Oral immunization with bacterial extracts for protection against acute bronchitis in elderly institutionalized patients with chronic bronchitis. Economic impact of using an immunostimulating agent to prevent severe acute exacerbations in patients with chronic obstructive pulmonary disease. Immunotherapy with an oral bacterial extract (OM-85 BV) for upper respiratory infections. [Efficacy of the immunostimulant Broncho-Vaxom]. [Multicenter double-blind study of the action of Broncho-Vaxom in chronic bronchitis]. Efficacy of oral immunotherapy on respiratory infections in hemodialysis patients: a double-blind, placebo-controlled study. Primary prevention of acute respiratory tract infections in children using a bacterial immunostimulant: a double-masked, placebo-controlled clinical trial. Immunomodulators and primary prevention of respiratory infections: methodological considerations. [Safety and efficacy of OM-85-BV plus amoxicillin/clavulanate in the treatment of subacute sinusitis and the prevention of recurrent infections in children]. Clinical and immunobiological effects of an orally administered bacterial extract. [Inhalative immunostimulation in patients with chronic bronchitis]. Use of a polyvalent bacterial lysate in patients with recurrent respiratory tract infections: results of a prospective, placebo-controlled, randomized, double-blind study. Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months. Immunostimulation with OM-85 in children with recurrent infections of the upper respiratory tract: a double-blind, placebo-controlled multicenter study. Clinical trials with C 1740, an immunomodulator compound proposed for prevention of acute infectious exacerbations in chronic bronchitis. Treatment of recurrent respiratory tract infections with a polyvalent bacterial lysate: Results of an open, prospective, multinational study [Immunomodulation therapy in chronic bronchitis (multicenter study)]. [Prevention of recurrent infection of the upper and lower airways. Multicenter, open study over three months]. Preventive effects of an immunostimulating product on recurrent infections of chronic bronchitis in the elderly Stimulation of nonspecific immunity to reduce the risk of recurrent infections in children attending day-care centers. The Epicrèche Research Group. Local airways immune modifications induced by oral bacterial extracts in chronic bronchitis. [Effect of Broncho-Vaxom on serum IgE and IgG levels in patients with bronchial asthma and chronic obstructive lung disease. A placebo-controlled double-blind study]. Effect of inhaled triamcinolone on the decline in pulmonary function in chronic obstructive pulmonary disease. [Immunotherapy of recurrent respiratory infections. Double-blind study of a new immunomodulator in 60 patients]. [Preventive effect of an immunomodulator, OM-85 BV, on acute exacerbations of chronic bronchitis in elderly patients. Preliminary results at six months in 291 patients]. Oral immunotherapy of chronic bronchitis: a double-blind placebo-controlled multicentre study. OM-85 BV: primary versus secondary prevention. Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease: the ISOLDE trial
Acute bronchitis is a major source of morbidity in elderly patients . The purpose of this study was to assess the preventive effects of oral immunisation with a bacterial extract .  Three hundred and fifty four patients with chronic bronchitis , living in institutions for the elderly ( aged > 65 yrs ) , were included in a r and omized , placebo-controlled , double-blind study . The purpose of the study was to assess preventive effects of OM-85 BV ( an immunostimulating agent consisting of lyophilized fractions of eight of the most common pathogens isolated in respiratory tract infections ) against acute lower respiratory tract infections . Two hundred and ninety patients completed the study ( 143 taking placebo and 147 taking OM-85 BV ) . There was a 28 % reduction in the number of lower respiratory tract infections in the patients treated with OM-85 BV ; this was entirely due to 40 % reduction in the number of episodes of acute bronchitis ( p < 0.01 ) , with no difference in the number of episodes of pneumonia and bronchopneumonia . A larger number of patients in the OM-85 BV group were free of acute bronchitis throughout the 6 month study period ( 96 vs 69 ) and there was a 28 % reduction in the number of antibiotic prescriptions in the OM-85 BV treated group . These results suggest that OM-85 BV has a protective effect against acute bronchitis in elderly patients living in institutions RATIONALE OM-85 BV , an immunostimulant made from bacterial extracts , has been shown to reduce the risk of hospitalization for acute exacerbation in patients with chronic obstructive pulmonary disease , as well as to reduce the length of stay for all hospitalizations . METHODS In conjunction with a placebo controlled , r and omized clinical trial , a cost effectiveness analysis was carried out to assess the economic impact of using OM-85 BV . In the analysis , effectiveness was defined as the difference in the number of severe acute exacerbations , assessed by the number of hospitalizations for a respiratory problem , between the  placebo and OM-85 BV-treated groups . RESULTS The median cost to prevent one day of hospitalization for a respiratory condition was CDN$45 , with a 95 % CI of CDN$18 to CDN$210 . Bootstrap of the study population and sensitivity analyses showed that the results were robust and not likely due to r and om fluctuation ; 98.8 % of the cost effectiveness and 96.8 % of the cost-benefit ratios favoured the use of OM-85 BV .  