• Diagnosis of COPD is based on a history of exposure to risk factors and the presence of airflow limitation that is not fully reversible, with or without the presence of symptoms.

• Patients who have chronic cough and sputum production with a history of exposure to risk factors should be tested for airflow limitation, even if they do not have dyspnea.

• For the diagnosis and assessment of COPD, spirometry is the gold standard as it is the most reproducible, standardized, and objective way of measuring airflow limitation. FEV₁/FVC < 70% and a postbronchodilator FEV₁ < 80% predicted confirms the presence of airflow limitation that is not fully reversible.

• Health care workers involved in the diagnosis and management of patients with COPD should have access to spirometry.

• Measurement of arterial blood gas tensions should be considered in all patients with FEV₁ < 40% predicted or clinical signs suggestive of respiratory failure or right heart failure.

Diagnosis. A diagnosis of COPD (Table 5) should be considered in any patient who has cough, sputum production, dyspnea, or a history of exposure to risk factors for the disease. The diagnosis is confirmed by an objective measure of airflow limitation, preferably spirometry.

Assessment of symptoms. Chronic cough, usually the first symptom of COPD to develop (67), may initially be intermittent, but later is present every day, often throughout the day, and is seldom entirely nocturnal. In some cases, significant airflow limitation may develop without the presence of a cough. Small quantities of tenacious sputum are commonly raised by patients with COPD after coughing bouts. Dyspnea is the reason most patients seek medical attention and is a major cause of disability and anxiety associated with the disease. As lung function deteriorates, breathlessness becomes more intrusive. Wheezing and chest tightness are relatively nonspecific symptoms and may vary between days and over the course of a single day. An absence of wheezing or chest tightness does not exclude a diagnosis of COPD.

Medical history. A detailed medical history of a new patient known or thought to have COPD should assess:

1. Exposure to risk factors.

2. Past medical history, including asthma, allergy, sinusitis or nasal polyps, respiratory infections in childhood, and other respiratory diseases.

3. Family history of COPD or other chronic respiratory disease.

4. Pattern of symptom development.

5. History of exacerbations or previous hospitalizations for respiratory disorder.

6. Presence of comorbidities, such as heart disease and rheumatic disease, that may also contribute to restriction of activity.

7. Appropriateness of current medical treatments.

8. Impact of disease on patient's life, including limitation of activity; missed work and economic impact; effect on family routines; and feelings of depression or anxiety.

9. Social and family support available to the patient.

10. Possibilities for reducing risk factors, especially smoking cessation.

Physical examination. Though an important part of patient care, a physical examination is rarely diagnostic in COPD. Physical signs of airflow limitation are rarely present until significant impairment of lung function has occurred (68, 69), and their detection has a relatively low sensitivity and specificity.

Measurement of airflow limitation. To help identify patients earlier in the course of the disease, spirometry should be performed for patients who have chronic cough and sputum production and a history of exposure to risk factors, even if they do not have dyspnea. Spirometry should measure the maximal volume of air forcibly exhaled from the point of maximal inhalation (FVC) and the volume of air exhaled during the first second of this maneuver (FEV₁), and the ratio of these two measurements (FEV₁/FVC) should be calculated. Patients with COPD typically show a decrease in both FEV₁ and FVC. The presence of a postbronchodilator FEV₁ < 80% of the predicted value in combination with an FEV₁/FVC < 70% confirms the presence of airflow limitation that is not fully reversible. The FEV₁/FVC on its own is a more sensitive measure of airflow limitation, and an FEV₁/FVC < 70% is considered an early sign of airflow limitation in patients whose FEV₁ remains normal (⩾ 80% predicted). This approach to defining airflow limitation is a pragmatic one in view of the fact that universally applicable reference values for FEV₁ and FVC are not available.

Assessment of severity. Assessment of severity (Table 2) is based on the level of symptoms, severity of the spirometric abnormality, and the presence of complications such as respiratory failure and right heart failure.

Additional investigations. For patients in Stage II: Moderate COPD and beyond, the following additional investigations may be useful:

1. Bronchodilator reversibility testing. Generally performed only once, at the time of diagnosis, this test is useful to help rule out a diagnosis of asthma, to establish a patient's best attainable lung function, to gauge a patient's prognosis, and to guide treatment decisions. However, even patients who do not show a significant FEV₁ response to a short-acting bronchodilator test can benefit symptomatically from long-term bronchodilator treatment.

