AUTHOR AND EDITOR INFORMATION

Section 1 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

INTRODUCTION

Section 2 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Background

Asthma, or hyperreactive airway disease, is one of the most common chronic diseases worldwide and is the most common cause of hospitalization for children in the United States. Despite recent advances in understanding of the pathophysiology and treatment of asthma, the condition continues to have significant medical and economic impacts worldwide. In 1991, the National Asthma Education and Prevention Program Expert Panel from the US National Institutes of Health issued its first report on the guidelines for the diagnosis and management of asthma. They defined asthma as follows:

Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular elements play a role, in particular, mast cells, eosinophils, T lymphocytes, macrophages, neutrophils, and epithelial cells. In susceptible individuals, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread but variable airflow obstruction that is often reversible either spontaneously or with treatment. The inflammation also causes an associated increase in the existing bronchial responsiveness to a variety of stimuli.

The Expert Panel Report 2¹ was issued in 1997 and further refined effective asthma management based on the following components: (1) objective measures of lung function, (2) environmental control measures, (3) comprehensive pharmacologic therapy, and (4) patient education.

Exercise-induced asthma (EIA), or exercise-induced bronchospasm (EIB), is an asthma variant defined as a condition in which exercise or vigorous physical activity triggers acute bronchospasm in persons with heightened airway reactivity. It is observed primarily in persons who are asthmatic but can also be found in patients with atopy, allergic rhinitis, or cystic fibrosis and even in healthy persons. EIA is often a neglected diagnosis, and the underlying asthma may be silent in as many as 50% of patients, except during exercise.

The following guidelines may be a useful resource:

• Guidelines for the Diagnosis and Management of Asthma -- Part 1: Introduction -- Diagnosing Asthma
• Guidelines for the Diagnosis and Management of Asthma -- Part 2 - Managing Asthma Long Term
• Guidelines for the Diagnosis and Management of Asthma -- Part 3: Medications
• Guidelines for the Diagnosis and Management of Asthma -- Part 4: Managing Special Situations and Exacerbations

Pathophysiology

The pathophysiology of asthma is complex and involves the following components: (1) airway inflammation, (2) intermittent airflow obstruction, and (3) bronchial hyperresponsiveness. The mechanism of inflammation in asthma may be acute, subacute, or chronic, and the presence of airway edema and mucus secretion also contributes to airflow obstruction and bronchial reactivity. Varying degrees of mononuclear cell and eosinophil infiltration, mucus hypersecretion, desquamation of the epithelium, smooth muscle hyperplasia, and airway remodeling are present.

Some of the principal cells identified in airway inflammation include mast cells, eosinophils, epithelial cells, macrophages, and activated T lymphocytes. T lymphocytes play an important role in the regulation of airway inflammation through the release of numerous cytokines. Other constituent airway cells, such as fibroblasts, endothelial cells, and epithelial cells, contribute to the chronicity of the disease. Other factors, such as adhesion molecules (eg, selectins, integrins), are critical in directing the inflammatory changes in the airway. Finally, cell-derived mediators influence smooth muscle tone and produce structural changes and remodeling of the airway.

The presence of airway hyperresponsiveness or bronchial hyperreactivity in asthma is an exaggerated response to numerous exogenous and endogenous stimuli. The mechanisms involved include direct stimulation of airway smooth muscle and indirect stimulation by pharmacologically active substances from mediator-secreting cells such as mast cells or nonmyelinated sensory neurons. The degree of airway hyperresponsiveness generally correlates with the clinical severity of asthma.

Airflow obstruction can be caused by a variety of changes, including acute bronchoconstriction, airway edema, chronic mucous plug formation, and airway remodeling. Acute bronchoconstriction is the consequence of immunoglobulin E–dependent mediator release upon exposure to aeroallergens and is the primary component of the early asthmatic response. Airway edema occurs 6-24 hours following an allergen challenge and is referred to as the late asthmatic response. Chronic mucous plug formation consists of an exudate of serum proteins and cell debris that may take weeks to resolve. Airway remodeling is associated with structural changes due to long-standing inflammation and may profoundly affect the extent of reversibility of airway obstruction.

The pathogenesis of EIA is controversial. The disease may be mediated by water loss from the airway, heat loss from the airway, or a combination of both. The upper airway is designed to keep inspired air at 100% humidity and body temperature at 37°C (98.6°F). The nose is unable to condition the increased amount of air required for exercise, particularly in athletes who breathe through their mouths. The abnormal heat and water fluxes in the bronchial tree result in bronchoconstriction, occurring within minutes of completing exercise. Results from bronchoalveolar lavage studies have not demonstrated an increase in inflammatory mediators. These patients generally develop a refractory period, during which a second exercise challenge does not cause a significant degree of bronchoconstriction.

