Nonobstructive Chronic Bronchitis Research Articles

Глутатион как прогностический фактор риска нарушения здоровья работающих лиц

Redox balance plays the key role in maintaining health. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although cause-effect relationships between glutathione status and disease risk or treatment have not been fully clarified. This study aims to estimate glutathione as a non-specific prognostic risk factor of health disorders in people exposed to industrial aerosols at their workplaces. Our observation covered the following occupational groups: workers employed at a metallurgic plant who contacted industrial aerosols (welding and silicon-containing aerosols with predominantly fibrogenic effects); patients with non-obstructive chronic industrial bronchitis (NCIB) without exacerbation; patients suffering from occupational chronic obstructive pulmonary disease (oCOPD) who were in a post-exposure period; workers who were not exposed to industrial aerosols at their workplaces. Total glutathione (TG), reduced glutathione (GSH) and oxidized glutathione (GSSG) were identified in whole blood by the Ellman method. Elevated GSSG levels (higher than 100 µmol/l) and low values of the GSH/GSSG ratio (less than 10 units) were identified in more than 50 % of the workers exposed to industrial aerosols. These markers were established to have diagnostic sensitivity of more than 50 %, diagnostic specificity of more than 85 % and prognostic significance of more than 80 % for the examined groups. The GSSG level and GSH/GSSG ratio can be used as a prognostic indicator of health disorders in workers exposed to industrial aerosols and a possibility of chronic bronchopulmonary pathology developing in future.

Glutathione as a prognostic factor of health risk in working population

Redox balance plays the key role in maintaining health. Optimizing glutathione levels has been proposed as a strategy for health promotion and disease prevention, although cause-effect relationships between glutathione status and disease risk or treatment have not been fully clarified. This study aims to estimate glutathione as a non-specific prognostic risk factor of health disorders in people exposed to industrial aerosols at their workplaces. Our observation covered the following occupational groups: workers employed at a metallurgic plant who contacted industrial aerosols (welding and silicon-containing aerosols with predominantly fibrogenic effects); patients with non-obstructive chronic industrial bronchitis (NCIB) without exacerbation; patients suffering from occupational chronic obstructive pulmonary disease (oCOPD) who were in a post-exposure period; workers who were not exposed to industrial aerosols at their workplaces. Total glutathione (TG), reduced glutathione (GSH) and oxidized glutathione (GSSG) were identified in whole blood by the Ellman method. Elevated GSSG levels (higher than 100 µmol/l) and low values of the GSH/GSSG ratio (less than 10 units) were identified in more than 50 % of the workers exposed to industrial aerosols. These markers were established to have diagnostic sensitivity of more than 50 %, diagnostic specificity of more than 85 % and prognostic significance of more than 80 % for the examined groups. The GSSG level and GSH/GSSG ratio can be used as a prognostic indicator of health disorders in workers exposed to industrial aerosols and a possibility of chronic bronchopulmonary pathology developing in future.

Clinical features and 1-year outcomes of chronic bronchitis in participants with normal spirometry: results from the ECOPD study in China

BackgroundEvidence regarding clinical features and outcomes of individuals with non-obstructive chronic bronchitis (NOCB) remains scarce, especially in never-smokers. We aimed to investigate the clinical features and 1-year outcomes of individuals...

Association of Nonobstructive Chronic Bronchitis With All-Cause Mortality: A Systematic Literature Review and Meta-analysis

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 I2 to assess for heterogeneity. We assessed publication bias by visual inspection of a funnel plot. Of 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; I2= 29%). Nonobstructive CB was associated with increased mortality in studies that defined CB as any respiratory symptoms (broad definition; HR, 1.28; 95%CI, 1.10-1.48; I2= 0%) as well as in the rest of the studies (HR, 1.40; 95%CI, 1.26-1.56; I2= 37%). Nonobstructive CB was associated with increased mortality in ever smokers (HR, 1.49; 95%CI, 1.35-1.64; I2= 0%), but was not associated with increased mortality in never smokers (HR, 1.22; 95%CI, 0.90-1.66), and moderate heterogeneity was found (P= .10; I2= 49%). The funnel plot did not indicate evidence of a publication bias because it showed symmetrical distribution of studies. Nonobstructive 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.

