Asthma

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Asthma
Girish D Sharma, MD, Associate Professor of Pediatrics, Rush Medical College; Director, Section of Pediatric Pulmonology and
Rush Cystic Fibrosis Center, Rush University Medical Center
Payel Gupta, MD, Fellow in Allergy and Immunology, Long Island College Hospital/SUNY Downstate
Updated: Jun 30, 2010
Introduction
Background
Asthma is a chronic inflammatory disorder of the airways characterized by an obstruction of airflow, which may be
completely or partially reversed with or without specific therapy. Airway inflammation is the result of interactions
between various cells, cellular elements, and cytokines. In susceptible individuals, airway inflammation may cause
recurrent or persistent bronchospasm, which causes symptoms including wheezing, breathlessness, chest
tightness, and cough, particularly at night or after exercise.
Airway inflammation is associated with airway hyperreactivity or bronchial hyperresponsiveness (BHR), which is
defined as the inherent tendency of the airways to narrow in response to various stimuli (eg, environmental
allergens and irritants). [1 ]
Asthma affects an estimated 300 million individuals worldwide. Evidence shows that the prevalence of asthma is
increasing, especially in children. Annually, the World Health Organization (WHO) has estimated that 15 million
disability-adjusted life-years are lost and 250,000 asthma deaths are reported worldwide.[2 ]Approximately 500,000
annual hospitalizations (34.6% in individuals aged 18 y or younger) are due to asthma. The cost of illness related
to asthma is around $6.2 billion. Each year, an estimated 1.81 million people (47.8% in individuals aged 18 y or
younger) require treatment in the emergency department. Among children and adolescents aged 5-17 years,
asthma accounts for a loss of 10 million school days and costs caretakers $726.1 million because of work absence.
[3 ]
Pathophysiology
Interactions between environmental and genetic factors result in airway inflammation, which limits airflow and leads
to functional and structural changes in the airways in the form of bronchospasm, mucosal edema, and mucus
plugs.
Airway obstruction causes increased resistance to airflow and decreased expiratory flow rates. These changes
lead to a decreased ability to expel air and may result in hyperinflation. The resulting overdistention helps maintain
airway patency, thereby improving expiratory flow; however, it also alters pulmonary mechanics and increases the
work of breathing.
Hyperinflation compensates for the airflow obstruction, but this compensation is limited when the tidal volume
approaches the volume of the pulmonary dead space; the result is alveolar hypoventilation. Uneven changes in
airflow resistance, the resulting uneven distribution of air, and alterations in circulation from increased intraalveolar
pressure due to hyperinflation all lead to ventilation-perfusion mismatch. Vasoconstriction due to alveolar hypoxia
also contributes to this mismatch. Vasoconstriction is also considered an adaptive response to ventilation/perfusion
mismatch.
In the early stages, when ventilation-perfusion mismatch results in hypoxia, hypercarbia is prevented by the ready
diffusion of carbon dioxide across alveolar capillary membranes. Thus, patients with asthma who are in the early
stages of an acute episode have hypoxemia in the absence of carbon dioxide retention. Hyperventilation triggered
by the hypoxic drive also causes a decrease in PaCO 2. An increase in alveolar ventilation in the early stages of an
acute exacerbation prevents hypercarbia. With worsening obstruction and increasing ventilation-perfusion
mismatch, carbon dioxide retention occurs. In the early stages of an acute episode, respiratory alkalosis results
from hyperventilation. Later, the increased work of breathing, increased oxygen consumption, and increased
http://emedicine.medscape.com/article/1000997-print 25/09/2010
cardiac output result in metabolic acidosis. Respiratory failure leads to respiratory acidosis.
Chronic inflammation of the airways is associated with increased BHR, which leads to bronchospasm and typical
symptoms of wheezing, shortness of breath, and coughing after exposure to allergens, environmental irritants,
viruses, cold air, or exercise. In some patients with chronic asthma, airflow limitation may be only partially
reversible because of airway remodeling (hypertrophy and hyperplasia of smooth muscle, angiogenesis, and
subepithelial fibrosis) that occurs with chronic untreated disease.
New insights in the pathogenesis of asthma suggest the role of lymphocytes. Airway inflammation in asthma may
represent a loss of normal balance between two "opposing" populations of Th lymphocytes. Two types of Th
lymphocytes have been characterized: Th1 and Th2. Th1 cells produce interleukin (IL)-2 and IFN-α, which are
critical in cellular defense mechanisms in response to infection. Th2, in contrast, generates a family of cytokines
(IL-4, IL-5, IL-6, IL-9, and IL-13) that can mediate allergic inflammation.
The current "hygiene hypothesis" of asthma illustrates how this cytokine imbalance may explain some of the
dramatic increases in asthma prevalence in Westernized countries.[4 ]This hypothesis is based on the concept that
the immune system of the newborn is skewed toward Th2 cytokine generation (mediators of allergic inflammation).
Following birth, environmental stimuli such as infections activate Th1 responses and bring the Th1/Th2 relationship
to an appropriate balance.
Evidence suggests that the prevalence of asthma is reduced in association with certain infections (Mycobacterium
tuberculosis, measles, or hepatitis A); country living, exposure to other children (eg, presence of older siblings and
early enrollment in childcare); and less frequent use of antibiotics. Furthermore, the absence of these lifestyle
events is associated with the persistence of a Th2 cytokine pattern.
Under these conditions, the genetic background of the child, with a cytokine imbalance toward Th2, sets the stage
to promote the production of immunoglobulin E (IgE) antibody to key environmental antigens (eg, dust mites,
cockroaches, Alternaria, and possibly cats). Therefore, a gene-by-environment interaction occurs in which the
susceptible host is exposed to environmental factors that are capable of generating IgE, and sensitization occurs.
A reciprocal interaction is apparent between the two subpopulations, in which Th1 cytokines can inhibit Th2
generation and vice versa. Allergic inflammation may be the result of an excessive expression of Th2 cytokines.
Alternately, the possibility that the loss of normal immune balance arises from a cytokine dysregulation in which
Th1 activity in asthma is diminished has been suggested in recent studies. [5 ]
In preschool children with asthma, 2 years of inhaled corticosteroid therapy did not change the asthma symptoms
or lung function during a third, treatment-free year. This suggests that no disease-modifying effect of inhaled
corticosteroids is present after the treatment is discontinued. [6 ]
Evidence suggests that rhinovirus is a significant risk factor for the development of wheeze in preschool children
and a frequent trigger of wheezing illnesses in children with asthma. [7 ]In addition, some studies highlight the
importance of genotypes. [8,9,10,11 ]
Attempts to identify clinical subtypes of asthma using cluster analysis resulted in the identification of 5 phenotypes
of asthma that differ in multiple ways, including age of onset, gender, body weight, degree of flow limitation, and
frequency of exacerbations. [12 ]
Frequency
United States
Approximately 34.1 million Americans have been diagnosed with asthma in their lifetime. The prevalence of

asthma in the general population is 5%, and it has increased 40% in the past decade. Asthma accounts for more
school absences and more hospitalizations than any other chronic illness. In most children's hospitals in the United
States, it is the most common diagnosis at admission. The current asthma prevalence is estimated to be 6.7% in
adults and 8.5% in children. [13 ] According to the most recent US Centers for Disease Control and Prevention
(CDC) Asthma Surveillance Survey, the burden of asthma has increased more than 75% from 1980-1999. [14 ]
International
Worldwide, 130 million people have asthma. The prevalence is 8-10 times higher in developed countries (eg,
United States, Great Britain, Australia, New Zealand) than in the developing countries. In developed countries, the
prevalence is higher in low income groups in urban areas and inner cities than in other groups.
Mortality/Morbidity
Globally, morbidity and mortality associated with asthma have increased over the last 2 decades. This increase is
attributed to increasing urbanization. Despite advancements in our understanding of asthma and the development
of new therapeutic strategies, the morbidity and mortality rates due to asthma definitely increased from 1980-1995.
In the United States, the mortality rate due to asthma has increased in all age, race, and sex strata. In the United
States, the mortality rate due to asthma is more than 17 deaths per 1 million people (ie, 5000 deaths per year).
From 1975-1993, the number of deaths nearly doubled in people aged 5-14 years. In the northeastern and
midwestern United States, the highest mortality rate has been among persons aged 5-34 years. According to the
most recent report from the CDC and the National Center for Health Statistics, 187 children aged 0-17 years died
from asthma, or 0.3 deaths per 100,000 children compared with 1.9 deaths per 100,000 adults aged 18 or older in
the year 2002.[13 ] Non-Hispanic blacks were the most likely to die from asthma and had an asthma death rate more
than 200% higher than non-Hispanic whites and 160% higher than Hispanics.
Race
The prevalence of asthma is higher in minority groups (eg, blacks, Hispanics) than in other groups; however,
findings from one study suggest that much of the recent increase in the prevalence is attributed to asthma in white
children. Approximately 5-8% of all black children have asthma at some time. The prevalence in Hispanic children
is reported to be as high as 15%. In blacks, the death rate is consistently higher than in whites.
Sex
Before puberty, the prevalence is 3 times higher in boys than in girls. During adolescence, the prevalence is equal
among males and females. Adult-onset asthma is more common in women than in men.
Age
In most children, asthma develops before age 5 years, and, in more than half, asthma develops before they age 3
years.
Among infants, 20% have wheezing with only upper respiratory tract infections (URTIs), and 60% no longer have
wheezing by age 6 years. Many of these children were called "transient wheezers" by Martinez et al. [15,16 ]They
tend to have no allergies, although their lung function is often abnormal. These findings have led to the idea that
they have small lungs. Children in whom wheezing begins early, in conjunction with allergies, are more likely to
have wheezing when they are aged 6-11 years. Similarly, children in whom wheezing begins after age 6 years
often have allergies, and the wheezing is more likely to continue when they are aged 11 years. [7 ]
Clinical
History
The updated guidelines from the National Asthma Education and Prevention Program highlight the importance of
correctly diagnosing asthma. [17 ]To establish the diagnosis of asthma, the clinician must establish the following: (1)
episodic symptoms of airflow obstruction are present, (2) airflow obstruction or symptoms are at least partially
reversible, and (3) alternative diagnoses are excluded. Thus, obtaining a good patient history is crucial when
diagnosing asthma and excluding other causes.