Frequency

United States

Asthma affects 5-10% of the population or an estimated 14-15 million persons, including 5 million children. The prevalence rate of EIA is 3-10% of the general population if persons who do not have asthma or allergy are excluded, but the rate increases to 12-15% of the general population if patients with asthma are included. The rate of exercise-induced symptoms in persons with asthma has been reported to vary from 40-90%.

International

Asthma is common in industrialized nations such as Canada, England, Australia, Germany, and New Zealand, where much of the data have been collected. The prevalence rate of severe asthma in industrialized countries ranges from 2-10%. Recent trends suggest an increase in both the prevalence and morbidity of the disease, especially in children younger than 6 years. Factors that have been implicated include urbanization, air pollution, passive smoking, and change in exposure to environmental allergens.

Mortality/Morbidity

• The estimate of lost work and school time from asthma is approximately 100 million days of restricted activity. More than 1.8 million emergency department evaluations occur annually. The figures from the 1997 National Institutes of Health report¹ indicate an estimated 500,000 hospitalizations and 5000 deaths annually. International asthma mortality is reported as high as 0.86 deaths per 100,000 persons in some countries. Mortality is primarily related to lung function, with an 8-fold increase in patients in the lowest quartile, but has also been linked with management failure, especially in young persons. Other factors that impact mortality include age older than 40 years, cigarette smoking greater than 20-pack years, blood eosinophilia, forced expiratory volume in one second (FEV₁) of 40-69% predicted, and greater reversibility.
• EIA has not been reported to cause death. Morbidity is associated with exercise limitation. This is observed most dramatically in elite athletes with high levels of exercise who may be limited by airway hyperreactivity.

Race

• Asthma occurs in persons of all races worldwide. In the United States, asthma prevalence, especially morbidity and mortality, are higher in blacks than in whites.
• Although genetic factors are of major importance in determining a predisposition to the development of asthma, environmental factors play a greater role than racial factors in the onset of disease. National concern is that some of the increased morbidity is due to differences in treatment afforded certain minority groups.

Sex

• Asthma predominantly occurs in boys in childhood, with a male-to-female ratio of 2:1 until puberty, when the male-to-female ratio becomes 1:1.
• Asthma prevalence is greater in females after puberty, and the majority of adult-onset cases diagnosed in persons older than 40 years occur in females.
• Boys are more likely than girls to experience a decrease in symptoms by late adolescence.

Age

• Asthma prevalence is increased in very young persons and very old persons because of airway responsiveness and lower levels of lung function. Two thirds of all asthma cases are diagnosed before the patient is aged 18 years. Approximately half of all children diagnosed with asthma have a decrease or disappearance of symptoms by early adulthood.
• The diagnosis of EIA is made more often in children and young adults than in older adults and is related to high levels of physical activity. It can be observed in persons of any age based on the level of underlying airway reactivity and the level of physical exertion.

CLINICAL

Section 3 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

History

• A detailed medical history should address (1) whether symptoms are attributable to asthma, (2) whether findings support the likelihood of asthma (eg, family history), (3) asthma severity, and (4) the identification of possible precipitating factors.
• • Symptoms may include the following:
  • • Cough
    • Wheezing
    • Shortness of breath
    • Chest tightness
    • Sputum production
    • Decreased exercise tolerance
  • Symptom patterns can vary as follows:
  • • Perennial versus seasonal
    • Continual versus episodic
    • Duration, severity, and frequency
    • Diurnal variations (nocturnal and early-morning awakenings)
  • Precipitating or aggravating factors, also discussed in Causes, may include the following:
  • • Allergens
    • Occupation
    • Medications
    • Exercise
  • Disease development variables include the following:
  • • Age at onset
    • History of injury early in life due to infection or passive smoke exposure
    • Progress of disease
    • Current response to management
    • Comorbid conditions
  • Family history may reveal the following conditions:
  • • Asthma
    • Allergy
    • Sinusitis
    • Rhinitis
  • Social history may reveal the following conditions:
  • • Home characteristics
    • Smoking
    • Workplace or school characteristics
    • Educational level
    • Employment
    • Social support
  • Determine the profile of a typical exacerbation.
  • The impact on the patient and family may have involved the following:
  • • Emergency department visits, hospitalizations, intensive care unit (ICU) admissions, intubations
    • Missed days from work or school or activity limitation
  • Assess the patient's disease perception based on the following elements:
  • • Knowledge of asthma and treatment
    • Use of medications
    • Coping mechanisms
    • Family support
    • Economic resources
• The clinical history for EIA is typical of asthma, with symptoms such as cough, wheezing, shortness of breath, and chest pain or tightness. Some individuals also may report sore throat or GI upset.
• • Symptoms are usually associated with exercise but may be related to exposure to cold air or other triggers, such as seasonal allergens, pollutants (eg, sulfur, nitrous oxide, ozone), or upper respiratory infections.
  • Initially, airway dilation is noted during exercise. If exercise extends beyond approximately 10 minutes, bronchoconstriction supervenes, resulting in asthma symptoms. If the exercise period is shorter, symptoms may develop up to 5-10 minutes after completion of exercise. A higher intensity level of exercise results in a more intense attack. Running produces more symptoms than walking.
  • Patients may note symptoms are related to seasonal changes or the ambient temperature and humidity in the environment in which a patient exercises. Cold, dry air generally provokes more obstruction than warm, humid air. Consequently, many athletes have good exercise tolerance in sports such as swimming. Athletes who are more physically fit may not notice the typical symptoms and may only report a reduced or more limited level of endurance.
  • Several modifiers in the history should prompt an evaluation for causes other than EIA. While patients may report typical obstructive symptoms, a history of a choking sensation with exercise, inspiratory wheezing, or stridor should prompt an evaluation for evidence of vocal cord dysfunction.

