Severe Chronic Bronchitis Research Articles

The expression of selected fibrotic factors in COPD and asthma.

Chronic Obstructive Pulmonary Disease (COPD) and asthma are associated with chronic inflammation leading to airway obstruction and remodelling. There is little information on possible differences in the TGFB signalling pathway in the pathologies compared to less severe chronic bronchitis without airway obstruction. To assess the expression of the selected TGFB signalling pathway-associated genes in the pathologies. RT-PCR was used to quantify the mRNAs in bronchoalveolar cells obtained from the Czech patients with chronic bronchitis (n = 26), COPD (n = 22), asthmatic (n = 14) patients. There was no difference in the BAL cell expression of TGFB1-3, TGFBR1-2, SMAD2,4,5, and 7 between our patients with COPD and those with chronic bronchitis. The expressions were also similar in the patients with asthma and chronic bronchitis. There was no difference between the patients with asthma and COPD. Although we observed no differences in our patients, other studies should investigate the genes and their possible correlation with advanced airway obstruction and emphysematous changes (Tab. 2, Fig. 3, Ref. 27). Text in PDF www.elis.sk Keywords: TGFB signalling pathway, COPD, asthma, chronic bronchitis, bronchoalveolar lavage.

Changes in the activity of enzymes in the blood in nonspecific lung diseases

Level of different ensymes was determined in blood serum of patients with bronchial asthma, chronic obstructive bronchitis, chronic nonobstructive bronchitis, pneumonia and 22 healthy persons. In severe chronic obstructive bronchitis in contrast to bronchial asthma, the increase of activity in blood serum was found which can serve as a differential and diagnostic indicator. In the acute phase of pneumonia and severe chronic nonobstructive bronchitis the increase of alkaline phosphatase, gamma-glutanul transferase activities occurred, and in pneumonia activity of aminotransferases increased as well. By discharde of patients from the hospital the studied indicators remained elevated. It is necessary to continul the search of further ways of Correction of enzyme changes with estimation of prognostic value of some indicators in case of favoreble outcome of pulmonary diseases.

Effect of the inhalation inhibitor PDE-4 CHF6001 on some pathogenetic links in chronic obstructive pulmonary disease development

CHF6001 is a new inhaled phosphodiesterase-4 inhibitor that is safe and well tolerated by both healthy people and patients with bronchial asthma. The effect of CHF6001, in addition to standard triple therapy for chronic obstructive pulmonary disease, was evaluated on some inflammatory markers in induced sputum and blood in 61 patients (54 completed the study) with chronic obstructive pulmonary disease and chronic bronchitis. From October 2016 to November 2017, a multicenter, three-period (every 32 days), tripartite, placebo-controlled, double-blind, complete block cross-sectional study was conducted in Great Britain and Germany. Patients were treated by CHF6001 at doses of 800 or 1600 g, or the corresponding placebo using the dry powder inhaler NEXThaler. The induced sputum was collected on day 1 before the treatment and days 20, 26, and 32 after the treatment. Blood was also collected on day 1 before the treatment and day 32 before and after the treatment. Result analyses took into account the inflammatory biomarkers in induced sputum and blood, respiratory function, and symptoms and side effects. CHF6001, which supplements triple therapy in patients with moderate to severe chronic obstructive pulmonary disease and chronic bronchitis, was well tolerated and significantly reduces the number of key biomarkers of airway inflammation in sputum and blood after 32 days of treatment. CHF6001, administered by inhalation, creates a high therapeutic concentration in the lungs compared with other systemic phosphodiesterase-4 inhibitors and improves the therapeutic index due to anti-inflammatory effects while minimizing the possible side effects typical of the latter.

Identification of the Phytoconstituents in Methanolic Extract of Adhatoda Vasica L. Leaves by GC-MS Analysis and Its Antioxidant Activity.

