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Asthma is
a disease of diffuse airway inflammation caused by a variety of
triggering stimuli resulting in partially or completely reversible bronchoconstriction.
Symptoms and signs include dyspnea, chest tightness, cough, and wheezing.
The diagnosis is based on history, physical examination, and pulmonary
function tests. Treatment involves controlling triggering factors
and drug therapy, most commonly with inhaled β2-agonists
and inhaled corticosteroids. Prognosis is good with treatment.
Epidemiology
The prevalence of asthma has increased continuously since the 1970s, and it now affects an estimated 4 to 7% of people worldwide. More than 20 million people in the US are affected. Asthma is one of the most common chronic diseases of childhood, affecting more than 6 million children; it occurs more frequently in boys before puberty and in girls after puberty. It also occurs more frequently in blacks and Puerto Ricans. Despite its increasing prevalence, however, there has been a recent decline in mortality. About 4000 deaths occur from asthma annually in the US. However, the death rate is 5 times higher for blacks than for whites. Asthma is the leading cause of hospitalization for children and is the number one chronic condition causing elementary school absenteeism. In 2002, the total cost of asthma care was $14 billion.
Etiology
Development of asthma is multifactorial and depends on the interactions among multiple susceptibility genes and environmental factors.
Susceptibility genes are thought to include those for T-helper 1 and 2 (Th1 and Th2) cells, IgE, cytokines (IL-3, -4, -5, -9, and -13), granulocyte-monocyte colony-stimulating factor (GM-CSF), tumor necrosis factor-α (TNF-α), and the ADAM33 gene, which may stimulate airway smooth muscle and fibroblast proliferation or regulate cytokine production.
Environmental factors may include the following:
Evidence clearly implicates household allergens (eg, dust mite, cockroach, pets) and other environmental allergens in disease development in older children and adults. Diets low in vitamins C and E and in ω–3 fatty acids have been linked to asthma, as has obesity. Asthma has also been linked to perinatal factors, such as young maternal age, poor maternal nutrition, prematurity, low birthweight, and lack of breastfeeding.
On the other hand, endotoxin exposure early in life can induce tolerance and may be protective. Air pollution is not definitively linked to disease development, though it may trigger exacerbations. The role of childhood exposure to cigarette smoke is controversial, with some studies finding a contributory and some a protective effect.
Genetic and environmental components may interact by determining the balance between Th1 and Th2 cell lineages. Infants may be born with a predisposition toward proallergic and proinflammatory Th2 immune responses, characterized by growth and activation of eosinophils and IgE production. Early childhood exposure to bacterial and viral infections and endotoxins may shift the body to Th1 responses, which suppresses Th2 cells and induces tolerance. Trends in developed countries toward smaller families with fewer children, cleaner indoor environments, and early use of vaccinations and antibiotics may deprive children of these Th2-suppressing, tolerance-inducing exposures and may partly explain the continuous increase in asthma prevalence in developed countries (the hygiene hypothesis).
Reactive airways
dysfunction syndrome (RADS):
Indoor exposures to nitrogen oxide and volatile organic compounds are implicated in the development of RADS, a persistent asthma-like syndrome in people with no history of asthma (see Environmental Pulmonary Diseases: Occupational Asthma). RADS appears to be distinct from asthma and may be, on occasion, a form of environmental lung disease. However, RADS and asthma have many clinical similarities (eg, wheezing, dyspnea, cough), and both may respond to corticosteroids.
Pathophysiology
Asthma involves
In patients with asthma, Th2 cells and other cell types—notably, eosinophils and mast cells, but also other CD4+ subtypes and neutrophils—form an extensive inflammatory infiltrate in the airway epithelium and smooth muscle, leading to airway remodeling (ie, desquamation, subepithelial fibrosis, angiogenesis, smooth muscle hypertrophy). Hypertrophy of smooth muscle narrows the airways and increases reactivity to allergens, infections, irritants, parasympathetic stimulation (which causes release of pro-inflammatory neuropeptides, such as substance P, neurokinin A, and calcitonin gene-related peptide), and other triggers of bronchoconstriction. Additional contributors to airway hyperreactivity include loss of inhibitors of bronchoconstriction (epithelium-derived relaxing factor, prostaglandin E2) and loss of other substances called endopeptidases that metabolize endogenous bronchoconstrictors. Mucus plugging and peripheral blood eosinophilia are additional classic findings in asthma and may be epiphenomena of airway inflammation.
