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The effect of nonobstructive chronic bronchitis (CB) on mortality is unclear.Is nonobstructive CB associated with increased all-cause mortality?We conducted a systematic literature review and meta-analysis to assess the association of nonobstructive CB and all-cause mortality. We searched for articles that included both CB and mortality in the title, abstract, or both in PubMed and EMBASE. We excluded studies in which participants demonstrated obstructive spirometry findings and studies in which CB and mortality were not defined. We used the Newcastle-Ottawa Quality Assessment Scale to assess study quality. We pooled adjusted hazard ratios (HRs) using the random effects model and inverse variance weighting. We conducted stratified analysis by the definition of CB and smoking status. We used Cochran's Q and IOf 5,014 titles identified, eight fulfilled the inclusion and exclusion criteria. Overall nonobstructive CB was associated with all-cause mortality (HR, 1.37; 95% CI, 1.26-1.50) with no statistically significant heterogeneity (P = .14; INonobstructive CB is associated with increased all-cause mortality, and this association seems to be present only in current and former smokers. Further research should investigate whether this high-risk population may benefit from early therapeutic intervention.PROSPERO; No.: CRD42021253596; URL: www.crd.york.ac.uk/prospero.

Background Effective management of protracted bacterial bronchitis (PBB) is needed to prevent chronic disease (eg, bronchiectasis). Understanding the contributions of ongoing airway infection and inflammation is important to achieving optimal PBB treatments. The aim of this study was to compare BAL microbiota, bacterial biomass, and inflammatory markers in children with PBB and age-matched control patients. Methods BAL was prospectively collected from 28 children with PBB (median age, 1.7 years; range, 0.6-7.4) and 8 control patients (median age, 1.9 years; range, 0.4-4.7). BAL microbiology was determined using culture, 16S ribosomal RNA gene sequencing and bacterial biomass quantification. BAL inflammatory cells, IL-8, and IL-1β were used to assess lower airway inflammation. Results Bacterial biomass, neutrophil percentage, IL-8, and IL-1β levels were significantly higher in children with PBB compared with control patients. BAL microbiota in children with PBB was significantly different to that of control patients (permutational multivariate analysis of variance P = .001) and clustered into four distinct profiles that were either dominated by a respiratory pathogen or contained a more diverse microbiota including Prevotella species. Alpha diversity was unrelated to bacterial biomass, culture of recognized respiratory pathogens, or inflammatory markers. Conclusions Neutrophilic inflammation in children with PBB was associated with multiple BAL microbiota profiles. Significant associations between inflammatory markers and bacterial biomass, but not alpha diversity, suggest that inflammation in children with PBB is not driven by single pathogenic species. Understanding the role of the entire respiratory microbiota in PBB pathogenesis may be important to determining whether bacteria other than the recognized pathogens contribute to disease recurrence and progression to bronchiectasis.

BACKGROUND: Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George’s Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. METHODS: We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB(+) or classic CB(–), using the classic definition. In addition, subjects were divided into SGRQ CB(+) or SGRQ CB(–). Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. RESULTS: There were 1,434 classic CB(+) subjects and 2,290 SGRQ CB(+) subjects. The classic CB(+) group had a greater exacerbation frequency compared with the classic CB(–) group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P < .0001) and a greater severe exacerbation frequency (0.26 ± 0.74 vs 0.13 ± 0.46 severe exacerbations per patient per year; P < .0001). There were similar differences between the SGRQ CB(+) and SGRQ CB(–) groups. In multivariable analysis, both SGRQ CB and classic CB were independent predictors of exacerbation frequency, but SGRQ CB had a higher regression coefficient. In addition, SGRQ CB was an independent predictor of severe exacerbation frequency whereas classic CB was not. CONCLUSIONS: The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