Questions that need to be addressed include, but are not limited to, the following:
 Symptoms
 Wheezing
 Cough
 Cough at night or with exercise
 Shortness of breath
 Chest tightness
 Sputum production
 Pattern of symptoms
 Perennial, seasonal, or both
 Continuous or intermittent
 Daytime or nighttime
 Onset and duration
 Precipitating and/or aggravating factors

 Viral infections
 Environmental allergens
 Irritants (eg, smoke exposure, chemicals, vapors, dust)
 Exercise
 Emotions
 Home environment (eg, carpets, pets, mold)
 Stress
 Drugs (eg, aspirin, beta blockers)
 Foods
 Changes in weather
 Other conditions (eg, thyroid disease, pregnancy, menses, gastroesophageal reflux disease [GERD],
sinusitis, rhinitis)
 Development of disease and treatment

 Age at onset and diagnosis
 Progression of symptoms (better or worse)
 Improvement with bronchodilators
 Use of oral corticosteroids
 Family history - History of asthma, allergy, sinusitis, rhinitis, eczema, or nasal polyps in close relatives
 Social history - Factors that may contribute to nonadherence of asthma medications, illicit drug use
 History of exacerbations - Usual prodromal signs of symptoms, rapidity of onset, associated illnesses,
number in the last year, need for hospitalization
Symptoms of asthma may include wheezing, coughing, and chest tightness, among others.
 Wheezing
 A musical, high-pitched, whistling sound produced by airflow turbulence is one of the most common
symptoms.
 In the mildest form, wheezing is only end expiratory. As severity increases, the wheeze lasts
throughout expiration. In a more severe asthmatic episode, wheezing is also present during
inspiration. During a most severe episode, wheezing may be absent because of the severe limitation
of airflow associated with airway narrowing and respiratory muscle fatigue.
 Asthma can occur without wheezing when obstruction involves predominantly the small airways.
Thus, wheezing is not necessary for the diagnosis of asthma. Furthermore, wheezing can be
associated with other causes of airway obstruction, such as cystic fibrosis and heart failure.
 Patients with vocal cord dysfunction have a predominantly inspiratory monophonic wheeze (different
from the polyphonic wheeze in asthma), which is heard best over the laryngeal area in the neck.
Patients with bronchomalacia and tracheomalacia also have a monophonic wheeze.
 In exercise-induced or nocturnal asthma, wheezing may be present after exercise or during the night,
respectively.
 Coughing: Cough may be the only symptom of asthma, especially in cases of exercise-induced or nocturnal
asthma. Usually, the cough is nonproductive and nonparoxysmal. Also, coughing may be present with
wheezing. Children with nocturnal asthma tend to cough after midnight, during the early hours of morning.
 Chest tightness: A history of tightness or pain in the chest may be present with or without other symptoms of
asthma, especially in exercise-induced or nocturnal asthma.
 Other nonspecific symptoms: Infants or young children may have history of recurrent bronchitis,
bronchiolitis, or pneumonia; a persistent cough with colds; and/or recurrent croup or chest rattling. Most
children with chronic or recurrent bronchitis have asthma. Asthma is the most common underlying diagnosis
in children with recurrent pneumonia. Older children may have a history of chest tightness and/or recurrent
chest congestion.
During an acute episode, symptoms vary according to the severity.
 Symptoms during a mild episode: Patients may be breathless after physical activity such as walking. They
can talk in sentences and lie down, and they may be agitated.
 Symptoms during a moderate severe episode: Patients are breathless while talking. Infants have feeding
difficulties and a softer, shorter cry.
 Symptoms during a severe episode: Patients are breathless during rest, are not interested in feeding, sit
upright, talk in words (not sentences), and are usually agitated.
 Symptoms with imminent respiratory arrest (in addition to the aforementioned symptoms): The child is
drowsy and confused. However, adolescents may not have these symptoms until they are in frank
respiratory failure.
Physical
The clinical picture varies. Symptoms may be associated with upper respiratory infections (URTIs), nocturnal or
exercise-induced asthmatic symptoms, and status asthmaticus. Status asthmaticus, or an acute severe asthmatic
episode that is resistant to appropriate outpatient therapy, is a medical emergency that requires aggressive
hospital management. This may include admission to an ICU for the treatment of hypoxia, hypercarbia, and
dehydration and possibly for assisted ventilation because of respiratory failure.
Physical findings vary with the absence or presence of an acute episode and its severity, as follows:
 Physical examination in the absence of an acute episode (eg, during an outpatient visit between acute
episodes)
 The physical findings vary with the severity of the asthma. During an outpatient visit, a patient with
mild asthma may have normal findings upon physical examination. Patients with more severe
asthma are likely to have signs of chronic respiratory distress and chronic hyperinflation.
 Signs of atopy or allergic rhinitis, such as conjunctival congestion and inflammation, ocular shiners, a
transverse crease on the nose due to constant rubbing associated with allergic rhinitis, and pale
violaceous nasal mucosa due to allergic rhinitis, may be present.
 The anteroposterior diameter of the chest may be increased because of hyperinflation. Hyperinflation
may also cause an abdominal breathing pattern.
 Lung examination may reveal prolongation of the expiratory phase, expiratory wheezing, coarse
crackles, or unequal breath sounds.
 Clubbing of the fingers is not a feature of straightforward asthma and indicates a need for more
extensive evaluation and work-up to exclude other conditions, such as cystic fibrosis.
 Physical examination during an acute episode may reveal different findings in mild, moderately severe, and
severe episodes and in status asthmaticus with imminent respiratory arrest.
 Mild episode: The respiratory rate is increased. Accessory muscles of respiration are not used. The
heart rate is less than 100 beats per minute. Pulsus paradoxus is not present. Auscultation of chest
reveals moderate wheezing, which is often end expiratory. Oxyhemoglobin saturation with room air is
greater than 95%.
 Moderately severe episode: The respiratory rate is increased. Typically, accessory muscles of
respiration are used, and suprasternal retractions are present. The heart rate is 100-120 beats per
minute. Loud expiratory wheezing can be heard. Pulsus paradoxus may be present (10-20 mm Hg).
Oxyhemoglobin saturation with room air is 91-95%.
 Severe episode: The respiratory rate is often greater than 30 breaths per minute. Accessory muscles
of respiration are usually used, and suprasternal retractions are commonly present. The heart rate is
more than 120 beats per minute. Loud biphasic (expiratory and inspiratory) wheezing can be heard.
Pulsus paradoxus is often present (20-40 mm Hg). Oxyhemoglobin saturation with room air is less
than 91%.
 Status asthmaticus with imminent respiratory arrest: Paradoxical thoracoabdominal movement
occurs. Wheezing may be absent (associated with most severe airway obstruction). Severe
hypoxemia may manifest as bradycardia. Pulsus paradoxus noted earlier may be absent; this finding
suggests respiratory muscle fatigue.
Causes
In most cases of asthma in children, multiple triggers or precipitants are recognized, and the patterns of reactivity
may change with age. Treatment can also change the pattern. Certain viral infections, such as respiratory syncytial
virus (RSV) bronchiolitis in infancy, predispose the child to asthma.
 Respiratory infections: Most commonly, these are viral infections. In some patients, fungi (eg, allergic
bronchopulmonary aspergillosis), bacteria (eg, mycoplasmata, pertussis), or parasites may be responsible.
Most infants and young children who continue to have a persistent wheeze and asthma have high
immunoglobulin E (IgE) production and eosinophilic immune responses (in the airways and in circulation) at
the time of the first viral URTI. They also have early IgE-mediated responses to local aeroallergens.
 Allergens: In patients with asthma, 2 types of bronchoconstrictor responses to allergens are recognized.
 Early asthmatic responses occur via IgE-induced mediator release from mast cells within minutes of
exposure and last for 20-30 minutes.
 Late asthmatic responses occur 4-12 hours after antigen exposure and result in more severe
symptoms that can last for hours and contribute to the duration and severity of the disease.
Inflammatory cell infiltration and inflammatory mediators play a role in the late asthmatic response.
Allergens can be foods, household inhalants (eg, animal allergens, molds, fungi, roach allergens,
dust mites), or seasonal outdoor allergens (eg, mold spores, pollens, grass, trees).
 Irritants: Tobacco smoke, cold air, chemicals, perfumes, paint odors, hair sprays, air pollutants, and ozone
can initiate bronchial hyperresponsiveness (BHR) by inducing inflammation.
 Weather changes: Asthma attacks can be related to changes in atmospheric temperature, barometric
pressure, and the quality of air (eg, humidity, allergen and irritant content).
 Exercise: Exercise can trigger an early asthmatic response. Mechanisms underlying exercise-induced
asthmatic response remain somewhat uncertain. Heat and water loss from the airways can increase the
osmolarity of the fluid lining the airways and result in mediator release. Cooling of the airways results in
congestion and dilatation of bronchial vessels. During the rewarming phase after exercise, the changes are
magnified because the ambient air breathed during recovery is warm rather than cool.
 Emotional factors: In some individuals, emotional upsets clearly aggravate asthma.
 Gastroesophageal reflux (GER): The presence of acid in the distal esophagus, mediated via vagal or other
neural reflexes, can significantly increase airway resistance and airway reactivity.
 Allergic rhinitis, sinusitis, and chronic URTI: Inflammatory conditions of the upper airways (eg, allergic
rhinitis, sinusitis, or chronic and persistent infections) must be treated before asthmatic symptoms can be
completely controlled.
 Nocturnal asthma: Multiple factors have been proposed to explain nocturnal asthma. Circadian variation in
lung function and inflammatory mediator release in the circulation and airways (including parenchyma) have
been demonstrated. Other factors, such as allergen exposure and posture-related irritation of airways (eg,
GER, sinusitis), can also play a role. In some patients, abnormalities in CNS control of the respiratory drive
may be present, particularly in patients with a defective hypoxic drive and obstructive sleep apnea.
Differential Diagnoses
Airway Foreign Body Cystic Fibrosis

Allergic Rhinitis Gastroesophageal Reflux
Aspergillosis Laryngomalacia
Aspiration Syndromes Primary Ciliary Dyskinesia
Bronchiectasis Subglottic Stenosis
Bronchiolitis Vascular Ring, Right Aortic Arch
Bronchopulmonary Dysplasia
Other Problems to Be Considered
Tracheobronchomalacia
Hyperventilation syndrome
Vocal cord dysfunction
Pulmonary edema
Collagen vascular disease
Reactive airway disease
Workup
Laboratory Studies
The following tests are indicated in the assessment of asthma:
 Pulmonary function tests (PFTs): These results are not reliable in patients younger than 5 years. In young
children (3-6 y) and older children who are unable to perform the conventional spirometry maneuver, newer
techniques, such as measurement of airway resistance using impulse oscillometry system, are used.
Measurement of airway resistance before and after a dose of inhaled bronchodilator may help to diagnose
bronchodilator responsive airway obstruction.
 Spirometry: In a typical case, an obstructive defect is present in the form of normal forced vital
capacity (FVC), reduced FEV 1, and reduced forced expiratory flow more than 25-75% of the FVC
(FEF 25-75). The flow-volume loop can be concave. Documentation of reversibility of airway
obstruction after bronchodilator therapy is central to the definition of asthma. FEF 25-75 is a
sensitive indicator of obstruction and may be the only abnormality in a child with mild disease. In an
outpatient or office setting, measurement of the peak flow rate by using a peak flow meter can
provide useful information about obstruction in the large airways. Take care to ensure maximum
patient effort. However, a normal peak flow rate does not necessarily mean a lack of airway
obstruction.
 Plethysmography: Patients with chronic persistent asthma may have hyperinflation, as evidenced by
an increased total lung capacity (TLC) at plethysmography. Increased residual volume (RV) and
functional residual capacity (FRC) with normal TLC suggests air trapping. Airway resistance is
increased when significant obstruction is present.
 Bronchial provocation tests: Bronchial provocation tests may be performed to diagnose bronchial
hyperresponsiveness (BHR). These tests are performed in specialized laboratories by specially trained
personnel to document airway hyperresponsiveness to substances (eg, methacholine, histamine).
Increasing doses of provocation agents are given, and FEV1 is measured. The endpoint is a 20% decrease
in FEV1 (PD20).
 Exercise challenge: In a patient with a history of exercise-induced symptoms (eg, cough, wheeze, chest
tightness or pain), the diagnosis of asthma can be confirmed with the exercise challenge. In a patient of
appropriate age (usually >6 y), the procedure involves baseline spirometry followed by exercise on a
treadmill or bicycle to a heart rate greater than 60% of the predicted maximum, with monitoring of the
electrocardiogram and oxyhemoglobin saturation. The patient should be breathing cold, dry air during the
exercise to increase the yield of the study. Spirographic findings and the peak expiratory flow (PEF) rate
(PEFR) are determined immediately after the exercise period and at 3 minutes, 5 minutes, 10 minutes, 15
minutes, and 20 minutes after the first measurement. The maximal decrease in lung function is calculated
by using the lowest postexercise and highest pre-exercise values. The reversibility of airway obstruction can
be assessed by administering aerosolized bronchodilators.
 Blood testing: Eosinophil counts and IgE levels may help when allergic factors are suspected.
 Fraction of exhaled nitric oxide (FeNO) testing: Evidence suggests the usefulness of measuring the FeNO
as a noninvasive marker of airway inflammation, in order to adjust the dose of inhaled corticosteroids
treatment. Currently FeNO measurement, due to high cost of equipment, is used primarily as a research
tool.
Imaging Studies
 Chest radiography: Include chest radiography in the initial workup if the asthma does not respond to therapy
as expected. In addition to typical findings of hyperinflation and increased bronchial markings, a chest
radiograph may reveal evidence of parenchymal disease, atelectasis, pneumonia, congenital anomaly, or a
foreign body. In a patient with an acute asthmatic episode that responds poorly to therapy, a chest
radiograph helps in the diagnosis of complications such as pneumothorax or pneumomediastinum.
 Paranasal sinus radiography or CT scanning: Consider using these to rule out sinusitis.
Other Tests
 Allergy testing: Allergy testing can be used to identify allergic factors that may significantly contribute to the
asthma. Once identified, environmental factors (eg, dust mites, cockroaches, molds, animal dander) and
outdoor factors (eg, pollen, grass, trees, molds) may be controlled or avoided to reduce asthmatic
symptoms. Allergens for skin testing are selected on the basis of suspected or known allergens identified
from a detailed environmental history. Antihistamines can suppress the skin test results and should be
discontinued for an appropriate period (according to the duration of action) before allergy testing. Topical or
systemic corticosteroids do not affect the skin reaction.
Histologic Findings
 Asthma is an inflammatory disease characterized by the recruitment of inflammatory cells, vascular