Triggers:
Common triggers of an asthma attack include
Infectious triggers in young children include respiratory syncytial virus, rhinovirus, and parainfluenza virus infection. In older children and adults, URIs (particularly with rhinovirus) and pneumonia are common infectious triggers. Exercise can be a trigger, especially in cold or dry environments. Inhaled irritants, such as air pollution, cigarette smoke, perfumes, and cleaning products, are often involved. Emotions such as anxiety, anger, and excitement sometimes trigger attacks. Aspirin is a trigger in up to 30% of older patients and in patients with more severe asthma. Aspirin -induced asthma is typically accompanied by nasal polyps with nasal and sinus congestion.Gastroesophageal reflux disease (GERD) is a common exacerbating factor in some patients with asthma, possibly via esophageal acid-induced reflex bronchoconstriction or by microaspiration of acid.Allergic rhinitis often coexists with asthma; it is unclear whether the two are different manifestations of the same allergic process or whether rhinitis is a discrete asthma trigger.
Response:
In the presence of triggers, there is reversible airway narrowing and uneven lung ventilation. Relative perfusion exceeds relative ventilation in lung regions distal to narrowed airways; thus, alveolar O2 tensions fall and alveolar CO2 tensions rise. Most patients can compensate by hyperventilating, but in severe exacerbations, diffuse bronchoconstriction causes severe gas trapping, and the respiratory muscles are put at a marked mechanical disadvantage so that the work of breathing increases. Under these conditions, hypoxemia worsens and Paco2 rises. Respiratory and metabolic acidosis may result and, if left untreated, cause respiratory and cardiac arrest.
Classification
Unlike, eg, hypertension, in which one parameter (BP) defines the severity of the disorder and the efficacy of treatment, asthma causes a number of clinical and testing abnormalities. Also unlike most hypertension, asthma manifestations typically wax and wane. Thus, monitoring (and studying) asthma requires a consistent terminology and defined benchmarks.
Severity is the intrinsic intensity of the disease process (ie, how bad it is). Severity can usually be assessed directly only before treatment is started, because patients who have responded well to treatment by definition have few symptoms. Asthma severity is categorized as
The term status asthmaticus describes severe, intense, prolonged bronchospasm that is resistant to treatment.
Control is the degree to which symptoms, impairments, and risks are minimized by treatment. Control is the parameter assessed in patients receiving treatment. Good control is the goal of asthma management whatever the disease severity. Control is classified as
Severity and control are assessed in terms of patient impairment and risk (see Table 1: Asthma: Classification of Asthma Control*† ).