Adhatoda vasica L. is a medicinal plant, known as Malabar nut in English, belonging to the family Acanthaceae. It has been used traditionally to treat respiratory disorders like severe coughs, colds, chronic bronchitis, asthma, tuberculosis, and other illnesses. The multifunctional range of bioactives found in it has piqued the interest of pharmaceutical companies, who are looking for more evidence-based ways to develop new formulations. To analyse the A. vasica leaves by GC-MS technique and evaluation of its antioxidant activity. Methanolic extract of A. vasica L. (MEAV) leaves was analyzed by GC-MS for identification and characterization of its bioactives and traditional therapeutic claims. A widely anticipated 2,2-diphenyl-1-picrylhydrazyl (DPPH) method was used to determine the antioxidant activity of MEAV. The major compounds revealed in MEAV leaves are: 1,3,5-triazine-2,4,6-triamine (3.06%); 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one (5.35%); 5-hydroxymethylfurfural (16.82%); 2-butylphenol (6.85%); 3,4-dihydroxy-5-methyl-dihydro-furan-2-on (2.5%); 2(OR 3)-(1,1-dimethylethyl)-4-methoxyphenol (3.52%); megastigmatrienone 3 (1.02%); tetradecanoic acid (1.52%); vomifoliol (0.58%); oxalic acid, cyclobutylhexyl ester (6.03%); hexadecanoic acid (6.06%); 4-ethyl-2-oxo-2,5,6,7-tetrahydro-1H-cyclopenta[B]pyridine-3-carbonitrile (10.08%); phytol (2.01%); and vitamin E (3.18%). A significant reduction in free radicals against DPPH was observed, which revealed the antioxidant potential of MEAV. MEAV consists of both polar and nonpolar components. GC-MS analysis was used to identify these compounds. The current work validates that the antioxidant activity of MEAV is attributed to the presence of compounds such as vitamin E and terpenes. This work validates the antioxidant activity of methanolic extract of A. vasica attributed to the presence of compounds like vitamin E and terpenes.

PP128 Quantifying The Relative Importance Of Chronic Obstructive Pulmonary Disease Symptoms To Patients

IntroductionPrevious qualitative research analyzing social media and online community discussions highlighted the symptomatic burden of cough and mucus (sputum), alongside shortness of breath, in patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to determine the relative importance of these symptoms and their consequences (for example, disturbed sleep) to COPD patients, compared with conventional COPD endpoints (lung function and exacerbations).MethodsA total of 1,050 patients (at least 40 years of age) with moderate to severe COPD or chronic bronchitis, and regular symptoms of cough and excess mucus production, are to be recruited through patient advocacy groups (PAGs) from five countries (Australia, France, Japan, the United Kingdom, and the United States; 150 to 400 patients per country). A discrete choice experiment was designed with input from clinical experts and the PAGs, plus scientific advice from the National Institute for Health and Care Excellence (NICE) in the United Kingdom. Patients’ preferences for the conditional relative importance of symptoms and impact of COPD will be quantified based on trade-offs they are willing to make among hypothetical COPD disease state profiles, described by differing attributes and levels. Hierarchical Bayesian analysis with effect-coding parameterization will be undertaken on the choice data to estimate (using Gibbs sampling) the relative value each respondent places on an attribute level.ResultsThe feedback from NICE informed the selection of screening criteria and the statistical analysis plan, as well as the inclusion of a health status measure, the EQ-5D-3L. Qualitative patient interviews and pilot testing of the attributes and levels grid have been completed, informing finalization of the online survey design.ConclusionsPatient preference studies evaluating the relative importance of symptom burden through assessment of disease state preference values are an important new form of patient-based evidence for informing value-based decision making in HTA. The present study should facilitate a more patient-centered approach to developing new treatments for and improving the care of patients with COPD.

P53 in Bronchial Club Cells Facilitates Chronic Lung Inflammation by Promoting Senescence

The tumor suppressor p53 limits tumorigenesis by inducing apoptosis, cell cycle arrest, and senescence. Although p53 is known to limit inflammation during tumor development, its role in regulating chronic lung inflammation is less well understood. To elucidate the function of airway epithelial p53 in such inflammation, we subjected genetically modified mice, whose bronchial epithelial club cells lack p53, to repetitive inhalations of lipopolysaccharide (LPS), an exposure that leads to severe chronic bronchitis and airway senescence in wild-type mice. Surprisingly, the club cell p53 knockout mice exhibited reduced airway senescence and bronchitis in response to chronic LPS exposure and were significantly protected from global lung destruction. Furthermore, pharmacological elimination of senescent cells also protected wild-type mice from chronic LPS-induced bronchitis. Our results implicate p53 ininduction of club-cell senescence and correlate epithelial cell senescence of chronic airway inflammation and lung destruction.