2. Glucocorticosteroid reversibility testing. The simplest, and potentially safest, way to identify patients most likely to respond to long-term glucocorticosteroid treatment is with a treatment trial of inhaled glucocorticosteroids for 6 wk to 3 mo, using as criteria for glucocorticosteroid reversibility an FEV₁ increase of 200 ml and 15% above baseline (70, 71). The response to glucocorticosteroids should be evaluated with respect to the postbronchodilator FEV₁ (that is, the effect of treatment with inhaled glucocorticosteroids should be in addition to that of regular treatment with a bronchodilator).

3. Chest X-ray. A chest radiograph is seldom diagnostic in COPD unless obvious bullous disease is present, but it is valuable in excluding alternative diagnoses. Computed tomography (CT) of the chest is not routinely recommended. However, when there is doubt about the diagnosis of COPD, high-resolution CT (HRCT) might help in the differential diagnosis. In addition, if a surgical procedure such as bullectomy or lung volume reduction is contemplated, chest CT is helpful.

4. Arterial blood gas measurement. In advanced COPD, measurement of arterial blood gases is important. This test should be performed in patients with FEV₁ < 40% predicted or with clinical signs suggestive of respiratory failure or right heart failure. Clinical signs of respiratory failure or right heart failure include central cyanosis, ankle swelling, and an increase in the jugular venous pressure. Clinical signs of hypercapnia are extremely nonspecific outside of acute exacerbations. Respiratory failure is indicated by Pa_O2 < 8.0 kPa (60 mm Hg) with or without Pa_CO2 > 6.0 kPa (45 mm Hg) while breathing air at sea level. Measurement of arterial blood gases should be obtained by arterial puncture; finger or ear oximeters for assessing Sa_O2 are less reliable.

5. α₁-Antitrypsin deficiency screening. In patients who develop COPD at a young age (< 45 yr) or who have a strong family history of the disease, it may be valuable to identify coexisting α₁-antitrypsin deficiency. This could lead to family screening and appropriate counseling.

Differential diagnosis. A major differential diagnosis is asthma. In some patients with chronic asthma, a clear distinction from COPD is not possible using current imaging and physiologic testing techniques. In these cases, current management is similar to that of asthma. Other potential diagnoses are usually easier to distinguish from COPD (Table 6).

• Reduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD.

• Smoking cessation is the single most effective—and cost-effective—way to reduce the risk of developing COPD and stop its progression (Evidence A).

• Brief tobacco dependence treatment is effective (Evidence A) and every tobacco user should be offered at least this treatment at every visit to a health care provider.

• Three types of counseling are especially effective: practical counseling, social support as part of treatment, and social support arranged outside of treatment (Evidence A).

• Several effective pharmacotherapies for tobacco dependence are available (Evidence A), and at least one of these medications should be added to counseling if necessary and in the absence of contraindications.

• Progression of many occupationally induced respiratory disorders can be reduced or controlled through a variety of strategies aimed at reducing the burden of inhaled particles and gases (Evidence B).

Smoking Prevention and Cessation. Comprehensive tobacco control policies and programs with clear, consistent, and repeated nonsmoking messages should be delivered through every feasible channel. Legislation to establish smoke-free schools, public facilities, and work environments should be encouraged by government officials, public health workers, and the public. Smoking cessation is the single most effective—and cost-effective—way to reduce the risk of developing COPD and stop its progression. Even a brief, 3-min period of counseling to urge a smoker to quit can be effective, and at the very least this should be done for every smoker at every visit (72, 73). Health education, public policy, and information dissemination programs are all vital components in a comprehensive cessation effort.

Guidelines for smoking cessation. Guidelines for smoking cessation were published by the U.S. Agency for Health Care Policy and Research (AHCPR) in 1996 (74) and updated in 2000 by the U.S. Public Health Service in Treating Tobacco Use and Dependence: A Clinical Practice Guideline (75).