Background Chronic bronchitis (CB) increases risk of COPD exacerbations. We have shown that the St. George's Respiratory Questionnaire (SGRQ) CB definition identifies patients with a similar clinical phenotype as classically defined CB. Whether the SGRQ CB definition is a predictor of future COPD exacerbations is unknown. Methods We analyzed 7,557 smokers with normal spirometry and Global Initiative for Chronic Obstructive Lung Disease stage 1-4 COPD in the Genetic Epidemiology of COPD study with longitudinal follow-up data on exacerbations. Subjects were divided into classic CB+ or classic CB–, using the classic definition. In addition, subjects were divided into SGRQ CB+ or SGRQ CB–. Exacerbation frequency and severe exacerbation frequency were determined in each group. Multivariable linear regressions were performed for exacerbation frequency with either classic CB or SGRQ CB and relevant covariates. Results There were 1,434 classic CB+ subjects and 2,290 SGRQ CB+ subjects. The classic CB+ group had a greater exacerbation frequency compared with the classic CB– group (0.69 ± 1.26 vs 0.36 ± 0.90 exacerbations per patient per year; P Conclusions The SGRQ CB definition identified more subjects at risk for future exacerbations than the classic CB definition. SGRQ CB was at least a similar if not better predictor of future exacerbations than classic CB.

COPD includes the chronic bronchitis (CB) and emphysema phenotypes. Although it is generally assumed that emphysema or chronic airflow obstruction (CAO) is associated with worse quality of life (QOL) than is CB, this assumption has not been tested.The current study's analyses from the Lovelace Smokers' Cohort (LSC) were validated in the COPD Gene Cohort (COPDGene). CB without CAO (CB only) was defined as self-reported cough productive of phlegm for ≥ 3 mo/y for 2 consecutive years and postbronchodilator FEV1/FVC ≥ 70%. CAO without CB (CAO only) was defined as a postbronchodilator FEV1/FVC70% with no evidence of CB. QOL outcomes were obtained from the St. George's Respiratory Questionnaire (SGRQ) and the 36-Item Short Form Health Survey (SF-36) questionnaires. A priori covariates included age, sex, pack-years of smoking, current smoking, and FEV1.Smokers with CB without CAO (LSC = 341; COPDGene = 523) were younger and had a greater BMI and less smoking exposure than did those with CAO only (LSC = 302; COPDGene = 2,208). Compared with the latter group, QOL scores were worse for those with CB only. Despite similar SGRQ Activity and SF-36 Role Physical and Physical Functioning, SGRQ Symptoms and Impact scores and SF-36 emotional and social measures were worse in the CB-only group, in both cohorts. After adjustment for covariates, the CB-only group remained a significant predictor for "worse" symptoms and emotional and social measures.To our knowledge, this analysis is the first to suggest that among subjects with COPD, those with CB only present worse QOL symptoms and mental well-being than do those with CAO only.

Smokers with persistent cough and sputum production (chronic bronchitis [CB]) represent a distinct clinical phenotype, consistently linked to negative clinical outcomes. However, the mechanistic link between physiologic impairment, dyspnea, and exercise intolerance in CB has not been studied, particularly in those with mild airway obstruction. We, therefore, compared physiologic abnormalities during rest and exercise in CB to those in patients without symptoms of mucus hypersecretion (non-CB) but with similar mild airway obstruction.Twenty patients with CB (≥ 3 months cough/sputum in 2 successive years), 20 patients without CB but with GOLD (Global Initiative for Chronic Obstructive Lung Disease) grade IB COPD, and 20 age- and sex-matched healthy control subjects underwent detailed physiologic testing, including tests of small airway function and a symptom-limited incremental cycle exercise test.Patients with CB (mean ± SD postbronchodilator FEV1, 93% ± 12% predicted) had greater chronic activity-related dyspnea, poorer health-related quality of life, and reduced habitual physical activity compared with patients without CB and control subjects (all P.05). The degree of peripheral airway dysfunction and pulmonary gas trapping was comparable in both patient groups. Peak oxygen uptake was similarly reduced in patients with CB and those without compared with control subjects (% predicted ± SD, 70 ± 26, 71 ± 29 and 106 ± 43, respectively), but those with CB had higher exertional dyspnea ratings and greater respiratory mechanical constraints at a standardized work rate than patients without CB (P.05).Patients with CB reported greater chronic dyspnea and activity restriction than patients without CB and with similar mild airway obstruction. The CB group had greater dynamic respiratory mechanical impairment and dyspnea during exercise than patients without CB, which may help explain some differences in important patient-centered outcomes between the groups.

