Oral Fabrol (oral N-acetyl-cysteine) in chronic bronchitis. The National Mucolytic Study. Results of a randomized, double-blind, placebo-controlled study of iodinated glycerol in chronic obstructive bronchitis. Iodinated glycerol has no effect on pulmonary function, symptom score, or sputum properties in patients with stable chronic bronchitis. Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. The PARI-IS Study Steering Committee and Research Group. Prevention of Acute Respiratory Infection by an Immunostimulant. Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis. Results at 1 year of outpatient multidisciplinary pulmonary rehabilitation: a randomised controlled trial Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis. Efficacy and Tolerability of Oral Acetylcysteine (Fabrol®) in Chronic Bronchitis: A Double-Blind Placebo Controlled Study S-carboxymethylcysteine in the fluidification of sputum and treatment of chronic airway obstruction. Efficacy and tolerability of myrtol standardized in long-term treatment of chronic bronchitis. A double-blind, placebo-controlled study. Study Group Investigators. N-isobutyrylcysteine, a donor of systemic thiols, does not reduce the exacerbation rate in chronic bronchitis. Prevention of acute exacerbations of chronic obstructive bronchitis with carbocysteine lysine salt monohydrate: a multicenter, double-blind, placebo-controlled trial. Ambroxol for the prevention of chronic bronchitis exacerbations: long-term multicenter trial. Protective effect of ambroxol against winter semester exacerbations: a double-blind study versus placebo. Effect of long-term treatment with sobrerol on the exacerbations of chronic bronchitis.
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 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 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 The clinical effect of N-acetylcysteine ( NAC ) controlled-release tablets , 300 mg b.i.d . , and placebo , in chronic bronchitis was investigated . The study was performed as a double-blind six month comparison between active drug and placebo in two parallel groups , with statistical evaluation after four and six months . The patients were chosen from nine centres . One hundred and sixteen out- patients were included and ninety one of them completed the six month study . The acetylcysteine-treated group had a significantly reduced number of sick-leave days caused by exacerbations of chronic bronchitis after the four winter months December-March compared with the control group ( NAC 173 , placebo 456 ) . The number of exacerbation days was also very much reduced , however , not significantly ( NAC 204 , placebo 399 ) . At the end of the six month trial , including also two spring months , the absolute numbers of sick-leave days and exacerbation days were still fewer in the acetylcysteine-treated group , ( NAC 260 , placebo 739 ) and ( NAC 378 , placebo 557 ) respectively . This study demonstrates a significant reduction in sick-leave days after four months of NAC-treatment . A constant tendency to reduction in the number of exacerbations and exacerbation days was also registered after four and six months . The differences in these parameters were , however , not statistically significant . This was probably due to the small number of patients participating BACKGROUND Pulmonary rehabilitation seems to be an effective intervention in patients with chronic obstructive pulmonary disease . We undertook a r and omised controlled trial to assess the effect of outpatient pulmonary rehabilitation on use of health care and patients ' wellbeing over 1 year . METHODS 200 patients with disabling chronic lung disease ( the majority with chronic obstructive pulmonary disease ) were r and omly assigned a 6-week multidisciplinary rehabilitation programme ( 18 visits ) or st and ard medical management . Use of health services was assessed from hospital and general- practice records . Analysis was by intention to treat . FINDINGS There was no difference between the rehabilitation ( n=99 ) and control ( n=101 ) groups in the number of patients admitted to hospital ( 40 vs 41 ) but the number of days these patients spent in hospital differed significantly ( mean 10.4 [ SD 9.7 ] vs 21.0 [ 20.7 ] , p=0.022 ) . The rehabilitation group had more primary -care consultations at the general-practitioner 's premises than did the control group ( 8.6 [ 6.8 ] vs 7.3 [ 8.3 ] , p=0.033 ) but fewer primary -care home visits ( 1.5 [ 2.8 ] vs 2.8 [ 4.6 ] , p=0.037 ) . Compared with control , the rehabilitation group also showed greater improvements in walking ability and in general and disease-specific health status . INTERPRETATION For patients chronically disabled by obstructive pulmonary disease , an intensive , multidisciplinary , outpatient programme of rehabilitation is an effective