Exacerbations of chronic obstructive pulmonary disease

The diagnosis and treatment of acute exacerbations (AEs) of chronic obstructive pulmonary disease (COPD) is controversial. In this section, we review (1) the epidemiology of this condition; (2) the etiology--many patients with AECOPD are thought to have a combination of viral and bacterial infections, which contribute to their exacerbation. Bacterial organisms are isolated more commonly after viral infections in patients with COPD. The role that bacterial infections play in AECOPD remains a very controversial topic; (3) the use of diagnostic procedures; (4) efficacy of antibiotics; (5) clinical parameters to stratify patients' severity; (6) different groups of antibiotics that can be used; and (7) other therapies, including bronchodilators. We summarize the current literature, with special emphasis on the assessment of the long-term impact of this condition.     

Prevention of exacerbations: how are we doing and can we do better?

Prevention of exacerbations of chronic obstructive pulmonary disease (COPD) can involve removing the cause or reducing the patient's vulnerability to the cause. This article addresses the following issues: What is the problem during an exacerbation, what are the causes of an exacerbation, what can prevent exacerbations, and who are we? The difference between a patient with COPD during an exacerbation and after recovery is small. It is unlikely that patients with early COPD experience less exposure to exacerbation causes than those with severe disease; it is just that the consequences are more severe for those with severe disease. Interventions that produce small absolute benefits can therefore have a disproportionately large effect on exacerbation reduction. Recognized causes include season, cold weather, pollution events, bacterial infection, viral infection, and treatment withdrawal. Countries with warmer climates have much larger mortality in cold weather than those with colder climates. Reducing exacerbations in more temperate climates may be altered as much by changes in clothing and bedroom heating as by changes in treatment. Taking more exercise in cold weather may be the underlying reason for the reduction of exacerbations after pulmonary rehabilitation. Influenza vaccination reduces influenza severity and reduces transmission from health care workers to patients. There are a number of pharmacologic interventions shown to reduce (the effect of) exacerbations, including inhaled corticosteroids, long-acting beta-agonists, long-acting anticholinergics, mucolytics, and perhaps antibiotics that reduce Haemophilus carriage. The effect of the bronchodilators is additive to inhaled corticosteroids; how far the other interventions are complementary is unclear. So far, we have had a very medical response to COPD exacerbations. Altering social and behavioral aspects is likely to be complementary.     

Factors Associated With Outcomes of Acute Exacerbations of Chronic Obstructive Pulmonary Disease

The purpose of this article is to provide a general review of the current literature on the factors associated with the outcomes of hospitalizations, survival and health‐related quality of life in acute exacerbations of chronic obstructive pulmonary disease (AECOPD), highlighting the limitations and the complexities in interpretation of the results of current studies. There is no consensus definition for AECOPD; onsets may be difficult to define and the determination of duration elusive. The prevalence of acute exacerbations of COPD (AECOPD) in the community appears to be underestimated as exacerbations are underreported by patients and their doctors. Hospitalization for COPD is due mainly to severe AECOPDs which drive the cost of care. There are few longitudinal epidemiological studies on factors associated with hospitalizations for AECOPD. The results of current studies do not allow clear differentiation between associations that are predictors of event, the consequences of the event, or indicators of severity. Strategies to reduce severe exacerbations of COPD include pharmacological treatment, vaccinations, pulmonary rehabilitation, and home care programs. The optimal strategy for the reduction of hospitalization in COPD remains unclear. Long-term interventional studies are needed to provide clearer information for the prevention of exacerbations and hospitalizations in COPD.     

COPD exacerbations: defining their cause and prevention

Exacerbations of chronic obstructive pulmonary disease (COPD) are episodes of worsening of symptoms, leading to substantial morbidity and mortality. COPD exacerbations are associated with increased airway and systemic inflammation and physiological changes, especially the development of hyperinflation. They are triggered mainly by respiratory viruses and bacteria, which infect the lower airway and increase airway inflammation. Some patients are particularly susceptible to exacerbations, and show worse health status and faster disease progression than those who have infrequent exacerbations. Several pharmacological interventions are effective for the reduction of exacerbation frequency and severity in COPD such as inhaled steroids, long-acting bronchodilators, and their combinations. Non-pharmacological therapies such as pulmonary rehabilitation, self-management, and home ventilatory support are becoming increasingly important, but still need to be studied in controlled trials. The future of exacerbation prevention is in assessment of optimum combinations of pharmacological and non-pharmacological therapies that will result in improvement of health status, and reduction of hospital admission and mortality associated with COPD.     

