Bronchial asthma is a disease manifested reversible (fully or partially),
bronchial obstruction, which is based on pathogenetic allergic inflammation of
airways and, in most cases, bronchial hyperreactivity.
It is characterized
by recurring attacks of breathlessness, resulting from smooth muscle spasm,
edema of mucous membrane of the bronchi and their blockage by viscid secret
that leads to the BOS.
Etiology
and pathogenesis.
Asthma may be allergic origin, ie, occurs in
individuals with increased sensitivity to certain chemicals or physical factors
- allergens. Increased sensitivity may be a manifestation of
hereditary-constitutional features of the organism, or develops as a result of
prolonged contact with the allergen, while the impact on the body of a number
of adverse factors (cooling, fatigue, chronic inflammatory diseases, etc.).
Asthma may also be infectious
origin. At the outbreak of infectious bronchial asthma important role have bacteria,
viruses and other microbes, which in interaction with the organism cause its
allergic restruction. Most often it develops on a background of chronic
respiratory diseases or paranasal sinusitis, at which in the body there is
infection focus of a long time, as well as products of the microbes and substances
produced during inflammation, have the properties of allergens.
Noninfectious asthma is caused by
allergens of animal and vegetable origin. Allergens of animal origin include
wool, horse hair, fish scales, etc. Sensitivity is sometimes also observed in
some insect - bugs, cockroaches, butterflies, etc. Among the allergens of plant
pollens play a special role. Bronchial asthma caused by plant allergens occur
in a certain season of the year (April - July) - the period of flowering
plants. In addition, the cause of asthma may be house dust and dry food for
aquarium fish, etc., certain foods (eggs, crabs, chocolate, mushrooms,
strawberries, oranges, etc.), some medicines.
In the event of attack of asthma there
are importance of individual
characteristics of nervous and endocrine systems. There are known occasions that
in the patient with sensitiveness to the
smell of roses, attack started at the sight of artificial roses. Negative
emotions may provoke attacks also. In some patients attacks of asthma do not
appear in periods of intense work, or during deep sleep.
The development and course of
bronchial asthma depend on climatic factors. Exacerbations of the disease are
often observed in spring and fall moon, patients often feel worse in windy
weather, with sudden changes in temperature and atmospheric pressure at high
humidity. In addition, high humidity contribute to the exacerbation of chronic
bronchial and lung infections, which aggravates the course of bronchial asthma.
The modern theory of the
pathogenesis of asthma is the concept of allergic inflammation, which has
become an integrating, connecting the mediator (histamine), lipid membranes -
receptor (β2 - adrenergic receptors), neurovegetative
(vagotonia), reagine (Ig E) and other concepts. Development of suffocation is
conditioned directly by three major pathophysiological mechanisms:
bronchospasm, edema of bronchial mucosa and hypersecretion of bronchial glands.
The inflammatory response in asthma is
illustrated in this airway section from a patient with mild asthma who died in
an accident. There is a submucosal infiltration of eosinophils and a marked
deposition of collagen below the basement membrane. (From Hilman BC (ed):
Pediatric Respiratory Disease. Philadelphia, WB Saunders, 1993, p.625.)
Classification of bronchial asthma
The severity of asthma is
classified on the basis of complex clinical and functional signs of bronchial
obstruction. The physician evaluates the frequency, severity and duration of
attacks of expiratory dyspnea, patient's condition during the period between
attacks, severity, variabillity, and repayment of functional bronchial
obstruction, response to treatment. Evaluation of functional indicators for
determining the severity of the disease is carried out in the absence of
episodes expiratory dyspnea. According to this classification, the patient's
condition is determined by the degrees of seriousness of bronchial asthma. So
there are intermittent (episodic)
course; persistent (constant) course: mild, moderate and severe.
The
National Asthma Education and Prevention Program Expert Panel Report II
(EPR-2), "Guidelines for the Diagnosis and Management of Asthma,"
highlight the importance of correctly diagnosing asthma. To establish the
diagnosis of asthma, the clinician must establish the following: (a) episodic
symptoms of airflow obstruction are present, (b) airflow obstruction or
symptoms are at least partially reversible, and (c) alternative diagnoses are
excluded.
