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Current management of acute bronchitis in ambulatory care: The use of antibiotics and bronchodilators.

OBJECTIVE: To examine the treatment regimens for acute bronchitis in adults in a Medicaid population seen in ambulatory care settings. DESIGN: Cross-sectional sample of Kentucky Medicaid claims (July 1, 1993, through June 30, 1994). PARTICIPANTS: Individuals 18 years old or older seen in an ambulatory setting for acute bronchitis. Anyone with a primary diagnosis of asthma or chronic obstructive pulmonary disease within the time frame was excluded. Twelve hundred ninety-four individuals accounted for 1635 separate outpatient and emergency department encounters for acute bronchitis. Outpatient visits accounted for 89% (n=1448) of the encounters. RESULTS: In 22% (n=358) of the encounters, no medication was prescribed; in 61% (n=997), antibiotics alone were prescribed, in 3% (n=43), bronchodilators alone were prescribed; and in 14% (n=237), both antibiotics and bronchodilators were prescribed. Some type of medication was more likely to be prescribed in emergency departments than in outpatient settings (P=.04), and antibiotic/bronchodilator combination therapy was more likely to be prescribed in rural practices than in urban practices (P<.001). Broad-spectrum were more likely than narrow-spectrum antibiotics to be used in combination with a bronchodilator (P=.001). Penicillins were the most widely used antibiotics (37%), but broad-spectrum agents, such as second- and third-generation cephalosporins (10%) and fluoroquinolones (5%), were also prescribed. CONCLUSIONS: Although evidence suggests that antibiotic treatment is not usually indicated for treatment of acute bronchitis, these results indicate that antibiotics are still the predominant treatment regimen in ambulatory care. Furthermore, the evidence suggesting that bronchodilators are effective symptomatic treatments has not been widely adopted. These results have significant implications for the production of antibiotic-resistant bacteria and suggest investigation into why physicians have not used this information in their treatment of acute bronchitis.

Acute Disease↗

Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis.

CONTEXT: The spread of antibiotic-resistant bacteria is associated with antibiotic use. Children receive a significant proportion of the antibiotics prescribed each year and represent an important target group for efforts aimed at reducing unnecessary antibiotic use. OBJECTIVE: To evaluate antibiotic-prescribing practices for children younger than 18 years who had received a diagnosis of cold, upper respiratory tract infection (URI), or bronchitis in the United States. DESIGN: Representative national survey of practicing physicians participating in the National Ambulatory Medical Care Survey conducted in 1992 with a response rate of 73%. SETTING: Office-based physician practices. PARTICIPANTS: Physicians completing patient record forms for patients younger than 18 years. MAIN OUTCOME MEASURES: Principal diagnoses and antibiotic prescriptions. RESULTS: A total of 531 pediatric office visits were recorded that included a principal diagnosis of cold, URI, or bronchitis. Antibiotics were prescribed to 44% of patients with common colds, 46% with URIs, and 75% with bronchitis. Extrapolating to the United States, 6.5 million prescriptions (12% of all prescriptions for children) were written for children diagnosed as having a URI or nasopharyngitis (common cold), and 4.7 million (9% of all prescriptions for children) were written for children diagnosed as having bronchitis. After controlling for confounding factors, antibiotics were prescribed more often for children aged 5 to 11 years than for younger children (odds ratio [OR], 1.94; 95% confidence interval [CI], 1.13-3.33) and rates were lower for pediatricians than for nonpediatricians (OR, 0.57; 95% CI, 0.35-0.92). Children aged 0 to 4 years received 53% of all antibiotic prescriptions, and otitis media was the most frequent diagnosis for which antibiotics were prescribed (30% of all prescriptions). CONCLUSIONS: Antibiotic prescribing for children diagnosed as having colds, URIs, and bronchitis, conditions that typically do not benefit from antibiotics, represents a substantial proportion of total antibiotic prescriptions to children in the United States each year.