Association Between Non-obstructive Chronic Bronchitis and Incident Chronic Obstructive Pulmonary Disease and All-Cause Mortality: A Systematic Review and Meta-Analysis

BackgroundChronic bronchitis in patients with chronic obstructive pulmonary disease (COPD) is associated with poor respiratory health outcomes. However, controversy exists around whether non-obstructive chronic bronchitis (NOCB) is associated with airflow obstruction, lung function decline, and all-cause mortality in ever smoker or never smoker.Research QuestionThis systematic review and meta-analysis aimed to clarify the relationship between NOCB and incident COPD, lung function decline, and all-cause mortality, and to quantify the magnitude of these associations.Study Design and MethodsWe searched PubMed, Embase, and Web of Science for studies published up to October 1, 2021. Eligibility screening, data extraction, and quality assessment of the retrieved articles were conducted independently by two reviewers. Studies were included if they were original articles comparing incident COPD, lung function decline, and all-cause mortality in normal spirometry with and without chronic bronchitis. The primary outcomes were incident COPD and all-cause mortality. The secondary outcomes were respiratory disease-related mortality and lung function decline. Pooled effect sizes and 95% confidence intervals (CIs) were calculated using the random-effects model.ResultsWe identified 17,323 related references and included 14 articles. Compared with individuals without NOCB, individuals with NOCB had an increased risk of incident COPD (odds ratio: 1.98, 95% CI: 1.21–3.22, I2 = 76.3% and relative risk: 1.44, 95%CI: 1.13–1.85, I2 = 56.1%), all-cause mortality (hazard ratio [HR]: 1.38, 95%CI: 1.26–1.51, I2 = 29.4%), and respiratory disease-related mortality (HR: 1.88, 95%CI: 1.37–2.59, I2 = 0.0%). Data on the decline in lung function could not be quantitatively synthesized, but the five articles that assessed the rate of decline in lung function showed that lung function declines faster in individuals with NOCB. The mean difference in the additional decline in forced expiratory volume in 1 s ranged from 3.6 to 23.2 mL/year.InterpretationIndividuals with NOCB are at a higher risk of incident COPD and all-cause mortality than individuals without NOCB, highlighting the crucial need for strategies to screen for and reduce NOCB risk.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/ PROSPERO, identifier CRD42020202837

From GOLD 0 to Pre-COPD.

Currently the diagnosis of chronic obstructive pulmonary disease (COPD) requires the demonstration of airflow limitation, defined as a post-bronchodilator FEV1/FVC <0.7, a measurement that remains methodologically robust and widely available. FEV1 is one of the most powerful predictors of clinically relevant outcomes including symptoms, exacerbations and mortality. However, reliable data suggest that respiratory symptoms, in particular chronic bronchitis, airway abnormality and emphysema detected using modern imaging techniques such as computed tomography (CT), and certain physiologic measures including rapid decline in FEV1 and DLCO are present among individuals who do not meet spirometric criteria for COPD. These abnormalities may help to identify individuals at increased risk for developing airflow limitation in the future. Here, we review the evidence that support the use of the term "pre-COPD" in individuals with symptoms (e.g., "Non-Obstructive Chronic Bronchitis" (NOCB)), physiologic (e.g., low DLCO) and/or imaging abnormalities (e.g. CT emphysema) but spirometry in the normal range, who are at risk of developing COPD defined by a reduced FEV1/FVC ratio. We acknowledge, however, that further research on early disease in young individuals will be critical to develop a clinically operable definition of "pre-COPD" that demonstrates good sensitivity and specificity. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Association of Nonobstructive Chronic Bronchitis With Respiratory Health Outcomes in Adults