The
severity of asthma is classified as mild intermittent, mild persistent,
moderate persistent, or severe persistent, according to the frequency and
severity of symptoms, including nocturnal symptoms, characteristics of acute
episodes, and pulmonary function.
These categories do not always work well in
children. First, lung function is difficult to assess in younger children.
Second, asthma that is triggered solely by viral infections does not fit into
any category. While the symptoms may be intermittent, they may be severe enough
to warrant hospitalization. Therefore, a category of severe intermittent asthma
has been suggested.
Features of the categories include the
following:
Patients with mild intermittent disease have
symptoms fewer than 2 times a week, and pulmonary function is normal between
exacerbations. Exacerbations are brief, lasting from a few hours to a few days.
Nighttime symptoms occur less than twice a month. The variation in peak
expiratory flow (PEF) is less than 20%.
Patients with mild persistent asthma have symptoms
more than 2 times a week but less than once a day. Exacerbations may affect
activity. Nighttime symptoms occur more than twice a month. Pulmonary function
test results (in age-appropriate patients) demonstrate that the forced
expiratory volume in 1 second (FEV1) or PEF is less than 80% of the predicted
value, and the variation in PEF is 20-30%.
Patients with moderate persistent asthma have
daily symptoms and use inhaled short-acting beta2-agonists every day. Acute
exacerbations in patients with moderate persistent asthma may occur more than 2
times a week and last for days. The exacerbations affect activity. Nocturnal
symptoms occur more than once a week. FEV1 and PEF values are 60-80% of the
predicted values, and PEF varies by more than 30%.
Patients with severe persistent asthma have
continuous or frequent symptoms, limited physical activity, and frequent
nocturnal symptoms. FEV1 and PEF values are less than 60% of the predicted
values, and PEF varies by more than 30%.
Disease with any of their features
is assigned to the most severe grade. The presence of one severe feature is
sufficient to diagnose severe persistent asthma. The characteristics in this
classification system are general and may overlap because asthma is highly
variable. The 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.
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.
Clinic
Asthma may be manifested in
the form of whistles, wheezing when breathing, shortness of breath (dyspnea) with
exertion or at rest, in the form of coughing, which may be paroxysmal.
The classic manifestation of
bronchial asthma is the attack of asphyxia. Typically, it begins suddenly,
usually at night. The patient feels a pain and lack of air. Breathing is
difficult, exhaling long and is accompanied by a loud whistling wheezing
(so-called, expiratory dyspnea). Cough may join soon. In order to facilitate
breathing patient takes the forced position - rising or setting, leaning on the
edge of the bed, chair, straining his pectoral muscle.
After some time, breathing
becomes calmer, sputum is separating; attack stops. Attacks last from several
minutes to several hours or even days. Such prolonged or frequent (occurring at
short intervals during the day) the attacks are called an asthmatic state.
Occasional attacks do not leave behind any changes in the lungs, but with the
development of the disease and the increasing frequency of attacks may occur
emphysema, impairment of the heart. It should be in mind that asphyxia may be
caused not only by asthma but other diseases. In most cases, the doctor during
the examination of the patient may
determine the nature and origin of suffocation, with the need to use
instrumental and laboratory methods.
Objectively: skinis pale, cyanosis of the lips,
nasolabial triangle, acrocyanosis. Thorax is blown, shoulders are raised, lung
percussion sound is bandbox, auscultation reveals relaxed breathing, prolonged exhaling,
a large number of dry whistling wheezing and
changing moist rales. Borders of the heart are not defined, the tones are
weakened, tachycardia.
Diagnostic criteria
Anamnesis. Symptoms:
wheezing, shortness of breath, cough, fever, the formation of phlegm, and other
allergic disorders. There is possible presence of contributing factors
(allergens, infection, etc.), occurrence of asthma attacks at night. Attacks
are curable. The outcome of previous attacks (the need for hospitalization,
treatment with steroids).
Physical examination.