Physical

• General
• • Evidence of respiratory distress manifests as increased respiratory rate, increased heart rate, diaphoresis, and use of accessory muscles of respiration.
  • Marked weight loss or severe wasting may indicate severe emphysema.
• Pulsus paradoxus: This is an exaggerated fall in systolic blood pressure during inspiration and may occur during an acute asthma exacerbation.
• Depressed sensorium: This finding suggests a more severe asthma exacerbation with impending respiratory failure.
• Chest examination
• • End-expiratory wheezing or a prolonged expiratory phase is found most commonly, although inspiratory wheezing can be heard.
  • Diminished breath sounds and chest hyperinflation may be observed during acute exacerbations.
  • The presence of inspiratory wheezing or stridor may prompt an evaluation for an upper airway obstruction such as vocal cord dysfunction, vocal cord paralysis, thyroid enlargement, or a soft tissue mass (eg, malignant tumor).
• Upper airway
• • Look for evidence of erythematous or boggy turbinates or the presence of polyps from sinusitis, allergic rhinitis, or upper respiratory infection.
  • Any type of nasal obstruction may result in worsening of asthma or symptoms of EIA.
• Skin: Observe for the presence of atopic dermatitis, eczema, or other manifestations of allergic skin conditions.

Causes

• Factors that can contribute to asthma or airway hyperreactivity may include any of the following:
• • Environmental allergens (House dust mites, animal allergens [especially cat and dog], cockroach allergens, and fungi are most commonly reported.)
  • Viral respiratory infections
  • Exercise; hyperventilation
  • Gastroesophageal reflux disease (GERD)
  • Chronic sinusitis or rhinitis
  • Aspirin or nonsteroidal anti-inflammatory drug hypersensitivity, sulfite sensitivity
  • Use of beta-adrenergic receptor blockers (including ophthalmic preparations)
  • Obesity (Based on a prospective cohort study of 86,000 patients, those with an elevated body mass index are more likely to have asthma.)
  • Environmental pollutants, tobacco smoke
  • Occupational exposure
  • Irritants such as household sprays and paint fumes
  • A variety of high and low molecular weight compounds are associated with the development of occupational asthma such as insects, plants, latex, gums, diisocyanates, anhydrides, wood dust, and fluxes.
  • Emotional factors or stress
  • Perinatal factors (Prematurity and increased maternal age increase the risk for asthma; breastfeeding has not been definitely shown to be protective. Both maternal smoking and prenatal exposure to tobacco smoke also increase the risk of developing asthma.)
• Factors that contribute to EIA symptoms include the following:
• • Exposure to cold or dry air
  • Environmental pollutants (eg, sulfur, ozone)
  • Level of bronchial hyperreactivity
  • Chronicity of asthma and symptomatic control
  • Duration and intensity of exercise
  • Allergen exposure in atopic individuals
  • Coexisting respiratory infection

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Other Problems to be Considered

Allergic bronchopulmonary aspergillosis
Aspirin hypersensitivity
Viral respiratory infections
Occupational asthma
Reactive airways dysfunction syndrome
Congestive heart failure (cardiac asthma)
Tracheal and bronchial tumors
Other causes of upper airway obstruction