Adolescent↗

Haemophilus influenzae oral whole cell vaccination for preventing acute exacerbations of chronic bronchitis.

BACKGROUND: Acute bronchitis leading to ongoing exacerbations is a serious condition predisposed to by viruses, bacteria or environmental factors. It can be fatal. Antibiotic therapy is not particularly useful. An oral Haemophilus influenzae vaccine has been developed. OBJECTIVES: To assess the effects of an oral, monobacterial whole-cell, killed, nontypeable H. influenzae vaccine in protecting against recurrent acute episodes in chronic bronchitis. SEARCH STRATEGY: In this updated review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to January Week 4 2006), EMBASE (1990 to September 2005) and ISI Current Contents (2004 to May 2006). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing the effects of the H. influenzae vaccine on patients with recurrent acute exacerbations of chronic bronchitis were included when there was overt matching of the vaccine and placebo groups on clinical grounds. DATA COLLECTION AND ANALYSIS: Three authors extracted data and assessed trial quality independently from original records and publications for incidence and severity of bronchitis episodes and carriage rate of nontypeable H. influenzae measured in the upper respiratory tract every three months following vaccination. MAIN RESULTS: Six trials were included in the study with a total of 440 participants. The vaccine reduced the incidence of bronchitic episodes at three months after vaccination (rate ratio is 0.69; 95% CI 0.41 to 1.14) and at six months after vaccination (rate ratio 0.82; 95% CI 0.62 to 1.09). If these results been statistically significant, they would have represented a reduction in acute bronchitic attacks for vaccinated individuals of 31% at three months, and 18% at six. The effect had disappeared by nine months. The severity of exacerbations in the treatment group, as measured by requirement to prescribe antibiotics, was likewise reduced by 58% at three months (Peto odds ratio = 0.42; 95% CI 0.16 to 1.13), and by 65% at six months (Peto odds ratio = 0.35; 95% CI 0.16 to 0.75). AUTHORS' CONCLUSIONS: Vaccinating patients with recurrent acute exacerbations of chronic bronchitis in the autumn may reduce the number and severity of exacerbations over the following winter. A large clinical trial is needed.

Administration, Oral↗

Prophylactic antibiotic therapy for chronic bronchitis.

BACKGROUND: The use of prophylactic antibiotics to reduce the frequency and severity of acute exacerbations of chronic bronchitis is controversial. OBJECTIVES: To determine if prophylactic antibiotics reduce the frequency of exacerbations and/or days of disability in subjects with chronic bronchitis. SEARCH STRATEGY: We searched the Cochrane Airways Group Register of Clinical Trials and the bibliographies of relevant articles. SELECTION CRITERIA: Randomised controlled trials of prophylactic antibiotics in patients with chronic bronchitis and/or COPD were selected. DATA COLLECTION AND ANALYSIS: The eligibility of studies for inclusion was evaluated by three independent reviewers. MAIN RESULTS: Nine trials involving 1055 subjects were included in the analysis. All were performed before 1970. Concealment of allocation was assessed as clearly adequate in only 3 studies. The likelihood of having a exacerbation at any time during the course of the study was decreased with treatment (Relative Risk 0.91, 95% Confidence Intervals (CI) 0.84, 0.99). There was a small reduction in the number of exacerbations per patient per year with prophylactic antibiotics but this was not statistically significant ( Weighted Mean Difference (WMD) -0.15, 95%CI -0.34, 0.04 ). There was a modest but significant reduction of 22% in the number of days of disability per patient per month treated ( WMD -0.95, 95%CI -1.89 to - 0.01 ). A parallel reduction in the days of disability for each exacerbation (WMD -2.08, 95% CI -4.08 to -0.07) was seen. There was a small increase in adverse effects with antibiotics. REVIEWER'S CONCLUSIONS: Prophylactic antibiotics in chronic bronchitis / COPD have a small but statistically significant effect in reducing the days of illness due to exacerbations of chronic bronchitis. They do not have a place in routine treatment because of concerns about the development of antibiotic resistance and the possibility of adverse effects. The available data are over 30 years old, so the pattern of antibiotic sensitivity may have changed and there is a wider range of antibiotics in use.

