Biomedical Engineering Reference
In-Depth Information
et al. (7) showed that the rhinovirus can be recovered from induced sputum
more frequently using PCR techniques than from nasal aspirates at exacerba-
tion, suggesting that wild type rhinovirus can infect the lower airway and con-
tribute to inflammatory changes at exacerbation. They also found that
exacerbations associated with the presence of rhinovirus in induced sputum
had larger increases in airway IL-6 levels, compared to exacerbations where
rhinovirus was not detected. This suggests that viruses increase the severity
of lower airway inflammation at exacerbation. This finding is in agreement
with the data that respiratory viruses produce longer and more severe exacer-
bations and have a major impact on health care utilization (3,8).
As respiratory viruses are associated with more severe exacerbations
and increased airway inflammation, the mechanisms of virus-associated
exacerbations require discussion. The major group of rhinovirus (account-
ing for 90% of total rhinovirus types) attach to airway epithelium through
ICAM-1, inducing ICAM-1 expression. This then promotes inflammatory
cell recruitment and activation as seen in the inflammatory response at
exacerbations (28). The minor rhinovirus group uses members of the
LDL-receptor family as cell surface receptors, though ICAM-1 surface
expression may also be upregulated (17). There is some evidence for upregu-
lation of ICAM-1 in the bronchial mucosa of patients with chronic bronchi-
tis (29), and thus ICAM-1 is an important potential therapeutic target in
COPD exacerbations associated with rhinoviruses. Experimental rhinovirus
infection has been shown to increase sputum IL-6 in normal subjects and
asthmatics (30-32). Lower airway IL-8 has been shown to increase with
experimental rhinovirus infection in normal and asthmatic patients in some
studies (31), but not in others (32).
Viral infections have been associated with increased oxidant stress that
is increased at COPD exacerbation (33). Rhinovirus infection of human
respiratory epithelial cells increases production of reactive oxygen species
and stimulates the activation of NF-
k
B important in the regulation of the
IL-8 gene (34). In patients with experimental rhinoviral infections, nasal
IL-8 levels have been related to common cold symptoms (35). Viral infec-
tions can also induce the expression of stress-response genes e.g., heme-
oxygenase-1 and genes encoding antioxidant enzymes e.g., glutathione
peroxidase, MnSOD (36), and these responses may be important in poten-
tiating the effects of the virally mediated inflammation at COPD exacerba-
tion. We have also shown that exacerbations are associated with increased
airway and systemic endothelin-l levels (10). Endothelin-1 is an important
bronchoconstrictor peptide that has been found to be proinflammatory
and mucogenic and has been also implicated in the pathogenesis of virally
mediated inflammation (37). Sputum ET-1 levels increase at COPD exacer-
bation and these increases are related to sputum IL-6 levels. Further work
with specific ET receptor antagonists may provide a new therapeutic option
for virus-induced inflammation associated with COPD exacerbations.