Chronic bronchitis has been associated with cigarette smoking as well as with e-cigarette use among young adults, but the association of chronic bronchitis in persons without airflow obstruction or clinical asthma, described as nonobstructive chronic bronchitis, with respiratory health outcomes remains uncertain. To assess whether nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes in adult ever smokers and never smokers. This prospective cohort study included 22 325 adults without initial airflow obstruction (defined as the ratio of forced expiratory volume in the first second [FEV1] to forced vital capacity [FVC] of <0.70) or clinical asthma at baseline. The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 9 US general population-based cohorts. Thus present study is based on data from 5 of these cohorts. Participants were enrolled from August 1971 through May 2007 and were followed up through December 2018. Nonobstructive chronic bronchitis was defined by questionnaire at baseline as both cough and phlegm for at least 3 months for at least 2 consecutive years. Lung function was measured by prebronchodilator spirometry. Hospitalizations and deaths due to chronic lower respiratory disease and respiratory disease-related mortality were defined by events adjudication and administrative criteria. Models were stratified by smoking status and adjusted for anthropometric, sociodemographic, and smoking-related factors. The comparison group was participants without nonobstructive chronic bronchitis. Among 22 325 adults included in the analysis, mean (SD) age was 53.0 (16.3) years (range, 18.0-95.0 years), 58.2% were female, 65.9% were non-Hispanic white, and 49.6% were ever smokers. Among 11 082 ever smokers with 99 869 person-years of follow-up, participants with nonobstructive chronic bronchitis (300 [2.7%]) had accelerated decreases in FEV1 (4.1 mL/y; 95% CI, 2.1-6.1 mL/y) and FVC (4.7 mL/y; 95% CI, 2.2-7.2 mL/y), increased risks of chronic lower respiratory disease-related hospitalization or mortality (hazard ratio [HR], 2.2; 95% CI, 1.7-2.7), and greater respiratory disease-related (HR, 2.0; 95% CI, 1.1-3.8) and all-cause mortality (HR, 1.5; 95% CI, 1.3-1.8) compared with ever smokers without nonobstructive chronic bronchitis. Among 11 243 never smokers with 120 004 person-years of follow-up, participants with nonobstructive chronic bronchitis (151 [1.3%]) had greater rates of chronic lower respiratory disease-related hospitalization or mortality (HR, 3.1; 95% CI, 2.1-4.5) compared with never smokers without nonobstructive chronic bronchitis. Nonobstructive chronic bronchitis was not associated with FEV1:FVC decline or incident airflow obstruction. The presence of at least 1 of the component symptoms of nonobstructive chronic bronchitis (ie, chronic cough or phlegm), which was common in both ever smokers (11.0%) and never smokers (6.7%), was associated with adverse respiratory health outcomes. The findings suggest that nonobstructive chronic bronchitis is associated with adverse respiratory health outcomes, particularly in ever smokers, and may be a high-risk phenotype suitable for risk stratification and targeted therapies.

Long-term Sequelae of Nonobstructive Chronic Bronchitis—Is Airflow Obstruction Important?

Long-term Sequelae of Nonobstructive Chronic Bronchitis—Is Airflow Obstruction Important?

Current asthma contributes as much as smoking to chronic bronchitis in middle age: a prospective population-based study.

Background and objectivePersonal smoking is widely regarded to be the primary cause of chronic bronchitis (CB) in adults, but with limited knowledge of contributions by other factors, including current asthma. We aimed to estimate the independent and relative contributions to adult CB from other potential influences spanning childhood to middle age.MethodsThe population-based Tasmanian Longitudinal Health Study cohort, people born in 1961, completed respiratory questionnaires and spirometry in 1968 (n=8,583). Thirty-seven years later, in 2004, two-thirds responded to a detailed postal survey (n=5,729), from which the presence of CB was established in middle age. A subsample (n=1,389) underwent postbronchodilator spirometry between 2006 and 2008 for the assessment of chronic airflow limitation, from which nonobstructive and obstructive CB were defined. Multivariable and multinomial logistic regression models were used to estimate relevant associations.ResultsThe prevalence of CB in middle age was 6.1% (95% confidence interval [CI]: 5.5, 6.8). Current asthma and/or wheezy breathing in middle age was independently associated with adult CB (odds ratio [OR]: 6.2 [95% CI: 4.6, 8.4]), and this estimate was significantly higher than for current smokers of at least 20 pack-years (OR: 3.0 [95% CI: 2.1, 4.3]). Current asthma and smoking in middle age were similarly associated with obstructive CB, in contrast to the association between allergy and nonobstructive CB. Childhood predictors included allergic history (OR: 1.3 [95% CI: 1.1, 1.7]), current asthma (OR: 1.8 [95% CI: 1.3, 2.7]), “episodic” childhood asthma (OR: 2.3 [95% CI: 1.4, 3.9]), and parental bronchitis symptoms (OR: 2.5 [95% CI: 1.6, 4.1]).ConclusionThe strong independent association between current asthma and CB in middle age suggests that this condition may be even more influential than personal smoking in a general population. The independent associations of childhood allergy and asthma, though not childhood bronchitis, as clinical predictors of adult CB raise the possibility of some of this burden having originated in childhood.

