Acute exacerbation of chronic obstructive pulmonary disease and antibiotics: analysis of comparative trials

OBJECTIVE: The authors had for aim to assess the role of antibiotics in acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: Comparative antibiotic trials were collected through systematic search on Medline data base--well-designed studies were selected. RESULTS: Eight equivalence studies were selected. No clear difference between antibiotics was demonstrated. The shortest treatment was as effective as the longest. CONCLUSION: No antibiotic has demonstrated its superiority. A new generation of antibiotic comparative trials for exacerbation of COPD is clearly needed.     

Exacerbations of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease is characterised by a progressive decline in lung function, reduced exercise performance, and worsening of health status. Exacerbations are important clinical events in chronic obstructive pulmonary disease and are defined as sudden worsening of respiratory symptoms and function requiring medical intervention. The most common causes of chronic obstructive pulmonary disease exacerbations are bacterial or viral infections, but comorbidity may be important. A major issue is the decision regarding home management or hospital management of exacerbations. Because of exacerbations, a frequent assessment of severity of chronic obstructive pulmonary disease is required for targeting pharmacological therapy.     

Epidemiology of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is an important cause of morbidity and mortality, all over the world. COPD, which was the sixth leading cause of death worldwide in 1990, will become the third one in 2020. COPD is a complex disease, influenced by genetic, behavioral, and environmental factors. The most important factor for developing COPD is tobacco smoke. Also environmental conditions represents risk for developing COPD. Furthermore, diet and a low socioeconomic status are correlated to the disease. Genetic factors, familial history, and childhood lower respiratory tract infections play an important role in the etiology of COPD. Burden of COPD is very high for community. Furthermore, the disease often is under-diagnosed and treated only at advanced stages, whilst it is a substantial health problem even among young adults. This needs to be taken into account by health personnel and decision-makers.     

Pathology of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder of the lung characterized by poorly reversible airflow limitation. It is not a unique disease entity but rather a complex of conditions which include emphysema, chronic bronchitis and, sometimes, asthma. Moreover, COPD is a progressive disease often associated with exacerbations. Cigarette smoking, which is the most important risk factor for the development of COPD, induces pathological changes involving lung parenchyma, peripheral airways and central airways. Since lung parenchyma and peripheral airways are the sites responsible for airflow limitation and central airways are the main site of mucus hypersecretion, pathological changes in these compartments may be relevant in the development of COPD.     

Pathophysiology of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a disease state characterised by airflow obstruction that is not fully reversible and progressive. Symptoms, as cough, sputum production and dyspnoea, functional impairment and complications of COPD can all be explained on the basis of the underlying lung inflammation and the resulting pathology. The chronic airflow obstruction is caused by a mixture of small airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema). On one hand, chronic inflammation causes remodelling and narrowing of the small airways. On the other hand, destruction of the lung parenchyma, also by an inflammatory process, leads to the loss of alveolar attachments to the small airways and decreases lung elastic recoil. In turn, these changes reduce the ability of the airways to remain open during expiration.     

Circulating visfatin in chronic obstructive pulmonary disease

ObjectiveMalnutrition and continuous systemic inflammation occur frequently in patients with chronic obstructive pulmonary disease (COPD). Visfatin is a new adipokine, which increases in some inflammatory diseases. Its plasma level and relation with nutritional status and inflammation in COPD remain unknown. This study compared visfatin levels, nutritional status, and inflammation markers in patients with COPD and healthy controls.MethodsPlasma visfatin, tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured in 35 patients with COPD and 28 healthy controls. Body composition was assessed with bioelectrical impedance analysis.ResultsSignificantly lower body mass index and percentage of body fat were observed in patients with COPD compared with control subjects. The levels of plasma visfatin were higher in the COPD group compared with healthy controls (2.07 ± 0.18 versus 1.88 ± 0.15 ng/mL, P < 0.001). Levels of TNF-α and CRP were also significantly higher in patients with COPD compared with controls. Plasma CRP and TNF-α were positively correlated with visfatin in the COPD group. No significant correlations were found between visfatin and body mass index or percentage of body fat in both groups.ConclusionPlasma visfatin levels increased in patients with COPD. This increased adipocytokine was significantly correlated with TNF-α and CRP. Visfatin may be a new proinflammatory adipocytokine in this disease.     

