eMedicine Specialties > Pulmonology > Obstructive Airways Diseases

Asthma

Michael J Morris, MD, Clinical Assistant Professor, Pulmonary Disease/Critical Care Service, Department of Medicine, Brooke Army Medical Center; Associate Program Director, Internal Medicine Residency, San Antonio Uniformed Services Health Education Consortium

Updated: Sep 9, 2009

Introduction

Background

Asthma is an airway disorder that causes respiratory hypersensitivity, inflammation, and intermittent obstruction. Asthma commonly causes constriction of the smooth muscles in the airway, wheezing, and dyspnea.

Asthma is a common chronic disease worldwide and affects 22 million persons in the United States. Asthma is the most common chronic disease in childhood, affecting an estimated 6 million children, and it is a common cause of hospitalization for children in the United States.

Despite recent advances in the understanding of the pathophysiology, assessment, 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. Reversibility of airflow limitation may be incomplete in some patients with asthma.

The most recent 2007 Expert Panel Report 3 simplified the definition to the following:

Asthma is a common chronic disorder of the airways that is complex and characterized by variable and recurring symptoms, airflow obstruction, bronchial hyperresponsiveness, and an underlying inflammation. The interaction of these features of asthma determines the clinical manifestations and severity of asthma and the response to treatment.

• Objective measures of lung function 
• Environmental control measures
• Comprehensive pharmacologic therapy
• Patient education

The most recent and updated Expert Panel Report 3 was recently published in 2007 and emphasizes new areas of severity, control, impairment, and risk that are key to maintaining asthma control.² A major difference is the emphasis on asthma control. The revised paradigm for asthma management now recommends that asthma management and assessment decisions should be initially based on categorization of asthma severity and, subsequently, on assessment of asthma control.

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 have asthma (exercise-induced bronchospasm in asthmatic persons) but can also be found in patients with normal resting spirometry findings with atopy, allergic rhinitis, or cystic fibrosis and even in healthy persons, many of whom are elite athletes (exercise-induced bronchospasm in athletes). Exercise-induced bronchospasm is often a neglected diagnosis, and the underlying asthma may be silent in as many as 50% of patients, except during exercise.^3,4

Currently, 2 comprehensive guidelines (published in 2007) are available for asthma diagnosis, assessment, and asthma treatment. Additionally, both publications have summary guidelines that were developed for clinicians. These 2 extensive publications are as follows:

• National Asthma Education and Prevention Program. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. National Institutes of Health, 2007 Revision.²
• National Heart, Lung, and Blood Institute. Global strategy for asthma management and prevention. National Institutes of Health, 2008 Revision.⁵

Additionally, the following summary guidelines may be a helpful resource:

• Key clinical activities for quality asthma care: recommendations of the National Asthma Education and Prevention Program.⁶
• Education for a partnership in asthma care. In: National Asthma Education and Prevention Program (NAEPP). Expert panel report 3: guidelines for the diagnosis and management of asthma.⁷
• Managing asthma long term-special situations. In: National Asthma Education and Prevention Program (NAEPP). Expert panel report 3: guidelines for the diagnosis and management of asthma.⁸
• Managing exacerbations of asthma. In: National Asthma Education and Prevention Program (NAEPP). Expert panel report 3: guidelines for the diagnosis and management of asthma.⁹
• Measures of asthma assessment and monitoring. In: National Asthma Education and Prevention Program (NAEPP). Expert panel report 3: guidelines for the diagnosis and management of asthma.¹⁰
• Medications. In: National Asthma Education and Prevention Program (NAEPP). Expert panel report 3: guidelines for the diagnosis and management of asthma.¹¹
• Managing asthma long term in children 0-4 years of age and 5-11 years of age. In: National Asthma Education and Prevention Program (NAEPP). Expert panel report 3: guidelines for the diagnosis and management of asthma.¹²
• Managing asthma long term in youths >=12 years of age and adults. In: National Asthma Education and Prevention Program (NAEPP). Expert panel report 3: guidelines for the diagnosis and management of asthma.¹³

Pathophysiology

The pathophysiology of asthma is complex and involves the following components:

• Airway inflammation
• Intermittent airflow obstruction
• 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.¹⁴

Asthma causes and symptoms. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.

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.¹⁷

• The critical role of inflammation has been further substantiated, but evidence is emerging for considerable variability in the pattern of inflammation, thus indicating phenotypic differences that may influence treatment responses.
• Of the environmental factors, allergic reactions remain important. Evidence also suggests a key and expanding role for viral respiratory infections in these processes.
• The onset of asthma for most patients begins early in life, with the pattern of disease persistence determined by early, recognizable risk factors including atopic disease, recurrent wheezing, and a parental history of asthma.
• Current asthma treatment with anti-inflammatory therapy does not appear to prevent progression of the underlying disease severity.

The pathogenesis of exercise-induced bronchospasm 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 22 million persons, including 6 million children. The overall prevalence rate of exercise-induced bronchospasm 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 underlying asthma are included. The rate of exercise-induced symptoms in persons with asthma has been reported to vary from 40-90%.¹⁸

International

Asthma is common in industrialized nations such as Canada, England, Australia, Germany, and New Zealand, where much of the asthma data have been collected. The prevalence rate of severe asthma in industrialized countries ranges from 2-10% and is estimated to affect 300 million persons worldwide. Trends suggest an increase in both the prevalence and morbidity of asthma, 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 for asthma occur annually. The figures from the 1997 National Institutes of Health report¹ an estimated 500,000 hospitalizations and 5,000 deaths from asthma annually. International asthma mortality is reported as high as 0.86 deaths per 100,000 persons in some countries. US asthma mortality rates in 2002 were reported at 1.5 deaths per 100,000 persons. Mortality is primarily related to lung function, with an 8-fold increase in patients in the lowest quartile, but mortality has also been linked with asthma management failure, especially in young persons. Other factors that impact mortality include age older than 40 years, cigarette smoking more than 20-pack years, blood eosinophilia, forced expiratory volume in one second (FEV₁) of 40-69% predicted, and greater reversibility.¹⁹
• Exercise-induced bronchospasm 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. Exercise-induced bronchospasm in asthmatic persons generally does not cause significant morbidity.

Race

• Asthma occurs in persons of all races worldwide. In the United States, asthma prevalence, especially morbidity and mortality, is 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 asthma onset. A national concern is that some of the increased morbidity is due to differences in asthma 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.²⁰ 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.²¹
• The assessment and diagnosis of exercise-induced bronchospasm is made more often in children and young adults than in older adults and is related to high levels of physical activity. Exercise-induced bronchospasm can be observed in persons of any age based on the level of underlying airway reactivity and the level of physical exertion.

Clinical

History

A detailed assessment of the 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.

• Asthma symptoms may include the following:
  • Cough, worse particularly at night²²
  • Wheezing
  • Shortness of breath
  • Chest tightness
  • Sputum production
  • Decreased exercise tolerance
• Asthma 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 for asthma, also discussed in Causes, may include the following:
  • Environmental allergen exposure (dust mites, pet dander, pollens)
  • Occupation
  • Medications
  • Exercise
  • Viral upper respiratory tract infections
  • Strong emotional expression
  • Menstrual cycles
  • Airborne dusts or chemicals
• Asthma 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 asthma management
  • Comorbid conditions (sinusitis, rhinitis, gastroesophageal reflux)
• Family history may reveal the following conditions:
  • Asthma
  • Allergy
  • Sinusitis
  • Rhinitis
  • Eczema
• 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 asthma exacerbation.
• The impact asthma has on the patient and family may have involved the following:
  • Emergency department visits, hospitalizations, 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 findings for exercise-induced bronchospasm are typical of asthma but are only associated with exercise. Typical symptoms include cough, wheezing, shortness of breath, and chest pain or tightness. Some individuals also may report sore throat or GI upset.

