Global Initiative for Chronic Obstructive Lung Disease - GOLD

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remodeling because tissue repair in the airways, as
elsewhere in the body, may involve scar tissue formation.
In any case, this injury-and-repair process results in a
structural remodeling of the airway wall, with increasing
collagen content and scar tissue formation, that narrows
the lumen and produces fixed airways obstruction 87 .
The peripheral airways become the major site of airways
obstruction in COPD, and direct measurements of
peripheral airways resistance 88 show that the structural
changes in the airway wall are the most important cause
of the increase in peripheral airways resistance in COPD.
Inflammatory changes such as airway edema and
mucus hypersecretion also contribute to airway narrowing
in COPD. So does loss of elastic recoil, but fibrosis of
the small airways plays the largest role.
Fibrosis in the peripheral airways, as elsewhere in the
body, is characterized by the accumulation of mesenchymal
cells (fibroblasts and myofibroblasts) and extracellular
connective tissue matrix. Several cell types including
mononuclear phagocytes and epithelial cells may produce
mediators that drive this process. The mediators that
drive the accumulation of these cells and of the matrix
are incompletely defined, but it is likely that several
mediators including TGF-ß, ET-1, Insulin-like growth
factor-1, fibronectin, platelet-derived growth factor
(PDGF), and others are involved 89 .
Figure 4-9. Normal and Emphysematous Lungs
Figure 4-10. Normal Respiratory Bronchioles
and Centrilobular Emphysema
(A) shows a photomicrograph of the pleural surface
of a normal lung, with a secondary lobule defined by
a connective tissue septum (solid arrow) and several
terminal bronchioles (TB) filled with opaque material.
(B) shows a low-power photomicrograph of a normal
terminal bronchiole (TB) branching into a respiratory
bronchiole (RB), which eventually end in alveolar
ducts (AD). (C) is a schematic diagram of centrilobular
emphysema and (D) shows the bronchographic
appearance of this lesion (TB=terminal bronchiole;
CLE=centrilobular emphysema).
Printed with permission of Dr. James C. Hogg and Stuart Greene.
Photomicrographs of paper-mounted whole lung sections
prepared from (A) a normal lung, (B) a lung with
mild centrilobular emphysema, and (C) a lung with
severe panacinar emphysema. Note that the centrilobular
form affects mainly the upper lung regions whereas
the panacinar form is more apparent in the lower
lung regions.
Printed with permission of Dr. James C. Hogg and Stuart Greene.
Lung Parenchyma
The lung parenchyma includes the gas exchanging surface
of the lung (respiratory bronchioles and alveoli) and the
pulmonary capillary system (Figure 4-9). The most
common type of parenchymal destruction in COPD
patients is the centrilobular form of emphysema (Figure
4-10), which involves dilatation and destruction of the
respiratory bronchioles 90 . These lesions occur more
frequently in the upper lung regions in milder cases, but
in advanced disease they may appear diffusely throughout
the entire lung and also involve destruction of the pulmonary
capillary bed. Panacinar emphysema, which extends
throughout the acinus, is the characteristic lesion seen in
alpha-1 antitrypsin deficiency and involves dilatation and
destruction of the alveolar ducts and sacs as well as the
respiratory bronchioles. It tends to affect the lower more
than upper lung regions. Because this process usually
affects all of the acini in the secondary lobule, it is also
referred to as panlobular emphysema. The primary
mechanism of lung parenchyma destruction, in both
smoking-related COPD and alpha-1 antitrypsin deficiency,
is thought to be an imbalance of endogenous proteinases
and antiproteinases in the lung. Oxidative stress, another
consequence of inflammation, may also contribute 91 .
PATHOGENESIS, PATHOLOGY, AND PATHOPHYSIOLOGY 35