intervention , in the short term and the long term , that decreases use of health services This multicentre trial was undertaken to confirm previous results indicating that long-term treatment with oral acetylcysteine reduces the exacerbation rate in patients with chronic bronchitis . Two hundred and eighty-five patients , smokers or ex-smokers , with chronic bronchitis started a pre-trial placebo-period of 1 month . After this run-in period 259 patients were included in the trial and r and omized into two parallel groups . The patients were treated in a double-blind way either with acetylcysteine 200 mg b.i.d . or placebo b.i.d . for 6 months . The trial was completed by 98 patients in the acetylcysteine group and by 105 patients in the placebo group . Initially , there were no significant differences between the groups . Twice weekly , the patients filled in a diary card concerning symptoms . The number of exacerbations was assessed from these cards and at visits 2 , 4 and 6 months after institution of therapy . The exacerbation rate was significantly lower in the acetylcysteine group in which 40 % of the patients remained free from exacerbations compared to 19 % in the placebo group . Sick-leave due to acute exacerbation was significantly less common in the acetylcysteine group . The drug was well tolerated Summary In 69 out- patients with chronic bronchitis in 6 centres the effects of acetylcysteine 600 mg daily , 3 days a week for 6 months , and a placebo have been compared in a double-blind controlled trial . Thirty-five patients were treated with the mucolytic and 34 with the dummy preparation .  In the former the clinical course of the chronic bronchitis improved to a greater extent and a significantly lower number of exacerbations was observed . The advantages of long-term oral treatment with the mucolytic in chronic bronchitis suggest that it may be useful as an alternative to long-term antibiotic prophylaxis , or to complement brief courses of antibiotics , in addition to the usual physiotherapy Oral N-acetylcysteine ( NAC ) exerts a beneficial action in chronic bronchitis by reducing the number of exacerbations . There have been few studies of the effect of NAC ( or of any other drug ) on general well-being in chronic bronchitis . We used an established psychiatric instrument ( General Health Question naire ; GHQ ) and a visual analogue scale ( VAS ) to measure well-being in a 22-week , placebo-controlled , double-blind , parallel-group study of NAC administered as sustained release tablets 600 mg b.i.d . , including during the winter months , to patients with mild chronic bronchitis . One hundred and fifty-three patients were accepted for r and omized treatment , 129 finished the study ( 59 NAC , 70 placebo ) , and well-being was measured in 105 ( 46 NAC , 59 placebo ) . The number of observed exacerbations was unexpectedly low in both groups . The number was lowest in the NAC group , however , the difference did not reach statistical significance in the present study ( P = 0.08 ) . There were no statistically significant differences between NAC and placebo in subjective symptom scores , FEV1 or FVC . The distribution of GHQ score at baseline was uneven , but NAC was significantly superior to placebo in terms of a favourable effect on GHQ score . GHQ score correlated with the number of exacerbations , and VAS correlated with GHQ score . This study therefore demonstrates the validity of measuring general well-being in patients with mild chronic bronchitis . Future studies of the treatment of chronic bronchitis should use a battery of more specifically adapted instruments which are now becoming available to measure well-being This multicentre , double-blind , placebo controlled , between-patient study in general practice in the United Kingdom examined the effect of oral N-acetylcysteine ( Fabrol ® ) on the symptomatology of patients with chronic bronchitis over a 3-month period . Although improvement in subjective symptoms ( sputum viscosity and character , difficulty in expectoration and cough severity ) occurred in both treatment groups over the trial period , improvements in difficulty in expectoration and cough severity were greater in patients receiving N-acetylcysteine compared to matching placebo . Trial medication was well tolerated , with a greater number of side-effects attributed to therapy occurring in patients receiving placebo The clinical results and changes in sputum found in both a short-term inpatient trial and a subsequent long-term outpatient investigation ( three-month double-blind controlled study ) of 82 patients with chronic bronchitis treated with a new mucolytic agent , S-carboxymethylcysteine ( Mucodyne )  , are reported . Fluidification of sputum with reduction in certain measurements of the viscosity of morning sputum aliquots , associated with improvement in the ability to cough up bronchial secretions , significant increase in sputum volume output , and improvement in ventilation ( as estimated by the forced expiratory volume in one second ) , were observed in both trials as dose-related responses , with an increase in the ease of expectoration and a reduction in cough frequency and dyspnea . Therapy with S-carboxymethylcysteine was well tolerated , and there were no serious adverse effects , either immediate or delayed . We suggest that the effect of the drug in fluidifying sputum may be due to a mucoregulatory mechanism which reverses the sputum macromolecular disturbances seen in chronic bronchitis This multicenter , placebo-controlled , double-blind , r and omized parallel-group trial was conducted to investigate the efficacy and tolerability of myrtol st and ardized ( MYS , Gelomyrtol forte , 3 x 300 mg ) in the long-term treatment of patients with chronic bronchitis during the winter . 246 patients received the investigational treatments  ( MYS : 122 , placebo : 124 ) for at least 1 month ; 215 subjects ( 110 under MYS and 105 under placebo )  were evaluable in terms of efficacy ( exacerbation rate , the need for antibiotics , symptom scores and general well-being ) for the protocol -defined 6 months of treatment . Statistically significantly ( p < 0.01 ) more patients remained without acute exacerbation in the myrtol st and ardized group ( 72 % ) compared to the placebo group ( 53 % ) . In the placebo group , there was an evident peak in the incidence of exacerbations during the third month of treatment , which was not observed in the active treatment group . In the MYS group , 51.6 % of the patients with an acute exacerbation required  antibiotics  vs. 61.2 % under placebo . 62.5 % of the patients treated with antibiotics in the MYS group required them for < or = 7 days , whereas 76.7 % of the patients in the placebo group treated with antibiotics for exacerbation needed antibiotics for > 7 days . Well-being ( assessed in terms of general health and health impairment by cough and expectoration ) was significantly better under treatment with MYS . The overall therapeutic efficacy evaluation scored higher for MYS . Therefore , it is concluded that long-term treatment with MYS is equally well tolerated as placebo but is clearly superior in efficacy in terms of protecting against acute exacerbations in patients with chronic bronchitis : it reduces the frequency and intensity of acute exacerbations , the need of antibiotics for them and the health impairment by cough and expectoration N-isobutyrylcysteine ( NIC ) , a new thiol compound that is not rapidly hydrolysed to give higher levels of free thiols in the body than N-acetylcysteine ( NAC ) , was used to test if the effect of NAC on exacerbations in chronic bronchitis was an effect of the unhydrolysed thiol compound . Smokers or exsmokers with chronic bronchitis forced expiratory volume in one second ( FEV1 ) > 40 % and reversibility < or = 10 % predicted were treated with oral  NIC 300 mg b.i.d . or placebo for 24 weeks . Steroids , NAC , antibiotics , and nonsteroid anti-inflammatory drugs use were restricted . Exacerbations were recorded by a respiratory symptom diary card and the time to onset of the first exacerbation after the start of treatment was measured using life-table analysis . Spirometry was performed at each visit . Six hundred and thirty-seven patients were r and omized to treatment with  NIC ( n=316 ) or placebo ( n=321 ) . NIC did not prolong the time to first exacerbation ( life-table analysis , p=0.59 ) and no increase in FEV1 or forced vital capacity was observed . Altered taste perception , taste loss and anosmia occurred more often in the NIC group ( p<0.001 ) . In conclusion , N-isobutyrylcysteine , a N-acetylcysteine-like drug with a greater bioavailability has , contrary to N-acetylcysteine , no effect on exacerbations in chronic bronchitis . This suggests that the effect of N-acetylcysteine on exacerbations in chronic bronchitis is not due to the relatively low free thiol levels ( other than glutathione ) produced by N-acetylcysteine therapy The efficacy and safety of carbocysteine lysine salt monohydrate ( SCMC-Lys ) in the prevention of acute exacerbations associated with chronic obstructive bronchitis were evaluated in a multicenter double-blind , placebo-controlled , parallel group trial in 662 out patients . After a 1-month run-in period , patients were r and omized to three groups and assigned to receive one of the following oral treatments : continuous SCMC-Lys 2.7 g once daily , intermittent SCMC-Lys at the same dosage ( 1-week courses alternating with 1-week intervals on placebo ) or placebo . Each treatment lasted for 6 months and spanned the cooler months of the year . Evaluation was based on a daily