2003—2016年上海市杨浦区阻塞性肺疾病死亡趋势分析

了解上海市宝山区户籍居民10年间慢性阻塞性肺疾病（COPD）的死亡率和潜在寿命损失年数（PYLL）的变化情况,为今后开展COPD防治工作提供策略和依据。

基于2010—2019年上海市宝山区居民死因监测系统,采用Excel 2010软件、SPSS 22.0软件和Joinpoint回归模型整理历年数据并综合分析,计算粗死亡率、标准化死亡率、年龄别死亡率、PYLL、年度变化百分比（APC）等指标。

2010—2019年间,上海市宝山区COPD年均粗死亡率为48.08/10万,标化后死亡率为39.95/10万,占同期总死亡人数的5.82%,位列宝山区死因顺位第3位。10年间,COPD男性粗死亡率、标化死亡率始终高于女性（P<0.01）。COPD粗死亡率和标化死亡率随年份增加均呈下降趋势（P<0.001）。COPD死亡率随年龄的增长呈现上升的趋势,其中≥75岁组的死亡占比最高,占全年龄段的85.71%。因COPD死亡所导致的PYLL总计为2 352.5年,其中男性为1 977.5年,女性为375.0年,COPD导致的每万人中的男性减寿年数（4.18年）远高于女性（0.82年）。

2010—2019年间上海市宝山区户籍居民COPD标化后死亡率呈明显下降趋势,但由于COPD患病带来的疾病负担重,尤其对老年、男性居民的健康危害影响深远,建议将COPD作为公共卫生服务中慢性病防制的重点疾病,并采取有效的干预防制措施。

     

Functional diagnosis of chronic obstructive pulmonary disease

Functional diagnosis of chronic obstructive pulmonary disease is important for identifying and quantifying airflow limitation, reversibility, disease severity and exacerbations. Functional diagnosis is also important for long-term therapeutic monitoring and for establishing the need for pulmonary rehabilitation. From the functional standpoint, chronic obstructive pulmonary disease is characterised by a progressive airflow limitation which is not fully reversible. Spirometry is the gold standard for diagnosing the disease and monitoring its progression as it is non-invasive, standardised, reproducible, and objective. Spirometry should measure forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and the ratio of these two measurements. Post-bronchodilator FEV1 < 80% of the predicted value and FEV1/FVC ratio < 70% confirms the diagnosis of chronic obstructive pulmonary disease.     

Use of factor analysis to consolidate multiple outcome measures in chronic obstructive pulmonary disease

Multiple outcome measures are often used in clinical research and practice. However, the use of multiple measures inflates the probability of a type I error. In this paper, we used factor analysis techniques to reduce multiple outcome measures to a lesser number of orthogonal dimensions. The data were obtained from 119 patients with chronic obstructive pulmonary disease. Each patient had measurements made of 28 variables, including multiple parameters of pulmonary function, exercise tolerance and gas exchange. Factor analysis using a maximum likelihood iterative solution was performed. The factors were then rotated to a varimax solution. The analysis yielded four meaningful factors: exercise tolerance, disease severity, lung volumes and flow rates. Exercise tolerance and disease severity were the most important factors accounting, respectively, for 44 and 13% of the common variance. For further analyses, these composite factors could be used or a representative clinical measure from each factor might be chosen. We conclude that many physiologic measures provide highly correlated information about chronic obstructive pulmonary disease patients. Factor analysis may help reduce these measures into a smaller number of reliable composites.     

Occupational causes of chronic obstructive pulmonary disease

The relation between Chronic Obstructive Pulmonary Disease (COPD, including chronic bronchitis and emphysema (CBE), and exposure to coal dust is well established. This paper reviews the evidence relating to other occupational causes of COPD, including industries associated with exposure to fumes, chemical substances, and dusts. A review of key literature has been carried out with a focus on the magnitude of risks and levels of exposure causing disabling health effects. The literature suggests that elevated risks of developing COPD are clearly associated with several occupations, with risk estimates being high in some, even after taking into account the effect of confounders, such as smoking. Of particular concern are agricultural workers who can be exposed to a variety of gases and organic dusts, among whom CBE is clearly elevated, particularly for pig farmers and exposure to endotoxins, with an increased annual decline in lung function. Similarly, cotton textile workers are exposed to a mixture of substances affecting development of atopy, byssinosis, and CBE, and across-shift and long-term decline in lung function. Atopy also has an important role in the development of COPD in flour mill workers and bakers, with those sensitized to bakery allergens having a greater lung function decline than non-sensitized individuals. Welding processes involve a range of potential chemical, physical and radiation hazards. The average reduction in FEV1 associated with welding fumes is similar to that associated with smoking. Challenges in assessing the evidence include variation in diagnostic methods; concurrent exposure to cigarette smoke (direct or second-hand) and multiple work-place irritants; healthy worker selection/survivor effects; poor exposure definition. Raising awareness of occupational causes of COPD among employers, employees, and health service professionals is important.     