• Asthma 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 tract infections.
• Initially, airway dilation is noted during exercise. If exercise continues 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 asthma 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 asthma 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 exercise-induced bronchospasm. 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 asthma physical findings
  • 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 (especially in children) may be observed during acute asthma 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 tract infection.
  • Any type of nasal obstruction may result in worsening of asthma or symptoms of exercise-induced bronchospasm.
• 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 tract infections
  • Exercise; hyperventilation
  • Gastroesophageal reflux disease
  • Chronic sinusitis or rhinitis
  • Aspirin or nonsteroidal anti-inflammatory drug (NSAID) 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 (eg, household sprays, paint fumes)
  • Various high and low molecular weight compounds: 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 exercise-induced bronchospasm symptoms (in both people with asthma and athletes) 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

Differential Diagnoses

Other Problems to Be Considered

Aspirin or NSAID hypersensitivity
Occupational asthma
Reactive airways dysfunction syndrome
Tracheal and bronchial tumors
Other causes of upper airway obstruction

Workup

Laboratory Studies

• Laboratory assessments and studies are not routinely indicated for asthma, but they 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. Elevated serum IgE levels are required for chronic asthma patients to be treated with omalizumab (Xolair).
• In assessing 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.²³  A controlled prospective study has shown that adjusting inhaled corticosteroid (ICS) treatment to control sputum eosinophilia—as opposed to controlling symptoms, short-acting beta-agonist (SABA) use, nocturnal awakenings, and pulmonary function—significantly reduced both the rate of asthma exacerbations and the cumulative dose of inhaled corticosteroids.²⁴
• Nair et al studied the capability of mepolizumab to allow prednisone sparing in those rare individuals who have sputum eosinophilia and airway symptoms despite continued prednisone treatment. The agent reduced blood and sputum eosinophils and permitted prednisone sparing.²⁵

Imaging Studies

• In most patients with asthma, chest radiography findings are normal or may 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. Chest radiography should be considered in all patients being evaluated for asthma to exclude other diagnoses.
• Sinus CT scanning may be useful to help exclude acute or chronic sinusitis as a contributing factor. In patients with chronic sinus symptoms, CT scanning 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 gastroesophageal reflux disease (GERD), 24-hour pH monitoring can help determine if GERD is a contributing factor.

Procedures

• Pulmonary function testing (spirometry)
  • Spirometry assessments should be obtained as the primary test to establish the asthma diagnosis. Spirometry should be performed prior to initiating treatment in order to establish the presence and determine the severity of baseline airway obstruction.²⁶ Optimally, the initial spirometry should also include 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 (FVC), the maximal amount of air expired from the point of maximal inhalation, and the FEV₁. A reduced ratio of FEV₁ to FVC, when compared with predicted values, demonstrates the presence of airway obstruction. Reversibility is demonstrated by an increase of 12% and 200 mL after the administration of a short-acting bronchodilator.
  • The assessment and diagnosis of asthma cannot be based on spirometry findings alone because many other diseases are associated with obstructive spirometry indices.
  • As a preliminary assessment for exercise-induced asthma (EIA), or exercise-induced bronchospasm (EIB), 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 asthma symptoms. Bronchoprovocation testing helps determine if airway hyperreactivity is present, and a negative test result usually excludes the diagnosis of asthma.
  • Trained individuals should perform this asthma testing in an appropriate facility and in accordance with the guidelines of the American Thoracic Society published in 1999.²⁷ 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 avoid performing the test.
• Exercise testing
  • Exercise spirometry is the standard method for assessing patients with exercise-induced bronchospasm. 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 exercise-induced bronchospasm symptoms, and results have a lower sensitivity for asthma 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 exercise-induced asthma and has been shown to produce results similar to those of methacholine-challenge asthma 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. Peak-flow monitoring should not be used as a substitute for spirometry to establish the initial diagnosis of asthma.
  • Results can be used to determine the severity of an exacerbation and to help guide therapeutic decisions as part of an asthma action plan.
• Guidelines for the use of peak-flow meters for asthma
  • 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 nitric oxide
  • Exhaled nitric oxide analysis has been shown to predict airway inflammation and asthma control; however, it is technically more complex and not routinely used in the monitoring of patients with asthma.
  • A prospective, controlled study has shown that when inhaled corticosteroid asthma treatment was adjusted to control the fraction of exhaled nitric oxide, as opposed to controlling the standard indices of asthma, the cumulative dose of ICS was reduced, with no worsening of the frequency of asthma exacerbations.²⁸

Treatment

Medical Care

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

• Objective measures of lung function
• Environmental control measures and avoidance of risk factors
• Comprehensive pharmacologic therapy
• Patient education

Further clarification for classifying and treating asthma was added by the 2007 Expert Panel Report 3 recommendations. The functions of asthma assessment and monitoring are closely linked to the concepts of severity, control, and responsiveness to treatment. Severity is the intrinsic intensity of the disease process. Asthma severity is measured most easily and directly in a patient not receiving long-term-control therapy. Asthma control is the degree to which the manifestations of asthma (symptoms, functional impairments, and risks of untoward events) are minimized and the goals of therapy are met. Asthma responsiveness is the ease with which asthma control is achieved by therapy.

Both asthma severity and asthma control include the domains of current impairment and future risk. Impairment is the frequency and intensity of symptoms and functional limitations the patient is experiencing or has recently experienced as a result of asthma. Risk is the likelihood of either asthma exacerbations, progressive decline in lung function (or, for children, reduced lung growth), or risk of adverse effects from medication.

On June 25, 2009, The American Thoracic Society and the European Respiratory Society jointly released new official standards on asthma assessment and evaluation for clinical trials and practice.²⁹ Also see the Medscape Medical News article, New Guidelines Issued for Asthma Assessment.
 
Two additional asthma treatment 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 asthma severity and treatment options are as follows:

• Step 1 - Intermittent asthma
  • 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 asthma
  • 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
  • FEV₁ or PEF rate greater than 80% predicted, with variability of 20-30%
• Step 3 - Moderate persistent asthma
  • Daily symptoms
  • Exacerbations affect activity and sleep
  • Nocturnal symptoms occurring more than once a week
  • FEV₁ or PEF rate 60-80% of predicted, with variability greater than 30%
• Step 4 - Severe persistent asthma
  • Continuous symptoms
  • Frequent exacerbations
  • Frequent nocturnal asthma symptoms
  • Physical activities limited by asthma symptoms
  • FEV₁ or PEF rate less than 60%, with variability greater than 30%

Note that the above guidelines apply to the general asthma population and may vary depending on age, especially the pediatric population and the elderly population. Specific guidelines were published in 2003 on caring for asthmatic persons in the elderly population, and they contain more specific information. See NAEPP Working Group Report: Considerations for Diagnosing and Managing Asthma in the Elderly. NIH Publication No. 96-3662.³⁰

Surgical Care

Considerations for persons with asthma who undergo surgery are as follows³¹ :

• Asthma-related complications associated with surgery include acute bronchoconstriction resulting from intubation, impaired cough, hypoxemia, hypercapnia, atelectasis, respiratory tract infection, and exposure to latex. The likelihood of these complications occurring depends on the severity of the underlying asthma, the type of surgery (thoracic and upper abdominal), and the type of anesthesia.
• Patients with asthma should have an evaluation before surgery that includes a review of asthma symptoms, medication use (particularly oral systemic corticosteroids for longer than 2 wk in the past 6 mo), and measurement of pulmonary function. If possible, attempts should be made to improve lung function preoperatively to either their predicted values or their personal best level. A short course of oral systemic corticosteroids may be necessary to optimize lung function.
• If evidence of airflow obstruction (<80% of baseline values) is present, a brief course of corticosteroids is recommended. Patients who have received oral corticosteroids for an asthma exacerbation in the past 6 months should receive systemic corticosteroids (100 mg hydrocortisone IV q8h) in the perioperative period.