WORKUP

Section 5 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Laboratory studies are not routinely indicated for asthma but may be used to exclude other diagnoses.
• Blood eosinophilia greater than 4% or 300-400/µL supports the diagnosis of asthma, but an absence of this finding is not exclusionary. Eosinophil counts greater than 8% may be observed in patients with concomitant atopic dermatitis. This finding should prompt an evaluation for allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome, or eosinophilic pneumonia.
• Total serum immunoglobulin E levels greater than 100 IU are frequently observed in patients experiencing allergic reactions, but this finding is not specific for asthma and may be observed in patients with other conditions (eg, allergic bronchopulmonary aspergillosis, Churg-Strauss syndrome). A normal total serum immunoglobulin E level does not exclude the diagnosis of asthma.
• In monitoring of asthma control, the British Thoracic Society recommends using sputum eosinophilia determinations to guide therapy. An improvement in asthma control, a decrease in hospitalizations, and a decrease in exacerbations were noted in those patients in whom sputum-guided therapy was used.²
• Exhaled nitric oxide (NO) analysis has been shown to predict airway inflammation and asthmatic control; however, it is technically more complex and not routinely used in the monitoring of patients with asthma.

Imaging Studies

• In most patients, chest radiography findings are normal or indicate hyperinflation. Findings may help rule out other pulmonary diseases such as allergic bronchopulmonary aspergillosis or sarcoidosis, which can manifest with symptoms of reactive airway disease.
• Sinus CT scan may be useful to help exclude acute or chronic sinusitis as a contributing factor. In patients with chronic sinus symptoms, a CT scan of the sinuses can also help rule out chronic sinus disease.

Other Tests

• Allergy skin testing is a useful adjunct in individuals with atopy. Results help guide indoor allergen mitigation or help diagnose allergic rhinitis symptoms. The allergens that most commonly cause asthma are aeroallergens such as house dust mites, animal danders, pollens, and mold spores. Two methods are available to test for allergic sensitivity to specific allergens in the environment: allergy skin tests and blood radioallergosorbent tests (RAST). Allergy immunotherapy may be beneficial in controlling allergic rhinitis and asthma symptoms for some patients.
• In patients with asthma and symptoms of GERD, 24-hour pH monitoring can help determine if GERD is a contributing factor.

Procedures

• Pulmonary function testing (spirometry)
• • Perform spirometry measurements before and after inhalation of a short-acting bronchodilator in all patients in whom the diagnosis of asthma is considered. Spirometry measures the forced vital capacity, the maximal amount of air expired from the point of maximal inhalation, and the FEV₁. A reduced ratio of FEV₁ to forced vital capacity, when compared with predicted values, demonstrates the presence of airway obstruction. Reversibility is demonstrated by an increase of 12% and  200 mL after administration of a short-acting bronchodilator.
  • The diagnosis of asthma cannot be based on spirometry findings alone because many other diseases are associated with obstructive spirometry indices.
  • As a preliminary evaluation for EIA, perform spirometry in all patients with exercise symptoms to determine if any baseline abnormalities (ie, the presence of obstructive or restrictive indices) are present.
• Methacholine- or histamine-challenge testing
• • Bronchoprovocation testing with either methacholine or histamine is useful when spirometry findings are normal or near normal, especially in patients with intermittent or exercise-induced symptoms. Bronchoprovocation testing helps determine if hyperreactive airways are present, and a negative test result usually excludes the diagnosis of asthma.
  • Trained individuals should perform this testing in an appropriate facility and in accordance with the guidelines of the American Thoracic Society published in 1999.³ Methacholine is administered in incremental doses up to a maximum dose of 16 mg/mL, and a 20% decrease in FEV₁, up to the 4 mg/mL level, is considered a positive test result for the presence of bronchial hyperresponsiveness. The presence of airflow obstruction with an FEV₁ less than 65-70% at baseline is generally an indication to not perform the test.
• Exercise testing
• • Exercise spirometry is the standard method for evaluating patients with EIA. Testing involves 6-10 minutes of strenuous exertion at 85-90% of predicted maximal heart rate and measurement of postexercise spirometry for 15-30 minutes. The defined cutoff for a positive test result is a 15% decrease in FEV₁ after exercise.
  • Exercise testing may be accomplished in 3 different ways, using cycle ergometry, a standard treadmill test, or free running exercise. This method of testing is limited because laboratory conditions may not subject the patient to the usual conditions that trigger EIA symptoms, and results have a lower sensitivity compared with other methods.
• Eucapnic hyperventilation
• • Eucapnic hyperventilation with either cold or dry air is an alternate method of bronchoprovocation testing.
  • It has been used to evaluate patients for EIA and has been shown to produce results similar to those of methacholine-challenge testing.
• Peak-flow monitoring
• • Peak-flow monitoring is designed for ongoing monitoring of patients with asthma because the test is simple to perform and the results are a quantitative and reproducible measure of airflow obstruction.
  • It can be used for short-term monitoring, exacerbation management, and daily long-term monitoring.
  • Results can be used to determine the severity of an exacerbation and to help guide therapeutic decisions.
• Guidelines for the use of peak-flow meters are as follows:
  
