C h a p t e r 2 3
Disorders of Ventilation and Gas Exchange
577
long-term treatment of asthma. Inhaled corticosteroids
administered by MDI usually are preferred because of
minimal systemic absorption and reduced disruption in
hypothalamic-pituitary-adrenal function.
The long-acting
β
2
-agonists, available for administra-
tion by the inhaled or oral routes, act by relaxing bron-
chial smooth muscle. They are used as an adjunct to
anti-inflammatory medications for providing long-term
control of symptoms, especially nocturnal symptoms,
and for preventing exercise-induced bronchospasm. The
long-acting
β
2
-agonists have durations of action of at
least 12 hours and should not be used to treat acute
symptoms or exacerbations.
19
The leukotriene receptor antagonists (monelukast and
zafirlukast) block the action of the leukotrienes, which are
arachidonic acid derivatives synthesized by a number of
inflammatory cells in the airways, including eosinophils,
mast cells, macrophages, and basophils.
19,31
Several of the
leukotrienes exert many of the effects known to occur in
asthma, including bronchoconstriction, increased bron-
chial reactivity, mucosal edema, and mucus hypersecre-
tion. A particular advantage of the leukotriene receptor
antagonists is that they are taken orally.
Theophylline, a phosphodiesterase inhibitor, is a
bronchodilator that acts by relaxing bronchial smooth
muscle. The sustained-release form of the drug is used
as an adjuvant therapy, particularly to relieve nighttime
symptoms.
19
It may be used as an alternative, but not
preferred, medication in long-term preventative therapy
when there are issues concerning adherence with regi-
mens using inhaled medications or when cost is a factor.
Because elimination of the drug varies widely among
persons, blood levels are required to ensure that a thera-
peutic but not toxic dose is achieved.
17
The anti-IgE monoclonal antibody omalizumab is the
first biologic immunoregulatory agent available to treat
asthma.
29
It binds to the portion of the IgE that recog-
nizes its receptor on the surface of mast cells and baso-
phils. Omalizumab, which is indicated for treatment of
moderate and severe persistent asthma, is administered
subcutaneously every 2 to 4 weeks, depending on the
dose. The drug has been approved for adults and chil-
dren 12 years of age and older.
Severe Asthma
Severe (or refractory) asthma represents a subgroup
(probably <10%) of persons with asthma who have high
medication requirements to maintain good symptom con-
trol, or who continue to have persistent symptoms despite
high medication use.
32,33
The condition has been described
as persistent asthma that required continuous high-dose
inhaled or oral corticosteroids for more than 50% of the
previous year and the need for additional daily treatment
with controller medications, exhibited evidence of disease
exacerbations or instability, and required hospitalizations
or emergency room visits.
19,21,32,33
Persons with severe
asthma are at increased risk for a fatal or near-fatal asth-
matic attack. Underestimating the severity of the attack
may be a contributing factor.
34
Deterioration often occurs
rapidly during an acute attack, and underestimation of
its severity may lead to a life-threatening delay in seeking
medical attention.
Little is known about the causes of severe asthma.
Among the proposed risk factors are genetic predisposi-
tion, continued allergen or tobacco exposure, infection,
intercurrent sinusitis or gastroesophageal reflux disease,
and lack of compliance or adherence with treatment mea-
sures.
33
Because bronchial asthma likely involves multiple
genes, mutations in genes regulating cytokines (e.g., IL-4),
growth factors, or receptors for medications used in treat-
ment of asthma (
β
2
-adrenergic agonist or glucocorticoid)
could be involved. Environmental factors include both
allergen and tobacco exposure, with the strongest reac-
tion occurring in response to house dust mite antigens,
cockroach allergen, and
Alternaria
exposure.
Bronchial Asthma in Children
Asthma is a common chronic illness in children. In the
United States, asthma is the most common cause of
childhood emergency department visits, hospitaliza-
tions, and missed school days.
35–38
Although childhood
asthma may have its onset at any age, up to 80% of
children who develop asthma are symptomatic before
5 years of age.
19
Asthma is more prevalent among black
than white children.
36–39
Worldwide, childhood asthma
appears to be increasing in prevalence.
35
It is particularly
common in children living in suburban areas, as com-
pared to rural areas of developing countries.
As with adults, asthma in children commonly is asso-
ciated with an IgE-related reaction. It has been suggested
that IgE directed against respiratory viruses in particular
may be important in the pathogenesis of wheezing ill-
nesses in infants (i.e., bronchiolitis), which often precede
the onset of asthma.
37,38
Previous severe infections with
the respiratory syncytial virus (RSV) are a risk factor
in the development of asthma. Other contributing fac-
tors include exposure to environmental allergens such as
pet dander, dust mite antigens, and cockroach allergens.
Exposure to environmental tobacco smoke also contrib-
utes to asthma in children.
36–39
The signs and symptoms of asthma in infants and
small children vary with the stage and severity of an
attack. Because airway patency decreases at night, many
children have acute signs of asthma at this time. Often,
previously well infants and children develop what may
seem to be a cold with rhinorrhea, rapidly followed by
irritability, nonproductive cough, wheezing, tachypnea,
dyspnea with prolonged expiration, and use of acces-
sory muscles of respiration. Cyanosis, hyperinflation of
the chest, and tachycardia indicate increasing severity
of the attack. Wheezing may be absent in children with
extreme respiratory distress. The symptoms may prog-
ress rapidly and require a trip to the emergency depart-
ment or hospitalization.
As with adults and older children, the Expert Panel of
the NAEPP recommends a stepwise approach to diag-
nosing and managing childhood asthma.
19
Treatment
involves not only pharmacologic agents but also
