GUIDELINE SYNTHESIS
Asthma Treatment
Guidelines
1. National Heart, Lung, and Blood Institute (U.S.) (NHLBI). Expert
Panel Report 2: guidelines for the diagnosis and management of asthma.
<http:/FRAMESETS/guideline_fs.asp?guideline=000335> Bethesda (MD): U.S.
Department of Health and Human Services, Public Health Service, National
Institutes of Health, National Heart, Lung, and Blood Institute; 1997 Jul.
146 p. [79 references]
2. World Health Organization (WHO) and National Heart, Lung, and Blood
Institute (U.S.) (NHLBI). Global Initiative for Asthma.
<http:/FRAMESETS/guideline_fs.asp?guideline=001116> Bethesda (MD): Global
Initiative for Asthma, National Heart, Lung, and Blood Institute; 1995 Jan
(revised 1998). 249 p. [544 references]
3. Institute for Clinical Systems Improvement (ICSI). Diagnosis and
management of asthma. <http:/FRAMESETS/guideline_fs.asp?guideline=001339>
Bloomington, MN: Institute for Clinical Systems Improvement; 1999 Jun. 32 p.
[28 references]
4. University of Michigan Health System (UMHS). Asthma.
<http:/FRAMESETS/guideline_fs.asp?guideline=1507> Ann Arbor (MI):
University of Michigan Health System; 2000 Jan. 14 p. [14 references]
5. American Academy of Allergy, Asthma and Immunology (AAAAI);
American College of Allergy, Asthma and Immunology (ACAAI); Joint Council of
Allergy, Asthma, and Immunology (JCAAI). Practice parameters for the
diagnosis and treatment of asthma.
<http:/FRAMESETS/guideline_fs.asp?guideline=000675> J Allergy Clin Immunol
1995 Nov;96(5 Pt 2):707-870. [1195 references]
INTRODUCTION:
Clinical practice guidelines on asthma issued by NHLBI, WHO/NHLBI, ICSI,
UMHS, and AAAAI/ACAAI/JCAAI are compared in the following table. The
comparison is restricted to recommendations for treatment of asthma and does
not include recommendations concerning diagnosis or other issues. It should
be noted that certain recommendations that originated in the NHLBI guideline
were subsequently incorporated into the WHO/NHLBI, ICSI, and UMHS
guidelines. The WHO/NHLBI guideline extends and interprets NHLBI’s original
guideline in a global context. The NHLBI classification scheme for asthma
severity and the stepwise approach to pharmacological therapy was also
endorsed by ICSI and adapted for use in their medical groups.
Following the content comparison table and discussion, the areas of
agreement and differences among the guidelines are identified. In general,
the timing of the guideline with respect to available data is an important
factor to consider when evaluating areas of differences among guidelines.
The rationale behind disparate recommendations that cannot be attributed to
the evidence base available and considered during guideline development is
also explored in the discussion of areas of differences.
Abbreviations used in the text and tables follow:
* AAAAI, American Academy of Allergy, Asthma and Immunology
* ACAAI, American College of Allergy, Asthma and Immunology
* DPI, dry powder inhaler
* FEV, forced expiratory volume
* ICSI, Institute for Clinical Systems Improvement
* JCAAI, Joint Council of Allergy, Asthma, and Immunology
* MDI, metered dose inhaler
* NHLBI, National Heart, Lung, and Blood Institute
* NSAID, nonsteroidal anti-inflammatory drugs
* PEF, peak expiratory flow
* PEFR, peak expiratory flow rate
* UMHS, University of Michigan Health System
* URI, upper respiratory infection
* WHO, World Health Organization
Note: To print the following large tables, users may have to change their
printer settings to landscape, print on legal size paper, and/or use a small
font size.
NHLBI (1997)
WHO/NHLBI (1998)
ICSI (1999)
UMHS (2000)
AAAAI/ACAAI/JCAAI (1995)
OBJECTIVE AND SCOPE
* To improve asthma care and the quality of life for patients with asthma
and their families.
* To facilitate the successful management of asthma; to prevent chronic
disability and premature death due to asthma; and to facilitate productive
and fulfilling lives for people with asthma.
* To extend the relevance of and impact of the National Heart, Lung, and
Blood Institute's (NHLBI) "International Consensus Report on Diagnosis and
Management of Asthma," by adapting the recommendations for the clinical
management of asthma in order to ensure their appropriateness throughout the
global community.
* To deliver information to public health officials about the costs of
asthma, prevention activities, and education methods; so that they can
develop asthma care services and programs responsive to the particular needs
and circumstances of their countries.
* To develop information, recommendations and tools to assist health care
professionals and public health officials in appreciating the magnitude of
the asthma problem in their countries and in designing and delivering
effective asthma management and prevention programs in their communities.
* To identify areas for future research investigations.
* To promote the accurate assessment of asthma severity through the use of
objective measures of lung function (spirometry and PEFR).
* To promote long-term control of persistent asthma through the use of
anti-inflammatory drug therapy.
* To promote the partnership of patients and parents with health care
professionals through education and use of written action plans.
* To improve the patient's quality of life by achieving and maintaining
control of symptoms; attaining normal lung function; minimizing need for
as-needed beta2-agonists; avoiding adverse effects from asthma medications;
preventing exacerbations; attaining normal activity levels, including
exercise; and preventing emergency visits and hospitalizations.
* To provide scientific information to the health care community and foster
improvement in the overall quality of the diagnosis and treatment of
patients who suffer from asthma.
TARGET POPULATION
* United States
* Infants, children, adolescents, and adults with asthma
* International
* Patients of all ages with asthma
* United States
* Patients 5 years of age and older who present with asthma-like symptoms
and/or have been diagnosed with asthma
* The guideline is intended for treatment of outpatients, not critically ill
patients
* United States
* Children, adolescents, and adults with asthma
* United States
* Children, adolescents and adults with asthma
INTENDED USERS
* Physicians; Nurses; Nurse Practitioners; Physician Assistants; Health
Plans
* Physicians; Nurses; Nurse Practitioners; Health Care Providers; Public
Health Departments
* Physicians; Nurses; Nurse Practitioners; Physician Assistants; Allied
Health Care Practitioners
* Physicians; Nurses; Nurse Practitioners; Physician Assistants;
Respiratory Care Practitioners; Pharmacists
* Physicians (primary care and specialists)
INTERVENTIONS AND PRACTICES CONSIDERED
* Periodic assessment and monitoring of signs and symptoms, pulmonary
function (spirometry, peak flow monitoring) quality of life/functional
status, history of asthma exacerbations, pharmacotherapy, patient-provider
communication and patient satisfaction
* Control factors contributing to asthma severity
* Pharmacological therapy for managing asthma long term: The stepwise
approach to identify minimum amount of medication necessary to maintain
control.
* Long-term medications:
* Corticosteroids
* Long-acting beta2-agonists
* Cromolyn sodium and nedocromil
* Methylxanthines (theophylline)
* Leukotriene modifiers
* Quick-relief medications:
* Short-acting beta2-agonists
* Anticholinergics
* Systemic corticosteroids
* Management of asthma exacerbations:
* Beta2-agonist (inhaled)
* Systemic corticosteroid (moderate-to-severe exacerbations)
* Oxygen to relieve hypoxia (moderate-to-severe exacerbations)
* Monitoring response to therapy with serial measurement of lung function
* Referral to an asthma specialist
* Patient education
A six-part asthma management program, including the following elements:
1. Assess and monitor asthma severity with both symptom reports and, as much
as possible, measurements of lung function (using peak expiratory flow or
PEF information). Measurement of arterial blood gases is also considered,
especially for patients in the emergency department.
2. Avoid or control asthma triggers: controlling exposure to allergens,
pollutants, and pharmacologic agents. Influenza vaccination and specific
immunotherapy are also considered.
3. Establish individual medication plans for long-term management.
a. Long-term preventive (controller) medications:
* Corticosteroids, inhaled and systemic
* Sodium cromoglycate
* Nedocromil sodium
* Sustained-release theophylline
* Long-acting beta2-agonists; inhaled and oral
* Ketotifen
* Antileukotrienes
b. Quick-relief (reliever) medications:
* Short-acting inhaled beta2-agonists
* Systemic corticosteroids
* Inhaled anticholinergics
* Short-acting theophylline
* Short-acting oral beta2-agonists
* Epinephrine/adrenaline injection
4. Traditional methods of healing or therapies (i.e., alternative and
complementary medicines)
5. Establish plans for managing exacerbations: including assessment of the
severity of the exacerbation, and:
a. Home management of exacerbations: action plan and treatment including
bronchodilators and corticosteroids; and additional care (continued
medications).
b. Hospital-based management of exacerbation: including assessment of the
patient; treatment (including oxygen, beta2-agonists, epinephrine,
additional bronchodilators, and corticosteroids); and considerations of
other treatments.
6. Provide regular follow-up care.
7. Educate patients to develop a partnership in asthma management.
* Chronic management of asthma with interval evaluation, including history
and physical examination, measurement of pulmonary function, PEFR.
* Step care of pharmacologic treatment: Control of asthma symptoms with the
least amount of medication necessary. Long term medications include:
* Systemic corticosteroids
* Cromolyn and nedocromil
* Long-active beta2-agonists
* Methylxanthines (theophylline)
* Leukotriene modifiers
* Management of acute asthma
1. Emergency care
* Beta-agonists
* Corticosteroids
2. Home-based care
* Beta-agonists (inhaled)
* Corticosteroids (inhaled or oral)
* Cromolyn/ nedocromil
* Leukotriene modifiers
* Antibiotics for bacterial infection
* Consultation with an asthma specialist
* Patient education
* Education of patients to develop a partnership in asthma management
* Assessment of asthma severity with objective measures of lung function
(PEFR monitoring)
* Avoidance or control of asthma triggers:
* Indoor allergens (domestic mites, animal allergens, cockroach allergens,
fungi, occupational allergens and irritants)
* Outdoor allergens (pollens, molds)
* Food additives (sulfites, tartrazine [yellow dye], parabens, monosodium
glutamate)
* Indoor air pollution (tobacco or other smoke, air pollutants)
* Medications (aspirin, NSAIDs, beta-blockers)
* Exercise
* Concurrent medical conditions: infections [e.g., viral upper respiratory
infection, bronchitis, sinusitis]; allergic rhinitis; gastroesophageal
reflux disease
* Establishment of medication plans for chronic management
* Anti-inflammatory medications:
* Inhaled corticosteroids
* Systemic corticosteroids:
* Leukotriene modifier agents:
* Non-steroidal drugs with anti-inflammatory properties (mast cell
stabilizers)
* Bronchodilator medications:
* Inhaled, short-acting beta2-agonists
* Inhaled, long-acting beta2-agonists
* Methylxanthines
* Anticholinergics
* Use of bronchodilators: pediatric considerations and home nebulizers
* Establishment of plans for managing exacerbations
* Regular follow-up care and consideration of consultation or referral
* Classification of asthma severity
* Environmental avoidance
* Airborne triggers
* Food hypersensitivity
* Pharmacotherapy
* Beta-adrenergic agonist bronchodilators
* Theophylline
* Anticholinergic agents
* Antihistamines
* Cromolyn and nedocromil
* Corticosteroids
* Hydration and pharmacomucolytic agents
* Alternative therapy (troleandomycin, methotrexate, gold and intravenous
globin therapy)
* Antibiotics for bacterial infection
* Polypharmacy
* Influenza immunization for patients with moderately severe or severe
asthma
* Allergen immunotherapy
* Management of severe acute intractable asthma
* Administration of oxygen
* Use of beta2-agonists (sympathomimetics)
* Use of corticosteroids
* Monitoring blood levels and cardiopulmonary function after administration
of aminophylline/ theophylline
* Fluid hydration and danger of overhydration
* Possible need for mechanical ventilation and intubation
* Consultation with an asthma specialist
* Patient education
TREATMENT RECOMMENDATIONS
NHLBI (1997)
WHO, NHLBI (1998)
ICSI (1999)
UMHS (2000)
AAAAI, ACAAI, JCAAI (1995)
Goals of Asthma Therapy
The goals of therapy are as follows:
* Prevent chronic and troublesome symptoms (e.g., coughing or breathlessness
in the night, in the early morning, or after exertion)
* Maintain (near) "normal" pulmonary function
* Maintain normal activity levels (including exercise and other physical
activity)
* Prevent recurrent exacerbations of asthma and minimize the need for
emergency department visits or hospitalizations
* Provide optimal pharmacotherapy with minimal or no adverse effects
* Meet patients’ and families’ expectations of, and satisfaction with,
asthma care
The primary goal of asthma management is to achieve control of asthma, which
is defined as:
* Minimal (ideally no) chronic symptoms, including nocturnal symptoms
* Minimal (infrequent) exacerbations
* No emergency visits
* Minimal (ideally no) need for p.r.n. (as needed) beta2-agonist
* No limitations on activities, including exercise
* Peak expiratory flow (PEF) circadian variation of less than 20 percent
* (Near) normal PEF
* Minimal (or no) adverse effects from medicine
Additional goals include:
* Prevention of development of irreversible airflow limitation
Prevention of asthma mortality
* The goal of managing patients with acute asthma exacerbation is prompt
evaluation and treatment to improve symptoms in the short term, prevent
recurrence of symptoms and provide for follow-up.
