Biomedical Engineering Reference
In-Depth Information
an excess of FEV
1
decline and an increased risk of subsequent hospitaliza-
tion because of COPD suggested a role for mucus hypersecretion in the
development of chronic airflow obstruction (7). This hypothesis, however,
appears to be counter to recent data showing that chronic sputum produc-
tion in smokers with normal lung function (GOLD stage 0) (8) does not pre-
dict a subsequent establishment of airflow obstruction (9). Taken together,
these observations suggest that mucus hypersecretion may play a role in the
progression of COPD, but only in patients who have already developed a
chronic airflow obstruction.
It is now widely accepted that inflammation plays a key role in the
pathogenesis of COPD, so that recently this concept has been included
for the first time in the definition of the disease. Indeed, according to the
most recent guidelines, COPD is defined as a disease state characterized
by not fully reversible airflow obstruction that is usually both progressive
and associated with an abnormal inflammatory response of the lungs to
noxious particles or gases (8), particularly to cigarette smoking. The smok-
ing habit has been identified as the most important risk factor for the estab-
lishment of COPD and several studies have shown that cigarette smoking is
able to elicit an inflammatory process in the lung (10,11), which is thought
to represent a normal nonspecific response to injury. However, among smo-
kers, only a minority develop COPD, suggesting that the development of the
disease requires both exposure to cigarette smoke and individual susceptibil-
ity. It has been hypothesized that, in susceptible individuals, an amplifica-
tion of the nonspecific inflammatory response initiated by cigarette
smoking is responsible for most of the structural changes associated with
the progression of the disease (12,13). Indeed, the extent of lung inflamma-
tion appears to progressively increase from smokers with normal lung func-
tion to smokers with severe COPD (10,14,15). Although the hypothesis is
attractive, convincing evidence that the development of structural changes
is dependent on the prior development of chronic inflammation is still lack-
ing (16). It seems equally plausible that structural changes could arise
regardless of chronic inflammation.
Although the mechanisms of individual susceptibility to the develop-
ment of COPD are not completely understood, a possible explanation for
the amplification of the inflammatory response in susceptible smokers could
be an altered production of inflammatory mediators. This impairment may
be due to a genetic predisposition involving polymorphism in genes encod-
ing proinflammatory cytokines (17-19). Environmental conditions including
viral infections and pollutants may also play a role in triggering or maintain-
ing the disease. Retamales et al. suggest that susceptible smokers may have
an amplified inflammatory response in the lung parenchyma as a conse-
quence of a latent viral infection (15). Interestingly, although smoking is
the principal cause of COPD, quitting smoking does not appear to result
in resolution of the lung inflammation (20,21), suggesting that there are