congestion, increased vascular permeability, increased tissue volume, and the presence of an exudate.
 Eosinophilic infiltration, a universal finding, is considered a major marker of the inflammatory activity of the
disease.
 Histologic evaluations of the airways in a typical patient reveal infiltration with inflammatory cells, narrowing
of airway lumina, bronchial and bronchiolar epithelial denudation, and mucus plugs.
 Additionally, a patient with severe asthma may have a markedly thickened basement membrane and airway
remodeling in the form of subepithelial fibrosis and smooth muscle hypertrophy or hyperplasia.
Staging
Asthma severity is defined as "the intensity of the disease process" prior to initiating therapy and helps in
determining the initiation of therapy in a patient who is not on any controller medications.[17 ]
 The severity of asthma is classified as intermittent, mild persistent, moderate persistent, or severe
persistent.
 Asthma severity is classified according to the impairment and risk related to disease, which is measured by
frequency and severity of symptoms, including nocturnal symptoms, characteristics of acute episodes,
pulmonary function, and exacerbations at the onset of disease prior to initiating treatment. Features of these
categories have been divided into 3 charts to reflect classification in different age groups (0-4 y, 5-11 y, and
12 y and older), according to the new National Asthma Education and Prevention Program guidelines. [17 ]
See image below.
Pediatric asthma. Classification of asthma control.
Chart available at http://img.medscape.com/pi/emed/ckb/pediatrics_general/1331341-1331361-

1000997-1544741.pdf.
 An important point to remember is that the presence of one severe feature is sufficient to diagnose severe
persistent asthma. Also, the characteristics in this classification system are general and may overlap
because asthma severity widely varies. A patient’s classification may change over time .
 Patients with asthma of any level of severity may have mild, moderate, or severe exacerbations.
 Some patients with intermittent asthma have severe and life-threatening exacerbations separated by
episodes with almost normal lung function and minimal symptoms; however, they are likely to have other
evidence of increased BHR (exercise or challenge testing) due to ongoing inflammation.
Treatment
Medical Care
The National Asthma Education and Prevention Program guidelines highlight the importance of treating impairment
and risk domains of asthma. [17 ]The goal for therapy is to control asthma by reducing impairment through
prevention of chronic and troublesome symptoms (eg, coughing or breathlessness in the daytime, in the night, or
after exertion), reduction in the need for short-acting beta2-agonist (SABA) for quick relief of symptoms (not
including prevention of exercise-induced bronchospasm), maintenance of near normal pulmonary function,
maintenance of normal activity levels (including exercise and other physical activity and attendance at work or
school), and satisfaction in terms of patients' and families' expectations for asthma care.
A reduction in risk can be achieved by prevention of recurrent exacerbations of asthma and minimization of the
need for emergency room visits and hospitalizations and prevention of progressive loss of lung function. For
children, preventing reduced lung growth and providing optimal pharmacotherapy with minimal or no adverse
effects is important.
The current guidelines emphasize 4 important components of asthma care: (1) assessment and monitoring, (2)
education, (3) control of environmental factors and comorbid conditions, and (4) medications.[17 ]
 Assessment and monitoring

 Once the patient's condition is classified and therapy has been initiated, continual assessment is
important for disease control. Asthma control is defined as "the degree to which the manifestations of
asthma are minimized by therapeutic intervention and the goals of therapy are met." [17 ]
 In order to assess asthma control and adjust therapy, impairment and risk must be assessed.
 Assessment of impairment focuses on the frequency and intensity of symptoms and the
functional limitations associated with these symptoms.
 Risk assessment focuses on the likelihood of asthma exacerbations, adverse effects from
medications, and the likelihood of the progression of lung function decline; spirometry should
be measured every 1-2 years or more frequently for uncontrolled asthma.
 Because asthma varies over time, follow-up every 2-6 weeks is initially necessary (when gaining
control of the disease) and then every 1-6 months thereafter.
 Education
 Patient education continues to be important in all areas of medicine and is particularly important in
asthma. Self-management education should focus on teaching patients the importance of
recognizing their own their level of control and signs of progressively worsening asthma symptoms.
 Both peak flow monitoring and symptom monitoring have been shown to be equally effective;
however, peak flow monitoring may be more helpful in cases in which patients have a history of
difficulty in perceiving symptoms, a history of severe exacerbations, or moderate-to-severe asthma.
 Educational strategies should also focus on environmental control and avoidance strategies and
medication use and adherence (eg, correct inhaler techniques and use of other devices).
 The use of various methods in reinforcing educational messages to patients is crucial in patient
understanding. The use of written asthma action plans in partnership with the patient (make sure to
review the differences between long-term control and quick-relief medications), education through
the involvement of other members of the healthcare team (eg, nurses, pharmacists, physicians), and
education at all points of care (eg, clinics, hospitals, schools) are examples of various educational
tools that are available and are important tools for good patient adherence and understanding.
 Control of environmental factors and comorbid conditions

 As mentioned above, environmental exposures and irritants can play a strong role in symptom
exacerbations. Therefore, in patients who have persistent asthma, the use of skin testing or in vitro
testing to assess sensitivity to perennial indoor allergens is important. Once the offending allergens
are identified, counsel patients on avoidance from these exposures. In addition, education to avoid
tobacco smoke (both first-hand and second-hand exposure) is important for patients with asthma.
 Lastly, treatment of comorbid conditions that may affect asthma as mentioned above must be
appropriately managed. These include bronchopulmonary aspergillosis, gastroesophageal reflux
disease (GERD), obesity, obstructive sleep apnea, rhinitis, sinusitis, depression, and stress.
Inactivated influenza vaccine may be helpful in those who are older than 6 months.
 Medications
 Medical care includes treatment of acute asthmatic episodes and control of chronic symptoms,
including nocturnal and exercise-induced asthmatic symptoms.
 Pharmacologic management includes the use of control agents, such as inhaled corticosteroids,
inhaled cromolyn or nedocromil, long-acting bronchodilators, theophylline, leukotriene modifiers, and
more recent strategies such as the use of anti-immunoglobulin E (IgE) antibodies (omalizumab).
 Relief medications include short-acting bronchodilators, systemic corticosteroids, and ipratropium.
 For all but the most severely affected patients, the ultimate goal is to prevent symptoms, minimize
morbidity from acute episodes, and prevent functional and psychological morbidity to provide a
healthy (or near healthy) lifestyle appropriate to the age of child.
 A stepwise approach to pharmacologic therapy is recommended to gain and maintain control of
asthma in both the impairment and risk domains. The type, amount, and scheduling of medication is
dictated by asthma severity (for initiating therapy) and the level of asthma control (for adjusting
therapy). Step-down therapy is essential to identify the minimum medication necessary to maintain
control
 Concerns about the safety of long-acting beta2-agonists and resultant US Food and Drug (FDA)
drug safety communications creates a question as to the course of treatment if asthma is not
controlled by inhaled corticosteroids. [18 ]A study by Lemanske et al addressed this question and
concluded that addition of long-acting beta2-agonist was more likely to provide the best response
than either inhaled corticosteroids or leukotriene-receptor antagonists.[19 ]Asthma therapy should be
regularly monitored and adjusted accordingly.
 The pharmacotherapy is divided into 3 groups based on age (0-4 y, 5-11 y, 12 y and older).
 For all patients, quick-relief medications include rapid-acting beta2-agonists as needed for
symptoms. The intensity of treatment depends on the severity of symptoms. If rapid-acting beta2-
agonists are used more than two days a week for symptom relief (not including use of rapid-acting
beta2-agonists for prevention of exercise induce symptoms), stepping up treatment may be
considered.
 In general, patients should be assessed every 1-6 months for asthma control. At every visit,
adherence, environmental control, and comorbid conditions should be checked. If the patient has
good control of their asthma for at least 3 months, treatment can be stepped down; however, the
patient should be reassessed in 2-4 weeks to make sure that control is maintained with the new
treatment. If patients require step 2 asthma medications or higher, consultation with an asthma
specialist should be considered.
Treatment goals of acute severe asthmatic episodes (status asthmaticus) are as follows:
 Correction of significant hypoxemia with supplemental oxygen: In severe cases, alveolar hypoventilation
requires mechanically assisted ventilation.
 Rapid reversal of airflow obstruction by using repeated or continuous administration of an inhaled beta2-
agonist: Early administration of systemic corticosteroids (eg, oral prednisone or intravenous
methylprednisolone) is suggested in children with asthma that fails to respond promptly and completely to
inhaled beta2-agonists.
 Reduction in the likelihood of recurrence of severe airflow obstruction by intensifying therapy: Often, a short
course of systemic corticosteroids is helpful.
Achieving these goals requires close monitoring by means of serial clinical assessment and measurement of lung
function (in patients of appropriate ages) to quantify the severity of airflow obstruction and its response to
treatment. Improvement in FEV 1 after 30 minutes of treatment is significantly correlated with a broad range of
indices of the severity of asthmatic exacerbations, and repeated measurement of airflow in the emergency
department can help reduce unnecessary admissions.
The use of the peak flow rate or FEV 1 values, patient's history, current symptoms, and physical findings to guide
treatment decisions is helpful in achieving the aforementioned goals. When using the peak expiratory flow (PEF)
expressed as a percentage of the patient's best value, the effect of irreversible airflow obstruction should be
considered. For example, in a patient whose best peak flow rate is 160 L/min, a decrease of 40% represents
severe and potentially life-threatening obstruction.
An Australian study by Vuillermin et al studied whether asthma severity decreased in school-aged children when
parents initiated a short course of prednisolone for acute asthma.[20 ]Children who received parent-initiated
prednisolone for episodes of asthma had lower daytime and nighttime asthma scores, reduced risk of health
resource use, and reduced school absenteeism compared with children who received placebo.
Consultations
Referral to an asthma specialist for consultation or comanagement of the patient is recommended if difficulty in
achieving or maintaining control of asthma is noted; if additional education is needed to improve adherence; if the
patient requires step 4 care or higher (step 3 care or higher for children aged 0–4 y); or if the patient has had an
exacerbation requiring hospitalization. Consider referral if a patient requires step 3 care (step 2 care for children
aged 0–4 y) or if additional testing for the role of allergy is indicated. [17 ]
Consider consultation with an allergist; ear, nose, and throat (ENT) specialist; or gastroenterologist.
 An allergist may help with further evaluation and management when the history and physical examination
findings suggest significant allergies (especially systemic involvement and allergies to dietary products).
 An ENT specialist may help in managing chronic rhinosinusitis.
 A gastroenterologist may help in excluding and/or treating gastroesophageal reflux.
Diet
When a patient has major allergies to dietary products, avoidance of particular foods may help. In the absence of
specific food allergies, dietary changes are not necessary. Unless compelling evidence for a specific allergy exists,
milk products do not have to be avoided.
Activity
One of the goals of therapy is to adequately control exercise-induced asthmatic symptoms so that physical activity
is not restricted.
Medication
Medical care includes treatment of acute asthmatic episodes and control of chronic symptoms, including nocturnal
and exercise-induced asthmatic symptoms. Pharmacologic management includes the use of control agents such
as inhaled corticosteroids, inhaled cromolyn or nedocromil, long-acting bronchodilators, theophylline, leukotriene
modifiers, and more recent strategies such as the use of anti-immunoglobulin E (IgE) antibodies (omalizumab).
Relief medications include short-acting bronchodilators, systemic corticosteroids, and ipratropium.
For all but the most severely affected patients, the ultimate goal is to prevent symptoms, minimize morbidity from
acute episodes, and prevent functional and psychological morbidity to provide a healthy (or near healthy) lifestyle
appropriate to the age of child.
A stepwise (step-up if necessary and step-down when possible) approach to asthma management continues to be
used in the new guidelines and is now divided into 3 groups based on age (0-4 y, 5-11 y, 12 y and older).[17 ]
For all patients, quick-relief medications include rapid-acting beta2-agonists as needed for symptoms. The intensity
of treatment depends on the severity of symptoms. If rapid-acting beta2-agonists are used more than 2 days a
week for symptom relief (not including use of rapid-acting beta2-agonists for prevention of exercise-induced
symptoms), stepping up on treatment may need be considered.
In general, patients should be assessed every 1-6 months for asthma control. At every visit, adherence,
environmental control, and comorbid conditions should be checked. If the patient has good control of their asthma
for at least 3 months, treatment can be stepped down; however, the patient should be reassessed in 2-4 weeks to
make sure that control is maintained with the new treatment.
If patients require step 2 asthma medications or higher, consultation with an asthma specialist should be
considered.
Delivery Devices and Best Route of Administration
In pediatric asthma, inhaled treatment is the cornerstone of asthma management. Inhaler devices currently used to
deliver inhaled corticosteroids (ICSs) fall into the following 4 categories:
 Pressurized metered dose inhaler (pMDI) - Propellant used to dispense steroid when canister is pressed
manually
 Dry powder inhaler (DPI) - Does not require hand-breath coordination to operate
 Breath-actuated pMDI - Propellant used to dispense steroid when patient inhales
 Nebulized solution devices
In pediatrics, the inhaler device must be chosen on the basis of age, cost, safety, convenience, and efficacy of drug
delivery.[2 ]
Based on current research, the preferred device for children younger than 4 years is a pMDI with spacer and age-
appropriate mask. Children aged 4-6 years should use a pMDI plus a valved holding chamber. Lastly, children
older than 6 years can use either a pMDI, a DPI, or a breath-actuated pMDI. For all 3 groups, a nebulizer with a
valved holding chamber (and mask in children younger than 4 y) is recommended as alternate therapy. [2 ]
Stepwise Approach to Asthma Medications
Intermittent Persistent Asthma: Daily Medication

