Drugs affecting remodelling

Since a major mechanism of airway obstruction in COPD is loss of elastic recoil due to proteolytic destruction of lung parenchyma, it seems unlikely that this could be reversible by drug therapy, although it might be possible to reduce the rate of progression by preventing the inflammatory and enzymatic disease process.

Retinoic acid increases the number of alveoli in rats and, remarkably, reverses the histological and physiological changes induced by elastase treatment [33]. It is not certain whether such alveolar proliferation is possible in adult human lungs, however. Retinoic acid activates intracellular retinoic acid receptors, which act as transcription factors to regulate the expression of many genes. The molecular mechanisms involved and whether this can be extrapolated to humans is not yet known. Several retinoic acid receptor subtype agonists have now been developed that may have a greater selectivity for this effect.

Hepatic growth factor (scatter factor) appears to be a major growth factor responsible for alveolar development, and alveolar cells respond to it during lung development [34]. If responsiveness could be restored, this might be a strategy for repairing damaged lung.

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