Antibiotic Prophylaxis↗

Chinese medicinal herbs for acute bronchitis.

BACKGROUND: Acute bronchitis is one of the most common diagnoses made by primary-care physicians. It is traditionally treated with antibiotics, (although the evidence for their effectiveness is weak and modest at best), and other even less effective treatments. Chinese medicinal herbs have been also used as treatment. OBJECTIVES: This review aims to summarise the existing evidence on the comparative effectiveness and safety of Chinese medicinal herbs for treating uncomplicated acute bronchitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), which includes the Cochrane Acute Respiratory Infections Group's specialised register; The Chinese Cochrane Centre's Controlled Trials Register (up to December 2004); MEDLINE (1966 to March Week 1, 2005); EMBASE (1988 to December 2004); and the Chinese Biomedical Database (CBM) (1980 to December 2004). SELECTION CRITERIA: Randomised controlled trials comparing Chinese medicinal herbs with placebo, antibiotics or other Western medicines for the treatment of uncomplicated acute bronchitis. DATA COLLECTION AND ANALYSIS: At least two authors extracted data and assessed trial quality. MAIN RESULTS: Four trials reported the time to improvement of cough, fever, and rales associated with bronchitis and showed that patients treated with Chinese herbs had a shorter duration of signs and symptoms. Two trials reported the proportion of patients with improved signs and symptoms at follow up and showed that Chinese herbs were beneficial in terms of relief of signs and symptoms. Thirteen trials analysed the data on physician global assessment of improvement at follow up. Nine of thirteen trials showed that Chinese herbs were superior to routine treatment and the other four trials showed a similar effect to routine treatment. In general, Chinese herbs appeared beneficial. Only one trial reported on adverse effects during treatment. AUTHORS' CONCLUSIONS: There is insufficient quality data to recommend the routine use of Chinese herbs for acute bronchitis. The benefit found in this systematic review could be due to publication bias and study-design limitations of the individual studies. In addition, the safety of Chinese herbs is unknown due to the lack of toxicological evidence on these Chinese herbs, though adverse events are rarely reported. Chinese herbs should be used carefully.

Acute Disease↗

An interview study to estimate prevalence of asthma and chronic bronchitis. The obstructive lung disease in northern Sweden study.

A questionnaire of respiratory symptoms and diseases completed by 6610 adults in 3 age cohorts (35-36 y; 50-51 y and 65-66 y) in northern Sweden was followed-up by interview and lung function testing of 1243 subjects with asthmatic or bronchitic symptoms and 263 subjects assessed from the postal questionnaire as being healthy. We report the results of this follow-up study. According to the criteria used, 292 subjects (5.1% of the original study sample) were diagnosed as having asthma. Out of the 1243 subjects 334 (5.9% of the original study population) were diagnosed as having chronic bronchitis. However, examination of the 263 subjects who were healthy according to the postal questionnaire showed that elderly smokers, in particular, under-reported bronchitic symptoms; taking this into account, the prevalence of chronic bronchitis is estimated to be of the order of 9%. Diagnostic difficulties were noted in 70 subjects (corresponding to 1.2% of the original study sample) in whom asthma or chronic bronchitis were strongly suspected. Further investigation of these subjects was considered necessary. In this cross-sectional study, FEV1 < 80% of predicted values was found in 36% of subjects diagnosed as having asthma and in 31% of those with chronic bronchitis. Among subjects with attacks of breathlessness and wheezing, diagnostic criteria often used for asthma in questionnaire studies, 70% were diagnosed as having asthma. Of those with chronic productive cough, 62% were diagnosed as having chronic bronchitis. We consider that trained nurses provide reliable data that may be used in epidemiological surveys of obstructive lung diseases.