* The aim of pharmacological therapy is to achieve and maintain control of
chronic asthma using the least amount of medication necessary and hence
minimizing the risk for adverse effects.
Goals of treatment include:
* Symptomatic relief
* Normalization of lung function.
* Minimization of need for as needed beta2-agonists
* Avoidance of adverse effects from asthma medication
* Prevention of exacerbations
* Attainment of normal activity levels, including exercise
* Prevention of emergency visits and hospitalizations
* Patient self-management, including ability to measure their peak
expiratory flow rate (PEFR) at home and modify their therapy or seek help
based on their performance relative to their personal best peak flow value.
Individualized treatment aimed at the following outcome goals:
* Reduction in emergency care
* Reduction in hospitalization
* Prevention of nocturnal symptoms
* Tolerance of physical activity appropriate for the patient’s age
* Improvement in pulmonary function
* Minimization of time lost from work, school, and daily activities
* Improved self-image based on a full understanding of the disease and
confidence in outlined approaches to treatment
* Optimal control of asthma with the use of the least amount of medication
possible, administered in a manner that permits the most normal lifestyle,
and is associated with minimal side effects
* General improvement in patients’ quality of life
Asthma Trigger Avoidance
Allergens
Reduce or eliminate exposure to allergen(s) the patient is sensitive to,
including:
* Animal dander: Remove animal from home or: keep pet out of patient’s
bedroom, keep door closed, consider placing dense filtering material over
forced air outlets, either remove upholstered furniture or try to keep pet
away from them.
* House-dust mites: Essential control measures include encasing bed mattress
in allergen-impermeable cover, encase pillow likewise or wash weekly, and
wash sheets and blankets on patient’s bed weekly in hot water (>130* F).
Desirable control measures: reduce indoor humidity to <50%; remove carpets
from bedroom, avoid sleeping or lying on upholstery; remove carpets laid on
concrete.
* Cockroaches: Use poison bait or traps to control. Do not leave food or
garbage exposed.
* Pollens and outdoor molds: Stay indoors with windows closed during allergy
season, especially during afternoon.
* Indoor mold: Fix leaks and eliminate water sources associated with mold
growth; clean moldy surfaces. Consider reducing indoor humidity to <50%.
Indoor/Outdoor Pollutants and Irritants
* Tobacco Smoke: advise patients and others in the home to stop smoking or
smoke outside the home
Discuss ways to reduce exposure to the following:
* Wood-burning stoves or fireplaces
* Unvented stoves or heaters
* Other irritants (e.g., perfumes, cleaning agents, sprays)
Other Factors That Can Influence Asthma Severity
* Aspirin sensitivity: patients who have experienced a reaction to aspirin
or other NSAIDs should be advised to use alternative medications
* Non-selective beta-blockers should be avoided
* Sulfite sensitivity: patients with asthma symptoms associated with shrimp,
dried fruit, beer, wine, or processed potatoes should avoid these products
* Annual influenza vaccinations are recommended for patients with persistent
asthma
* Rhinitis/sinusitis and gastroesophageal reflux are often associated with
asthma
Avoidance or Control of Asthma Triggers
* Domestic mites: Mattresses, box springs, and pillows should receive
allergen-proof casing. Bed linens and blankets should be washed once a week
in hot water (> 55* C). Ideally, carpets should be replaced with vinyl or
polished wooden floor boards. If carpet cannot be removed, cover with
polyethylene sheeting. Children’s soft toys should be removed, washed in hot
water, or deep frozen once a week. Fabric-covered furniture should be
eliminated. Maintaining low humidity (< 50%) with dehumidifiers or air
conditioning is desirable.
* Animal allergens: Animals should be removed from home or, at minimum, from
sleeping area. Washing cat fur weekly appears to reduce allergen load.
* Cockroaches: Control by regular cleaning and pesticides. Asthmatic persons
should not be present when spray is used.
* Fungi: Remove or clean mold-laden objects. Maintain low humidity (< 50%)
and clean dehumidifier frequently. Air conditioning is also recommended. In
tropical and subtropical climates fungi may grow on walls; they should be
tiled or cleaned as necessary.
* Outdoor allergens (pollen and mold spores): Reduce exposure by closing
windows and doors, remaining indoors when pollen and mold counts are
highest, and using air conditioning if available.
* Viral respiratory infections: Primarily cause asthma in children and are
difficult to avoid.
* Indoor air pollutants: Avoid passive and active smoking. Parents of
asthmatics should be advised to not smoke and not allow smoking in rooms
their children use. Vent all furnaces to the outdoors, maintain heating
systems adequately. Gas appliances should have sufficient flues or ducts.
Avoid wood smoke, household sprays, and volatile organic compounds (e.g.
polishes and cooking oils).
* Outdoor air pollutants: Pollutants such as ozone, nitrogen oxides, acidic
aerosols, and particulate matter can reach intense local concentrations in
defined geographic areas. During such episodes, patients are advised to
avoid unnecessary physical activity, avoid smoking and smoke-filled rooms,
avoid exposure to dust and other irritants, avoid exposure to respiratory
infectious agents, and try to stay indoors in a clean environment. If
possible, leave polluted area temporarily.
* Avoid occupational exposures
* Food avoidance: Foods containing sulfites should be avoided by sensitive
patients. Specific food allergies may occur in children and must be
diagnosed carefully before food avoidance is recommended.
* Avoidance of certain drugs: Aspirin and other NSAIDs should be avoided by
patients with a history of reacting to these agents. Beta-blocker drugs
should not be used by patients with asthma.
* Influenza vaccination: Asthma patients might be advised to receive this
vaccination to avoid respiratory illness.
Concomitant Conditions That May Influence Asthma Severity
* Rhinitis, sinusitis, and nasal polyps: These upper airway disorders may
increase asthma severity.
* Gastroesophageal reflux: Condition commonly found in asthma patients.
Asthma Triggers
* Viral respiratory infections
* Environmental allergens
* Exercise, temperature, humidity
* Occupational and recreational allergens or irritants
* Environmental irritants (perfume, tobacco smoke, wood-burning stoves)
* Drugs (aspirin, NSAIDs, beta-blockers) and food (sulfites)
Asthma triggers are mentioned in the context of diagnosis of asthma and
interval evaluation. The stepwise approach calls for patient education
regarding appropriate environmental control measures to avoid exposure to
known allergens and irritants. Specific recommendations on avoidance of
triggers in patients diagnosed with asthma are not presented.
Measures for avoiding or controlling asthma triggers:
* House dust mites. Effective mite control measures include washing (every
1-2 weeks) bedding materials in hot water to denature mite allergens,
encasing the mattress and box spring, reducing humidity to less than 50% and
treating carpets and furniture with acaricides (to kill dust mites) or
tannic acid (to denature dust mite allergen). Mite-allergic patients should
avoid the environment when it is being cleaned or vacuumed as this causes
dispersion of allergen.
* Warm-blooded pets (especially cats, but also including dogs, rodents, and
birds). Remove animals from the patient’s environment. The perceived benefit
may not be immediate because animal allergens may linger for months after
animal removal.
* Occupational trigger exposure. PEFR monitoring on and off the job and
Material Safety Data Sheets can help identify occupational triggers.
* Outdoor allergens (pollens and molds): Reduce exposure by closing windows
and doors and by using air-conditioning and filtering devices, especially
during peak pollen and mold seasons.
* Food triggers. Avoid food triggers, such as sulfites, the yellow dye
tartrazine, parabens, and monosodium glutamate. Be educated in
self-administration of epinephrine for inadvertent food exposures.
* Indoor air pollution. Avoid tobacco smoke, smoke from wood stoves or
heating, aerosols, household sprays, volatile organic compounds, strong
odors and scents, and air pollutants.
* Medications. In certain patients aspirin and NSAIDs can cause severe
exacerbations, but may be useful for those without contraindications.
* Exercise. Anti-inflammatory therapy often results in the disappearance of
exercise-induced symptoms. The inhalation of a beta2-agonist 10 to 20
minutes before exercise is often the most effective means of preventing
exercise-induced asthma exacerbations. Cromolyn inhalers and oral
montelukast are also of demonstrated efficacy for exercise-induce asthma.
Training and sufficient warm up also reduce the incidence and severity of
exercise-induced asthma.
* Concurrent medical conditions Concurrent medical conditions that can
exacerbate asthma include infections (e.g., viral upper respiratory
infections, bronchitis, sinusitis), allergic rhinitis, and gastroesophogeal
reflux disease.
Airborne Triggers
* House-dust mites
* Cockroaches
* Domestic animals
* Tree, grass, and weed pollen
* Molds and fungi
* Nonallergic environmental triggers (tobacco smoke, chemical irritants, or
strong odors)
Recommendations to minimize exposure:
* Minimize house-dust mite exposure in mite-allergic patients with asthma
* Lessen exposure to domestic animals
* Do not allow smoking in the home
* Avoid strong odors and chemical fumes
* Install kitchen and bathroom exhaust fans
* Use humidifiers with caution in homes with mite- and mold-sensitive
patients
* Use air conditioners in bedrooms and family rooms when appropriate
* Use high-efficiency particulate air filters or electrostatic air purifiers
* Install a dehumidifier and reduce water entry in damp basements
* Initiate other measures for specific allergies as appropriate
Food Allergies
* Evaluation of food hypersensitivity should be considered in patients with
chronic symptoms
Other Factors That Can Influence the Severity of Asthma
* Concomitant conditions (obesity, sleep apnea, tuberculosis, diabetes,
hyperthyroidism, Addison’s disease, hypertension and heart disease, peptic
ulcer, gastritis, and esophagitis, fixed obstructive disorders,
bronchiolitis obliterans)
* Anaphylaxis – may be induced by food, insect venom, allergenic extracts or
drugs such as beta-blockers
* Nasal and sinus disease (sinusitis, nasal polyps)
* Gastroesophageal reflux
* Aspirin/NSAID/ preservative sensitivity (preservatives include sulfites,
Azo dyes and monosodium glutamate)
Allergen Immunotherapy
Allergen Immunotherapy may be considered for asthma patients when:
* There is clear evidence of relationship 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
* There is difficulty controlling symptoms with pharmacologic management
For safety reasons, immunotherapy should only be performed in a physician’s
office where facilities and personnel are available to treat a rare, but
possible, life-threatening reaction.