Roflumilast: A Review in COPD.

Roflumilast (Daliresp®, Daxas®) is a selective phosphodiesterase 4 (PDE4) inhibitor that decreases systemic and pulmonary inflammation and improves disease symptoms in patients with severe chronic obstructive pulmonary disease (COPD). This article reviews the pharmacological properties of roflumilast and its clinical efficacy and tolerability in patients with COPD. Roflumilast is an effective treatment in patients with moderate to severe COPD; it improves lung function and is generally associated with a lower risk of exacerbation, particularly in patients with more severe disease and/or chronic bronchitis, cough and sputum. It is generally well tolerated; the most common adverse event was diarrhoea. While associated with an increased risk of psychiatric adverse events and weight loss, roflumilast is not associated with an increased risk of respiratory disease and infection, and may decrease the risk of cardiovascular adverse events. Roflumilast is a useful addition to the treatment options for patients with COPD.

Two cases of COPD benefitting from therapy with roflumilast

Two clinical cases of chronic obstructive pulmonary disease (COPD) stage II patients are reported here. One case refers to a patient with hypoxemia associated to severe air flow limitation, chronic bronchitis and frequent exacerbation events. A significant improvement of patient’s conditions was observed after pharmacological treatment with roflumilast. The second case refers to a patient who refused to adhere to prescribed therapy but adhered to roflumilast therapy, eventually achieving a good response. Both cases highlight roflumilast’s efficacy in improving health conditions of COPD patients.

Effect of roflumilast on exacerbations in patients with severe chronic obstructive pulmonary disease uncontrolled by combination therapy (REACT): a multicentre randomised controlled trial

Roflumilast reduces exacerbations in patients with severe chronic obstructive pulmonary disease. Its effect in patients using fixed combinations of inhaled corticosteroids and longacting β2 agonists is unknown. We postulated that roflumilast would reduce exacerbations in patients with severe chronic obstructive pulmonary disease at risk for exacerbations, even in combination with inhaled corticosteroid and longacting β2 agonist treatment. For this 1-year double-blind, placebo-controlled, parallel group, multicentre, phase 3-4 trial, the Roflumilast and Exacerbations in patients receiving Appropriate Combination Therapy (REACT) study, we enrolled patients with severe chronic obstructive pulmonary disease from 203 centres (outpatient clinics, hospitals, specialised pulmonologists, and family doctors) in 21 countries. Eligible patients were 40 years of age or older with a smoking history of at least 20 pack-years and a diagnosis of chronic obstructive pulmonary disease with severe airflow limitation, symptoms of chronic bronchitis, and at least two exacerbations in the previous year. We used a computerised central randomisation system to randomly assign patients in a 1:1 ratio to the two treatment groups: roflumilast 500 μg or placebo given orally once daily together with a fixed inhaled corticosteroid and longacting β2 agonist combination. Background tiotropium treatment was allowed. All patients and investigators were masked to group assignment. The primary outcome was the rate of moderate to severe chronic obstructive pulmonary disease exacerbations per patient per year, analysed by intention to treat. This study is registered with ClinicalTrials.gov, number NCT01329029. Between April 3, 2011, and May 27, 2014, we enrolled 1945 eligible participants and randomly assigned 973 to the roflumilast group and 972 to the placebo group. The rate of moderate-to-severe chronic obstructive pulmonary disease exacerbations was 13·2% lower in the roflumilast group than in the placebo group according to a Poisson regression analysis (roflumilast 0·805 vs placebo 0·927; rate ratio [RR] 0·868 [95% CI 0·753-1·002], p=0·0529), and 14·2% lower according to a predefined sensitivity analysis using negative binomial regression (0·823 vs 0·959; 0·858 [0·740-0·995], p=0·0424). Adverse events were reported by 648 (67%) of 968 patients receiving roflumilast and by 572 (59%) of 967 patients in the placebo group; adverse event-associated patient withdrawal from the study was also more common in the roflumilast group (104/968 [11%]) than in the placebo group (52/967 [5%]). The most frequently reported serious adverse events were chronic obstructive pulmonary disease exacerbations and pneumonia, and 17 (1·8%) deaths occurred in the roflumilast group compared with 18 (1·9%) in the placebo group. Our findings suggest that roflumilast reduces exacerbations and hospital admissions in patients with severe chronic obstructive pulmonary disease and chronic bronchitis who are at risk of frequent and severe exacerbations despite inhaled corticosteroid and longacting β2 agonist therapy, even in combination with tiotropium. Takeda.