Adult↗

IgG subclass deficiency in children with recurrent bronchitis.

We studied the incidence of IgG subclass deficiency in children with recurrent bronchitis. Recurrent bronchitis was defined as three or more episodes a year during at least 2 consecutive years, of bronchopulmonary infection, productive cough with or without fever and/or diffuse râles by physical examination in the absence of asthma or atopy. Fifty three children were selected, of whom 30 (57%) were deficient in one of the IgG subclasses. None had an IgG1 deficiency. Nine (17%) were deficient in IgG2, 9 (17%) in IgG3 and 20 (38%) in IgG4. Isolated IgG subclass deficiencies were most frequently seen for IgG4 (14, 26%), less for IgG3 (6, 12%) and even less for IgG2 (4, 7%). Nine (17%) children were IgA deficient and 8 (15%) IgG deficient with a combined IgG subclass deficiency in 8 and 7 of them respectively. By subdivision into different age groups most patients were encountered in the youngest group. The mean content of IgG2, IgG3 and IgG4 in 3- to 4-year-old children with recurrent bronchitis was significantly lower than in the age matched controls. The mean value for IgG4 in the 5- to 6-year-olds was significantly lower than in the control group. This study demonstrates the correlation between recurrent bronchitis in childhood and IgG subclass deficiency. IgG subclass deficiency and recurrent bronchitis are both quite prominent phenomena in young children but rare in older children, suggesting a transient immaturity of the immune system as one of the possible pathogenetic factors. An IgA or an IgG deficiency is highly suggestive for the existence of a combined IgG subclass deficiency.

Bronchitis↗

Chronic bronchitis and pesticide exposure: a case-control study in Lebanon.

OBJECTIVE: Pesticides are widely used toxics. The objective of the study is to evaluate the odds of exposure to pesticides in chronic bronchitis patients. METHODS: Using the American Thoracic Society standardized questionnaire confirmed by medical diagnosis of chronic bronchitis, a case-control study was performed in Lebanon. Pesticide exposure was estimated and between groups comparison was made. RESULTS: The study involved 262 controls and 110 chronic bronchitis outpatient subjects from 10 medical centers. Any exposure to pesticides was associated to chronic bronchitis (OR = 2.46 [1.53-3.94]; p < 10(-4)). Occupational use presented the highest association (15.92 [3.50-72.41]; p < 10(-4)), followed by regional exposure (3.70 [2.05-6.70]; p < 10(-4)). Results were confirmed by multivariate and subgroup analysis. CONCLUSION: Pesticide exposure was associated with chronic bronchitis in Lebanese adults. Pesticides toxicological effects may explain chronic respiratory effects associations found with all exposure types.

Adult↗

Plastic bronchitis: is thoracic duct ligation a real surgical option?

Plastic bronchitis is an unusual clinical scenario of unknown cause and occurs in multiple clinical settings. The disease is characterized by the development of arborizing, thick, tenacious casts of the tracheobronchial tree that results in airway obstruction. Patients with congenital heart disease who have undergone a Fontan operation are at high risk for having this problem develop. Management of this distressing situation is difficult with only palliative options being available, such as repeated bronchoscopies, inhaled heparin, tissue plasminogen activator, inhaled bronchodilators, or azithromycin. The patients with Fontan circuits have a myriad of unique complications develop, such as atrial arrhythmias, recurrent pleural effusions, chylothoraces, protein-losing enteropathy, and plastic bronchitis. High intrathoracic lymphatic pressures with nondemonstrable lympho-bronchial fistulas were believed to be the cause for the development of these recurrent bronchial casts in plastic bronchitis. Faced with recurrent plastic bronchitis resistant to medical management in 2 Fontan patients with normal Fontan pressures on cardiac catheterization, we decided to explore a surgical solution by performing a thoracic duct ligation. This resulted in complete resolution of the formation of casts in both patients, who were discharged home and remain asymptomatic on continued follow-up. Thoracic duct ligation provides a surgical cure for plastic bronchitis by decreasing intrathoracic lymphatic pressure and flow.