Asthma
Age Step 1 Step 2 Step 3 Step 4 Step 5 Step 6
<5 y Rapid- Low-dose ICS Medium-dose Medium-dose High-dose ICS High-dose ICS
acting ICS ICS plus either plus either plus either LABA
beta2- Alternate long-acting LABA or or montelukast;
agonist regimen: beta2-agonist montelukast Oral systemic
prn cromolyn or (LABA) or corticosteroid
montelukast montelukast
5-11 Rapid- Low-dose ICS Either low-dose Medium-dose High-dose ICS High-dose ICS
y acting ICS plus either ICS plus LABA plus LABA plus LABA plus
beta2- LABA, LTRA, or oral systemic
agonist theophylline OR corticosteroid
prn Medium-dose
Alternate Alternate Alternate Alternate regimen:
regimen: regimen: regimen: high- high-dose ICS
cromolyn, medium-dose dose ICS plus plus LRTA or
leukotriene ICS plus either either LABA or theophylline plus
receptor LTRA or theophylline systemic
antagonist theophylline corticosteroid
(LTRA), or
theophylline
12 y Rapid- Low-dose ICS Low-dose ICS Medium-dose High-dose ICS High-dose ICS
or acting plus LABA OR ICS plus LABA plus LABA (and plus either LABA
older beta2- Medium-dose consider plus oral
agonist ICS omalizumab for corticosteroid (and
as patients with consider
needed Alternate Alternate Alternate allergies) omalizumab for
regimen: regimen: low- regimen: patients with
cromolyn, dose ICS plus medium-dose allergies)
LTRA, or either LTRA, ICS plus either
theophylline theophylline, or LTRA,
zileuton theophylline, or
zileuton
Valved holding chambers are important. The addition of a valved holding chamber can increase the amount of drug
reaching the lungs to 20%. The use of a valved holding chamber helps reduce the amount of drug particles
deposited in the oropharynx, thereby helping to reduce systemic and local effects from oral and gastrointestinal
absorption. A Cochrane review on the use of valved holding chambers versus nebulizers for inhaled steroids found
no evidence that nebulizers are better than valved holding chamber. [21 ]Nebulizers are expensive, inconvenient to
use, require maintenance, and have been shown to have imprecise dosing.
Newer devices are showing greater efficacy. Recently, chlorofluorocarbon (CFC) MDI (thought to cause ozone
depletion) have been phased out in favor of the new hydrofluoroalkane-134a (HFA) MDI. Surprisingly, the HFA
component was not only more environmentally friendly but was also more effective due to the smaller aerosol
particle size of the propellant, which shows improved deposition in the small airways and greater efficacy at
equivalent doses compared with CFC-MDIs.
Bronchodilator, beta2-agonists
These agents act as bronchodilators, used to treat bronchospasm in acute asthmatic episodes, and used to
prevent bronchospasm associated with exercise-induced asthma or nocturnal asthma. Several studies have
suggested that short-acting beta2-agonists such as albuterol may produce adverse outcomes (eg, decreased peak
flow or increased risk of exacerbations) in patients homozygous for arginine (Arg/Arg) at the 16th amino acid
position of beta-adrenergic receptor gene compared with patients homozygous for glycine (Gly-Gly). Similar
findings are reported for LABA, such as salmeterol.
Albuterol sulfate (Proventil HFA, Ventolin HFA, ProAir HFA)
This beta2-agonist is the most commonly used bronchodilator that is available in multiple forms (eg, solution for
nebulization, MDI, PO solution). This is most commonly used in rescue therapy for acute asthmatic symptoms.
Used as needed. Prolonged use may be associated with tachyphylaxis due to beta2-receptor downregulation and
receptor hyposensitivity.
Dosing
Adult
PO inhaler: 1-2 inhalations q4-6h; recent guidelines suggest 8-10 inhalations for more severe symptoms
Nebulizer: Dilute 0.5 mL (2.5 mg) of 0.5% inhalation solution in 1-2.5 mL of NS solution; administer 2.5-5 mg via
nebulization q4-6h, diluted in 2-5 mL sterile sodium chloride solution or water
Pediatric
PO inhaler: 90 mcg per inhalation, 2 inhalations q4-6h; more inhalations may be used in severe, acute episodes;
more frequent dosing can be used to treat acute symptoms
Nebulizer: 2.5 mg via nebulization of 0.5% solution in 2-3 mL of sodium chloride solution q4-6h
Interactions
Beta-adrenergic blockers antagonize effects; inhaled ipratropium may increase duration of bronchodilatation;
cardiovascular effects may increase with MAOIs, inhaled anesthetics, tricyclic antidepressants, and
sympathomimetic agents
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits
outweigh risk to fetus
Precautions
Large amounts (eg, those used in ICU in acute episodes) may cause muscular tremors, tachycardia,
hyperglycemia, and hypokalemia; caution in hyperthyroidism, diabetes mellitus, and cardiovascular disorders
Pirbuterol acetate (Maxair Autohaler)
Available as a breath-actuated or ordinary inhaler. The ease of administration with the breath-actuated device
makes it an attractive choice in the treatment of acute symptoms in younger children who otherwise cannot use an
MDI. Autohaler delivers 200 mcg per actuation.
Dosing
Adult
PO inhalation: 1-2 inhalations q4-6h; not to exceed 12 inhalations q24h
Pediatric
Administer as in adults
Interactions
Beta-adrenergic blockers antagonize effects; cardiovascular effects may increase with MAOIs, inhaled anesthetics,
tricyclic antidepressants, and sympathomimetic agents
Contraindications
Precautions
Pregnancy
Precautions
Caution in hyperthyroidism, diabetes mellitus, or cardiovascular disorders
Nonracemic form of the beta2-agonist albuterol

This nonracemic form of albuterol was recently introduced. One advantage is better efficacy; hence, lower doses
have a therapeutic effect, and a significant reduction in the adverse effects associated with racemic albuterol (eg,
muscle tremors, tachycardia, hyperglycemia, hypokalemia) is reported.
Levalbuterol (Xopenex)
Nonracemic form of albuterol, levalbuterol (R isomer) is effective in smaller doses and is reported to have fewer
adverse effects (eg, tachycardia, hyperglycemia, hypokalemia). The dose may be doubled in acute severe
episodes when even a slight increase in the bronchodilator response may make a big difference in the
management strategy (eg, in avoiding patient ventilation). Available as MDI (45 mcg per actuation) or solution for
nebulized inhalation.
Dosing
Adult
MDI: 45-90 mcg (1-2 inhalations) q4-6h