Allergen Immunotherapy
* May be considered when avoiding allergens is not possible or when
appropriate medication is not available or fails to control asthma symptoms.
* Can be dangerous and should only be performed by health care professionals
especially trained for this form of treatment.
* Factors to be considered when comparing immunotherapy to other therapies:
* Potential severity of allergic asthma to be treated
* Efficacy of available immunotherapy
* Cost and availability of each type of treatment
* Risk of morbidity and mortality due to asthma compared to the risk of the
treatments
* To minimize risk and improve efficacy, the following suggestions are made:
* Patients with multiple allergen sensitivities and/or nonallergic triggers
may not benefit from specific immunotherapy
* Specific immunotherapy is more effective in children and young adults
than later in life
* Patient should be asymptomatic at time of injections because lethal and
adverse reactions more often occur in patients with severe airflow
limitation.
* Patients should remain in provider’s office under close supervision for
30 minutes following administration of the allergen extract.
FEV or PEV1 with pharmacological treatment should be > 70% of predicted
value for both efficacy and safety reasons.
Allergen immunotherapy is not addressed.
Desensitization injections (allergy shots) are not indicated for most
patients, but they may have a place in the management of a subset of
selected patients with extrinsic (allergic) asthma.
Allergen Immunotherapy
* Allergen immunotherapy can be effective in patients with asthma and may
lessen the effect of chronic allergen stimulation on hyperresponsive airways
* Allergen immunotherapy should be considered a long-term therapeutic
modality. It should be part of a well-planned program that includes
pharmacotherapy and avoidance measures
* Patient compliance is essential for effective and safe application
* Immediate and delayed local and systemic reactions may occur in the course
of allergen immunotherapy; patients should be informed of the relative
risks.
Patients and medical personnel should be instructed in detail about
prevention and treatment of reactions to allergen immunotherapy
Assessment of Asthma Severity
The NHLBI stepwise classification scheme considers clinical features before
treatment:
Step 4: Severe Persistent
* Continual symptoms
* Limited physical activity
* Frequent nighttime symptoms
* Frequent exacerbations
* FEV1 or PEF <60% predicted
* PEF variability >30%
Step 3: Moderate Persistent
* Daily symptoms
* Daily use of inhaled short-acting beta2-agonist
* Exacerbations affect activity
* Exacerbations >2 times a week; may last days
* Nighttime symptoms >1 time a week
* FEV1 or PEF >60% - < 80% predicted
* PEF variability >30%
Step 2: Mild Persistent
* Symptoms >2 times a week but <1 time per day
* Exacerbations may affect activity
* Nighttime symptoms >2 times per month
* FEV1 or PEF >80% predicted
* PEF variability 20-30%
Step 1: Mild Intermittent
* Symptoms <2 times per week
* Asymptomatic and normal PEF between exacerbations
* Exacerbations brief (from a few hours to a few days); intensity may vary
* Nighttime symptoms <2 times per month
* FEV1 or PEF >80% predicted
* PEF variability <20%
From NHLBI Expert Panel Report 2:
Step 4: Severe Persistent
* Continual symptoms
* Limited physical activity
* Frequent nighttime symptoms
* Frequent exacerbations
* FEV1 or PEF < 60% predicted
* FEV1 or PEF variability > 30%
Step 3: Moderate Persistent
* Daily symptoms
* Daily use of inhaled short-acting beta2-agonist
* Exacerbations affect activity and sleep
* Nighttime symptoms > 1 time a week
* FEV1 or PEF > 60% - < 80% predicted
* FEV1 or PEF variability > 30%
Step 2: Mild Persistent
* Symptoms > 2 times a week but < 1 time per day
* Exacerbations may affect activity and sleep
* Nighttime symptoms > 2 times per month
* FEV1 or PEF > 80% predicted
* FEV1 or PEF variability 20-30%
Step 1: Mild Intermittent
* Intermittent symptoms < 1 time per week
* Asymptomatic and normal lung function between exacerbations
* Exacerbations brief (from a few hours to a few days)
* Nighttime symptoms < 2 times per month
* FEV1 or PEF > 80% predicted
* FEV1 or PEF variability < 20%
From NHLBI Expert Panel Report 2:
Step 4: Severe Persistent
* Continual symptoms
* Limited physical activity
* Frequent nighttime symptoms
* Frequent exacerbations
* FEV1 or PEF < 60% predicted
* PEF variability > 30%
Step 3: Moderate Persistent
* Daily symptoms
* Daily use of inhaled short-acting beta2-agonist
* Exacerbations affect activity
* Exacerbations >2 times a week; may last days
* Nighttime symptoms <1 time a week
* FEV1 or PEF > 60% - <80% predicted
* PEF variability >30%
Step 2: Mild Persistent
* Symptoms >2 times a week but <1 time per day
* Exacerbations may affect activity
* Nighttime symptoms >2 times per month
* FEV1 or PEF >80% predicted
* PEF variability 20-30%
Step 1: Mild Intermittent
* Symptoms < 2 times per week
* Asymptomatic and normal PEF between exacerbations
* Exacerbations brief (from a few hours to a few days); intensity may vary
* Nighttime symptoms < 2 times per month
* FEV1 or PEF > 80% predicted
* PEF variability < 20%
Adapted from the NHLBI Expert Panel Report 2:
Step 4: Severe Persistent
* Continual symptoms
* Limited physical activity
* Frequent nighttime symptoms
* Frequent exacerbations
* FEV1< 60% predicted
* PEF diurnal variability >30%
Step 3: Moderate Persistent
* Daily symptoms
* Daily use of short-acting B2-agnoist
* Exacerbations affect activity, sleep
* Nighttime symptoms > 1/week
* FEV1> 60% but less than 80% predicted
* PEF diurnal variability >30%
Step 2: Mild Persistent
* Symptoms >2/week but < 1/day
* Exacerbations may affect activity and sleep
* Nighttime symptoms > 2/month
* FEV1 > 80% predicted
* PEF diurnal variability 20-30%
Step 1: Mild Intermittent
* Symptoms <2 times per week
* asymptomatic, normal lung function between exacerbations
* Brief exacerbations
* Nighttime symptoms <2/month
* FEV1 >80% predicted
* PEF diurnal variability <20%
There is no recommended classification scheme, because of difficulty in
applying one toward an individualized treatment approach. Instead, the
following characteristics of asthma that deserve consideration in assessment
of asthma severity are discussed:
* Symptoms – can be ranked on the basis of duration throughout the day or
night, as well as persistence throughout the week
* Restriction of activity – can be based on inability to work or attend
school, as well as how many days per week or month the restriction is
present
* Pulmonary function tests – can be used to assess severity of asthma based
on the predicted normal value or patient’s best attainable value
* Nonspecific bronchial hyperresponsiveness
* Hospitalization and emergency care visits
* Medication use
Long-Term Pharmacologic Treatment for Patients Older Than 5 Years (preferred
treatments are in bold type)
Stepwise Approach
Step 4: Severe Persistent
Daily medications:
* Anti-inflammatory; inhaled corticosteroid (high dose)
* Long-acting bronchodilator; either long-acting inhaled beta2-agonist,
sustained-release theophylline, or long-acting beta2-agonist tablets
and
* Corticosteroid tablets or syrup long term (2 mg/kg/day, generally do not
exceed 60 mg per day)
Step 3: Moderate Persistent
Daily medication:
* Anti-inflammatory: inhaled corticosteroid (medium dose)
or
* Inhaled corticosteroid (low-medium dose) and add a long-acting
bronchodilator, especially for nighttime symptoms: either long-acting
inhaled beta2-agonist, sustained release theophylline, or long-acting
beta2-agonist tablets
* If needed: anti-inflammatory inhaled corticosteroids (medium-high dose)
and
* Long-acting bronchodilator, especially for nighttime symptoms; either
long-acting inhaled beta2-agonist, sustained-release theophylline, or
long-acting beta2-agonist tablets
Step 2: Mild Persistent
One daily medication:
* Anti-inflammatory: either inhaled corticosteroid (low doses) or cromolyn
or nedocromil (usually begun in children)
* Sustained-release theophylline to serum concentration of 5-15 mcg/ml is an
alternative, but not preferred, therapy. Zafirlukast or zileuton may also be
considered for patients > 12 years of age, although their position in
therapy is not fully established.
Step 1: Mild Intermittent
No daily medication needed
Review treatment every 1-6 months; a gradual stepwise reduction in treatment
may be possible.
If control is not maintained, consider stepwise increase in treatment. First
review patient medication technique, adherence and environmental control
(avoidance of allergens or other factors that contribute to asthma
severity).
Based on NHLBI Expert Panel Report 2:
Stepwise Approach
Step 4: Severe Persistent
Daily medications:
* Anti-inflammatory; inhaled corticosteroid (high dose)
* Long-acting bronchodilator; either long-acting inhaled beta2-agonist,
sustained-release theophylline, or long-acting beta2-agonist tablets
and
* Oral corticosteroid tablets or syrup long term in lowest possible dose
(alternate or single daily dose after a 3- to 7-day burst)
Step 3: Moderate Persistent
Daily medication:
* Anti-inflammatory: inhaled corticosteroid (medium dose, 800-2000 mcg)
or
* Inhaled corticosteroid (low-medium dose, 800-2000 mcg) and add a
long-acting bronchodilator, especially for nighttime symptoms: either
long-acting inhaled beta2-agonist, sustained release theophylline, or
long-acting beta2-agonist tablets or syrup (long acting beta2-agonist may
provide more effective symptom control when added to low-medium dose steroid
compared to increasing the steroid dose)
* Consider adding anti-leukotriene, especially for aspirin-sensitive
patients and for preventing exercise-induced bronchospasm.
Step 2: Mild Persistent
One daily medication:
* Anti-inflammatory: either inhaled corticosteroid (low doses, 200-500mcg)
or cromolyn or nedocromil (usually begun in children)
* Sustained-release theophylline to serum concentration of 5-15 mcg/mL is an
alternative, but not preferred, therapy.
* If needed, increase inhaled corticosteroids. If inhaled corticosteroids
currently equal 500 mcg, increase the dosage to 800 mcg or add long-acting
bronchodilator (especially for nighttime symptoms): either long-acting
inhaled beta2-agonist, sustained-release theophylline, or long-acting oral
beta-agonist. Anti-leukotrienes may be considered, but their position in
therapy has not been fully established.
Step 1: Intermittent
No daily medication needed.
Review treatment every 3 to 6 months. If control is sustained for at least 3
months, a gradual stepwise reduction in treatment may be possible.
If control is not achieved, consider step-up. But first: review patient
medication technique, compliance, and environmental control (avoidance of
allergens or other trigger factors).
Based on NHLBI Expert Panel Report 2:
Stepwise Approach
Step 4: Severe Persistent
Daily medications:
* Anti-inflammatory; inhaled corticosteroid (high dose)
* Long-acting bronchodilator; either long-acting inhaled beta2-agonist,
sustained-release theophylline, or long-acting beta2-agonist tablets
and
* Corticosteroid tablets or syrup long term (2 mg/kg/day, generally do not
exceed 60 mg per day).
Step 3: Moderate Persistent
Daily medication:
* Anti-inflammatory: inhaled corticosteroid (medium dose)
or
* Inhaled corticosteroid (low-medium dose) and add a long-acting
bronchodilator, especially for nighttime symptoms: either long-acting
inhaled beta2-agonist, sustained release theophylline, or long-acting
beta2-agonist tablets.
