Acute exacerbations of COPD

Acute exacerbations of COPD (AECOPD) are a common cause of morbidity and mortality. There is a need for a standardised definition of an exacerbation of COPD. The common aetiological factors are bacterial, viral infection and air pollutants. Exacerbations of COPD may adversely affect the natural history of COPD. Several strategies are available now to prevent or reduce exacerbations of COPD including immunisation against influenza and inhaled corticosteroids in patients with moderate/severe disease. The mainstay of treatment involves increasing bronchodilator therapy, systemic glucocorticoids which have now been shown to have a beneficial effect. The circumstances for the use of antibiotic therapy is now established in patients with increased breathlessness, increased sputum production and/or sputum purulence. In those with respiratory failure, noninvasive ventilation has been shown to reduce intubation rates, shorten lengths of hospitalisation, and improve mortality. Early or immediate supported discharge for selected patients has been shown to be effective in the management of patients with COPD.     

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.     

Pathogenesis of bacterial exacerbations of COPD

Acute exacerbations are significant events in the course of COPD. The pathogenesis of exacerbations was poorly understood, specifically, the role of bacteria was highly controversial. Recent observations have demonstrated that bacterial infection is involved in about half of the exacerbations. The predominant mechanism of bacterial exacerbation in COPD appears to be acquisition of new strains of bacterial pathogens from the environment that are able to establish infection in the tracheobronchial tree in COPD because of compromised innate lung defenses. These pathogens interact with airway cells, elicit an inflammatory response, which underlies the pathophysiology and symptoms characteristic of exacerbation. An immune response that can be mucosal, systemic or both develops to the infecting bacterial strain. This immune response contains the infectious process, could eradicate the infecting pathogen and prevent re-infection with the same strain. However, because of antigenic diversity among bacterial strains, this immunity tends to be strain-specific rather than widely protective. Other mechanisms, including increase in bacterial load and interaction with other etiologies such as viruses, also could contribute to bacterial exacerbations. Improved understanding of the host-pathogen interaction in the airways in COPD will lead to novel approaches to prevention and treatment of exacerbations.     

Non-invasive ventilation in exacerbations of COPD

Randomized controlled trials have confirmed the evidence and helped to define when and where non invasive mechanical ventilation (NIV) should be the first line treatment of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Noninvasive ventilation has its best indication in moderate-to-severe respiratory acidosis in patients with AECOPD. For this indication, studies conducted in ICU, in wards and in accident and emergency departments confirmed its effectiveness in preventing endotracheal intubation and reducing mortality. The skill of the health care team promotes proper NIV utilization and improves the patient outcome. Patients with severe acidosis or with altered levels of consciousness due to hypercapnic acute respiratory failure are exposed to high risk of NIV failure. In these patients a NIV trial may be attempted in closely monitored clinical settings where prompt endotracheal intubation may be assured.     

Macrolide effects on the prevention of COPD exacerbations

The number of senile patients with chronic obstructive pulmonary disease (COPD) has recently increased due to an increase in life expectancy, the habit of smoking and the inhalation of toxic particles. COPD exacerbations are caused by airway bacterial and viral infections, as well as the inhalation of oxidative substrates. COPD exacerbations are associated with the worsening of symptoms and quality of life, as well as an increased mortality rate. Several drugs, including long-acting anti-cholinergic agents, long-acting β(2)-agonists and inhaled corticosteroids, have been developed to improve symptoms in COPD patients and to prevent COPD exacerbations. Treatment with macrolide antibiotics has been reported to prevent COPD exacerbations and improve patient quality of life and symptoms, especially in those patients who have frequent exacerbations. In addition to their antimicrobial effects, macrolides have a variety of physiological functions, such as anti-inflammatory and anti-viral effects, reduced sputum production, the inhibition of biofilm formation and the inhibition of bacterial virulence factor production. These unique activities may relate to the prevention of exacerbations in COPD patients who receive macrolides. Herein, we review the inhibitory effects that macrolides have on COPD exacerbations and explore the possible mechanisms of these effects.     

BODE指数预测慢性阻塞性肺疾病急性发作的意义

目的探讨BODE指数对慢性阻塞性肺疾病（COPD）急性加重的预测价值。方法选取2006年～2007年确诊为COPD的患者168例，分别测定BODE指数。依据指数分为4组：0～2分为A组，3～4分为B组，5～6分为C组，7～10分为D组。进行为期3年的随访，记录急性加重发病的次数及时间。结果Kaplan—Meier法分析表明BODE指数能较好的预测4组COPD患者急性发作的不同趋势（P〈0．05）；ROC曲线表明BODE指数是优于FEV1的预测指标（P〈0．05）。结论BODE指数是预测COPD患者急性发作的较好指标之一。     

Strategies for improving outcomes of COPD exacerbations

COPD is uniquely situated as a chronic disease at the beginning of the 21st century; it is not only an established major cause of mortality and morbidity but is increasing in prevalence despite current medical interventions. In addition COPD is not a stable disease but its natural history is punctuated by periods of acute deterioration or exacerbations. Exacerbations generate considerable additional morbidity and mortality, and directly affect patients’ quality of life. However, despite significant advances in understanding and treating this disease, exacerbations continue to be the major cause of COPD-associated hospitalization, and provision for their management incurs considerable health care costs. This review will consider the current management of COPD exacerbations and how new clinical strategies may improve outcome of these important clinical events.     