Airway Obstruction↗

Inhaled fluticasone reduces bronchial responsiveness and airway inflammation in cats with mild chronic bronchitis.

This study investigated the effect of inhaled fluticasone on lower airway inflammation and bronchial responsiveness (BR) to inhaled carbachol in cats with very mild, chronic bronchitis (n = 5) that were compared with healthy cats serving as controls (n = 6). Chest radiographs, BR tests performed non-invasively by barometric whole body plethysmography (BWBP) and bronchoalveolar lavage (BAL) were performed before and after treatment. BR was quantified by calculating the concentration of carbachol inducing bronchoconstriction (C-Penh300%), defined as a 300% increase of baseline Penh, an index of bronchoconstriction obtained by BWBP. BAL fluid was analyzed cytologically and the oxidant marker 8-iso-PGF2alpha was determined. At test 1, healthy cats and cats with bronchitis were untreated, whereas for test 2 inhalant fluticasone (250 microg once daily) was administrated for 2 consecutive weeks to cats with bronchitis. Control cats remained untreated. Inhaled fluticasone induced a significant increase in C-Penh300% and a significant decrease of BAL fluid total cells, macrophages, neutrophils and 8-iso-PGF2alpha in cats with bronchitis, whilst untreated control cats did not show significant changes over time. This study shows that a 2-week fluticasone treatment significantly reduced lower airway inflammation in very mild bronchitis. BR could be successfully monitored in cats using BWPB and decreased significantly in response to inhaled fluticasone. 8-Iso-PGF2alpha in BAL fluid was responsive to treatment and appeared as a sensitive biomarker of lower airway inflammation in cats.

Administration, Inhalation↗

Antibiotic prescribing in ambulatory care settings for adults with colds, upper respiratory tract infections, and bronchitis.

BACKGROUND: Imprudent prescribing of antibiotics for patients with colds, upper respiratory tract infections (URIs), and bronchitis may contribute to antibiotic resistance and waste economic resources. OBJECTIVE: The purpose of this study was to determine the antibiotic prescribing rate for adults diagnosed with colds, URIs, and bronchitis in 1996 and to compare these rates with those reported for 1992. METHODS: This was a retrospective, cross-sectional analysis of a US government data base of ambulatory physician practices. The number of adults ( > or = 18 years of age) with a diagnosis of cold, URI, or bronchitis and the percentage receiving antibiotics were determined from the 1996 National Ambulatory Medical Care Survey (NAMCS). The antibiotic prescribing rate was the main outcome measure. RESULTS: In 1996, approximately 13.9 million office visits resulted in a primary diagnosis of cold, URI, or acute bronchitis; of these visits, 46%, 47%, and 60%, respectively, resulted in the prescribing of an antibiotic. The respective rates in 1992 were 51%, 52%, and 66%. The rates of antibiotic prescribing were 12% to 16% higher when all drugs, not just the first drug listed in the NAMCS database, were analyzed. In 1996, antibiotic prescribing rates for persons 45 to 64 years of age and persons > 64 years of age were significantly lower than for those aged 18 to 44 years. CONCLUSIONS: The rates of potentially inappropriate antibiotic prescribing decreased modestly from 1992 to 1996; however, previous rates may have been underestimated. The antibiotic prescribing rates for colds, URIs, and acute bronchitis may be as high as 61%, 63%, and 72%, respectively, when all drug information is analyzed. Antibiotics are over-prescribed, which may increase antibiotic resistance and waste health care resources.

Adolescent↗

Nucleolar silver staining patterns and HLA-DR antigen expression in bronchial epithelial cells in chronic bronchitis.

