Biomedical Engineering Reference
In-Depth Information
can be operative: (a) tobacco smoke can cause significant extrapulmonary
damage (such as endothelial dysfunction) independently of COPD (21,22);
(b) cytokines produced by inflammatory lung cells (such as TNF
a
, IL-6,
and IL-1
b
) may reach the systemic circulation and
=
or contribute to the acti-
vation of inflammatory cells during their transit through the pulmonary
circulation; (c) other organs rather than the lungs can contribute to
systemic inflammation in COPD. For example, the bone marrow can release
increased numbers of inflammatory cells in response to inhaled pollutants
(23) and skeletal muscle increases the release of circulating cytokines in
COPD (19); and, finally, (d) theoretically, at least, some of the abnormalities
described in the peripheral circulation of patients with COPD (e.g., the
increased surface expression of several neutrophil adhesion molecules
(CD11b) and down-regulation of G-protein subunit (G
a
s (12))) may be a
cause rather than a consequence of COPD. Due to their specific genetic
background, these cells can exhibit a more vigorous response to the same
degree of stimulation, including a higher expression of surface adhesion
molecules, which would facilitate their recruitment to the site of inflamma-
tion (12), and an increased respiratory burst that would enhance their
damaging potential (11).
III. WEIGHT LOSS
Unexplained weight loss is common in COPD, particularly (but not exclu-
sively) in patients with severe COPD (24). Weight loss is an important prog-
nostic factor in COPD (25,26). Its prognostic value is independent of the
degree of lung function impairment present (25,26). It is a reversible prog-
nostic factor because if body weight recovers, prognosis improves and, inter-
estingly, this occurs in the absence of any change in lung function (25).
Therefore, unexplained weight loss identifies a new systemic domain of
COPD not considered by the traditional measures of lung function.
Atrophy of skeletal muscle mass is the main cause of weight loss in
COPD, while loss of fat mass contributes to a lesser extent (24). The cause(s)
of skeletal muscle atrophy in COPD are unclear but, very likely, they are
multiple. These are discussed below.
IV.
SKELETAL MUSCLE DYSFUNCTION (SMD)
Over the past few years, there has been increasing realization that skeletal
muscle is abnormal in COPD (27). Killian et al. (28) were probably the first
to report that many patients with COPD stop exercise because of leg fatigue,
not dyspnea (29). Several publications since then confirmed that an SMD is
common in COPD, and that it is a relevant contributor to the clinical pic-
ture of the disease (27,30). In particular, an SMD in COPD has two obvious
