Biomedical Engineering Reference
In-Depth Information
perpetuating mechanisms that maintain the chronic inflammatory process
once it has become established (18,19).
In this chapter, we will focus on the inflammatory and destructive
processes present in the lung parenchyma of smokers to highlight their
relationship with airway pathology and pulmonary function, in an attempt
to identify the possible mechanisms contributing to the development of
chronic airflow obstruction in these subjects.
II. PARENCHYMAL INFLAMMATION
Only a few studies have attempted to quantify the alveolar inflammation in
smokers by direct examination of surgical lung specimens. Eidelman et al.
(22) found an increased number of inflammatory cells in the alveolar wall
of smokers which was directly related to the degree of parenchymal destruc-
tion (Fig. 1). Subsequently, Finkelstein et al. (23) characterized this alveolar
inflammatory process showing that the enhanced inflammatory response in
smokers was due to an increase in macrophages and T-lymphocytes and that
the number of these cells was directly correlated with the extent of emphy-
sema. The phenotype of these T-lymphocytes has been recently identified,
and it has been shown that it is the CD8
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T cell subtype that predominates
in smokers with COPD (14). Indeed, CD8 T-lymphocytes are increased not
only in the alveolar walls, but also in central and peripheral airways, sug-
gesting that a consistent inflammatory process is present along the entire
tracheobronchial tree in smokers with COPD (14,24,25). It is noteworthy
that, in all these lung compartments, CD8-T-lymphocytes show a significant
correlation with the degree of airflow obstruction, suggesting a role for these
cells in the progression of the disease (14,24,25).
Interestingly, the neutrophilia reported in bronchoalveolar lavage
(26,27) by several studies has not been observed in the alveolar walls of smo-
kers with COPD (14). A possible explanation for the discrepancy between
lavage and parenchymal tissue is the rapid migration of neutrophils through
the alveolar tissue to the alveolar spaces, so that the effect of accumulation
of these cells is undetectable by tissue analysis but becomes evident by
lavage analysis. Even if the mechanism of neutrophil accumulation is not
entirely clear, it probably involves neutrophil chemotactic factors, such as
interleukin ( IL)-8, which has been reported to be increased in both bronch-
oalveolar lavage and sputum of smokers with COPD (28-30).
Although an increased number of inflammatory cells, particularly
neutrophils, macrophages, and CD8-T-lymphocytes has been clearly shown
in COPD (Table 1), the role of these cell types in the pathogenesis of the dis-
ease is largely unknown (12,18,31,32).
Neutrophils have been implicated in the pathogenesis of emphysema
since the appreciation of emphysema associated with deficiency of
