Definition and Epidemiology
Asthma is a syndrome characterized by airflow obstruction that varies both spontaneously and with specific treatment. Chronic airway inflammation causes airway hyperresponsiveness to a variety of triggers, leading to airflow obstruction and respiratory symptoms including dyspnea and wheezing. Although asthmatics typically have periods of normal lung function with intermittent airflow obstruction, a subset of pts develop chronic airflow obstruction.
The prevalence of asthma has increased markedly over the past 30 years. In developed countries, approximately 10% of adults and 15% of children have asthma. The majority of asthmatics have childhood-onset disease. Most asthmatics have atopy, and they often have atopic dermatitis (eczema) and/or allergic rhinitis. A minority of asthmatic pts do not have atopy (negative skin prick tests to common allergens and normal serum total IgE levels). These individuals, occasionally referred to as intrinsic asthmatics, often have adult-onset disease. Occupational asthma can result from a variety of chemicals, including toluene diisocyanate and trimellitic anhydride, and often has onset in adulthood.
Asthmatics can develop increased airflow obstruction and respiratory symptoms in response to a variety of different triggers. Inhaled allergens can be potent asthma triggers for individuals with specific sensitivity to those agents. Viral upper respiratory infections (URIs) commonly trigger asthma exacerbations. β-Adrenergic blocking medications can markedly worsen asthma symptoms and should typically be avoided in asthmatics. Exercise often triggers increased asthma symptoms, which usually begin after exercise has ended. Other triggers of increased asthma symptoms include air pollution, cold air, occupational exposures, and stress.
Clinical Evaluation of the Patient History
Common respiratory symptoms in asthma include wheezing, dyspnea, and cough. These symptoms often vary widely within a particular individual, and they can change spontaneously or with age, season of the year, and treatment. Symptoms may be worse at night, and nocturnal awakenings are an indicator of inadequate asthma control. The severity of a pt’s asthmatic symptoms, as well as the pt’s need for systemic steroid treatment, hospitalization, and intensive care treatment, are important to ascertain. Types of asthmatic triggers for the particular pt, and their recent exposure to them, should be determined. Approximately 1–5% of asthmatics have sensitivity to aspirin and other cyclooxygenase inhibitors; they typically are nonatopic and have nasal polyps. Cigarette smoking leads to more hospital admissions and more rapid decline in lung function in asthmatics; smoking cessation is essential.
It is important to assess for signs of respiratory distress, including tachypnea, use of accessory respiratory muscles, and cyanosis. On lung examination, there may be wheezing and rhonchi throughout the chest, typically more prominent in expiration than inspiration. Localized wheezing may indicate an endobronchial lesion. Evidence of allergic nasal, sinus, or skin disease should be assessed. When asthma is adequately controlled, the physical examination may be normal.
Spirometry often shows airflow obstruction, with a reduction in forced expiratory volume in 1 s (FEV1) and FEV1/forced vital capacity (FVC) ratio. However, spirometry may be normal, especially if asthma symptoms are adequately treated. Bronchodilator reversibility is demonstrated by an increase in FEV1 by ≥200 mL and ≥12% from baseline FEV1 15 min after a short-acting β agonist (often albuterol metered-dose inhaler two puffs or 180 μg). Many but not all asthmatics will demonstrate significant bronchodilator reversibility; optimal pharmacologic treatment may reduce bronchodilator reversibility. Airway hyperresponsiveness is characteristic of asthma; it can be assessed by exposure to direct bronchoconstrictors such as methacholine or histamine. Greater airway responsiveness is associated with increased asthmatic symptoms. The peak expiratory flow rate (PEFR) can be used by the pt to track asthma control objectively at home. Measurement of lung volumes is not typically performed, but increases in total lung capacity and residual volume may be observed. The diffusing capacity for carbon monoxide is usually normal.
Blood tests are usually not helpful. CBC may demonstrate eosinophilia. Specific IgE measurements for inhaled allergens (radioallergosorbent test [RAST]) or allergy skin testing may assist in determining allergic triggers. Total serum IgE is markedly elevated in bronchopulmonary aspergillosis (BPA). Exhaled nitric oxide levels can provide an assessment of eosinophilic airway inflammation.
Chest x-ray is usually normal. In acute exacerbations, pneumothorax may be identified. In BPA, eosinophilic pulmonary infiltrates may be observed. Chest CT scan is not typically performed in routine asthma but may show central bronchiectasis in BPA.