Diagnosis and pharmacotherapy of stable chronic obstructive pulmonary disease: the finnish guidelines.

The Finnish Medical Society Duodecim initiated and managed the update of the Finnish national guideline for chronic obstructive pulmonary disease (COPD). The Finnish COPD guideline was revised to acknowledge the progress in diagnosis and management of COPD. This Finnish COPD guideline in English language is a part of the original guideline and focuses on the diagnosis, assessment and pharmacotherapy of stable COPD. It is intended to be used mainly in primary health care but not forgetting respiratory specialists and other healthcare workers. The new recommendations and statements are based on the best evidence available from the medical literature, other published national guidelines and the GOLD (Global Initiative for Chronic Obstructive Lung Disease) report. This guideline introduces the diagnostic approach, differential diagnostics towards asthma, assessment and treatment strategy to control symptoms and to prevent exacerbations. The pharmacotherapy is based on the symptoms and a clinical phenotype of the individual patient. The guideline defines three clinically relevant phenotypes including the low and high exacerbation risk phenotypes and the neglected asthma–COPD overlap syndrome (ACOS). These clinical phenotypes can help clinicians to identify patients that respond to specific pharmacological interventions. For the low exacerbation risk phenotype, pharmacotherapy with short-acting β2-agonists (salbutamol, terbutaline) or anticholinergics (ipratropium) or their combination (fenoterol–ipratropium) is recommended in patients with less symptoms. If short-acting bronchodilators are not enough to control symptoms, a long-acting β2-agonist (formoterol, indacaterol, olodaterol or salmeterol) or a long-acting anticholinergic (muscarinic receptor antagonists; aclidinium, glycopyrronium, tiotropium, umeclidinium) or their combination is recommended. For the high exacerbation risk phenotype, pharmacotherapy with a long-acting anticholinergic or a fixed combination of an inhaled glucocorticoid and a long-acting β2-agonist (budesonide–formoterol, beclomethasone dipropionate–formoterol, fluticasone propionate–salmeterol or fluticasone furoate–vilanterol) is recommended as a first choice. Other treatment options for this phenotype include combination of long-acting bronchodilators given from separate inhalers or as a fixed combination (glycopyrronium–indacaterol or umeclidinium–vilanterol) or a triple combination of an inhaled glucocorticoid, a long-acting β2-agonist and a long-acting anticholinergic. If the patient has severe-to-very severe COPD (FEV1 < 50% predicted), chronic bronchitis and frequent exacerbations despite long-acting bronchodilators, the pharmacotherapy may include also roflumilast. ACOS is a phenotype of COPD in which there are features that comply with both asthma and COPD. Patients belonging to this phenotype have usually been excluded from studies evaluating the effects of drugs both in asthma and in COPD. Thus, evidence-based recommendation of treatment cannot be given. The treatment should cover both diseases. Generally, the therapy should include at least inhaled glucocorticoids (beclomethasone dipropionate, budesonide, ciclesonide, fluticasone furoate, fluticasone propionate or mometasone) combined with a long-acting bronchodilator (β2-agonist or anticholinergic or both).

Vulnerable COPD patients with comorbidities: the role of roflumilast.

