Biomedical Engineering Reference
In-Depth Information
Although smoking is the major causal mechanism in COPD, quitting
smoking does not appear to result in resolution of the inflammatory
response in the airways, particularly in advanced disease (52,57,58). This
suggests that there are perpetuating mechanisms that maintain the chronic
inflammatory process once it has become established. This may account
for presentation of COPD in patients who stopped smoking many years
before their first symptoms develop. The mechanisms of disease persistence
are currently unknown.
V. THE IMPORTANCE OF TRANSLATIONAL RESEARCH
As discussed above, COPD has been very poorly investigated and our
understanding of cellular and molecular mechanisms lags behind our under-
standing of asthma. Yet, in some ways, it is an easier disease to investigate,
as the cause is known. The reason why only a proportion of smokers
develop COPD is still not known, however. This might be due to genetic
factors that amplify the inflammatory response to irritants, or reduce the
endogenous anti-inflammatory mechanisms that would normally dampen
down the inflammatory response.
It is clear that COPD is a heterogeneous disease and the reason why
some patients have predominant emphysema, whereas others have predomi-
nant small airway disease, is not understood. The natural history of these
different patterns of disease is also poorly understood. What is now needed
is careful phenotyping and genotyping of patients to understand the cell and
molecular mechanisms that determine the different patterns of pathology
and progression, using a multidisciplinary approach to measure inflamma-
tion (including non-invasive markers of lung inflammation and high resolu-
tion imaging) (76).
It is only through careful phenotyping of patients and longitudinal
studies to follow disease progression that we will begin to understand the
role of specific genes, proteins, cells, and mediators. The techniques of mole-
cular genomics, proteomics, and metabonomics clearly have important
contributions to play in this understanding.
Ultimately better understanding of cell and molecular mechanisms
of COPD should lead to more effective therapy, and in particular anti-
inflammatory or disease modifying therapies that reduce disease progression
that are currently lacking.
REFERENCES
1. Lopez AD, Murray CC. The global burden of disease, 1990-2020. Nat Med
1998; 4:1241-1243.
2. Murray CJL, Lopez AD, Mathers CD, Stein C. The Global Burden of Disease
2000 Project: global programme on evidence for health policy discussion, paper
#36. Geneva, WHO, 2001.
