Biomedical Engineering Reference
In-Depth Information
II. AIRWAY INFLAMMATION AT EXACERBATION
COPD exacerbations are associated with airway inflammation (3), though
there has been relatively little information available on the nature of inflam-
matory markers especially when studied close to an exacerbation, as per-
forming bronchial biopsies at exacerbation are difficult in patients with
moderate-to-severe COPD. In stable COPD, there is an increase in the
CD8
รพ
lymphocytes and macrophages in the bronchial mucosa and an
increase in neutrophils with more severe disease. In one study, where biop-
sies were performed at exacerbation in patients with chronic bronchitis,
increased airway eosinophilia was found, though the patients studied had
only mild COPD (4). In these patients at exacerbation, there were more
modest increases observed in neutrophils, T-lymphocytes (CD3), and
TNF
a
positive cells. However, in patients with more severe COPD, there
are increases seen in airway neutrophils when stable that increase further
at exacerbation. In a recent study, Qiu et al. (5) studied biopsies from
patients, with severe COPD, who were treated with tracheal intubation
and showed that there was considerable airway neutrophila and neutrophil
elastase expression in the biopsies obtained. Neutrophil chemoattraction
occurs through the mediation of a number of neutrophil selective chemo-
kines and in this study Qiu et al. studied gene expression for a number of
CXC cytokines in the airway mucosa. The authors found that at exacerba-
tions CXCL8 (interleukin-8), CXCR2, and CXCL5 (epithelial-derived neu-
trophil attractant-78) were upregulated at exacerbation compared to stable
COPD (Fig. 1). They also describe an association between the neutrophil
number in the biopsies at exacerbation and chemokines especially CXCL5,
which they found to be the dominant chemokine in the airway and CXCL8.
Furthermore, they showed the importance of CXCR2 and that the increase
in neutrophils at exacerbation was related to the increase in CXCR2 expres-
sion but not to CXCR1 expression. They showed that CXCL8 correlated
with CXCR1 and CXCL5 was related to CXCR2 and these chemokines
had important roles in neutrophil recruitment at exacerbations. However,
there are some limitations to this study as the patients were intubated and
the results may have been complicated by secondary infection.
Sputum induction allows study of these patients at exacerbation and it
has been shown that it is a safe and well-tolerated technique in COPD
patients (6). In the East London COPD study, there was a relation between
exacerbation frequency and sputum cytokines, in that there was increased
sputum interleukin (IL) -6 and IL-8 found in patients at baseline when
stable with a history of frequent exacerbations compared to those with infre-
quent exacerbations (3) (Fig. 2). Exacerbations that were triggered by viral
infections were associated with increased airway inflammatory markers
compared to those when viruses were not detected at exacerbations.
(3,7,8) Rhinovirus is commonly detected at exacerbation and rhinovirus
