C h a p t e r 2 3
Disorders of Ventilation and Gas Exchange
573
vascular permeability, and mucus production.
15,16
In some
persons, persistent changes in airway structures occur,
including injury to epithelial cells, smooth muscle hyper-
trophy, and blood vessel proliferation.
Recent research has focused on the role of T lym-
phocytes in the pathogenesis of bronchial asthma. It is
now known that there are two subsets of T-helper cells
(T
H
1 and T
H
2) that develop from the same precursor
CD4
+
T lymphocyte (see Chapter 15).
15
T
H
1 cells dif-
ferentiate in response to microbes and stimulate the
differentiation of B cells into immunoglobulin (Ig)
M and IgG-producing plasma cells. T
H
2 cells, on the
other hand, respond to allergens by stimulating B cells
to differentiate into IgE-producing plasma cells that
bind to mucosal mast cells. Subsequent IgE-mediated
reactions to inhaled allergens elicit an asthmatic attack
(see Chapter 16, Fig. 16-1). In persons with allergic
asthma, T-cell differentiation appears to be skewed
toward T
H
2 cells. Although the molecular basis for this
preferential differentiation is unclear, it seems likely that
both genetic and environmental factors play a role.
Atopic Asthma.
Atopic asthma is typically initiated by
a type I hypersensitivity reaction induced by exposure
to an extrinsic antigen or allergen.
15,16
It usually has its
onset in childhood or adolescence and is seen in persons
with a family history of atopic allergy (see Chapter 16).
Persons with atopic asthma often have other allergic
disorders, such as hay fever, urticaria, and eczema.
Attacks are related to exposure to specific allergens.
Among air-borne allergens implicated in perennial (year-
round) asthma are house dust mite allergens, cockroach
allergens, animal danders, and
Alternaria
(a fungus).
The mechanisms of response to allergens in atopic
asthma can be described in terms of the early-phase
and the late-phase responses
15,16
(Fig. 23-4). The symp-
toms of the
early-phase response
(also called the
acute-
phase response
), which usually develop within 10 to
20 minutes of exposure to the allergen, are caused by
the release of chemical mediators from presensitized
IgE-coated mast cells. In the case of air-borne antigens,
the reaction occurs when antigen binds to previously
sensitized mast cells on the mucosal surface of the air-
ways (Fig. 23-5A). Mediator release results in the infil-
tration of inflammatory cells, opening of the mucosal
intercellular junctions, and increased access of antigen
to the more prevalent submucosal mast cells. In addi-
tion, there is bronchospasm caused by stimulation of
parasympathetic receptors, mucosal edema caused by
increased vascular permeability, and increased mucus
secretions. The acute response usually can be inhibited
or reversed by bronchodilators, such as
β
2
-agonists, but
not by the anti-inflammatory actions of corticosteroids.
The
late-phase response,
which develops 4 to 8 hours
after exposure to an asthmatic trigger, involves inflam-
mation and increased airway responsiveness that
Edema
Epithelial injury
Impaired mucociliary function
Airflow
limitation
Bronchospasm
Increased airway
responsiveness
Airway inflammation
Allergen
Mast cells
Early-phase
response
Late-phase
response
Release histamine, leukotrienes,
interleukins, and prostaglandins
Infiltration of inflammatory cells
Release cytokines, interleukins,
and other inflammatory mediators
FIGURE 23-4.
Mechanisms of early- and
late-phase IgE-mediated bronchospasm.