Smoking cessation intervention process. The Public Health Service Report recommends a five-step program for intervention (Table 7), which provides a strategic framework helpful to health care providers interested in helping their patients stop smoking. Three types of counseling are especially effective: practical counseling, social support as part of treatment, and social support arranged outside of treatment (74-79) (Evidence A).

Pharmacotherapy. Numerous effective pharmacotherapies for smoking cessation now exist (75, 79, 80) (Evidence A). Except in the presence of special circumstances, pharmacotherapy is recommended when counseling is not sufficient to help patients quit smoking. Numerous studies indicate that nicotine replacement therapy in any form (nicotine gum, inhaler, nasal spray, transdermal patch, sublingual tablet, or lozenge) reliably increases long-term smoking abstinence rates (75, 80). The antidepressants bupropion and nortriptyline have also been shown to increase long-term quit rates, although fewer studies have been conducted with these medications (75, 80). The effectiveness of the antihypertensive drug clonidine is limited by side effects (80). Special consideration should be given before using pharmacotherapy in selected populations: people with medical contraindications, light smokers (fewer than 10 cigarettes/day), and pregnant and adolescent smokers.

Occupational Exposures. Although it is not known how many individuals are at risk of developing respiratory disease from occupational exposures in either developing or developed countries, many occupationally induced respiratory disorders can be reduced or controlled through a variety of strategies aimed at reducing the burden of inhaled particles and gases (81). Emphasis should be on primary prevention, which is best achieved by the elimination or reduction of exposures to various substances in the workplace. Secondary prevention, achieved through epidemiologic surveillance and early case detection, is also of great importance.

Indoor/Outdoor Air Pollution. Individuals experience diverse indoor and outdoor environments throughout the day, each of which has its own unique set of air contaminants. Although outdoor and indoor air pollution are generally thought of separately, the concept of total personal exposure may be more relevant for COPD. Reducing the risk from indoor and outdoor air pollution requires a combination of public policy and protective steps taken by individual patients.

The health care provider should consider susceptibility (including family history, exposure to indoor/outdoor pollution) for each individual patient (82). Those who are at high risk should avoid vigorous exercise outdoors during pollution episodes. If various solid fuels are used for cooking and heating, adequate ventilation should be encouraged. Persons with severe COPD should monitor public announcements of air quality and should stay indoors when air quality is poor. Under most circumstances, health care providers should not suggest respiratory protection as a method for reducing the risks of ambient air pollution. Air cleaners have not been shown to have health benefits, whether directed at pollutants generated by indoor sources or at those brought in with outdoor air.

• The overall approach to managing stable COPD should be characterized by a stepwise increase in treatment, depending on the severity of the disease.

• For patients with COPD, health education can play a role in improving skills, ability to cope with illness, and health status. It is effective in accomplishing certain goals, including smoking cessation (Evidence A).

• None of the existing medications for COPD has been shown to modify the long-term decline in lung function that is the hallmark of this disease (Evidence A). Therefore, pharmacotherapy for COPD is used to decrease symptoms and complications.

• Bronchodilator medications are central to the symptomatic management of COPD (Evidence A). They are given on an as-needed basis or on a regular basis to prevent or reduce symptoms.

• The principal bronchodilator treatments are β₂-agonists, anticholinergics, theophylline, and a combination of one or more of these drugs (Evidence A).

• Regular treatment with inhaled glucocorticosteroids should only be prescribed for symptomatic patients with COPD with a documented spirometric response to glucocorticosteroids or for those with an FEV₁ < 50% predicted and repeated exacerbations requiring treatment with antibiotics or oral glucocorticosteroids (Evidence B).

• Chronic treatment with systemic glucocorticosteroids should be avoided because of an unfavorable benefit-to-risk ratio (Evidence A).

• All patients with COPD benefit from exercise training programs, improving with respect to both exercise tolerance and symptoms of dyspnea and fatigue (Evidence A).

• The long-term administration of oxygen (> 15 h per day) to patients with chronic respiratory failure has been shown to increase survival (Evidence A).

