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Mucolytic agents for chronic bronchitis or chronic obstructive pulmonary disease.

BACKGROUND: Individuals with chronic bronchitis or chronic obstructive pulmonary disease (COPD) may suffer recurrent exacerbations with an increase in volume and/or purulence of sputum. Because of the personal and healthcare costs associated with exacerbations, any therapy that reduces the number of exacerbations is useful. There is a marked difference between countries in terms of prescribing of mucolytics depending on whether or not they are perceived to be effective. OBJECTIVES: To assess the effects of oral mucolytics in adults with stable chronic bronchitis or COPD. SEARCH STRATEGY: We have searched the Cochrane Airways Group Specialised Register and reference lists of articles on four separate occasions, the most recent being in June 2005. This is the third major update. SELECTION CRITERIA: Randomised trials that compared oral mucolytic therapy with placebo for at least two months in adults with chronic bronchitis or COPD. Studies of people with asthma and cystic fibrosis were excluded. DATA COLLECTION AND ANALYSIS: One reviewer extracted data. Study authors and drug companies were contacted for missing information. MAIN RESULTS: Twenty six trials were included (7335 participants). Compared with placebo, there was a significant reduction in the number of exacerbations per patient with oral mucolytics (weighted mean difference (WMD) -0.05 per month, 95% confidence interval -0.05, -0.04). Using the annualised rate of exacerbations in the control patients of 2.6 per year, this is a 20% reduction. The number of days of disability also fell (WMD -0.56, 95% confidence interval -0.77, -0.35). A recent study has shown that the benefit may apply only to those patients not already receiving inhaled corticosteroids. The number of patients who remained exacerbation-free was greater in the mucolytic group (OR 2.13 (95% CI 1.86 to 2.42)). There was no difference in lung function or in adverse effects reported between the treatments. AUTHORS' CONCLUSIONS: In subjects with chronic bronchitis or COPD, treatment with mucolytics was associated with a small reduction in acute exacerbations and a reduction in total number of days of disability. Benefit may be greater in individuals who have frequent or prolonged exacerbations, or those who are repeatedly admitted to hospital with exacerbations with COPD. They should be considered for use, through the winter months at least, in patients with moderate or severe COPD in whom inhaled corticosteroids (ICS) are not prescribed.

Adult↗

Beta2-agonists for acute bronchitis.

BACKGROUND: There are no clearly effective treatments for the cough of acute bronchitis, and beta2-agonists are often prescribed, perhaps because clinicians suspect many patients also have reversible airflow restriction contributing to the symptoms. OBJECTIVES: To determine whether beta2-agonists improve symptoms of acute bronchitis in patients who do not have underlying pulmonary disease. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2005), MEDLINE (January 1966 to November 2005) and EMBASE (1974 to November 2005). SELECTION CRITERIA: Trials in which patients (adults or children over two years of age) who were diagnosed with acute bronchitis or acute cough (without known pulmonary disease and without other cause) were randomized to beta2-agonist versus placebo, no treatment or alternative treatment. DATA COLLECTION AND ANALYSIS: Three authors independently selected outcomes and evaluated trial quality while blinded to study results, they then extracted data. Trials in children and in adults were analyzed separately. MAIN RESULTS: Two trials in children (n = 109) with acute cough and no evidence of airway obstruction did not find any benefits from beta2-agonists. Combined data did not show a significant difference in daily cough scores between patients given oral beta2-agonists and those in the control groups. Five trials in adults (n = 418) with acute cough or acute bronchitis had mixed results but overall summary statistics did not reveal any significant benefits from oral (three trials) nor inhaled (two trials) beta2-agonists. There were no significant differences in daily cough scores nor in the number of patients still coughing after seven days (control rate 73%; relative risks (RR) 0.77, 95% CI 0.54 to 1.09). Subgroups of patients with evidence of airflow limitation had lower symptom scores if given beta2-agonists, in one trial. Furthermore, the trials that did note quicker resolution of cough in patients given beta2-agonists were those that had a higher proportion of patients with wheezing at baseline. Patients given beta2-agonists were more likely to report tremor, shakiness or nervousness than patients in the control groups (for trials in children: control rate 0%; RR 6.76, 95% CI 0.86 to 53.12; number needed to harm (NNH) 9, 95% CI 5 to 100; for trials in adults: control rate 11%; RR 7.94, 95% CI 1.17 to 53.94; NNH 2.3, 95% CI 2 to 3). AUTHORS' CONCLUSIONS: There is no evidence to support the use of beta2-agonists in children with acute cough who do not have evidence of airflow obstruction. There is also little evidence that the routine use of beta2-agonists is helpful for adults with acute cough. These agents may reduce symptoms, including cough, in patients with evidence of airflow obstruction. However, this potential benefit is not well-supported by the available data and must be weighed against the adverse effects associated with beta2-agonists.

