Perspective

Asthma is a chronic inflammatory disorder characterized by increased responsiveness of the airways to multiple stimuli. Many cells and cellular elements, such as mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells, play a role in development of the inflammatory response.¹ The inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are associated with airflow obstruction that is reversible either spontaneously or with treatment. Although patients appear to clinically recover completely, evidence suggests that some asthmatic patients have chronic airflow limitation. The recognition that asthma is a chronic inflammatory disorder of the airways has significant implications for the diagnosis, management, and potential prevention of acute exacerbations.

Epidemiology

Asthma affects approximately 4% to 5% of the population in the United States.² Although it is the most common chronic disease of childhood, with a prevalence of 5% to 10%, it also affects 7% to 10% of the elderly. Epidemiologic studies suggest that asthma is underdiagnosed and undertreated in all age groups. Part of the problem is that the transient nature of asthma allows many patients to tolerate intermittent respiratory symptoms before seeking medical care. Another important factor resulting in underdiagnosis of asthma is the sometimes nonspecific nature of the symptoms.

About half of cases of asthma develop before 10 years of age and another third before 40 years. The 2 : 1 male-to-female preponderance of asthma in childhood equalizes by 30 years of age.³ The average asthmatic patient has 15 days of restricted activity each year and spends 5.8 days in bed. Approximately 2 million emergency department (ED) visits, 484,000 hospitalizations, and more than 4000 deaths per year are attributed to asthma. In the United States alone, the estimated direct and indirect cost of asthma in all age groups was $56 billion in 2007.⁴

Pathophysiology

All asthmatic patients have hyperresponsive airways that narrow when exposed to various stimuli: allergic, infectious, pharmacologic, environmental, occupational, exercise related, and emotional.

Allergic asthma occurs when inhaled allergens bind to immunoglobulin E molecules bound to mast cells in the lining of the tracheobronchial tree. During the early response, various mediators are released and cause greater vascular permeability, mucosal edema, and contraction of bronchial smooth muscle. A second wave of reaction, the late response, is seen hours to days later; it involves accumulation of inflammatory cells in the bronchial mucosa, thus perpetuating the reaction. The release of mediators and regulation of the inflammatory process in asthma are complex, redundant, and self-perpetuating.⁵

Although several theories attempt to explain the pathophysiologic changes that occur in nonallergic asthma, none adequately explain all clinically observed phenomena. Research suggests that even patients without atopy have pathophysiology similar to that in atopic patients.⁵ Respiratory infections, particularly viral infections, may precipitate bronchospasm. Viruses cause mucosal inflammation and lower the firing threshold of the subendothelial vagal receptors, which results in enhanced airway reactivity that may last up to 8 weeks, even in nonasthmatic persons. Pharmacologic agents, such as aspirin and nonsteroidal antiinflammatory compounds, coloring agents, and beta-blockers, also induce acute asthma. In addition, sulfating agents, which are used widely as food preservatives and antioxidants in pharmaceutical products, can exacerbate asthma.

A large variety of occupational dust and fumes may provoke acute airway obstruction. Patients with occupational asthma classically report a cyclic history; they are symptom free during weekends, vacations, and on arrival at work. Exercise may also stimulate an asthma attack. Exercise-induced bronchospasm is usually noted within 5 to 20 minutes after the completion of exercise and is related to thermal changes in the respiratory tree. Exercising in a cold, dry environment causes a more marked response than does exercising in a warm, humid environment. Finally, endocrine factors, such as variations in progesterone and estradiol levels, also influence asthma exacerbations, probably through modification of vagal efferent activity.

Most patients with asthma seem to display an exaggerated bronchoconstrictive response to a variety of exogenous and endogenous stimuli, and inflammation plays a key role. The final common pathway is as follows¹:

Presenting Signs and Symptoms

When evaluated in the ED, many patients relay a history of asthma, but some do not. Patients with a severe asthma attack may be in obvious respiratory distress, with rapid breathing and loud wheezing, but patients with mild exacerbation may exhibit coughing and end-expiratory wheezing. The classic symptoms of asthma consist of the triad of dyspnea, wheezing, and coughing, but physical findings during an asthma exacerbation can be variable. Early symptoms include a sensation of chest constriction and coughing. As the exacerbation progresses, wheezing becomes apparent, expiration becomes prolonged, and use of the accessory respiratory muscles may become evident. Patients may sit upright or lean forward in an attempt to decrease the work of breathing. Use of the accessory muscles of inspiration indicates diaphragmatic fatigue, whereas the appearance of paradoxic respirations reflects impending ventilatory failure. Alteration in mental status heralds respiratory arrest.