The clinical impact of non-obstructive chronic bronchitis in current and former smokers

As the clinical significance of chronic bronchitis among smokers without airflow obstruction is unclear, we sought to determine morbidity associated with this disorder. We examined subjects from the COPDGene study and compared those with FEV1/FVC ≥ 0.70, no diagnosis of asthma and chronic bronchitis as defined as a history of cough and phlegm production for ≥ 3 months/year for ≥ 2 years (NCB) to non-obstructed subjects without chronic bronchitis (CB-). Multivariate analysis was used to determine factors associated with and impact of NCB. We identified 597 NCB and 4283 CB- subjects. NCB participants were younger (55.4 vs. 57.2 years, p < 0.001) with greater tobacco exposure (42.9 vs. 37.8 pack-years, p < 0.001) and more often current smokers; more frequently reported occupational exposure to fumes (52.8% vs. 42.2%, p < 0.001), dust for ≥ 1 year (55.3% vs. 42.0%, p < 0.001) and were less likely to be currently working. NCB subjects demonstrated worse quality-of-life (SGRQ 35.6 vs. 15.1, p < 0.001) and exercise capacity (walk distance 415 vs. 449 m, p < 0.001) and more frequently reported respiratory "flare-ups" requiring treatment with antibiotics or steroids (0.30 vs. 0.10 annual events/subject, p < 0.001) prior to enrollment and during follow-up (0.34 vs. 0.16 annual events/subject, p < 0.001). In multivariate analysis, current smoking, GERD, sleep apnea and occupational exposures were significantly associated with NCB. While longitudinal data will be needed to determine whether NCB progresses to COPD, NCB patients have poorer quality-of-life, exercise capacity and frequent respiratory events. Beyond smoking cessation interventions, further research is warranted to determine the benefit of other therapeutics in this population. Clinical Trials Registration # NCT00608764 (http://clinicaltrials.gov/show/NCT00608764). Link to study protocol: http://www.copdgene.org/sites/default/files/COPDGeneProtocol-5-0_06-19-2009.pdf.

The value of blood plasma low-molecular-weight DNA for diagnostics of pathological processes of different genesis

The low-molecular-weight DNA appears in blood plasma a few hours after exposure of rats to ionizing radiation, and its content correlates directly with the irradiation dose. Cloning has shown, that the lowmolecular-weight DNA is enriched with C + G pairs and features of its primary structure characterize its capacity to form rather stable nucleosomes. DNA isolated after irradiation of rats with principally different doses 8 and 100 Gy differed not only quantitatively, but also by the content of the dinucleotides CpG and CpT; this suggests that they originate from different regions of the genome. It has been shown for the first time that exposure of animals to low-frequency noise results in an increase of the content of blood plasma low-molecular-weight DNA. Strokes are characterized by the increase of this DNA during 3 days after the beginning of the acute period, and dynamics of its excretion differs in patients with ischemic and hemorrhagic forms of this disease. In the case of ischemia low-molecular-weight DNA appears in cerebrospinal fluid. In contrast to patients with non-obstructive chronic bronchitis, patients with the chronic obstructive pulmonary disease in the state of remission are characterized by decreased levels of blood plasma low-molecular-weight DNA. The clear dependence between formation and specific features of the low-molecular-weight DNA fraction in blood plasma suggests that it may serve as a universal quantitative marker of apoptosis, which differentiates basically different conditions of the body.