Acute Disease↗

Treatment of cast bronchitis with low-dose oral azithromycin.

Cast or plastic bronchitis is an unusual disorder that is rarely encountered in the pediatric population. It is characterized by the expectoration of large, branching plugs of airway debris. These "casts" conform to the shape of portions of the tracheobronchial tree, and give the disorder its name. Cast bronchitis is typically seen in association with several primary pulmonary disorders and cyanotic congenital heart disease. It can be classified as inflammatory or acellular, based on the histologic characteristics of the casts. The presence of large, obstructive plugs filling the airways of lobes or entire lungs can result in a variety of clinical signs and symptoms, and may ultimately lead to respiratory failure and death. Conventional treatment of cast bronchitis has focused on the clearance of obstructing material from the airways combined with therapy for any underlying cardiopulmonary disease. Unfortunately, this approach has not proven very effective, and patient mortality remains high. We report on a case in which a patient with cast bronchitis was treated with long-term, low-dose oral azithromycin. This therapy resulted in clinical, spirometric, and radiographic improvement of the patient.

Adolescent↗

The effect of the neurokinin antagonist FK-224 on the cough response to inhaled capsaicin in a new model of guinea-pig eosinophilic bronchitis induced by intranasal polymyxin B.

Eosinophilic bronchitis without asthma can cause a persistent non-productive cough which is resistant to bronchodilator therapy. To understand the mechanism of the cough in this disorder, an animal model of eosinophilic bronchitis was developed. Guinea-pigs were treated with transnasal administration of polymyxin B or saline twice a week for 3 weeks. The number of eosinophils in bronchoalveolar lavage fluid increased in polymyxin B-treated animals when compared with those treated with saline. In addition, histological examination showed that the number of eosinophils infiltrated into the tracheal epithelium increased; injury to the tracheal epithelium was greater in polymyxin B-treated animals. The numbers of coughs induced by saline and each concentration of capsaicin (10(-18), 10(-16), 10(-14) M) were greater in the polymyxin B-treated animals. FK-224 (a neurokinin receptor antagonist) decreased the heightened cough reflex in this animal model of eosinophilic bronchitis. These findings suggest that neuropeptides, and particularly neurokinins, are involved in the heightened cough receptor sensitivity in eosinophilic bronchitis without asthma. This has implications for better understanding of this disorder and its treatment.

Administration, Inhalation↗

Risk factors for childhood asthma and recurrent wheezy bronchitis.

Using cross-sectional data of an epidemiological study, risk factors for asthma and recurrent wheezy bronchitis were investigated in 1812 primary school children. Children with asthma (n = 63) had a similar pattern but a higher frequency of chronic respiratory symptoms than those with recurrent wheezy bronchitis (n = 136). Logistic regression analyses showed similar risk factors for both disorders, however, more pronounced for asthma. Prematurity was a significant risk factor for asthma and for recurrent wheezy bronchitis. Children with asthma more often had a family history of paternal or maternal asthma and their mothers tended to be younger. Effects of paternal asthma and prematurity were also found when the atopic status of the child (defined as skin test positivity to any of seven aero allergens) was taken into account. Next to genetic effects, adverse circumstances in early life seem to be important for the development of asthma. In school children recurrent wheezy bronchitis and asthma seem to be similar disorders which differ in quantitative but not qualitative aspects.

Asthma↗

Eosinophilic bronchitis: clinical features, management and pathogenesis.