Consultations

Refer any patient with moderate-to-severe persistent asthma that is difficult to control to a pulmonologist or allergist to ensure proper stepwise asthma management, or refer for further evaluation to help rule out other diagnoses such as vocal cord dysfunction. Other criteria for referral include the following:  

• Consideration for alternative diagnoses should be given in all patients, and in particular in those older than 30 years and  younger than 2 years with new symptoms suggestive of asthma.
• A significant history of smoking greater than 20-pack years should make the diagnosis of chronic obstructive pulmonary disease (COPD) more likely than asthma.
• An absence of airway obstruction on initial spirometry findings should prompt consideration for alternative diagnoses and additional testing.
• Abnormalities found on chest radiography screening should prompt referral to a specialist for further evaluation.

Refer patients to a pulmonologist for evaluation of symptoms consistent with exercise-induced asthma (EIA), or exercise-induced bronchospasm (EIB). 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.³² 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

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 body mass index have an increased risk for developing asthma. A prospective cohort study of 86,000 adults observed for 5 years showed a linear relationship between body mass index and the risk of developing asthma.³³

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 exercise-induced bronchospasm, and baseline control of their disease should be adequate to prevent exertional symptoms. The ability of patients with exercise-induced bronchospasm 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 than they do outdoors or in a cold, dry environment.

Medication

Asthma medications 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 exercise-induced asthma (EIA), or exercise-induced bronchospasm (EIB) symptoms. These medications include short-acting beta-agonists (SABAs), anticholinergics (used only for severe exacerbations), and systemic corticosteroids, which speed recovery from acute exacerbations. Long-term control medications include inhaled corticosteroids (ICSs),^34,35 cromolyn sodium, nedocromil, long-acting beta-agonists (LABAs), combination inhaled corticosteroids and long-acting beta-agonists, methylxanthines, and leukotriene antagonists. Inhaled corticosteroids are considered the primary drug of choice for control of chronic asthma. Use of these medications by the stepwise approach is outlined in Medical Care.

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. It is indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens, in whom symptoms are not controlled by inhaled corticosteroids.

Other medications that are rarely 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.

Beta2-adrenergic agonist agents

These agents relieve reversible bronchospasm by relaxing the smooth muscles of the bronchi.

Levalbuterol (Xopenex, Xopenex-HFA)

R-isomer of albuterol. Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on heart rate.

Dosing

Adult

MDI
1-2 puffs q4-6h prn
0.63 mg tid at intervals of 6-8 h; dosage may be increased to 1.25 mg tid with close monitoring for adverse effects

Pediatric

Aerosol
<4 years: Not established
>4 years: Administer as in adults
Nebulizer
<6 years: Not established
6-12 years: 0.31 mg tid; 0.63 mg tid maximum
>12 years: Refer to adult dosing

Interactions

Decreased efficacy with beta-blockers; digoxin levels may be decreased; may potentiate the kaliuretic effects of drugs such as loop or thiazide diuretics; decreases serum digoxin levels by 16-22%; MAOIs may potentiate vascular constriction, extreme caution advised with coadministration

Contraindications

Documented hypersensitivity to levalbuterol, albuterol, or any formulation component; arrhythmia associated with tachycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in patients with cardiovascular disease (arrhythmia, hypertension, CHF), convulsive disorders, diabetes, glaucoma, hyperthyroidism, or hypokalemia; beta-agonists may cause elevation in blood pressure and heart rate and result in CNS stimulation/excitation; beta2-agonists may increase risk of arrhythmia, increase serum glucose levels, or decrease serum potassium levels

Salmeterol (Serevent)

Can relieve bronchospasm by relaxing smooth muscles of the bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis. Effect also may facilitate expectoration.
Adverse effects are more likely when administered at high doses or more frequent doses than recommended; prevalence of adverse effects is higher. Regular use in patients with EIA associated with smaller decrease in FEV₁ during exercise.

Dosing

Adult

2 inhalations (42 mcg) bid approximately 12 h apart
Serevent Diskus
1 inhalation (50 mcg) bid approximately 12 h apart

Pediatric

<4 years: Not established
4-12 years: 1 puff (50 mcg) q12h
>12 years: Administer as in adults

Interactions

Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may worsen when coadministered

Contraindications

Documented hypersensitivity; angina, tachycardia, and cardiac arrhythmias associated with tachycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

[US Boxed Warning] Long-acting beta2-agonists may increase the risk of asthma-related deaths; in a large, randomized clinical trial, salmeterol was associated with a small, but statistically significant increase in asthma-related deaths (when added to usual asthma therapy); risk may be greater in blacks versus whites; should only be used as adjuvant therapy in patients not adequately controlled on ICSs or whose disease requires 2 maintenance therapies; not meant to relieve acute asthmatic symptoms, should not be initiated in patients with significantly worsening or acutely deteriorating asthma, and is not a substitute for inhaled or oral corticosteroids; short-acting beta2-agonist should be used for acute symptoms and symptoms occurring between treatments; corticosteroids should not be stopped or reduced when salmeterol initiated; during initiation of salmeterol, watch for signs of worsening asthma

Formoterol (Foradil Aerolizer, Perforomist inhalant solution)

By relaxing smooth muscles of bronchioles in conditions associated with bronchitis, emphysema, asthma, or bronchiectasis, can relieve bronchospasms. Effect may also facilitate expectoration. Shown to improve symptoms and morning peak flows.
Incidence of adverse effects increased when administered at more frequent doses than recommended. Bronchodilating effect lasts >12 h. Use in addition to regular use of anticholinergic agents. Useful in patients in whom bronchodilators are used frequently. Available as oral inhalant powder capsule and administered via Aerolizer inhaler.

