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

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Cigarette smoke
(and other irritants)
CHAPTER 36
Fibroblast
Epithelial cells
Macrophage
T H 1 T C 1 Neutrophil
Monocyte
PULMONARY PHARMACOLOGY
Proteases
Fibrosis
(small airways)
Alveolar wall destruction
(emphysema)
Mucus
hypersecretion
Figure 36–2. Cellular mechanisms in chronic obstructive pulmonary disease. Cigarette smoke and other irritants activate epithelial cells
and macrophages in the lung to release mediators that attract circulating inflammatory cells, including monocytes (which differentiate
to macrophages within the lung), neutrophils, and T lymphocytes (T H
1 and T C
1 cells). Fibrogenic factors released from epithelial
cells and macrophages lead to fibrosis of small airways. Release of proteases results in alveolar wall destruction (emphysema) and
mucus hypersecretion (chronic bronchitis).
T-lymphocytes (Tc1 cells). The inflammation predominantly
affects small airways, resulting in progressive
small airway narrowing and fibrosis (chronic obstructive
bronchiolitis) and destruction of the lung parenchyma
with destruction of the alveolar walls (emphysema)
(Figure 36–2) (Barnes, 2008b). These pathological
changes result in airway closure on expiration, leading
to air trapping and hyperinflation, particularly on exercise
(dynamic hyperinflation). This accounts for shortness
of breath on exertion and exercise limitation that are
characteristic symptoms of COPD.
Bronchodilators reduce air trapping by dilating
peripheral airways and are the mainstay of treatment in
COPD. In contrast to asthma, the airflow obstruction of
COPD tends to be progressive. The inflammation in the
peripheral lung of COPD patients is mediated by
multiple inflammatory mediators and cytokines, although
the pattern of mediators differs from that of asthma
(Barnes, 2004; Barnes, 2008a). In marked contrast to
asthma, the inflammation in COPD patients is largely corticosteroid
resistant, and there are currently no effective
anti-inflammatory treatments for this disease. In addition
to pulmonary disease, many patients with COPD have
systemic manifestations (skeletal muscle wasting, weight
loss, depression, osteoporosis, anemia) and comorbid diseases
(ischemic heart disease, hypertension, congestive
heart failure, diabetes) (Barnes and Celli, 2009). Whether
these are due to spillover of inflammatory mediators from
the lung or due to common causal mechanisms (such as
smoking) is not yet clear, but it may be important to treat
the systemic components in the overall management
of COPD.