Background Approximately 15% of cases of COPD, including chronic bronchitis, is attributable to occupational exposures. An occupational history is essential to identify exposures responsible for work-related chronic bronchitis. Methods We conducted a structured retrospective analysis of the medical records of veterans, 18 to 70 years of age, newly diagnosed with chronic bronchitis in order to achieve the following: (1) to assess the quality of documented occupational histories; and (2) to characterize the management of patients with a history of exposure to a potentially hazardous respiratory substance. We also analyzed occupational exposure data reported by patients on a structured questionnaire. Results Sixty patients were included in the final analysis. A total of 6,150 notes were reviewed. Occupational status was documented in the records of 54 patients (90%). A description of occupational duties was recorded in 32 records (53%), and work exposure data in 26 records (43%). Clinicians concluded that occupational exposures potentially contributed to chronic bronchitis in three patients (5%). A recommendation for exposure avoidance was documented for six patients (10%). On the questionnaire, most patients reported a history of occupational exposure to respirable substances and symptoms of cough and/or shortness of breath. Conclusions Details about job duties and occupational respiratory exposures were documented in the records of approximately half of patients with newly diagnosed chronic bronchitis. Patient self-reports of occupational exposures and respiratory symptoms were common. A determination that occupational exposures contributed to chronic bronchitis was rare. Few patients were counseled to take measures to avoid occupational exposures. Work-related chronic bronchitis may be incompletely assessed and undermanaged by clinicians.

Background: Nonasthmatic eosinophilic bronchitis (NAEB) is an important cause of chronic cough, and it can be diagnosed by an induced-sputum (IS) examination. However, an IS examination is a complex and time-consuming procedure, and it has limited clinical application. This study aimed to evaluate the role of exhaled nitric oxide (NO) for the investigation of chronic cough, especially of NAEB. Methods: Two hundred eleven nonsmoking patients with a cough lasting > 3 weeks were enrolled in the study. The patients were examined and investigated with conventional diagnostic tools, including an IS examination. Exhaled NO was measured by a chemoluminescent analyzer. Results: One hundred seventeen patients with adequate IS results were analyzed: asthma, n 14; NAEB, n 21; and “others,” n 82. Exhaled NO and IS eosinophils were significantly higher in the asthma group and NAEB group than in the others group. Exhaled NO and IS eosinophils were significantly correlated in the asthma and NAEB groups. In the nonasthmatic group, the sensitivity and specificity of exhaled NO for detecting NAEB, using 31.7 parts per billion as the exhaled NO cutoff point, were 86% and 76%, respectively. Positive and negative predictive values were 47% and 95%, respectively, and positive and negative likelihood ratios were 3.51 and 0.19, respectively. Conclusion: We concluded that exhaled NO measurement may be useful as part of the initial evaluation for chronic cough, especially for the exclusion of NAEB. A low level of exhaled NO suggested little likelihood of NAEB for the nonasthmatic patients with chronic cough. (CHEST 2008; 134:990–995)

Background: Biomass smoke has been associated with many diseases. The aim of this study was to evaluate the relationship between biomass smoke and chronic bronchitis in women in the rural setting of Peshawar, Pakistan. Methods: Three villages in rural Peshawar were randomly selected as “test villages” where biomass fuel was used. The women responsible for cooking in these villages were interviewed for the prevalence of bronchitis, and data were compared to those obtained from three matching “control villages” where liquid petroleum gas was used as fuel. Crude odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a statistical software package (EPI Info, version 6.0 [public domain software]; Centers for Disease Control and Prevention; Atlanta, GA). Results: This study was carried out in 1,426 female test patients and 1,131 female control subjects. Chronic bronchitis was found in 100 women (7.01%) in the test group and 33 women (2.92%) in the control group. The OR was 2.51 (95% CI, 1.65 to 3.83). A strong association was found between bronchitis and the use of wood (OR, 2.38; 95% CI, 2.12 to 3.01), dung cake (OR, 2.01; 95% CI, 1.72 to 2.42), rice straws (OR, 3.32; 95% CI, 1.11 to 9.88), and kai grass (OR, 1.96; 95% CI, 1.75 to 2.45). Cooking in the living room and bronchitis were highly associated (OR, 2.5; 95% CI, 1.94 to 3.66). An association between the presence of a kitchen and bronchitis was established with an OR of 2.65 (95% CI, 2.10 to 3.42). In the test group, 75% of kitchens were ventilated; in the control group, 82% were ventilated. The difference between the two groups was nonsignificant (p > 0.6; 2 0.39; OR, 0.83; 95% CI, 0.5 to 1.4). Conclusions: Biomass fuel exposure is strongly associated with chronic bronchitis in women who are involved in cooking in rural Peshawar. (CHEST 2007; 132:1472–1475)

