC+vitamin C and control groups ) for six mo . The primary outcome was changes in body mass index by estimating power of 90 % and significance level of p<0.05 . Repeated Measure ANOVA showed that there was a significant interaction effect on BMI ( p=0.046 ) and carbohydrate intake ( p=0.030 ) , especially in the NAC group . Plasma glutathione ( GSH ) increased significantly in all intervention groups , especially in vitamin C ( p=0.005 ) . A single supplementation of NAC or vitamin C improved nutritional and antioxidant status of subjects 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 / aim Lysozyme ( mucopeptide N-acetyl-muramyl hydrolase ) is widely used as a mucolytic and anti-inflammatory agent in Japan . We evaluated the effects of long-term lysozyme administration on COPD exacerbation .  Methods In a 1-year , r and omized , double-blind , placebo-controlled , parallel trial , patients with moderate-to-severe COPD and one or more episodes of COPD exacerbation in the previous year before enrollment were selected .  Lysozyme ( 270 mg ) or placebo was administered orally for 52 weeks as an add-on to the st and ard therapies such as bronchodilators .  COPD exacerbation , pulmonary function , and COPD assessment test scores were analyzed . An exacerbation was defined as worsening of more than one symptom of COPD ( cough , sputum volume , purulent sputum , or breathlessness ) leading to a change in medication . The primary endpoint was exacerbation rate . Results A total of 408 patients were r and omly assigned to the lysozyme and placebo groups . The baseline characteristics were similar between the two groups . The ex 
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The type or dose of mucolytic did not seem to alter the effect size , nor did the severity of COPD , including exacerbation history .
Mucolytic treatment was not associated with any significant increase in the total number of adverse effects , including mortality ( Peto OR 1.03 , 95 % CI 0.52 to 2.03 ; participants = 2931 ; studies = 8 ; I(2 ) = 0 % ) , but the confidence interval is too wide to confirm that the treatment has no effect on mortality .
AUTHORS ' CONCLUSIONS In participants with chronic bronchitis or COPD , we are moderately confident that treatment with mucolytics may produce a small reduction in acute exacerbations and a small effect on overall quality of life .
Our confidence in the results is reduced by the fact that effects on exacerbations shown in early trials were larger than those reported by more recent studies , possibly because the earlier smaller trials were at greater risk of selection or publication bias , thus benefits of treatment may not be as great as was suggested by previous evidence