Roflumilast is a selective phosphodiesterase-4 (PDE-4) inhibitor that was approved by the US Food and Drug Administration in February 2011 for the management of chronic obstructive pulmonary disease (COPD). Literature was retrieved through PubMed using the terms “roflumilast” and “COPD”. Reference citations from publications identified were also reviewed. All articles published in English using the terms “roflumilast” and “COPD” were retrieved. For evaluation of clinical efficacy, published Phase III studies and pooled analyses of Phase III trials were included. In seven published Phase III trials, roflumilast at 500 μg daily showed improvements in lung function as measured by pre- and post-bronchodilator forced expiratory volume in 1 second. Roflumilast appears to be useful in vulnerable patients who are at high risk for exacerbations. Roflumilast was found to be effective when administered alone and with concomitant long-acting bronchodilator therapy in the Caucasian and Asian population. Patients with severe-to-very severe COPD, chronic bronchitis, and frequent history of exacerbations derived the greatest benefit with roflumilast. Compared to the standard of care therapies, roflumilast is more cost-prohibitive. Roflumilast was well tolerated, with the most common adverse events observed in clinical trials being diarrhea, nausea, and headache. Weight loss and increased risk of psychiatric events have also been observed with roflumilast in clinical trials. Roflumilast is a safe and effective option for the treatment of COPD.

Clinico- Immunological Parallels in Chronic Obstructive Bronchitis in Adolescents

The aim of this work was to study the concentration of IL-8 in conjunction with clinical and functional parameters of the COB in adolescents. Surveyed 52 teenagers and young men suffering from COB aged 11 to 21 years old. The control group consisted of 22 healthy individuals. Options for clinical COB 3 subgroups were identified. To examine the extent of production of IL-8, depending on the severity of the disease showed that IL- 8 levels in the serum increased significantly PC. It is noted that higher concentrations of IL- 8 cytokine was observed in patients with severe chronic obstructive bronchitis. ERF also made observations in these patients, depending on the stage and severity of disease. When functional examination in adolescents with COB were indicators showed a reduction in FVC, FEV1, PEF, MEF25, MEF50, MEF75, MEF25-75 which corresponded to a mixed disorders of pulmonary ventilation function with a predominance of obstructive variant. Thus, in patients with COB stradayushih adolescent relationship marked functional performance parameters of pulmonary cytokine status, in particular IL- 8.

MANAGEMENT OF CHRONIC BRONCHITIS: A CLINICAL STUDY

Chronic Bronchitis is a common condition which is characterized by persistent cough, with expectoration for at least three months of the year for t wo consecutive years. It is more prevalent these days because of the exposure to both active and passive smoke, air pollution, occupational hazards etc; Prevalence is directly related to that of tobacco chewing, smoking and excess usage of biomass fuels es pecially in low and middle income countries. Current estimate suggest that 80 million people worldwide suffer from moderate to severe chronic obstructive bronchitis. In India this is the second most common disorder after pulmonary tuberculosis. Kaphaja Kas a, a Vata Kapha pradhana pranavaha srotovikara, bears a greater resemblance with Chronic Bronchitis. In the present situation as there is a need to come up with a more comprehensive, economical and safe medication, a clinical observational study was conduc ted to evaluate the combined effect of Pippalyadi Qwatha, Shatyadi leha and Vasa Swarasa in the management of chronic bronchitis. Total 50 patients were incidentally selected and assigned into single group. All patients were administered with Pippalyadi qw atha, Shatyadi leha and Vasa Swarasa for 48 days. Data was collected on 0 day, 15 th day, 30 th day and 48 th day of study period. Results were statistically analyzed before and after the treatment. Combined effect of drugs showed statistically highly signifi cant results with 'P' value 0.000. Overall assessment showed marked relief in 22 patients followed by 26 patients with Moderate relief and 2 patients with no relief.

Severe Chronic Bronchitis in Advanced Emphysema Increases Mortality and Hospitalizations