Factors associated with outcomes of acute exacerbations of chronic obstructive pulmonary disease

The purpose of this article is to provide a general review of the current literature on the factors associated with the outcomes of hospitalizations, survival and health-related quality of life in acute exacerbations of chronic obstructive pulmonary disease (AECOPD), highlighting the limitations and the complexities in interpretation of the results of current studies. There is no consensus definition for AECOPD; onsets may be difficult to define and the determination of duration elusive. The prevalence of acute exacerbations of COPD (AECOPD) in the community appears to be underestimated as exacerbations are underreported by patients and their doctors. Hospitalization for COPD is due mainly to severe AECOPDs which drive the cost of care. There are few longitudinal epidemiological studies on factors associated with hospitalizations for AECOPD. The results of current studies do not allow clear differentiation between associations that are predictors of event, the consequences of the event, or indicators of severity. Strategies to reduce severe exacerbations of COPD include pharmacological treatment, vaccinations, pulmonary rehabilitation, and home care programs. The optimal strategy for the reduction of hospitalization in COPD remains unclear. Long-term interventional studies are needed to provide clearer information for the prevention of exacerbations and hospitalizations in COPD.     

Recovery Following Acute Exacerbations of Chronic Obstructive Pulmonary Disease – A Review

Acute exacerbations are associated with disease progression, hospital admission and death in people with chronic obstructive pulmonary disease (COPD). The detrimental outcomes associated with acute exacerbations highlights a need to understand the time course of recovery following acute exacerbation of COPD (AECOPD) so that effective and timely interventions can be provided. The aim of this narrative review was to describe the natural recovery in physiology, symptoms and function following AECOPD. Substantial recovery of lung function and airway inflammation occurs in the first week after onset of an AECOPD, whilst systemic inflammatory markers may take up to two weeks to recover. Symptoms generally improve over the first 14 days, however marked variation is evident between studies and individuals. There are limited data regarding the time course of recovery for functional capacity, quality of life and strength. In a small number of patients (<10%) recovery of lung function and symptoms has not occurred by three months. Features of patients at risk of a prolonged recovery following AECOPD include older age, more severe lung disease, presence of chronic bronchitis, lower body mass index and more chronic dyspnoea. Exacerbation features associated with prolonged recovery are symptoms of the common cold at exacerbation onset, evidence of viral infection, more severe dyspnoea during the exacerbation and persistent systemic inflammation. In clinical practice efforts should be made to recognise prolonged recovery, which puts patients at risk of poor outcomes, and to address the consequences of AECOPD including physical inactivity and skeletal muscle weakness. Whether delivery of specific interventions at distinct time points in the recovery process can enhance recovery remains to be determined.     

COPD-Exazerbation und Intensivtherapie

Chronic obstructive pulmonary disease (COPD) is regarding prevalence, morbidity and mortality one of the most important disorders in medicine. Severe COPD exacerbation may cause admission to the intensive care unit (ICU). COPD exacerbation is defined as an increase of symptoms that goes beyond usual day-to-day variation and that necessitates a change in drug therapy. The in-hospital mortality of COPD patients with severe exacerbations lies between 3–10%. By admission to an ICU, mortality rises to 40% and above. Besides inhalation with bronchodilators, systemic steroids play a major role in COPD exacerbation therapy. Therapy with systemic steroids should not exceed 10–14 days. Antibiotics have a role if bacterial infection is probable. Macrolides should be used with caution, because up to 40% of Streptococcus pneumoniae spp. show resistance. Beside drug therapy, physiotherapy may have an impact on COPD exacerbation outcome, although prospective and randomized trials are missing. Patients with severe exacerbations may need temporary non-invasive or invasive ventilation. There is a clear priority for non-invasive ventilation. This article focuses on diagnosis and therapy of exacerbated COPD patients including ventilatory support.     