Bronchial epithelial cells obtained by brush biopsy during fiberoptic bronchoscopy performed in 12 patients with chronic bronchitis and 12 healthy control subjects, were investigated for HLA-DR antigen expression and nucleolar silver staining patterns. In all patients with chronic bronchitis the number of bronchial epithelial cells positive to HLA-DR antigen was highly increased (> 90%), whereas in the controls only a few epithelial cells (< 10%) showed a weak HLA-DR antigen expression. Patients with chronic bronchitis showed an increased lymphocytic reaction compared to the control subjects. Both in the patients with chronic bronchitis and in the healthy controls the number of nucleoli was the same. The number of silver stained dots per nucleus was significantly higher in patients with chronic bronchitis than in the control subjects (7.70 +/- 0.87 as against 5.11 +/- 0.52; p < 0.0001). The intensity of the lymphocytic reaction correlated with the HLA-DR antigen expression and the increase in silver staining (Spearman's r = 0.543; p < 0.01). This indicates the influence of inflammation on the activation of epithelial cells derived from the respiratory tract.

Adult↗

Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis.

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 Questionnaire; 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 randomized 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.

Acetylcysteine↗

Prevalence of chronic bronchitis and chronic respiratory symptoms in adults over the age of 35 years in Isfahan, Iran in 1998.

OBJECTIVE: Chronic obstructive airways disease (COPD) in older patients is reported to be not only common, but also frequently overlooked and untreated by general practitioners. Chronic bronchitis is one of the major components of COPD and can be readily screened. This study investigates the prevalence of chronic bronchitis and related symptoms in Iran with special reference to COPD. METHODOLOGY: A random sample of 4636 participants aged 35 years and over, attended a research clinic for interview and physical examinations. Those reporting classic symptoms of chronic bronchitis were referred to a pulmonary clinic for pulmonary function testing. RESULTS: Two hundred and sixteen patients (4.65%) had chronic bronchitis. Among these, 78 (36.1%) had obstructive airways disease. Decreased forced expiratory volume in 1 s/forced vital capacity to levels of less than 70% were recorded in 45 patients (42.9% of the tested population). Less than 25% of the patients had a previous diagnosis of chronic bronchitis and/or airways disease. CONCLUSION: Obstructive airway diseases are under-diagnosed in developing countries. Physicians practising in such areas of the world should be aware, and try to detect the subclinical illnesses, especially in urban areas.

Adult↗

Prevalence and risk factors for asthma and chronic bronchitis in the capitals Helsinki, Stockholm, and Tallinn.

The aim of this part of the FinEsS-studies was to assess whether differences existed in prevalence of asthma, chronic bronchitis, and respiratory symptoms between three Baltic capitals, and to examine risk factor profiles for respiratory conditions. In 1996, a postal survey was performed in these cities with a response rate of 72% in Stockholm, 76% in Helsinki, and 68% in Tallinn. The prevalence of physician-diagnosed asthma was 76% in Stockholm, 6.2% in Helsinki, and 2.3% in Tallinn, while respiratory symptoms were most common in Tallinn. The prevalence of physician-diagnosed chronic bronchitis was 10.6% in Tallinn, 3.4% in Helsinki, and 3.0% in Stockholm. Risk factor analyses revealed a significantly increased risk for those living in Tallinn compared to that of Stockholm for wheezing conditions, OR 1.56-1.69, longstanding cough, OR 1.92 (1.74-2.13), attacks of shortness of breath during the previous 12 months, OR 1.35 (1.20-1.52), and chronic productive cough, OR 1.49 (1.28-1.74). Subjects having symptoms common in asthma were more likely to have physician-diagnosed asthma in Stockholm and Helsinki than in Tallinn, while subjects having bronchitis symptoms had more often physician-diagnosed chronic bronchitis in Tallinn. Prevalence of respiratory symptoms was higher in Tallinn than in Stockholm and Helsinki, while physician-diagnosed asthma was more common in Stockholm and Helsinki. The prevalence of physician-diagnosed chronic bronchitis was three times as high in Tallinn as in Helsinki or Stockholm. Our results also suggest large differences in diagnostic practices between the three countries, while the differences between the capitals in true prevalence of disease may be small.