Complex Analysis for Antiprotease–Protease Enzyme Gene Polymorphisms in Patients with Chronic Obstructive Pulmonary Diseases

Based on the protease-antiprotease hypothesis in the pathogenesis of chronic lung diseases, we investigated the influence of Z and S mutations and TaqI-polymorphism of alpha1-antitrypsin gene (PI) and Ala - 15Thr polymorphism in signal peptide of alpha1-antichymotrypsin gene (AACT) in patients with COPD (n = 239), nonobstructive chronic bronchitis (n = 34), brochiectases (n = 33), chronic infant lung disease (n = 151) and cystic fibrosis (n = 57). The allele and genotype frequency of any genetic polymorphism was not statistically different between the groups and control subjects (n = 225). Furthermore, promoter polymorphism G - 1607GG in interstitial collagenase gene (MMP1) was determined in patients with COPD, chronic nonobstructive bronchitis and bronchiectases. In patients with COPD it was marked prevalence of mutant homozygous genotype GG/GG compared to controls (30.6 % and 18.0%, respectively, OR = 1.99; 95% CI 1.11-3.59). These findings suggest that genetic polymorphism in the promoter of MMPI gene may be associated with individual susceptibility to the development of COPD.

The impact of smoking cessation on respiratory symptoms, lung function, airway hyperresponsiveness and inflammation.

Smoking is the main risk factor in the development of chronic obstructive pulmonary disease (COPD), and smoking cessation is the only effective treatment for avoiding or reducing the progression of this disease. Despite the fact that smoking cessation is a very important health issue, information about the underlying mechanisms of the effects of smoking cessation on the lungs is surprisingly scarce. It is likely that the reversibility of smoke-induced changes differs between smokers without chronic symptoms, smokers with nonobstructive chronic bronchitis and smokers with COPD. This review describes how these three groups differ regarding the effects of smoking cessation on respiratory symptoms, lung function (forced expiratory volume in one second), airway hyperresponsiveness, and pathological and inflammatory changes in the lung. Smoking cessation clearly improves respiratory symptoms and bronchial hyperresponsiveness, and prevents excessive decline in lung function in all three groups. Data from well-designed studies are lacking regarding the effects on inflammation and remodelling, and the few available studies show contradictory results. In chronic obstructive pulmonary disease, a few histopathological studies suggest that airway inflammation persists in exsmokers. Nevertheless, many studies have shown that smoking cessation improves the accelerated decline in forced expiratory volume in one second, which strongly indicates that important inflammatory and/or remodelling processes are positively affected.

Bronchial brush biopsies for studies of epithelial inflammation in stable asthma and nonobstructive chronic bronchitis.

Recently, bronchial brush biopsy (BBB) has been introduced as a complimentary method to bronchial forceps biopsy for the study of bronchial epithelial cells. We wanted to determine whether epithelial inflammatory cells in bronchial brush biopsies can reflect mucosal inflammation assessed indirectly by levels of cellular activation markers in bronchial lavage fluid. We studied 15 healthy controls, 11 asthmatics with regular steroid inhalation therapy, 13 asthmatics without steroids, and 10 smokers with nonobstructive chronic bronchitis. Differential counts of epithelial and inflammatory cells were made from the BBB material. Bronchial lavage levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, hyaluronan and interleukin-8 (IL-8) were measured as indirect markers for inflammatory cell activation. We found an increased percentage of eosinophil granulocytes in the BBB from the steroid-untreated asthmatic patients (1.16%) in comparison to the other groups (0.11%, 0.09% and 0.02%, respectively; p<0.01). In the steroid-untreated asthmatic patients, the percentage of eosinophils correlated with ECP in bronchial lavage fluid (r=0.73; p<0.01), indicating that the BBB method can reflect the degree of eosinophilic activation. A negative correlation was found for the percentage of eosinophils in BBB with levels of provocative concentration of methacholine causing a 20% fall in forced expiratory volume in one second (PC20) for the asthmatic patients in the study (r= -0.67; p<0.003). The bronchial brush biopsy method appears to give information on the changes present in superficial bronchial epithelium in inflammatory airways disease. These changes appear to relate to the degree of inflammatory activity and disease severity in asthma.