Introduction. The overall approach to managing stable COPD should be characterized by a stepwise increase in treatment, depending on the severity of the disease. The management strategy is based on an individualized assessment of disease severity and response to various therapies. Disease severity is determined by the severity of symptoms and airflow limitation, as well as other factors such as the frequency and severity of exacerbations, complications, respiratory failure, comorbidities (cardiovascular disease, sleep-related disorders, etc.), and the general health status of the patient. Treatment depends on the patient's educational level and willingness to apply the recommended management, on cultural and local conditions, and on the availability of medications.

Education. Although patient education alone does not improve exercise performance or lung function (83-86), it can play a role in improving skills, ability to cope with illness, and health status (87). In addition, patient education is effective in accomplishing certain specific goals, including smoking cessation (38) (Evidence A), initiating discussions and understanding of advance directives and end-of-life issues (88) (Evidence B), and improving patient responses to acute exacerbations (89, 90) (Evidence B).

Education may take place in many settings: consultations with physicians or other health care workers, home care or outreach programs, and comprehensive pulmonary rehabilitation programs. It should be tailored to the needs and environment of the patient, interactive, directed at improving quality of life, simple to follow, practical, and appropriate to the intellectual and social skills of the patient and the caregiver. The topics that seem most appropriate for an education program to cover include: smoking cessation; basic information about COPD and pathophysiology of the disease; general approach to therapy and specific aspects of medical treatment; self-management skills; strategies to help minimize dyspnea; advice about when to seek help; self-management and decision-making in exacerbations; and advance directives and end-of-life issues.

Pharmacologic Treatment. Pharmacologic therapy (Table 8) is used to prevent and control symptoms, reduce the frequency and severity of exacerbations, improve health status, and improve exercise tolerance. None of the existing medications for COPD has been shown to modify the long-term decline in lung function that is the hallmark of this disease (38, 91-94) (Evidence A). However, this should not preclude efforts to use medications to control symptoms.

Bronchodilators. Bronchodilator medications are central to the symptomatic management of COPD (95-98) (Evidence A) (Table 9). They are given either on an as-needed basis for relief of persistent or worsening symptoms, or on a regular basis to prevent or reduce symptoms. Dose–response relationships using FEV₁ as the outcome are relatively flat with all classes of bronchodilators. Side effects are pharmacologically predictable and dose-dependent. Adverse effects are less likely and resolve more rapidly after treatment withdrawal with inhaled than with oral treatment. When treatment is given by the inhaled route, attention to effective drug delivery and training in inhaler technique is essential.

The classes of bronchodilator drugs commonly used in treating COPD, β₂-agonists, anticholinergics, and methylxanthines, are shown in Table 10. The choice depends on the availability of the medication and the patient's response. All categories of bronchodilators have been shown to increase exercise capacity in COPD, without necessarily producing significant changes in FEV₁ (99-101) (Evidence A). Regular treatment with short-acting bronchodilators is cheaper but less convenient than treatment with long-acting bronchodilators. The long-acting, inhaled β₂-agonist salmeterol has been shown to improve health status significantly in doses of 50 μg twice daily (102) (Evidence B). Similar data for short-acting β₂-agonists are not available. Use of inhaled ipratropium (an anticholinergic) four times daily also improves health status (Evidence B) (103). Theophylline is effective in COPD, but because of its potential toxicity, inhaled bronchodilators are preferred when available. All studies that have shown efficacy of theophylline in COPD were done with slow-release preparations.

Combining drugs with different mechanisms and durations of action might increase the degree of bronchodilation for equivalent or lesser side effects. A combination of a short-acting β₂-agonist and the anticholinergic drug ipratropium in stable COPD produces greater and more sustained improvements in FEV₁ than either alone and does not produce evidence of tachyphylaxis over 90 d of treatment (104-106) (Evidence A). Combination of a β₂-agonist, an anticholinergic, or theophylline may produce additional improvements in lung function (104, 107-109) and health status (101, 104, 107, 110). Increasing the number of drugs usually increases costs, and an equivalent benefit may occur by increasing the dose of one bronchodilator when side effects are not a limiting factor. Detailed assessments of this approach have not been carried out.