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Table 1
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Classification of Asthma
Control*†
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Component
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Well Controlled
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Not Well Controlled
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Very Poorly Controlled
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Symptoms
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All ages except children 5–11 yr: ≤2 days/wk
Children 5–11 yr: ≤ 2 days/wk but not > once/day
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All ages except children 5–11 yr: > 2 days/wk
Children 5–11 yr: > 2 days/wk or multiple times on ≤2 days/wk
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For all ages: Throughout the day
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Nighttime awakenings
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≤ 2 /mo
Children 5–11 yr: ≤ 1 /mo
Children 0–4 yr: ≤ 1 /mo
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1–3/wk
Children 5–11 yr: ≥ 2/mo
Children 0–4 yr: > 1/mo
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≥4/wk
Children 5–11 yr: ≥ 2/wk
Children 0–4 yr: > 1/wk
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Interference with normal activity
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None
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Some limitation
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Extreme limitation
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Use of short-acting β2-agonist for symptom control (not prevention of exercise-induced asthma)
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≤ 2 days/wk
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> 2 days/wk
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Several times/day
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FEV1 or peak flow
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> 80% predicted/personal best
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60–80% predicted/personal best
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< 60% predicted/personal best
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FEV1/FVC (children 5–11 yr)
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> 80%
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75–80%
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< 75%
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Validated questionnaires
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ATAQ
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0
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1–2
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3−4
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ACQ
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≤ 0.75†
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≥ 1.5
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Ν/Α
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ACT
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≥ 20
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16−19
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≤ 15
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Exacerbations requiring oral systemic corticosteroids‡
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0–1/yr
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≥ 2/yr
Children 0–4 yr: 2–3/yr
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≥ 2/yr
Children 0–4 yr: > 3/yr
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Recommended action
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Maintain current step
Follow up every 1–6 mo
Consider step down if well controlled for ≥ 3 mo
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Step up 1 step
Reevaluate in 2–6 wk
For adverse effects, consider treatment options
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Consider short course of systemic corticosteroids
Step up 1 or 2 steps
Reevaluate in 2 wk
For adverse effects, consider treatment options
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ACQ = Asthma control questionnaire; ACT = asthma control test; ATAQ = asthma therapy assessment questionnaire; FEV1 = forced expiratory volume in 1 sec; FVC = forced vital capacity.
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*All ages unless specified differently.
†Level of control is based on the most severe impairment or risk category. Additional factors to consider are progressive loss of lung function on pulmonary function tests, significant adverse effects, and severity and interval between exacerbations (ie, one exacerbation requiring intubation or 2 hospitalizations within 1 mo may be considered very poor control).
‡At present, there are inadequate data to correlate frequencies of exacerbations with different levels of asthma control. In general, more frequent and intense exacerbations (eg, requiring urgent, unscheduled care, hospitalization, or ICU admission) indicate poorer asthma control.
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Adapted from National Heart, Lung, and Blood Institute: Expert Panel Report 3: Guidelines for the diagnosis and management of asthma—full report 2007. August 28, 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm.
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Impairment refers to the frequency and intensity of patients' symptoms and functional limitations. Impairment is assessed by spirometry, mainly forced expiratory volume in 1 sec (FEV1), and the ratio of FEV1 to forced vital capacity (FVC), as well as clinical features such as:
Risk refers to the likelihood of future exacerbations or decline in lung function and the risk of adverse drug effects. Risk is assessed by long-term trends in spirometry and clinical features such as:
It is important to remember that the severity category does not predict how serious an exacerbation a patient may have. For example, a patient who has mild asthma with long periods of no or mild symptoms and normal pulmonary function may have a severe, life-threatening exacerbation.
Symptoms and Signs
Patients with mild asthma are typically asymptomatic between exacerbations. Patients with more severe disease and those with exacerbations experience dyspnea, chest tightness, audible wheezing, and coughing. Coughing may be the only symptom in some patients (cough-variant asthma). Symptoms can follow a circadian rhythm and worsen during sleep, often around 4 am. Many patients with more severe disease waken during the night (nocturnal asthma).
Signs include wheezing, pulsus paradoxus (ie, a fall of systolic BP > 10 mm Hg during inspiration—see Approach to the Cardiac Patient: Pulsus paradoxus), tachypnea, tachycardia, and visible efforts to breathe (use of neck and suprasternal [accessory] muscles, upright posture, pursed lips, inability to speak). The expiratory phase of respiration is prolonged, with an inspiratory:expiratory ratio of at least 1:3. Wheezes can be present through both phases or just on expiration, but patients with severe bronchoconstriction may have no audible wheezing because of markedly limited airflow.
Patients with a severe exacerbation and impending respiratory failure typically have some combination of altered consciousness, cyanosis, pulsus paradoxus > 15 mm Hg, O2 saturation (O2sat) < 90%, Paco2 > 45 mm Hg, or hyperinflation. Rarely, pneumothorax or pneumomediastinum is seen on chest x-ray.