Indirect costs , defined as a need for help , were reduced by 36 % in the group treated with OM-85 BV : 779 h of help compared with 1212 h in the placebo group . This trend , while not significant , is consistent with other results and suggests a decrease in the severity of exacerbations in the OM-85 BV-treated group . CONCLUSION Given the high prevalence of chronic obstructive pulmonary disease worldwide and the high cost of acute exacerbations , immunostimulants may become a key element in the improved control of this condition The efficacy of Broncho-Vaxom/Imocur ( OM-85 BV ) , an orally administered lyophilized bacterial extract , for recurrent respiratory and ear , nose and throat ( ENT ) infections was evaluated in 116 children aged 6 months to 19 years by comparing its activity in 61 children with that of a placebo in 55 children . The study was r and omized , double-blind , and comprised a 90-day treatment period followed by a 90-day follow-up period without test drugs . Over the 180 days , 39.5 % of patients taking OM-85 BV  remained free from infection compared with 16.5 % on placebo ( p less than 0.01 ) . 44 % on OM-85 BV did not need antibiotics  compared with 23.5 % on placebo ( p less than 0.05 ) . These differences were even greater in the subgroup of children aged 6 years and less ( 34 vs. 3.5 % for the absence of infections , p less than 0.01 and 37 vs. 10 % for the need of antibiotics , p less than 0.05 ) . Tolerance to OM-85 BV was excellent , and laboratory investigations showed no abnormalities attributable to this product . This work confirms that the immunomodulator OM-85 BV is an effective immunotherapy for recurrent respiratory and ENT infections in children In a 6-month placebo-controlled double-blind multicenter study in 230 patients with recurrent respiratory tract infections , the therapeutic efficacy of Broncho-Vaxom was demonstrated by comparing infection incidence and severity as well as antibacterial medication . Investigators and patients agreed that Broncho-Vaxom exerts a significantly greater protective effect than placebo . Reports of side effects were more frequent with placebo as compared to Broncho-Vaxom The efficacy of Broncho-Vaxom has been evaluated by a multicentric working group of physicians in 75 patients with chronic bronchitis using a r and omized double-blind trial . Initial data of the selected patients showed no significant differences in history , previous medication , individual state and spirometric lung function values between the control group ( n = 39 ) and the cases treated with the test medication ( n = 36 ) . After 30-day initial treatment both physician and patient favoured the active substance ( p less than 0.01 ) although there was statistically no evidence of a curative effect measured by objective criteria . Longterm follow-up over a period of six months again revealed a more effective course in the Broncho-Vaxom group according to individual observations ( p less than 0.05 ) . In fact there was an impressive trend towards reduction of clinical symptoms with Broncho-Vaxom medication . However , statistical analysis of individual symptoms ' scores and lung function tests did not show significant alterations within the two groups . Taking in account the complexity of bronchitic disease , statistical demonstration of a beneficial effect of Broncho-Vaxom with respect to clinical symptoms and lung function tests probably needs a longer observation period , a larger population and a choice of more sensitive methods BACKGROUND Hemodialysis ( HD ) patients suffer from several immune defects that make them prone to develop bacterial infections , in particular respiratory tract infections ( RTIs ) . PATIENTS AND METHODS As previous studies have shown that oral immunotherapy with an immunomodulating bacterial extract ( IBE ) is effective against RTIs , we decided to test its efficacy and safety in HD patients during a double-blind placebo-controlled prospect i ve study . 