  
  • Advise the patient to use the peak-flow meter upon awakening in the morning before using a bronchodilator.
  • Instruct the patient on how to establish a personal best peak expiratory flow (PEF) rate.
  • Inform the patient that a peak flow of less than 80% of the patient's personal best indicates a need for additional medication and a peak flow below 50% indicates severe exacerbation.
  • Advise the patient to use the same peak-flow meter over time.
• Exhaled NO
• • The use of exhaled NO as a measurement of airway inflammation has been suggested as a nonspecific marker. Elevated levels of NO have been shown in people with asthma compared with people without asthma, but limited data exist on the applicability of exhaled NO in the diagnosis of asthma.

TREATMENT

Section 6 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical Care

The goals for successful management of asthma outlined in the 2002 US National Heart, Lung, and Blood Institute publication "Global Strategy for Asthma Management and Prevention" include the following⁴:

• Achieve and maintain control of symptoms.
• Prevent asthma exacerbations.
• Maintain pulmonary function as close to normal levels as possible.
• Maintain normal activity levels, including exercise.
• Avoid adverse effects from asthma medications.
• Prevent the development of irreversible airflow limitation.
• Prevent asthma mortality.

The long-term outpatient management of asthma should follow the stepwise therapy model based on the Global Initiative for Asthma guidelines. These recommendations were updated during the 1997 National Asthma Education and Prevention Program, the results of which were published by the National Institutes of Health.¹ Management should incorporate 4 treatment components: (1) objective measures of lung function, (2) environmental control measures and avoidance of risk factors, (3) comprehensive pharmacologic therapy, and (4) patient education. Two additional management strategies include management of exacerbations and regular follow-up care. Classify the severity of asthma before treatment, based on symptom prevalence and measurement of lung function. Classification of severity and treatment options are shown below.

• Step 1 - Intermittent
• • Intermittent symptoms occurring less than once a week
  • Brief exacerbations
  • Nocturnal symptoms occurring less than twice a month
  • Asymptomatic with normal lung function between exacerbations
  • No daily medication needed
  • FEV₁ or PEF rate greater than 80%, with less than 20% variability
• Step 2 - Mild persistent
• • Symptoms occurring more than once a week but less than once a day
  • Exacerbations affect activity and sleep
  • Nocturnal symptoms occurring more than twice a month
  • Inhaled steroid (low dose), cromolyn (adult: 2-4 puffs tid/qid; child: 1-2 puffs tid/qid), or nedocromil (adult: 2-4 puffs bid/qid; child: 1-2 puffs bid/qid) (Children usually begin with a trial of cromolyn or nedocromil.)
  • FEV₁ or PEF rate greater than 80% predicted, with variability of 20-30%
• Step 3 - Moderate persistent
• • Daily symptoms
  • Exacerbations affect activity and sleep
  • Nocturnal symptoms occurring more than once a week
  • Anti-inflammatory, inhaled steroid (medium dose), or inhaled steroid (low-to-medium dose) and long-acting bronchodilator, especially for nighttime symptoms (either long-acting inhaled beta2-agonist [adult: 2 puffs q12h, child: 1-2 puffs q12h], sustained-release theophylline, or long-acting beta2-agonist tablets) (If needed, give inhaled steroids in a medium-to-high dose.)
  • FEV₁ or PEF rate 60-80% of predicted, with variability greater than 30%
• Step 4 - Severe persistent
• • Continuous symptoms
  • Frequent exacerbations
  • Frequent nocturnal asthma symptoms
  • Physical activities limited by asthma symptoms
  • Anti-inflammatory or inhaled steroid (high dose) and long-acting bronchodilator (either long-acting inhaled beta2-agonist [adult: 2 puffs q12h, child: 1-2 puffs q12h] and sustained-release theophylline or long-acting beta2-agonist tablets and steroid tablets or syrup long term) (Make repeated attempts to reduce systemic steroid and maintain control with high-dose inhaled steroid.)
  • FEV₁ or PEF rate less than 60%, with variability greater than 30%