Role of Antimicrobial Agents in the Management of Exacerbations of COPD

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a common occurrence and characterize the natural history of the disease. Over the past decade, new knowledge has substantially enhanced our understanding of the pathogenesis, outcome and natural history of AECOPD. The exacerbations not only greatly reduce the quality of life of these patients, but also result in hospitalization, respiratory failure, and death. The exacerbations are the major cost drivers in consumption of healthcare resources by COPD patients. Although bacterial infections are the most common etiologic agents, the role of viruses in COPD exacerbations is being increasingly recognized. The efficacy of antimicrobial therapy in acute exacerbations has established a causative role for bacterial infections. Recent molecular typing of sputum isolates further supports the role of bacteria in AECOPD. Isolation of a new strain of Haemophilus influenzae, Moraxella catarrhalis, or Streptococcus pneumoniae was associated with a considerable risk of an exacerbation. Lower airway bacterial colonization in stable patients with COPD instigates airway inflammation, which leads to a protracted self-perpetuating vicious circle of progressive lung damage and disease progression. A significant proportion of patients treated for COPD exacerbation demonstrate incomplete recovery, and frequent exacerbations contribute to decline in lung function. The predictors of poor outcome include advanced age, significant impairment of lung function, poor performance status, comorbid conditions and history of previous frequent exacerbations requiring antibacterials or systemic corticosteroids. These high-risk patients, who are likely to harbor organisms resistant to commonly used antimicrobials, should be identified and treated with antimicrobials with a low potential for failure. An aggressive management approach in complicated exacerbations may reduce costs by reducing healthcare utilization and hospitalization.     

Relation Between Chronic Obstructive Pulmonary Disease and Antibiotics

Chronic obstructive pulmonary disease (COPD) constitutes a major health problem. Recurrent acute exacerbations are characteristic of the course of COPD (AECOPD) associated with significant healthcare costs and contribute to the progress of the disease. Given that almost half of AECOPD is caused by bacteria, administration of antibacterial agents is recommended for patients with severe exacerbations or severe underlying COPD. Optimal antibiotic selection for exacerbations has therefore incorporated quantifying the risk for a poor outcome of the exacerbation and choosing antibiotics differently for low risk and high risk patients. It is unclear whether antibiotics should be provided as prophylactic agents in COPD patients although ongoing trials are reexamining the question of whether the antiinflammatory action of antibiotics such as macrolides can be useful in preventing exacerbations. In addition, nowadays, the occurrence of pneumonia in COPD has received considerable recent attention as it appears to be increased by the use of inhaled corticosteroids.     

COPD急性加重危险因素的研究进展

COPD是呼吸系统疾病中的常见病和多发病,患病率及病死率均居高不下,近年来研究表明COPD的患病率有所增加.而COPD急性加重(acute exacerbation of chronic obstructivepulmonary disease,AECOPD)增加了医疗卫生资源的耗用,是COPD患者医药费用的首要负担,也是COPD患者的主要死因.当下临床研究的重点是对急性加重的管理,预防AECOPD尚未引起临床工作者足够重视,如何预防和减少AECOPD的发生和发展成为降低COPD患病率和病死率及减轻COPD经济负担的研究重点.本文通过研究阅读国内外相关最新研究成果,就AECOPD危险因素作出总结、探讨,阐明AECOPD相关危险因素,更好地指导临床实践,从而为AECOPD患者提供更佳的医疗服务.     