Dosing

Adult

12 mcg inhaled (1 inhalation) bid at least 12 h apart

Pediatric

<5 years: Not established
>5 years: Administer as in adults

Interactions

Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta agonists; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics, corticosteroids, or theophylline derivatives may worsen; drugs that widen QTc interval (eg, quinidine, procainamide, pimozide, moxifloxacin, sparfloxacin, gatifloxacin, sotalol, thioridazine, amiodarone) may potentiate adverse cardiovascular effects; concomitant use with other beta-adrenergic agonists may result in additive effects

Contraindications

Documented hypersensitivity, angina, acutely deteriorating asthma, and cardiac arrhythmias associated with tachycardia

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not indicated to treat acute asthmatic symptoms or acute deterioration of COPD; not a substitute for ICSs; adverse effects include paroxysmal bronchospasm, tremors, nervousness, and tachycardia; caution in coronary insufficiency, arrhythmias, hypertension, diabetes mellitus, hyperthyroidism; higher incidence of cardiovascular risks with doses >12 mcg bid; black box FDA warning describes that chronic use of long-acting beta2-adrenergic inhalers may result in increased asthma morbidity and mortality; use only as additional therapy for patients not adequately controlled on other asthma-controlling medications (eg, low- to medium-dose ICSs) or patients whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies, including formoterol

Albuterol (Ventolin, Proventil, Proventil-HFA)

Relaxes bronchial smooth muscle by action on beta2-receptors, with little effect on cardiac muscle contractility.

Dosing

Adult

PO
2-4 mg/dose divided tid/qid; not to exceed 32 mg/d
MDI
1-2 puffs q4-6h; not to exceed 12 puffs/d; may use 2-4 puffs q20min for 3 doses to treat an acute exacerbation; a tube spacer is recommended unless the patient can demonstrate excellent technique without it
Nebulizer
Dilute 0.5 mL (2.5 mg) 0.5% inhalation solution in 1-2.5 mL of NS; administer 2.5-5 mg q4-6h, diluted in 2-5 mL sterile saline or water

Pediatric

PO
2-5 years: 0.1-0.2 mg/kg/dose divided tid; not to exceed 12 mg/d
5-12 years: 2 mg/dose divided tid/qid; not to exceed 24 mg/d
>12 years: Administer as in adults
MDI
<12 years: 1-2 puffs qid with tube spacer
>12 years: Administer as in adults
Nebulizer
<5 years: Dilute 0.25-0.5 mL (1.25-2.5 mg) 0.5% inhalation solution in 1-2.5 mL of NS and administer q4-6h in divided doses
>5 years: Administer as in adults

Interactions

Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation by albuterol; cardiovascular effects may increase with MAOIs, inhaled anesthetics, TCAs, and sympathomimetic agents

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders

Corticosteroids

These are 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).

Fluticasone (Flovent)

Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.

Dosing

Adult

44-mcg MDI: 2 puffs bid for mild persistent asthma
110- to 220-mcg MDI: 2 puffs bid for moderate-to-severe persistent asthma

Pediatric

44-mcg MDI: 2 puffs bid

Interactions

None reported

Contraindications

Documented hypersensitivity; viral, fungal, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not indicated to treat acute asthma exacerbation or status asthmaticus; prolonged use may increase systemic absorption and may cause Cushing syndrome, reversible HPA-axis suppression, hyperglycemia, and glycosuria; localized infections of the pharynx due to Candida albicans (5%) may occur; rare manifestation of systemic eosinophilic conditions consistent with Churg-Strauss syndrome reported

Triamcinolone (Azmacort)

Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.

Dosing

Adult

2 puffs tid/qid or 4 puffs bid; not to exceed 4 puffs qid for mild persistent or easily controlled moderately severe asthma

Pediatric

<6 years: Not established
6-12 years: 1-2 puffs tid/qid or 2-4 puffs bid; not to exceed 3 puffs qid
<12 years: Administer as in adults

Interactions

Coadministration with barbiturates, phenytoin, or rifampin decreases effects

Contraindications

Documented hypersensitivity; fungal, viral, and bacterial skin infections

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Not indicated to treat acute asthma exacerbation or status asthmaticus; symptoms of adrenal insufficiency due to suppression of HPA axis may occur when being withdrawn from systemically active corticosteroids; small number of patients may develop hypercortisolism and adrenal suppression; localized infections of the pharynx due to C albicans (5%) reported

Beclomethasone (Vanceril, Beclovent, QVAR)

Alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.

Dosing

Adult

2 puffs (84 mcg) tid/qid; alternatively, 4 puffs (168 mcg) bid
Severe asthma: 12-16 puffs (504-672 mcg)/d; adjust dose downward to response; not to exceed 20 puffs (840 mcg)/d
QVAR: 80 and 160 mcg/puff

Pediatric

<6 years: Not established
6-12 years: 1-2 puffs (42-84 mcg) tid/qid to response; alternatively, 4 puffs (168 mcg) bid; not to exceed 10 puffs (420 mcg)/d
>12 years: Administer as in adults

Interactions

Coadministration with ketoconazole may increase plasma levels but does not appear to be clinically significant

Contraindications

Documented hypersensitivity; bronchospasm, status asthmaticus, and other types of acute episodes of asthma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Symptoms of adrenal insufficiency due to suppression of the HPA axis may occur when being withdrawn from systemically active corticosteroids; small number of patients may develop hypercortisolism and adrenal suppression (weight gain, increased bruising, cushingoid features, acneiform lesions, mental disturbances, and cataracts may occur); localized infections of the pharynx due to C albicans (5%) reported

Prednisone (Deltasone, Orasone, Meticorten)

Systemic steroidal anti-inflammatory medication. Used primarily for moderate-to-severe asthma exacerbations to speed recovery and prevent late-phase response. Can be used long-term to control severe asthma.

Dosing

Adult

5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve

Pediatric

1-2 mg/kg PO qd or divided bid/qid; taper over 2 wk as symptoms resolve

Interactions

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Contraindications

Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections, and fungal or tubercular skin infections; GI disease

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

Budesonide (Pulmicort Turbuhaler, Rhinocort)

Inhibits bronchoconstriction mechanisms, produces direct smooth muscle relaxation, and may decrease number and activity of inflammatory cells, which, in turn, decreases airway hyperresponsiveness.

Dosing

Adult

200-400 mcg via PO inhalation twice initially; may increase to 800 mcg bid

Pediatric

200 mcg via PO inhalation twice initially; may increase to 400 mcg bid

Interactions

Coadministration with ketoconazole may increase plasma levels but does not appear to be clinically significant

Contraindications

Documented hypersensitivity; bronchospasm, status asthmaticus, and other types of acute episodes of asthma

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Coughing, upper respiratory tract infection, and bronchitis may occur

Bronchodilators

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 exercise-induced asthma. An MDI can be used for administration.

Ipratropium (Atrovent)

Decreases vagal tone in the airways through antagonism of muscarinic receptors and inhibition of vagally mediated reflexes. Chemically related to atropine. Has antisecretory properties and, when applied locally, inhibits secretions from serous and seromucous glands lining the nasal mucosa. Only 50% of patients who are asthmatic bronchodilate with ipratropium and, to a lesser degree, with beta-adrenergic agonists. Used primarily in conjunction with beta-agonists for severe exacerbations. No additive or synergistic effects observed with long-term treatment of asthma.

Dosing

Adult

Nebulizer
1-dose vial (500 mcg) q2h for acute exacerbations
MDI
2 puffs qid; not to exceed 12 puffs/d

Pediatric

Nebulizer
250 mcg tid
MDI
1-2 puffs tid; not to exceed 6 puffs/d

Interactions

Drugs with anticholinergic properties (eg, dronabinol) may increase toxicity; albuterol increases effects

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Not indicated for acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and bladder neck obstruction; eye pain or blurred vision may occur if sprayed in eyes

Theophylline (Slo-bid, Theo-Dur, Uniphyl)

Mild-to-moderate bronchodilator used as an adjuvant in the treatment of stable asthma and prevention of nocturnal asthma symptoms. Potentiates exogenous catecholamines and stimulates endogenous catecholamine release and diaphragmatic muscular relaxation, which, in turn, stimulates bronchodilation.