40 HD patients with a documented history of RTIs in the previous year were treated for 24 weeks of the endemic season with one capsule daily of IBE ( n = 21 ) or placebo ( PL , n = 19 ) . Clinical examinations , measurements of Mac-1 and gp150.95 on circulating phagocytes and routine laboratory evaluations were performed at week 0 , 4 , 12 and 24 . Patients were also examined at each dialysis session allowing an accurate recording of any infectious episode , its treatment and of any untoward effect . RESULTS During the last period of the study ( weeks 13 - 24 ) , IBE significantly reduced the number of patients with RTIs and consequently of antibiotic treatment courses as compared to PL ( p = 0.018 ) , whereas no difference was detected between IBE and PL during periods I ( weeks 0 - 4 ) and II ( weeks 5 - 12 ) . There was no difference between IBE and PL for other , non respiratory infections . IBE was associated at several time points with an increased expression on phagocytes of adhesion molecules involved in phagocytosis ( Mac-1 and gp150.95 ) . However , the expression of these molecules was not predictive for the occurrence of RTI . IBE was on the whole as well tolerated as PL , 7 patients presented side effects ( 5 IBE , 2 PL , NS ) which led to drop-out in 4 cases ( 3 IBE , 1 PL ) . No serious side effect was recorded , gastrointestinal upset being the most prevalent type . CONCLUSION The results of this study indicate that immunomodulation with selected bacterial extracts constitutes a promising approach for the prevention of bacterial airway infections in groups at risk , such as HD patients BACKGROUND Acute respiratory tract infections ( ARTIs ) are among the main causes of morbidity and mortality in children . The bacterial extract OM-85 BV has shown some protective effect for ARTIs in preschool children and a reduction in exacerbations of chronic bronchitis in adults . OBJECTIVES This trial reports results of a double-masked , placebo-controlled , parallel-group clinical study that assessed the efficacy and tolerability of OM-85 BV in the prevention of ARTIs in school girls living in an orphanage . METHODS Two hundred girls ( age range , 6 to 13 years ) living in an orphanage entered the trial . Participants were r and omly allocated to receive either OM-85 BV or placebo for 10 consecutive days a month for 3 consecutive months . Patients were followed up for 6 months , including the administration period . The trial began in September 1996 and finished in March 1997 . Primary end points were the type and number of infections . Secondary end points included when an infection occurred , time to clinical cure , severity of infection , absenteeism from school due to an ARTI , number of antibiotics or other drugs prescribed , and duration of concomitant drug treatment . RESULTS During the trial , patients in the OM-85 BV group experienced 143 ARTIs ( 135 upper ARTIs and 8 otitis episodes ) and patients in the placebo group experienced 299 ARTIs ( 273 upper ARTIs , 1 lower ARTI , and 25 otitis episodes ) . The median number of ARTIs was 1.0 ( 0.0 , 3.0 ; 5th percentile , 95th percentile ) in the OM-85 BV group compared with 3.0 ( 2.0 , 4.0 ; 5th percentile , 95th percentile ) in the placebo group . This difference was statistically significant ( P < 0.001 ) . Participants who received OM-85 BV also showed significantly better results ( P < 0.001 ) than participants who received placebo in terms of median duration of illness , median number of missed school days due to an ARTI , median number of antibiotic and drug courses , and median duration of concomitant treatment . There were significant differences ( P < 0.05 ) in severity of ARTIs during month 4 of the trial , with patients receiving OM-85 BV showing less severe ARTIs than patients receiving placebo and shorter mean time to clinical cure from the second month to the fourth month . No adverse events related to the trial medications were reported . CONCLUSIONS OM-85 BV had a preventive effect on ARTIs in the school girls , with a reduction in the antibiotic requirements and the duration of ARTIs . Future studies are needed to further explore the role of OM-85 BV in the prevention of ARTIs Immunomodulators have been evaluated mainly for their efficacy as a secondary preventive treatment to protect sick children from the recurrence of infections . We investigated the efficacy of one such product , IMOCURR , as a primary preventive treatment in children attending daycare , who face a very high risk of recurrent infections . EPICUR is a double-blind trial which was design ed to study the efficacy of IMOCURR versus placebo . In order to have sufficient statistical power , data collection was based on a daily follow-up procedure and all important concomitant risk factors , such as age , environment and season , were controlled at the study design stage . The sample size required was calculated to be at least 400 children and a total of 423 were actually included . The results obtained for the total follow-up period and those obtained for the treatment period only were very different . This finding raises important questions which have method ological implication s. This paper discusses these implication A 6-month double-blind , prospect i ve , r and omized , placebo-controlled trial was conducted to establish the safety and efficacy of OM-85-BV in the treatment of  subacute sinusitis  and in the following prevention of the respiratory tract infections in 56 children from 18 months to 9 years of age . In the subacute phase of the sinusitis the patients were given one OM-85-BV capsule ( 3.5 mg of bacterial extracts ) ( n = 26 ) or placebo ( n = 30 ) , daily for ten days ; additionally both groups took amoxicillin/clavulanate 40/10 mg/kg daily in three divided doses for 21 days . For the following two months the patients took one OM-85-BV capsule or placebo , ten days a month . In the subacute phase the OM-85-BV group of patients improved sooner ( 5.56 + /- 4.98 vs 10 + /- 8.49 days ) and had a shorter convalescence ( 15.38 + /- 8.91 vs 20.28 + /- 7.17 days ) . During the six month follow-up the patients in the OM-85-BV group had a lower number of infections ( 1.56 + /- 0.3 vs 2.22 + /- 0.43 ) and required a lower number of drug treatments ( 1.47 + /- 0.32 vs 1.94 + /- 0.42 ) . One patient treated with OM-85-BV presented a mild rash which disappeared three days after the drug discontinuation . We conclude that OM-85-BV is safe at pediatric ages , as well as accelerates the cure and improvement of subacute sinusitis while it lowers the incidence of respiratory infections The effect of a bacterial extract orally administered to 20 children with recurrent infections of the upper respiratory tract , was investigated in a double-blind study . The composition of the peripheral blood mononuclear cells ( T and B-lymphocytes , monocytes ) and some of their biochemical properties ( 5'-nucleotidase , beta-N-acetyl-glucosaminidase and non-specific esterase ) were unaffected . In contrast , the allogeneic mixed lymphocyte reaction was significantly increased in patients treated with the bacterial extract . In the treated group the number of infectious episodes decreased significantly and the clinical response correlated positively with the mixed lymphocyte reaction . These findings suggest that the bacterial extract has the capacity of restoring depressed immune functions by acting through the gut-associated lymphoid tissue 80 patients with chronic bronchitis were treated inhalatively for a time of 3 weeks with a polyvalent bacterial lysate ( IRS 19 ) or with placebo . The study was carried out in a double-blind fashion . Treatment with IRS 19 result ed in improved bronchoscopic findings compared with the pretherapy findings . Patients with bronchial hyperreactivity showed in the IRS 19 group small improvement of the hyperreactivity . In this group the contents of IgG in the BAL fluid showed a significant reduction , the other parameters were unchanged Respiratory tract infections ( RTIs ) are the most common infections in humans , and it is difficult to effectively treat patients with increased susceptibility to these ailments . LW 50020 ( Luivac ; Paspat oral ) , an oral immunomodulator consisting of the antigens of seven bacteria commonly involved in RTIs , has been developed for the induction of specific and nonspecific immune responses of the mucosa-associated lymphoid tissue . In this placebo-controlled study , the efficacy and safety of the tablet formulation of LW 50020 were evaluated in children and adults with recurrent RTIs . Tablets were taken once daily during two periods of 4 weeks each , interrupted by a treatment-free interval of 4 weeks . The main endpoint of the study , a clinical severity score that evaluated treatment benefits , was significantly lower in the second study period in patients treated with the bacterial lysate compared to patients given placebo . A comparison of the infection rates in the first and second study periods of patients treated with LW 50020 revealed a placebo-corrected reduction of 39 % in children and a placebo-corrected reduction of 44 % in adolescents and adults . The placebo-corrected duration of infections was shortened by 47 % in children and by 55 % in older patients . No serious drug-related side effects occurred . This study demonstrated that the oral bacterial immunomodulator LW 50020 is efficacious in treating patients with recurrent RTIs BACKGROUND Acute respiratory tract infections ( ARTIs ) are among the main causes of morbidity and mortality in children . The bacterial extract OM-85 BV ( bronchovaxom ) has shown protective effect for ARTIs on children . We report a double-blind , placebo-controlled , parallel , prospect i ve clinical trial to assess the safety and efficacy of two courses of OM-85 BV in the prevention of ARTIs in susceptible children during 12 months . METHODS Fifty-four susceptible children from 1 to 12 years of age living in the metropolitan area of Chihuahua City were selected . They were r and omized to receive either OM-85 BV or placebo ( one capsule a day for 10 days a month for 3 consecutive months ) at the beginning of the trial and 6 months later with the same schedule . Patients were followed up for 12 months , including the administration period . The trial began in July 1997 and ended in April 1999 . RESULTS The number ( mean + /- SD ) of ARTIs was 5.04 + /- 1.99 ( median , 5.0 ) in the OM-85 BV group vs 8.0 + /- 2.55 ( median , 8.0 ) in the placebo group , with a mean difference of - 2.96 ( 95 % confidence interval [ CI ] , - 4.22 to - 1.7 ) . The number of antibiotic courses was 2.46 + /- 2.08 ( median , 1.5 ) in the treatment group vs 4.46 + /- 2.08 ( median , 4.0 ) in the control group , a difference of - 2.0 ( 95 % CI , - 