Management of acute exacerbations of COPD

Exacerbations of COPD are common and cause a considerable burden to the patient and the healthcare system. To optimize the hospital care of patients with exacerbations of COPD, clinicians should be aware of some key points: management of exacerbations is broadly based on clinical features and severity. Initial clinical evaluation is crucial to define those patients requiring hospital admission and those who could be managed as outpatients. In hospitalized patients, the appropriate level of care should be determined by the initial severity and response to initial medical treatment. Medical treatment should follow recent recommendations, including rest, titrated oxygen therapy, inhaled or nebulized short-acting bronchodilators (Beta2-agonists and anticholinergic agents), DVT prevention with LMWH, steroids in most severely ill patients, unless there are contraindications and antibiotics in the case of a clear bacterial infectious aetiology. Severe exacerbations may lead to acute hypercapnic respiratory failure. Unless contraindicated, non-invasive ventilation (NIV) should be the first line ventilatory support for these patients. NIV should be commenced early, before severe acidosis ensues, to avoid the need for endotracheal intubation and to reduce mortality and treatment failures. Several randomised controlled clinical trials support the use of NIV in the management of acute exacerbations of COPD, demonstrating a decreased need for mechanical ventilation and an improved survival. In most severe cases, NIV should be provided in ICU. Although it has been shown that for less severe patients (with pH values>7.30), NIV can be administered safely and effectively on general medical wards, a lead respiratory consultant and trained nurses are mandatory. Mechanical ventilation through an endotracheal tube should be considered when patients have contraindications to the use of NIV or fail to improve on NIV. The duration of mechanical ventilation should be shortened as much as possible by an early weaning process, including preventive post-extubation NIV in hypercapnic patients. hospital stay could be shortened by non-invasive treatments. Future exacerbations should be avoided by respiratory specialist management of the patients, including education, optimization of long-term medical treatment, vaccinations, nutritional support, and pulmonary rehabilitation.     

合并右心衰竭对慢性阻塞性肺疾病急性加重频率及严重程度的影响

目的:探讨合并右心衰竭对慢性阻塞性肺疾病(COPD)急性加重频率以及严重程度的影响。方法:选择COPD患者274例,其中无右心衰竭患者194例,合并右心衰竭患者80例,随访1年,记录其急性加重事件发生情况。结果:合并右心衰竭组急性加重次数明显高于无右心衰竭组[(1.33±0.49)次/年vs(0.86±0.25)次/年,P0.05]。合并右心衰竭组急性加重严重程度(血气分析、呼吸困难评分、不良事件和严重不良事件)显著高于无右心衰竭组(均P0.05)。结论 :合并右心衰竭可能是COPD发生多次和严重急性加重的重要危险因素。     

Roflumilast: clinical benefit in patients suffering from COPD

Background and aims: Chronic obstructive pulmonary disease (COPD) is associated with substantial morbidity and mortality and is characterised by persistent airway inflammation, which leads to impaired airway function, quality of life and intermittent exacerbations. In spite of recent advances in the treatment of COPD, new treatment options for COPD are clearly necessary. The oral phosphodiesterase‐4 (PDE4) inhibitor roflumilast represents a new class of drugs that has shown efficacy and acceptable tolerability in preclinical and short‐term clinical studies in patients with COPD. Methods and results: The available long‐term clinical studies reviewed here suggest that the clinical efficacy of roflumilast is likely because of the suppression of airway inflammation and not through bronchodilation. Furthermore, the clinical studies have shown a modest improvement in airway function, including FEV₁, and a reduction in frequency and severity of COPD exacerbations, as well as a positive effect on several patient‐reported outcomes. The clinical benefit of roflumilast appears to be greatest in patients with more symptomatic and severe disease who experience exacerbations. The most common adverse effects are gastrointestinal events, primarily diarrhoea, nauseas and weight loss. Conclusion: Roflumilast is beneficial for maintenance treatment of patients with severe and symptomatic COPD and with a history of frequent acute exacerbations as an add‐on to treatment with long‐acting bronchodilators. It may have a role as an alternative to inhaled corticosteroids in more symptomatic COPD patients with frequent exacerbations, although direct comparisons are currently lacking. Please cite this paper as: Ulrik CS and Calverley PMA. Roflumilast: clinical benefit in patients suffering from COPD. Clin Respir J 2010; 4: 197–201.     

