Perspective

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease that encompasses clinical entities such as emphysema and chronic bronchitis.¹ Although a variety of guidelines have addressed the definition and diagnosis of COPD, a major issue is that most guidelines include a combination of clinical terms and anatomic pathology, which limits their utility for emergency physicians (EPs). The American Thoracic Society defines COPD as a disease state characterized by the presence of airflow obstruction as a result of chronic bronchitis or emphysema. Chronic bronchitis is defined as the presence of a chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of chronic cough have been excluded. Emphysema is defined as abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls without obvious fibrosis.² A potentially more useful definition for EPs comes from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), which states that COPD is a disease state characterized by airflow limitation that is not fully reversible.³ The limitation in airflow is usually both progressive and associated with an inflammatory response of the lungs to noxious particles or gases, such as tobacco smoke in particular. This definition encompasses chronic bronchitis, emphysema, bronchiectasis, and to a lesser extent, asthma and acknowledges that most patients with COPD have a combination of these different diseases.

Epidemiology

Lack of agreement among definitions of COPD, combined with delayed diagnosis in many patients, makes estimates of prevalence difficult. In 2008, 13.1 million U.S. adults (aged 18 and older) were estimated to have COPD,⁴ but close to 24 million U.S. adults have evidence of impaired lung function, thus indicating underdiagnosis of COPD.⁵

COPD accounted for 1.5 million emergency department (ED) visits and 726,000 hospitalizations in 2000.⁶ In 2010, the cost to the nation for COPD was projected to be approximately $49.9 billion, including $29.5 billion in direct health care expenditures, $8.0 billion in indirect morbidity costs, and $12.4 billion in indirect mortality costs.⁷ COPD was the third leading cause of death in the United States in 2007 with 124,477 victims, more than half of whom were female.⁸ Of note, the prevalence of COPD in women has doubled in the past few decades but has remained stable in men.

In industrialized countries, 80% to 90% of the risk for COPD is from cigarette smoking. Tobacco smoke is the major risk factor for the development of COPD, but only 15% of smokers experience COPD. Other factors associated with the development of COPD, in addition to smoking, are occupational dust, chemical exposure, and air pollution.

Pathophysiology

Chronically Compensated Chronic Obstructive Pulmonary Disease

The lung reacts to irritants such as tobacco smoke by increasing the number of macrophages and neutrophils in the airways, lung interstitium, and alveoli. In susceptible individuals, these inflammatory cells release proteases that if left unchecked, eventually break down lung parenchyma and stimulate mucus secretion. Cells that normally secrete surfactant and protease inhibitors are replaced by mucus-secreting cells. At the alveolar and bronchiolar level there is loss of elastic recoil caused by tissue destruction, as well as collapse and narrowing of the smaller airways because of loss of surfactant-producing cells. At the bronchial level, irritants cause pooling of mucus and resultant colonization by bacteria.

Acute Exacerbations

Acute exacerbations of COPD are usually triggered by an event, such as an infection or other respiratory irritant, that starts an inflammatory cascade. In more than 75% of patients with acute exacerbations an infectious agent is found.⁹ In addition, it is likely that up to 50% of acute exacerbations are bacterial in nature.¹⁰ Other important triggers for exacerbation are oxidative stress, lower temperatures,¹¹ and medications. Beta-blockers, sedatives, and narcotics are the medications that most frequently contribute to exacerbations. Regardless of the specific trigger or triggers, inflammatory mediators cause bronchoconstriction and pulmonary vasoconstriction.

Another aspect of the pathophysiology of acute exacerbation is the potential for acute respiratory acidosis. When high levels of inspired oxygen are administered during management of a COPD exacerbation, the vasoconstriction that normally shunts blood away from inadequately ventilated areas is reversed, thereby leading to worsening ventilation-perfusion mismatch and acute rises in the arterial CO₂ concentration. Contrary to previous dogma, the hypoxic drive in this process has no significant role.

The overall clinical picture during acute exacerbations of COPD is caused by bronchospasm, inflammation, and mucus hypersecretion, which results in airway narrowing, worsening ventilation-perfusion mismatch, and hypoxemia. The work of breathing increases during an exacerbation as a result of greater airway resistance and hyperinflation. This increase creates a higher oxygen demand by the respiratory muscles, which further contributes to the physiologic stress on the patient.¹² The limitation in expiratory airflow is not significantly increased during acute exacerbations, and the majority of the pathophysiologic manifestations result from ventilation-perfusion mismatch.¹³

Presenting Signs and Symptoms

Classic

The signs and symptoms in a chronically compensated patient depend largely on the stage of the patient’s disease. Very early in the course of the disease, patients often do not carry the diagnosis of COPD and have subtle findings, such as mild exertional dyspnea and a chronic cough that is frequently identified as a “smoker’s cough.”

Acute exacerbations produce signs and symptoms that represent the impact on multiple body systems. See Table 49.1 for the signs and symptoms of both chronically compensated COPD and acute exacerbations of COPD.

