The Effect of Pulmonary Rehabilitation in Mountain Environment on Exercise Capacity and Quality of Life in Patients with Chronic Obstructive Pulmonary Disease (COPD) and Chronic Bronchitis.

BACKGROUND We aimed to test the effectiveness of the pulmonary rehabilitation in a mountain environment on the pulmonary function, physical performance, dyspnea, affective factors, and quality of life (QoL) in patients with chronic obstructive pulmonary disease (COPD) and chronic bronchitis (CB), as well as to determine predictors of clinical improvement. MATERIAL AND METHODS 128 consecutive patients (90 diagnosed with COPD and 38 diagnosed with CB) underwent comprehensive pulmonary rehabilitation for a duration of 3 weeks in one of 3 mountain health resorts in the High Tatras. The examination included spirometry (FEV1 and FEV1/FVC), 6-minute walk test (6MWT), Borg scale of dyspnea, and assessment of depression (Zung score), anxiety (Beck score), and QoL using the SF-36 scales. RESULTS After the study intervention, all patients in both monitored groups demonstrated significant improvements in objective measurements in which large treatment effect was achieved (for FEV1 η²=0.218, for 6MWT η²=0.771). Similarly, in subjective measurements a large effect was achieved (for the Beck score: η²=0.599, for the Zung score: η²=0.536). QoL improved after the intervention in all the monitored SF-36 scales in both groups (P<0.001 for all). In patients with COPD, the improvement of exercise capacity was positively correlated with baseline 6MWT and FEV1, and negatively with the Beck anxiety score and the Borg dyspnea score, whereas, only improvement in the mental summary component of QoL was negatively correlated with baseline 6MWT and FEV1 (P<0.05 for all). CONCLUSIONS Rehabilitation in a mountain environment has proven to be effective in both the reported diagnoses of COPD and CB. Improvements in both functional and subjective indicators were observed. These findings support the use of this treatment modality.

Effect of ELOM-080 on exacerbations and symptoms in COPD patients with a chronic bronchitis phenotype - a post-hoc analysis of a randomized, double-blind, placebo-controlled clinical trial.

BACKGROUND: Treating symptoms and preventing exacerbations are key components of chronic obstructive pulmonary disease (COPD) long-term management. Recently, a more tailored treatment approach has been proposed, in particular for two well-established clinical phenotypes, frequent exacerbators and chronic bronchitis-dominant COPD. ELOM-080 has demonstrated clinical efficacy in treating symptoms and preventing exacerbations in subjects with chronic bronchitis. However, little is known about the potential effects of ELOM-080 in COPD patients. AIM: To evaluate the effect on exacerbation, cough sputum, and general state of health of long-term treatment with ELOM-080 in COPD patients with an exacerbation history and chronic bronchitis. METHODS: We performed a post-hoc analysis of a randomized, double-blinded, placebo-controlled parallel-group clinical trial of a 6-month treatment with ELOM-080 (3×300 mg) in patients with chronic bronchitis and concomitant COPD. The primary outcome was the proportion of subjects with at least one exacerbation over the 6-month study period. Secondary outcomes included the total number of exacerbations (ie, cumulative occurrence of exacerbations during the study period) and the proportion of acute exacerbations necessitating an antibiotic treatment, monthly evaluations of sputum and cough symptoms, and the general state of health and a safety analysis. RESULTS: Of 260 randomized subjects, 64 patients fulfilled the inclusion criteria for COPD (ELOM-080: 35, placebo: 29). Compared to placebo, ELOM-080 reduced the percentage of subjects with at least one exacerbation (29% versus 55%, P=0.031) and a reduction in the overall occurrence of exacerbations (ELOM-080: 10, placebo: 21, P=0.012) during the winter season. The percentage of asymptomatic or mildly symptomatic patients (sputum/expectoration and cough) was consistently higher in the ELOM-080 group compared to placebo, with statistical significant differences after 2 and 3 months of treatment (2 months: ELOM-080 25%, placebo 11%, P<0.005; 3 months: ELOM-080 26%, placebo 14%, P<0.05). Likewise the subjective rating of general health status was better in the ELOM-080 group with statistically significant superiority after 2 and 3 months of treatment (2-month treatment: P=0.015; 3-month treatment: P=0.024). Tolerability results were comparable between ELOM-080 and placebo. CONCLUSION: ELOM-080 is efficacious in patients with COPD and a chronic bronchitis phenotype. Prophylactic use reduces the rate of exacerbations and improves the key symptoms of sputum and cough with a favorable long-term tolerability profile.