* If needed: Anti-inflammatory inhaled corticosteroids (medium-high dose)
and
* Long-acting bronchodilator, especially for nighttime symptoms; either
long-acting inhaled beta2-agonist, sustained-release theophylline, or
long-acting beta2-agonist tablets.
Step 2: Mild Persistent
One daily medication:
* Anti-inflammatory: either inhaled corticosteroid (low doses) or cromolyn
or nedocromil (usually begun in children)
* Sustained-release theophylline to serum concentration of 5-15 mcg/ml is an
alternative, but not preferred, therapy. Zafirlukast or zileuton may also be
considered for patients > 12 years of age, although their position in
therapy is not fully established.
Step 1: Mild Intermittent
No daily medication needed
Review treatment every 1-6 months; a gradual stepwise reduction in treatment
may be possible.
If control is not maintained, consider stepwise increase in treatment. First
review patient medication technique, adherence and environmental control
(avoidance of allergens or other factors that contribute to asthma
severity).
Adapted from the NHLBI Expert Panel Report 2:
Stepwise Approach
Step 4: Severe Persistent
Daily medications:
* Anti-inflammatory: inhaled corticosteroids, 800-2000 mcg
and
* Long-acting bronchodilator; either long-acting inhaled beta2-agonist,
sustained-release theophylline, or long-acting beta2-agonist tablets
(inhaled beta2-agonists preferred due to lower toxicity)
and
* Corticosteroid tablets or syrup long term (2mg/kg/day, max 60 mg/day)
Step 3: Moderate Persistent
Daily medication:
* Either Anti-inflammatory: inhaled corticosteroid (medium dose)
or
* Inhaled corticosteroid (low-medium dose) and add a long-acting
bronchodilator, especially for nighttime symptoms: either long-acting
inhaled beta2-agonist, sustained-release theophylline, or long-acting
beta2-agonist tablets
* If needed: Anti-inflammatory: inhaled corticosteroids (medium-high dose)
and
* Add a long-acting bronchodilator, especially for nighttime symptoms either
long-acting inhaled beta2-agoinst, sustained-release theophylline, or
long-acting beta2-agonist tablets.
Step 2: Mild Persistent
Daily medications:
* Anti-inflammatory; either inhaled corticosteroid, 200-400 mcg, cromolyn
sodium, or nedocromil (children begin with trial of cromolyn or nedocromil).
* Sustained-release theophylline to serum concentration of 5-15 mcg/mL is an
alternative, but not preferred, therapy. Zafirlukast or zileuton may also be
considered for patients >12 years of age; Montelukast may be used in
patients >6 years of age, although their position in therapy is not fully
established.
Step 1: Mild Intermittent
* None needed
* Inhaled beta2-agonists, preferable to oral beta2 agonists in the treatment
of chronic asthma because they have a rapid onset of action, are generally
more effective than other routes of administration, and infrequently produce
adverse reactions.
* Inhaled beta2-agonists may be more effective when administered on an
as-needed basis rather than a regular basis in the treatment of many
patients with chronic asthma. If more than 8 inhalations per day (or
approximately one canister per month) are needed, the addition of cromolyn,
nedocromil, or inhaled corticosteroids should be considered.
* Sustained-release oral beta2-agonists may be indicated when long duration
of effect is desired or patient does not tolerate inhaled beta2-agonists.
* It is generally felt that inhaled corticosteroids should be used as
primary therapy in patients with moderate and severe chronic asthma.
* Long-term administration of systemic (oral) corticosteroids should be
considered only in patients with inadequate control of asthma despite
maximal use of other treatments. Prolonged use can generate significant side
effects.
* Cromolyn can be effective in many patients (alone or in conjunction with
bronchodilators) in preventing the symptoms of mild-to-moderate asthma.
* Nedocromil sodium is clinically useful in the preventive treatment of mild
and moderate asthma
* Nedocromil sodium is indicated primarily as a preventive drug in the
management of asthma-associated chronic inflammation. If used appropriately,
it is effective in improving symptom scores and reducing use of
bronchodilators and, in some cases, other concomitant medications such as
inhaled corticosteroids or cromolyn.
* Maintenance therapy with theophylline is effective in reducing the
frequency and severity of the symptoms of chronic asthma. It may be similar
in effectiveness to cromolyn or beta2-agonists, and long-acting preparations
allow for effective control of nocturnal symptoms.
* Inhaled anticholinergic agents such as ipratropium may be indicated in
patients in whom alternative agents have not been sufficiently effective,
are inappropriate because of other medical conditions, or have produced
unacceptable side effects.
* Adequate hydration is recommended for asthma patients, but overhydration
must be prevented by careful monitoring of fluid and electrolyte balance,
especially in infants, severely ill patients, and the elderly.
* Patients who do not respond to systemic corticosteroids may benefit from
alternatives such as troleandomycin, methotrexate, gold, and intravenous
g -globulin therapy. Certain of these regimens are contraindicated in some
patients and/or may be associated with significant adverse effects.
Quick-Relief Medication (Initial Treatment) for Acute Exacerbations in
Patients Older Than 5 Years
Same treatment for all patients (no step-wise approach)
* Short-acting bronchodilator: inhaled beta2-agonists as needed for
symptoms.
* Intensity of treatment will depend on severity of exacerbation
* Use of short-acting inhaled beta2-agonists on a daily basis, or increasing
use, indicates the need for additional long-term-control therapy.
* Anticholinergics (ipratropium bromide) are an alternative for patients
with intolerance to beta2-agonists. They are the treatment of choice in
patients with bronchospasm due to beta-blocker medication.
* Systemic corticosteroids are sometimes used for
moderate-to-severe-exacerbations to speed recovery and prevent recurrence of
exacerbations.
Exercise-Induced Asthma
* Short-acting inhaled beta2-agonists may prevent exercise-induced
bronchospasm if taken just prior to exercise.
* Cromolyn and nedocromil are also acceptable for preventing
exercise-induced bronchospasm.
Step 4: Severe Persistent
* Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms.
Step 3: Moderate Persistent
* Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms,
not to exceed 3-4 times in one day
Step 2: Mild Persistent
* Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms,
not to exceed 3-4 times in one day
Step 1: Intermittent
* Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms,
but less than once a week
* Intensity of treatment will depend on severity of exacerbation
Additional reliever medications:
* Systemic corticosteroids may be used for acute severe exacerbations to
prevent progression of the exacerbation, prevent early relapse, and reduce
morbidity of illness. Oral therapy for 3 to 10 days is preferred.
* Anticholinergics – Inhaled ipratropium bromide may have an additive effect
when nebulized together with short-acting beta2-agonist.
* Short acting oral beta2-agonists are appropriate for use in patients
unable to use inhaled medication.
Exercise-induced asthma
Inhaled beta2-agonist or cromoglycate or nedocromil before exercise or
exposure to allergen
Same treatment for all patients (no step-wise approach)
* Short-acting bronchodilator: inhaled beta2-agonists as needed for
symptoms.
* Intensity of treatment will depend on severity of exacerbation
Use of short-acting inhaled beta2-agonists on a daily basis, or increasing
use, indicates the need for additional long-term control therapy.
Step 4: Severe Persistent
* Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms
* Increasing use of beta2-agonist indicates the need for assessment and
increasing inflammatory therapy.
Step 3: Moderate Persistent
* Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms,
not to exceed 3-4 times in one day
* Increasing use of beta2-agonist indicates the need for assessment and
increasing inflammatory therapy.
Step 2: Mild Persistent
* Short-acting bronchodilator: inhaled beta2-agonist as needed for symptoms,
not to exceed 3-4 times in one day
Step 1: Mild Intermittent
* Short-acting bronchodilator: inhaled beta2-agonist as needed, but < 1/week
* Intensity of treatment will depend on severity of exacerbation
* Inhaled beta2-agonist, cromolyn, or nedocromil before exercise or exposure
to allergen
* With viral infection:
* Inhaled beta2-agonist q 4-6 hrs. up to 24 hrs. (longer with physician
consult) but no more than once every 6-8 wks
* Systemic corticosteroid if severe attack or history of severe attacks
with infection
Exercise-induced asthma
* The inhalation of a beta2-agonist 10 to 20 minutes before exercise is
often the most effective means of preventing exercise-induced asthma
exacerbations.
* Cromolyn inhalers and oral montelukast are also of demonstrated efficacy
for exercise-induce asthma.
* Inhaled beta2-agonists are generally the safest and most effective
treatment for acute asthma.
* Oral beta2-agonists should not be administered for the treatment of acute
severe asthma.
* Systemic corticosteroids should be considered in the management of acute
asthma when the patient does not respond readily to bronchodilators. Early
use of corticosteroids shortens the course of asthma, prevents relapses, and
reduces the need for hospitalization.
* The early use of corticosteroids is of particular importance in patients
who have a history consistent with fatality-prone asthma.
* Intravenous corticosteroids may be lifesaving in the treatment of severe
intractable asthma. After episodes of severe intractable asthma, complete
restoration of pulmonary function may require weeks of treatment. Therefore
after such events, corticosteroids should be continued at least until
symptoms are controlled and pulmonary function is restored.
* Inhaled anticholinergic medication may provide benefit when combined with
a beta2-agonist or other primary therapeutic agent in patients with acute
severe asthma.
* Nedocromil sodium is not indicated in the treatment of acute asthma
Exercise-induced asthma
* Inhaled beta2-agonists, when administered 15 to 30 minutes before
exercise, prevent exercise-induced bronchospasm in many patients. Inhaled
beta2-agonists are generally the agent of choice for this purpose.
* Cromolyn can be effective in preventing or diminishing exercise-induced
asthma when given 15 to 30 minutes before exercise.
Long-Term Pharmacologic Treatment for Infants and Young Children
Stepwise Approach
Step 4: Severe Persistent
Daily anti-inflammatory medication:
* Inhaled corticosteroid (high dose) with spacer/holding chamber and face
mask
* If needed, add systemic corticosteroids (2 mg/kg/day and reduce to lowest
daily or alternate day use that stabilizes symptoms)
Step 3: Moderate Persistent
Daily anti-inflammatory medication. Either:
* Inhaled corticosteroid (medium dose) with spacer/holding chamber and face
mask
or, once control is established:
* Inhaled corticosteroid (medium dose) and nedocromil
or
* Inhaled corticosteroid (medium dose) and long-acting bronchodilator
(theophylline)
Step 2: Mild persistent
Daily anti-inflammatory medication. Either:
* Cromolyn (nebulizer is preferred, or MDI) or nedocromil (MDI only)
* Infants and young children usually begin with a trial of cromolyn or
nedocromil
or
* Inhaled corticosteroid (low dose) with spacer/holding chamber and face
mask
Step 1: Mild Intermittent
No daily medication needed
Review treatment every 1-6 months; If control is sustained for 3 months, a
gradual stepwise reduction in treatment may be possible.
If control is not maintained, consider stepwise increase in treatment. First
review patient medication technique, adherence and environmental control
(avoidance of allergens or other factors that contribute to asthma
severity).
Stepwise Approach
Step 4: Severe Persistent
Daily medications:
* Nebulized budesonide (corticosteroid) > 1 mg twice a day
* If needed, add oral corticosteroids in lowest possible dose on an
alternate day, early morning schedule
Step 3: Moderate Persistent
Daily medication:
* Nebulized budesonide (corticosteroid) < 1 mg twice a day
Step 2: Mild persistent
Daily medication:
* Either inhaled corticosteroids or cromoglycate (use MDI with a spacer and
face mask or use a nebulizer)
Step 1: Intermittent
No controller medication needed
Review treatment every 3 to 6 months. If control is sustained for at least 3
months, a gradual stepwise reduction in treatment may be possible.