The differential diagnosis of asthma includes other disorders that can cause wheezing and dyspnea. Upper airway obstruction by tumor or laryngeal edema can mimic asthma, but stridor in the large airways is typically noted on physical examination. Localized wheezing in the chest may indicate an endobronchial tumor or foreign body. Congestive heart failure can cause wheezing but is typically accompanied by bibasilar crackles. Eosinophilic pneumonias and Churg-Strauss syndrome may present with wheezing. Vocal cord dysfunction can mimic severe asthma and may require direct laryngoscopy to assess. When asthma involves chronic airflow obstruction, distinguishing it from chronic obstructive pulmonary disease (COPD) can be very difficult.
TREATMENT: CHRONIC ASTHMA
If a specific inciting agent for asthmatic symptoms can be identified and eliminated, that is an optimal part of treatment. In most cases, pharmacologic therapy is required. The two major classes of drugs are bronchodilators, which provide rapid symptomatic relief by relaxing airway smooth muscle, and controllers, which limit airway inflammation.
Bronchodilators The most widely used class of bronchodilators is β2-adrenergic agonists, which relax airway smooth muscle by activating β2-adrenergic receptors. Two types of inhaled β2 agonists are widely used in asthma treatment: short-acting β2 agonists (SABAs) and long-acting β2 agonists (LABAs). SABAs, which include albuterol, have rapid onset of action and last for up to 6 h. SABAs are effective rescue medications, but excessive use indicates inadequate asthma control. SABAs can prevent exercise-induced asthma if administered before exercise. LABAs, which include salmeterol and formoterol, have a slower onset of action but last for >12 h. LABAs have replaced regularly scheduled use of SABAs, but they do not control airway inflammation and should not be used without inhaled corticosteroid (ICS) therapy. Combinations of LABAs with ICS reduce asthma exacerbations and provide an excellent long-term treatment option for asthma severity of moderate persistent degree or greater.
Common side effects of β2-adrenergic agonists include muscle tremors and palpitations. These side effects are more prominent with oral formulations, which should not generally be used. There have been ongoing concerns about mortality risks associated with β2-adrenergic agonists, which have not been completely resolved. LABAs taken without concomitant inhaled steroid treatment may increase this risk.
Other available bronchodilator medications include anticholinergics and theophylline. Anticholinergics, which are available in short-acting and long-acting inhaled formulations, are commonly used in COPD. They appear to be less effective than β2-adrenergic agonists in asthma, and they are typically considered as an additional treatment option only if other asthma medications do not provide adequate asthma control. Theophylline may have both bronchodilator and anti-inflammatory effects; it is not widely used due to the potential toxicities associated with high plasma levels. Low doses of theophylline may have additive effects with ICS at levels below the standard therapeutic range, and this can be a useful treatment option for severe asthma.
Controller Therapies ICSs are the most effective controller treatments for asthma. ICSs are usually given twice daily; a variety of ICS medications are available. Although they do not provide immediate symptom relief, respiratory symptoms and lung function often begin to improve within several days of initiating treatment. ICS reduces exercise-induced symptoms, nocturnal symptoms, and acute exacerbations. ICS treatment typically leads to reductions in airway hyperresponsiveness.
ICS side effects include hoarseness and oral candidiasis; these effects may be minimized by use of a spacer device and by rinsing out the mouth after taking ICS.
Other available controller therapies for asthma include systemic corticosteroids. Although quite helpful in the management of acute asthma exacerbations, oral or IV steroid use should be avoided if at all possible in the chronic management of asthma due to multiple potential side effects. Antileukotrienes, such as montelukast, may be quite beneficial in some pts. Cromolyn sodium and nedocromil sodium are not widely used due to their brief durations of action and typically modest effects. Omalizumab is a blocking antibody that neutralizes IgE; with SC injection every 2–4 wk, it appears to reduce acute asthma exacerbation frequency in severe asthmatics. However, it is expensive and considered only for highly selected pts with elevated total serum IgE levels and refractory asthma symptoms despite maximal inhaled bronchodilator and ICS therapy.
Overall Treatment Approach In addition to limiting exposure to their environmental triggers for asthma, pts should receive stepwise therapy appropriate for their disease severity (Fig. 129-1). Asthmatics with mild intermittent symptoms are typically managed adequately with SABAs taken on an as-needed basis. Use of SABAs more than three times a week suggests that controller therapy, typically with an ICS twice per day, is required. If symptoms are not adequately controlled with ICS, LABAs can be added. If symptoms are still not adequately controlled, higher doses of ICS and/or alternative controller therapies should be considered.
Stepwise approach to asthma therapy according to the severity of asthma and ability to control symptoms. ICS, inhaled corticosteroid; LABA, long-acting β2 agonists; OCS, oral corticosteroid.