574
U N I T 6
Respiratory Function
prolong the asthma attack and set into motion a vicious
cycle of exacerbations.
18
Typically, the response reaches
a maximum within a few hours and may persist for
12 to 24 hours or longer. An initial trigger in the late-
phase response causes the release of inflammatory medi-
ators from mast cells, macrophages, and epithelial cells.
These substances induce the migration and activation
of other inflammatory cells (e.g., basophils, eosinophils,
neutrophils), which then produce epithelial injury and
edema, changes in mucociliary function, reduced clear-
ance of respiratory tract secretions, and increased airway
responsiveness (see Fig. 23-5B). Chronic inflammation
can lead to airway remodeling, in which case airflow
limitations may be only partially reversible.
19
NonatopicAsthma.
Intrinsic or nonatopic asthma trig-
gers include respiratory tract infections, exercise, hyper-
ventilation, cold air, drugs and chemicals, hormonal
changes and emotional upsets, air-borne pollutants,
and gastroesophageal reflux. Respiratory tract infec-
tions, especially those caused by viruses, may produce
their effects by causing epithelial damage and stimulat-
ing the production of IgE antibodies directed toward
the viral antigens. In addition to precipitating an asth-
matic attack, viral respiratory infections increase airway
responsiveness to other asthma triggers. This hyperre-
sponsiveness may persist for weeks beyond the original
infection.
Exercise-induced asthma occurs in a number of per-
sons with bronchial asthma.
23
Although the cause of
exercise-induced asthma is unclear, hyperventilation
and corresponding changes in airway physiology may
play a role. It has been suggested that the increased ven-
tilatory rate required to meet higher oxygen demands
during exercise challenges the ability of the airways to
condition the inhaled air to the correct moist and heat
levels before the air reaches the alveoli. Vigorous exer-
cise results in the inhalation of increased volumes of
relatively cold and dry air and loss of body heat from
the respiratory mucosa, which in turn induces mast cells
and epithelial cells to release proinflammatory media-
tors such as histamine and leukotrienes. The response
commonly is exaggerated when the person exercises
in a cold environment. Wearing a mask over the nose
and mouth often minimizes the attack or prevents it.
In addition to inflammatory cytokines, airway cooling
stimulates cholinergic receptors in the airways, with
a resultant increase in airway resistance. A warm-up
period alleviates the symptoms for some persons.
Inhaled irritants, such as tobacco smoke and strong
odors, are thought to induce bronchospasm by way
of irritant receptors and a vagal reflex. Exposure to
parental smoking has been reported to increase asthma
severity in children.
24
Occupational asthma is caused by
sensitizing agents or irritants encountered in the work-
place.
25,26
Occupational asthma from sensitizers usually
presents with a latent period of exposure, followed by
the onset of disease. Irritant or nonimmunologic asthma
results from high levels of exposure to irritant gases such
as sulfur dioxide, nitrogen dioxide, and ozone, which
may induce inflammatory exacerbations of airway
Antigen
IgE
Mast cell
Increased
mucus
production
Mucus-
producing
goblet cell
Cytokines
Bronchial
smooth
muscle
Bronchospasm
Epithelial
cell injury
Mucus
Neutrophil
Basophil
Eosinophil
Afferent and efferent
vagal fibers
Bronchospasm and heightened
airway responsiveness
A
B
Increased
vascular
permeability
and edema
FIGURE 23-5.
Pathogenesis of bronchial asthma.
(A)
The
early-phase response triggered by an IgE-mediated release of
mediators from sensitized mast cells.The release of chemical
mediators results in increased mucus production, opening of
mucosal intercellular junctions with exposure of submucosal
mast cells to antigen, and bronchospasm.
(B)
The late-phase
response involves epithelial cell injury with decreased
mucociliary function and accumulation of mucus; release
of inflammatory mediators with recruitment of neutrophils,
eosinophils, and basophils; increased vascular permeability
and edema; and increased airway responsiveness and
bronchospasm.