Dosing

Adult

5-8 mg/kg/d IV initially to maintain concentration in the range of 5-15 mcg/mL; 5.6 mg/kg loading dose (based on aminophylline) IV over 20 min, followed by maintenance infusion of 0.1-1.1 mg/kg/h

Pediatric

<6 weeks: Not established
6 weeks to 6 months: 0.5 mg/kg/h loading dose IV in first 12 h (based on aminophylline), followed by maintenance infusion of 12 mg/kg/d thereafter; may administer continuous infusion by dividing total daily dose by 24 h
6 months to 1 year: 0.6-0.7 mg/kg/h loading dose IV in first 12 h, followed by maintenance infusion of 15 mg/kg/d; may administer as continuous infusion, as above
>1 year: Administer as in adults

Interactions

Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins, phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease effects; effects may increase with allopurinol, beta-blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine, cimetidine, erythromycin, macrolides, propranolol, and interferon

Contraindications

Documented hypersensitivity; uncontrolled arrhythmias, peptic ulcers, hyperthyroidism, and uncontrolled seizure disorders

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in peptic ulcer, hypertension, tachyarrhythmias, hyperthyroidism, and compromised cardiac function; do not inject IV solution >25 mg/min; patients with pulmonary edema or liver dysfunction are at greater risk of toxicity because of reduced drug clearance; signs of toxicity include nausea, vomiting, tremors, nervousness, ventricular arrhythmias, and seizures

Combination beta2-agonist/corticosteroid

This inhaled combination medication is used frequently in the treatment of asthma. It typically consists of a long-acting beta-agonist and inhaled corticosteroid that results in improved control of asthma.

Salmeterol/Fluticasone (Advair Diskus)

Salmeterol: Relieves bronchospasm by relaxing the smooth muscles of the bronchioles in conditions associated with asthma.
Fluticasone: ICS that alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.
Dosage forms
100/50: Fluticasone 100 mcg and salmeterol 50 mcg (28s, 60s)
250/50: Fluticasone 250 mcg and salmeterol 50 mcg (28s, 60s)
500/50: Fluticasone 500 mcg and salmeterol 50 mcg (28s, 60s)

Dosing

Adult

Advair Diskus is available in 3 strengths; initial dose prescribed should be based upon previous asthma therapy; dose should be increased after 2 wk if adequate response not achieved; patients should be titrated to lowest effective dose once stable; because each strength contains salmeterol 50 mcg/inhalation, dose adjustments should be made by changing inhaler strength; no more than 1 inhalation of any strength should be taken more than twice a day
Maximum dose: Fluticasone 500 mcg/salmeterol 50 mcg, one inhalation bid
Patients not currently on ICSs: Fluticasone 100 mcg/salmeterol 50 mcg or fluticasone 250 mcg/salmeterol 50 mcg

Pediatric

Children 4-11 years: Fluticasone 100 mcg/salmeterol 50 mcg bid, 12 h apart (maximum dose)
Children 12 years: Administer as in adults

Interactions

Antifungal agents (imidazole) may decrease metabolism, via CYP isoenzymes, of orally ICSs; atomoxetine may enhance tachycardia effect of beta-agonists; beta-agonists may diminish bradycardia effect of beta-blockers (beta1 selective); beta-blockers (nonselective) may diminish bronchodilator effect of beta-agonists; CYP3A4 inhibitors (eg, amprenavir, atazanavir, clarithromycin, delavirdine, diclofenac, fosamprenavir, imatinib, indinavir, isoniazid, itraconazole, ketoconazole, miconazole, nefazodone, nelfinavir, nicardipine, propofol, quinidine, ritonavir, and telithromycin) may increase levels/effects of fluticasone and salmeterol; protease inhibitors may decrease metabolism, via CYP isoenzymes, of orally inhaled corticosteroids (eg, amprenavir, atazanavir, fosamprenavir, indinavir, lopinavir, nelfinavir, ritonavir, and saquinavir), with the exception of tipranavir); sympathomimetics may enhance adverse/toxic effect of salmeterol

Contraindications

Documented hypersensitivity to fluticasone, salmeterol, or any component of formulation; status asthmaticus; acute episodes of asthma

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

[US Boxed Warning] Long-acting beta2-agonists may increase the risk of asthma-related deaths; in a large, randomized clinical trial, salmeterol was associated with a small, but statistically significant increase in asthma-related deaths (when added to usual asthma therapy); risk may be greater in whites versus blacks; should only be used as adjuvant therapy in patients not adequately controlled on ICSs or whose disease requires 2 maintenance therapies; salmeterol is not meant to relieve acute asthmatic symptoms, should not be initiated in patients with significantly worsening or acutely deteriorating asthma, and is not a substitute for inhaled or oral corticosteroids; short-acting beta2-agonist should be used for acute symptoms and symptoms occurring between treatments; corticosteroids should not be stopped or reduced when salmeterol initiated; during initiation of salmeterol, watch for signs of worsening asthma

Budesonide and Formoterol (Symbicort)

Formoterol: Relieves bronchospasm by relaxing the smooth muscles of the bronchioles in conditions associated with asthma.
Budesonide: ICS that alters level of inflammation in airways by inhibiting multiple types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic response.

Dosing

Adult

2 inhalations bid
Aerosol for oral inhalation
Symbicort 80/4.5: Budesonide 80 mcg and formoterol fumarate dehydrate 4.5 mcg per actuation
Symbicort 160/4.5: Budesonide 160 mcg and formoterol fumarate dehydrate 4.5 mcg per actuation

Pediatric

<12 years: Not established
>12 years: 2 inhalations bid

Interactions

Budesonide: None reported
Formoterol: Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists; concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics, corticosteroids, or theophylline derivatives may worsen; drugs that widen QTc interval (eg, quinidine, procainamide, pimozide, moxifloxacin, sparfloxacin, gatifloxacin, sotalol, thioridazine, amiodarone) may potentiate adverse cardiovascular effects; concomitant use with other beta-adrenergic agonists may result in additive effects

Contraindications

Documented hypersensitivity to adrenergic amines, formoterol, budesonide, or any component of formulation; need for acute bronchodilation (including status asthmaticus)