Consultations

• Refer any patient with difficult-to-control asthma to a pulmonologist or allergist to ensure proper stepwise management of asthma, or refer for further evaluation to help rule out other diagnoses such as vocal cord dysfunction.
• Refer patients to a pulmonologist for evaluation of symptoms consistent with EIA. These patients should undergo either exercise or bronchoprovocation testing to document evidence of airway hyperreactivity and response to exercise.
• Refer patients to an otolaryngologist for treatment of nasal obstruction from polyps, sinusitis, or allergic rhinitis or for the diagnosis of upper airway disorders.
• Refer patients to an allergist or immunologist for skin testing to guide indoor allergen mitigation efforts and consideration of immunotherapy to treat seasonal allergic rhinitis. The use of immunotherapy for the treatment of asthma is controversial. Several large, well-conducted studies did not demonstrate any benefit, but a meta-analysis of 54 randomized controlled trials confirmed efficacy in asthma.⁵ The National Asthma Education and Prevention Program Expert Panel Report recommends that immunotherapy be considered if the following criteria are fulfilled:
• • A relationship is clear between symptoms and exposure to an unavoidable allergen to which the patient is sensitive.
  • Symptoms occur all year or during a major portion of the year.
  • Symptoms are difficult to control with pharmacologic management because the medication is ineffective, multiple medications are required, or the patient is not accepting of medication.

Diet

New information from prospective cohort studies and population-based studies in the past several years suggests an association between asthma and obesity. Patients with an elevated BMI have an increased risk for developing asthma. A prospective cohort study of 86,000 adults observed for 5 years showed a linear relationship between BMI and the risk of developing asthma.⁶

No special diets are generally indicated. Food allergy as a trigger for asthma is uncommon. Avoidance of foods is recommended after a double-blind food challenge that yields positive results. Sulfites have been implicated in some severe asthma exacerbations and should be avoided in sensitive individuals.

Activity

• Activity is generally limited by patients' ability to exercise and their response to medications. No specific limitations are recommended for patients with asthma, although they should avoid exposure to agents that may exacerbate their disease.
• A significant number of patients with asthma also have EIA, and baseline control of their disease should be adequate to prevent exertional symptoms. The ability of patients with EIA to exercise is based on the level of exertion, degree of fitness, and environment in which they exercise.
• Many patients have fewer problems when exercising indoors or in a warm, humid environment compared with outdoors or in a cold, dry environment.

MEDICATION

Section 7 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medications used for asthma are generally divided into 2 categories, quick relief (also called reliever medications) and long-term control (also called controller medications). Quick relief medications are used to relieve acute asthma exacerbations and to prevent EIA symptoms. These medications include short-acting beta-agonists, anticholinergics (used for severe exacerbations), and systemic corticosteroids, which speed recovery from acute exacerbations. Long-term control medications include inhaled corticosteroids, cromolyn sodium, nedocromil, long-acting beta-agonists, methylxanthines, and leukotriene antagonists. Use of these medications by the stepwise approach is outlined in Medical Care.

Other medications that have been used to reduce oral systemic corticosteroid dependence include cyclosporine, methotrexate, gold, intravenous immunoglobulin, dapsone, troleandomycin, and hydroxychloroquine. Their use in patients with asthma is extremely limited because of variable responses, adverse effects, and limited experience. Only an asthma specialist should administer these medications.

The newest asthma medication is omalizumab (Xolair), a recombinant DNA-derived humanized immunoglobulin G monoclonal antibody that binds selectively to human immunoglobulin E on the surface of mast cells and basophils. The drug reduces mediator release, which promotes an allergic response. Indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens, in whom symptoms are not controlled by inhaled corticosteroids. The dose (adults and children >12 y) is 150-375 mg subcutaneously every 2-4 weeks (precise dose and frequency is established by serum immunoglobulin E levels). The estimated annual cost is $12,000-15,000.

Two 52-week pivotal phase 3 clinical trials with 1071 asthma subjects were designed to study a reduction in asthma exacerbations with omalizumab. Subjects were randomized to receive subcutaneous omalizumab or placebo every 2 or 4 weeks. Inhaled corticosteroid doses were kept stable over the initial 16 weeks of treatment (stable-steroid phase) and tapered during a further 12-week treatment period (steroid-reduction phase). When used as an add-on therapy to inhaled corticosteroids, in both pivotal clinical trials, omalizumab reduced mean asthma exacerbations (ie, asthma attacks) per subject by 33-75% during the stable-steroid phase and by 33-50% during the steroid-reduction phase.

Drug Category: Bronchodilators

Provide symptomatic relief of bronchospasm due to acute asthma exacerbation (short-acting agents) or long-term control of symptoms (long-acting agents). Also used as the primary medication for prophylaxis of EIA. A metered-dose inhaler (MDI) can be used for administration.

Drug Category: Leukotriene receptor antagonists

Direct antagonist of mediators responsible for airway inflammation in asthma. Used for prophylaxis of EIA and long-term treatment of asthma as alternative to low doses of inhaled corticosteroids.

Drug Category: Corticosteroids

Highly potent agents that are the primary DOC for treatment of chronic asthma and prevention of acute asthma exacerbations. Numerous inhaled corticosteroids are used for asthma and include beclomethasone (Beclovent, Vanceril), budesonide (Pulmicort Turbuhaler), flunisolide (AeroBid), fluticasone (Flovent), and triamcinolone (Azmacort).