recording of relevant clinical symptoms and signs and subsequent evaluation of the collected data by three blinded independent physicians . A total of 146 patients ( 23 % ) failed to complete the 6-month treatment ( mostly due to difficulties in complying with protocol requirements ) , without clear-cut differences in the dropout rate in the three groups . An intention-to-treat analysis revealed that the incidence of patients without exacerbations in the group assigned to continuous SCMC-Lys treatment was significantly higher than in the placebo-treated group ( p < 0.001 ) . The total number of patients with at least one exacerbation was 66 ( 29.6 % ) in the group treated with continuous SCMC-Lys compared with 100 ( 45.9 % ) with placebo . In the former group the time between initiation of treatment and first exacerbation was significantly prolonged . The average number of days with acute respiratory illness was significantly decreased in the group receiving continuous SCMC-Lys compared with the group receiving placebo , and this was associated with a significant reduction in the antibiotic consumption during the trial period . In patients assigned to intermittent treatment , results of the assessed endpoints did not differ significantly from those observed in the placebo group . No serious adverse effects were reported . It is concluded that continuous administration of SCMC-Lys throughout the winter season is effective in preventing acute exacerbations in patients with chronic obstructive bronchitis and it is well tolerated In a 6-month , double-blind multicenter trial conducted over the winter , the effects of daily administration of ambroxol retard ( 75 mg ) were compared with those of placebo in preventing exacerbations and improving symptoms and clinical signs in chronic bronchitis patients . The trial was completed by 110 patients in the ambroxol group and by 104 in the placebo group . Initially , there were no significant differences between the groups . By the end of the 2nd month of treatment , 67.2 % of the ambroxol group had had no exacerbations compared to 50.4 % in the placebo group . At the end of the 6-month trial , 45.5 % of the treatment group had had no exacerbations , compared to only 14.4 % of the control group . These differences were statistically significant . Patients in the treatment group lost significantly fewer days through illness ( 442 ) and had fewer days when they needed antibiotic therapy ( 371 ) compared to the placebo group patients ( 837 and 781 ) . Ambroxol also produced statistically significant symptomatic improvement , measured as difficulty in expectoration , coughing , presence of dyspnea and the auscultatory signs as compared to controls . Since ambroxol was well tolerated and compliance was good , it appears like a drug of choice for pharmacological prophylaxis of chronic bronchitis 706 chronic bronchitic patients were admitted to a double-blind controlled multicenter study to evaluate the effect of the prolonged administration of sobrerol on exacerbations , clinical signs and respiratory function indexes .  Patients were treated at r and om with sobrerol 300 mg b.i.d . or placebo b.i.d . for 3 consecutive months during the winter of 1983/1984 . At the beginning of the study , sex , body surface , smoking habits , environment , anti-influenzal vaccination , concomitant pathologies and therapies , respiratory anamnesis , clinical condition and spirometric indexes were equivalent in the two groups . Among the patients admitted to the study , 76 % of the sobrerol group did not complain of any exacerbations compared to 58 % of the placebo group ( p less than 0.001 ) , moreover the risk of exacerbation was about twice higher than with the drug . The use of antibiotics was equivalent in the two groups , whilst the consumption of bronchodilators/theophyllines was markedly lower in the sobrerol group . The response of the clinical signs ( dyspnea and auscultatory semeiotics ) and of the spirometric indexes ( RV , VC and FEV1 ) to therapy , was significantly higher in the patients treated with sobrerol compared to the placebo group . The opinion expressed by the experimenter and by the patient at the end of each month of treatment was again in favor of sobrerol .  Side effects , which were minor and no different from those cl aim ed by the patients treated with placebo , and the hematological and hematochemical assessment s , carried out before and after treatment , support the good tolerance of sobrerol . These results let us hope for a more appropriate use of the mucus-regulating agents , particularly in the chronic bronchopulmonary pathologies for which these drugs seem to represent the most rational care
OBJECTIVE To assess the effects of oral mucolytics in adults with stable chronic bronchitis and chronic obstructive pulmonary disease .