Background: Chronic bronchitis in COPD has been associated with an increased exacerbation rate, more hospitalizations, and an accelerated decline in lung function. The clinical characteristics of patients with advanced emphysema and chronic bronchitis have not been well described. Methods: Patients randomized to medical therapy in the National Emphysema Treatment Trial were grouped based on their reports of cough and phlegm on the St. George's Respiratory Questionnaire(SGRQ) at baseline: chronic bronchitis(CB+) and no chronic bronchitis(CB–). The patients were similarly categorized into severe chronic bronchitis(SCB+) or no severe chronic bronchitis (SCB–) based on the above definition plus report of chest trouble. Kaplan-Meier survival analysis was used to determine the relationships between chronic bronchitis and severe chronic bronchitis and survival and time to hospitalization. Lung function and SGRQ scores over time were compared between groups. Results: The CB+(N = 234; 38%) and CB- groups(N = 376; 62%) had similar survival (median 60.8 versus 65.7 months, p = 0.19) and time to hospitalization (median 26.9 versus 24.9 months, p = 0.84). The SCB+ group(N = 74; 12%) had worse survival (median 47.7 versus 65.7 months, p = 0.02) and shorter time to hospitalization (median 18.5 versus 26.7 months, p = 0.02) than the SCB- group (N = 536; 88%). Mortality and hospitalization rates were not increased when chest trouble was analyzed by itself. The CB+ and CB–groups had similar lung function and SGRQ scores over time. The SCB+ and SCB–groups had similar lung function over time, but the SCB+ group had significantly worse SGRQ scores. Conclusions: Severe chronic bronchitis is associated with worse survival, shorter time to hospitalization, and worse health-related quality of life.

Aortic Valve Replacement in Octogenarians With Severe Aortic Stenosis. Experience in a Series of Consecutive Patients at a Single Center

Greater life-expectancy has led to an increase in the incidence of severe aortic stenosis, which accounts for a significant proportion of the workload of cardiology departments. With the imminent arrival of percutaneous aortic valve prostheses, it is important to know how effective surgery currently is in octogenarians. The study included all patients aged >or=80 years with severe aortic stenosis who underwent cardiac catheterization prior to aortic valve replacement between May 1996 and May 2006. The percentage of patients who underwent surgery, outcomes at 30 days, long-term survival, and predictors of mortality were analyzed. Of the 137 patients evaluated, 104 (75.9%) underwent surgery, while 33 did not due to a low ejection fraction or severe chronic bronchitis, or because the patient's family did not give consent. The patients' mean age was 81.7 (1.5) years, 61.5% were female, 18.4% had diabetes, 7.8% had had a previous infarction, and 32.7% had coronary disease. Three patients (2.9%) had a perioperative myocardial infarction, six (5.8%) had a stroke, and six (5.8%) had a permanent pacemaker. Four patients (3.8%) died during the first 30 days. The survival rates at 1, 2, 3, 4, 5 and 6 years were 90 (2.9), 81 (4.2), 78 (4.8), 75 (5.3), 65 (7.2) and 60 (8.2)%, respectively. The following predictors of long-term mortality were identified: creatinine level, emergency surgery, and reintervention because of bleeding. Some 76.3% of patients remained in New York Heart Association functional class I-IV. Aortic valve replacement can be performed successfully in patients aged >or=80 years with severe aortic stenosis; the complication rate was low, and the survival rate and long-term results were good. Predictors of mortality in this series were the creatinine level, emergency surgery, and reintervention because of bleeding.

Prone position improves expiratory airway mechanics in severe chronic bronchitis

Based on lung parenchyma-airways' interdependence, the present authors hypothesised that prone positioning may reduce airway resistance in severe chronic bronchitis. A total of 10 anaesthetised/mechanically ventilated patients were enrolled. Partitioned respiratory system (RS) mechanics during iso-flow experiments (flow = 0.91 L x s(-1), tidal volume (VT) varied within 0.2-1.2 L), haemodynamics, gas-exchange, expiratory airway resistance (Raw,exp), functional residual capacity (FRC), change in FRC (DeltaFRC), end-expiratory lung volume (EELV), expiratory airway resistance at EELV (Raw,exp,EELV), intrinsic positive end-expiratory pressure (PEEPi), and mean end-expiratory flow were determined in baseline semirecumbent (SRBAS), prone, and post-prone semirecumbent (SRPP) postures. Pronation versus SRBAS resulted in significantly reduced Raw,exp (at VT > or =0.8 L), Raw,exp,EELV (18.3+/-1.4 versus 31.6+/-2.6 cm H2O x L(-1) x s(-1)), inspiratory airway resistance (at VT > or =1.0 L), static lung elastance (at VT < or =0.6 L), "additional" RS/lung resistance (at a range of VTs), DeltaFRC (0.35+/-0.03 versus 0.47+/-0.03 L), EELV (4.92+/-0.49 versus 5.65+/-0.65 L), RS/lung PEEPi (6.7+/-1.1/5.4+/-0.6 versus 8.9+/-1.7/7.8+/-1.1 cm H2O), mean end-expiratory flow (63.9+/-4.2 versus 47.9+/-4.0 mL x s(-1)), and shunt fraction (0.16+/-0.03 versus 0.21+/-0.03); benefits were reversed in SRPP. In severe chronic bronchitis, prone positioning reduces airway resistance and dynamic hyperinflation.

