Special Feature
Update on COPD Exacerbations: Part I —Overview and Patient Assessment
By David J. Pierson, MD, Editor, Professor, Pulmonary and Critical Care Medicine, Harborview Medical Center, University of Washington, Seattle, is Editor for Critical Care Alert.
Exacerbations of chronic obstructive pulmonary disease (COPD) are an important cause of morbidity and mortality, and have substantial economic consequences. Patients with COPD exacerbations account for a substantial proportion of ICU admissions. Despite the frequency with which they are encountered by intensivists and other clinicians, however, and a large number of available studies and published guidelines on different aspects of their management, COPD exacerbations are often managed suboptimally, and poor outcomes are frequent.
This article reviews some of the evidence underlying current guideline recommendations for the assessment and management of patients with severe COPD exacerbations, and attempts to place such recommendations into practical clinical perspective. The definition, pathogenesis, and etiologies of exacerbations are covered this month, along with an algorithmic scheme for patient assessment. How best to approach the use of bronchodilators, corticosteroids, antibiotics, oxygen, and noninvasive and invasive mechanical ventilation in managing patients with COPD exacerbations will be discussed in the second installment.
What Are Exacerbations and Why Are They Important?
An exacerbation is a sustained worsening of the patient's symptoms from his or her usual stable state that is beyond normal day-to-day variation and acute in onset, generally coming on over 1 to 3 days.1,2 The term should not be applied to an acute respiratory deterioration due to another specific process, such as pneumonia or pneumothorax, or to the sudden episodes of respiratory distress to which patients with very severe obstruction are prone when faced with emotional upset, unaccustomed exertion, or prolonged coughing. The widely used term "acute exacerbation" is technically redundant, since COPD exacerbations are acute by definition.
Exacerbations are important both at the time they occur and in a larger sense because of their influence on the natural course of COPD. Although outcomes vary somewhat by health system and national context, about 10% of patients admitted to US hospitals because of COPD exacerbations die during that hospitalization.3 Having been admitted because of an exacerbation is a marker of increased mortality thereafter. Mortality is as high as 40% during the succeeding year among patients who survive, and the likelihood of dying during that period increases with increasing age.2,3 Exacerbations—especially those requiring hospitalization—account for about 70% of the direct medical costs of COPD.4
Much of our current understanding about the causes and effects of exacerbations5-7 comes from the East London COPD Study, a cohort study carried out during the 1990s. Patients in that study completed daily diary cards on their symptoms, activities, and treatment, and also monitored their pulmonary function at home. The findings of the various arms of the study include the following:
- Exacerbations are more common than previously thought (median, 2.5-3.0 per year), and about half of them are not brought to the attention of the clinicians caring for the patient.8
- Patients with more frequent exacerbations have worse quality of life.9
- Both functional and symptomatic recovery to the patient's baseline status following an exacerbation may take longer than previously appreciated. After one-fourth of exacerbations, patients were not back to their baseline peak flow one month later.9
- Patients who experience more frequent exacerbations have a more rapid overall decline in lung function over time, as measured by forced expiratory flow in the first second (FEV1).10
- Early therapy of exacerbations both hastens functional and symptomatic recovery and is associated with improved quality of life.11
What Causes COPD Exacerbations?
In addition to increased dyspnea and cough, exacerbations are typically associated with an increase in the amount and overt purulence of sputum. Increased amounts of various markers for airway inflammation—such as tumor necrosis factor alpha and interleukins 6 and 8—can be demonstrated at such times.5,6 Studies have demonstrated that the majority of exacerbations are associated with (and presumably caused by) acute airway infection.
From one-third to one-half of all exacerbations are caused by viruses,12 of which the most common by far appears to be rhinovirus. Other viruses that may be isolated from the sputum of patients with COPD exacerbations include coronavirus, influenza virus, parainfluenza virus, adenovirus, and respiratory syncytial virus. One recent study of 107 COPD exacerbations requiring invasive mechanical ventilation found that 64% of these had a probable infectious etiology, with viruses isolated in 43% and a viral infection the presumed sole infection in 33%.13 Patients with viral infection could not be distinguished from the others in the study by any of the clinical or laboratory features examined.
The lower airways of as many as one-third of patients—particularly those with very severe airflow obstruction and those who continue to smoke—are chronically colonized with bacteria, chiefly Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis.5,14 However, despite the frequent presence of airway colonization at baseline, the weight of evidence supports the concept that these bacteria increase in numbers and are responsible for most non-viral infectious exacerbations.15 In addition, patients may acquire new strains of these or other common airway bacteria, and that this event can be associated with severe exacerbations.16
Other causes of COPD exacerbations include atypical organisms such as Chlamydia pneumoniae and Mycoplasma pneumoniae, and exposure to pollutants such as ozone, particulates, sulphur dioxide, and nitrogen dioxide. The latter agents account for most episodes that are not caused by infection. Some patients experiencing exacerbations without features suggesting infection or environmental exposure (a distinct minority of cases) have acute pulmonary embolism,17 as discussed elsewhere in this issue of Critical Care Alert. "Patient noncompliance," with prescribed medications and other therapy, is frequently offered as an explanation for exacerbations, and likely does sometimes precipitate acute clinical deterioration, although this etiology should never be assumed without first excluding other, much more common mechanisms.