Differential Diagnosis

Wheezing, coughing, and dyspnea may be cause by many common conditions, including pneumonia, bronchitis, croup, bronchiolitis, chronic obstructive pulmonary disease, congestive heart failure, pulmonary embolism, allergic reactions, and upper airway obstruction from edema or a foreign body. Less common conditions with similar symptoms are cystic fibrosis, hypersensitivity pneumonitis, carcinoid syndrome, and exposure to odors, dust, and gas. A careful history and physical examination should help differentiate asthma from these other conditions.

Diagnostic Testing

As for all patients who come to the ED for care, a directed history and physical examination should be performed. Key historical points should be elicited, such as the duration and onset of the current attack, identification of precipitating causes, type and amount of medications used before arrival at the ED, response to previous therapy, including current or previous use of corticosteroids, frequency of ED visits and hospitalizations, previous need for intubation or ventilation, history of concurrent medications and allergies, and history of concurrent medical problems. At some point during the patient’s ED stay, effort should be made to evaluate both the severity of the obstruction and the adequacy of ongoing asthma control (Table 48.1).

The physical examination should focus on observing respiratory effort and use of accessory muscles and listening for wheezing or other abnormal breath sounds and prolongation of the expiratory phase. Although wheezing results from movement of air through narrowed airways, the intensity of the wheeze may not correlate with the severity of airflow obstruction. Tachycardia and tachypnea are usually present in patients with acute asthma, but vital signs normalize very quickly as the airflow obstruction is relieved.¹⁰ Therefore, a normal heart rate and respiratory rate are not reliable indicators of the degree of relief from obstruction.

Bedside spirometry provides a rapid, objective assessment of patients and helps both indicate the effectiveness of and guide therapy. Sequential measurements assist emergency physicians in assessing the severity of the problem and determining the response to therapy. Although forced expiratory volume in 1 second (FEV₁) and the peak expiratory flow (PEF) rate measure the extent of large airway obstruction, patient cooperation is essential for these tests to be reliable. When possible, management decisions should be guided by a patient’s personal best PEF rate or FEV₁ value or, if unknown, a percentage of the predicted value in addition to other physiologic and historical factors.¹

Pulse oximetry is a useful and convenient method for accessing oxygenation and monitoring oxygen saturation during treatment. Analysis of arterial blood gases is not indicated in the majority of patients with mild to moderate asthma exacerbation, but it is helpful if there is concern for hypoventilation with carbon dioxide retention and respiratory acidosis. Patients with the latter problems almost always have clinical evidence of severe attacks or spirometry demonstrating PEF or FEV₁ less than 25% of the predicted value.^11,12 Practitioners should be aware that a normal or slightly elevated PaCO₂ (e.g., 42 mm Hg or higher) indicates extreme airway obstruction and fatigue and may herald the onset of acute ventilatory failure.^11,12

Routine radiography is unnecessary but is indicated if the possibility of pneumothorax, pneumomediastinum, pneumonia, or other medical conditions is a concern. In up to one third of asthmatic patients requiring admission, an abnormality is demonstrated on chest radiographs.¹³

A routine complete blood cell count is not indicated and would probably show modest leukocytosis secondary to the administration of β₂-agonist therapy or corticosteroid treatment. In patients taking theophylline before ED evaluation, a serum theophylline level should be determined. A routine electrocardiogram is also unnecessary; electrocardiographic abnormalities noted include right ventricular strain, abnormal P waves, and nonspecific ST-T wave abnormalities, which resolve with treatment. Older patients, especially those with coexisting heart disease, should undergo cardiac monitoring during treatment. Asthma severity index scores have failed to predict outcome better than clinical judgment does.

Use of exhaled nitric oxide measurements and other serum and urine markers for detection of the severity of the asthma exacerbation is currently under investigation.^14–17

Treatment