Symptoms and signs disappear between acute attacks, although soft wheezes may be audible during forced expiration at rest, or after exercise in some asymptomatic patients. Hyperinflation of the lungs may alter the chest wall in patients with long-standing uncontrolled asthma, producing a barrel-shaped thorax.
All symptoms and signs are nonspecific, are reversible with timely treatment, and typically are brought on by exposure to one or more triggers.
Diagnosis
Diagnosis is based on history and physical examination and is confirmed with pulmonary function tests. Diagnosis of causes and the exclusion of other disorders that cause wheezing are also important. Asthma and COPD are sometimes easily confused; they cause similar symptoms and produce similar results on pulmonary function tests but differ in important biologic ways that are not always clinically apparent.
Pulmonary function
tests:
Patients suspected of having asthma should undergo pulmonary function testing to confirm and quantify the severity and reversibility of airway obstruction. Pulmonary function data quality is effort-dependent and requires patient education before the test. If it is safe to do so, bronchodilators should be stopped before the test: 6 h for short-acting β2-agonists, such as albuterol ; 8 h for ipratropium ; 12 to 36 h for theophylline ; 24 h for long-acting β2-agonists, such as salmeterol and formoterol ; and 48 h for tiotropium .
Spirometry (see Tests of Pulmonary Function (PFT)) should be done before and after inhalation of a short-acting bronchodilator. Signs of airflow limitation before bronchodilator inhalation include reduced FEV1 and a reduced FEV1/FVC ratio. The FVC may also be decreased because of gas trapping, such that lung volume measurements may show an increase in the residual volume, the functional residual capacity, or both. An improvement in FEV1 of > 12% or an increase ≥10% of predicted FEV1 in response to bronchodilator treatment confirms reversible airway obstruction, although absence of this finding should not preclude a therapeutic trial of bronchodilators. Spirometry should be repeated at least every 1 to 2 yr in patients with asthma to monitor disease progression.
Flow-volume loops should also be reviewed to diagnose vocal cord dysfunction, a common cause of upper airway obstruction that mimics asthma.
Provocative testing, in which inhaled methacholine (or alternatives, such as inhaled histamine, adenosine , or bradykinin, or exercise testing) is used to provoke bronchoconstriction, is indicated for patients suspected of having asthma who have normal findings on spirometry and flow-volume testing, and for patients suspected of having cough-variant asthma, provided there are no contraindications. Contraindications include FEV1 < 1 L or < 50%, recent MI or stroke, and severe hypertension (systolic BP > 200 mm Hg; diastolic BP > 100 mm Hg). A decline in FEV1 of > 20% on provocative testing supports the diagnosis of asthma. However, FEV1 may decline in response to these drugs in other disorders, such as COPD.
Other
tests:
Other tests may be helpful in some circumstances: DLco testing can help distinguish asthma from COPD. Values are normal or elevated in asthma and usually reduced in COPD, particularly in patients with emphysema.
A chest x-ray may help exclude some causes of asthma or alternative diagnoses, such as heart failure or pneumonia. The chest x-ray in asthma is usually normal but may show hyperinflation or segmental atelectasis, a sign of mucous plugging. Infiltrates, especially those that come and go and that are associated with findings of central bronchiectasis, suggest allergic bronchopulmonary aspergillosis (see Asthma: Allergic Bronchopulmonary Aspergillosis (ABPA)).
Allergy testing may be indicated for children whose history suggests allergic triggers (particularly for allergic rhinitis) because these children may benefit from immunotherapy. It should be considered for adults whose history indicates relief of symptoms with allergen avoidance and for those in whom a trial of therapeutic anti-IgE antibody therapy (see Asthma: Drug therapy) is being considered. Skin testing and measurement of allergen-specific IgE via radioallergosorbent testing (RAST) can identify specific allergic triggers (see Allergic and Other Hypersensitivity Disorders: Specific tests).