Total: tachypnea, tachycardia, part of the auxiliary respiratory muscles,
cyanosis, paradoxical pulse (the inclusion of support muscles and paradoxical
pulse are correlated with the severity of obstruction). Lungs: adequate
aeration, with auscultation the symmetry of breath, wheezing, long exhalation,
increased volume of lungs are determined. Heart: signs of CVF. Allergic
rhinitis and (or) sinusitis or dermatitis.
The clinical picture varies. Symptoms may be
associated with 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, it is not uncommon
for a patient with mild asthma to have normal findings at 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.
Allergic shiners. (From Marks M: Physical
Signs of Allergy of the Respiratory Tract in Children. New
York, American College
of Allergy, Asthma and
Immunology, 1990.)
Nose wrinkling of an allergic child. (From
Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy,
Asthma and Immunology, 1990.)
Allergic salute. (From Marks M: Physical
Signs of Allergy of the Respiratory Tract in Children. New
York, American College
of Allergy, Asthma and
Immunology, 1990.)
Transverse nasal crease in an allergic child.
(From Marks M: Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy,
Asthma and Immunology, 1990.)
"Rabbit nose" of allergic
rhinitis. (From Marks M: Physical Signs of Allergy of the Respiratory Tract in
Children. New York, American College of Allergy,
Asthma and Immunology, 1990.)
Dark
circles beneath the eyes of a child with allergic rhinitis. (From Marks M:
Physical Signs of Allergy of the Respiratory Tract in Children. New York, American College of Allergy,
Asthma and Immunology, 1990.)
Ocular allergy. (From Marks M: Physical Signs of Allergy of the
Respiratory Tract in Children. New York,
American College
of Allergy, Asthma and
Immunology, 1990.)
Polymorphis erythema (Courtesy of Robert A.
Silverman, M.D.)
Urticaria.
(Courtesy of LM Pachter, M.D.)
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.
Additional
data. Despite the fact that lung function tests are not
decisive in the diagnosis, they help assess the severity of airway obstruction
and subsequent response to therapy in chronic and acute situations. VC,
FVC,, FEV, the maximum air velocity in the middle of expiration, the maximum
expiratory flow rate (test Tiffno), FEV / VC decrease, residual volume (RV) and
total lung capacity (TLC) increase during
episodes of obstruction. Reduced FVC <25% of the proper or <0,75 after
the appointment of bronchodilator indicates the severity of the disease.
Pulmonary function test (PFT) results are
not reliable in patients younger than 5 years. In young children (3-6 y) and
older children who can't perform the conventional spirometry maneuver, newer
techniques, such as measurement of airway resistance using impulse oscillometry
system, are being tried. 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 FEV1, and reduced forced expiratory flow
over 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.
Spirograph
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.
Air Displacement Plethysmography (ADP)
Bronchial provocation tests:
Bronchial provocation tests may be performed to diagnose 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 PEF rate (PEFR) are determined immediately after
the exercise period and at 3, 5, 10, 15, and 20 minutes after the first
measurement. The maximal decrease in lung function is calculated by using the
lowest postexercise and highest preexercise 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.
Recent evidence suggests the
usefulness of measuring
the fraction of exhaled nitric oxide (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.
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.
Peakflowmetria allows,
though tentatively, to control state of the respiratory system and helps to
some extent monitor of the effectiveness of treatment.
Peakflowmeter
Portable spirometer MicroLoop
(Micro Medical Ltd., UK)
with color sensor screen.
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. Chest x-ray is not always necessary. It can document the
increase of pulmonary volume, infiltrates areas due to atelectasis of distal obturated
airway, this feature is important in suspecting of their infection.
Asthma. A. The typical X-ray data 9-year-old child.
The inflation and increased lung
pattern. B. 7-year-old child with a more pronounced changes. C. Side projection
showing swelling with flattening of the diaphragm and increased anteroposterior
diameter at the top.
(From Edwards D III: The child who wheezes. <IT+>In:<IT->
von Waldenburg Hilton S, Edwards DIII (eds): Practical Pediatric Radiology, 2nd
ed. Philadelphia, WB Saunders, 1994, p 106.)
