Deaths due to asthma are declining, but still remain a serious problem. Patients with severe, chronic asthma are at higher risk of death compared to other asthma patients and do not respond to steroid treatment. Asthma-related deaths are caused by inflammation, mucus production, and airway hyperresponsiveness. Clearly, it is important for the lung to quickly resolve the inflammation and mucous, yet the mechanisms of inflammatory cell clearance are poorly studied. One group of enzymes, the matrix metalloproteinases (MMPs), may shed light on this issue. MMP 2 and MMP9 are enzymes that degrade elastin and collagen and have been implicated in lung tissue destruction. Increasingly, MMPs have been found to play important roles in post-translational modification of other proteins that may be beneficial during resolution of inflammation. Mice lacking MMP2 and MMP9 have a decreased ability to clear inflammatory cells from the lung after induction of experimental asthma. One hypothesis is that these MMPs modify proteins in ways that increase cell clearance from sites of inflammation. Since most asthma-related deaths occur due to the inability of the patient to recover from the episode, one possible treatment could be to administer MMPs or other proteinases. Also, since only a subset of asthma patients die from asthma attacks, it is possible that they have differences in the quantity or quality of their MMPs. ? ? ? ?