Eosinophilic bronchitis is a common and treatable cause of chronic cough. The major pathological feature is eosinophilic airway inflammation, similar to that seen in asthma. However, the associated airway dysfunction is quite different, with evidence of heightened cough reflex sensitivity, but no variable airflow obstruction or airway hyperresponsiveness. Recent evidence suggests that the differences in functional association are related to differences in localization of mast cells in airway wall, with airway smooth muscle infiltration occurring in asthma and epithelial infiltration in eosinophilic bronchitis. Diagnosis is usually made with induced sputum analysis after exclusion of other causes for chronic cough on clinical, radiological and lung function assessment. The cough responds well to inhaled corticosteroids but dose and duration of treatment remain unclear. Little is known about the natural history of this condition. However, some patients with COPD without a history of previous asthma have sputum eosinophilia, so one possibility is that some cases of eosinophilic bronchitis may develop fixed airflow obstruction. Further study of this interesting condition will increase our understanding of airway inflammation and airway responsiveness, leading to novel targets for therapeutics for both eosinophilic bronchitis and asthma.

Administration, Inhalation↗

Non specific immunity in aged healthy subjects and in patients with chronic bronchitis.

We investigated the effects of aging on some functional activities (chemotaxis, phagocytosis, nitroblue tetrazolium reduction and candidacidal activity) of peripheral polymorphonuclear and mononuclear phagocytes in 96 healthy subjects and 89 patients with chronic bronchitis, aged 40 to 100 years. The subjects were divided according to age into younger (40-65 years) and older (66-100 years) individuals. No subject was taking any drug known to affect phagocytic functions. A few abnormalities in PMN and monocyte functions were observed in aged healthy subjects, in comparison to the younger ones; in fact, only the chemotactic response to complement-derived chemotactic factors was significantly impaired in elderly healthy individuals. On the contrary, multiple alterations of phagocyte activities, i.e., chemotaxis, phagocytosis, and candidacidal activity were observed in aged subjects with chronic bronchitis, compared to healthy adults. However, the results obtained in older and younger patients with chronic bronchitis were superimposable. The present data suggest that the decline in functional activities of phagocytes in the aged could depend on the effect of the underlying chronic bronchitis on the cellular components of the non-specific host defense system, rather than a direct effect of the aging process.

Adult↗

Genetic polymorphisms in the cytochromes P-450 (1A1, 2E1), microsomal epoxide hydrolase and glutathione S-transferase M1, T1, and P1 genes, and their relationship with chronic bronchitis and relapsing pneumonia in children.

The purpose of this study was to investigate the possible roles of the genes functioning in xenobiotic metabolism and antioxidant pathways in the development of severe chronic lung disease in children. Polymorphisms in the genes encoding CYP1A1, CYP2E1, EPHX1, GSTM1, GSTT1, and GSTP1 were investigated in cases of Tatar children with chronic bronchitis (n=129) and relapsing pneumonia (n=50) and in cases of ethnically matched healthy individuals (n=227) living in the city of Ufa, the Republic of Bashkortostan (South Ural region of Russia), by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) method. The frequency of the *2C allele of the CYP1A1 gene was significantly higher in patients than in the healthy control group (chi2=15.02, P=0.0007, Pcor=0.0021). This allele was associated with a higher risk of chronic bronchitis in children (OR 4.14, 95% CI 1.83-9.53; Pcor=0.0024). Similar results were obtained in cases of patients with relapsing pneumonia (OR 3.86, 95% CI 1.34-10.95; Pcor=0.027 for the *2C allele of the CYP1A1 gene). The frequency of the *5B allele of the CYP2E1 gene was higher in the relapsing pneumonia patients (7.0 vs 1.98% in the control group; chi2=5.68, P=0.018, Pcor=0.054; OR 3.72, 95% CI 1.21-11.24). The increase in the GSTT1 gene deletion was significant only in cases of chronic bronchitis (39.53 compared to 21.15% in the control group; chi2=12.96, P=0.001, Pcor=0.003; OR 2.44, 95% CI 1.48-4.04). Our results show that the presence of the GSTM1 gene deletion is unfavorable for the development of chronic lung disease in females (chi2=9.57; P=0.0029, Pcor=0.0116) and was associated with increased risk (OR 2.44, 95% CI 1.36-4.38). The distribution of EPHX1 and GSTP1 gene genotypes was similar in the control and patient groups. Our findings indicate that the polymorphisms of the CYP1A1, CYP2E1, and GSTT1 genes probably play a substantial part in susceptibility to severe airway and lung injury in cases of children with chronic bronchitis and relapsing pneumonia.