Elevated blood eosinophils (> 400 cells/μL) and nonspecific IgE (> 150 IU) are suggestive but not diagnostic of allergic asthma because they can be elevated in other conditions.
Sputum evaluation for eosinophils is not commonly done; finding large numbers of eosinophils is suggestive of asthma but is neither sensitive nor specific.
Peak expiratory flow (PEF) measurements with inexpensive handheld flow meters are recommended for home monitoring of disease severity and for guiding therapy.
Evaluation
of exacerbations:
Patients with asthma with an acute exacerbation should have certain tests:
All 3 measures help establish the severity of an exacerbation and document treatment response. PEF values are interpreted in light of the patient's personal best, which may vary widely among patients who are equally well controlled. A 15 to 20% reduction from this baseline indicates a significant exacerbation. When baseline values are not known, the percent predicted value gives a general idea of airflow limitation but not the individual patient's degree of worsening.
Chest x-ray is not necessary for most exacerbations but should be obtained in patients with symptoms suggestive of pneumonia or pneumothorax.
ABG measurements should be obtained in patients with marked respiratory distress or signs and symptoms of impending respiratory failure.
Prognosis
Asthma resolves in many children, but for as many as one in four, wheezing persists into adulthood or relapse occurs in later years. Female sex, smoking, earlier age of onset, sensitization to household dust mites, and airway hyperresponsiveness are risk factors for persistence and relapse.
About 4000 deaths/yr in the US are attributable to asthma, most of which are preventable with treatment. Thus, the prognosis is good with adequate access and adherence to treatment. Risk factors for death include increasing requirements for oral corticosteroids before hospitalization, previous hospitalization for acute exacerbations, and lower peak flow measurements at presentation. Several studies show that use of inhaled corticosteroids decreases hospital admission and mortality rates.
Over time, the airways in some patients with asthma undergo permanent structural changes (remodeling) that prevent return to normal lung functioning. Early aggressive use of anti-inflammatory drugs may help prevent this remodeling.
Treatment
Treatment objectives are to minimize impairment and risk, including preventing exacerbations and minimizing chronic symptoms, including nocturnal awakenings; to minimize the need for emergency department visits or hospitalizations; to maintain baseline (normal) pulmonary function and activity levels; and to avoid adverse treatment effects.
Control
of triggering factors:
Triggering factors in some patients may be controlled with use of synthetic fiber pillows and impermeable mattress covers and frequent washing of bed sheets, pillowcases, and blankets in hot water. Upholstered furniture, soft toys, carpets, and pets should be removed (dust mites, animal dander). Dehumidifiers should be used in basements and in other poorly aerated, damp rooms (molds). Steam treatment of homes diminishes dust mite allergens. House cleaning and extermination to eliminate cockroach exposure is especially important. Although control of triggering factors is more difficult in urban environments, the importance of these measures is not diminished. High-efficiency particulate air (HEPA) vacuums and filters may relieve symptoms, but beneficial effects on pulmonary function and on the need for drugs are unproved. Sulfite-sensitive patients should avoid red wine. Nonallergenic triggers, such as cigarette smoke, strong odors, irritant fumes, cold temperatures, high humidity, and exercise, should also be avoided or controlled when possible. Avoidance of viral URIs is also important.Patients with aspirin -induced asthma can use acetaminophen , choline magnesium salicylate , or selective cyclooxygenase-2 (COX-2) inhibitors in place of NSAIDs.Asthma is a relative contraindication to the use of nonselective β-blockers, including topical formulations, but cardioselective drugs (eg, metoprolol , atenolol ) probably have no adverse effects.