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Use only as adjuvant therapy in patients not adequately controlled on other asthma-controller medications; not meant to relieve acute asthmatic symptoms or rapidly-deteriorating symptoms (treat acute episodes with short-acting beta2 agonist); caution in patients with cardiovascular disease (arrhythmia or hypertension or heart failure); beta-agonists may cause elevation in blood pressure and heart rate and result in CNS stimulation/excitation and may also increase risk of arrhythmias
Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose levels; use with caution in patients with GI diseases (eg, diverticulitis, peptic ulcer, ulcerative colitis), owing to perforation risk; caution in patients with hepatic impairment and patients with hypokalemia (beta2-agonists may decrease serum potassium levels); caution in myasthenia gravis (exacerbation of symptoms has occurred during initial treatment with corticosteroids); caution following acute MI (corticosteroids associated with myocardial rupture); caution in patients with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have occurred with prolonged use; high doses or long-term use of corticosteroids has been associated with increased bone loss and osteoporotic fractures
Caution in renal impairment (fluid retention may occur); beta-agonists may result in CNS stimulation/excitation (caution in patients with seizure disorders); changes in thyroid status may necessitate dosage adjustments; metabolic clearance of corticosteroids increases in hyperthyroid patients and decreases in hypothyroid ones; HPA-axis suppression may lead to adrenal crisis (withdrawal and discontinuation of corticosteroids should be performed slowly and carefully); particular care required when patients transferred from systemic corticosteroids to inhaled products because of possible adrenal insufficiency or withdrawal from steroids, including increase in allergic symptoms (patients receiving >20 mg/d of prednisone (or equivalent) may be most susceptible); steroids do not provide systemic steroid needed to treat patients having trauma, surgery, or infections
[US Boxed Warning] Long-acting beta2-agonists may increase risk of asthma-related deaths; rarely paradoxical bronchospasm may occur with use of inhaled bronchodilating agents (should be distinguished from inadequate response); immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) reported; prolonged use of corticosteroids may increase incidence of secondary infection, mask acute infection (including fungal infections), prolong or exacerbate viral infections, or limit response to vaccines; exposure to chickenpox should be avoided; corticosteroids should not be used to treat ocular herpes simplex or cerebral malaria; close observation is required in patients with latent tuberculosis and/or TB reactivity restrict use in active TB (only in conjunction with antituberculosis treatment); may cause psychiatric manifestations, including depression, euphoria, insomnia, mood swings, and personality changes (preexisting psychiatric conditions may be exacerbated by corticosteroid use); do not exceed recommended dose (serious adverse events, including fatalities, associated with excessive use of inhaled sympathomimetics

Leukotriene receptor antagonists

These drugs are direct antagonists of mediators responsible for airway inflammation in asthma. They are used for prophylaxis of exercise-induced bronchospasm and long-term treatment of asthma as alternative to low doses of inhaled corticosteroids.

Montelukast (Singulair)

Selective and competitive receptor antagonist of leukotriene D4 and E4, components of slow-reacting substance of anaphylaxis.
Indicated for stable, mild, persistent asthma or prophylaxis for EIA.

Dosing

Adult

Chronic asthma:
10 mg PO qhs
Exercise-induced asthma:
10 mg PO at least 2 h before exercise; do not repeat dose within 24 h

Pediatric

Chronic asthma
1 year: Not established
12-23 months: 1 packet of 4 mg oral granules PO hs
2-6 years: 4 mg PO qhs
6-14 years: 5 mg PO qhs
³15 years: Administer as in adults
Exercise-induced asthma
<15 years: Not established; some pediatric subspecialists recommend 5 mg PO qd
³15 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Not indicated for treatment of acute asthma exacerbations, use appropriate short-acting inhaled beta2-agonist inhaler for exacerbations; systemic eosinophilia and vasculitis consistent with Churg-Strauss syndrome rarely reported; not for use as monotherapy in management of EIB; if already taking montelukast daily (eg, chronic asthma, allergic rhinitis), do not take an additional dose to prevent EIB
Administration for chronic asthma has not been established to prevent acute EIB; chewable tab contains phenylalanine, so caution with phenylketonuria
Neuropsychiatric events reported, and following further FDA evaluation, prescribing information updated to include case reports during postmarketing surveillance that include agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor

Zafirlukast (Accolate)

Selective and competitive receptor antagonist of leukotriene D4 and E4, components of slow-reacting substance of anaphylaxis. Indicated for stable, mild, persistent asthma or prophylaxis for EIA.

Dosing

Adult

20 mg PO bid; must be taken 30 min prior to breakfast and supper

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

Increases half-life of warfarin; erythromycin and theophylline decrease serum levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Elevations of liver enzymes occur rarely, but routine LFT monitoring not required; systemic eosinophilia and vasculitis consistent with Churg-Strauss syndrome also rarely reported; not indicated for acute asthma exacerbations
Neuropsychiatric events reported, and following further FDA evaluation, prescribing information updated to include case reports during postmarketing surveillance that include agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor

Mast cell stabilizers

Mast cell stabilizers prevent the release of mediators from mast cells that cause airway inflammation and bronchospasm. They are indicated for maintenance therapy of mild-to-moderate asthma or prophylaxis for exercise-induced bronchospasm.

Cromolyn (Intal)

Inhibits degranulation of sensitized mast cells following exposure to specific antigens. Attenuates bronchospasm caused by exercise, cold air, aspirin, and environmental pollutants.

Dosing

Adult

Chronic asthma: 2 puffs qid
EIA: 2 puffs 15-60 min prior to exercise or exposure

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity; severe renal or hepatic impairment

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Do not use in patients with severe renal or hepatic impairment; caution when withdrawing because symptoms may recur

5-Lipoxygenase inhibitors

These asthma medications 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.

Zileuton (Zyflo)

Inhibits leukotriene formation, which, in turn, decreases neutrophil and eosinophil migration, neutrophil and monocyte aggregation, leukocyte adhesion, capillary permeability, and smooth muscle contractions.

Dosing

Adult

600 mg PO pc and hs

Pediatric

Not established

Interactions

Increases toxicity of propranolol, warfarin, and theophylline

Contraindications

Documented hypersensitivity; active liver disease or transaminase elevation >3 times upper limit of normal

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Caution in liver disease; elevation of LFT findings may occur; not indicated for reversal of acute asthma attacks
Neuropsychiatric events reported, and following further FDA evaluation, prescribing information updated to include case reports during postmarketing surveillance that include agitation, aggression, anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking and behavior (including suicide), and tremor

Monoclonal antibodies

These recombinant DNA-derived humanized immunoglobulin G monoclonal antibodies bind selectively to human immunoglobulin E on the surface of mast cells and basophils. They reduce mediator release, which promotes an allergic response. They are indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens, in whom symptoms are not controlled by inhaled corticosteroids.

Omalizumab (Xolair)

Recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE on surface of mast cells and basophils. Reduces mediator release, which promotes allergic response. Indicated for moderate-to-severe persistent asthma in patients who react to perennial allergens in whom symptoms are not controlled by ICSs.

Dosing

Adult

150-375 mg SC q2-4wk; inject slowly over 5-10 seconds due to viscosity; not to exceed 150 mg/injection site
Precise dose and frequency established by serum total IgE level (IU/mL) and body weight

Pediatric

<12 years: Not established
>12 years: Administer as in adults

Interactions

None reported

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Not effective to treat acute asthma; do not abruptly discontinue ICSs when initiating omalizumab; anaphylaxis may occur following any dose, even if no reaction occurred to the first dose (observe patient for at least 2 h after administration in setting able to manage life-threatening anaphylaxis); patients should carry an epinephrine syringe (EpiPen) and know how to initiate emergency self-treatment; malignancy incidence among omalizumab-treated patients (0.5%) was numerically higher than among patients in control groups (0.2%); malignancies were of various types, and further long-term observation is needed to fully assess risk; may cause injection-site reaction

Follow-up

Further Inpatient Care

The initial assessment of acute asthma exacerbations should focus on several key areas.³⁶   

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 asthma 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, to evaluate the overall patient status, to assess for 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 radiography to assess for complications, and electrocardiography 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.^37,38
• 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 asthma 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 asthma signs and symptoms: 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 asthma 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