3.14 to - 0.86 ) . The total duration of ARTIs was 35.23 + /- 17.64 days ( median , 30.5 days ) in the OM-85 BV group vs 60.75 + /- 25.44 days ( median , 55.0 days ) in the placebo group , ie , a difference of - 25.52 days ( 95 % CI , - 37.56 to - 13.47 days ) , p < 0.001 by Student 's t test and Mann-Whitney U test for all the items . Four patients in the OM-85 BV group had five adverse events . Only one episode of skin rash was related to the medication intake . Six patients in the control group had six adverse events . CONCLUSIONS OM-85 BV had a preventive effect on ARTI in the susceptible children for 12 months with an important reduction on  the  antibiotic requirements and the number of days of suffering ARTIs OBJECTIVE Recurrent upper respiratory tract infections ( URTIs ) are common illnesses in young children . As the immunoactive bacterial extract OM-85 has been shown to prevent these infections in both adults and children , the aim of the present trial was to investigate further its efficacy and safety in infection-prone children . METHODS This is a r and omized , double-blind , placebo-controlled , multicenter study with OM-85  in 232 patients aged 36 to 96 months with recurrent URTIs . Treatment was one capsule daily during month 1 and during 10 days in months 3 to 5 . URTI was defined by the presence of at least two of the following : rhinitis , pharyngitis , cough , hoarseness , temperature > or = 38.5 degrees C , or URTI-related prescription of an antibiotic . RESULTS OM-85-treated patients had a lower rate of URTIs ( p < 0.05 ) . The cumulated difference in URTIs between the two groups reached - 0.40 URTIs per patient in 6 months , corresponding to a 16 % reduction in the active-treatment group with respect to placebo . The largest difference was observed in the patients having had three or more URTIs during the study period ; odds ratios for three or more URTIs were 0.51 ( 95 % confidence interval , 0.29 to 0.91 ) and 0.65 ( 95 % confidence interval , 0.37 to 1.11 ) after 5 months and 6 months , respectively . The difference between OM-85 and placebo was independent of age but was more important in patients reporting a larger number of URTIs in the previous year . Patients ' global assessment showed improvement in comparison to the previous season in the majority of the cases ( OM-85 , 78.4 % of cases ; placebo , 75.5 % ) ; however , there were more cases reporting worsening with placebo ( 6.4 % vs 0.9 % ; p = 0.05 ) . CONCLUSIONS OM-85 treatment significantly reduced the rate of URTIs , particularly in children with a history of frequent URTIs .  Safety and tolerance of test medication were good , comparable to placebo C 1740 is an immunmodulating agent of biological origin proposed for the prevention of infectious exacerbations in chronic bronchopathy . The first placebo-controlled double-blind r and omized clinical trials have led to opposite conclusions regarding the utility of C 1740 . The rate of infectious exacerbations in the placebo group and a large Type II error could explain the " negative clinical trials " . However , two out of four " positive clinical trials " were associated with high risk of falsely positive results . The activity of C 1740 is discussed here This multicenter , open study , carried out in 14 countries in Europe , Latin America , and Asia , recruited 4965 patients suffering from recurrent respiratory tract infections to investigate the safety and acceptability of the oral bacterial lysate immunomodulator LW 50020 . Patients remained in the study for 4 months ( two 4-week courses of LW 50020 separated by a 28-day treatment-free interval and follow-up ) . The incidence of all adverse events was 7.2 % ; that of adverse drug reactions was 0.6 % . Adverse drug reactions were mild to moderate and not more frequent in the large subgroup of patients ( 77 % ) with a known history of allergies or underlying respiratory diseases ; however , the incidence of adverse events in this subgroup was twofold higher than in the study population as a whole , probably indicating a generally increased vulnerability to disease . No clinical ly relevant changes in laboratory variables followed treatment . Comparison of the first study period ( first course of LW 50020 and drug-free interval ) with the second study period ( second course of LW 50020 and follow-up ) showed an overall reduction of at least 50 % in the number , severity , and duration of respiratory tract infections , the number of antibiotic and symptomatic treatments , and the number of days absent from school or work . Tolerability and acceptability were assessed as good or very good in 99 % of patients who completed the study ( A multicentre clinical trial ) The authors treated 120 patients showing the symptoms of chronic bronchitis with BV or placebo for 6 months during the winter period of 1992 - 93 in a multicentre double-blind clinical trial . The status of the patients was evaluated monthly and the data were analyzed at an independent computer company . The clinical symptoms were significantly milder in the BV group as compared with the