Mechanisms of Pulmonary Vascular Changes - Chronic Obstructive Pulmonary Disease - page 473

number of studies showing increased number of CD8 þ T-lymphocytes in
large and small airways, as well as in alveolar septa, in patients with different
degrees of COPD severity (63,64).
It is of note that inflammatory cells in pulmonary arteries are confined
to the adventitia and that they are rarely identified either in the muscularis
or in the intima (62). This suggests that it is unlikely that these cells might
originate from circulating blood in pulmonary arteries since both internal
and external elastic laminas may represent an anatomic barrier to their
migration from the arterial lumen to the adventitia. Presumably, adventitial
inflammatory cells might originate from nutritional vessels (vasa vasorum)
derived from the bronchial circulation. Indeed, in a bovine model of
hypoxia-induced pulmonary hypertension, it has been shown that
circulating blood precursor cells migrate to the pulmonary vessel wall
through expanded adventitial vasa vasorum (37).
In patients with mild-to-moderate COPD, the intensity of the inflam-
matory cell infiltrate in pulmonary arteries correlates with the degree of air-
flow obstruction, suggesting that as the disease progresses the inflammatory
reaction in pulmonary arteries may become more severe (62). Nevertheless,
in a recent study conducted in specimens obtained at lung volume reduction
surgery, no differences in the number of inflammatory cells in pulmonary
arteries were shown between patients with severe emphysema and patients
with mild COPD (14). This finding is at variance with what occurs in lung
parenchyma (65) and small airways (14), where increased COPD severity
is associated with greater inflammatory infiltrate. The intensity of the
inflammatory infiltrate shown in the wall of pulmonary arteries is directly
related to the thickness of the intimal layer and inversely related to the
endothelial function (62), thus suggesting a potential role of inflammatory
mediators in the pathogenesis of the structural and functional changes that
occur in the pulmonary circulation of COPD.
Compared with nonsmokers, smokers with normal lung function exhi-
bit an increased number of CD8 þ T-cells in the arterial adventitia, with a
reduction of the CD4 þ = CD8 þ ratio that does not differ from patients with
COPD (62). This finding is in keeping with the observation that smokers
with and without airflow obstruction have reduced CD4 þ = CD8 þ ratio
in peripheral blood (66) and bronchoalveolar lavage samples (67). Overall,
this suggests that cigarette smoking might induce inflammatory changes in
pulmonary arteries at stages in which there are no detectable alterations
in the lung function examination.
V. GROWTH FACTORS
Growth factors are intercellular signaling molecules that regulate cell
proliferation by autocrine and paracrine mechanisms. Their role in the