Circulating leukocyte adhesion molecules in stable asthma and nonobstructive chronic bronchitis.

Leukocyte adhesion molecules have been associated with airway inflammatory diseases such as asthma and obstructive chronic bronchitis. Lately, it has become possible to measure circulating forms of cell adhesion molecules (cCAMs) in body fluids. Elevated serum levels have been found in acute asthma and in obstructive chronic bronchitis. We investigated whether the patterns of cICAM-1, cVCAM-1, and cE-selectin could serve as markers for airway inflammation in stable asthma and stable nonobstructive chronic bronchitis. Small-volume bronchial lavage (BL) and serum from 15 controls, 13 asthmatics without steroid inhalation therapy, 11 asthmatics with regular steroid inhalation therapy, and 10 smokers with chronic bronchitis were analyzed. We found cICAM-1, cVCAM-1, and cE-selectin to be present in serum from patients with stable asthma and stable nonobstructive chronic bronchitis. Only cICAM-1 was found in BL fluid. No differences were seen between the subject groups for either cCAM, but levels of ECP were increased in the non-steroid-treated asthmatic group. Subject atopy or smoking did not increase the cCAM levels. In conclusion, the degree of airway inflammation in stable nonobstructive chronic bronchitis and stable asthma does not appear to be well associated with circulating ICAM-1, cVCAM-1, and cE-selectin.

Bronchial inflammation in chronic bronchitis assessed by measurement of cell products in bronchial lavage fluid.

Bronchial inflammation in chronic bronchitis has not been characterised as well as in asthma. The present study was undertaken to assess whether a characteristic pattern of bronchial inflammatory markers could be found in patients with chronic bronchitis. Bronchoscopy with bronchial lavage was performed in 42 patients with chronic bronchitis and in 13 healthy controls. Twenty three of the patients had non-obstructive chronic bronchitis and 19 had chronic bronchitis and chronic obstructive pulmonary disease (COPD). Eighteen of the patients with bronchitis had recurrent infective exacerbations and 24 did not. Intrabronchial bacterial cultures were taken with a protected specimen brush. Increased activity of neutrophils, fibroblasts, and eosinophils was found in the patients with chronic bronchitis as assessed by the levels of myeloperoxidase (MPO) and interleukin-8 (IL-8), hyaluronan, and eosinophil cationic protein (ECP), respectively. The levels of tryptase did not differ from the controls. High correlations were found between the levels of MPO and IL-8, as well as ECP and IL-8. No differences were found between the patients with COPD and those with non-obstructive chronic bronchitis. Recruitment and activation of both neutrophils and eosinophils seem to be a characteristic of chronic bronchitis. This activation is associated with IL-8. The patients with intrabronchial cultures of Streptococcus pneumoniae had the highest individual levels of MPO, ECP, and IL-8 of all subjects in the study, indicating that colonisation with S pneumoniae could promote bronchial inflammation.

Bacterial adhesion to oropharyngeal and bronchial epithelial cells in smokers with chronic bronchitis and in healthy nonsmokers

Bacterial adhesion is probably a prerequisite for colonization of mucous membranes, but adhesion to the bronchial mucosa has not been studied in detail. We investigated adhesion of respiratory pathogens to bronchial epithelial cells, and asked whether chronic bronchitis had an influence on bacterial adhesion. Oropharyngeal and bronchial cells were collected during bronchoscopy from 14 healthy nonsmokers, 22 smokers with nonobstructive chronic bronchitis, and 19 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD). Patients with a forced expiratory volume in one second (FEV1) less than 50% predicted were excluded. Adhesion of highly adherent test strains of H. influenzae and S. pneumoniae to these cells were studied. The test strains of H. influenzae and S. pneumoniae were found to adhere well to both oropharyngeal and bronchial cells. H. influenzae showed a higher degree of adhesion both to ciliated and goblet cells from the patients with nonobstructive bronchitis than to cells from the healthy nonsmokers. No corresponding difference was found for S. pneumoniae. The patients with COPD did not differ from the controls in their adhesion values. Our results indicate that bacterial adhesion is of importance for the colonization and retention of H. influenzae in the human airways. For S. pneumoniae the role of adhesion is more uncertain.