Adolescent↗

Peculiarities of the GSTM1 0/0 genotype in French heavy smokers with various types of chronic bronchitis.

A homozygous gene deletion of the glutathione S-transferase M1 (GSTM1) locus of genomic DNA from blood spots was studied by the polymerase chain reaction in a group of French heavy smokers (n = 361), which included patients with severe chronic bronchitis (SCB; n = 87), moderate chronic bronchitis (MCB: n = 102) and hard smokers (HS) with no permanent clinical symptoms of chronic bronchitis (n = 172). The GSTM1 0/0 genotype was found in 71.3% and 65.7% of cases in SCB and MCB, respectively, compared with only 47.1% in the control HS group (P = 0.0002). This latter figure (47.1%) is consistent with the average GSTM1 deletion frequency in French Caucasians. Moreover, the results showed a significant difference in the distribution of the GSTM1 0/0 genotype for both the SCB and MCB groups against the control HS group, according to gender (SCB: P = 0.001; MCB: P = 0.005), age (SCB: P = 0.0001; MCB: P = 0.005) and smoking history (SCB: P = 0.0001; MCB: P = 0.005). Thus, individuals homozygous for the GSTM1 gene deletion, especially in the under-41 age group (SCB: P = 0.001; MSB: P = 0.04) with an average smoking history of 16-30 pack-years (SCB: P = 0.002; MSB: P = 0.01) are more prone to chronic lung diseases, such as SCB and MCB, than are GSTM1 +/+ or 0/+ subjects. Population screening of young people for the identification of GSTM1 0/0 subjects, with special emphasis on smoking habits, might be useful (1) for the early detection of individuals at high risk of lung complications caused by environmental toxins and pollutants and (2) in clinical practice, in order to prevent the development of chronic bronchitis, which is a common disease.

Adult↗

Pneumocystis jiroveci isolates with dihydropteroate synthase mutations in patients with chronic bronchitis.

Since mutations in the dihydropteroate synthase (DHPS) gene possibly associated with sulfonamide resistance have been reported in patients with Pneumocystis jiroveci (previously carinii) pneumonia, and since P. jiroveci colonization has been recently demonstrated in patients with chronic pulmonary diseases, the present study aimed to investigate the possible occurrence of P. jiroveci DHPS mutations in patients with chronic bronchitis. P. jiroveci colonization was detected in 15 of 37 non-selected patients with chronic bronchitis by amplifying the large subunit of the mitochondrial gene of the ribosomal RNA using nested PCR. DHPS mutations were demonstrated using touchdown PCR and restriction enzyme analysis in two of eight patients with chronic bronchitis and in two of six patients from the same region who had AIDS-associated Pneumocystis pneumonia. In all cases, mutations were observed in subjects with no prior exposure to sulfonamides. These data could have important implications for public health, since (i) P. jiroveci colonization could speed the progression of chronic bronchitis, and (ii) these patients, who are customary sputum producers, could represent a reservoir for sulfonamide-resistant strains with the potential ability to transmit them to immunocompromised hosts susceptible to Pneumocystis pneumonia.

Age Distribution↗

Acute bronchitis: results of U.S. and European trials of antibiotic therapy.

Acute bronchitis, an illness frequently encountered by primary-care physicians, is an inflammation of the tracheobronchial tree that results from a respiratory tract infection. It is characterized by persistent cough and sputum production and is occasionally accompanied by fever and/or chest pain. Acute bronchitis may have a viral or bacterial origin and is often treated with antibiotics. Four clinical trials were conducted to compare high and low doses of loracarbef, a new oral beta-lactam antibiotic, with three agents commonly used to treat acute bronchitis: amoxicillin/clavulanate, cefaclor, and amoxicillin. Results of these studies indicated that loracarbef, 400 and 200 mg twice daily, had clinical and bacteriologic efficacy against the common respiratory pathogens Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella (Branhamella) catarrhalis that was comparable with that of the comparative agents. Loracarbef was as well tolerated as cefaclor and amoxicillin; moreover, it produced a significantly lower incidence of diarrhea than did amoxicillin/clavulanate. Loracarbef may be considered a safe and effective alternative agent for the treatment of patients with acute bronchitis.