Zabofloxacin for chronic bronchitis.

Treatment of lower respiratory tract infection poses as an ongoing challenge among respiratory tract diseases. Bacterial infections are causes of acute exacerbations in chronic bronchitis and indications for antibacterial therapy. Several antibiotics were applied to treat bacterial infections in chronic bronchitis, among them fluoroquinolones are considered potent, broad-spectrum agents with excellent tissue penetration. This monograph focuses on zabofloxacin, a novel fluoroquinolone agent recently approved and launched in South Korea, and summarizes the drug's antibacterial efficacy, pharmacokinetic properties and toxicity. Recent advances concerning fluoroquinolones in chronic bronchitis will be discussed, along with a comparison between zabofloxacin and moxifloxacin. Zabofloxacin has proved to be noninferior to moxifloxacin against major community-acquired Gram-positive and Gram-negative respiratory tract pathogens and found to be well tolerated in both oral and parenteral administrations. These features can make it a potential antimicrobial agent in therapy of chronic bronchitis and other lower respiratory tract infections.

Aclidinium bromide inhalation powder for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease including chronic bronchitis and emphysema.

Aclidinium is a twice-daily long-acting muscarinic receptor antagonist (LAMA) with an interesting pharmacological profile. Recent evidence indicates that this LAMA, in addition to causing a significant improvement in lung function and other important supportive outcomes, such as health related quality of life, dyspnea and nighttime/early morning symptoms in patients suffering from COPD, is also able to significantly reduce the rate of exacerbations of any severity, is extremely effective in controlling the COPD symptoms, is able to reduce lung hyperinflation, and has an excellent cardiovascular safety profile. Consequently, aclidinium should be considered a first-line approach at least for the symptomatic treatment of COPD although there are still few head-to-head studies comparing this LAMA with other bronchodilators. In any case, aclidinium can be taken into account in the treatment of different COPD phenotypes (emphysema, chronic bronchitis, exacerbators and patients with overlap COPD asthma).

Identifying patients at risk of late recovery (≥ 8 days) from acute exacerbation of chronic bronchitis and COPD.

OBJECTIVES: To identify factors associated with late recovery (≥ 8 days from exacerbation start) in patients with acute exacerbations of chronic bronchitis/COPD (AECB/AECOPD). METHODS: An international, observational, non-interventional study in outpatients with AECB/AECOPD who received treatment for their exacerbation with the antibiotic moxifloxacin. Factors analyzed for late recovery included patient demographic characteristics, geographic region and disease severity. Additionally, logistic regression analysis was undertaken to identify factors associated with late recovery. RESULTS: The analysis population was 40,435 patients aged ≥ 35 years, from Asia-Pacific, Europe, the Americas and Middle East/Africa. Most were male (63.1%), mean age 60.4 years and current or ex-smokers (60.6%) with history of ≥ 2 exacerbations in the previous year. Patients who underwent spirometry (n = 6408, 19.7%) had moderate airflow obstruction (mean FEV(1) 1.7 L). Both clinicians and patients reported that moxifloxacin provided clinical improvement in a mean of 3 days and recovery in 6 days. Clinical factors significantly associated with late recovery were: age ≥ 65 years, duration of chronic bronchitis >10 years, cardiac comorbidity, >3 exacerbations in the previous 12 months, current exacerbation type (Anthonisen I/II) and hospitalization in the last 12 months. CONCLUSIONS: In a large cohort of patients, all treated with the same antibiotic for an exacerbation of chronic bronchitis or COPD, the main factors associated with late recovery (≥ 8 days) were: older age, history of frequent exacerbations, current exacerbation type of Anthonisen I/II, history of prior hospitalizations and cardiac comorbid conditions.