Nebulizer: 0.63-1.25 mg by nebulizer q8h
Pediatric
MDI: Administer as in adults

Nebulizer: 0.63 mg by nebulizer q8h
Interactions
Decreased efficacy with beta-blockers; digoxin levels may be decreased; may potentiate the kaliuretic effects of
drugs, such as, loop or thiazide diuretics; decreases serum digoxin levels by 16-22%; MAOIs may potentiate
vascular constriction, extreme caution advised with coadministration
Contraindications
Precautions
Pregnancy
Precautions
May cause muscular tremors, tachycardia, hyperglycemia, or hypokalemia (although these are less likely than with
albuterol)
Long-acting beta2-agonists
Long-acting bronchodilators are not used for the treatment of acute bronchospasm. They are used for the
preventive treatment of nocturnal asthma or exercise-induced asthmatic symptoms, for example. Currently, 2 LABA
are available in the United States: salmeterol (Serevent) and formoterol (Foradil). Salmeterol and formoterol are
available as combination products with inhaled corticosteroids in the United States.
LABA may increase the chance of severe asthma episodes and death when those episodes occur. Most cases
have occurred in patients with severe and/or acutely deteriorating asthma; they have also occurred in a few
patients with less severe asthma. LABAs are not considered first-line medications to treat asthma. LABAs should
not be used as isolated medications and should be added to the asthma treatment plan only if other medicines do
not control asthma, including the use of low-or-medium dose corticosteroids. If used as isolated medication, LABAs
should be prescribed by a subspecialist (ie, pulmonologist, allergist).
In the Salmeterol Multicenter Asthma Research Trial (SMART), salmeterol use in asthma patients, particularly
African-Americans, was associated with a small but significantly increased risk of serious asthma-related events.
[22 ] This trial was a large, double-blind, randomized, placebo-controlled, safety trial in which salmeterol 42 mcg
twice daily or placebo was added to usual asthma therapy for 28 weeks.
The study was halted following interim analysis of 26,355 participants because patients exposed to salmeterol
(n=13,176) were found to experience a higher rate of fatal asthma events compared with individuals receiving
placebo (n=13,179); the rates were 0.1% and 0.02%, respectively (relative risk [RR], 4.37; 95% confidence interval
[CI], 1.25 to 15.34). This resulted in an estimated 8 (95% CI, 3 to 13) excess deaths per 10,000 patients treated
with salmeterol. In the post-hoc subgroup analysis, the relative risks of asthma-related deaths were similar among
whites (n=18,642; salmeterol 0.07% vs placebo 0.01%; RR, 5.82; 95% CI, 0.7 to 48.37) and blacks (n=4685;
salmeterol 0.31% vs placebo 0.04%; RR, 7.26; 95% CI, 0.89 to 58.94), although the corresponding estimated
excess deaths per 10,000 patients exposed to salmeterol were higher among blacks (27; 95% CI, 8 to 46) than
whites (6; 95% CI, 1 to 10).
A meta-analysis by Salpeter et al reviewed data on the use of LABAs that resulted in adverse asthma events.[23 ]
The large pooled trial included 36,588 patients, most of them adults. LABAs increased the risk for asthma-related
intubations and deaths by 2-fold, even when used in a controlled fashion with concomitant inhaled corticosteroids.
However, the absolute number of adverse events remains small.
The FDA has reviewed the data and the issues and has published the following guidelines:[18 ]
 LABAs should only be used long-term in patients whose asthma cannot be adequately controlled on inhaled
steroids.
 LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and
discontinued, if possible, once asthma control is achieved. Patients should then be switched to an asthma
controller medication.
 Pediatric and adolescent patients who require the addition of a LABA to an inhaled corticosteroid should use
a combination product containing both an inhaled corticosteroid and a LABA to ensure compliance with both
medications.
The FDA has determined that the benefits of LABAs in improving asthma symptoms outweigh the potential risks
when used appropriately with an asthma controller medication in patients who need the addition of LABAs. The
FDA believes the safety measures recommended will improve the safe use of these drugs.
Salmeterol (Serevent Diskus)
This long-acting preparation of a beta2-agonist is used primarily to treat nocturnal or exercise-induced symptoms. It
has no anti-inflammatory action and is not indicated in the treatment of acute bronchospastic episodes. It may be
used as an adjunct to inhaled corticosteroids to reduce the potential adverse effects of the steroids. Delivered via
Diskus DPI.
Dosing
Adult
Serevent Diskus: 1 inhalation (50 mcg) q12h
Pediatric
<4 years: Not established

>4 years: Administer as in adults
Interactions
Concomitant use of beta-blockers may decrease bronchodilating and vasodilating effects of beta-agonists such as
salmeterol; concurrent administration with methyldopa may increase pressor response; coadministration with
oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics may
worsen with coadministration
Contraindications
Documented hypersensitivity; angina, tachycardia, and cardiac arrhythmias associated with tachycardia
Precautions
Pregnancy
Precautions
Use only as preventive treatment, not indicated for acute asthmatic symptoms; not a substitute for inhaled
corticosteroids; adverse effects include paroxysmal bronchospasm, tremors, nervousness, and tachycardia;
caution in coronary insufficiency, arrhythmias, hypertension, diabetes mellitus, hyperthyroidism; higher incidence of
cardiovascular risks when recommended dose exceeded; black box FDA warning describes that chronic use of
LABA inhalers may result in increased asthma morbidity and mortality, use only as additional therapy for patients
not adequately controlled on other asthma-controller medications (eg, low-dose to medium-dose inhaled
corticosteroids) or patients whose disease severity clearly warrants initiation of treatment with 2 maintenance
therapies
Formoterol (Foradil Aerolizer)
Formoterol relieves bronchospasm by relaxing the smooth muscles of the bronchioles in conditions associated with
asthma. Budesonide is an inhaled corticosteroid that alters level of inflammation in airways by inhibiting multiple
types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic
response. Available as MDI in 2 strengths; each actuation delivers formoterol 4.5 mcg with either 80 mcg or 160
mcg.
Dosing
Adult
12 mcg inhaled (contents of 1 cap inhaled PO) bid at least 12 h apart
Pediatric

Interactions
Concomitant use of beta-blockers may decrease bronchodilating, and vasodilating effects of beta agonists;
concurrent administration with methyldopa may increase pressor response; coadministration with oxytocic drugs
may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics, corticosteroids, or
theophylline derivatives may worsen; drugs that widen QTc interval (eg, quinidine, procainamide, pimozide,
moxifloxacin, sparfloxacin, gatifloxacin, sotalol, thioridazine, amiodarone) may potentiate cardiovascular side
effects; concomitant use with other beta-adrenergic agonists may result in additive effects
Contraindications
Documented hypersensitivity, angina, acutely deteriorating asthma, and cardiac arrhythmias associated with
tachycardia
Precautions
Pregnancy
Precautions
Not indicated to treat acute asthmatic symptoms or acute deterioration of COPD; not a substitute for inhaled
corticosteroids; adverse effects include paroxysmal bronchospasm, tremors, nervousness, and tachycardia;
caution in coronary insufficiency, arrhythmias, hypertension, diabetes mellitus, hyperthyroidism; higher incidence of
cardiovascular risks with doses >12 mcg bid; black box FDA warning describes that chronic use of LABA inhalers
may result in increased asthma morbidity and mortality, use only as additional therapy for patients not adequately
controlled on other asthma-controller medications (eg, low-dose to medium-dose inhaled corticosteroids) or
patients whose disease severity clearly warrants initiation of treatment with 2 maintenance therapies, including
formoterol
Methylxanthines
These agents are used for long-term control and prevention of symptoms, especially nocturnal symptoms.
Theophylline (Theo-24, Theochron, Uniphyl)
Available in short-acting and long-acting formulations. Because of the need to monitor the drug levels (see
Precautions below), this agent is used infrequently. Dose and frequency depends on particular product selected.
Dosing
Adult
200-600 mg PO q12-24h
Pediatric
Initial dose: 10 mg/kg PO sustained-release tablets and capsules; not to exceed 300 mg/d
First dose adjustment: 13 mg/kg PO; not to exceed 450 mg/d
Second dose adjustment: 16 mg/kg PO; not to exceed 600 mg/d
Interactions
Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins,

phenobarbital, phenytoin, rifampin, isoniazid, and sympathomimetics may decrease levels; allopurinol, beta-
blockers, ciprofloxacin, corticosteroids, disulfiram, quinolones, thyroid hormones, ephedrine, carbamazepine,
cimetidine, erythromycin, macrolides, propranolol, and interferon may increase levels
Contraindications
Documented hypersensitivity; uncontrolled arrhythmias, peptic ulcers, hyperthyroidism, uncontrolled seizure

disorders
Precautions
Pregnancy
Precautions
Narrow therapeutic range; serum concentration monitoring is mandatory; 10-15 mcg/mL required for maximum
effectiveness; adverse effects at usual therapeutic doses include insomnia, gastric upset, aggravation of ulcer or
reflux, increase in hyperactivity; dose-related acute toxicity includes tachyarrhythmia (SVT), nausea, vomiting,
headache, CNS stimulation, seizures, hematemesis, hyperglycemia, hypokalemia
Mast cell stabilizers

These agents block early and late asthmatic responses, interfere with chloride channels, stabilize the mast cell
membrane, and inhibit the activation and release of mediators from eosinophils and epithelial cells. They inhibit
acute responses to cold air, exercise, and sulfur dioxide.
Cromolyn sodium (Intal)
These NSAIDs are primarily used in preventive therapy.
Dosing
Adult
MDI: 2 inhalations q6h initially; once control achieved, may attempt gradual downward titration to 2 inhalations
q12h
Nebulizer: 20 mg in 2 mL nebulizer solution q6-8h
Pediatric
MDI:
Nebulizer:
Interactions
None reported
Contraindications
Precautions
Pregnancy
Precautions
Do not use in severe renal or hepatic impairment; symptoms may reoccur when withdrawing drug; unpleasant taste
Corticosteroids, inhaled
Steroids are the most potent anti-inflammatory agents. Inhaled forms are topically active, poorly absorbed, and
least likely to cause adverse effects. No study has shown significant toxicity with inhaled steroid use in children at
doses less than the equivalent of 400 mcg of beclomethasone per day. They are used for long-term control of
symptoms and for the suppression, control, and reversal of inflammation. Inhaled forms reduce the need for
systemic corticosteroids. They block late asthmatic response to allergens; reduce airway hyperresponsiveness;
inhibit cytokine production, adhesion protein activation, and inflammatory cell migration and activation; and reverse
beta2-receptor downregulation and subsensitivity (in acute asthmatic episodes with LABA use).
A systematic review of 18 placebo-controlled clinical trials evaluating monotherapy with inhaled corticosteroids
supports their safety and efficacy in children with asthma.[24 ]In addition, the data provide new evidence linking
inhaled corticosteroids use in children with asthma to improved asthma control.
Inhaled steroids include beclomethasone, triamcinolone, flunisolide, fluticasone, budesonide, and mometasone.
Ciclesonide (Alvesco)
Aerosol inhaled corticosteroid indicated for maintenance treatment of asthma as prophylactic therapy in adult and
adolescent patients aged 12 y and older. Not indicated for relief of acute bronchospasm.
Corticosteroids have wide range of effects on multiple cell types (eg, mast cells, eosinophils, neutrophils,
macrophages, lymphocytes) and mediators (eg, histamines, eicosanoids, leukotrienes, cytokines) involved in
inflammation.
Individual patients experience variable time to onset and degree of symptom relief. Maximum benefit may not be
achieved for 4 wk or longer after initiation of therapy.
After asthma stability achieved, best to titrate to lowest effective dosage to reduce possibility of side effects. For
patients who do not adequately respond to starting dose after 4 wk of therapy, higher doses may provide additional
asthma control.
Dosing
Adult
PO inhalation:
Patients previously on bronchodilator therapy alone: 80 mcg bid; not to exceed 160 mcg bid
Patients on previous inhaled corticosteroids: 80 mcg bid; not to exceed 320 mcg bid
Patients on previous PO corticosteroids: 320 mcg bid; not to exceed 320 mcg bid
Pediatric
<12 years: Not indicated

Interactions
Coadministration with PO ketoconazole may increase AUC but does not appear to be clinically significant
Contraindications
Documented hypersensitivity; bronchospasm, status asthmaticus, other types of acute episodes of asthma
Precautions
Pregnancy
Precautions
Not for acute attack; caution when replacing systemic corticosteroids because of risk of adrenal insufficiency; may
decrease growth velocity in pediatric patients; caution with active or quiescent tuberculosis infection or with
untreated fungal, viral, or bacterial infections; rare instances of wheezing, nasal septum perforation, cataracts,
glaucoma, and increased intraocular pressure reported
Beclomethasone (QVAR)
Inhibits bronchoconstriction mechanisms; causes direct smooth muscle relaxation; and may decrease the number
and activity of inflammatory cells, which, in turn, decreases airway hyperresponsiveness. Available as 40
mcg/actuation or 80 mcg/actuation.
Dosing
Adult
Taking bronchodilators alone: 40-80 mcg inhaled bid initially; may increase to 320 mcg bid
Taking inhaled corticosteroids: 40-160 mcg inhaled bid initially; may increase to 320 mcg bid
Pediatric