Impact of COPD exacerbations on patient-centered outcomes

BACKGROUND: Frequent exacerbations are associated with a faster decline in FEV(1), impaired health status, and worse survival. Their impact and temporal relationship with other outcomes such as functional status, dyspnea, and the multidimensional body mass index, obstruction, dyspnea, exercise capacity (BODE) index remain unknown. HYPOTHESIS: We reasoned that exacerbations affect the BODE index and its components, and that changes in the BODE index could be used to monitor the effect of exacerbations on the host. STUDY DESIGN: Prospective observational study in a Veterans Affairs medical center. METHODS: We studied 205 patients with COPD (mean [+/- SD] FEV(1), 43 +/- 15% predicted), and recorded the body mass index, FEV(1) percent predicted, modified Medical Research Council dyspnea scale, 6-min walk distance, and the BODE index at baseline, during the exacerbation, and at 6, 12, and 24 months following the first episode, and documented all exacerbations for 2 years after the first acute exacerbation. RESULTS: From the cohort, 130 patients (63%) experienced 352 exacerbations or (0.85 exacerbations per patient per year); 48 patients (23%), experienced one episode, 82 patients (40%) experienced 2 or more exacerbations, and 50 patients required hospitalization. At study entry, exacerbators had a worse mean baseline BODE index score (4.2 +/- 2.1 vs 3.57 +/- 2.3, respectively; p < 0.03). The BODE index score worsened by 1.38 points during the exacerbation, and remained 0.8 and 1.1 points above baseline at 1 and 2 years, respectively. There was little change in BODE index score at 2 years in nonexacerbators. CONCLUSION: COPD exacerbations negatively impact on the BODE index and its components. The BODE index is a sensitive tool used to assess the impact of exacerbations and to monitor COPD disease progression.     

COPD exacerbations: the importance of a standard definition

Efforts to assess the efficacy of new therapies in the treatment of acute exacerbations of chronic obstructive pulmonary disease (COPD) have been hampered by the lack of a widely agreed and consistently used definition. A variety of definitions have been used in clinical studies, based on changes in patient symptoms or the requirement for antibiotic therapy, oral steroids or hospitalisation. To date, none of these definitions have been assessed in detail for their reliability, responsiveness and validity determined. Considerable heterogeneity in the aetiology and manifestation of COPD exacerbations makes identification and quantification of defining symptoms extremely difficult. New approaches are therefore being sought with a view to identifying a serum or tissue marker that can be used as a valuable diagnostic tool. Improvements in data recording will also contribute to the accuracy of data retrieval and assessment. If we are to progress to a level of sophistication seen in the diagnosis and management of other diseases, it is evident that considerable research efforts will be required to improve our understanding of COPD exacerbations and develop a standard definition for these events, thereby facilitating the assessment of therapeutic approaches.     

Evidence-based approach to acute exacerbations of COPD

Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death in the United States, and it accounts for approximately 500,000 hospitalizations for exacerbations each year. New definitions of acute COPD exacerbation have been suggested, but the one used by Anthonisen et al. is still widely accepted. It requires the presence of one or more of the following findings: increase in sputum purulence, increase in sputum volume, and worsening of dyspnea. Patients with COPD typically present with acute decompensation of their disease one to three times a year, and 3% to 16% of these will require hospital admission. Hospital mortality of these admissions ranges from 3% to 10% in severe COPD patients, and it is much higher for patients requiring ICU admission. The etiology of the exacerbations is mainly infectious (up to 80%). Other conditions such as heart failure, pulmonary embolism, nonpulmonary infections, and pneumothorax can mimic an acute exacerbation or possibly act as "triggers." Baseline chest radiography and arterial blood gas analysis during an exacerbation are recommended. Oxygen administration through a venturi mask seems to be appropriate and safe, and the oxygen saturation should be kept just above 90%. Either a short acting beta 2-agonist or an anticholinergic is the preferred bronchodilator agent. The choice between the two depends largely on potential undesirable side effects and the patient's coexistent conditions. Adding a second bronchodilator to the first one does not seem to offer much benefit. The evidence suggests similar benefit of MDIs when compared with nebulized treatment for bronchodilator delivery. If MDIs are to be used, spacer devices are recommended. Steroids do improve several outcomes during an acute COPD exacerbation, and a 10- to 14-day course seems appropriate. Antibiotic use has been shown to be beneficial, especially for patients with severe exacerbation. Changes in bacteria strains have been documented during exacerbations, and newer generations of antibiotics might offer a better response rate. There is no role for mucolytic agents or chest physiotherapy in the acute exacerbation setting. Noninvasive positive pressure ventilation might benefit a group of patients with rapid decline in respiratory function and gas exchange. It has the potential to decrease the need for intubation and invasive mechanical ventilation and possibly decrease in-hospital mortality.