Increasing the dose of either a β₂-agonist or an anticholinergic, especially when given by a wet nebulizer, appears to provide subjective benefit in acute episodes (111) (Evidence B). Some patients may request regular treatment with high-dose, nebulized bronchodilators (112), especially if they have experienced subjective benefit from this treatment during an acute exacerbation. Clear scientific evidence for this approach is lacking, but one option is to examine the improvement in mean daily peak expiratory flow (PEF) recording during 2 wk of treatment in the home and continue with nebulizer therapy if a significant improvement occurs (112). In general, nebulized therapy for a stable patient is not appropriate unless it has been shown to be better than conventional dose therapy.

Glucocorticosteroids. Prolonged treatment with inhaled glucocorticosteroids does not modify the long-term decline in FEV₁ in patients with COPD (91-94). Regular treatment with inhaled glucocorticosteroids is only appropriate for symptomatic COPD patients with a documented spirometric response to inhaled glucocorticosteroids (see Component 1) or in those with FEV₁ < 50% predicted (Stage IIB: Moderate COPD and Stage III: Severe COPD) and repeated exacerbations requiring treatment with antibiotics or oral glucocorticosteroids (91– 94) (Evidence B). The dose–response relationships and long-term safety of inhaled glucocorticosteroids in COPD are not known. The present guidelines recommend a trial of 6 wk to 3 mo with inhaled glucocorticosteroids to identify COPD patients who may benefit from long-term inhaled glucocorticosteroid therapy. Many existing COPD guidelines recommend the use of a short course (2 wk) of oral glucocorticosteroids to identify patients with COPD who might benefit from long-term treatment with oral or inhaled glucocorticosteroids. There is mounting evidence, however, that a short course of oral glucocorticosteroids is a poor predictor of the long-term response to inhaled glucocorticosteroids in COPD (93, 113).

Long-term treatment with oral glucocorticosteroids is not recommended in COPD (114-116) (Evidence A). There is no evidence of long-term benefit from this treatment. Moreover, a side effect of long-term treatment with systemic glucocorticosteroids is steroid myopathy (115, 116), which contributes to muscle weakness, decreased functionality, and respiratory failure in patients with advanced COPD.

• Exacerbations of respiratory symptoms requiring medical intervention are important clinical events in COPD.

• The most common causes of an exacerbation are infection of the tracheobronchial tree and air pollution, but the cause of approximately one-third of severe exacerbations cannot be identified (Evidence B).

• Inhaled bronchodilators (particularly inhaled β₂-agonists or anticholinergics), theophylline, and systemic, preferably oral, glucocorticosteroids are effective for treatments for acute exacerbations of COPD (Evidence A).

• Patients experiencing COPD exacerbations with clinical signs of airway infection (e.g., increased volume and change of color of sputum, or fever) may benefit from antibiotic treatment (Evidence B).

• Noninvasive positive pressure ventilation (NIPPV) in acute exacerbations improves blood gases and pH, reduces in-hospital mortality, decreases the need for invasive mechanical ventilation and intubation, and decreases the length of hospital stay (Evidence A).

COPD is often associated with acute exacerbations of symptoms (162-165). The economic and social burden of COPD exacerbations is extremely high. The most common causes of an exacerbation are infection of the tracheobronchial tree (166-170) and air pollution (171), but the cause of approximately one-third of severe exacerbations cannot be identified (172). The role of bacterial infections, once believed to be the main cause of COPD exacerbations, is controversial (166-170, 173-175). Conditions that may mimic an acute exacerbation include pneumonia, congestive heart failure, pneumothorax, pleural effusion, pulmonary embolism, and arrhythmia.

Diagnosis and Assessment of Severity. Increased breathlessness, the main symptom of an exacerbation, is often accompanied by wheezing and chest tightness, increased cough and sputum, change of the color or tenacity of sputum, and fever. Exacerbations may also be accompanied by a number of nonspecific complaints, such as malaise, insomnia, sleepiness, fatigue, depression, and confusion. A decrease in exercise tolerance, fever, or new radiologic anomalies suggestive of pulmonary disease may herald a COPD exacerbation. An increase in sputum volume and purulence points to a bacterial cause, as does a prior history of chronic sputum production (170).