Background Polymorphonuclear neutrophil (PMN)-dominated inflammation is prominent in the airways of subjects with cystic fibrosis (CF) and chronic bronchitis (CB). Interleukin (IL)-8, myeloperoxidase (MPO), and DNA are markers of neutrophilic inflammation. We hypothesized that sputum MPO, DNA, and IL-8 concentrations would negatively correlate with pulmonary function and sputum transportability. Methods We measured pulmonary function and analyzed sputum IL-8, MPO, and DNA concentrations, as well as the transport properties of sputum samples obtained from 16 subjects with CF and 15 subjects with CB. We also evaluated changes in these measurements in paired sputum samples from these subjects obtained 2 to 12 months apart. Results IL-8 and MPO concentrations in the sputum of CF subjects was inversely correlated with FEV 1 percent predicted (IL-8: r = −0.40; p = 0.003; MPO: r = −0.38; p = 0.003) and FVC percent predicted (IL-8: r = −0.4; p = 0.02; MPO: r = −0.4; p = 0.02). IL-8 and DNA concentrations were inversely correlated with sputum cough transportability (CTR) [IL-8: r = −0.4; p = 0.02; DNA: r = −0.36; p = 0.048]. Changes in DNA concentration in sputum samples from CF subjects over time were inversely correlated with changes in FEV 1 percent predicted ( r = −0.58; p = 0.02), FVC percent predicted ( r = −0.74; p = 0.002), and CTR ( r = −0.59; p = 0.02). There was no correlation among pulmonary function, sputum properties, and inflammatory markers in the sputum from subjects with CB. Conclusions The sputum concentrations of IL-8, MPO, and DNA appear to be closely associated with pulmonary function in subjects with CF but not in subjects with CB.

Background: Chronic bronchitis is a disease of the bronchi that is manifested by cough and sputum expectoration occurring on most days for at least 3 months of the year and for at least 2 consecutive years when other respiratory or cardiac causes for the chronic productive cough are excluded. The disease is caused by an interaction between noxious inhaled agents (eg, cigarette smoke, industrial pollutants, and other environmental pollutants) and host factors (eg, genetic and respiratory infections) that results in chronic inflammation in the walls and lumen of the airways. As the disease advances, progressive airflow limitation occurs, usually in association with pathologic changes of emphysema. This condition is called COPD. When a stable patient experiences a sudden clinical deterioration with increased sputum volume, sputum purulence, and/or worsening of shortness of breath, this is referred to as an acute exacerbation of chronic bronchitis as long as conditions other than acute tracheobronchitis are ruled out. The purpose of this review is to present the evidence for the diagnosis and treatment of cough due to chronic bronchitis, and to make recommendations that will be useful for clinical practice. Methods: Recommendations for this section of the review were obtained from data using a National Library of Medicine (PubMed) search dating back to 1950, performed in August 2004, of the literature published in the English language. The search was limited to human studies, using the search terms “cough,” “chronic bronchitis,” and “COPD.” Results: The most effective way to reduce or eliminate cough in patients with chronic bronchitis and persistent exposure to respiratory irritants, such as personal tobacco use, passive smoke exposure, and workplace hazards is avoidance. Therapy with a short-acting inhaled β-agonist, inhaled ipratropium bromide, and oral theophylline, and a combined regimen of inhaled long-acting β-agonist and an inhaled corticosteroid may improve cough in patients with chronic bronchitis, but there is no proven benefit for the use of prophylactic antibiotics, oral corticosteroids, expectorants, postural drainage, or chest physiotherapy. For the treatment of an acute exacerbation of chronic bronchitis, there is evidence that inhaled bronchodilators, oral antibiotics, and oral corticosteroids (or in severe cases IV corticosteroids) are useful, but their effects on cough have not been systematically evaluated. Therapy with expectorants, postural drainage, chest physiotherapy, and theophylline is not recommended. Central cough suppressants such as codeine and dextromethorphan are recommended for short-term symptomatic relief of coughing. Conclusions: Chronic bronchitis due to cigarette smoking or other exposures to inhaled noxious agents is one of the most common causes of chronic cough in the general population. The most effective way to eliminate cough is the avoidance of all respiratory irritants. When cough persists despite the removal of these inciting agents, there are effective agents to reduce or eliminate cough.

