Biomedical Engineering Reference
In-Depth Information
Figure 1
Targets for COPD therapy. Many new treatments for COPD are now in
development based on logical targets revealed by a better understanding of cellular
and molecular mechanisms involved in disease pathogenesis. More effective smoking
cessation drugs are needed. Antagonists of specific mediators, such as LTB4, and
chemokines, such as interleukin-8, are in clinical trial, but may be too specific. Inhibi-
tion of TNF-
a
is more likely to be successful, particularly in patients with systemic
features. Other approaches include inhibiting proteases (elastases) such as neutrophil
elastase (NE), cathepsins, or MMP. Drugs with a broader spectrum of anti-
inflammatory effects, such as PDE-4 inhibitors or inhibitors of signal transduction
pathways, such as inhibitors or inhibitor of nuclear factor-
k
B kinase (IKK2), p38
MAP kinase, or phosphoinositide-3-kinase are promising. Drugs that inhibit TGF-
b
may inhibit the fibrosis in small airways. Drugs targeted at mucus hypersecretion
include inhibitors of epidermal growth factor receptors (EGFR) and CACC. There
are also approaches to repair emphysema using retinoids (that are effective in rodent
lungs) and stem cells.
are not very satisfactory and require long exposure times to cigarette smoke
to induce emphysema (11). There are still many uncertainties about how to
test new drugs for COPD, which may require long-term studies (over 3
years) in relatively large numbers of patients. It is difficult to give new che-
mical entities for such prolonged periods, so that the drug would need to
show efficacy in more short-term clinical parameters, such as a reduction
in exacerbations. Many patients with COPD may have comorbidities, such
as ischemic heart disease and diabetes, which may exclude them from clin-
ical trials of new therapies. There is little information about surrogate
markers, for example, biomarkers in blood, sputum, or breath, to monitor
the short-term efficacy and predict
the long-term potential of new