Management of acute exacerbations in chronic obstructive pulmonary disease

An acute exacerbation of chronic obstructive pulmonary disease (COPD) is characterized by an acute worsening of symptoms accompanied by lung infection. In severe cases, an acute exacerbation may cause respiratory failure and death. Successful management of acute exacerbation of COPD in either the inpatient or outpatient setting requires attention to a number of key issues. In this review, issues regarding the management of acute exacerbations of COPD are discussed. An inhaled beta-2 agonist along with the inhaled anticholinergic bronchodilator are recommended. Antibiotic therapy has been demonstrated to improve clinical recovery and physical outcomes. It should be directed against the most commonly occurring pathogens and, in more severe cases, coverage against Gram-negative bacteria is considered. Short course of systemic steroids does provide benefit in hospitalized patients. Supplemental oxygen is appropriate for all patients with hypoxemia. Ventilatory support treatment may be necessary, noninvasive ventilatory assistance being preferable early in the course of the acute episode. In a high number of cases, endotracheal intubation may be avoided. Promoting smoking cessation and the use of influenzae and pneumococcal vaccination may help decrease frequency of episodes of these exacerbations.     

肺部固有免疫力相关指标与COPD急性加重关系的研究进展

COPD是一种常见的慢性气道炎症性疾病,病情呈进行性发展。COPD病程中可因细菌、病毒感染、环境污染恶化等因素导致COPD急性加重（AECOPD）,越来越多的研究提示AECOPD加速疾病的进展,降低患者的生活质量,增加住院率及病死率。肺部的固有免疫系统在肺脏抵抗病原体入侵中起重要作用,与急性加重的发生有着密切的相关性。现就溶菌酶、人细胞表面活性因子、白细胞蛋白酶抑制因子、分泌型IgA、克拉拉细胞分泌蛋白16等肺部固有免疫力指标的变化与AECOPD的相关性作一分析。     

Acute exacerbations and respiratory failure in chronic obstructive pulmonary disease

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) describe the phenomenon of sudden worsening in airway function and respiratory symptoms in patients with COPD. These exacerbations can range from self-limited diseases to episodes of florid respiratory failure requiring mechanical ventilation. The average patient with COPD experiences two such episodes annually, and they account for significant consumption of health care resources. Although bacterial infections are the most common causes of AECOPD, viral infections and environmental stresses are also implicated. AECOPD episodes can be triggered or complicated by other comorbidities, such as heart disease, other lung diseases (e.g., pulmonary emboli, aspiration, pneumothorax), or systemic processes. Pharmacologic management includes bronchodilators, corticosteroids, and antibiotics in most patients. Oxygen, physical therapy, mucolytics, and airway clearance devices may be useful in selected patients. In hypercapneic respiratory failure, noninvasive positive pressure ventilation may allow time for other therapies to work and thus avoid endotracheal intubation. If the patient requires invasive mechanical ventilation, the focus should be on avoiding ventilator-induced lung injury and minimizing intrinsic positive end-expiratory pressure. These may require limiting ventilation and "permissive hypercapnia." Although mild episodes of AECOPD are generally reversible, more severe forms of respiratory failure are associated with a substantial mortality and a prolonged period of disability in survivors.     

COPD management. Part I. Strategies for managing the burden of established COPD.

Effective management of chronic obstructive pulmonary disease (COPD) is dependent on an accurate diagnosis and assessment of severity. COPD is a clinical diagnosis, based on a history of exposure to known risk factors and the presence of airway obstruction that is not fully reversible. Maximal therapy and support for smoking cessation should be offered to all patients. Symptoms may only develop when a significant loss of lung function has occurred, and the diagnosis is frequently made late in the course of the disease. Earlier diagnosis is dependent on a high index of suspicion, particularly in current and ex-smokers or those exposed to occupational dusts and indoor pollution, and accurate performance and interpretation of spirometry. Established COPD associated with symptoms should initially be treated with bronchodilators as needed, but long-acting bronchodilators should be used when symptoms persist and inhaled corticosteroids added for moderate to severe airflow limitation, particularly when associated with exacerbations. Combination long-acting bronchodilators and inhaled corticosteroids reduce the exacerbation rate and improve the quality of life and symptoms, but they have not been shown to improve survival. Exacerbations are associated with worsening health status and can be managed effectively at home. When symptoms worsen despite optimal treatment for exacerbations, hospital admission is necessary. Non-invasive ventilation has reduced the need for mechanical ventilation, but hospital admission and respiratory failure are associated with a significantly worse prognosis. Pulmonary rehabilitation plays an important role in improving exercise capacity at all severities of COPD, and should be widely available.     