Paranasal sinus
radiography or CT scanning: Consider using these to rule out
sinusitis.
Computor
tomography. Emphysema.
Chronic
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.
In the period of remission allergic skin tests are
conducted, positive analysis of which gives the possibility to exclude contact
with the causative allergen, that is the key of the recovery.
Allergic prick
text. (Courtesy of MR Sly, M.D.)
The analysis of sputum:
eosinophilia, Kurshman spiral (cylinders of the bronchioles), crystals Charcot
- Leiden; neutrophilia proves the existence of bronchial infection.
A–eosinophyles
B– Charcot - Leiden crystals
C– Kurshman spiral
Arterial blood gases: typical
symptoms of hypoxemia during attacks and is usually expressed in hypocapnia and
respiratory alkalosis, a normal or increased partial pressure pCO2
showes a significant fatigue of respiratory muscles and airway obstruction.
Differential diagnosis
"Any wheezing" - is
not bronchial asthma. Differentiated with CNS diseases, chronic bronchitis and
(or) emphysema, obstruction URT caused by foreign body, tumor, edema of the
larynx, carcinoid tumors (usually followed by a crowing, but not wheezing), repeated
emphysema, eosinophilic pneumonia, dysfunction of the vocal folds, systemic
vasculitis with lesions of the lungs.
Clinically the most important
is differential diagnosis with bronchiolitis and laryngotracheal stenosis
due to similar clinical picture.
Differential diagnostics
attack of bronchial asthma that
laryngotracheal stenosis
Criteria |
Bronchial
asthma
|
Laryngotracheal stenosis
|
|
Background of process
|
Period of precursors
|
ARVI (parainfluenza)
|
|
Cough
|
Dry, with transition in moist one
|
Dry, barking |
|
Temperature
|
Normal
|
Subfebrile
|
|
Change of voice
|
Absent
|
Hoarse of voice
|
|
Shortness of breath
|
Expiration
|
Inciter
|
|
Forsed position
|
Characteristically
|
Non characteristically
|
|
Auscultation
|
The
loosened breathing, the prolonged inspiration, dry whistling and moist
wheezes
|
Strict breathing
Dry
wheezes
|
|
Percussion
|
Box sound
|
Pulmonary sound
|
|
“Mute” lights
|
Characteristically
|
Not characteristically
|
Treatment of the
patients
Medical Care
The goals of asthma therapy
are to prevent chronic and troublesome symptoms, maintain normal or near-normal
pulmonary function, maintain normal physical activity levels (including
exercise), prevent recurrent exacerbations of asthma, and minimize the need for
emergency department visits or hospitalizations, provide optimal
pharmacotherapy with minimal or no adverse effects, and meet the family's
expectations for asthma care.
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 recently introduced strategies such as
the use of anti-IgE antibodies. Relief medications include short-acting
bronchodilators, systemic corticosteroids, and ipratropium. Nonpharmacologic
management includes measures to improve patient compliance and adherence. 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 step-down
approach based on the asthma severity classification system emphasizes the initiation
of high-level therapy to establish prompt control and then decreasing therapy
(National Asthma Education and Prevention Program Expert Panel Report II,
1997). Treatment should be reviewed every 1-6 months; a gradual stepwise
reduction in treatment may be possible. If control is not maintained despite
adequate medication and adherence and the exclusion of contributing
environmental factors, increased therapy should be considered. Long- and
short-term therapy is based on the severity of asthma, as follows:
ü
Mild intermittent
asthma
ü
Long-term control:
Usually, no daily medication is needed.
ü
Quick relief: Short-acting
bronchodilators in the form of inhaled beta2-agonists should be used as needed
for symptom control.
The use of short-acting
inhaled beta2-agonists more than 2 times a week may indicate the
need to initiate long-term control therapy.
Mild persistent asthma
Long-term control:
Anti-inflammatory treatment in the form of low-dose inhaled corticosteroids or
nonsteroidal agents (eg, cromolyn, nedocromil) is preferred. Some evidence
suggests that leukotriene antagonists may be useful as first-line therapy in
children. Recently, the use of montelukast was approved for children aged 2
years and older.