placebo group and  antibiotics consumption in the BV group was almost half of that recorded in the placebo group . These findings confirm that BV can be effective in the prophylaxis of the exacerbation of chronic bronchitis In a multicenter open study involving 620 patients suffering from recurrent infections of the upper and lower respiratory tract aged between 12 and 89 years , the tolerability of an oral bacterial lysate was investigated . On the basis of the nature and frequency ( 1.9 % ) of adverse effects , and an analysis of the laboratory investigations over an observation period of three months , overall tolerability was adjudged to be excellent . The frequency and severity of infections was reduced . In 75 % of the cases , both physician and patient considered the augmentation of the body 's defense mechanisms by immunoactivation to have been of benefit . The favourable risk-to-benefit ratio results in a high level of acceptance of immunotherapy , and 96 % of the patients completed the study as planned The effect of an immunostimulating drug , OM-85 BV , was demonstrated on recurrent infection rates in 265 elderly patients with a defined state of chronic bronchitis , during a 6-month , double-blind , placebo-controlled trial . Patients receiving OM-85 BV presented less infections ( p = 0.005 ) and a significantly reduced intake of antibiotics  ( p = 0.02 ) as compared to those receiving a placebo and the  antibiotic intake was significantly reduced ( p = 0.02 ) A r and omized , double blind , placebo-controlled clinical trial was performed in 423 children attending day-care centers to assess whether stimulating nonspecific immunity would reduce the incidence of recurrent infections . The drug used for the trial ( Imocur ) is an extract obtained from eight different species of bacteria . At the end of the total follow-up period ( 3 months with treatment and 4.5 months without ) , the risk for > or = 4 episodes of upper respiratory infections was not significantly lower in the treated group than in the placebo group ( 26.7 % vs. 33.8 % , relative risk , 0.79 ; 95 % confidence interval , 0.59 to 1.06 ) . In an exploratory analysis limited to the 3-month treatment period , however , we observed a 48 % reduction in the risk of presenting > or = 3 episodes of upper respiratory infections : 9.5 % vs. 18.3 % , respectively , in the treatment group and the placebo group ( relative risk , 0.52 ; 95 % confidence interval , 0.31 to 0.86 ) . Similar results were found for the risk of > or = 1 episode of gastroenteritis . We also observed a strong correlation between the drug efficacy and age ; this observation is coherent with the underlying pathophysiologic model in which the immune system matures with age Bacterial extracts can act as immune stimulants and in some instances have been used , rather empirically , to prevent recurrent infections in the nonimmunocompromised host . Some agents are administered via oral route with the goal to increase airways immune defenses . In animal models and in normal humans , gut-associated lymphoid tissue ( GALT ) stimulation is able to induce a generalized response by the whole mucosal-associated lymphoid tissue ( MALT ) . The aim of this placebo-controlled , double-blind , parallel-group study was to evaluate whether the stimulation of the GALT through oral administration of a polyvalent bacterial extract ( BE ) could lead to significant immune modifications either systemically or locally in the respiratory tract in patients suffering from chronic bronchitis . We selected 20 subjects ( 5 nonsmokers , 6 smokers , and 9 ex-smokers ) for at least 3 years . According to a balanced-block r and omization method , ten patients received active treatment and ten received placebo . Either drug or placebo was to be taken as one capsule daily the first 10 days of 3 consecutive months . Each capsule of the active product contained 7 mg of a BE obtained from eight different bacterial strains . On entry ( T0 ) and 90 days after beginning of treatment ( T90 ) , all patients underwent bronchoalveolar lavage ( BAL ) and peripheral blood withdrawal to assay BAL fluids and serum sample s for immune parameters . The BAL recoveries , cellularity , cell differentials , and lymphocyte subsets ( CD19 , CD3 , CD4 , CD8 ) did not show significant differences . IgG/albumin and IgA/albumin values were not significantly different , but IgA/albumin was significantly increased in the treatment ( T0 = 0.14 , 0.01 to 0.27 , median and range , T90 = 0.15 , 0.08 to 0.45 , p = 0.028 ) vs the placebo group when data from current smokers were excluded . Functional tests on alveolar macrophages ( AM ) ( leading front stimulated motility and superoxide anion-O2(-)-release ) showed a significant increase of r and om migration ( T0 = 10.6 , 7.0 to 23.6 , T90 = 13.4 , 8.1 to 28.8 microns , p = 0.02 ) and of stimulated motility after FMLP 10(-7 ) M ( T0 = 13.2 , 8.3 to 46.4 , T90 = 18.3 , 8.4 to 49.6 microns , p = 0.04 ) , a significant increase of O2- release in basal conditions ( T0 = 6.0 , 1.7 to 30.5 nM/10(6 ) AM/10 ' , T90 = 11.1 , 5.5 