Characterisation of exacerbations of chronic bronchitis and COPD in Europe: the GIANT study.

OBJECTIVE: The GIANT study collected information on patients with acute exacerbations of chronic bronchitis (AECB) and chronic obstructive pulmonary disease (COPD) and the effect of treatment with moxifloxacin. METHODS: AECB history, concomitant diseases, moxifloxacin treatment, concomitant medication, clinical symptoms and adverse events were recorded. A questionnaire at the end of treatment recorded the impact on patients' daily lives. RESULTS: Among 9225 patients from eight European countries, marked variation was seen in characteristics including age, smoking history and type of exacerbation. Spirometry use was more common among chest physicians (66.7%) than GPs (15.5%). Patients with Anthonisen type 1 and 2 exacerbations had more frequent exacerbations and these patients experienced a greater impact on daily activities compared with patients with type 3 episodes. Patient symptoms improved with moxifloxacin treatment after a mean (SD) of 3.4 (1.8) days, allowing return to normal daily activities after 5.4 (4.4) days and with full recovery taking 6.5 (3.1) days. CONCLUSIONS: Characteristics of patients with AECB and acute exacerbations of COPD differ among European countries. Spirometry is under-used, particularly in primary care and antibiotic treatment does not always follow current guidelines. Results confirm the efficacy of moxifloxacin in the treatment of AECB in real-life conditions.

[Low-intensity laser radiation in the combined treatment of patients with chronic obstructive bronchitis].

This study included 89 patients with chronic obstructive bronchitis (COB) that were exposed to harmful occupational factors. The control group consisted of 30 healthy subjects. Chronic obstructive bronchitis is characterized by serious disturbances in the cardiorespiratory system that manifest themselves in the form of bronchogenic pneumosclerosis with moderate lung emphysema and pulmonary hypertension associated with impaired general resistance. Simultaneously, activity of lipid peroxidation reactions decreases. Application of low-intensity laser radiation in combination with other therapeutic modalities for the treatment of patients with chronic obstructive bronchitis accelerates elimination of clinical symptoms, increases its efficiency, promotes drainage function of the bronchi, facilitates normalization of the patient's immune status, and contributes to the optimization of lipid peroxidation processes.

Determining factors in the prescription of moxifloxacin in exacerbations of chronic bronchitis in the primary-care setting.

OBJECTIVE: To describe the characteristics of patients and exacerbations that may determine the choice of an antibacterial in exacerbations of chronic bronchitis (ECB). METHODS: This was a multicentre, observational study in ECB. A group of 225 primary-care practitioners were randomly selected to include 1007 patients. A logistic regression model was used to identify the characteristics of the physicians, patients and exacerbations associated with the choice of an antibacterial. RESULTS: The mean age of the patients was 67.6 years (+/- SD 11) and 72.1% were male. In 91.4% of patients, the exacerbation was type I or II according to Anthonisen's classification. Most exacerbations (68.2%) were treated with moxifloxacin while only 31.8% were treated with other antibacterials. The more experienced practitioners (those with the longest professional careers and those who had higher numbers of patient-visits for chronic bronchitis) prescribed moxifloxacin more frequently (per each year of experience: OR 1.05; 95% CI 1.02, 1.07; per each additional patient-visit per week: OR 1.02; 95% CI 1.003, 1.04). The probability of receiving moxifloxacin increased with the severity of baseline dyspnoea (OR 1.94; 95% CI 1.27, 2.96) and decreased in smokers (OR 0.54; 95% CI 0.36, 0.81) and in patients receiving oral corticosteroids (OR 0.61; 95% CI 0.41, 0.90). CONCLUSIONS: Prescription of moxifloxacin in primary care is significantly associated with more years of physician practice and with a higher severity of disease. The use of oral corticosteroids in exacerbations is commonly associated with other antibacterials (non-quinolones), either to improve antibacterial efficacy or because of doubtful bacterial aetiology, thus the preference for a narrow-spectrum antibacterial combined with an anti-inflammatory drug.