How Should Patients Be Assessed?
The initial clinical assessment of a patient presenting with a presumed COPD exacerbation should answer 3 questions:
- Is this a COPD exacerbation, or something else?
- Should the patient be admitted to the hospital?
- Should the patient be admitted to the ICU?
Answering these most urgent questions requires a careful history and physical examination, along with judicious and stepwise application of laboratory and imaging studies. It would be an unjustifiable use of medical resources to obtain arterial blood gases, complete blood count, a chest X-ray, sputum gram stain and culture, and other studies on every patient with known or suspected COPD who presents with increased symptoms. Current guidelines2,3,18 and a substantial body of experimental evidence indicate that such studies can be applied selectively, depending on the urgency of the situation and the findings on initial assessment (see Figure 1 and Table 1).
Not everyone presenting with respiratory distress and a long smoking history has COPD. The discussion in this article applies to patients who meet the diagnostic criteria for COPD, and these rely heavily on the presence of airflow obstruction.20 Many patients who carry the diagnosis of COPD have never had spirometry, and a substantial number of these individuals do not have airflow obstruction—and thus have something other than COPD—despite a suggestive history. All current guidelines rely on pulmonary function testing (primarily the forced expiratory volume in the first second [FEV1] and its relation to the vital capacity), both for diagnosing COPD and for tailoring management to disease severity.20 It may not be technically feasible to obtain spirometry during initial management of acute illness, but the clinician should make a mental note to have this done as soon as possible when the patient improves.
Nearly 20 years ago Anthonisen and colleagues19 classified COPD exacerbations into 3 levels of severity based on just 3 symptoms: increased dyspnea, increased sputum volume, and increased sputum purulence. Exacerbations in patients with all 3 of these symptoms were categorized as Type 1 (most severe). A Type 2 exacerbation (intermediate severity) was present if only 2 of the symptoms were present. If there was only 1 of the symptoms, plus the presence of cough, wheeze, or symptoms of an upper respiratory tract infection, the exacerbation was Type 3 (least severe). This widely accepted clinical classification scheme was modified slightly in the East London COPD Study: an exacerbation was diagnosed if 2 new respiratory symptoms were present for 2 days, with at least one of them one of the 3 major symptoms in the Anthonisen classification.6
These modified Anthonisen criteria permit the clinical diagnosis of a COPD exacerbation in many cases without the need for further investigation. However, current guidelines agree that there are clinical features suggesting a potentially life-threatening exacerbation or the presence of a serious complicating process. Table 1 lists these features. If one or more of the findings in the table are present, evaluation beyond the history and physical should be done, and in most instances this should include an arterial blood gas (not just pulse oximetry), a complete blood count, and a chest radiograph. Patients with chest pain, arrhythmias, or signs of heart failure should also have an electrocardiogram. The rapid measurement of B-type natriuretic peptide (BNP) in the emergency department has been shown to be both clinically helpful and cost-effective in cases of diagnostic uncertainty when evaluating patients with acute dyspnea, particularly when the differential is between congestive heart failure and COPD exacerbation (see Critical Care Alert, July 2006, pp 28-29).
Sputum purulence does not necessarily mean infection. The green color of sputum is due to the action of leukocyte myeloperoxidase, particularly in the presence of stasis, and is not a very reliable indicator of bacterial infection. Most exacerbations in ambulatory patients are managed without staining or culturing the sputum. Current guidelines do not recommend the latter as routine.2,3,18 Gram stain and culture of sputum are more likely to be helpful in patients with severe exacerbations requiring admission to the hospital.18
Table 2 lists criteria for hospitalizing the patient with a COPD exacerbation. These criteria are agreed upon by current guidelines, and are intended to assure that patients at risk for developing acute respiratory failure or other life-threatening complications are appropriately managed, while avoiding unnecessary use of hospital resources.
Because of the huge impact of hospitalization on the patient's quality of life as well as on health care costs, interest has recently focused on "hospital at home," whereby inpatient admission can be avoided in selected patients. This approach has mainly been applied in Europe, but a recent study has demonstrated its feasibility in the United States as well.21 A Cochrane Review found that patients managed for exacerbations with "hospital at home" had acute outcomes and rates of hospital readmission that were equivalent to those of inpatient management, with patient and caregiver preference for the former.22 Management of severe exacerbations without admission to the hospital requires a complex, coordinated application of resources, as well as carefully selected patients, and this approach is not yet widely feasible in this country.
Which Patients with COPD Exacerbations Should Be Admitted to the ICU?