to 24.5 , p = 0.05 ) and after stimulation with opsonized zymosan ( T0 = 17.7 , 4.7 to 35.2 , T90 = 22.1 , 13.8 to 53.3 , p = 0.009 ) in the treatment group only . Data were not significantly different in the placebo group between T0 and T90 . No modifications in systemic immunity were ever observed . ( ABSTRACT TRUNCATED AT 400 WORDS In a double-blind study of 33 patients with bronchial asthma or chronic obstructive pulmonary disease , of whom 17 had proven atopies , the results showed a distinct diminution of the mean IgE level in the atopic patients at the end of 1-month treatment with Broncho-Vaxom , though not attaining statistical significance ( trend with p less than 0.10 ) , compared to a slight increase under placebo . Simultaneously the mean IgG level increased slightly in the atopic patients under Broncho-Vaxom and remained stable in the patients under placebo ( p less than 0.10 ) . The IgE and IgG values of the non-atopic patients in both treatment groups remained practically unchanged . Considering the small number of patients in each group , and the clear tendency towards a diminution of the IgE level , it may be concluded that the administration of Broncho-Vaxom to atopic patients does not lead to an increased IgE level but , on the contrary , seems rather to favour a decrease BACKGROUND Chronic obstructive pulmonary disease ( COPD ) results from a progressive decline in lung function , which is thought to be the consequence of airway inflammation . We hypothesized that antiinflammatory therapy with inhaled corticosteroids would slow this decline . METHODS We enrolled 1116 persons with COPD whose forced expiratory volume in one second ( FEV1 ) was 30 to 90 percent of the predicted value in a 10-center , placebo-controlled , r and omized trial of inhaled triamcinolone acetonide administered at a dose of 600 microg twice daily . The primary outcome measure was the rate of decline in FEV1 after the administration of a bronchodilator . The secondary outcome measures included respiratory symptoms , use of health care services , and airway reactivity . In a sub study of 412 participants , we measured bone density in the lumbar spine and femur at base line and one and three years after the beginning of treatment . RESULTS The mean duration of follow-up was 40 months . The rate of decline in the FEV1 after bronchodilator use was similar in the 559 participants in the triamcinolone group and the 557 participants in the placebo group ( 44.2+/-2.9 vs. 47.0+/-3.0 ml per year , P= 0.50 ) . Members of the triamcinolone group had fewer respiratory symptoms during the course of the study ( 21.1 per 100 person-years vs. 28.2 per 100 person-years , P=0.005 ) and had fewer visits to a physician because of a respiratory illness ( 1.2 per 100 person-years vs. 2.1 per 100 person-years , P=0.03 ) . Those taking triamcinolone also had lower airway reactivity in response to methacholine challenge at 9 months and 33 months ( P=0.02 for both comparisons ) . After three years , the bone density of the lumbar spine and the femur was significantly lower in the triamcinolone group ( P < or = 0.007 ) . CONCLUSIONS Inhaled triamcinolone does not slow the rate of decline in lung function in people with COPD , but it improves airway reactivity and respiratory symptoms and decreases the use of health care services for respiratory problems . These benefits should be weighed against the potential long-term adverse effects of triamcinolone on bone mineral density A new immunomodulator , SLO4 oral drops , was tested for treatment and prevention of recurrent respiratory infections in a double-blind , drug versus placebo trial conducted in 60 adults with chronic bronchitis or asthma . This agent brought about a highly significant reduction in the frequency and duration of infectious episodes , as well as a decrease in antibiotic consumption and lost work time . Well tolerated from the clinical and laboratory points of view , it proved remarkably effective . It has been hypothesized that induction of interferon may account for the excellent clinical results obtained with SLO4 , and numerous authors regard this compound as one of the basic keys to regulation of immune reactivity . Pharmacological trials under way with SLO4 should help answer this question Three hundred fifty six patients aged 65 years or more ( mean age 81.8 years ) who were suffering from chronic bronchitis were included in a double-blind trial against placebo to assess the preventative effect of OM-85 BV against acute exacerbations of chronic bronchitis .  OM-85 BV is an immunostimulant composed of lyophilised factions of 8 bacteria which are most frequently encountered during the course of respiratory tract infections . 