Epidemiology of Chlamydia pneumoniae

Chlamydia pneumoniae is the most commonly occurring intracellular bacterial pathogen. It is frequently involved in respiratory tract infections and to a lesser degree in extrapulmonary diseases. According to seroepidemiologic surveys, C. pneumoniae infection seems to be both endemic and epidemic. Such studies indicate that C. pneumoniae infection is widespread, with frequent reinfection during a lifetime. In Western countries the highest rate of new infections occurs between the ages of 5 and 15. The antibody prevalence worldwide is higher in adult males than in females. Currently available data suggest that C. pneumoniae is primarily transmitted from human to human without any animal reservoir. Transmission seems to be inefficient, although household outbreaks with high transmission rates are reported. Most reports rank C. pneumoniae among the three most common etiologic agents of community-acquired pneumonia, with an incidence ranging from 6% to 25%, and generally presenting a mild and, in some cases, self-limiting clinical course. Recent reports also indicate a possible role for C. pneumoniae in severe forms of community-acquired pneumonia and in respiratory infections in immunocompromised patients. C. pneumoniae infection has also been implicated in the pathogenesis of asthma in both adults and children. The hypothesis that C. pneumoniae infection could lead to asthma is based on clinical studies and on the evidence of specific IgE production, direct epithelial damage, induction of T-cell immunopathologic diseases, and vascular smooth cell infection. Chronic C. pneumoniae infection seems to be common in patients with chronic bronchitis whether exacerbated or not, and is characterized by a strong humoral immune response to this intracellular microorganism, which is present in the majority of patients with severe chronic bronchitis. More than 60% of subjects with chronic bronchitis have specific C. pneumoniae antibody titers, and the microorganism may be identified by culture or PCR in almost 40% of these patients. This pathogen has also been recently associated with atherosclerosis and coronary heart disease (CHD). Seroepidemiological evidence indicates that the majority of patients with CHD present an anti-C. pneumoniae antibody pattern consistent with chronic infection. Furthermore, C. pneumoniae has been detected in atherosclerotic coronary plaques by several methods, including immunocytochemistry, transmission electron microscopy and molecular biology techniques. Recently, we detected C. pneumoniae DNA in a high percentage (51%) of aortic aneurysm plaques. Moreover, our serologic data support the hypothesis that a chronic C. pneumoniae antibody pattern may be a possible risk marker for atherosclerosis. Recently, C. pneumoniae has been isolated by culture from the coronary artery of a patient with coronary atherosclerosis, providing direct evidence of the presence of viable organisms in atheromatous lesions. Moreover, we recently demonstrated an association between C. pneumoniae reinfection and acute myocardial infarction.

Chronic glandular bronchitis in young individuals residing in a metropolitan area.

A study of 161 Los Angeles County residents aged 12-28 years old who had died sudden violent deaths showed frequent and severe chronic glandular bronchitis (CGB), that is to say grade > or =5 (0-10) chronic inflammation involving at least one, half or more, and all submucosal glands in 53.4%, 21%, and 4.4% of the main stem bronchi, respectively. The mean plasma cell/gland/bronchus was high (> or =5) for 22 subjects (13.7%), while only 2 bronchi (1.2%) had a correspondingly high lymphocyte mean (P<0.001). Of the bronchi, 75.2% were affected by glandular atrophy (> or =5 in 8.1%), 10.6% had neutrophil infiltration of glands, and 3.1% had acute sialadenitis. Of the total of 1040 glands, CGB was found in 83.8% (> or =5 in 26.5%). Of 25 non-smokers identified, 14 (56%) had some degree of CGB in > or =50% of the glands, severe in 7 (26%). Severe CGB in many young individuals raises concern that a subpopulation of living cohorts may have an increased susceptibility to disease and a rising incidence of chronic lung disease. Demographic analysis is pending, but respiratory infection, smoking, adverse socioeconomic factors, and air pollution are all potential causative factors. Since pollution in Los Angeles frequently exceeds air quality standards, an ongoing multicity study is attempting to distinguish between the suspected effects of air pollution and confounding variables.

