Management of a chronic obstructive pulmonary disease (COPD) exacerbation begins with an accurate diagnosis. Although more than 80% of exacerbations are managed on an outpatient basis, hospitalization is all too common and associated with considerable health care costs and mortality. Irrespective of the site of treatment, the treatment modalities are the same. Noninvasive ventilation has greatly decreased the mortality in exacerbations that require ventilatory support. Across the range of exacerbation severity, treatment failure and relapses are frequent, and should be carefully evaluated. New therapeutic options to address infection and inflammation in COPD are needed to improve the outcome of exacerbations.
Key points
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Exacerbations in patients with chronic obstructive pulmonary disease are events that worsen quality of life, impact on lung function decline, and increase the risk of subsequent events and death.
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The diagnosis rests on a clinical diagnosis based on the presence of worsening dyspnea and cough and phlegm.
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Its clinical presentation ranges from a mild illness only requiring additional rescue inhaler use to acute respiratory failure requiring ventilatory support.
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Irrespective of the site of treatment, the treatment modalities are the same, with the universal intensification of bronchodilator therapy and selective application of systemic corticosteroids and antibiotics.
Introduction
An acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is a flare of chronic respiratory symptoms, including worsening shortness of breath, cough, and sputum production requiring an increase in need of rescue medications or/and supplementation of additional treatment. It has a heterogeneous presentation and is one of the most common reasons for hospitalization, with an in-hospital mortality rate of 3.9%. Its severity spectrum ranges from a mild illness only requiring additional rescue inhaler use to acute respiratory failure requiring ventilatory support. The treatment of exacerbations depends on the severity, which itself is a complex sum of the severity of the acute event, the underlying chronic disease, and associated patient comorbidities.
Diagnosis
A careful history and physical examination remain the basis of the diagnosis of an AECOPD. Despite years of study, there is no specific diagnostic test or biomarker that is the sine qua non for exacerbations. It is a diagnosis of exclusion. Most laboratory and radiological evaluation in a patient with suspected AECOPD is to exclude other cardiopulmonary causes and determine the contribution of comorbidities. Therefore, use of evaluation methods are not prescriptive and formulaic, but should be guided by the clinical assessment.
The diagnosis of an AECOPD requires the presence of underlying COPD ( Fig. 1 ). Similar respiratory symptoms in an individual without COPD should be designated as acute bronchitis, a clinical entity with substantially different etiology, prognosis, and treatment. This is easy in patients with established COPD diagnosis and previous spirometry demonstrating airflow obstruction. However, not infrequently the first presentation of COPD is an acute exacerbation episode. In fact, an average delay of 2 years between the first acute episode and the establishment of a COPD diagnosis has been described. An assessment for COPD risk factors is indicated in every adult patient with a lower respiratory tract infection. If present, consideration for treatment as an exacerbation and an evaluation for undiagnosed COPD in the convalescent phase are indicated.
Once the presence of COPD is established or suspected, the health care practitioner needs to consider other entities in the differential diagnosis. These include common ones such as pneumonia and congestive heart failure and less common ones such as pneumothorax, pulmonary embolism, pleural effusion, lung carcinoma, and rib fractures. , , Recently added to the list is vaping-associated lung injury. The extent of evaluation is dictated by the severity of the exacerbation and the site of treatment ( Table 1 ). In mild-moderate exacerbations that are being evaluated in the office, ascertaining absence of hypoxemia with pulse oximetry is the only essential test, if the clinical assessment does not support an alternative diagnosis. In patients who are severe enough to require emergency department evaluation, a more extensive evaluation is indicated to ensure appropriate management and prevent poor outcomes. A small autopsy study showed that in patients who died within 24 hours of admission for a COPD exacerbation, the primary causes of death were heart failure, pneumonia, pulmonary thromboembolism, and COPD in 37%, 28%, 21%, and 14% of patients, respectively.
