DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

1032
Allergen
Dendritic cell
Mast cell
Neutrophil
SECTION IV
Mucus plug
T H
2 cell
Eosinophil
Epithelial shedding
INFLAMMATION, IMMUNOMODULATION, AND HEMATOPOIESIS
Mucus
hypersecretion
Hyperplasia
Vasodilation
New vessels
Nerve
activation
Plasma leak
Edema
Airway smooth muscle cells
Myofibroblast
Bronchoconstriction
Hypertrophy/hyperplasia
Subepithelial
fibrosis
Sensory nerve
Cholinergic reflex
Figure 36–1. Cellular mechanisms of asthma. Myriad inflammatory cells are recruited and activated in the airways, where they release
multiple inflammatory mediators, which can also arise from structural cells. These mediators lead to bronchoconstriction, plasma
exudation and edema, vasodilation, mucus hypersecretion, and activation of sensory nerves. Chronic inflammation leads to structural
changes, including subepithelial fibrosis (basement membrane thickening), airway smooth muscle hypertrophy and hyperplasia, angiogenesis,
and hyperplasia of mucus-secreting cells.
Chronic inflammation may lead to structural
changes in the airways, including an increase in the number
and size of airway smooth muscle cells, blood vessels,
and mucus-secreting cells. A characteristic
histological feature of asthma is collagen deposition
(fibrosis) below the basement membrane of the airway
epithelium (Figure 36–1). This appears to be the result of
eosinophilic inflammation and is found even at the onset
of asthmatic symptoms. The complex inflammation of
asthma is suppressed by corticosteroids in most patients,
but even if asthma is well controlled, the inflammation
and symptoms return if corticosteroids are discontinued.
Asthma usually starts in early childhood, then may disappear
during adolescence and reappear in adulthood. It
is characterized by variable airflow obstruction and typically
shows a good therapeutic response to bronchodilators
and corticosteroids. Asthma severity usually does
not change, so that patients with mild asthma rarely
progress to severe asthma and patients with severe
asthma usually have this from the onset, although some
patients, particularly with late-onset asthma, show a progressive
loss of lung function like patients with COPD.
Patients with severe asthma may have a pattern of
inflammation more similar to COPD and are characterized
by reduced responsiveness to corticosteroids
(Wenzel and Busse, 2007).
MECHANISMS OF CHRONIC
OBSTRUCTIVE PULMONARY DISEASE
Chronic obstructive pulmonary disease involves
inflammation of the respiratory tract with a pattern that
differs from that of asthma. In COPD, there is a predominance
of neutrophils, macrophages, and cytotoxic