Rational and appropriate antibiotic use for patients with acute exacerbation of chronic bronchitis (AECB) is a major concern, as approximately half of these patients do not have a bacterial infection. Typically, the result of antimicrobial therapy for patients with acute bacterial exacerbation of chronic bronchitis (ABECB) is not eradication of the pathogen but resolution of the acute symptoms. However, the length of time before the next bacterial exacerbation can be another important variable, as the frequency of exacerbations will affect the overall health of the patient and the rate of lung deterioration over time. Clinical trials comparing antimicrobial therapies commonly measure resolution of symptoms in AECB patients as the primary end point, regardless of whether the exacerbation is documented as bacterial in nature. Ideally, the scientific approach to assessing the efficacy of antibiotic therapy for ABECB should include a measurement of acute bacterial eradication rates in patients with documented bronchial bacterial infection followed by measurement of the infection-free interval (IFI), ie, the time to the next ABECB. The use of these variables can provide a standard for comparing various antimicrobial therapies. As we learn more about how antibiotics can affect the IFI, treatment decisions should be adapted to ensure optimal management of ABECB for the long-term.

To examine the differences in the inflammatory cell and cytokine profile between patients with chronic bronchitis (CB) with and without airway obstruction compared to control subjects.We used bronchial biopsy samples from the patients and control subjects and analyzed them for the presence of CD3 T cells, CD68, major basic protein (MBP), elastase, and tryptase, as well as expression of messenger RNA (mRNA) coding for interleukin (IL)-4, IL-5, interferon (IFN)-gamma, IL-9, eotaxin, and IFN-gamma-inducible protein (IP)-10. The techniques of immunocytochemistry and in situ hybridization were used. Results were expressed as the number of immunoreactive and mRNA-positive cells per field.Increased number of elastase, CD68, and MBP-positive cells (n = 9, p0.01) was demonstrated in both groups of patients with CB compared to control subjects. In patients with CB and obstruction, the number of elastase, CD68, and the number of CD3-positive cells was significantly increased compared to patients with CB without obstruction (n = 9, p0.01). IFN-gamma mRNA expression was increased in both groups of patients with CB compared to control subjects (n = 9, p0.01). IL-9 mRNA was significantly increased only in patients with CB and obstruction (n = 9, p0.01). Co-localization studies demonstrated80% of all IL-9-positive cells to be CD3-positive T cells. IP-10 mRNA was significantly increased in both groups of patients with CB compared to control subjects (n = 9, p0.01).These results indicate a differential expression of inflammatory markers and cytokine mRNA in patients with obstructive CB. Increased presence of T lymphocytes and up-regulation of IL-9 and IP-10 mRNA expression in the bronchial biopsy samples may contribute to the airway obstruction in these patients.

Background: Although it is defined as cough and sputum production for at least 3 months per year for at least 2 consecutive years, difficulties exist in the use of the term chronic bronchitis for clinical diagnosis. In particular, the relationship between diagnosis and symptoms has been difficult to ascertain. Study objectives: To determine, in a large epidemiologic study, the degree to which a new self-reported diagnosis of chronic bronchitis (NCBR) satisfies the symptom criteria for that diagnosis, and to determine the relationship between self-reported physician-confirmed diagnoses and symptom criteria. Methods: We analyzed data obtained from the Tucson Epidemiologic Study of Obstructive Lung Diseases. Using responses to standardized respiratory questionnaires administered to 4,034 subjects, those with NCBRs were selected and assessed as to whether they met symptom criteria for that diagnosis. Descriptive statistics pertaining to gender, age, and smoking status were obtained. Furthermore, we determined how often symptom criteria were met among a subset of subjects with physician-confirmed self-reported diagnoses. Results: Of 481 subjects with NCBRs, only 56 subjects (11.6%) met the required symptom criteria. Men compared with women and current smokers compared with ex-smokers or neversmokers were more likely to meet symptom criteria. Four hundred fifteen of 481 subjects with NCBRs had physician-confirmed self-reported diagnoses. Of these, only 52 subjects (12.5%) met symptom criteria. Within the subgroup of subjects who met symptom criteria, higher percentages were observed in the older age groups, but this was not statistically significant. Conclusion: Only a minority of subjects with NCBRs satisfy the symptom criteria of cough and sputum production for at least 3 months per year for at least 2 consecutive years. This relationship holds true even among those with physician-confirmed self-reported diagnoses. (CHEST 2002; 122:1234 –1239)