Drug Category: Mast cell stabilizers

Prevent the release of mediators from mast cells that cause airway inflammation and bronchospasm. Indicated for maintenance therapy of mild-to-moderate asthma or prophylaxis for EIA.

Drug Category: Combination beta-agonist/corticosteroid

Advair is a unique inhaled combination medication used frequently in the treatment of asthma. It consists of a long-acting beta-agonist (salmeterol) and inhaled corticosteroid (fluticasone).

Drug Category: 5-Lipoxygenase inhibitors

Inhibit the formation of leukotrienes. Leukotrienes activate receptors that may be responsible for events leading to the pathophysiology of asthma, including airway edema, smooth muscle constriction, and altered cellular activity associated with inflammatory reactions.

FOLLOW-UP

Section 8 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Further Inpatient Care

• The initial assessment of acute asthma exacerbations should focus on several key areas.
• • Perform a functional assessment of airway obstruction with a measurement of the FEV₁ or PEF initially to assess the patient's response to treatment.
  • Assess the adequacy of arterial oxygen saturation in patients with severe distress.
  • Obtain a brief history to include symptoms, onset of exacerbation, medications, prior emergency department visits, and hospitalizations (including endotracheal intubations).
  • Perform a physical examination to assess the severity of the exacerbation, the overall patient status, the presence of other diseases or complications, and to rule out upper airway obstruction.
  • Laboratory studies should be considered based on the status of the patient. These and other studies may include arterial blood gas measurement, complete blood cell count, serum theophylline level (if indicated), chest radiograph to assess for complications, and electrocardiograms in patients older than 50 years.
• Once the initial assessment is completed, begin treatment based on the severity of the asthma exacerbation.
• • Supplemental oxygen should be used in most patients to maintain oxygen saturations greater than 90%.
  • Inhaled short-acting beta-agonists are the initial treatment.
  • • Repetitive or continuous administration by nebulizer
    • In the emergency department, 3 treatments every 20-30 minutes as initial therapy
    • High-dose (6-12 puffs) beta-agonist by MDI or nebulizer therapy (Nebulizer is most effective with more severe exacerbations.)
  • Consider inhaled ipratropium bromide in patients with severe exacerbations.
  • Administer systemic corticosteroids early in the course of disease in patients with an incomplete response to beta-agonists. Oral administration is equivalent in efficacy to intravenous administration. Corticosteroids speed the resolution of airway obstruction and prevent a late-phase response.
  • Methylxanthines (theophylline) can be considered in patients with severe exacerbations, but their use is controversial.
  • Antibiotics should be reserved for patients with fever and purulent sputum or other evidence of pneumonia or sinusitis.
  • Aggressive hydration is not recommended for adults.
  • Chest physiotherapy, mucolytics, and sedation are not recommended.
• Indications for hospitalization are based on findings from the repeat assessment of a patient after the patient receives 3 doses of an inhaled bronchodilator. Determine the decision to admit on (1) the duration and severity of symptoms, (2) the severity of airflow obstruction, (3) the course and severity of prior exacerbations, (4) medication use and access to medications, (5) the adequacy of support and home conditions, and (6) the presence of psychiatric illness.
• In certain situations, admit the patient to the ICU for close observation and monitoring.
• • Rapidly worsening asthma or a lack of response to the initial therapy in the emergency department is an indication for ICU admission.
  • If patients have confusion, drowsiness, signs of impeding respiratory arrest, or loss of consciousness, they should be admitted to the ICU.
  • Impending respiratory arrest, as indicated by hypoxemia (PO₂ <60 mm Hg) despite supplemental oxygen and/or hypercarbia with PCO₂ greater than 45 mm Hg, should prompt ICU admission.
  • If intubation is required because of the continued deterioration of the patient's condition despite optimal treatment, admit the patient to the ICU.

Further Outpatient Care

• For all patients with asthma, monitoring should be performed on a continual basis based on the following parameters, which helps in the overall management of the disease:
• • Monitoring signs and symptoms of asthma: Patients should be taught to recognize inadequate asthma control, and providers should assess control at each visit.
  • Monitoring pulmonary function: Regularly perform spirometry and peak-flow monitoring.
  • Monitoring quality of life and functional status: Inquire about missed work or school days, reduction in activities, sleep disturbances, or change in caregiver activities.
  • Monitoring history of asthma exacerbations: Determine if patients are monitoring themselves to detect exacerbations and if these exacerbations are self-treated or treated by health care providers.
  • Monitoring pharmacotherapy: Ensure compliance with medications and usage of short-acting beta-agonists.
  • Monitoring patient-provider communication and patient satisfaction