Drug therapy:
Major drug classes commonly used in the treatment of chronic asthma and asthma exacerbations include
Drugs in these classes (see Table 2: Asthma: Drug Treatment of Chronic Asthma ) are inhaled or taken orally; inhaled drugs come in aerosolized and powdered forms. Use of aerosolized forms with a spacer or holding chamber facilitates deposition of the drug in the airways rather than the pharynx; patients are advised to wash and dry their spacers after each use to prevent bacterial contamination. In addition, use of aerosolized forms requires coordination between actuation of the inhaler (drug delivery) and inhalation; powdered forms reduce the need for coordination, because drug is delivered only when the patient inhales. In addition, powdered forms reduce the release of fluorocarbon propellants into the environment.
β2-Agonists relax bronchial smooth muscle, decrease mast cell degranulation and histamine release, inhibit microvascular leakage into the airways, and increase mucociliary clearance. β2-Agonists come in short- and long-acting preparations (see Table 2: Asthma: Drug Treatment of Chronic Asthma ). Short-acting β2-agonists (eg, albuterol ) inhaled 2 puffs q 4 h as needed are the drug of choice for relieving acute bronchoconstriction and preventing exercise-induced asthma. They are not used for long-term maintenance. They take effect within minutes and are active for up to 6 to 8 h, depending on the drug. Tachycardia and tremor are the most common acute adverse effects of inhaled β2-agonists and are dose-related. Mild hypokalemia occurs uncommonly. Use of levalbuterol (a solution containing the R-isomer of albuterol ) theoretically minimizes adverse effects, but its long-term efficacy and safety are unproved. Oral β2-agonists have more systemic effects and generally should be avoided.
Long-acting β2-agonists (eg, salmeterol ) are active for up to 12 h and are used for moderate and severe asthma but should never be used as monotherapy. They interact synergistically with inhaled corticosteroids and permit lower dosing of corticosteroids. The safety of regular long-term use of β2-agonists is controversial. Long-acting β2-agonists may increase the risk of asthma-related death. Therefore, when treating patients with asthma, salmeterol should only be used as additional therapy, not monotherapy, for patients whose condition is not adequately controlled with other asthma-controllers (eg, low- to medium-dose inhaled corticosteroids) or whose disease severity clearly warrants additional maintenance therapies. Daily use of β2-agonists, increased dosing or diminishing effects, or use of one or more canisters a month suggests inadequate control and the need to begin or intensify other therapies.
Anticholinergics relax bronchial smooth muscle through competitive inhibition of muscarinic (M3) cholinergic receptors. Ipratropium may have an additive effect when combined with short-acting β2-agonists. Adverse effects include pupillary dilation, blurred vision, and dry mouth. Tiotropium is a 24-h inhaled anticholinergic that has not been adequately evaluated for asthma use.
Corticosteroids inhibit airway inflammation, reverse β-receptor down-regulation, and inhibit cytokine production and adhesion protein activation. They block the late response (but not the early response) to inhaled allergens. Routes of administration include oral, IV, and inhaled. In acute asthma exacerbation, early use of systemic corticosteroids often aborts the exacerbation, decreases the need for hospitalization, prevents relapse, and speeds recovery. Oral and IV routes are equally effective. Inhaled corticosteroids have no role in acute exacerbation but are indicated for long-term suppression, control, and reversal of inflammation and symptoms. They substantially reduce the need for maintenance oral corticosteroid therapy. Adverse local effects of inhaled corticosteroids include dysphonia and oral candidiasis, which can be prevented or minimized by having the patient use a spacer, gargle with water after corticosteroid inhalation, or both. Systemic effects are all dose-related, can occur with oral or inhaled forms, and occur mainly with inhaled doses > 800 μg/day. They include suppression of the adrenal-pituitary axis, osteoporosis, cataracts, skin atrophy, hyperphagia, and easy bruisability. Whether inhaled corticosteroids suppress growth in children is controversial: Most children reach their predicted adult height. Latent TB may be reactivated by systemic corticosteroid use.
Mast
cell stabilizers inhibit histamine release from mast cells, reduce airway hyperresponsiveness, and block the early and late responses to allergens. They are given by inhalation prophylactically to patients with exercise-induced or allergen-induced asthma. They are ineffective once symptoms have occurred. They are the safest of all antiasthmatic drugs but the least effective.