CT scanning allows assessment of airway-wall thickness and is useful for diagnosing and assessing various lung diseases, including asthma and COPD. Several studies have reported that CT scan-estimated dimensions are positively correlated with pulmonary function test results and a positive response to treatment. However, to our knowledge, airway disease complicated by inflammatory bowel disease has not yet been assessed using CT scan-estimated dimensions. A 61-year-old woman with ulcerative colitis (UC) complained of cough, sputum, and fever 4 months after undergoing a total colectomy and rectal mucosectomy. Examination of bronchial biopsy samples demonstrated lymphocytic and plasma cell infiltration of the epithelium and submucosa. CT scan-estimated dimensions indicated thickening of the airways. Chronic bronchitis complicated with UC was diagnosed, and high-dose inhaled corticosteroid therapy was prescribed. Three months later, the CT scan-estimated dimensions of the patient's airways, her symptoms, and pulmonary function test results were dramatically improved.

Normal airway mucus lines the epithelial surface and provides an important innate immune function by detoxifying noxious molecules and by trapping and removing pathogens and particulates from the airway via mucociliary clearance. The major macromolecular constituents of normal mucus, the mucin glycoproteins, are large, heavily glycosylated proteins with a defining feature of tandemly repeating sequences of amino acids rich in serine and threonine, the linkage sites for large carbohydrate structures. The mucins are composed of two major families: secreted mucins and membrane-associated mucins. Membrane-associated mucins have been reported to function as cell surface receptors for pathogens and to activate intracellular signaling pathways. The biochemical and cellular functions for secreted mucin glycoproteins have not been definitively assigned. In contrast to normal mucus, sputum production is the hallmark of chronic inflammatory airway diseases such as asthma, chronic bronchitis, and cystic fibrosis (CF). Sputum has altered macromolecular composition and biophysical properties which vary with disease, but unifying features are failure of mucociliary clearance, resulting in airway obstruction, and failure of innate immune properties. Mucin glycoprotein overproduction and hypersecretion are common features of chronic inflammatory airway disease, and this has been the underlying rationale to investigate the mechanisms of mucin gene regulation and mucin secretion. However, in some pathologic conditions such as CF, airway sputum contains little intact mucin and has increased content of several macromolecules including DNA, filamentous actin, lipids, and proteoglycans. This review will highlight the most recent insights on mucus biology in health and disease.

Childhood idiopathic bronchiectasis (IB) unrelated to cystic fibrosis (CF) or known immunodeficiency remains a common problem among indigenous populations in developed and developing countries. The physical and transport properties of sputum among children with IB have not been described, and these properties may suggest therapies that would be particularly effective for this group of children.Sputum from children in stable condition with IB and chronic daily productive cough was collected to measure viscosity, elasticity, cohesivity, adhesivity, and mucociliary and cough transportability in vitro. The results were compared to banked data from the sputa of children with CF and adults with chronic bronchitis (CB) measured by the same methods.Sputa from children with CF and adults with CB had similar values for viscosity, elasticity, frictional adhesion, cough transportability, and mucociliary transportability. The elasticity of sputum from children with IB was 12 to 20%, respectively, of the value of CB and CF sputum (p0.01). The viscosity of sputum from children with IB was 23 to 32%, respectively, of the value of CB and CF sputum (p0.02). The surface frictional adhesion for sputum from children with IB was 55% of the values from both CF and CB sputa (p0.0001). Cough transportability for sputum from children with IB was 43 to 54% greater, respectively, than that for sputum from CB and CF patients (p0.0001). Mucociliary transportability was similar for all three groups (p0.05).The physical and transport properties of sputum from children with IB who are stable in the outpatient setting are substantially different and lead to improved cough transportability compared to sputum from children with CF or adults with CB. Therapies that focus on cough may be sufficient to improve airway mucus clearance in children with IB. Sputum properties may explain in part the different clinical course of children with IB compared to children with CF.