Moxifloxacin in the management of exacerbations of chronic bronchitis and COPD.

Bacteria are isolated in more than 50% of exacerbations of chronic bronchitis (CB) and chronic obstructive pulmonary disease (COPD). The most prevalent respiratory pathogens include Gram-positive (Streptococcus pneumoniae) and Gram-negative (Haemophilus influenzae, Moraxella catarrhalis) microorganims. Moxifloxacin is a fourth-generation fluoroquinolone that has been shown to be effective against respiratory pathogens, including atypicals and those resistant to most common antibiotics. The bioavailability and half-life ofmoxifloxacin provides potent bactericidal effects at a dose of 400 mg once daily. Among the fluoroquinolones, the ratio of the area under the concentration-time curve (AUC) to minimal inhibitory concentration of moxifloxacin is the highest against S. pneumoniae. Moxifloxacin has demonstrated better eradication in exacerbations of CB and COPD compared with standard therapy, in particular, with macrolides. Patients treated with moxifloxacin showed a prolonged time to the next exacerbation and observational studies suggest that moxifloxacin induces a faster release of symptoms of exacerbation. Some guidelines recommend the use of moxifloxacin as first-line therapy in bacterial exacerbations in patients with moderate to severe COPD and in patients with mild COPD with risk factors. The current article reviews the use of moxifloxacin in bacterial exacerbations of CB and COPD.

Short-term and long-term outcomes of moxifloxacin compared to standard antibiotic treatment in acute exacerbations of chronic bronchitis.

STUDY OBJECTIVES: To compare the effectiveness of oral moxifloxacin with standard antibiotic therapy in acute exacerbation of chronic bronchitis (AECB). DESIGN: Multicenter, multinational, randomized, double-blind study of two parallel treatment arms. PATIENTS: Outpatients >or= 45 years old with stable chronic bronchitis, smoking history of >or= 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. INTERVENTIONS: 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]). MEASUREMENTS: 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. RESULTS: 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 (p < 0.01). 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). CONCLUSIONS: Moxifloxacin was equivalent to standard therapy for clinical success and showed superiority over standard therapy in clinical cure, bacteriologic eradication, and long-term outcomes.

[Effect of Eucalyptus globulus oil on lipopolysaccharide-induced chronic bronchitis and mucin hypersecretion in rats].

OBJECTIVE: To study the effect of Eucalyptus globulus oil on bronchiolitis and mucin hypersecretion in chronic bronchitis induced by lipopolysaccharide in rats. METHOD: Rat model was established by intratracheal instillation of lipopolysaccharide 0.2 mg. Pathological changes, alteration in bronchoalveolar lavage fluid (BALF) and immunohistochemistry characters were examined after 3 weeks and the effect of E. globulus oil was observed. RESULT: Characters of pathological manifestations of chronic bronchitis were found after instillation of LPS. Inflammatory cell infiltration and bronchiolitis severity were significantly reduced after administration of E. globulus oil. Especially in 300 mg x kg(-1) treated rats, there were significant decreases of mucin content in BALF and MUC5ac expression in trachea and bronchiole epithelium. Optical density and mucins area% detected by image analysis system were apparently lower than those in model group. CONCLUSION: E. globulus oil has the anti-inflammatory effect on chronic bronchitis induced by lipopolysaccharide in rats and the inhibitio effect on hypersecretion of airway mucins.

Hypothalamic digoxin, hemispheric chemical dominance, and chronic bronchitis emphysema.

