There is considerable evidence that matrix metalloproteases (MMPs) are up and/or downregulated in COPD, particularly in emphysema where they probably participate in proteolytic attack on the alveolar wall matrix. Recent data suggest that MMPs also have major roles in driving inflammation or shutting it down, as well as modifying the release of fibrogenic growth factors, processes that are important in the genesis of the various lesions of COPD.

In cigarette smoke-induced animal models of emphysema MMP-12 appears to play a consistent and important role, whereas the data for other MMPs are difficult to interpret. In human lungs evidence for a role for MMPs is more tenuous and there are numerous contradictions in the literature. Little is known about the effects of MMPs in small airway remodeling, smoke-induced pulmonary hypertension, and chronic bronchitis, but MMP-12 participates in experimental small airway modeling.

At this point the accumulated data suggest that selective inhibition of MMP-12 might be a viable therapy for emphysema and small airway remodeling but subtle differences in the functions of MMP-12 in animals and humans mandate caution with this approach. Whether inhibition of other MMPs might be useful is unclear.