Acute Disease↗

Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with secondary bacterial infections of acute bronchitis.

Two independent, investigator-blinded, multicenter, randomized clinical trials compared the clinical and bacteriologic efficacy and safety of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of patients with secondary bacterial infections of acute bronchitis (hereafter denoted acute bronchitis). Three hundred sixty patients with signs and symptoms of acute bronchitis were enrolled at 22 centers and were randomly assigned to receive 10 days of treatment with either cefuroxime axetil 250 mg twice daily (BID) (n= 177) or amoxicillin/clavulanate 500 mg three times daily (TID) (n = 183). Patients were assessed for both clinical and bacteriologic responses once during treatment (at 3 to 5 days) and twice after treatment (at 1 to 3 days and at 13 to 15 days). Bacteriologic assessments were based on sputum specimen cultures obtained before treatment and, when possible, after treatment. Organisms were isolated from the pretreatment sputum specimens of 162 (45%) of 360 patients, with the primary pathogens being Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (28%, 25%, 11%, 9%, and 8% of isolates, respectively). Thirty-four percent of the H influenzae isolates and 94% of the M catarrhalis isolates that were tested for beta-lactamase production were positive. A satisfactory clinical outcome (cure or improvement) was achieved in 86% (117 of 136) and 83% (130 of 157) of the clinically assessable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.45). With respect to the eradication of bacterial pathogens, a satisfactory outcome (cure, presumed care, or cure with colonization) was obtained in 91% (53 of 58) and 86% (60 of 70) of bacteriologically assessable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.32). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events than was treatment with cefuroxime axetil (39% vs 23%; P = 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (37% vs 15%; P < 0.001), particularly diarrhea and nausea. Four patients in the cefuroxime axetil group and eight patients in the amoxicillin/clavulanate group withdrew from the study because of drug-related adverse events. These results indicate that cefuroxime axetil 250 mg BID is as effective as amoxicillin/clavulanate 500 mg TID in the treatment of patients with acute bronchitis but produces fewer gastrointestinal adverse events, particularly diarrhea and nausea.

Acute Disease↗

Labelling shift from acute bronchitis may be contributing to the recent rise in asthma mortality in the 5-34 age group.

To test the hypothesis that labelling shift from acute bronchitis to asthma may be contributing to the rise in deaths from asthma in the U.K., we studied mortality rates for males, females and both sexes combined for all ages and for the 5-34 age group, from published mortality tables from 1950 to 1985. The 5-34 age group mortality from asthma showed the 1960s peak and a more gradual increase from 1975. Mortality (all ages) from acute bronchitis showed a decline over the period, but in the 5-34 age group mortality was remarkably stable from 1950-1974 with a mean rate of 2.61 per million (95% confidence intervals, 2.44-2.78). From 1975 to 1985 the rate declined linearly to 0.75 per million. The number of acute bronchitis deaths 'saved' over this period was 366 compared to the number of excess asthma deaths during the same period (taking the 1974 rate as baseline) of 514. These findings lend support to the hypothesis that, in the 5-34 age group, labelling shift from acute bronchitis to asthma may be a contributing factor to the recent rise in asthma mortality. They also raise the question whether different factors contributing to the rise in asthma may have proportionately different weights of effect according to the age of the patients involved.

Acute Disease↗

Generation of a recombinant avian coronavirus infectious bronchitis virus using transient dominant selection.