The isoprenoid pathway produces three key metabolites--endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator, and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins), and ubiquinone (free radical scavenger). This was assessed in patients with chronic bronchitis emphysema. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find the role of hemispheric dominance in the pathogenesis of chronic bronchitis emphysema. All the 15 patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. In patients with chronic bronchitis emphysema there was elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate levels of RBC membrane in patients with chronic bronchitis emphysema. The same biochemical patterns were obtained in individuals with right hemispheric dominance. Endogenous digoxin by activating the calcineurin signal transduction pathway of T-cell can contribute to immune activation in chronic bronchitis emphysema. Increased free radical generation can also lead to immune activation. Endogenous synthesis of nicotine can contribute to the pathogenesis of the disease. Altered glycoconjugate metabolism and membranogenesis can lead to defective lysosomal stability contributing to the disease process by increased release of lysosomal proteases. The role of an endogenous digoxin and hemispheric dominance in the pathogenesis of chronic bronchitis emphysema and in the regulation of lung structure/function is discussed. The biochemical patterns obtained in chronic bronchitis emphysema is similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Chronic bronchitis emphysema occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance can play a role in the regulation of lung function and structure.

[Objectives for antibiotic therapy in acute exacerbations of chronic bronchitis]. / Quels objectifs pour l'antibiothérapie dans les exacerbations aiguës de la bronchite chronique?

ANTIBIOTIC EFFICACY: According to early studies, antibiotics have moderate efficacy in acute exacerbation of chronic bronchitis. The lack of efficacy is particularly clear for patent exacerbation with marked alteration of respiratory function. Recent studies have shown that newer compounds exhibit an efficacy similar (no proven superiority) to comparison compounds (75 to 95% favorable outcome with treatment). The recommendations of the IVth Consensus Conference on Anti-infectious Therapy thus propose first line antibiotic therapy for patients with a forced expiratory volume in 1 second (FEV1) between 80 and 35% and broader spectrum and new antibiotics in case of failure of the first line treatment for patients with severe obstruction or frequently recurrent exacerbation. EVALUATION CRITERIA: Using exacerbation-free interval, reduction in the number of exacerbations, duration of treatment and/or hospital stay as evaluation criteria, interesting results are obtained with amoxicillin/clavulanic acid, azithromycin, and ciprofloxacin. Independent factors predictive of therapeutic failure are, according to one study, FEV1 less than 35%, ambulatory administration of oxygen, more than 4 acute exacerbations within 24 months, history of pneumonia or sinusitis, and requirement for long-term corticosteroid therapy. Factors predictive of recurrence are, according to another study, dependence on oxygen therapy, prolonged corticosteroid therapy, smoking, and/or heart disease. Cost effectiveness is particularly interesting with ciprofloxacin, especially in more severe patients. PERSPECTIVES: It is important to target antibiotic therapy for acute exacerbation of chronic bronchitis specifically for patients who will truly benefit, adapting the prescribed compound to the bacterial target.

[Moxifloxacin in the treatment of chronic bronchitis--clinical evaluation and assessment by patients]. / Moxifloxacin bei akuter Exazerbation der chronischen Bronchitis. Klinische Bewertung und Beurteilung durch Patienten.

BACKGROUND AND METHOD: The aim of this trial conducted in the offices of pneumologists was to evaluate the clinical success of a 5-day course of oral moxifloxacin administered once daily at a dose of 400 mg in 328 patients with acute exacerbation of chronic bronchitis (Anthonisen type 1). In this non-comparative study, the results of treatment were assessed not merely on the basis of the clinical parameters, but also, for the first time, by the surrogate marker of patient satisfaction and the improvement in cough, dyspnea, chest pain and sputum, the severity of which was scored daily by the patient himself. RESULTS: Cough, chest pain and the purulence of the sputum improved rapidly within the first five days of treatment. At least 90% of the patients reported their satisfaction with the antibiotic. The clinical success rate (cure and improvement) for all the patients involved (ITT analysis) was 90.5%. The most common side effect was diarrhea, while the other side effects showed no specific pattern.