Leukotriene
modifiers are taken orally and can be used for long-term control and prevention of symptoms in patients with mild persistent to severe persistent asthma. The main adverse effect is liver enzyme elevation (which occurs with zileuton). Although rare, patients have developed a clinical syndrome resembling that of Churg-Strauss syndrome.
Methylxanthines relax bronchial smooth muscle (probably by inhibiting phosphodiesterase) and may improve myocardial and diaphragmatic contractility through unknown mechanisms. Methylxanthines appear to inhibit intracellular release of Ca, decrease microvascular leakage into the airway mucosa, and inhibit the late response to allergens. They decrease the infiltration of eosinophils into bronchial mucosa and of T lymphocytes into epithelium. Methylxanthines are used for long-term control as an adjunct to β2-agonists; extended-release theophylline helps manage nocturnal asthma. Theophylline is falling into disuse because of its many adverse effects and interactions compared with other drugs. Adverse effects include headache, vomiting, cardiac arrhythmias, and seizures. Methylxanthines have a narrow therapeutic index; multiple drugs (any metabolized by the cytochrome P450 pathway, eg, macrolide antibiotics) and conditions (eg, fever, liver disease, heart failure) alter methylxanthine metabolism and elimination. Serum theophylline levels should be monitored periodically and maintained between 5 and 15 μg/mL (28 and 83
μmol/L).
Immunomodulators include omalizumab , an anti-IgE antibody developed for use in severely allergic patients with asthma who have elevated IgE levels. Omalizumab may decrease asthma exacerbations, decreases corticosteroid requirements, and relieves symptoms. Dosing is determined by a dosing chart based on the patient's weight and IgE levels. The drug is administered sc q 2 to 4 wk. Clinicians who administer omalizumab should be prepared to identify and treat anaphylaxis, which may occur.
Other drugs are used uncommonly in specific circumstances. Magnesium is often used in the acute setting of the emergency department, but it is not recommended in the management of chronic asthma. Immunotherapy may be indicated when symptoms are triggered by allergy, as suggested by history and confirmed by allergy testing. Immunotherapy is generally more effective in children than adults. If symptoms are not significantly relieved after 24 mo, then therapy is stopped. If symptoms are relieved, therapy should continue for ≥ 3 yr, although the optimum duration is unknown. Other drugs that suppress the immune system are occasionally prescribed to reduce dependence on high-dose oral corticosteroids, but these drugs have a significant risk of toxicity. Low-dose methotrexate (5 to 15 mg once/wk) can lead to modest improvements in FEV1 and modest decreases in daily oral corticosteroid use. Gold and cyclosporine are also modestly effective, but toxicity and need for monitoring limit their use. Other therapies for management of chronic asthma include nebulized lidocaine , nebulized heparin , colchicine , and high-dose IV immune globulin. Limited evidence supports the use of any of these therapies, and their benefits are unproved, so none are currently recommended for routine clinical use.
Monitoring
response to treatment:
Guidelines recommend office use of spirometry (FEV1, FEV1/FVC, FVC) to measure airflow limitation and assess impairment and risk. Outside the office, home PEF monitoring, in conjunction with patient symptom diaries and the use of an asthma action plan, is especially useful for charting disease progression and response to treatment in patients with moderate to severe persistent asthma. When asthma is quiescent, one PEF measurement in the morning suffices. Should PEF measurements fall to < 80% of the patient's personal best, then twice/day monitoring to assess circadian variation is useful. Circadian variation of > 20% indicates airway instability and the need to re-evaluate the therapeutic regimen.
Patient education:
The importance of patient education cannot be overemphasized. Patients do better when they know more about asthma—what triggers an attack, what drug to use when, proper inhaler technique, how to use a spacer with a metered-dose inhaler (MDI), and the importance of early use of corticosteroids in exacerbations. Every patient should have a written action plan for day-to-day management, especially for management of acute attacks, that is based on the patient's best personal peak flow rather than on a predicted normal value. Such a plan leads to much better asthma control, largely attributable to improved adherence to therapies.