The Diagnosis and Treatment of Elderly Patients with Acute Exacerbation of Chronic Obstructive Pulmonary Disease and Chronic Bronchitis

The syndrome of chronic obstructive pulmonary disease (COPD) consists of chronic bronchitis (CB), bronchiectasis, emphysema, and reversible airway disease that combine uniquely in an individual patient. Older patients are at risk for COPD and its components—emphysema, CB, and bronchiectasis. Bacterial and viral infections play a role in acute exacerbations of COPD (AECOPD) and in acute exacerbations of CB (AECB) without features of COPD. Older patients are at risk for resistant bacterial organisms during their episodes of AECOPD and AECB. Organisms include the more‐common bacteria implicated in AECOPD/AECB such as Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Less‐common nonenteric, gram‐negative organisms including Pseudomonas aeruginosa, gram‐positive organisms including Staphylococcus aureus, and strains of nontuberculosis Mycobacteria are more often seen in AECOPD/AECB episodes involving elderly patients with frequent episodes of CB or those with bronchiectasis. Risk‐stratified antibiotic treatment guidelines appear useful for purulent episodes of AECOPD and episodes of AECB. These guidelines have not been prospectively validated for the general population and especially not for the elderly population. Using a risk‐stratification approach for elderly patients, first‐line antibiotics (e.g., amoxicillin, ampicillin, pivampicillin, trimethoprim/sulfamethoxazole, and doxycycline), with a more‐limited spectrum of antibacterial coverage, are used in patients who are likely to have a low probability of resistant organisms during AECOPD/AECB. Second‐line antibiotics (e.g., amoxicillin/clavulanic acid, second‐ or third‐generation cephalosporins, and respiratory fluoroquinolones) with a broader spectrum of coverage are reserved for patients with significant risk factors for resistant organisms and those who have failed initial antibiotic treatment.     

The chronic obstructive pulmonary disease exacerbation

Chronic obstructive pulmonary disease is the only leading cause of death with a rising prevalence. The medical and economic costs arising from acute exacerbations of COPD are therefore expected to increase over the coming years. Although exacerbations may be initiated by multiple factors, the most common identifiable associations are with bacterial and viral infections. These are associated with approximately 50% to 70% and 20% to 30% of COPD exacerbations, respectively. In addition to smoking cessation, annual influenza vaccination is the most important method for preventing exacerbations. Controlled O2 is the most important intervention for patients with acute hypoxic respiratory failure. Evidence from randomized, controlled trials justifies the use of corticosteroids, bronchodilators (but not theophylline), noninvasive positive-pressure ventilation (in selected patients), and antibiotics, particularly for severe exacerbations. Antibiotics should be chosen according to the patient's risk for treatment failure and the potential for antibiotic resistance. In the acute setting, combined treatment with beta-agonist and anticholinergic bronchodilators is reasonable but not supported by randomized controlled studies. Physicians should identify and, when possible, correct malnutrition. Chest physiotherapy has no proven role in the management of acute exacerbations.     

Neue Therapiekonzepte bei COPD

Classification of severity of the disease is the basis of the therapeutic concept for chronic obstructive lung disease (COPD). Besides pharmacological treatment, preventive measures and rehabilitation with training are the main parts of COPD therapy. Weaning patients of cigarette smoking is of utmost importance in every stage for the course of the disease. Inhalative short acting bronchodilators on demand are the basis of treatment in all stages as well as long acting bronchodilators from stage II on as continuous medication. Theophyllines are of additional importance in higher degrees of the disease. Inhalative steroids are indicated in severe stages III or higher, systemic steroids only during exacerbations as short course therapy. Oxygen long time treatment, intermittent non-invasive ventilation, and operations in some cases are additional therapies.