5-11 years:
40 mcg inhaled bid initially; may increase to 80 mcg bid
Interactions
None reported
Contraindications
Documented hypersensitivity, bronchospasm, status asthmaticus, other types of acute episodes of asthma
Precautions
Pregnancy
Precautions
Inhaled corticosteroids can cause PO thrush and hoarseness (prevented by rinsing the mouth after a dose and by
using a spacer with an MDI), and large doses (>800 mcg/d) have systemic adverse effects, including growth
retardation and HPA inhibition
Fluticasone (Flovent Diskus, Flovent HFA)
Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary
adrenocortical axis inhibitory potency when applied topically. Available as an MDI aerosolized product (HFA) or
DPI (Diskus).
Dosing
Adult
MDI:
Taking bronchodilators alone: 88 mcg inhaled bid; may increase, not to exceed 440 mcg bid
Taking inhaled corticosteroids: 88-220 mcg inhaled bid; may increase, not to exceed 440 mcg bid
Taking PO corticosteroids: 440 mcg inhaled bid; may increase, not to exceed 880 mcg bid
Diskus:
Taking bronchodilators alone: 100 mcg inhaled bid; not to exceed 500 mcg bid
Taking inhaled corticosteroids: 100-250 mcg inhaled bid; not to exceed 500 mcg bid
Taking PO corticosteroids: 500-1000 mcg inhaled bid
Pediatric
MDI:
88 mcg inhaled bid
Diskus:
4-11 years: 50 mcg inhaled bid; may increase, not to exceed 100 mcg bid
Interactions
None reported
Contraindications
Precautions
Pregnancy
Precautions
Inhaled corticosteroids can cause PO thrush and hoarseness (prevented by rinsing the mouth after a dose and by
using a spacer with an MDI), and large doses (>800 mcg/d) have systemic adverse effects, including growth
retardation and HPA inhibition; high-dose long-term therapy has been associated with HPA inhibition and might
retard growth
Budesonide (Pulmicort Flexhaler or Respules)
Has extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak hypothalamic-pituitary
adrenocortical axis inhibitory potency when applied topically. Available as a DPI in 90 mcg/actuation (delivers
about 80 mcg/actuation) or 180 mcg/actuation (delivers about 160 mcg/actuation). A nebulized susp (ie, Respules)
is also available for young children.
Dosing
Adult
DPI: 360 mcg inhaled bid initially (some patients may respond to 180 mcg bid initially); may increase dose, not to
exceed 720 mcg bid
Pediatric
Nebulizer (inhalation susp):

<1 year: Not established
1-8 years: 0.25-0.5 mg bid; not to exceed 1 mg/d
DPI:
6-17 years: 180 mcg inhaled bid initially (for some patients, 360 mcg bid initially may be appropriate); may increase
dose, not to exceed 360 mcg bid
Interactions
None reported
Contraindications
Precautions
Pregnancy
Precautions
Inhaled corticosteroids can cause PO thrush and hoarseness (prevented by rinsing mouth after a dose or using a
spacer with a MDI); large doses (>800 mcg/d) have systemic adverse effects, including growth retardation and
HPA inhibition. The manufacturer recommends not mixing the nebulizer solution with any other nebulized
medications. The nebulized solution must be delivered with a tight-fitting mask or mouthpiece.
Mometasone furoate inhalation powder (Asmanex Twisthaler)
Corticosteroid for PO inhalation. Indicated for asthma as prophylactic therapy.
Dosing
Adult
Patients who received bronchodilators alone: 220 mcg inhaled PO qhs; if needed, may increase to 220 mcg bid
Patients who received inhaled corticosteroids: 220 mcg inhaled PO qhs; if needed, may increase to 220 mcg bid
Patients who received PO corticosteroids: 440 mcg inhaled PO bid
Once-daily administration should be taken only in the evening
Pediatric

4-11 years: 110 mcg inhaled PO qhs
Interactions
Strong CYP 3A4 inhibitors (eg, ketoconazole) may increase plasma levels
Contraindications
Documented hypersensitivity; status asthmaticus or other acute asthmatic episodes
Precautions
Pregnancy
Precautions
Not effective for relief of acute bronchospasm; PO inhaled corticosteroids may cause Candida albicans infection in
the mouth and pharynx; may worsen tuberculosis or fungal, bacterial, viral, and parasitic infections; may suppress
HPA axis; long-term use may reduce bone mineral density and suppress growth in children; increases risk for
glaucoma and cataracts; common adverse effects include headache, allergic rhinitis, pharyngitis, URTI, sinusitis,
PO candidiasis, dysmenorrhea, musculoskeletal pain, back pain, and dyspepsia
Systemic corticosteroids
These agents are used for short courses (3-10 d) to gain prompt control of inadequately controlled acute asthmatic
episodes. They are also used for long-term prevention of symptoms in severe persistent asthma as well as for
suppression, control, and reversal of inflammation. Frequent and repetitive use of beta2-agonists has been
associated with beta2-receptor subsensitivity and downregulation; these processes are reversed with
corticosteroids.
Higher-dose corticosteroids have no advantage in severe asthma exacerbations, and intravenous administration
has no advantage over oral therapy, provided that GI transit time or absorption is not impaired. The usual regimen
is to continue frequent multiple daily dosing until the FEV1 or peak expiratory flow (PEF) is 50% of the predicted or
personal best values; then, the dose is changed to twice daily. This usually occurs within 48 hours.
Prednisone (Deltasone, Orasone) and prednisolone (Pediapred, Prelone, Orapred)
Immunosuppressants for the treatment of autoimmune disorders; may decrease inflammation by reversing
increased capillary permeability and suppressing PMN activity.
Dosing
Adult
5-60 mg/d PO qd or divided bid/qid; taper over 2 wk as symptoms resolve
Pediatric
1-2 mg/kg/d PO for 3-10 d; not to exceed 60-80 mg/d
Interactions
Coadministration with estrogens may decrease prednisone clearance; concurrent use with digoxin may cause
digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of
glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics
Contraindications
Documented hypersensitivity, viral infection, peptic ulcer disease, hepatic dysfunction, connective-tissue infections,
fungal or tubercular skin infections, GI disease
Precautions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Short-term use may be associated with adverse effects including reversible abnormalities of glucose metabolism,
increased appetite, fluid retention, weight gain, mood alteration, hypertension, peptic ulcer, and (rarely) aseptic
necrosis of femur; conditions such as tuberculosis, herpes viral infections, varicella, hypertension, and peptic ulcer,
may worsen with long-term systemic corticosteroids
Methylprednisolone (Solu-Medrol)
May decrease inflammation by reversing increased capillary permeability and suppressing PMN activity.
Dosing
Adult
0.5-1 mg/kg/dose IV q6h; not to exceed 5 d
Pediatric
1 mg/kg IV q6h
Interactions
Coadministration with digoxin may increase digitalis toxicity secondary to hypokalemia; estrogens may increase
levels; phenobarbital, phenytoin, and rifampin may decrease levels (adjust dose); monitor for hypokalemia with
concurrent diuretics
Contraindications
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Precautions
Pregnancy
Precautions
Hyperglycemia, edema, osteonecrosis, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis,
growth suppression, myopathy, and infections are possible complications of glucocorticoid use
Leukotriene modifier
Knowledge that leukotrienes cause bronchospasm, increased vascular permeability, mucosal edema, and
inflammatory cell infiltration leads to the concept of modifying their action by using pharmacologic agents. These
are either 5-lipoxygenase inhibitors or leukotriene-receptor antagonists.
Zafirlukast (Accolate)
Selective competitive inhibitor of LTD4, LTE4 receptors.
Dosing
Adult
20 mg PO bid
Pediatric

5-11 years: 10 mg PO bid
Interactions
Levels decrease when administered with erythromycin, terfenadine, and theophylline; may increase risk of bleeding
if administered with warfarin
Contraindications
Precautions
Pregnancy
Precautions
Take on an empty stomach; potential adverse effects include reversible hepatitis; bilirubin may accumulate in liver
dysfunction; Churg-Strauss vasculitis
Neuropsychiatric events have been reported; following further FDA evaluation, the prescribing information has
been updated to include case reports during postmarketing surveillance that include agitation, aggression,
anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking
and behavior (including suicide), and tremor
Montelukast (Singulair)
Last agent introduced in its class. The advantages are that it is chewable, it has a once-a-day dosing, and it has no
significant adverse effects.
Dosing
Adult
Chronic persistent asthma:

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

6-23 months: 1 packet of 4 mg PO granules PO hs
2-5 years: 4 mg PO hs
6-14 years: 5 mg PO hs
Exercise-induced asthma:
<15 years: Not established; some pediatric subspecialists recommend 5 mg PO qd
Interactions
Phenobarbital and rifampin may reduce montelukast AUC
Contraindications
Precautions
Pregnancy
Precautions
4 and 5 mg are chewable; may cause headache or dyspepsia; not indicated for immediate relief of acute asthma
symptoms, use appropriate short-acting inhaled beta2-agonist inhaler for exacerbations; not for use as
monotherapy in management of exercise-induced bronchospasm; if already taking montelukast daily (eg, chronic
asthma, allergic rhinitis), do not take an additional dose to prevent EIB; administration for chronic asthma has not
been established to prevent acute EIB; chewable tab contains phenylalanine, caution with phenylketonuria
Neuropsychiatric events have been reported; following further FDA evaluation, the prescribing information has
been updated to include case reports during postmarketing surveillance that include agitation, aggression,
anxiousness, dream abnormalities, hallucinations, depression, insomnia, irritability, restlessness, suicidal thinking
and behavior (including suicide), and tremor
Monoclonal Antibody
These agents bind selectively to human IgE on the surface of mast cells and basophils.
Omalizumab (Xolair)
Recombinant, DNA-derived, humanized IgG monoclonal antibody that binds selectively to human IgE on surface of
mast cells and basophils. Reduces mediator release, which promotes allergic response. Indicated for moderate-to-
severe persistent asthma in patients who react to perennial allergens in whom symptoms are not controlled by
inhaled corticosteroids.
Dosing
Adult
150-375 mg SC q2-4wk; inject slowly over 5-10 seconds because of viscosity; not to exceed 150 mg per injection
site
Precise dose and frequency established by serum total IgE level (IU/mL)
Pediatric

Interactions
None reported
Contraindications
Precautions
Pregnancy
Precautions
Not effective to treat acute asthma; do not abruptly discontinue inhaled corticosteroids when initiating omalizumab;
malignancy incidence among omalizumab-treated patients (0.5%) was numerically higher than among patients in
control groups (0.2%); malignancies were of various types, and further long-term observation is needed to fully
assess risk; may cause injection-site reaction
Combination inhaled steroid/long-acting beta2-agonist

These combinations may decrease asthma exacerbations when inhaled short-acting beta2-agonists and
corticosteroids have failed. Refer to previous discussion in the LABAs section regarding increased risk of severe
asthma episodes and death with LABAs.
Budesonide and formoterol (Symbicort)
Formotero relieves bronchospasm by relaxing the smooth muscles of the bronchioles in conditions associated with
asthma. Budesonide is an inhaled corticosteroid that alters level of inflammation in airways by inhibiting multiple
types of inflammatory cells and decreasing production of cytokines and other mediators involved in the asthmatic
response. Available as MDI in 2 strengths; each actuation delivers formoterol 4.5-mcg with either 80-mcg or 160-
mcg.
Dosing
Adult
Patients previously on medium-to-high dose inhaled steroids: 2 inhalations of 4.5/160 PO bid

Patients previously on low-to-medium dose inhaled steroids: 2 inhalations of 4.5/80 PO bid
Patients not currently receiving inhaled corticosteroids: 2 inhalations PO bid (strength depends on asthma severity)
Do not exceed 2 inhalations of 160/4.5 daily
Pediatric