Treatment
of acute exacerbation:
The goal of asthma exacerbation treatment is to relieve symptoms and return patients to their best lung function. Treatment includes
Patients having an attack are instructed to self-administer 2 to 4 puffs of inhaled albuterol or a similar short-acting β2-agonist up to 3 times spaced 20 min apart for an acute exacerbation and to measure PEF if possible. When these short-acting rescue drugs are effective (symptoms are relieved and PEF returns to > 80% of baseline), the acute exacerbation may be managed in the outpatient setting. Patients who do not respond, have severe symptoms, or have a PEF persistently < 80% should follow a treatment management program outlined by the physician or should go to the emergency department (see Table 3: Asthma: Drug Treatment of Asthma Exacerbations for specific dosing information).
Inhaled bronchodilators (β2-agonists and anticholinergics) are the mainstay of asthma treatment in the emergency department. In adults and older children, albuterol given by an MDI and spacer is as effective as that given by nebulizer. Nebulized treatment is preferred for younger children because of difficulties coordinating MDIs and spacers; evidence suggests that bronchodilator response improves when the nebulizer is powered with helium-O2 (heliox) rather than with O2. Subcutaneous epinephrine 1:1000 solution or terbutaline is an alternative for children. Terbutaline may be preferable to epinephrine because of its lesser cardiovascular effect and longer duration of action, but it is no longer produced in large quantities and is expensive. Subcutaneous administration of β2-agonists in adults raises concerns of adverse cardiostimulatory effects. However, clinically important adverse effects are few, and subcutaneous administration may benefit patients unresponsive to maximal inhaled therapy or patients unable to receive effective nebulized treatment (eg, those who cough excessively, have poor ventilation, or are uncooperative). Nebulized ipratropium can be co-administered with nebulized albuterol for patients who do not respond optimally to albuterol alone; some evidence favors simultaneous high-dose β2-agonist and ipratropium as first-line treatment, but no data favor continuous β2-agonist nebulization over intermittent administration. Theophylline has very little role in treatment.
Systemic corticosteroids ( prednisone , prednisolone , methylprednisolone ) should be given for all but the mildest acute exacerbation; they are unnecessary for patients whose PEF normalizes after 1 or 2 bronchodilator doses. IV and oral routes of administration are probably equally effective. IV methylprednisolone can be given if an IV line is already in place and can be switched to oral dosing whenever necessary or convenient. Tapering usually starts after 7 to 10 days and should last 2 to 3 wk.
Antibiotics are indicated only when history, examination, or chest x-ray suggests underlying bacterial infection; most infections underlying asthma exacerbations are probably viral in origin.
Supplemental O2 is indicated for hypoxemia and should be given by nasal cannula or face mask at a flow rate or concentration sufficient to maintain O2sat > 90%.
Reassurance is the best approach when anxiety is the cause of asthma exacerbation. Anxiolytics and morphine are relatively contraindicated because they are associated with increased mortality and the need for mechanical ventilation.
Hospitalization generally is required if patients have not returned to their baseline within 4 h of aggressive emergency department treatment. Criteria for hospitalization vary, but definite indications are failure to improve, worsening fatigue, relapse after repeated β2-agonist therapy, and significant decrease in Pao2 (< 50 mm Hg) or increase in Paco2 (> 40 mm Hg), indicating progression to respiratory failure.
Patients who continue to deteriorate despite aggressive treatment are candidates for noninvasive positive pressure ventilation or endotracheal intubation and invasive mechanical ventilation (see Respiratory Failure and Mechanical Ventilation). Patients requiring intubation may benefit from sedation, but neuromuscular blocking agents should be avoided because of possible interactions with corticosteroids that can cause prolonged neuromuscular weakness.
Generally, volume-cycled ventilation in assist |