Pharmacological therapy of chronic obstructive pulmonary disease

None of the available drugs for chronic obstructive pulmonary disease is able to reduce the progressive decline in lung function which is the hallmark of this disease. Smoking cessation is the only intervention that has been shown so far to reduce disease progression. The current pharmacological therapy for chronic obstructive pulmonary disease is largely symptomatic and is based on bronchodilators including selective beta2-adrenoceptor agonists (short- and long-acting), anticholinergics, theophylline, or a combination of these drugs. Due to the lack of efficacy, side effects at high doses, and high costs, glucocorticoids should not be used routinely for management of stable chronic obstructive pulmonary disease, although they are effective for exacerbations. New pharmacological strategies for chronic obstructive pulmonary disease are needed because the current management is inadequate.     

Clinical aspects of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease represents a complex syndrome including chronic bronchitis, pulmonary emphysema and chronic asthma, characterised by persistent airway obstruction with different degree of reversibility. Clinical manifestations depend on the relative contribution of these different diseases in the single patient. Relationship between symptoms and severity (as expressed by forced expiratory volume in one second) is weak, and chronic airway obstruction generally precedes symptoms. Cough, sputum, wheezing, and dyspnea are the main symptoms of chronic obstructive pulmonary disease, and they must be carefully inquired and quantified. Symptoms and signs of chronic obstructive pulmonary disease depend on the type of disease (chronic bronchitis or emphysema), and also on the complications and comorbidities. Accurate definition of the heterogeneity of chronic obstructive pulmonary disease can be useful in the prognosis and management of the disease.     

Risk factors of chronic obstructive pulmonary disease

Many personal and environmental risk factors are associated to increased prevalence and severity of chronic obstructive pulmonary disease (COPD). In this review, we shortly describe most of these risk factors, aiming at defining each factor as causative or modifier of the natural history of the disease. It is clear that the environmental risk factors do have an outstanding relevance for both the initiation and the evolution of COPD. This review focuses on the crucial importance of prevention in order to decrease the public health burden of COPD in the western countries during the next decades.     

Preserved muscle metaboreflex in chronic obstructive pulmonary disease

The objective of this study was to measure the magnitude of the muscle metaboreflex in people with chronic obstructive pulmonary disease (COPD) compared with healthy controls and to assess the relationships between disease severity, exercise capacity, and the magnitude of the muscle metaboreflex. Nine people with mild-to-severe COPD and 11 age- and gender-matched healthy controls performed isometric handgrip exercise (IHG), followed by postexercise circulatory occlusion (PECO) while hemodynamic changes were measured. Continuous measures of heart rate, arterial pressure, leg blood flow, leg vascular resistance, and total peripheral resistance were obtained. Participants then performed a cycle test to exhaustion. Heart rate, blood pressure, and blood flow responses during IHG and PECO were similar between the COPD group and healthy controls (p > 0.05). There was no association between disease severity or exercise capacity and the magnitude of the muscle metaboreflex. We observed a preserved muscle metaboreflex in mild-to-severe COPD, suggesting the metaboreflex is not a contributing factor to the development of exercise intolerance in this population.     

New treatments for chronic obstructive pulmonary disease

No currently available treatments reduce the progression of chronic obstructive pulmonary disease (COPD) or suppress the inflammation in small airways and lung parenchyma. However, several new treatments now in development for COPD are targeted at the inflammation process. Antagonists of mediators, such as leukotriene B4, interleukin-8, and tumour necrosis factor-alpha and inhibitors of oxidative and nitrative stress are in clinical development. Phosphodiesterase-4 inhibitors are in clinical trials and drugs that inhibit p38 MAP kinase, nuclear factor-kappaB and phosphoinositide-3 kinase-gamma are now in early development. There is also a search for elastase inhibitors to prevent the development of emphysema and drugs that may even reverse the lung destruction.