The assessment of the severity of an acute exacerbation is based on the patient's medical history before the exacerbation, symptoms, physical examination, lung function tests, arterial blood gas measurements, and other laboratory tests. The medical history should cover how long worsening or new symptoms have been present, the frequency and severity of breathlessness and coughing attacks, sputum volume and color, limitation of daily activities, any previous episodes/exacerbations and whether they required hospitalization, and the present treatment regimen. When available, prior measurements of lung function and arterial blood gases are extremely useful for comparison with those made during the acute episode, as an acute change in these tests is more important than their absolute values. In patients with very severe COPD, the most important sign of severe exacerbation is a change in alertness and this signals a need for immediate evaluation in the hospital.

Lung function tests. Even simple lung function tests can be difficult for a sick patient to perform properly. In general, PEF < 100 L/min or FEV₁ < 1.00 L indicates a severe exacerbation (176-178).

Assessment of arterial blood gases. In the hospital, measurement of arterial blood gases is essential to assess the severity of an exacerbation. Pa_O2 < 8.0 kPa (60 mm Hg) or Sa_O2 < 90% (when breathing room air) indicates respiratory failure. In addition, Pa_O2 < 6.7 kPa (50 mm Hg), Pa_CO2 > 9.3 kPa (70 mm Hg), and pH < 7.30 point toward a life-threatening episode that needs close monitoring or intensive care unit (ICU) management (179).

Chest X-ray and ECG. Chest radiographs (posterior/anterior plus lateral) are useful in identifying alternative diagnoses that can mimic the symptoms of an exacerbation. An ECG aids in the diagnosis of right ventricular hypertrophy, arrhythmias, and ischemic episodes. Pulmonary embolism can be very difficult to distinguish from an acute exacerbation, especially in severe COPD, because right ventricular hypertrophy and large pulmonary arteries lead to confusing ECG and radiographic results. Spiral CT scanning and angiography and perhaps specific d-dimer assays are the best tools presently available for diagnosis of pulmonary embolism in patients with COPD but ventilation–perfusion scanning is of no value. A low systolic blood pressure and an inability to increase the Pa_O2 above 8.0 kPa (60 mm Hg) despite high flow oxygen also suggest pulmonary embolism. If there are strong indications that pulmonary embolism has occurred, it is best to treat for this along with the exacerbation.

Other laboratory tests. The whole blood count may identify polycythemia (hematocrit > 55%) or bleeding. White blood cell counts are usually not very informative. The presence of purulent sputum during an exacerbation of symptoms is sufficient indication for starting antibiotic treatment. Streptococcus pneumoniae, Hemophilus influenzae, and Moraxella catarrhalis are the most common bacterial pathogens involved in COPD exacerbations. If an infectious exacerbation does not respond to initial antibiotic treatment, a sputum culture and an antibiogram should be performed. Biochemical tests can reveal whether the cause of the exacerbation is an electrolyte disturbance (hyponatremia, hypokalemia, etc.), a diabetic crisis, or poor nutrition (low proteins), and may suggest a metabolic acid–base disorder.

Home Management. There is increasing interest in home care for patients with end-stage COPD, although economic studies of home care services have yielded mixed results. A major outstanding issue is when to treat an exacerbation at home and when to hospitalize the patient.

Bronchodilator therapy. Home management of COPD exacerbations involves increasing the dose or frequency of existing bronchodilator therapy (Evidence A). If not already used, an anticholinergic can be added until the symptoms improve. In more severe cases, high-dose nebulized therapy can be given on an as-needed basis for several days if a suitable nebulizer is available. However, long-term use of nebulizer therapy after an acute episode is not routinely recommended.

Glucocorticosteroids. Systemic glucocorticosteroids are beneficial in the management of acute exacerbations of COPD. They shorten recovery time and help to restore lung function more quickly (180-182) (Evidence A). They should be considered in addition to bronchodilators if the patient's baseline FEV₁ is < 50% predicted. A dose of 40 mg prednisolone per day for 10 d is recommended (Evidence D).

Antibiotics. Antibiotics are only effective when patients with worsening dyspnea and cough also have increased sputum volume and purulence (Evidence B) (165). The choice of agents should reflect local patterns of antibiotic sensitivity among S. pneumoniae, H. influenzae, and M. catarrhalis.