| Clinical Setting | Test | Potential Diagnosis |
|---|---|---|
| Physician’s office | Pulse oximetry | Hypoxemia |
| Emergency department | Complete blood count | Anemia, leukocytosis |
| Comprehensive metabolic panel | Electrolyte abnormalities, liver failure, kidney failure | |
| Brain natriuretic peptide | Heart failure | |
| Cardiac enzymes | Heart failure, myocardial infarction | |
| D Dimer | Pulmonary embolism | |
| Arterial blood gas measurement | Hypoxemia, hypercapnia, and respiratory acidosis | |
| Electrocardiography | Myocardial infarction, arrhythmias | |
| Chest radiography | Pneumonia, congestive heart failure, pneumothorax, pleural effusion, rib fractures | |
| Point of care ultrasound – if available | Heart failure, pneumothorax, pleural effusion, pericardial effusion, venous thromboembolism |
Usually the testing described in Table 1 is sufficient to rule out alternative diagnoses. On occasion, depending on clinical circumstances and the result of these evaluations, further tests might be indicated. For example, an atypical presentation with sudden onset of dyspnea with or without an elevated D-dimer, would lead to a computed tomography (CT) pulmonary angiogram to evaluate for pulmonary embolism. The presence of atelectasis or mass lesion on the chest radiograph would require a CT scan for further characterization.
Determination of etiology
Around 30% to 50% of AECOPD cases are associated with a bacterial infection. However, sputum Gram stain and culture are not recommended in the management of most exacerbations. Studies using molecular diagnostics have shown that sputum cultures have limited sensitivity. The presence of a respiratory pathogen on culture does not distinguish between chronic colonization and acute infection, therefore having limited specificity. The usual turn-around time of sputum culture results of 48 to 72 hours also limits their utility, as clinical decisions regarding treatment of an AECOPD require point-of-care results.
There are situations where a sputum culture could be useful. These include patients who fail to respond to initial empiric antibiotic therapy, patients with risk factors for Pseudomonas aeruginosa or other antibiotic-resistant bacteria, and patients requiring hospitalization. Even in these scenarios, the limited accuracy of this test should be kept in mind when interpreting the results, with the clinical picture taking precedence. For instance, in a hospitalized patient responding well to current antibiotics despite the sputum culture yielding a resistant pathogen, a change of antibiotics is unnecessary.
Around 30% to 50% of AECOPD cases are associated with a viral infection. Viral cultures are now rarely performed. During the influenza season, a rapid diagnostic test for influenza is useful if acute onset of fever, myalgias, and coryza are seen with exacerbation symptoms. More extensive respiratory viral diagnostic panels have limited utility in the absence of specific antiviral treatment. Detection of a virus does not mean absence of a concurrent bacterial infection; as such, coinfection is seen in about 25% of exacerbations.
Biomarkers for bacterial infection like procalcitonin and C-reactive protein (CRP) have been evaluated in AECOPD to guide antibiotic therapy. Although these biomarkers perform well with parenchymal and systemic infections such as pneumonia and sepsis, they have been unreliable in AECOPD. , A likely explanation is that bacterial exacerbations are mucosal infections, and therefore not enough of a stimulus to induce robust hepatic production of these acute phase reactants. Studies with these biomarkers in AECOPD have not correlated them with careful sputum microbiology and have not used the speed of resolution as an endpoint. They have not shown their utility beyond the reliable, simple and no-cost clinical symptom biomarkers of bacterial infection in exacerbations.
Clinical symptom biomarkers of bacterial infection are useful and accurate in AECOPD. These include the presence of purulent sputum, especially when the purulence emerged or increased with the onset of the exacerbation. Also useful are the Anthonisen criteria, where the probability of bacterial etiology in type 1 and 2 exacerbations is substantial and reliable enough to recommend antibiotic use ( Box 1 ). Sputum purulence can be assessed readily by questioning the patient or visual examination of a sputum sample if available. Another option is the use of a standardized color chart that has a sensitivity of 94.4% and specificity of 77.0% for a positive sputum culture and provides greater reproducibility.