In/Out Patient Meds

• The pharmacologic treatment of asthma is based on stepwise therapy. Medications should be added or deleted as the frequency and severity of the patient's symptoms change.
• Step 1: Intermittent asthma is present.
• • A controller medication is not needed.
  • The reliever medication is a short-acting beta-agonist as needed for symptoms.
• Step 2: Mild persistent asthma is present.
• • The controller medication is an inhaled corticosteroid (200-500 mcg), cromolyn, nedocromil, or a leukotriene antagonist. If needed, increase the dose of corticosteroid and add a long-acting beta-agonist or sustained-release theophylline, especially for nocturnal symptoms.
  • The reliever medication is a short-acting beta-agonist as needed for symptoms.
• Step 3: Moderate persistent asthma is present.
• • The controller medication is an inhaled corticosteroid (800-2000 mcg) and a long-acting bronchodilator (either beta-agonist or sustained-release theophylline) A combination medication of salmeterol/fluticasone (Advair) is a preferred choice to improve compliance. Other agents may include leukotriene modifying agents or omalizumab.
  • The reliever medication is a short-acting beta-agonist as needed for symptoms.
• Step 4: Severe persistent asthma is present.
• • The controller medication is an inhaled corticosteroid (800-2000 mcg), a long-acting bronchodilator (beta-agonist and/or theophylline), and long-term oral corticosteroid therapy.
  • The reliever medication is a short-acting beta-agonist as needed for symptoms.
• In patients with EIA, the primary aim of therapy is prophylaxis to prevent acute episodes.
• • A warm-up period of 15 minutes is recommended prior to a scheduled exercise event and has been shown to have a duration of effect as long as 40 minutes. This approach is not helpful for unscheduled events, prolonged exercise, or elite athletes.
  • One of the primary treatments is to ensure good control of the underlying asthma.
  • Regularly scheduled medications are generally not indicated for persons with isolated EIA without underlying asthma. Prophylaxis in the form of inhaled medications administered 15-30 minutes prior to exercise is usually required.
• The most commonly used medications are short-acting beta-agonists such as albuterol. Sodium cromolyn and nedocromil used 30 minutes prior to exercise have also been effective. The use of long-acting beta-agonists such as salmeterol (at least 90 min before exercise) can be effective for repetitive exercise. Newer agents such as the leukotriene antagonists, inhaled heparin, and inhaled furosemide have demonstrated an ability to prevent EIB. Inhaled corticosteroids have a limited role in the treatment of EIA, except to control underlying asthma.

Deterrence/Prevention

• Another essential component in the treatment of asthma is the control of factors contributing to asthma severity.
• Exposure to irritants or allergens has been shown to increase asthma symptoms and cause exacerbations. Clinicians should evaluate patients with persistent asthma for allergen exposures and sensitivity to seasonal allergens. Skin testing results should be used to assess sensitivity to perennial indoor allergens, and any positive results should be evaluated in the context of the patient's medical history.
• All patients with asthma should be advised to avoid exposure to allergens to which they are sensitive, especially in the setting of occupational asthma. Other factors may include the following:
• • Environmental tobacco smoke
  • Exertion during high levels of air pollution
  • Use of beta-blockers
  • Avoidance of aspirin and other nonsteroidal anti-inflammatory drugs if the patient is sensitive
  • Avoidance of sulfites or other food items/additives to which the patient may be sensitive
  • Occupational exposures

Complications

• The most common complications of asthma include pneumonia, pneumothorax or pneumomediastinum, and respiratory failure requiring intubation in severe exacerbations.
• Risk factors for death from asthma include the following:
• • Past history of sudden severe exacerbations, history of prior intubation, or ICU admission
  • Two or more hospitalizations or 3 or more emergency department visits in the past year; hospitalization or emergency department visit in the past month
  • Use of more than 2 short-acting beta-agonist canisters per month
  • Current use of systemic corticosteroids or recent taper
  • Comorbidity from cardiovascular disease
  • Psychosocial, psychiatric, or illicit drug use problems
  • Low socioeconomic status or urban residence
• Complications associated with most medications used for asthma are relatively rare. However, in those patients requiring long-term corticosteroid use, complications may include osteoporosis, immunosuppression, cataracts, myopathy, weight gain, addisonian crisis, thinning of skin, easy bruising, avascular necrosis, diabetes, and psychiatric disorders.

Prognosis

• Approximately half the children diagnosed with asthma in childhood outgrow their disease by late adolescence or early adulthood and require no further treatment.
• Patients with poorly controlled asthma develop long-term changes over time, ie, with airway remodeling. This can lead to chronic symptoms and a significant irreversible component to their disease.
• Many patients who develop asthma at an older age also tend to have chronic symptoms.