Hospital Management. The risk of dying from an acute exacerbation of COPD is closely related to the development of respiratory acidosis, the presence of significant comorbidities, and the need for ventilatory support (183). Patients lacking these features are not at high risk of dying, but those with severe underlying COPD often require hospitalization in any case. Attempts at managing such patients entirely in the community have met with only limited success (184), but returning them to their homes with increased social support and a supervised medical care package after an initial emergency room assessment has been much more successful (185). However, detailed cost-benefit analyses of these approaches are awaited.

Hospital assessment/admission should be considered for all patients who fit the criteria shown in Table 11. Some patients need immediate admission to an ICU (Table 12). Admission of patients with severe COPD exacerbations to intermediate or special respiratory care units may be appropriate if personnel, skills, and equipment are available to identify and manage acute respiratory failure successfully. The first actions when a patient reaches the emergency department are to provide controlled oxygen therapy and to determine whether the exacerbation is life-threatening. If so, the patient should be admitted to the ICU immediately. Otherwise, the patient may be managed in the emergency department or hospital as detailed in Table 13.

Controlled oxygen therapy. Oxygen therapy is the cornerstone of hospital treatment of COPD exacerbations. Adequate levels of oxygenation (Pa_O2 > 8.0 kPa, 60 mm Hg or Sa_O2 > 90%) are easy to achieve in uncomplicated exacerbations, but CO₂ retention can occur insidiously with little change in symptoms. Once oxygen is started, arterial blood gases should be checked 30 min later to ensure satisfactory oxygenation without CO₂ retention or acidosis. Venturi masks are more accurate sources of controlled oxygen than are nasal prongs but are more likely to be removed by the patient.

Bronchodilator therapy. Short-acting, inhaled β₂-agonists are usually the preferred bronchodilators for treatment of acute exacerbations of COPD (Evidence A) (81, 123, 124). If a prompt response to these drugs does not occur, the addition of an anticholinergic is recommended, even though evidence concerning the effectiveness of this combination is rather controversial (186, 187). Despite its widespread clinical use, the role of aminophylline in the treatment of COPD exacerbations remains controversial. Most studies of aminophylline have demonstrated minor improvements in lung volumes but also worsening of gas exchange and hypoxemia (188, 189). In more severe exacerbations, addition of an oral or intravenous methylxanthine to the treatment can be considered. However, close monitoring of serum theophylline is recommended to avoid the side effects of these drugs (188, 190-192).

Glucocorticosteroids. Oral or intravenous glucocorticosteroids are recommended as an addition to bronchodilator therapy (plus eventually antibiotics and oxygen therapy) in the hospital management of acute exacerbations of COPD (180– 182) (Evidence A). The exact dose that should be given is not known, but high doses are associated with a significant risk of side effects. Thirty to 40 mg of oral prednisolone daily for 10 to 14 d is a reasonable compromise between efficacy and safety (Evidence D). Prolonged treatment does not result in a greater efficacy and increases the risk of side effects.

Antibiotics. Antibiotics are only effective when patients with worsening dyspnea and cough also have increased sputum volume and purulence (165). The choice of agents should reflect local patterns of antibiotic sensitivity among S. pneumoniae, H. influenzae, and M. catarrhalis.

Ventilatory support. The primary objectives of mechanical support in patients with acute exacerbations in Stage III: Severe COPD are to decrease mortality and morbidity and to relieve symptoms. Ventilatory support includes both noninvasive mechanical ventilation using either negative or positive pressure devices, and invasive (conventional) mechanical ventilation by oro-/naso-tracheal tube or tracheostomy:

1. Noninvasive mechanical ventilation. NIPPV has been studied in many uncontrolled and five randomized controlled trials in acute respiratory failure (193). The studies show consistently positive results with success rates of 80 to 85% (194). Taken together they provide evidence that NIPPV increases pH, reduces Pa_CO2 , reduces the severity of breathlessness in the first 4 h of treatment, and decreases the length of hospital stay (Evidence A). More importantly, mortality—or its surrogate, intubation rate—is reduced by this intervention (195-198). However, NIPPV is not appropriate for all patients, as summarized in Table 14.