The intrabronchial microbial flora in chronic bronchitis patients: a target for N-acetylcysteine therapy?

Chronic bronchitis is common among smokers, often together with recurrent infectious exacerbations. Streptococcus pneumoniae and Haemophilus influenzae are the pathogens traditionally considered most important. N-acetylcysteine (NAC) treatment has been shown to reduce the number of infectious exacerbations in patients with chronic bronchitis. The mechanism behind this is unknown. We attempted to characterize the intrabronchial bacterial flora in patients with chronic bronchitis in an infection-free interval, and to determine whether pharmacological and immunological factors effected the bacterial occurrence. Twenty two smokers with non-obstructive chronic bronchitis, 19 smokers with chronic bronchitis and chronic obstructive pulmonary disease (COPD) and 14 healthy nonsmokers underwent bronchoscopy. To obtain uncontaminated intrabronchial samples, a protected specimen brush was used. Quantitative bacterial cultures and virus isolations were performed. Significantly positive bacterial cultures (> 1,000 colony-forming units (cfu).ml-1) were found only in the patients. S. pneumoniae and H. influenzae were found in five patients, and only in the patients without NAC treatment. The most common bacterium was alpha-haemolytic streptococcus. Negative cultures were more common in the healthy controls. Of the various factors examined, only NAC medication had an influence on bacterial numbers. Significantly fewer patients with NAC medication had positive cultures (3 out of 16) than in the group of patients without NAC therapy (15 out of 21). Our results confirm that chronic bronchitis in smokers leads to increased intrabronchial bacterial colonization. We could also confirm that 1,000 cfu.ml-1 is an adequate cut-off level for significant bacterial growth when using the protected specimen brush. NAC medication was associated with low bacterial numbers.

Influence of OM-85 BV on different humoral and cellular immune defense mechanisms of the respiratory tract.

To clarify the mode of action of an oral bacterial extract (OM-85 BV) on local airway immunity pre- and posttherapeutic washings from bronchoalveolar lavage (BAL) fluid of 28 adult patients with nonobstructive chronic bronchitis were analysed. In comparison to healthy controls, an elevation of total cell count due to an increased number of PMN leukocytes, and an impaired activity of the alveolar macrophages measured by the chemiluminescence response to opsonized zymosan was observed in patients with chronic bronchitis. After treatment with OM-85 BV, the BAL CD4+/CD8+ lymphocyte ratio and BAL interferon-gamma levels were increased. The alveolar macrophage activity was normalized and the BAL IgA was regulated from a reduced or hyperelevated to a moderately increased level.

Local Immunity in Patients with Chronic Bronchitis and the Effects of a Bacterial Extract, Broncho-Vaxom&lt;sup&gt;®&lt;/sup&gt;, on T Lymphocytes, Macrophages, Gamma-Interferon and Secretory Immunoglobulin A in Bronchoalveolar Lavage Fluid and Other Variables

In 28 adult patients with nonobstructive chronic bronchitis we investigated components of the immune system of the lower airways and the effects of treatment with Broncho-Vaxom (BV). An analysis of the washing from bronchoalveolar lavage (BAL) showed, in comparison with healthy controls, an elevation of total cell count (p = 0.003) as well as the IgA/albumin values (p = 0.02) and a reduction of the macrophage activity (p less than 0.001) in patients with chronic bronchitis. After BV a reduction in the total cell count (p = 0.05), an increase in the helper/suppressor T lymphocyte ratio (due mainly to the reduction in the suppressor cells; p = 0.04), a modulation of the IgA/albumin ratio, a stimulation of the impaired alveolar macrophage activity (p = 0.03) and increased concentrations of gamma-interferon (p = 0.03) were found in the BAL fluid of patients with chronic bronchitis. The salivary IgA/albumin ratio remained unchanged, the serum IgE concentration fell (p = 0.02) and the urinary IgA concentration rose (p = 0.002). Bronchial mucosa lesions, evaluated endoscopically in terms of structural damage, hyperemia and mucus production, were improved (p less than 0.01). These findings indicate that orally administered BV modulates disordered local and systemic immune functions in patients with chronic bronchitis.