Although acute exacerbations of chronic bronchitis (AECBs) are common, there has been no metaanalysis that focused on the optimum regimen.To evaluate the comparative effectiveness and safety of first-line antimicrobial agents (ie, amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline) and second-line antimicrobial agents (ie, amoxicillin/clavulanic acid, macrolides, second-generation or third-generation cephalosporins, and quinolones) for the treatment of patients with AECB, in an era of increasing antimicrobial resistance among the microbes responsible for AECB, we performed a metaanalysis of randomized controlled trials (RCTs) retrieved through searches of the PubMed and the Cochrane databases.Twelve RCTs were included in the metaanalysis. First-line antibiotics were associated with lower treatment success compared to second-line antibiotics in the clinically evaluable patients (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.34 to 0.75). There were no differences among the compared regimens regarding mortality (OR, 0.64; 95% CI, 0.25 to 1.66) or treatment success (OR, 0.56; 95% CI, 0.22 to 1.43) in microbiologically evaluable patients, or adverse effects in general (OR, 0.75; 95% CI, 0.39 to 1.45) or diarrhea in particular (OR, 1.58; 95% CI, 0.74 to 3.35).Compared to first-line antibiotics, second-line antibiotics are more effective, but not less safe, when administered to patients with AECB. The available data did not allow for stratified analyses according to the presence of risk factors for poor outcome, such as increased age, impaired lung function, airway obstruction, and frequency of exacerbations; this fact should be taken into consideration when interpreting the findings of this metaanalysis.

To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB).Multicenter, multinational, randomized, double-blind study of two parallel treatment arms.Outpatientsor= 45 years old with stable chronic bronchitis, smoking history ofor= 20 pack-years, two or more AECBs in the previous year, and FEV(1)85% of predicted value. Patients were enrolled when in a stable condition, and patients with exacerbations within 12 months of enrollment were randomized.Randomization (stratified on steroid use) between moxifloxacin (400 mg qd for 5 days) and standard therapy (amoxicillin [500 mg tid for 7 days], clarithromycin [500 mg bid for 7 days], or cefuroxime-axetil [250 mg bid for 7 days]).Assessment at enrollment, randomization (Anthonisen type 1 exacerbation), 7 to 10 days after treatment, and monthly until next AECB or up to 9 months. The primary efficacy variable was clinical success (sufficient improvement, no alternative antimicrobial therapy required) 7 to 10 days after therapy. Secondary predefined end points were clinical cure (return to pre-exacerbation status), further antimicrobial use, time to next AECB, and bacteriologic success.Three hundred fifty-four patients received moxifloxacin, and 376 patients received standard therapy. At 7 to 10 days after therapy, clinical success rates were similar in intention-to-treat (ITT) patients (95% confidence interval [CI], - 0.7 to 9.5) and per-protocol (PP) patients (95% CI, - 3.0 to 8.5). Moxifloxacin showed superior clinical cure rates over standard therapy in both ITT patients (95% CI, 1.4 to 14.9) and PP patients (95% CI, 0.3 to 15.6), and higher bacteriologic success in microbiologically valid patients (95% CI, 0.4 to 22.1). Fewer ITT patients required antimicrobials after treatment with moxifloxacin than standard therapy (p0.01). Time to next exacerbation was longer with moxifloxacin; median and mean times to new AECBs in ITT patients who did not require any further antibiotics were 131.0 days and 132.8 days in moxifloxacin, and 103.5 days and 118.0 days in standard therapy, respectively (p = 0.03). The occurrence of failure, new exacerbation, or any further antibiotic was less frequent in moxifloxacin-treated patients for up to 5 months of follow-up (p = 0.03).Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes.

This study attempted to determine the total direct costs derived from the management of chronic bronchitis and COPD in an ambulatory setting through a prospective, 1-year, follow-up study.A total of 1,510 patients with chronic bronchitis and COPD were recruited from 268 general practices located throughout Spain. Patients were followed up for 1 year. All direct medical costs incurred by the cohort and related to their respiratory disease were quantified. Costs were calculated for patients with confirmed COPD according to the degree of severity of airflow obstruction.The global mean direct yearly cost of chronic bronchitis and COPD was $1,876. The cost generated by patients with COPD was $1,760, but the cost of severe COPD ($2,911) was almost double that of mild COPD ($1,484). Hospitalization costs represented 43.8% of costs, drug acquisition costs were 40.8%, and clinic visits and diagnostic tests represented only 15.4% of costs.This is the first prospective follow-up study on a large cohort of patients with chronic bronchitis and COPD aimed at quantifying direct medical costs under usual clinical practice in the community. Costs of chronic bronchitis and COPD were almost twofold those reported for asthma. Patterns of COPD management in the community differ from those recommended in guidelines. COPD represents a great health-care burden in developed countries, and aging of the population and continuing smoking habits predict that it will continue to do so in the future.