A reverse genetics system for the avian coronavirus infectious bronchitis virus (IBV) has been described in which a full-length cDNA, corresponding to the IBV (Beaudette-CK) genome, was inserted into the vaccinia virus genome following in vitro assembly of three contiguous cDNAs [Casais, R., Thiel, V., Siddell, S.G., Cavanagh, D., Britton, P., 2001. Reverse genetics system for the avian coronavirus infectious bronchitis virus. J. Virol. 75, 12359-12369]. The method has subsequently been used to generate a recombinant IBV expressing a chimaeric S gene [Casais, R., Dove, B., Cavanagh, D., Britton, P., 2003. Recombinant avian infectious bronchitis virus expressing a heterologous spike gene demonstrates that the spike protein is a determinant of cell tropism. J. Virol. 77, 9084-9089]. Use of vaccinia virus as a vector for the full-length cDNA of the IBV genome has the advantage that modifications can be made to the IBV cDNA using homologous recombination, a method frequently used to insert and delete sequences from the vaccinia virus genome. We describe the use of homologous recombination as a method for modifying the Beaudette full-length cDNA, within the vaccinia virus genome, without the requirement for in vitro assembly of the IBV cDNA. To demonstrate the feasibility of the method we exchanged the ectodomain of the Beaudette spike gene for the corresponding region from IBV M41 and generated two recombinant infectious bronchitis viruses (rIBVs) expressing the chimaeric S protein, validating the method as an alternative way for generating rIBVs.

Animals↗

Pelargonium sidoides preparation (EPs 7630) in the treatment of acute bronchitis in adults and children.

Acute bronchitis, although mostly caused by viral infections, is commonly treated with antibiotics. As antibiotics should only be prescribed upon strict indication, treatment options like a liquid herbal drug preparation from the roots of Pelargonium sidoides (EPs 7630) gain more and more interest. To evaluate the efficacy and safety of treatment with EPs 7630 in patients with acute bronchitis, a multi-centre, prospective, open observational study was conducted in 440 study sites located in Germany. A total of 2099 patients aged 0-93 years with productive cough for less than six days without indication for treatment with antibiotics were given EPs 7630-solution in an age-dependent dosage for 14 days. The primary outcome criterion was the mean change of the Bronchitis Severity Score (BSS: cough, sputum, rales/rhonchi, chest pain at cough, dyspnoea) from baseline to patient's individual last observation. During treatment, the mean BSS of all patients decreased from 7.1+/-2.9 points at baseline to 1.0+/-1.9 points at patients' individual last visit. Subgroup analysis for children showed a decrease of mean BSS from 6.3+/-2.8 points to 0.9+/-1.8 points and analysis of children younger than three years showed a decrease of mean BSS from 5.2+/-2.5 points to 1.2+/-2.1 points. Adverse events occurred in 26/2099 (1.2%) patients. Serious adverse events were not reported. In conclusion, EPs 7630 is an effective and well tolerated treatment of acute bronchitis in adults, children and infants outside the strict indication for antibiotic treatment.

Acute Disease↗

Antibiotics in acute bronchitis: a meta-analysis.

PURPOSE: Most patients with acute bronchitis who seek medical care are treated with antibiotics, although the effectiveness of this intervention is uncertain. We performed a meta-analysis of randomized, controlled trials to estimate the effectiveness of antibiotics in the treatment of acute bronchitis. SUBJECTS AND METHODS: English-language studies published January 1966 to April 1998 were retrieved using MEDLINE, bibliographies, and consultation with experts. Only randomized trials that enrolled otherwise healthy patients with a diagnosis of acute bronchitis, used an antibiotic in the treatment group and a placebo in the control group, and provided sufficient data to calculate an effect size were included. RESULTS: We identified eight randomized controlled trials that satisfied all inclusion criteria. These studies used one of three antibiotics (erythromycin, doxycycline, trimethoprim/sulfamethoxazole). The use of antibiotics decreased the duration of cough and sputum production by approximately one-half day (summary effect size 0.21; 95% CI, 0.05 to 0.36). For specific symptoms, there were nonsignificant trends favoring the use of antibiotics: a decrease of 0.4 days of purulent sputum (95% CI, -0.1 to 0.8), a decrease of 0.5 days of cough (95% CI, -0.1 to 1.1), and a decrease of 0.3 days lost from work (95% CI, -0.6 to 1.1). CONCLUSION: This meta-analysis suggests a small benefit from the use of the antibiotics erythromycin, doxycycline, or trimethoprim/sulfamethoxazole in the treatment of acute bronchitis in otherwise healthy patients. As this small benefit must be weighed against the risk of side effects and the societal cost of increasing antibiotic resistance, we believe that the use of antibiotics is not justified in these patients.