The risk of dying during a COPD exacerbation is associated with the development of acute respiratory acidosis, the presence of significant comorbidities, and the need for ventilatory support. The likelihood of successful management depends on rapid and accurate diagnosis and early and appropriate intervention. Although all the elements of critical care, including assessment, monitoring, and intensive therapy, can be achieved on a respiratory ward, this demands an outlay of material and personnel resources not generally available in US hospitals. Thus, the more severely ill the patient, the more rapidly his or her condition is changing, and the more uncertainty there is about what is going on, the greater is the need for admission to the ICU.
Table 3 lists criteria for ICU admission taken both from current guidelines2,3,18 and from my own experience in managing patients with potentially life-threatening COPD exacerbations. Bed availability and other local factors must be taken into account but, generally speaking, even a brief stay in the ICU is preferable to the chance that the severity of the episode will be underestimated or important signs of deterioration missed on the ward.
Acute respiratory acidosis (initial arterial pH < 7.25) that does not respond to initial therapy, particularly in patients with very severe COPD (GOLD Stage IV), those on home oxygen, and those with severe comorbidities, should prompt admission to the ICU. Because hypoxemia in COPD is typically due to alveolar hypoventilation and ventilation-perfusion mismatching—physiologic processes that respond readily to administration of supplemental oxygen—a requirement for a high inspired oxygen fraction (eg, more than 0.40 or 0.50) suggests that something beyond the usual exacerbation may be going on, and should prompt consideration for admission to the ICU for closer observation than can be achieved on the floor. Abnormal mental status is an especially worrisome finding in a patient with a COPD exacerbation, suggesting the presence of a coexisting process, making administration of appropriate treatments problematic, and increasing the likelihood that intubation will be necessary.
Unless the intention is to provide comfort-care only, patients who have declared their wishes not to be resuscitated (DNAR) and/or not to be intubated (DNI) may nonetheless benefit from admission to the ICU. As many as half of such patients may respond to noninvasive positive-pressure ventilation and aggressive pharmacologic management and survive to hospital discharge, often to what is for them an acceptable quality of life.
References
- Burge S, Wedzicha JA. COPD exacerbations: definitions and classifications. Eur Respir J Suppl. 2003;41:46s-53s.
- National Collaborating Centre for Chronic Conditions. Chronic obstructive pulmonary disease. National clinical guideline on management of chronic obstructive pulmonary disease in adults in primary and secondary care. Thorax. 2004;59 (Suppl 1):1-232. www.thorax.bmjjournals.com/content/vol59/suppl_1/
- Global Initiative for Chronic Obstructive Lung Disease (GOLD). www.goldcopd.com
- Sullivan SD, et al. The economic burden of COPD. Chest. 2000;117(2 Suppl):5S-9S.
- Wedzicha JA. Exacerbations: etiology and pathophysiologic mechanisms. Chest. 2002;121(5 Suppl):136S-141S.
- Wedzicha JA, Donaldson GC. Exacerbations of chronic obstructive pulmonary disease. Respir Care. 2003;48:1204-1213.
- Sapey E, Stockley RA. COPD exacerbations. 2: aetiology. Thorax. 2006;61:250-258.
- Seemungal TA, et al. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 1998;157(5 Pt 1):1418-1422.
- Seemungal TA, et al. Time course and recovery of exacerbations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2000;161:1608-1613.
- Donaldson GC, et al. Relationship between exacerbation frequency and lung function decline in chronic obstructive pulmonary disease. Thorax. 2000;57:847-852.
- Wilkinson TM, et al. Early therapy improves outcomes of exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2004;169:1298-1303.
- Wedzicha JA. Role of viruses in exacerbations of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2004;1:115-120.
- Cameron RJ, et al. Virus infection in exacerbations of chronic obstructive pulmonary disease requiring ventilation. Intensive Care Med. 2006;32:1022-1029.
- Hurst JR, Wedzicha JA. Chronic obstructive pulmonary disease: the clinical management of an acute exacerbation. Postgrad Med J. 2004;80:497-505.
- Anthonisen NR. Bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 2002;347:526-527.
- Sethi S, et al. New strains of bacteria and exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 2002;347:465-471.
- Tillie-Leblond I, et al. Pulmonary embolism in patients with unexplained exacerbation of chronic obstructive pulmonary disease: prevalence and risk factors. Ann Intern Med. 2006;144:390-396.
- American Thoracic Society/European Respiratory Society Task Force. Standards for the Diagnosis and Management of Patients with COPD. http://www-test.thoracic.org/copd/.
- Anthonisen NR, et al. Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987;106:196-204.
- Pierson DJ. Clinical practice guidelines for chronic obstructive pulmonary disease: A review and comparison of current resources. Respir Care. 2006;51:277-288.
- Leff B, et al. Hospital at home: feasibility and outcomes of a program to provide hospital-level care at home for acutely ill older patients. Ann Intern Med. 2005;143:798-808.
- Ram FS, et al. Hospital at home for acute exacerbations of chronic obstructive pulmonary disease. Cochrane Database Syst Rev. 2003;(4):CD003573.
You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content