Quick relief:
Short-acting bronchodilators in the form of inhaled beta2-agonists should be
used as needed for symptom control. Use of short-acting inhaled beta2-agonists
on a daily basis or increasing use indicates the need for additional long-term
therapy.
Moderate persistent asthma
Long-term control:
Daily anti-inflammatory treatment in the form of inhaled corticosteroids
(medium dose) is preferred. Otherwise, low- or medium-dose inhaled
corticosteroids combined with a long-acting bronchodilator or leukotriene
antagonist can be used, especially for the control of nocturnal or
exercise-induced asthmatic symptoms.
Quick relief:
Short-acting bronchodilators in the form of inhaled beta2-agonists should be
used as needed for symptom control. The use of short-acting inhaled
beta2-agonists on a daily basis or increasing use indicates the need for
additional long-term therapy.
Severe persistent asthma
Long-term
control
Daily anti-inflammatory
treatment in the form of inhaled corticosteroids (high dose) is preferred.
Other medications, such as a long-acting bronchodilator leukotriene antagonist
or theophylline, can be added.
Patients with
moderate-to-severe asthma who react to perennial allergens despite inhaled
corticosteroids may benefit from omalizumab treatment. Two 52-week pivotal
Phase III clinical trials were designed to study asthma exacerbation reduction
in 1071 patients with asthma (aged 12-76 y). The coprimary endpoint of each
study was the number of asthma exacerbations per patient during the
stable-steroid phase and the steroid-reduction phase. Patients were randomized
to receive subcutaneous omalizumab or placebo every 2-4 weeks. Inhaled
corticosteroid doses were kept stable over the initial 16 weeks of treatment
(stable-steroid phase) and tapered during a further 12-week treatment period
(steroid-reduction phase).
In both pivotal clinical
trials, when used as an add-on therapy to inhaled corticosteroids, omalizumab
reduced mean asthma exacerbations (ie, asthma attacks) per patient by 33%-75%
during the stable-steroid phase and 33%-50% during the steroid-reduction phase.
Reduction in asthma exacerbations was confirmed by improvements in other
measurements of asthma control, including symptom scores (eg, nocturnal
awakenings, daytime asthma symptoms).
Quick relief:
Short-acting bronchodilators in the form of inhaled beta2-agonists should be
used as needed for symptom control. The use of short-acting inhaled
beta2-agonists on a daily basis or increasing use indicates the need for
additional long-term therapy.
Acute severe asthmatic episode (status asthmaticus)
Treatment goals are the
following:
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 FEV1 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. Use of the peak
flow rate or FEV1 values, along with the patient's history, current symptoms,
physical findings, to guide treatment decisions is helpful in achieving the
aforementioned goals. In using the 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.
Consultations
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 sinusitis. A gastroenterologist may help in excluding
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
Current treatment of asthma
includes the use of relievers, such as beta-adrenergic agonists, systemic
corticosteroids, and ipratropium, and controllers, such as cromolyn,
nedocromil, inhaled corticosteroids, long-acting beta-agonists, theophylline,
and leukotriene modifiers.
Drug Category: 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). Recently, similar findings are
reported for long-acting beta2-agonists (eg, salmeterol).
Albuterol sulfate
(Proventil, Ventolin) This
beta2-agonist is the most commonly used bronchodilator that is
available in multiple forms (eg, solution for nebulization, metered-dose
inhaler (MDI), oral solution). This is most commonly used in rescue therapy for
acute asthmatic symptoms. Albuterol is used as needed, and prolonged use may be
associated with tachyphylaxis due to beta2-receptor downregulation and receptor
hyposensitivity.
Pediatric:
Oral 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
Pirbuterol acetate (Maxair) 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. Strength is 200 mcg per inhalation.
Oral inhalation: 1-2
inhalations q4-6h; not to exceed 12 inhalations q24h
Drug Category: 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).
