Biomedical Engineering Reference
In-Depth Information
bFGF), as well as insulin growth factors IGF-I and IGF-II also promote
myofibroblast proliferation and ECM synthesis (64,82-84).
Studies performed in transgenic animals by Lee et al have shown that
over expression of IL-13 resulted in TGF-b1 production and activation by
pathways involving both plasmin and MMP-9 that initiated massive connec-
tive tissue deposition in the walls of the peripheral airways and also
increased the formation of lymphoid follicles (85). These findings are provo-
cative because the pathology produced in the peripheral airways by this
manipulation shares many of the features of human disease where there is
growing evidence that susceptibility to COPD is associated with an ampli-
fied inflammatory immune response (35,36). But much remains to be done
to precisely determine how either the innate or adaptive inflammatory
responses are linked to the repair and remodeling process that remodels
the airway walls.
In summary the small conducting airways are the major site of airway
obstruction in COPD and the pathology responsible for this obstruction can
be attributed to the innate and adaptive inflammatory immune response to
the chronic inhalation of toxic gases and particles. Although the extent and
severity of the infiltration of the airway walls is associated with a decline in
lung function in COPD there is a much closer association with the accumu-
lation of inflammatory exudates in the lumen of the airways as a result of
failure of the innate response to clear the airways and a thickening of the
airway wall by the repair and remodeling process associated with both the
innate and adaptive immune system. A clearer understanding of the molecu-
lar mechanisms that link the individual components of the overall response
in the peripheral
lung could lead to new therapeutic targets for this
condition.
REFERENCES
1. Horsefield K, Cumming G. The morphology of the bronchial tree in man. J
Appl Physiol 1968; 24:373.
2. Weibel ER. Morphometry of the Human Lung. Heidelburg: Springer, 1963.
3. Haefeli-Bleuer B, Weibel ER. Morphometry of the human pulmonary acinus.
Anat Rec 1988; 220:401-414.
4. Vincent NJ, Knudson R, Leith D, Macklem PT, Mead J. Factors influencing
pulmonary resistance. J Appl Physiol 1970; 29:236-243.
5. Macklem PT, Mead J. Resistance of central and peripheral airways measured
by the retrograde catheter. J Appl Physiol 1967; 22:395-401.
6. Hogg JC, Macklem PT, Thurlbeck WM. Site and nature of airways obstruction
in chronic obstructive lung disease. N Engl J Med 1968; 278:1355-1360.
7. Yanai M, Sekizawa K, Ohrui T, Sasaki H, Takishima T. Site of airway obstruc-
tion in pulmonary disease: direct measurement of intrabronchial pressure. J
Appl Physiol 1992; 72:1016-1023.