Adult↗

The role of the inflammatory response in chronic bronchitis: therapeutic implications.

Chronic bronchitis is diagnosed clinically by a chronic productive cough. As implied by the term "bronchitis," chronic airway inflammation is typically found in the central airways in patients with persistent cough and mucous hypersecretion. Although the exact pathogenesis of chronic bronchitis remains unclear, bacterial colonization and the resulting inflammatory response are thought to be of central importance. The generation of pro-inflammatory cytokines and chemotactic stimuli by the airway epithelium likely play central roles in propagating the inflammatory response in patients with chronic bronchitis. Further insights into the initiating events and underlying mechanisms that result in the clinical syndrome of chronic bronchitis will likely provide novel opportunities for therapeutic interventions.

Anti-Bacterial Agents↗

Efficacy and tolerability of a fixed combination of thyme and primrose root in patients with acute bronchitis. A double-blind, randomized, placebo-controlled clinical trial.

In a double-blind, randomized, placebo-controlled, multicenter, prospective study, the clinical efficacy and tolerability of a fixed combination of thyme fluid extract and primose root tincture (Bronchicum Tropfen) was investigated at a dosage of 30 drops (1 ml), taken orally five times daily. 150 outpatients (97 women, 53 men) suffering from acute, not previously treated bronchitis, lasting for less than 48 h, were randomized and treated with either verum (75 patients: 45 women, 30 men) or placebo (75 patients: 52 women, 23 men) over a time period of 7-9 days. 17 patients were excluded from the per-protocol (PP) collective because of either withdrawal from the trial (n = 2) or violations regarding examination time points and/or intake of the study medication (n = 15). The primary outcome criterion for efficacy assessment was the decrease of the Bronchitis Severity Score (BSS) at the end of the study compared to baseline. In the verum group, the BSS decreased from 12.0 +/- 4.4 points at baseline to 1.0 +/- 2.1 at study end compared to a decrease from 11.7 +/- 4.3 points at baseline to 6.5 +/- 4.8 at study end in the placebo group. The inter-group difference of 5.8 points was highly significant (p < or = 10(-3)) in favour of the verum medication [Intention-to-treat (ITT) analysis]. At the end of the study, significantly more patients were symptom free in the verum group (58.7%) than in the placebo group (5.3%) as compared by the ITT analysis (secondary outcome criterion). For both parameters, the PP analysis showed comparable results. The results for the concomitant variables of efficacy support the high superiority of the verum medication compared to placebo. The therapeutic effect was more pronounced the stronger the severity of the acute bronchitis was (as proofed by a stratified evaluation based on severity grade). The tolerability was very good in both groups; neither serious adverse events nor clinically relevant findings in the safety parameters were observed. A total of 7 adverse events occurred, 2 in the verum group and 5 in the placebo group. One of the two adverse events in the verum group was considered to be possibly related to the intake of the study medication. Neither serious nor unknown adverse drug reactions were observed. Two drop-outs occurred during the study related to adverse events, both in the placebo group. In the global safety assessment, the tolerability of both medications was rated as "good" or "very good" by more than 90% of the patients and physicians. In the present study, the fixed combination of thyme fluid extract and primrose root tincture was well tolerated and resulted in a clinically relevant and more pronounced decrease of the bronchitis symptoms (primary outcome criterion) and in shortening the duration of acute bronchitis (secondary outcome criterion) when compared to placebo.

Acute Disease↗

Efficacy and tolerability of myrtol standardized in acute bronchitis. A multi-centre, randomised, double-blind, placebo-controlled parallel group clinical trial vs. cefuroxime and ambroxol.