If control is not achieved, consider step-up. But first: review patient
medication technique, compliance, and environmental control (avoidance of
allergens or other trigger factors).
Outside scope of guideline
* MDIs can be used in infants and smaller children with appropriate spacer
devices and masks. Infants and smaller children need MDI doses equivalent to
adult doses because they inhale aerosols during tidal breathing without a
breath hold, thus decreasing retention time and effective drug delivery to
the lungs. Pediatric patients may be uncooperative with inhaled medication
delivery.
* Compressed air-driven, wet nebulizers are commonly available for home
administration of beta2-agonists, cromolyn sodium, ipratropium bromide, and
corticosteroids. Complete nebulization of medication is time consuming.
In general, treatment recommendations for infants and young children are not
specified.
Quick-Relief Medication (Initial Treatment) for Acute Exacerbations in
Infants and Young Children
Step 4: Severe Persistent
Medication:
Bronchodilator as needed for symptoms up to 3 times a day. Intensity of
treatment will depend upon severity of exacerbation. Either:
* Inhaled short-acting beta2-agonist by nebulizer or face mask and
spacer/holding chamber
or
* Oral beta2-agonist for symptoms
With viral respiratory infection
* Bronchodilator q 4-6 hours up to 24 hours (longer with physician consult)
but, in general, repeat no more than once every 6 weeks
* Consider systemic corticosteroid if current exacerbation is severe or
patient has history of previous severe exacerbations
Step 3: Moderate Persistent
Medication: See Step 4
Step 2: Mild Persistent
Medication: Bronchodilator as needed for symptoms <2 times a week. See Step
4 for more details.
Step 1: Mild Intermittent
Medication: See Step 2
Step 4: Severe Persistent
Medication:
* Inhaled short-acting bronchodilator: inhaled beta2-agonist or ipratropium
bromide or oral beta2-agonist as needed for symptoms, not to exceed 3-4
times in one day
Step 3: Moderate Persistent
Medication: See Step 4
Step 2: Mild Persistent
Medication: See Step 4
Step 1: Intermittent
Medication: Inhaled short-acting bronchodilator: inhaled beta2-agonist or
ipratropium bromide or oral beta2-agonist as needed for symptoms, but not
more than 3 times a week
Outside scope of guideline
Not stated
Medications:
* Use short-acting beta2-agonists as needed to relieve acute symptoms.
* Systemic corticosteroids are used in short bursts (usually days) for acute
severe asthma
Home and Emergency/ Hospital Management of Acute Exacerbations
Home Management
Assess Severity
* Measure PEF: Value <50% personal best or predicted suggests severe
exacerbation. Note other signs and symptoms.
Initial Treatment
* Inhaled short-acting beta2-agonist: up to three treatments of 2-4 puffs by
MDI at 20-minute intervals or single nebulizer treatment.
Good Response
Mild exacerbation
* PEF > 80% predicted or personal best
* No wheezing or shortness of breath
* Response to beta2-agonist sustained for 4 hours (may continue
beta2-agonist every 3-4 hours for 24-48 hours.
* For patients on inhaled corticosteroids, double dose for 7-10 days.
* Contact clinician for follow-up instructions.
Incomplete Response
Moderate Exacerbation
* PEF 50-80% predicted or personal best
* Persistent wheezing and shortness of breath
* Add oral corticosteroid
* Continue beta2-agonist
* Contact clinician urgently (this day) for instructions
Poor Response
Severe Exacerbation
* PEF <50% predicted or personal best
* Marked wheezing and shortness of breath
* Add oral corticosteroid
* Repeat beta2-agonist immediately
* If distress is severe and non-responsive, call your doctor and proceed to
emergency department; consider calling ambulance or 9-1-1.
Emergency Department or Hospital Management
Assess Severity
If impending or actual respiratory arrest:
* Intubation and mechanical ventilation with 100% O2
* Nebulized beta2-agonist and anticholinergic agent
* Intravenous corticosteroid
* Admit to hospital intensive care (see below)
If FEV1 or PEF >50% (moderate exacerbation):
* Inhaled beta2-agonist by metered-dose inhaler or nebulizer, up to three
doses in first hour
* Oxygen to achieve O2 saturation >90%
* Oral systemic corticosteroids if no immediate response or if patient
recently took oral systemic corticosteroid
If FEV1 or PEF <50% (severe exacerbation):
* Inhaled high-dose beta2-agonist and anticholinergic by nebulization every
20 minutes or continuously for 1 hour
* Oxygen to achieve O2 saturation >90%
* Oral systemic corticosteroid
For moderate or severe exacerbation, repeat assessment (symptoms, physical
examination, PEF, O2 saturation, other tests as needed)
Moderate Exacerbation (FEV1 or PEF 50-80% predicted/personal best. Physical
exam shows moderate symptoms.)
* Inhaled short-acting beta2-agonist every 60 minutes
* Systemic corticosteroid
* Continue treatment 1-3 hours, provided there is improvement
Severe Exacerbation (FEV1 or PEF <50% predicted/personal best. Physical exam
shows severe symptoms at rest, accessory muscle use, chest retraction.
History indicates high-risk. No improvement after initial treatment)
* Inhaled short-acting beta2-agonist, hourly or continuous + inhaled
anticholinergic agent
* Oxygen
* Systemic corticosteroid
Assess response in patients with moderate or severe exacerbation
Good Response
* FEV1 or PEF >70%
* Response sustained 60 minutes after last treatment
* No distress
* Physical exam normal
* Discharge home (continue treatment with inhaled beta2-agonist, continue
course of oral systemic corticosteroids, educate patient)
Incomplete Response
* FEV1 or PEF >50% but <70%
* Mild-to-moderate symptoms
* Either discharge home (continue treatment as described under good
response)
or
* Admit to hospital ward
* Inhaled beta2-agonist + inhaled anticholinergic
* Systemic (oral or intravenous) corticosteroid
* Oxygen
* Monitor FEV1 or PEF, O2 saturation, pulse
If patient improves, discharge home (continue treatment as described under
good response)
Poor Response
* FEV1 or PEF <50%
* PCO2 >42 mm Hg
* Physical exam shows severe symptoms, drowsiness, confusion
* Admit to hospital intensive care
* Inhaled beta2-agonist hourly or continuously + inhaled anticholinergic
* Intravenous corticosteroid
* Oxygen
* Possible intubation and mechanical ventilation
When patient stabilizes, admit to hospital ward (see above) and when patient
improves discharge home (see above).
Home Management
Assess Severity
* Measure PEF: Value < 80% personal best or predicted suggests exacerbation.
Clinical features include coughing, breathlessness, wheezing, chest
tightness, use of accessory muscles, and suprasternal retractions.
Initial Treatment
* Inhaled short-acting beta2-agonist: up to three treatments of 2-4 puffs at
20-minute intervals for the first hour.
Good Response
Mild episode
If PEF > 80% predicted or personal best, and response to beta2-agonist
sustained for 4 hours:
* May continue beta2-agonist every 3-4 hours for 24-48 hours.
* Contact clinician for follow-up instructions.
Incomplete Response
Moderate Episode
If PEF 60-80% predicted or personal best:
* Add oral corticosteroid
* Continue beta2-agonist
* Contact clinician urgently (this day) for instructions
Poor Response
Severe Episode
If PEF < 60% predicted or personal best:
* Add oral corticosteroid
* Repeat beta2-agonist immediately
* Immediate transport to hospital emergency department, consider ambulance.
Emergency Department or Hospital Management
Assess Severity
* History, physical examination, PEF or FEV1, oxygen saturation, arterial
blood gas of patient in extremis, and other tests as indicated
Initial Treatment
* Inhaled short-acting beta2-agonist, usually by nebulization, one dose
every 20 minutes for 1 hour
* Oxygen to achieve O2 saturation >90% (95% children)
* Systemic corticosteroids if no immediate response or if patient recently
took oral steroid, or if episode is severe
* Sedation is contraindicated in the treatment of exacerbations
Repeat assessment (symptoms, physical examination, PEF, O2 saturation, other
tests as needed)
Moderate Episode
* PEF 60-80% predicted/personal best
* Physical exam shows moderate symptoms, accessory muscle use
* Inhaled short-acting beta2-agonist every 60 minutes
* Consider corticosteroids
* Continue treatment 1-3 hours, provided there is improvement
Severe Episode
* PEF < 60% predicted/personal best
* Physical exam shows severe symptoms at rest, chest retraction
* History indicates high-risk
* No improvement after initial treatment
* Inhaled short-acting beta2-agonist (hourly or continuous) + inhaled
anticholinergic agent
* Oxygen
* Systemic corticosteroid
* Consider subcutaneous, intramuscular, or intravenous beta2-agonist
Assess response
Good Response
* PEF > 70%
* Response sustained 60 minutes after last treatment
* No distress
* Physical exam normal
If good response, discharge home (continue treatment with inhaled
beta2-agonist, continue course of oral systemic corticosteroids, educate
patient)
Incomplete Response
* FEV1 or PEF > 50% but < 70%
* History indicates high-risk
* Mild-to-moderate symptoms
* O2 saturation not improving
If incomplete response within 1-2 hours:
Admit to hospital ward
* Inhaled beta2-agonist + inhaled anticholinergic
* Systemic (oral or intravenous) corticosteroid
* Oxygen
* Monitor FEV1 or PEF, O2 saturation, pulse
Discharge home
* If PEF > 70% predicted or personal best and sustained on oral/inhaled
medication
* Continue treatment as described under good response.
Admit to intensive care (see below) if no improvement within 6-12 hours.
Poor Response
* PEF < 30%
* PCO2 > 45 mm Hg
* PO2 < 60 mm Hg
* History indicates high-risk
* Physical exam shows severe symptoms, drowsiness, confusion
If poor response within 1 hour:
Admit to hospital intensive care
* Inhaled beta2-agonist hourly or continuously + inhaled anticholinergic
* Intravenous corticosteroid
* Consider subcutaneous, intramuscular, or intravenous beta2-agonists
* Oxygen
* Consider intravenous aminophylline
* Possible intubation and mechanical ventilation
* Rehydration may be necessary for infants and young children
Home Management
Medications
* Inhaled beta2-agonist every 2-6 hours
* Initiate or increase anti-inflammatory medication (inhaled corticosteroids
or cromolyn/nedocromil). A course of oral corticosteroids should be given
serious consideration in patients with acute asthma exacerbation.
Emergency Management
Assess Severity
* Based on history and physical exam (vital signs, auscultation of chest,
use of accessory muscles, alertness, color, peak flow rate or FEV1
Initial Treatment
* Short acting nebulized beta2-agonist (Albuterol, Terbutaline) 2.5-5 mg q
20 min up to 3 doses.
* Alternatives:
* Epinephrine (Adult: 0.3-0.5 mg subq q 20 min up to 3 doses; Peds: 0.01
mg/kg subq q 20 min up to 3 doses)
* Terbutaline (Adult: 0.25 mg subq q 20 min up to 3 doses; Peds: 0.01 mg/kg
subq q 20 min up to 3 doses
Good Response
* Peak flow or FEV1 >70% predicted normal
* No wheezing on auscultation
* Transfer to home treatment
Incomplete Response
* Peak flow or FEV1 50-70% predicted normal
* Mild wheezing
* Consider hospitalization, particularly for high risk patients, if the
following conditions apply:
* Past history of sudden severe exacerbation
* Prior intubation for asthma
* Two or more hospitalizations for asthma in the past year
* Three or more emergency care visits for asthma within the past year
* Hospitalization or an emergency care visit for asthma within the past
month
* Use of > 2 canisters per month of inhaled short-acting beta2-agonists
* Current use of systemic corticosteroids or recent withdrawal from
systemic corticosteroids
* Difficulty perceiving airflow obstruction or its severity
* Comorbidity, as from cardiovascular disease or chronic obstructive
pulmonary disease
* Serious psychiatric disease or psychosocial problems
* Low socioeconomic status and urban residence
* Illicit drug use
* Sensitivity to Alternaria
Poor Response
* Peak flow or FEV1 < 50% predicted normal
* No improvement in respiratory distress
* Strongly consider hospitalization
* Continue inhaled beta-agonist q 60 minutes
* Consider starting prednisone (Adult: short course "burst" 40-60 mg/day as
single or 2 divided doses for 3 to 10 days; Child: short course "burst" 1-2
mg/kg day, maximum 60 mg/day for 3 to 10 days)
Home Management
Assess Severity: Home PEFR Monitoring Using the System of PEFR Zones
* Green Zone (80-100% of personal best) = "all clear" no change in therapy;
or if asymptomatic for a prolonged period, consider a reduction in
medication with continued monitoring.