Table 49.1 Signs and Symptoms of Chronic Obstructive Pulmonary Disease (COPD)

TYPE OF COPD	SYMPTOMS	SIGNS
Chronically compensated COPD
Earlier stages of disease (not likely to have a COPD diagnosis yet)	Mild to moderate exertional dyspnea Chronic cough, frequently with small-volume hemoptysis	Mild tachypnea Wheezing with forced expiration
Later stages of disease	Increasing exertional dyspnea	Prolonged expiratory phase (pursed-lip breathing) Increasing tachypnea End-expiratory wheezing with normal breathing Use of accessory respiratory muscles Weight loss caused by both reduced caloric intake and increased caloric demands from work of breathing Plethora from secondary polycythemia Barrel chest (predominantly emphysematous disease) Decreased breath sounds globally (predominantly emphysematous disease) Coarse crackles or rhonchi from increased secretions (predominantly bronchitic disease)
Acute exacerbations	Dyspnea at rest Exertional dyspnea that inhibits normal activities Increase in coughing frequency and/or change in appearance of sputum Apprehension	Tachypnea at rest Use of accessory respiratory muscles Diffuse expiratory wheezing at all times Tachycardia Cyanosis Altered mental status

Variations

Because COPD encompasses a wide range of severity of disease, it has a variety of different manifestations. The biggest variations are to be found at the extremes of disease.

Early in the course of the disease, patients may simply have a persistent cough without notable dyspnea. It is important to identify such patients and secure follow-up care. Patients may also note a dry cough that is triggered by deep breaths and may or may not be associated with wheezing and dyspnea. This symptom suggests an episode of bronchitis that could be an exacerbation of underlying lung disease in at-risk patients.

Patients in the late stages of COPD pose a new set of challenges. Those with significant airway obstruction may not generate enough air movement to wheeze and have a “silent chest.” Such patients need aggressive management to avoid progressive respiratory failure. Patients with a significantly enlarged chest from emphysematous changes may be difficult to auscultate. Finally, patients with severe hypoxemia or hypercapnia (or both) may have primarily symptoms of altered mentation.

Differential Diagnosis

The differential diagnosis of acute dyspnea is quite large. Because many of these conditions are life-threatening, it is critical to differentiate between them so that appropriate treatment can be initiated.

The EP must resist the temptation to automatically diagnose COPD as the sole cause of dyspnea in a patient with a history of COPD. Patients with COPD frequently have serious comorbid conditions that may be unrecognized and play a role in their ED visit. It is also important for the EP to continue to keep an open mind to the possibility of alternative diagnoses, particularly if the patient is not showing the expected response to standard treatment of COPD.

Asthma

Asthma and COPD coexist in some patients, and both diseases involve the presence of airway obstruction, with some key differences. In the ED setting the key point is that the initial stabilizing actions for severe manifestations of either disease do not vary greatly.

Congestive Heart Failure

Congestive heart failure (CHF) can pose a significant diagnostic challenge for EPs because it can be manifested similar to other causes of acute dyspnea and also coexists with other chronic causes of dyspnea such as COPD. Patients with a history of both conditions and acute dyspnea may have exacerbations of one or even both conditions at the same time.

Historical elements are minimally helpful in discriminating among patients. Although studies indicate that the presence of orthopnea (likelihood ratio [LR] = 2.0) and dyspnea with exertion (LR = 1.3) is more commonly associated with CHF, both symptoms are common in either disease.¹⁴

Physical examination can be of some assistance in clarifying the differentiation between CHF and COPD. The presence of jugular venous distention is helpful in pointing toward CHF, and evidence has shown that hepatojugular reflux is probably more reliable.¹⁵ To check hepatojugular reflux, the EP puts the head of the bed at 45 degrees and presses on the upper part of the patient’s abdomen for 10 seconds. The result is positive if the venous pulsations rise at least 3 cm over baseline. Wheezing can be present with both CHF and COPD and therefore does not have high diagnostic certainty.

The chest radiograph is most useful in patients with evidence of significant interstitial edema. Absence of this finding does not rule out CHF, however, because patients with chronic lung disease are less likely to have the classic chest radiographic findings of CHF.¹⁵

The brain natriuretic peptide (BNP) assay shows great promise in assisting in making the diagnosis of CHF. In one study it was more accurate than any other single variable (including the history, physical examination, chest radiographs, and electrocardiogram) in determining whether CHF was present.¹⁶ It is most helpful if the value is very high (>500 pg/mL) or very low (<100 pg/mL).^17,¹⁸ A number of disease states other than CHF can cause elevation of the BNP value; in particular, the presence of COPD with associated cor pulmonale elevates the BNP value to a lesser degree than does left-sided failure.¹⁹ Be aware that obesity can falsely decrease a BNP value.²⁰

Pulmonary Embolism

The diagnosis of pulmonary embolism (PE) must be considered in any dyspneic patient, particularly when risk factors for venous thromboembolism are present. There is evidence that 25% of patients with a severe COPD exacerbation of unknown origin actually have PE.^21,²² Key risk factors include older age, recent surgery or trauma, previous venous thromboembolism, hereditary thrombophilia such as factor V Leiden, malignancy, smoking, and use of estrogen-containing hormone replacement therapy. The classic manifestation of PE—pleuritic chest pain, dyspnea, tachycardia, and hypoxia—is not frequently encountered in the ED, but at least one of these elements is almost always present. Some historical clues to possible PE are a sudden onset of symptoms and syncope or near syncope in combination with the risk factors listed previously.

Physical examination offers no clues to the diagnosis of PE in 28% to 58% of patients.²³ The diagnosis is based on a combination of the initial clinical impression of a patient’s risk level and the results of additional testing such as pulmonary imaging. Patients with significant underlying asthma or COPD are frequently not good candidates for ventilation-perfusion scans because preexisting ventilation and perfusion abnormalities will reduce the utility of the test by increasing the likelihood of an intermediate-probability result. D-dimer testing may be of some assistance in patients with a sufficiently low pretest probability, as determined by various clinical decision rules in the literature. The EP must be aware of the many disease processes that cause false-positive results and make the utility of D-dimer assay questionable in many acutely ill patients. It is of highest utility in a population that is at low risk for PE and has a lower severity of symptoms, and it is unlikely to include patients with an exacerbation of COPD.