UNLABELLED: Myrtol standardized (Gelomyrtol forte) is a phytotherapeutic extract (distillate) consisting mainly of three monoterpenes: (+)alpha-pinene, d-limonene and 1,8-cineole. OBJECTIVE: This study describes and compares the efficacy, safety and tolerability of a 2-week treatment with myrtol stand. (4 x 300 mg, day 1-14), cefuroxime (CAS 55268-75-2) (2 x 250 mg daily for day 1-6), ambroxol (CAS 18683-91-5) (3 x 30 mg for day 1-3, 2 x 30 mg for days 4-14) and matched placebo in acute bronchitis. PATIENTS: 676 male and female outpatients, aged > or = 18 years, with acute bronchitis of recent onset (within last 5 days), with an FEV1 > 75% of the normal EGKS-value and without evidence or suspicion of chronic pulmonary disease or any further confounding illness were included in the study. INTERVENTION: Patients were randomly assigned to a 2-week treatment course with either myrtol stand. (N = 170), cefuroxime (N = 171), ambroxol (N = 163) or placebo (N = 172) in a double-blind, placebo-matched, parallel-group fashion. Evaluations were at baseline (visit 1), after 1 and 2 weeks of treatment (visits 2 and 3) and at 2 weeks after conclusion of the treatments (visit 4). CRITERIA: Responder- and non-responder rates (primary), signs (abnormal auscultation), symptoms (daily diary data on nightly cough, coughing fits during the day, sputum consistence and general well-being; visit data on bronchial hyperreactivity and absence/presence of associated symptoms), FEV1, overall efficacy, absence of relapse, safety and tolerability (adverse events, laboratory screens, vital signs and physical examination). Criteria were evaluated for the intention-to-treat data-set (ITT) and the 'efficacy evaluable' sample (EAP), i.e. excluding patients with missing values (incl. discontinued non-responders and drop-outs for other reasons) at the time of assessment. RESULTS: The signs and symptoms of acute bronchitis regressed readily in all treatment groups, but regression was slower and less complete in the patients treated with placebo. In patients treated with placebo, the acute bronchitis was considered to have deteriorated to such an extent that discontinuation was indicated ('non-responder') in 36 patients (ITT: 20.9%, 95% CI: 15.1 to 27.8% and EAP: 21.3%, CI: 15.4 to 28.3%) after 1 week (visit 2) and in 19 further patients (ITT: 11.0%, CI: 6.8 to 16.7%; EAP: 14.8%, CI: 9.2 to 22.2%) after 1 further week (visit 3). In contrast, in the group of patients treated with myrtol stand. the non-responder rates at visits 2 and 3 were only 5.3% (ITT, CI: 2.4 to 9.8%; EAP: 5.4%, CI: 2.5 to 10.0%) and 1.2% (ITT, CI: 0.1 to 4.2%; EAP: 1.3%, CI: 0.2 to 4.7%); the responder rates at visit 2 were statistically significantly higher (p < 0.001) for myrtol stand. (ITT: 92.9%, CI: 88.0 to 96.3) compared to placebo (ITT: 77.3%, CI: 70.3 to 83.4), and similar to those for cefuroxime (ITT: 92.4%, CI: 87.4 to 95.9) and ambroxol (ITT: 89.6%, CI: 83.8 to 93.8%). The superiority of the active treatments vs. placebo with little difference among the treatments was confirmed for all further criteria of evaluation. There was no evidence of bronchoconstriction or relapse in any treatment group for the patients continuing treatment (i.e. for those who were not discontinued because of non-response). The treatments were safe and comparably well tolerated. CONCLUSION: Compared to placebo, treatment with myrtol stand. was well tolerated but evidently superior in terms of efficacy, resulting in a more rapid and more complete recovery; although well comparable with the other active treatments, myrtol stand. tended to be superior to cefuroxime and ambroxol for several ancillary criteria. Myrtol stand. is a well-evidenced alternative to antibiotics for acute bronchitis without specified infective agent, without the risk to promote the development of bacterial resistance.

Acute Disease↗