Recent studies have suggested a relationship between asthma and obesity. Despite these reports, the effect of being underweight or overweight as a risk factor for airway obstructive diseases (AODs) is not clear.To determine whether a relation of body mass index (BMI) to asthma, chronic bronchitis (CB), or emphysema exists (analysis 1), and, if so, whether the association between obesity and asthma is modified by gender (analysis 2).Nested case-control study from the longitudinal cohort of the Tucson Epidemiologic Study of Airways Obstructive Diseases.Analysis 1: physician-confirmed incident cases of asthma (n = 102), CB (n = 299), or emphysema (n = 72) who denied any prior AODs. Analysis 2: all 169 incident cases of asthma, regardless of any previous AODs, stratified by gender and by other potential effect modifiers. In both analyses, we selected only subjects at least 20 years old who had weight and height measured during the study.BMI and other risk factors were assessed prior to the onset of the AOD (cases) or prior to the last completed survey (control subjects).A diagnosis of emphysema was significantly associated with a BMI18.5 (odds ratio [OR], 2.97; 95% confidence interval [CI], 1.33 to 6.68, when compared to healthy control subjects). A BMI/= 28 increased the risk of receiving a diagnosis of asthma (OR, 2.10; 95% CI, 1.31 to 3.36) and CB (OR, 1.80; 95% CI, 1.32 to 2.46). About 30% of the patients with asthma and 25% of the patients with CB (vs 16% of the control subjects, p0.001) were preobese or obese, regardless whether BMI was assessed before the diagnosis or before the onset of respiratory symptoms. The relation of elevated BMI to asthma was significant only among women.Patients with emphysema are more likely to be underweight, and patients with CB are more likely to be obese. However, the temporal relationship between abnormal BMI and the onset of COPD is uncertain. Preobese and obese women are at increased risk of acquiring asthma. This relation, particularly if it is causal, has potentially relevant public health implications.

Study objective Patients with COPD classically have neutrophilic bronchial inflammation and raised airway concentrations of the neutrophil chemoattractant leukotriene B 4 (LTB 4 ). A small phase II trial was conducted to assess the effects of a leukotriene synthesis inhibitor on bronchial inflammation in patients with stable COPD. Design A randomized, double-blind, placebo-controlled, parallel-group study. Setting Respiratory medicine department of a university hospital. Patients and intervention Seventeen patients with chronic bronchitis and COPD (mean FEV 1 , 35.5% predicted; SD, 14.8% predicted) were randomized to receive 14 days of the oral leukotriene synthesis inhibitor BAYx1005 (500 mg bid) or placebo. Measurements and results Spontaneous sputum samples obtained at baseline and at the end of treatment were assayed for LTB 4 , myeloperoxidase (an indirect marker of neutrophil numbers and/or activation), and chemotactic activity (Boyden chamber). After 14 days, there were no significant differences (p > 0.05) in absolute LTB 4 concentrations between the two treatment groups. However, BAYx1005 treatment produced a significantly greater median reduction in LTB 4 of − 3.1 nM (interquartile range [IQR], − 9.6 to − 0.2 nM) vs 3.0 nM (IQR, − 0.3 to 8.5 nM) [p = 0.001], with concentrations decreasing from 8.0 nM (IQR, 4.3 to 24.4 nM) at baseline to 4.2 nM (IQR, 1.9 to 11.9 nM) at the end of treatment (p = 0.03). There were no changes in the placebo group and no differences in sputum myeloperoxidase concentration or chemotaxis between the two treatment arms (p > 0.05). Conclusions This small study suggests that a leukotriene synthesis inhibitor can produce modest reductions in some measures of neutrophilic bronchial inflammation in patients with COPD. This class of anti-inflammatory agent requires further study in larger numbers of patients to determine clinical benefit.

Chronic bronchitis is in part characterized by mucus hypersecretion and the inability to clear airways of mucus. Despite years of research in this area, to date there are no pharmacologic therapies available to enhance or promote mucociliary clearance. P2Y(2) receptor agonists are a new class of mucoactive compounds that are currently under development for this purpose. This article will review the pharmacology of P2Y(2) receptor agonists, review the clinical studies performed to date, and highlight the challenges inherent in the development of therapies with these pharmacologic properties.