291 patients completed the study . In the group treated by OM-85 BV , a significant increase in the number of patients with no episode of acute bronchitis was noted ( 96 versus 71 , p = 0.006 ) . There was a 38.8 % reduction in the absolute numbers of episodes of acute bronchitis and a 33 % reduction in the number of prescriptions for antibiotics , however there was no difference in the number of pneumonias and bronchopneumonias . These results show the protective effect of OM-85 BV against bronchial superinfections in a large population of elderly patients suffering from chronic bronchitis 104 patients with chronic bronchitis were treated under r and omized double-blind conditions with either Broncho-Vaxom ( BV ) or a placebo over a period of 6 consecutive months . The beneficial effect of BV was manifested by a statistically significant reduction in the duration of acute episodes and of fever ( p less than 0.001 ) with respect to the placebo group . The consumption of antibiotics  dropped significantly in the BV group ( p less than 0.05 ) but not in the placebo group . The serum IgA levels increased in the BV group and the difference with the placebo group was statistically significant ( p less than 0.05 ) from the 3rd month onwards . In the patients with bronchitic exacerbations during the trial , T-lymphocyte counts increased steadily under BV therapy until 3 months after the exacerbation ( p less than 0.05 ) , but not under the placebo .  BV was generally well tolerated with the exception of 1 patient who reported nausea and upper abdominal pain . In their assessment of the overall therapeutic effect , the physician judged BV to be significantly superior ( p less than 0.001 ) to the placebo as regards both the curative and prophylactic efficacy Recurrent upper respiratory tract infections in children have an important socioeconomic impact , with consequences on both the quality of life of the children , the possible medical sequelae and the inherent direct and indirect costs . The possibility to prevent these infections is limited in the absence of specific vaccines against microorganisms responsible for most of the respiratory tract infections ( i.e. respiratory syncitial virus , adenovirus , rhinovirus ) . Immunoactive bacterial extracts that stimulate the nonspecific component of the immune system may protect against a large variety of microorganisms that enter the body by the oral and respiratory pathway ; they may , therefore , play an important role with regard to this preventive action . OM-85 BV is an IBE that has been used in children who suffer from repeated infections to prevent the occurrence of new episodes ( secondary prevention ) . In this condition , the drug has been shown to be effective in protecting children against recurrent airway infections . Its use as a primary preventive agent to prevent the development of repeated infections in children attending day-care centers ( a very high-risk environment for repeated infections ) , however , did not show a similar efficacy . The risk of having > or = 4 episodes of upper respiratory tract infections over a period of 7.5 months was 26.7 % in the verum group and 33.8 % in the placebo group ( relative risk 0.79 , confidence interval 0.59 - 1.06 ] . In an exploratory analysis concentrating on the 3-month treatment period , however , a 48 % reduction of the risk of presenting > or = 3 episodes was observed . Furthermore , this exploratory analysis showed a strong correlation between drug efficacy and age of the children . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objectives : To determine the effect of long term inhaled corticosteroids on lung function , exacerbations , and health status in patients with moderate to severe chronic obstructive pulmonary disease . Design : Double blind , placebo controlled study . Setting : Eighteen UK hospitals . Participants : 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second ( FEV1 ) 50 % of predicted normal . Interventions : Inhaled fluticasone propionate 500 μg twice daily from a metered dose inhaler or identical placebo . Main outcome measures : Efficacy measures : rate of decline in FEV1 after the bronchodilator and in health status , frequency of exacerbations , respiratory withdrawals . Safety measures : morning serum cortisol concentration , incidence of adverse events . Results : There was no significant difference in the annual rate of decline in FEV1 ( P=0.16 ) . Mean FEV1 after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo ( P<0.001 ) . Median exacerbation rate was reduced by 25 % from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate ( P=0.026 ) . Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate ( P=0.0043 ) . Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group ( 25 % v 19 % , P=0.034 ) . Conclusions : Fluticasone propionate 500 μg twice daily did not affect the rate of decline in FEV1 but did produce a small increase in FEV1 . Patients on fluticasone propionate  had fewer exacerbations and a slower decline in health status . These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease
BACKGROUND Oral lyophilized extracts of bacteria species have been used since the early 1970s to improve symptoms and to prevent exacerbations in COPD patients .
The value of these treatments , which are thought to be immunomodulating , is poorly understood .
Our aim was to quantify the efficacy of oral bacteria extracts in patients with chronic bronchitis and COPD .