Interactions
Budesonide: None reported

Formoterol: Concomitant use of beta-blockers may decrease bronchodilating, and vasodilating effects of beta
agonists; concurrent administration with methyldopa may increase pressor response; coadministration with
oxytocic drugs may result in severe hypotension; ECG changes and hypokalemia resulting from diuretics,
corticosteroids, or theophylline derivatives may worsen; drugs that widen QTc interval (eg, quinidine, procainamide,
pimozide, moxifloxacin, sparfloxacin, gatifloxacin, sotalol, thioridazine, amiodarone) may potentiate cardiovascular
side effects; concomitant use with other beta-adrenergic agonists may result in additive effects
Contraindications
Documented hypersensitivity to adrenergic amines, formoterol, budesonide, or any component of formulation; need
for acute bronchodilation (including status asthmaticus)
Precautions
Pregnancy
Precautions
Use only as adjuvant therapy in patients not adequately controlled on other asthma-controller medications; not
meant to relieve acute asthmatic symptoms or rapidly deteriorating symptoms (treat acute episodes with short-
acting beta2 agonist); caution in patients with cardiovascular disease (arrhythmia or hypertension or HF); beta
agonists may cause elevation in blood pressure and heart rate and may result in CNS stimulation and excitation;
may also increase risk of arrhythmias
Use with caution in patients with diabetes mellitus; beta2 agonists may increase serum glucose levels; use with
caution in patients with GI diseases (eg, diverticulitis, peptic ulcer, ulcerative colitis) due to perforation risk; caution
in patients with hepatic impairment and patients with hypokalemia (beta2 agonists may decrease serum
potassium); caution in myasthenia gravis (exacerbation of symptoms has occurred during initial treatment with
corticosteroids); caution following acute MI (corticosteroids associated with myocardial rupture); caution in patients
with cataracts and/or glaucoma; increased intraocular pressure, open-angle glaucoma, and cataracts have
occurred with prolonged use; high doses and/or long-term use of corticosteroids have been associated with
increased bone loss and osteoporotic fractures
Caution in renal impairment (fluid retention may occur); beta agonists may result in CNS stimulation/excitation
(caution in patients with seizure disorders); changes in thyroid status may necessitate dosage adjustments;
metabolic clearance of corticosteroids increases in patients with hyperthyroidism and decreases in patients with
hypothyroidism; HPA axis suppression may lead to adrenal crisis (withdrawal and discontinuation of corticosteroids
should be slow and careful); particular care required when patients transferred from systemic corticosteroids to
inhaled products due to possible adrenal insufficiency or withdrawal from steroids, including increase in allergic
symptoms (patients receiving >20 mg/d of prednisone (or equivalent) may be most susceptible); steroids do not
provide systemic steroid needed to treat trauma, surgery, or infections
Warning: LABAs may increase risk of asthma-related deaths; rarely, paradoxical bronchospasm may occur with
use of inhaled bronchodilating agents (should be distinguished from inadequate response); immediate
hypersensitivity reactions (eg, urticaria, angioedema, rash, bronchospasm) reported; prolonged use of
corticosteroids may increase incidence of secondary infection, mask acute infection (including fungal infections),
prolong or exacerbate viral infections, or limit response to vaccines; exposure to chickenpox should be avoided;
corticosteroids should not be used to treat ocular herpes simplex or cerebral malaria; close observation is required
in patients with latent tuberculosis and/or tuberculosis reactivity; restrict use in active tuberculosis (only in
conjunction with antituberculosis treatment); may cause psychiatric manifestations, including depression, euphoria,
insomnia, mood swings, and personality changes (preexisting psychiatric conditions may be exacerbated by
corticosteroid use); do not exceed recommended dose (serious adverse events, including fatalities, associated with
excessive use of inhaled sympathomimetics)
Fluticasone and salmeterol (Advair HFA, Advair Diskus)
Fluticasone inhibits bronchoconstriction mechanisms, produce direct smooth muscle relaxation, may decrease
number and activity of inflammatory cells, in turn decreasing airway hyper-responsiveness. Also has
vasoconstrictive activity. Salmeterol relaxes the smooth muscles of the bronchioles in conditions associated with
bronchitis, emphysema, asthma, or bronchiectasis, can relieve bronchospasms. Effect may also facilitate
expectoration.
Adverse effects are more likely to occur when administered at high or more frequent doses than recommended.
Two delivery mechanisms are available (ie, powder for inhalation [Diskus], MDI). Diskus available as combination
of salmeterol 50 mcg with fluticasone 100 mcg, 250 mcg, or 500 mcg. MDI available as 21 mcg salmeterol with
fluticasone 45 mcg, 115 mcg, or 230 mcg.
Dosing
Adult
Diskus: 1 inhalation PO bid (at least 12 h apart); dose based on asthma severity
MDI: 2 inhalations PO bid (at least 12 h apart); dose based on asthma severity
Pediatric
Diskus:
4-12 years: 1 inhalation PO bid (at least 12 h apart); not to exceed 100 mcg fluticasone/50 mcg salmeterol
MDI:
Interactions
Coadministration of fluticasone with CYP450 3A4 isoenzyme inhibitors (eg, amprenavir, atazanavir, darunavir,
delavirdine, fosamprenavir, indinavir, ketoconazole, nelfinavir, ritonavir, tipranavir) decreases fluticasone
elimination and increases plasma fluticasone levels, case reports of iatrogenic Cushingoid symptoms have been
reported
Concomitant use of salmeterol with beta-blockers may decrease bronchodilating, and vasodilating effects of beta
agonists; concurrent administration of salmeterol with methyldopa may increase pressor response;
coadministration of salmeterol with oxytocic drugs may result in severe hypotension; ECG changes and
hypokalemia resulting from diuretics may worsen when coadministered with salmeterol
Contraindications
Documented hypersensitivity; bronchospasm, status asthmaticus, other types of acute episodes of asthma, angina,
tachycardia, and cardiac arrhythmias associated with tachycardia
Precautions
Pregnancy
Precautions
Coughing, URTI, and bronchitis may occur with fluticasone; not indicated to treat acute asthmatic symptoms; black
box FDA warning describes that chronic use of salmeterol may result in increased asthma morbidity and mortality,
use only as additional therapy for patients not adequately controlled on other asthma-controller medications (eg,
low-dose to medium-dose inhaled corticosteroids) or patients whose disease severity clearly warrants initiation of
treatment with 2 maintenance therapies, including salmeterol
Mometasone and formoterol (Dulera)
Combination corticosteroid and LABA metered-dose inhaler. Mometasone elicits local anti-inflammatory effects to
respiratory tract with minimal systemic absorption. Formoterol elicits bronchial smooth muscle relaxation. Indicated
for prevention and maintenance of asthma symptoms in patients inadequately controlled with other asthma
controller medications (eg, low-dose to medium-dose inhaled corticosteroids) or whose disease severity clearly
warrants initiation of treatment with 2 maintenance therapies, including a LABA. Available in 2 strengths; each
actuation delivers mometasone/formoterol 100 mcg/5 mcg or 200 mcg/5 mcg.
Dosing
Adult
2 inhalations PO bid
Starting dose based on prior asthma therapy
Inhaled medium-dose corticosteroids: 100 mcg/5 mcg, 2 inhalations PO bid; not to exceed daily dose of 400
mcg/20 mcg
Inhaled high-dose corticosteroids: 200 mcg/5 mcg, 2 inhalations PO bid; not to exceed daily dose of 800 mcg/20
mcg
Pediatric

Interactions
Coadministration with other LABAs increases risk for overdose; coadministration with strong CYP3A4 inhibitors
(eg, ritonavir) increases risk of increased systemic corticosteroid effects
Contraindications
Documented hypersensitivity; status asthmaticus or other acute episodes of asthma
Precautions
Pregnancy
Precautions
Black box warning

LABAs may increase risk of asthma-related deaths; therefore, when treating asthma, use only as additional therapy
if not adequately controlled on other asthma controller medications (eg, low- to medium-dose inhaled
corticosteroids) or if asthma severity clearly warrants initiation of treatment with 2 maintenance therapies
Once asthma control achieved and maintained, assess patient at regular intervals and step down therapy (eg,
discontinue LABA) if possible without loss of asthma control, and maintain on a long-term asthma control
medication (eg, inhaled corticosteroid)
Do not use if asthma is adequately controlled on low- or medium-dose inhaled corticosteroids
Other precautions
Do not initiate in acutely deteriorating asthma or use for acute symptoms; oropharyngeal Candida albicans
infection may occur (advise patients to rinse mouth following inhalation); may cause immunosuppression and
potentially worsen existing ocular herpes simplex, tuberculosis, or fungal, bacterial, viral, or parasitic infections;
serious or even fatal course of chickenpox or measles can occur in susceptible patients
Risk of impaired adrenal function when switching from PO corticosteroids; taper patients slowly from systemic
corticosteroids; hypercorticism and adrenal suppression may occur with very high dosages or at regular dosage in
susceptible individuals; discontinue inhaler and institute alternative therapy if paradoxical bronchospasm occurs;
caution in cardiac conditions in which beta-adrenergic stimulation needs to be avoided
Corticosteroids may decrease bone mineral density; monitor growth of children because of potential for HPA
suppression; monitor for vision changes and caution with history of increased intraocular pressure, glaucoma,
and/or cataracts; monitor for hypokalemia and hyperglycemia; caution with convulsive disorders, thyrotoxicosis,
diabetes mellitus, and ketoacidosis
Anticholinergic Agent
These agents may be added to beta2-agonist therapy for acute exacerbation.
Ipratropium (Atrovent)
Chemically related to atropine. Has antisecretory properties and, when applied locally, inhibits secretions from
serous, and seromucous glands lining the nasal mucosa. MDI delivers 17 mcg/actuation. Solution for inhalation
contains 500 mcg/2.5 mL (ie, 0.02% solution for nebulization).
Dosing
Adult
Nebulizer: 1 vial (500 mcg) inhaled via nebulizer tid/qid

MDI: 2 inhalations PO qid; not to exceed 12 inhalations in 24 h
Pediatric
Nebulizer: 250 mcg (1.25 mL) inhaled via nebulizer tid

MDI: 1-2 inhalations PO tid; not to exceed 6 inhalations in 24 h
Interactions
Drugs with anticholinergic properties, such as dronabinol, may increase toxicity; albuterol increases effects of
ipratropium
Contraindications
Precautions
Pregnancy
Precautions
Not indicated for acute episodes of bronchospasm; caution in narrow-angle glaucoma, prostatic hypertrophy, and
bladder neck obstruction
Follow-up
Further Inpatient Care
 Admit patients with asthma for treatment of acute severe episodes if they are unresponsive to outpatient
care (eg, they have worsening bronchospasm, hypoxia, evidence of respiratory failure).
 Once the patient is admitted, further investigations (eg, pulmonary function tests [PFTs], allergy testing, and
investigations to rule out other associated conditions and complications) can be performed.
Further Outpatient Care
 Regular follow-up visits (1-6 mo) are essential to ensure control and appropriate therapeutic adjustments.
 Outpatient visits should include the following:

 Interval history of asthmatic complaints, including history of acute episodes (eg, severity, measures
and treatment taken, response to therapy)
 History of nocturnal symptoms
 History of symptoms with exercise and exercise tolerance
 Review of medications, including use of rescue medications
 Review of home-monitoring data (eg, symptom diary, peak flow meter readings, daily treatments)
 Patient evaluation should include the following:

 Assessment for signs of bronchospasm and complications
 Evaluation of associated conditions (eg, allergic rhinitis)
 Pulmonary function testing (in appropriate age group)
 Address issues of treatment adherence and avoidance of environmental triggers and irritants.
 Long-term asthma care pathways that incorporate the aforementioned factors can serve as roadmaps for
ambulatory asthma care and help streamline outpatient care by different providers.
 In the author's asthma clinic, a member of the asthma care team sits with each patient to review the written
asthma care plan and to write and discuss in detail a rescue plan for acute episode, which includes
instructions about identifying signs of acute episode, using rescue medications, monitoring, and contacting
the asthma care team. These items are reviewed at each visit.
Inpatient & Outpatient Medications
 Bronchodilators (short-acting and long-acting)
 Controlling medications (nonsteroidal, steroidal, newer agents such as leukotriene modifiers)
 Medications for the treatment of associated conditions (antiallergy medications, nasal steroids for allergic
rhinitis)
 Rescue medications for use in acute episodes (short burst of steroids)
Transfer
 Any patient with a high risk of asthma should be referred to a specialist. The following may suggest a high
risk:
 History of sudden severe exacerbations
 History of prior intubation for asthma
 Admission to an ICU because of asthma
 Two or more hospitalizations for asthma in the past year

 Three or more emergency department visits for asthma in the past year
 Hospitalization or an emergency department visit for asthma within the past month
 Use of 2 or more canisters of inhaled short-acting beta2-agonists per month
 Current use of systemic corticosteroids or recent withdrawal from systemic corticosteroids
 The choice between a pediatric pulmonologist and an allergist may depend on local availability and
practices. A patient with frequent ICU admissions, previous intubation, and a history of complicating factors
or comorbidity (eg, cystic fibrosis) should be referred to a pediatric pulmonologist. When allergies are
thought to significantly contribute to the morbidity, an allergist may be helpful.
Deterrence/Prevention
 The goal of long-term therapy is to prevent acute exacerbations.
 The patient should avoid exposure to environmental allergens and irritants that are identified during the
evaluation.
Complications
 Pneumothorax status asthmaticus with respiratory failure
 Fixed (nonreversible) airway obstruction
 Death
Prognosis
 Of infants who wheeze with upper respiratory tract infections (URTIs), 60% are asymptomatic by age 6
years; however, children who have asthma (recurrent symptoms continuing at age 6 y) have airway
reactivity later in childhood.
 Some findings suggest a poor prognosis if asthma develops in children younger than 3 years, unless it
occurs solely in association with viral infections.
 Individuals who have asthma during childhood have significantly lower FEV1 and airway reactivity and more
persistent bronchospastic symptoms than those with infection-associated wheezing.
 Children with mild asthma who are asymptomatic between attacks are likely to improve and be symptom-
free later in life.
 Children with asthma appear to have less severe symptoms as they enter adolescence, but half of these
children continue to have asthma.
 Asthma has a tendency to remit during puberty, with a somewhat earlier remission in girls. However,
compared with men, women have more bronchial hyperresponsiveness (BHR).
Patient Education
 Patient and parent education should include instructions on how to use medications and devices (eg,
spacers, nebulizers, metered dose inhalers [MDIs]). The patient's MDI technique should be assessed on
every visit.
 Discuss the management plan, which includes instructions about the use of medications, precautions with
drug and/or device usage, monitoring symptoms and their severity (peak flow meter reading), and
identifying potential adverse effects and necessary actions.
 Write and discuss in detail a rescue plan for an acute episode. This plan should include instructions for
identifying signs of an acute attack, using rescue medications, monitoring, and contacting the asthma care
team.
 Parents should understand that asthma is a chronic disorder with acute exacerbations; hence, continuity of
management with active participation by the patient and/or parents and interaction with asthma care
medical personnel is important.
 Emphasize the importance of compliance with and adherence to treatment.
 Incorporate the concept of expecting full control of symptoms, including nocturnal and exercise-induced
symptoms, in the management plans and goals (for all but the most severely affected patients).
 Avoid unnecessary restrictions in the lifestyle of the child or family. Expect the child to participate in
recreational activities and sports and to attend school as usual.
 Coffman and colleagues conducted a systematic review of the literature on school-based asthma education
programs that included 25 studies in children aged 4-17 years. [25 ]Most studies found that, compared with
usual care, school-based asthma education improved knowledge of asthma (7 of 10 studies), self-efficacy
(6 of 8 studies), and self-management behaviors (7 of 8 studies). Fewer studies reported favorable effects
on quality of life (4 of 8 studies), days of symptoms (5 of 11 studies), nights with symptoms (2 of 4 studies),
and school absences (5 of 17 studies).
 For excellent patient education resources, see eMedicine's Asthma Center. Also, visit eMedicine's patient
education articles Asthma, Asthma FAQs, Understanding Asthma Medications, Asthma in Children, and
Asthma in School Children: Educational Slides.
Miscellaneous
Medicolegal Pitfalls
 Failure to recognize the severity of an acute severe episode (ie, status asthmaticus) and to initiate
aggressive management (eg, intubation and ventilation) can lead to fatal complications such as respiratory
failure and even death.
 Failure to diagnose pneumothorax can lead to serious consequences.
 Identification of associated or complicating conditions (eg, allergic rhinitis or sinusitis) is important for
comprehensive management.
 Underdiagnosis of asthma, including recurrent bronchitis, chronic bronchitis, and asthmatic bronchitis can
be a problem.
Special Concerns
 In children, long-term use of high-dose steroids (systemic or inhaled) may lead to adverse effects, including
growth failure. Recent data from the Childhood Asthma Management Program (CAMP) study and results of
the long-term use of inhaled steroids (budesonide) suggest that the long-term use of inhaled steroids has no
sustained adverse effect on growth in children. [26,27 ]
Multimedia
Media file 1: Pediatric asthma. Classification of asthma control.
Chart available at http://img.medscape.com/pi/emed/ckb/pediatrics_general/1331341-1331361-1000997-

1544741.pdf.
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http://www.aanma.org/pharmacy/ph_medicaldevices.htm. Accessed Sep 24 2008.
Keywords
pediatric asthma, asthma in children, child asthma, pediatric asthma symptoms, pediatric asthma causes, asthma
Contributor Information and Disclosures
Author
Girish D Sharma, MD, Associate Professor of Pediatrics, Rush Medical College; Director, Section of Pediatric

Pulmonology and Rush Cystic Fibrosis Center, Rush University Medical Center
Girish D Sharma, MD is a member of the following medical societies: American Academy of Pediatrics, American
College of Chest Physicians, American Thoracic Society, and Royal College of Physicians of Ireland
Disclosure: Nothing to disclose.
Coauthor(s)
Payel Gupta, MD, Fellow in Allergy and Immunology, Long Island College Hospital/SUNY Downstate

Payel Gupta, MD is a member of the following medical societies: American College of Physicians
Medical Editor
Thomas Scanlin, MD, Chief, Division of Pulmonary Medicine and Cystic Fibrosis Center, Department of

Pediatrics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School
Thomas Scanlin, MD is a member of the following medical societies: American Association for the Advancement of
Science, American Society for Biochemistry and Molecular Biology, American Thoracic Society, Society for
Pediatric Research, and Society for Pediatric Research
Pharmacy Editor
Mary L Windle, PharmD, Adjunct Associate Professor, University of Nebraska Medical Center College of

Pharmacy; Pharmacy Editor, eMedicine
Managing Editor
Charles Callahan, DO, Professor, Deputy Chief of Clinical Services, Walter Reed Army Medical Center
Charles Callahan, DO is a member of the following medical societies: American Academy of Pediatrics, American
College of Chest Physicians, American College of Osteopathic Pediatricians, American Thoracic Society,
Association of Military Surgeons of the US, and Christian Medical & Dental Society
CME Editor
Mary E Cataletto, MD, Associate Director, Division of Pediatric Pulmonology, Winthrop University Hospital;

Professor of Clinical Pediatrics, State University of New York at Stony Brook; Director of Children's Sleep Services,
Winthrop University Hospital
Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and
American College of Chest Physicians
Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting
Chief Editor
Michael R Bye, MD, Professor of Clinical Pediatrics, Division of Pulmonary Medicine, Columbia University College
of Physicians and Surgeons; Attending Physician, Pediatric Pulmonary Medicine, Morgan Stanley Children's
Hospital of New York Presbyterian, Columbia University Medical Center
Michael R Bye, MD is a member of the following medical societies: American Academy of Pediatrics, American
College of Chest Physicians, and American Thoracic Society
Disclosure: Merck Honoraria Speaking and teaching
Further Reading
 Asthma resources from Medscape and eMedicine

 Asthma News and Articles
 Asthma Clinical Reference
 Asthma CME
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Asthma: [Print] - eMedicine Pediatrics: General Medicine Page 1 of 38

eMedicine Specialties > Pediatrics: General Medicine > Pulmonology

Approximately 34.1 million Americans have been diagnosed with asthma in their lifetime. The prevalence of

 Precipitating and/or aggravating factors

 Development of disease and treatment

During an acute episode, symptoms vary according to the severity.

 Emotional factors: In some individuals, emotional upsets clearly aggravate asthma.

Airway Foreign Body Cystic Fibrosis

 Asthma is an inflammatory disease characterized by the recruitment of inflammatory cells, vascular

Pediatric asthma. Classification of asthma control.

Chart available at http://img.medscape.com/pi/emed/ckb/pediatrics_general/1331341-1331361-

 Assessment and monitoring

 Control of environmental factors and comorbid conditions

course of systemic corticosteroids is helpful.

 An ENT specialist may help in managing chronic rhinosinusitis.

 A gastroenterologist may help in excluding and/or treating gastroesophageal reflux.

Delivery Devices and Best Route of Administration

 Breath-actuated pMDI - Propellant used to dispense steroid when patient inhales

 Nebulized solution devices

Stepwise Approach to Asthma Medications

Intermittent Persistent Asthma: Daily Medication

Age Step 1 Step 2 Step 3 Step 4 Step 5 Step 6

Albuterol sulfate (Proventil HFA, Ventolin HFA, ProAir HFA)

Pirbuterol acetate (Maxair Autohaler)

PO inhalation: 1-2 inhalations q4-6h; not to exceed 12 inhalations q24h

Caution in hyperthyroidism, diabetes mellitus, or cardiovascular disorders

Nonracemic form of the beta2-agonist albuterol

MDI: 45-90 mcg (1-2 inhalations) q4-6h

MDI: Administer as in adults

Salmeterol (Serevent Diskus)

Serevent Diskus: 1 inhalation (50 mcg) q12h

<4 years: Not established

Formoterol (Foradil Aerolizer)

12 mcg inhaled (contents of 1 cap inhaled PO) bid at least 12 h apart

<5 years: Not established

Theophylline (Theo-24, Theochron, Uniphyl)

Aminoglutethimide, barbiturates, carbamazepine, ketoconazole, loop diuretics, charcoal, hydantoins,

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

Mast cell stabilizers

Cromolyn sodium (Intal)

These NSAIDs are primarily used in preventive therapy.

<12 years: Not indicated

<5 years: Not established

Fluticasone (Flovent Diskus, Flovent HFA)

Budesonide (Pulmicort Flexhaler or Respules)

Nebulizer (inhalation susp):

Mometasone furoate inhalation powder (Asmanex Twisthaler)

Corticosteroid for PO inhalation. Indicated for asthma as prophylactic therapy.

<4 years: Not established

Documented hypersensitivity; status asthmaticus or other acute asthmatic episodes

Prednisone (Deltasone, Orasone) and prednisolone (Pediapred, Prelone, Orapred)

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

1-2 mg/kg/d PO for 3-10 d; not to exceed 60-80 mg/d

0.5-1 mg/kg/dose IV q6h; not to exceed 5 d

Documented hypersensitivity; viral, fungal, or tubercular skin infections

Selective competitive inhibitor of LTD4, LTE4 receptors.

<5 years: Not established

Chronic persistent asthma:

Chronic persistent asthma:

Phenobarbital and rifampin may reduce montelukast AUC

<12 years: Not established

Combination inhaled steroid/long-acting beta2-agonist

Budesonide and formoterol (Symbicort)