* Yellow Zone (50-80% of personal best) = "caution" indicating suboptimal
control or early exacerbation.
* Red Zone (<50% of personal best) = "alert" indicating need for initiation
of more intense treatment, often involving a course of corticosteroids.
Treatment
* Follow a written action plan based on signs and symptoms (Asthma Treatment
Plan) .
* For rapid reversal of airflow obstruction, repetitive or continuous
administration of an inhaled beta2-agonist.
Emergency Management
* Assess severity of asthma
* For rapid reversal of airflow obstruction, repetitive or continuous
administration of an inhaled beta2-agonist.
* Early administration of systemic corticosteroids in patients with severe
attacks or in patients who fail to respond promptly and completely to an
inhaled beta2-agonist.
* Correction of hypoxemia by administrating supplemental oxygen.
* Close monitoring of the patients' conditions by serial measurement of lung
function.
This guideline does not differentiate home management from hospital
management in summary statements concerning severe acute intractable asthma.
The following recommendations seem to be most relevant to emergency
department or hospital management.
* Prompt recognition and intervention is needed
* History must establish features of current attack and the presence of
medical conditions that could complicate treatment of intractable asthma.
* Oxygen administration is indicated
* A PaCO2 of 40 torr may be a sign of severe asthma
* Early in treatment, parenteral and sympathomimetic agents may be indicated
for patients who are not ventilating well enough to deliver adequate amounts
of nebulized drug to the lower respiratory tract.
* Patients with severe acute intractable asthma will require corticosteroid
administration. Early use is recommended because a lag time of several hours
may occur before any clinical effect is noted.
* If aminophylline theophylline is used, it is especially important to
monitor blood levels and cardiopulmonary function.
* Overhydration may increase vascular hydrostatic pressure and decrease
plasma colloid pressure, increasing the possibility of pulmonary edema,
which is also favored by large negative peak inspiratory intrapleural
pressures associated with acute asthma.
* The need for mechanical ventilation should be anticipated.
* Intubation may be difficult and, if possible, should be done by an
individual experienced in such procedures.
Guidelines for Referral to an Asthma Specialist
Referral for consultation or care to a specialist in asthma care is
recommended when:
* Patient has had a life-threatening asthma exacerbation
* Patient is not meeting the goals of asthma therapy
* Signs and symptoms are atypical or there are problems in differential
diagnosis
* Other conditions complicate asthma or its diagnosis (e.g., sinusitis,
nasal polyps, aspergillosis, severe rhinitis, vocal cord dysfunction,
gastroesophageal reflux, chronic obstructive pulmonary disease).
* Additional diagnostic testing is indicated (e.g., allergy skin testing,
rhinoscopy, complete pulmonary function studies, provocative challenge,
bronchoscopy)
* Patient requires additional education and guidance on complications of
therapy, problems with adherence, or allergen avoidance
* Patient is being considered for immunotherapy
* Patient has severe persistent asthma, requiring step 4 care (referral may
be considered for patients requiring step 3 care)
* Patient requires continuous oral corticosteroid therapy or high-dose
inhaled corticosteroids or has required more than two bursts of oral
corticosteroids in 1 year
* Patient is under age 3 and requires step 3 or 4 care. When patient is
under age 3 and requires step 2 care or initiation of daily long-term
therapy, referral should be considered.
* Patient requires confirmation of a history that suggests that an
occupational or environmental inhalant or ingested substance is provoking or
contributing to asthma. Depending on the complexities of diagnosis,
treatment, or the intervention required in the work environment, it may be
appropriate in some cases for the specialist to manage the patient over a
period of time or comanage with the primary care provider
Although most asthma care should be provided at the primary care level,
consultation with an asthma specialist may be appropriate for those patients
who do not respond favorably to treatment. More specific reasons for
referral are not provided.
Specialty consultation is recommended for:
* Adults with severe asthma; also consider referral for those with moderate
asthma.
* Children with moderate to severe asthma; also consider referral for those
with mild persistent asthma.
Specialty consultation is also recommended when:
* Patient has poorly controlled or complex asthma including previous
life-threatening asthma exacerbations, or asthma exacerbations requiring
more than 2 bursts of oral corticosteroids in one year, or asthma
complicated by other medical or psychosocial conditions.
* Patient needs additional diagnostic evaluations and/or testing (e.g.,
allergy skin testing, bronchoprovocation). Testing is recommended for
patients with persistent asthma who are exposed to perennial indoor
antigens.
* Patient needs evaluation and treatment of allergy for occupational asthma,
environmental counseling, or immunotherapy.
* Patients need additional or intensive asthma education not otherwise
available
Some situations may warrant a referral or consultation with a specialist in
asthma care. These include cases with:
* Diagnosis in doubt. Signs and symptoms are atypical, or there are problems
in differential diagnosis.
* Additional diagnostic testing indicated. (e.g., skin testing, provocative
challenge, rhinoscopy, bronchoscopy, complete pulmonary function studies).
* Inadequate response to asthma therapy. For example, patients considered to
have mild or moderate asthma who are hospitalized for exacerbations, or who
make more than two emergency room visits a year.
* Severe refractory asthma, particularly if the clinician cares for very few
such patients.
* Other chronic pulmonary disease complicating management.
* Immunotherapy or other complications of therapy.
Special cases meriting consultation with health care team members include:
* Occupational-related asthma. In this situation either the primary care
physician or the consultant may benefit from consultation with a physician
expert in occupational medicine.
* Patients who chronically do not adhere to their treatment regimen may
benefit from an intensive asthma health behavior/health education
intervention.
* Significant psychiatric or family problems interfering with treatment.
Additional consideration should be given to consultation or referral in the
following situations:
* When the cost of care for a patient becomes excessive.
* When patient disability is substantial despite adequate therapy.
A number of reasons exist for recommending that a patient consult an asthma
specialist early in the treatment program. These include:
* Instability of the patient’s asthma; uncontrolled asthma may be associated
with widely variable pulmonary functions and possibly high morbidity and
mortality. Early intervention may prevent these events. A long-term
treatment plan should be developed.
* A patient response to treatment that is limited, incomplete, or very slow
and poor control interferes with the patient’s quality of life.
* In spite of regular use of anti-inflammatory medications, the patient must
use an inhaled beta2-agonist frequently, exclusive of its use in
exercise-induced asthma
* If there is a need for frequent adjustments of therapy because of unstable
asthma
* For identification of allergens or other environmental factors that may be
causing the patient’s disease
* When allergen immunotherapy is a consideration.
* When the patient and primary caregiver need intensive education in the
role of allergens and other environmental factors
* When family dynamics interfere with patient care and/or there is a need
for further family education about asthma
* When a patient has a chronic cough, refractory to usual therapy
* When coexisting illnesses and/or their treatment complicate the management
of asthma
* When the patient has recurrent absences from school or work due to asthma.
* When the patient experiences continuing nocturnal episodes of asthma
* When the patient is unable to participate in normal daily activities and
sports because of limited exercise ability despite use of inhaled
beta2-agonists before exercise
* When the patient requires multiple medications on a long-term basis
* When frequent bursts of oral corticosteroids or daily oral corticosteroids
are required
* When the patient exhibits excessive lability of pulmonary function, such
as highly variable peak flow rates
* When the diagnosis of asthma is in doubt
* When there is concern about side effects that have occurred or may occur,
for example, with use of oral or orally inhaled corticosteroids in children
* When preventive measures need to be considered for the high-risk,
predisposed infant with a family history of asthma or atopy
* Sudden severe attacks of asthma
* Hospitalization of the patient for asthma
* Severe episodes of asthma resulting in loss of consciousness
* Seizures, near-death episodes, or respiratory failure requiring artificial
respiration
* When emergency visits are required to control the patient’s asthma
* When the patient asks for a consultation
Patient Education
Patient education is described in the context of the stepwise plan based on
asthma severity:
Step 1: Mild Intermittent
* Teach basic facts about asthma
* Teach inhaler/spacer/holding chamber technique
* Discuss roles of medications
* Develop self-management plan
* Develop action plan for when and how to take rescue actions, especially
for patients with a history of severe exacerbations
* Discuss appropriate environmental control measures to avoid exposure to
known allergens and irritants
Step 2: Mild Persistent
Step 1 actions plus:
* Teach self-monitoring
* Refer to group education if available
* Review and update self-management plan
Step 3: Moderate Persistent
Steps 1 and 2 actions
Step 4: Severe Persistent
Steps 2 and 3 actions plus:
* Refer to individual education/counseling
Patients should be actively involved in managing their asthma to prevent
problems and can live productive, physically active lives. Asthma patients
can learn to:
* Take medications correctly
* Understand the difference between "quick-relief" and "long-term
preventive" medications
* Avoid triggers
* Monitor their status using symptoms and, if available, PEF indicators
* Recognize signs that asthma is worsening and take action
* Seek medical help as appropriate.
Patients and their health care teams should prepare a written asthma
management plan that is not only medically appropriate but also practical.
Such an asthma management plan should cover:
* Prevention steps for long-term control
* What daily medication to take
* What asthma triggers to avoid
* Action steps to stop attacks
* How to recognize worsening asthma. List indicators such as increasing
cough, chest tightness, wheeze, difficult breathing, sleep disturbance, or
PEF measurements below personal best despite increased use of medications.
* How to treat worsening asthma. List the names and doses of quick-relief
bronchodilator medications and steroid tablets and when to use them.
* How and when to seek medical attention. List indicators such as feeling
panicky, an attack with sudden onset, shortness of breath while resting or
speaking a few words, PEF readings below a specified level, or a history of
severe attacks. List the name, location, and telephone number of the
physician's office or clinic.
Patient education is essential for successful management of asthma. It
should begin at the time of diagnosis and be ongoing. The following patient
education is recommended:
* Basic facts about asthma
* Role of medications (quick relief vs. long-term controller medications)
* Skills (use of inhalers, peak flow monitoring, monitoring of symptoms)
* Environmental control measures (to avoid asthma triggers)
* When and how to take actions (responding to changes in asthma severity). A
written action plan should be offered to patients.
* Emphasize need for regular follow-up visits
Patient education is described in the context of the stepwise plan based on
asthma severity:
Step 1: Mild Intermittent
* Teach basic facts about asthma
* Teach inhaler/spacer technique
* Discuss roles of medications
* Develop self-management plan
* Develop action plan for when and how to take rescue actions
* Discuss appropriate environmental control measures to avoid exposure to
known triggers
Step 2: Mild Persistent
Step 1 actions plus:
* Teach self-monitoring
* Refer to group education if available
* Review and update self-management plan
Step 3: Moderate Persistent
Same as Step 2 actions
Step 4: Severe Persistent
Step 2 and 3 actions plus:
* Refer to individual education/ counseling
Cooperative management through education involves the following:
* Educating asthmatic patients, parents, and family about asthma and
treatment methods is essential for effective control of asthma
* Educational programs have been successful in increasing patient
understanding and decreasing morbidity.