A 1-Year Community-Based Health Economic Study of Ciprofloxacin vs Usual Antibiotic Treatment in Acute Exacerbations of Chronic Bronchitis: The Canadian Ciprofloxacin Health Economic Study Group

To evaluate the costs, consequences, effectiveness, and safety of ciprofloxacin vs standard antibiotic care in patients with an initial acute exacerbation of chronic bronchitis (AECB) as well as recurrent AECBs over a 1-year period.Randomized, multicenter, parallel-group, open-label study.Outpatient general practice.A total of 240 patients, 18 years or older with chronic bronchitis, with a history of frequent exacerbations (three or more in the past year) presenting with a type 1 or 2 AECB (two or more of increased dyspnea, increased sputum volume, or sputum purulence).The assessment included AECB symptoms, antibiotics prescribed, concomitant medications, adverse events, hospitalizations, emergency department visits, outpatient resources such as diagnostic tests, procedures, and patient and caregiver out-of-pocket expenses. Patients completed the Nottingham Health Profile, St. George's Respiratory Questionnaire, and the Health Utilities Index. The parameters were recorded with each AECB and at regular quarterly intervals for 1 year. These variables were compared between the ciprofloxacin-treated group and the usual-care-treated group.Patients receiving ciprofloxacin experienced a median of two AECBs per patient compared to a median of three AECBs per patient receiving usual care. The mean annualized total number of AECB-symptom days was 42.9+/-2.8 in the ciprofloxacin arm compared to 45.6+/-3.0 days in the usual-care arm (p=0.50). The overall duration of the average AECB was 15.2+/-0.6 days for the ciprofloxacin arm compared to 16.3+/-0.6 days for the usual-care arm. Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care (relative risk=1.20; 95% confidence interval [CI], 0.91 to 1.58; p=0.19). Treatment assignment did not affect the interexacerbation period but a history of severe bronchitis, prolonged chronic bronchitis, and an increased number of AECBs in the past year were associated with shorter exacerbations-free periods. There was a slight, but not statistically significant, improvement in all quality of life measures with ciprofloxacin over usual care. The only factors predictive of hospitalization were duration of chronic bronchitis (odds ratio=4.6; 95% CI, 1.6, 13.0) and severity of chronic bronchitis (odds ratio=4.3; 95% CI, 0.8, 24.6). The incremental cost difference of $578 Canadian in favor of usual care was not significant (95% CI, -$778, $1,932). The cost for the ciprofloxacin arm over the usual care arm was $18,588 Canadian per quality-adjusted life year gained. When the simple base case analysis was expanded to examine the effect of risk stratification, the presence of moderate or severe bronchitis and at least four AECBs in the previous year changed the economic and clinical analysis to one favorable to ciprofloxacin with the ciprofloxacin-treated group having a better clinical outcome at lower cost ("win-win" scenario).Treatment with ciprofloxacin tended to accelerate the resolution of all AECBs compared to usual care; however, the difference was not statistically significant. Further, usual care was found to be more reflective of best available care rather than usual first-line agents such as amoxicillin, tetracycline, or trimethoprim-sulfamethoxazole as originally expected. Despite the similar antimicrobial activities and broad-spectrum coverage of both ciprofloxacin and usual care, the trends in clinical outcomes and all quality of life measurements favor ciprofloxacin. In patients suffering from an AECB with a history of moderate to severe chronic bronchitis and at least four AECBs in the previous year, ciprofloxacin treatment offered substantial clinical and economic benefits. In these patients, ciprofloxacin may be the preferred first antimicrobial choice.

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.