0.63 mg by
nebulizer q8h
Drug Category: Long-acting beta2-agonist
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 long-acting beta2-agonists are available in the United States:
salmeterol (Serevent) and formoterol (Foradil). Salmeterol is discussed below.
Salmeterol is available as a combination of salmeterol and fluticasone (Advair)
in the United States.
Advair has an expiration date of 30 days once the protective wrapper is
removed.
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.
<12 years: Not established
>12 years: 1 inhalation of
inhalation powder (50 mcg) q12h; data
in children are limited
Drug Category: Methylxanthines
These agents are used for
long-term control and prevention of symptoms, especially nocturnal symptoms.
Theophylline
(Theo-24, Theolair, Theo-Dur, Slo-bid) is available in short- and
long-acting formulations. Because of the need to monitor the drug levels (see
Precautions below), this agent is used infrequently.
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
Drug Category: 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), nedocromil sodium (Tilade). These nonsteroidal
anti-inflammatory agents are used primarily in preventive therapy.
Cromolyn: 20 mg in 2 mL
nebulizer solution q6-8h
Nedocromil: 2-4 inhalations bid/tid; 1.75
mg/actuation
Intal - cromolyn sodium
Tilade - nedocromil
Drug Category: Corticosteroids
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 long-term beta2-agonist use).
Inhaled steroids include
beclomethasone, triamcinolone, flunisolide, fluticasone, and budesonide.
Beclomethasone
(Beclovent, Vanceril, 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.
Low dose: 84-336 mcg/d (42
mcg/oral inhalation, 2-8 inhalations q24h)
Medium dose: 336-672 mcg/d (42 mcg/oral
inhalations, 8-16
inhalations q24h)
High dose: >672 mcg/d (42 mcg/oral
inhalation, >16 inhalations q24h)
Fluticasone (Flovent) has
extremely potent vasoconstrictive and anti-inflammatory activity. Has a weak
hypothalamic-pituitary adrenocortical axis inhibitory potency when applied
topically.
Low dose: 88-176 mcg/d (44
mcg/oral inhalation, 2-4 inhalations q24h)
Medium dose: 176-440 mcg/d (110 mcg/oral
inhalation, 2-4 inhalations
q24h)
High dose: >440 mcg/d (110 mcg/oral
inhalation, >4 inhalations q24h or 220
mcg/oral inhalation, 2 inhalations q24h)
Budesonide (Pulmicort Turbuhaler or
Respules) Has extremely
potent vasoconstrictive and anti-inflammatory activity. Has a weak
hypothalamic-pituitary adrenocortical axis inhibitory potency when applied
topically. Pulmicort is available in a powder inhaler (200 mcg per oral inhalation)
or as a nebulized susp (ie, Respules).
MDI: Low dose: 100-200 mcg/d
(1 inhalation q24h)
Medium dose: 200-400 mcg/d (1-2 inhalation
q24h)
High dose: >400 mcg/d (>2 inhalations
q24h)
Nebulizer (inhalation susp): 0.25-0.5 mg bid;
not to exceed 1 mg/d
Drug Category: 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
gastrointestinal transit time or absorption is not impaired. The usual regimen
is to continue frequent multiple daily dosing until the FEV1 or 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.
1-2 mg/kg/d PO
for 3-10 d; not to exceed 60-80 mg/d
Methylprednisolone (Solu-Medrol) May decrease inflammation by reversing
increased capillary permeability and suppressing PMN activity.
1 mg/kg IV q6h
Drug Category: 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). It is a selective competitive inhibitor of
LTD4, LTE4 receptors.
5-11 years: 10 mg PO bid
>12 years: Administer as in adults
Montelukast (Singulair) It is
a 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.
12-23 months: 1 packet of 4 mg
oral granules PO hs
2-6 years: 4 mg PO
hs
6-14 years: 5 mg PO
hs
>14 years: Administer as in adults
Drug Category: 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.
<12 years: Not established
>12 years: 150-375 mg SC
q2-4wk; inject slowly over 5-10 s because of viscosity; not to exceed 150 mg
per injection site
Precise dose and frequency established by
serum total IgE level (IU/mL)
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