* Patients should be educated to effectively monitor their asthmatic status
and know how to respond to changes
* Patients should learn how to effectively use inhalers
* Physicians must recognize and resolve patient concerns by increasing
patient confidence in the management approach.
* Asthma education requires an understanding of basic concepts related to
pathophysiology and treatment but must also be individualized for each
patient.
* Education can be important for improving patient compliance with the
treatment program.
BENEFITS OF TREATMENT
NHLBI (1997)
WHO/NHLBI (1998)
ICSI (1999)
UMHS (2000)
AAAAI, ACAAI, JCAAI (1995)
Potential Benefits
Effective asthma management, reflected by the following components:
* Use of objective measures of lung function to assess the severity of
asthma and to monitor the course of therapy
* Environmental control measures to avoid or eliminate factors that
precipitate asthma symptoms or exacerbations
* Comprehensive pharmacologic therapy for long-term management designed to
reverse and prevent the airway inflammation characteristic of asthma as well
as pharmacologic therapy to manage asthma exacerbations
* Patient education that fosters a partnership among the patient, his or her
family, and clinicians
* Primary prevention methods have considerable potential to prevent the
development of asthma.
* Effective management of asthma results in benefits including achievement
and maintenance of control of symptoms, prevention of asthma exacerbations;
maintenance of pulmonary function as close to normal levels as possible;
maintenance of normal activity levels, including exercise; avoidance of
adverse effects from asthma medications; prevention of the development of
irreversible airflow limitation; and prevention of asthma mortality.
Additional benefits include decreased health care costs, increased
productivity, increased participation in family life and a decrease of
chronic disability and premature death.
* Patient education increases the likelihood of lifelong success in treating
asthma
* Accurate diagnosis and assessment of asthma severity
* Effective long-term control of persistent asthma through the use of
anti-inflammatory medication
* Effective partnership of patients and parents with health care
professionals through education and use of written action plans
* Patients with asthma gain symptomatic relief and functional benefit from
several classes of anti-inflammatory and bronchodilator medications and from
education in self-management of the disease.
* Prevention of long-term effects of airway inflammation
* Improved patient compliance to therapeutic regimen by participating in
patient education program
* Reduction of the number of emergency room visits and hospitalizations due
to the exacerbation of asthma symptoms
* Improved quality of life
* Prevention of morbidity and mortality due to asthma
* Improved tolerance of physical activity/exercise
* Minimization of time lost from work, school, daily activities
* Improved self-image with control of asthma symptoms
Subgroup(s) Most Likely to Benefit
Not stated
Infants: Reducing exposure to indoor allergens, particularly domestic mites,
is one of the most promising measures for future preventive action,
especially for infants. Avoidance of passive smoking is also very likely to
be beneficial.
Not stated
Not stated
Persistent asthmatics
POTENTIAL HARMS OF TREATMENT
NHLBI (1997)
WHO, NHLBI (1998)
ICSI (1999)
UMHS (2000)
AAAAI, ACAAI, JCAAI (1995)
Potential Harms
Side effects of medications:
Long-Term Controller Medications
Inhaled Corticosteroids
* Cough, dysphonia, oral thrush
* In high doses, systemic effects may occur, such as potential impairment of
a child's linear growth, skin thinning and easy bruising, risk of
osteoporosis and fracture with long-term use
Systemic Corticosteroids
* Short-term use: reversible abnormalities in glucose metabolism, fluid
retention, weight gain, mood alteration, hypertension, peptic ulcer, and
rarely aseptic necrosis of femur.
* Long-term use: adrenal axis suppression, growth suppression, dermal
thinning, hypertension, diabetes, Cushing’s syndrome, cataracts, muscle
weakness, and, in rare instances, impaired immune function.
* Coexisting conditions such as herpes virus infections, varicella,
tuberculosis, hypertension, peptic ulcer, and Strongyloides could be
worsened by systemic corticosteroids
Long-Acting Beta2-Agonists
* Tachycardia, skeletal muscle tremor, hypokalemia, prolongation of QTc
interval in overdose
Methylxanthines (Theophylline)
* Dose-related acute toxicities include tachycardia, nausea and vomiting,
tachyarrhythmias (SVT), central nervous system stimulation, headache,
seizures, hematemesis, hyperglycemia, and hypokalemia
* Adverse effects at usual therapeutic doses include insomnia, gastric
upset, aggravation of ulcer or reflux, increase in hyperactivity in some
children, difficulty in urination in elderly males with prostatism.
Leukotriene Modifiers
* Zileuton tablets have been associated with elevation of liver enzymes.
Limited case reports of reversible hepatitis and hyperbilirubinemia.
Nedocromil
* Fifteen to 20% of patients complain of unpleasant taste.
Quick-Relief Medications
Short-Acting Inhaled Beta2-Agonists
* Tachycardia, skeletal muscle tremor, hypokalemia, increased lactic acid,
headache, hyperglycemia. Patients with preexisting cardiovascular disease
(especially the elderly) may have adverse cardiovascular reactions.
Anticholinergics (ipratropium bromide)
* Drying of mouth and respiratory secretions, increased wheezing in some
individuals, blurred vision if sprayed in eyes.
Systemic Corticosteroids
* See under long-term controller medications
Allergen Immunotherapy
* Some patients (particularly those with poorly-controlled asthma) may
experience adverse or life-threatening reaction (e.g., bronchoconstriction)
Side effects of medications:
Controller Medications
* Inhaled corticosteroids: Local adverse effects from inhaled
corticosteroids include oropharyngeal candidiasis, dysphonia, and occasional
coughing from upper airway irritation.
* Sodium cromoglycate: Minimal side effects include cough upon inhalation.
* Systemic corticosteroids: Long-term use may produce systemic effects
including osteoporosis, arterial hypertension, diabetes,
hypothalamic-pituitary-adrenal axis suppression, cataracts, obesity, skin
thinning leading to cutaneous striae and easy bruisability, and muscle
weakness.
* Theophylline: Sustained-release theophylline has the potential for
significant adverse effects. The signs and symptoms of theophylline
intoxication involve many different organ systems. Gastrointestinal
symptoms, nausea, and vomiting are the most common early events.
Theophylline intoxication can result in seizures and even death.
Cardiopulmonary effects include tachycardia, arrhythmias, and occasionally,
stimulation of the respiratory center.
* Beta2-agonists: Long-acting inhaled beta2-agonists are associated with
systemic adverse effects (although fewer than oral therapy) such as
cardiovascular stimulation, skeletal muscle tremor, anxiety, pyrosis,
headache, and hypokalemia. Long-acting oral beta2-agonists may cause
cardiovascular stimulation, anxiety, pyrosis, and skeletal tremor.
* Ketotifen: The most frequent side effect is sedation, especially in the
initial treatment period and in adults. Ketotifen may also cause weight
gain.
* Anti-leukotrienes: Elevation of liver enzymes is possible. Limited case
reports of reversible hepatitis and hyperbilirubinemia exist.
Reliever Medications:
* Beta2-agonists: Short-acting inhaled beta2-agonists may cause systemic
adverse effects (although fewer than oral therapy) such as cardiovascular
stimulation, skeletal muscle tremor, and hypokalemia. Oral beta2-agonists
are associated with the potential for cardiovascular stimulation, skeletal
muscle tremor, hypokalemia, and irritability.
* Systemic corticosteroids: Potential side effects include systemic adverse
effects such as cardiovascular stimulation, skeletal muscle tremor,
headache, irritability, and hypokalemia; reversible abnormalities in glucose
metabolism; increased appetite; fluid retention; weight gain; rounding of
the face; mood alteration; hypertension; peptic ulcer; and aseptic necrosis
of the femur.
* Anticholinergics: Inhalation of ipratropium or oxitropium can cause a
dryness of the mouth and a bad taste.
* Short-acting theophylline: Theophylline has the potential for significant
adverse effects. The signs and symptoms of theophylline intoxication involve
many different organ systems. Gastrointestinal symptoms, nausea, and
vomiting are the most common early events. Theophylline intoxication can
result in seizures and even death. Cardiopulmonary effects include
tachycardia, arrhythmias, and occasionally, stimulation of the respiratory
center.
* Epinephrine/adrenaline: Epinephrine/adrenaline injection is associated
with similar, but more significant effects than beta2-agonists. In addition,
convulsions, chills, fever, and hallucinations may occur.
Nontraditional Methods of Healing
* Acupuncture has been associated with hepatitis B, bilateral pneumothorax,
and burns.
* Homeopathy treatments may contain potent pharmacological agents that may
lead to adverse effects.
* Herbal medicines are potentially dangerous and toxic.
Allergen Immunotherapy
* Adverse or fatal reactions can occur, particularly in patients with severe
airflow obstruction
Side effects of medications:
Risk of adverse effects is associated with asthma pharmacotherapy. Specific
adverse effects are not described.
Side effects associated with pharmacotherapy:
1. Anti-inflammatory agents
* Inhaled corticosteroids: There is a dose-dependent reduction of
short-term growth with the use of conventional doses of beclomethasone
dipropionate. Inhaled corticosteroids in doses as high as 800 mcg/d exert
much less short-term growth suppression than low-dose oral corticosteroids.
High doses of inhaled corticosteroids may cause systemic side effects
(though to a much lesser extent than oral steroids will). Risk of side
effects with high-dose inhaled steroids can be minimized by having the
patient rinse his/her mouth immediately after inhalation and before
swallowing and by using a spacer device.
* Systemic corticosteroids: Chronic systemic corticosteroid therapy may be
associated with obesity, moon faces, supraclavicular and nuchal fat pads,
striae, easy bruisability, weakness, hypertension, and glucose intolerance.
Long-term (>2 weeks) corticosteroid therapy may cause suppression of the
hypothalamic-pituitary-adrenal axis. Full recovery of the axis can take up
to 12 months depending on the dose, frequency, and duration of antecedent
therapy. Adrenal insufficiency can evolve into acute adrenal crisis
precipitated by severe infection, trauma, or surgery. Systemic
corticosteroid therapy can cause osteopenia.
* Leukotriene modifier agents: The U.S. Food and Drug Administration (FDA)
mandates monitoring hepatic enzymes with use of the 5-lipoxygenase-inhibitor
zileuton. Churg-Strauss Vasculitis has rarely been reported in association
with montelukast or zafirlukast in patients tapering chronic systemic
corticosteroid.
2. Inhaled, short-acting beta2-agonists: Several epidemiologic studies have
found an association between excess use of beta2-agonist inhalers and asthma
mortality. A causal relationship has not been demonstrated, and it is
possible that beta2-agonists represent a mere marker for the severity of
disease, being more frequently prescribed for patients with life-threatening
asthma. If beta2-agonists do have a causative role, it may be an indirect
one, such as delaying presentation until airway obstruction is more severe.
Drug interactions:
Leukotriene modifier agents: Both zafirlukast and zileuton can potentiate
warfarin and theophylline as well as interact with several other
medications.
Side effects of medications:
Beta2-Agonists
* Cardiovascular effects (increased blood pressure and pulse rate,
arrhythmias, myocardial necrosis). Elderly patients or patients with
underlying cardiac disease must be closely monitored.
* Tremor and central nervous system effects (headache and irritability).
* Paradoxical bronchospasm may occur in some patients.
* Hypoxemia
* Metabolic effects: hypokalemia
* Increased bronchial hyperresponsiveness
Systemic Corticosteroids
* Long-term use associated with risk of adrenal suppression, central nervous
system complications (pseudotumor cerebri, psychiatric reactions), posterior
subcapsular cataracts, glaucoma, myopathy, osteoporosis, aseptic necrosis of
bone, nephrocalcinosis, nephrolithiasis, hypertension, aggravation of
congestive heart failure, growth retardation, hyperglycemia (steroid
diabetes), hypercalciuria, hyperlipidemia, and various cutaneous and
subcutaneous manifestations.