Inpatient & Outpatient Medications

The pharmacologic treatment of asthma is based on stepwise therapy. Asthma 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 indicated.
  • The reliever medication is a short-acting beta-agonist (SABA) as needed for symptoms.
• Step 2: Mild persistent asthma is present.
  • The preferred controller medication is a low-dose inhaled corticosteroid.
  • Alternatives include sodium cromolyn, nedocromil, or a leukotriene receptor antagonist (LTRA).³⁹
• Step 3: Moderate persistent asthma is present.
  • The preferred controller medication is either a low-dose inhaled corticosteroid plus a long-acting beta-agonist (LABA) (combination medication preferred choice to improve compliance)⁴⁰ or an inhaled medium-dose inhaled corticosteroid.
  • Alternatives include inhaled a low-dose ICS plus either a leukotriene receptor agonist, theophylline, or zileuton. 
• Step 4: Moderate-to-severe persistent asthma is present.
  • The preferred controller medication is an inhaled medium-dose inhaled corticosteroid plus a leukotriene receptor agonist (combination therapy). 
  • Alternatives include an inhaled medium-dose inhaled corticosteroid plus either a leukotriene receptor agonist, theophylline, or zileuton.
• Step 5:  Severe persistent asthma is present.
  • The preferred controller medication is an inhaled high-dose inhaled corticosteroid plus a leukotriene receptor agonist.
  • Consider omalizumab for patients who have allergies.
• Step 6:  Severe persistent asthma is present.
  • The preferred controller medication is a high-dose inhaled corticosteroid plus a leukotriene receptor agonist plus an oral corticosteroid.
  • Consider omalizumab for patients who have allergies.

Quick relief medication can be used for all patients and severities listed above. A short-acting beta-agonist, as needed for symptoms, can be used. The intensity of treatment depends on the severity of symptoms. Up to 3 treatments at 20-minute intervals as needed can be administered. A short course of oral systemic corticosteroids may be needed. The use of a short-acting beta-agonist more than 2 d/wk for symptom relief (not prevention of exercise-induced bronchospasm) generally indicates inadequate control and the need to step up treatment.

In patients with exercise-induced bronchospasm, 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.

With exercise-induced bronchospasm, 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 exercise-induced bronchospasm 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 exercise-induced bronchospasm. Inhaled corticosteroids have a limited role in the treatment of exercise-induced bronchospasm, except to control underlying asthma.

Deterrence/Prevention

Another essential component in asthma treatment 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:  

• Previous severe asthma exacerbation (eg, intubation or ICU admission for asthma)
• Two or more hospitalizations for asthma in the past year
• Three or more emergency department visits for asthma in the past year
• Hospitalization or emergency department visit for asthma in the past month
• Using more than 2 canisters of short-acting beta-agonists per month
• Difficulty perceiving asthma symptoms or severity of exacerbations
• Other risk factors - Lack of a written asthma action plan, sensitivity to Alternaria
• Social history - Low socioeconomic status or inner-city residence, illicit drug use, or major psychosocial problems
• Comorbidities - Cardiovascular disease, other chronic lung disease, chronic psychiatric disease

Complications associated with most medications used for asthma are relatively rare. However, in those patients who require 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.

A review by Cates et al addresses the possible link between beta2-agonists and increased asthma mortality and whether daily long-acting beta2-agonist use alone or with inhaled corticosteroids is safe. Adults and adolescents from 14 studies (8028 participants) and children and adolescents from 7 studies (2788 participants) were included in the review. The authors concluded that the data were insufficient to warrant either (1) reassuring asthma patients that inhaled corticosteroids with daily formoterol does not carry an increased risk of mortality when compared with inhaled corticosteroids alone or (2) concluding that evidence of harm has been determined. Further, Cates et al recommend that clinical decisions must take into account the potential benefits for the patient compared with the potential for harmful events, including mortality.⁴¹

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.

Patient Education

The Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma emphasizes the need for patient education about asthma and the establishment of a partnership between patient and clinician in the management of the disease. The key points of education include the following:

• Integrate patient education into every aspect of asthma care.
• All members of the health care team, including nurses, pharmacists, and respiratory therapists, provide education.
• Clinicians teach patients asthma self-management based on basic asthma facts, self-monitoring techniques, the role of medications, inhaler use, and environmental control measures.^42,43,44
• Develop treatment goals for the patient and family.
• Develop a written, individualized, daily self-management plan.
• Several well-validated asthma action plans are now available and are key in the management of asthma. These include the ACT (Asthma Control Test), ATAQ (Asthma Therapy Assessment Questionnaire), and ACQ (Asthma Control Questionnaire).⁴⁵

Additionally, Coffman et al conducted a systematic review of the literature on school-based asthma education programs that included 25 studies in children aged 4-17 years. Most studies found that compared with usual care, school-based asthma education improved knowledge of asthma (7 of 10 studies), self-efficacy (6 of 8 studies), and self-management behaviors (7 of 8 studies). Fewer studies reported favorable effects on quality of life (4 of 8 studies), days of symptoms (5 of 11 studies), nights with symptoms (2 of 4 studies), and school absences (5 of 17 studies).⁴⁶

For excellent patient education resources, visit eMedicine's Asthma Center. Also, see eMedicine's patient education articles Asthma, Asthma FAQs, Asthma in Children, and Understanding Asthma Medications.

Miscellaneous

Medicolegal Pitfalls

The most important factor in the diagnosis of asthma is to recognize exacerbating factors, comorbidities, or other diagnoses that may affect asthma treatment.

• Sinusitis: Of patients with asthma, 50% have concurrent sinus disease. Sinusitis is the most important exacerbating factor for asthma symptoms. Either acute infectious sinus disease or chronic inflammation may contribute to worsening airway symptoms. Treatment of nasal and sinus inflammation reduces airway reactivity. Treatment of acute sinusitis requires at least 10 days of antibiotics to improve asthma symptoms.⁴⁷
• Gastroesophageal reflux disease: Patients with asthma are 3 times more likely to also have GERD.⁴⁸ Aggressive antireflux therapy may improve asthma symptoms and pulmonary function in selected patients.  
  • Treatment with proton pump inhibitors, antacids, or H2 blockers may improve asthma symptoms or unexplained chronic cough. The treatment of asthma with agents such as theophylline may lower esophageal sphincter tone and induce GERD symptoms.
  • Some people with asthma have significant gastroesophageal reflux without esophageal symptoms. Gastroesophageal reflux was found to be a definite asthma-causing factor (defined by a favorable asthma response to medical antireflux therapy) in 64% of patients; clinically silent reflux was present in 24% of all patients.^49,50
• Respiratory tract infections: Viral respiratory tract infections have not been shown to cause asthma but can aggravate chronic asthma symptoms or induce symptoms in patients with allergic rhinitis. Rhinoviruses are the principal triggers of wheezing and worsening of asthma in older children and adults, but all viral respiratory tract infections are associated with increased asthma symptoms.
• Aspirin-induced asthma: The triad of asthma, aspirin sensitivity, and nasal polyps affects 5-10% of patients with asthma. Most patients experience symptoms during the third to fourth decade. A single dose can provoke an acute asthma exacerbation, accompanied by rhinorrhea, conjunctival irritation, and flushing of the head and neck. It can also occur with other nonsteroidal anti-inflammatory drugs and is caused by an increase in eosinophils and cysteinyl leukotrienes after exposure. Primary treatment is avoidance of these medications, but leukotriene antagonists have shown promise in treatment, allowing these patients to take daily aspirin for cardiac or rheumatic disease.
• Vocal cord dysfunction: Paradoxical inspiratory adduction of the vocal cords may mimic asthma. Patients with symptoms of inspiratory wheezing/stridor or those whose asthma is refractory to standard therapy should be evaluated for evidence of vocal cord dysfunction. Usually the diagnosis can be made using direct laryngoscopy, but only during symptomatic periods or after exercise. The presence of flattening of the inspiratory limb of the flow-volume loops may also suggest vocal cord dysfunction, but this is only seen in 28% of patients at baseline. Patients with chronic symptoms suggestive of asthma, normal spirometry, poor response to asthma medications, and frequent evaluations should be evaluated for vocal cord dysfunction.⁵¹
• Occupational asthma⁵² : Occupational factors are associated with 10% of adult asthma cases. More than 300 specific occupational agents have been associated with asthma. High-risk jobs include farming, painting, janitorial work, and plastics manufacturing. Two types of occupational asthma are recognized. Immune-mediated asthma has a latency of months to years after exposure. Non–immune-mediated asthma or irritant-induced asthma (reactive airway dysfunction syndrome) has no latency period and may occur within 24 hours of an accidental exposure to high concentrations of respiratory irritants. Pay careful attention to the patient's occupational history. Those with a history of asthma who report worsening of symptoms during the week and improvement during the weekends should be evaluated for occupational exposure. Peak-flow monitoring during work for 2 weeks and a similar period away from work is one recommended method to establish the diagnosis.⁵³