2. Invasive (conventional) mechanical ventilation. Patients who show impending acute respiratory failure and those with life-threatening acid–base status abnormalities or altered mental status despite aggressive pharmacologic therapy are likely to be the best candidates for invasive mechanical ventilation. The indications for initiating mechanical ventilation during exacerbations of COPD are shown in Table 15, the first being the commonest and most important reason. The three ventilatory modes most widely used are assisted-control ventilation, and pressure support ventilation alone or in combination with intermittent mandatory ventilation (199). The use of invasive ventilation in patients with end-stage COPD is influenced by the likely reversibility of the precipitating event, the patient's wishes, and the availability of intensive care facilities. Major hazards include the risk of ventilator-acquired pneumonia (especially when multiresistant organisms are prevalent), barotrauma, and failure to wean to spontaneous ventilation. Contrary to some opinions, mortality among COPD patients with respiratory failure is no greater than mortality among patients ventilated for non-COPD causes. When possible, a clear statement of the patient's own treatment wishes—an advance directive or “living will”—makes these difficult decisions much easier to resolve.

Weaning or discontinuation from mechanical ventilation can be particularly difficult and hazardous in patients with COPD, and the best method to wean patients from the ventilator remains a matter of debate (200, 201) Whether pressure support or a T-piece trial is used, weaning is shortened when a clinical protocol is adapted (Evidence A). Noninvasive ventilation (NIV) has been applied to facilitate the weaning process in COPD patients with acute or chronic respiratory failure (202). Compared with invasive pressure support ventilation, NIPPV during weaning shortened weaning time, reduced the stay in the ICU, decreased the incidence of nosocomial pneumonia, and improved 60-d survival rates (202). Similar findings have been reported when NIPPV is used after extubation for hypercapnic respiratory failure (203) (Evidence C).

Other Measures. Further treatment measures that can be used in the hospital include: fluid administration (accurate monitoring of fluid balance is essential); nutrition (supplementary when the patient is too dyspneic to eat); low-molecular-weight heparin in immobilized, polycythemic, or dehydrated patients with or without a history of thromboembolic disease; sputum clearance (by stimulating coughing and low-volume forced expirations as in home management). Manual or mechanical chest percussion and postural drainage may be beneficial in patients producing more than 25 ml sputum per day or with lobar atelectasis.

Hospital Discharge and Follow-up. Insufficient clinical data exist to establish the optimal duration of hospitalization for acute exacerbations of COPD (163, 204, 205). Consensus and limited data support the discharge criteria listed in Table 16. Table 17 provides items to include in a follow-up assessment 4 to 6 wk after discharge from the hospital. Thereafter, follow-up is the same as for stable COPD, including supervising smoking cessation, monitoring the effectiveness of each drug treatment, and monitoring changes in spirometric parameters (81). If hypoxemia developed during the exacerbation, arterial blood gases should be rechecked at discharge and at the follow-up visit. If the patient remains hypoxemic, long-term oxygen therapy should be instituted. Decisions about continuous domiciliary oxygen based on the severity of the acute hypoxemia during an exacerbation are frequently misleading.

The opportunities for prevention of future exacerbations should be reviewed before discharge with particular attention to future influenza vaccination plans, knowledge of current therapy including inhaler technique (206, 207), and how to recognize symptoms of exacerbations. Pharmacotherapy known to reduce the number of exacerbations should be considered. Social problems should be discussed and principal caregivers identified if the patient has a significant persisting disability.

Sherwood Burge (UK)

Moira Chan-Yeung (Hong Kong)

James Donohue (US)

Nicholas J. Gross (US)

Helgo Magnussen (Germany)

Donald Mahler (US)

Jean-Francois Muir (France)

Mrigrendra Pandey (India)

Peter Pare (Canada)

Thomas Petty (US)

Michael Plit (South Africa)

Sri Ram (US)

Harold Rea (New Zealand)

Andrea Rossi (Italy)

Maureen Rutten-van Molken (The Netherlands)

Marina Saetta (Italy)

Raj Singh (India)

Frank Speizer (US)

Robert Stockley (UK)

Donald Tashkin, M.D. (US)

Ian Town (New Zealand)

Paul Vermeire (Belgium)

Gregory Wagner (US)

Scott Weiss, M.D. (US)

Miel Wouters (The Netherlands)

Jan Zielinski (Poland)