* Fatal varicella has been reported with high-dose therapy. Patients exposed
to chickenpox or measles should be carefully monitored.
Theophylline
* At doses above 20 mcg/ml, side effects can include nausea, vomiting,
diarrhea, headache, nervousness, tachycardia, insomnia, cardiac arrhythmias,
and seizures which can result in permanent brain damage or death. Side
effects can occur at lower doses in infants and older patients with
sustained fever or influenza, or after medications which decrease the rate
of theophylline metabolism.
Cromolyn
* Inhaled cromolyn has the potential, in rare instances, to produce
life-threatening bronchospasm associated with acute cough, chest tightness
and/or other symptoms
Nedocromil
* Occasional headaches, nausea, vomiting, dizziness, and a bad taste.
Allergen immunotherapy
* In rare instances, allergen immunotherapy can produce a life-threatening
reaction. Fatalities have occasionally been reported.
Subgroup(s) Most Likely to be Harmed
* Children taking systemic corticosteroids are vulnerable to growth
suppression
* Patients with coexisting conditions are more vulnerable to adverse
effects of systemic corticosteroids
* Elderly patients or those with underlying cardiovascular disease are
particularly vulnerable to side effects from beta2-agonists
* Children taking inhaled corticosteroids may experience minor
growth delay or suppression (average 1 cm).
* Patients with comorbid conditions (tuberculosis, parasitic
infections, osteoporosis, glaucoma, hypertension, diabetes, severe
depression, or peptic ulcers) may experience side effects with the use of
systemic corticosteroids. Some patients exposed to herpes virus have
developed fatal infections while using systemic corticosteroids, even short
bursts.
* Patients taking a combination of beta2-agonists and theophylline have
experienced adverse cardiovascular reactions.
Not stated
1. Anti-inflammatory agents
* Long-term linear growth does not appear to be affected by moderate doses
(400-800 mcg/day) of inhaled corticosteroids, except in prepubertal males.
* Children may exhibit growth failure from chronic systemic corticosteroid
therapy.
* In pregnancy, both leukotriene receptor antagonists zafirlukast and
montelukast are category B while zileuton is category C.
2. Beta2-agonists:
* Safety and efficacy of the inhaled, long-acting beta2-agonist salmeterol
has not been established in children less than 12 years of age.
* Children younger than two years of age or at puberty are
particularly vulnerable to steroid-induced growth suppression when taking
systemic corticosteroids.
* Patients exposed to chickenpox or measles should be carefully monitored
when taking systemic corticosteroids.
* Elderly patients or those with underlying cardiac disease should be
carefully monitored when taking beta2-agonists.
GUIDELINE CONTENT COMPARISON
NHLBI, WHO/NHLBI, ICSI, UMHS and AAAAI/ACAAI/JCAAI present recommendations
for the diagnosis and treatment of asthma. Four of these guidelines are
interrelated. NHLBI extended its original recommendations in a global
initiative with WHO, resulting in the NHLBI/WHO guideline. ICSI also cites
the original NHLBI guideline with regard to several aspects of treatment,
discussed in greater detail below. UMHS adapted their guideline from the
original NHLBI guideline.
There are several points of comparison where one or two guidelines lack
information that appears in three or four of the other guidelines. ICSI does
not present recommendations concerning allergen immunotherapy, prevention of
exercise-induced asthma, or measures to avoid asthma triggers. ICSI also
does not provide specific information concerning adverse effects of
pharmacotherapy. Furthermore, ICSI does not formulate recommendations
concerning pharmacologic treatment of infants and young children (under 5
years of age).. Although UMHS provides broad recommendations concerning
long-term pharmacologic treatment of infants and young children (under 5
years of age), they do not formulate recommendations for pharmacologic
treatment of acute exacerbations in this age group. NHLBI, WHO/NHLBI, ICSI
clearly differentiate home management of acute exacerbations of asthma from
emergency room/hospital management of acute exacerbations, while UMHS and
AAAAI/ACAAI/JCAAI do not clearly differentiate. In discussions of
pharmacologic therapy, the AAAAI/ACAAI/JCAAI guideline is the only guideline
that does not discuss leukotriene modifiers (e.g., zileuton).). Zileuton did
not receive FDA approval until 1996, which explains its absence in the
original guideline. Leukotriene antagonists are included in an algorithm
that complements and updates the guideline, issued by AAAAI/ACAAI/JCAAI in
1998 (Ann Allergy Asthma Immunol 1998;81:415-420). The AAAAI/ACAAI/JCAAI
guideline contains the most comprehensive list of factors that can influence
the severity of asthma. The NHLBI guideline is the only guideline to compare
different aerosol delivery devices in terms of technique and therapeutic
issues.
Areas of Agreement
There are few areas of agreement that encompass all guidelines. However, the
four guidelines are in general agreement regarding preferred long-term
controller medications and quick-relief medications. In addition, all
guidelines agree on the value of patient education in the therapeutic
process and the types of education that should be provided. The NHLBI
guideline has integrated patient education into its model for stepwise
treatment based on asthma severity.
Areas of agreement occur more often among four out of five guidelines. All
guidelines, except the AAAAI/ACAAI/JCAAI guideline, generally agree on a
classification scheme for asthma severity and a consequent stepwise approach
to asthma treatment. As mentioned earlier, these recommendations originated
in the NHLBI guideline and were subsequently adopted in the ICSI, UMHS and
WHO/NHLBI guidelines. The contrasting viewpoints in the AAAAI/ACAAI/JCAAI
guideline will be discussed under Areas of Differences, below. The four
guidelines that report on prevention of exercise-induced asthma, NHLBI,
WHO/NHLBI, UMHS, and AAAAI/ACAAI/JCAAI, generally agree on the appropriate
medications to be used (although the AAAAI/ACAAI/JCAAI guideline does not
mention nedocromil). The guidelines that report side effects of medications
generally agree on the types of side effects that may occur with a given
medication, although the range of reported side effects differs slightly
among these documents. These guidelines also agree on the subgroups of
patients most vulnerable to adverse effects from pharmacotherapy (children,
the elderly, and patients with comorbidities). The same four guidelines are
in overall agreement concerning measures to avoid asthma triggers, although
the joint guideline issued by AAAAI/ACAAI/JCAAI contains less detail in
their recommendations compared to the other documents.
Areas of Differences
The discussion of areas of difference among the guidelines will focus
primarily on substantial differences in philosophy and implementation of
therapeutic approaches. These guidelines contain a number of minor
differences that would require an inordinate amount of space to enumerate
(e.g., PEF >70% vs. PEF >80% in defining a good treatment response). In most
cases, the overall treatment plans have more similarities than differences;
therefore, noting minor differences among studies creates a false
impression. The interested reader can identify relatively minor differences
among guidelines in the comparison table.
Most of the major differences in recommendations among these guidelines
appear when contrasting recommendations from the joint guideline issued by
AAAAI/ACAAI/JCAAI with those of the other guidelines. This is mainly because
the WHO/NHLBI, UMHS, and ICSI guidelines were at least partially derived
from the NHLBI guideline. The most significant difference appears when
comparing long-term therapeutic approaches. Whereas the other four
guidelines present a stepwise plan for pharmacologic treatment based on
assessment of asthma severity, the AAAAI/ACAAI/JCAAI guideline states that
classifications of asthma severity are often difficult to apply toward an
individualized treatment approach. For example, patients may not fit neatly
into a specific category, with the results of pulmonary function tests
placing them in one category and nocturnal symptoms assigning them to
another. Therefore, a classification scheme is not adopted by
AAAAI/ACAAI/JCAAI; instead, characteristics of asthma that deserve
consideration in assessment of asthma severity are discussed. The
individualized treatment philosophy expressed by AAAAI/ACAAI/JCAAI
translates into a treatment plan that is not as rigidly defined as what
appears in the other guidelines. This may also reflect disagreement among
asthma specialists concerning what is the best widely applicable treatment
program.
Another major difference occurs in the comparison of home and hospital
treatments for acute asthma exacerbations. Unlike the other guidelines, the
AAAAI/ACAAI/JCAAI and UMHS guidelines do not clearly differentiate home
treatment from hospital treatment, and the recommendations of
AAAAI/ACAAI/JCAAI seem to be based on emergency department/hospital
treatment. Neither guideline provides any definition of response to therapy
(e.g. good, incomplete, poor) while the other guidelines provide detailed
definitions. In general, the other three guidelines provide a comprehensive
treatment plan for acute exacerbations while the AAAAI/ACAAI/JCAAI guideline
provides general suggestions and important issues to be considered. Among
the guidelines with comprehensive plans, the ICSI guideline provides a
less-detailed plan for home management of exacerbations than the other two
guidelines.
Among the four guidelines providing recommendations that include infants and
young children, the AAAAI/ACAAI/JCAAI and UMHS guidelines do not provide
specific recommendations, and UMHS does not provide any recommendations for
managing acute exacerbations in this age group. Instead, the recommendations
include children of all age groups with asthma, with a few specific
notations concerning infants and young children. The NHLBI and WHO/NHLBI
guidelines provide specific treatment recommendations for infants and young
children as one group and older children/adults as another group.
In the context of acute asthma management, the ICSI guideline is the only
guideline to specifically state that critically ill patients are beyond the
scope of the guideline. UMHS does not reference critically ill patients..
The other guidelines all provide some reference to treatment for critically
ill patients, although they devote less space to this particular subgroup of
patients. Among the four guidelines that discuss allergen immunotherapy, the
AAAAI/ACAAI/JCAAI guideline does not specify the circumstances under which a
patient should receive such therapy. However, this group has published a
separate parameter focusing specifically on allergen immunotherapy (Practice
parameters for allergen immunotherapy. J Allergy Clin Immunol 1996 Dec;98[6
Pt 1]:1001-11). The WHO/NHLBI guideline provides the most specific
statements concerning when immunotherapy should be considered and issues
that should be evaluated before initiating therapy. UMHS suggests that
allergen immunotherapy is not indicated for most patients, but that it may
have a place in the management of a subset of selected patients with
extrinsic (allergic) asthma.
Although the WHO/NHLBI guideline makes a general statement concerning when
to refer a patient to an asthma specialist, it is the only guideline that
does not contain a list of specific recommendations concerning this issue.
This may reflect the global perspective of this document; the other four
guidelines were issued exclusively by organizations based in the United
States. The WHO/NHLBI guideline also states that most asthma care should be
provided at the primary care level. Although not specifically stated, the
implication in the WHO/NHLBI guideline is that in some countries, asthma
specialists are unlikely to play a significant role in asthma management.
The other guidelines are in general agreement concerning the conditions
under which a specialist consult is desirable, although the joint guideline
produced by AAAAI, ACAAI, and JCAAI contains the most comprehensive list of
conditions.
_____
This Synthesis was prepared by ECRI on June 12, 2000. It was reviewed by the
guideline developers as of August 14, 2000.The UMHS guideline was added to
this Synthesis by ECRI on December 6, 2000. It has been reviewed by UMHS as
of March 8, 2001.
Internet citation: National Guideline Clearinghouse (NGC). Guideline
synthesis: Asthma treatment. In: National Guideline Clearinghouse (NGC)
[website]. Rockville (MD): 2000 Aug 14 (updated 2001 Mar 23). [cited YYYY
Mon DD]. Available: http://www.guideline.gov.
_____
Edward E. Rylander,M.D.
D.A.B.F.P. AND D.A.B.P.M.