Major Criteria:
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Increased breathlessness,
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Increased sputum volume
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New or increased sputum purulence
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Minor criteria:
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Fever without other cause
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Increased wheezing or cough
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20% increase in respiratory or heart rate compared with baseline
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Upper respiratory tract infection in the previous 5 days
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Types of exacerbation:
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Type 1 exacerbations – All of major criteria.
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Type 2 exacerbations – Any 2 major criteria
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Type 3 exacerbations – consist of any 1 of major criteria along with at least 1 of the minor criteria
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Determination of the severity of an exacerbation
The symptomatic criteria proposed by Anthonisen have been sometimes thought of as a measure of exacerbation severity (see Box 1 ). However, they are more useful as an indication of etiology rather than as a measure of severity. For example, a patient could have a single symptom of increased dyspnea of such severity that it requires hospitalization but still have a type 3 exacerbation, which clearly is not a mild exacerbation.
Ideally, measures of severity of exacerbations should reflect the extent of acute pathophysiology (eg, the severity of lung dysfunction or the degree of mucosal inflammation). An exacerbation is an amplification of chronic disease. Therefore, a single measurement at the time of an acute exacerbation will not inform of the severity of the acute change, unless one takes the patient’s stable baseline state into account. For instance, a measured peak expiratory flow rate (PEFR) of 60 L/min at the time of an exacerbation could represent a small acute change in an individual whose baseline PEFR is 80 L/min or a large acute change in an individual with a baseline PEFR of 240 L/min. Although both will require the same level of care, the second individual has a more severe exacerbation based on pathophysiological impact.
The most used severity classification of AECOPD is based on the requirement for health care resources or the required level of care ( Box 2 ). However, this classification does not help in deciding how to manage an exacerbation. Other limitations of such an approach to defining severity include the inability to assess acute change and the variability in the application of health care interventions among practitioners and systems. However, such a severity classification is useful in clinical trials and is also used in determining future preventative care for exacerbations in an individual patient. More work needs to be done to develop a uniform, reproducible, and clinically relevant severity classification system for COPD exacerbations.
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Mild exacerbation – treated with rescue inhalers that is, short-acting bronchodilators
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Moderate exacerbation – treated with rescue inhalers, antibiotics and/or oral corticosteroids
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Severe exacerbation – Requires Emergency Room visit or hospitalization including an Intensive care unit admission
Site of treatment
Although more than 80% of patients with exacerbations are managed as outpatients, , patients with respiratory distress or at risk of such distress should be hospitalized to provide access to higher levels of care ( Box 3 ). Mortality risk in AECOPD increases with the development of respiratory acidosis, change in mental status, presence of significant comorbidities, and the need for ventilatory support. The emergency department plays an essential role in the triage and initial management of severe COPD exacerbations. A well-developed algorithm to standardize diagnosis, evaluation, treatment, and triage decisions in the emergency department can improve the care of COPD exacerbations.
Indications for inpatient general medicine admission:
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Dyspnea at rest
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New hypoxemia at rest or marked increase in oxygen requirements in a patient on home oxygen preceding the exacerbation
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Tachypnea (respiratory rate >30 breaths per minute)
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Tachycardia (heart rate >100 beats per minute)
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Unable to perform activities of daily living at home without excessive dyspnea
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Presence of serious comorbidities including pneumonia, cardiac arrhythmia, heart failure, diabetes mellitus, renal failure, or liver failure
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Failure of outpatient management or emergency department management
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Insufficient home support
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Frailty
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Indications for intensive care admission:
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Cardiopulmonary arrest
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Severe hemodynamic instability
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Deteriorating mental status and inability to protect the airway
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Agonal breathing
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Risk for respiratory failure presenting with cyanosis, pH less than 7.35, Pa co 2 greater than 45
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Hypoxia (SpO2 <88%) despite supplemental oxygen and requiring noninvasive ventilation
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Use of accessory muscles of respiration, paradoxic chest wall and abdominal movements.
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