Special Concerns

• Nocturnal asthma
  • A large percentage of patients with asthma experience nocturnal symptoms once or twice a month. Some patients only experience symptoms at night and have normal pulmonary function in the daytime. This is due, in part, to the exaggerated response to the normal circadian variation in airflow.
  • Bronchoconstriction is highest between the hours of 4:00 am and 6:00 pm (the highest morbidity and mortality from asthma is observed during this time). These patients may have a more significant decrease in cortisol levels or increased vagal tone at night. Studies also show an increase in inflammation compared with controls and with patients with daytime asthma.
  • Nocturnal asthma is a significant clinical problem that should be addressed aggressively. Peak-flow meters should be used to allow objective evaluation of symptoms and interventions. Sleep apnea, symptomatic GERD, and sinusitis should be controlled when present.
  • Medications should be appropriately timed and consideration should be given to the use of a long-acting inhaled or oral beta2-agonist, a leukotriene modifier, and inhaled corticosteroids. A once-daily sustained-release theophylline preparation and changing the timing of oral corticosteroids to the mid afternoon can be also be used.
• Pregnancy⁵⁴
  • Asthma complicates 4-8% of pregnancies. Mild and well-controlled moderate asthma can be associated with excellent maternal and perinatal pregnancy outcomes. Severe and poorly controlled asthma may be associated with increased prematurity and other perinatal complications, to include maternal morbidity and mortality. Optimal management of asthma during pregnancy includes objective monitoring of lung function, avoiding or controlling asthma triggers, patient education, and individualized pharmacologic therapy. Inhaled corticosteroids are the preferred medication for all levels of persistent asthma during pregnancy. Pregnant women with asthma are safer to be treated with asthma medications than to have asthma symptoms and exacerbations. The ultimate goal of asthma therapy is maintaining adequate oxygenation of the fetus by prevention of hypoxic episodes in the mother.
  • With the exception of alpha-adrenergic compounds other than pseudoephedrine and some antihistamines, most drugs used to treat asthma and allergic rhinitis have not been shown to increase any risk to the mother or fetus. The National Institute of Health stated that albuterol, cromolyn, beclomethasone, budesonide, prednisone, and theophylline, when clinically indicated, are considered appropriate for the treatment of asthma in pregnancy.
  • Poorly controlled asthma can result in low birth weight, increased prematurity, and increased perinatal mortality.
  • The American College of Obstetrics and Gynecology issued updated clinical guidelines for 2008.⁵⁵

Multimedia

Media file 1: Asthma causes and symptoms. Antigen presentation by the dendritic cell with the lymphocyte and cytokine response leading to airway inflammation and asthma symptoms.

Media file 2: Asthma symptoms and severity. Recommended guidelines for determination of asthma severity based on clinical symptoms, exacerbations, and measurements of airway function. Adapted from Global Strategy for Asthma Management and Prevention: 2002 Workshop Report.

Media file 3: Asthma Treatment. Stepwise approach to pharmacological management of asthma based on asthma severity. Adapted from Global Strategy for Asthma Management and Prevention: 2002 Workshop Report.

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Keywords

asthma, asthma medications, asthma treatment, asthma attack, asthma symptoms, asthma diagnosis, asthma assessment, asthma guidelines, asthma treatment guidelines, assessment of asthma, guidelines for asthma, asthma in children, adult asthma, asthma inhalers, status asthmaticus, hyperreactive airway disease, exercise-induced asthma, exercise-induced bronchospasm

airway inflammation, intermittent airflow obstruction, airway hyperresponsiveness, respiratory hypersensitivity, bronchial hyperresponsiveness, acute bronchospasm, acute bronchoconstriction, airway edema, chronic mucous plug formation, bronchial hyperreactivity, airway obstruction, wheezing, dyspnea, allergy-induced asthma, allergic asthma, acute asthma, chronic asthma, asthma nebulizer, asthma cough, steroids, asthma score,

Contributor Information and Disclosures

Author

Michael J Morris, MD, Clinical Assistant Professor, Pulmonary Disease/Critical Care Service, Department of Medicine, Brooke Army Medical Center; Associate Program Director, Internal Medicine Residency, San Antonio Uniformed Services Health Education Consortium
Michael J Morris, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians-American Society of Internal Medicine, and American Thoracic Society
Disclosure: Nothing to disclose.

Medical Editor

Helen M Hollingsworth, MD, Director, Adult Asthma and Allergy Services, Associate Professor, Department of Internal Medicine, Division of Pulmonary and Critical Care, Boston Medical Center
Helen M Hollingsworth, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American College of Chest Physicians, American Thoracic Society, and Massachusetts Medical Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Gregg T Anders, DO, Medical Director, Great Plains Regional Medical Command , Brook Army Medical Center; Clinical Associate Professor, Department of Internal Medicine, Division of Pulmonary Disease, University of Texas Health Science Center at San Antonio
Gregg T Anders, DO is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and American Thoracic Society
Disclosure: Nothing to disclose.

CME Editor

Timothy D Rice, MD, Associate Professor, Departments of Internal Medicine and Pediatrics and Adolescent Medicine, Saint Louis University School of Medicine
Timothy D Rice, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Physicians
Disclosure: Nothing to disclose.

Chief Editor

Zab Mosenifar, MD, Director, Division of Pulmonary and Critical Care Medicine, Director, Women's Guild Pulmonary Disease Institute, Executive Vice Chair, Department of Medicine, Cedars Sinai Medical Center; Professor of Medicine, David Geffen School of Medicine at UCLA
Zab Mosenifar, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, and American Thoracic Society
Disclosure: Nothing to disclose.

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