Acute Disease↗

Symptoms of chronic bronchitis and the risk of coronary disease.

BACKGROUND: Experimental and epidemiological studies show a positive association between coronary disease and various infections in different organs, both viral and bacterial and both acute and chronic. Most attention has been paid to dental infections and infections in the respiratory tract. We have studied how chronic respiratory infection predicts coronary disease. METHODS: We defined chronic respiratory infection by the occurrence of symptoms of chronic bronchitis. We also analysed whether any association with coronary disease incidence and mortality is independent of the known major cardiovascular risk factors and whether it is similar among persons in different occupations. Our cohort study was a 13-year follow-up of 19,444 randomly selected eastern Finnish men and women born between 1913 and 1947 and examined in either 1972 or 1977. FINDINGS: During follow-up, there were 1419 first coronary events, either fatal or non-fatal, and 614 coronary deaths. Among men, the age-adjusted and study-year-adjusted risk ratio of long lasting-symptoms of chronic bronchitis (during as much as 3 months in a year) was 1.52 (95% CI 1.33-1.75) for coronary disease and 1.74 (CI 1.43-2.11) for coronary death. Among women the risk ratios were 1.38 (1.07-1.78) and 1.49 (0.98-2.27), respectively. Inclusion of smoking, serum cholesterol, and systolic blood pressure into the models decreased risk ratios to 1.36 (1.17-1.56) and 1.55 (1.26-1.90) in men and to 1.34 (1.04-1.74) and 1.41 (0.92-2.16) in women, respectively. The risk of coronary disease associated with the symptoms of chronic bronchitis was similar among blue-collar and white-collar workers but the association was not found among farmers. INTERPRETATION: Symptoms of chronic bronchitis predicted the risk of coronary disease independently from the known major cardiovascular risk factors. If the observed association is causal, prevention and improved management of chronic infections may have played a role in the decrease in coronary disease mortality observed in eastern Finland in the past two decades.

Adult↗

Serum ECP and MPO are increased during exacerbations of chronic bronchitis with airway obstruction.

Many studies have demonstrated that, in asthma, serum levels of eosinophil cationic protein (ECP) are related to the activity and severity of the disease and can be used to evaluate the response to steroid treatment. During exacerbations of chronic bronchitis, airway inflammation shows some features of asthmatic inflammatory processes, with recruitment of eosinophils and recovery of significant amounts of ECP in bronchial lavage fluid (BAL). Involvement of neutrophils, with high levels of myeloperoxidase (MPO), is, on the contrary, typical of this latter disease, and not shared with asthma. In spite of the information collected with BAL and bronchial biopsy studies, few data still exist on serum levels of these proteins in chronic bronchitis. The objective of this study was to assess if serum levels of ECP and MPO are specifically increased in exacerbations of chronic bronchitis, as compared to other non-asthmatic acute respiratory disturbances. Serum ECP, MPO and immunoglobulin E (IgE) levels were measured in 17 non-atopic patients with exacerbation of chronic bronchitis with airway obstruction (COPD) and in 11 control subjects seeking emergency medical treatment for unrelated acute respiratory problems. Spirometry was performed in patients able to give the necessary collaboration. All the subjects of this study were recruited from the emergency department. Both ECP and MPO were significantly increased in serum from patients with exacerbated COPD (22.2 +/- 4.1 vs 9.5 +/- 1.4 mcg/L and 853 +/- 168 vs 375 +/- 41 mcg/L) and a strong correlation existed between these two variables (r = 0.782). A further control group was made of 11 patients with stable COPD. These subjects had levels of both ECP (13.1 +/- 2.7 mcg/L) and MPO (469 +/- 71) significantly lower than patients with exacerbated disease and higher than those without COPD. We conclude that serum ECP and MPO are increased during the exacerbations of COPD. These observations can give a basis for further studies aimed to evaluate the utility of these two proteins as markers of activity and severity of COPD.

Aged↗