Future Considerations New Therapies

Bronchodilators play an important role in the long-term management of patients with COPD, but they do not alter the progression of COPD. Major advances include the development of long-acting b2-adrenergic agents, such as salmeterol and formoterol, and anticholinergic agents, such as tiotropium bromide. Tiotropium bromide has the benefit of once-daily dosing. Inflammation is being investigated more closely in the pathogenesis of COPD, especially the role of neutrophils. 30 Corticosteroids, chemokine (interleukin 8) inhibitors, leukotriene B 4 inhibitors, adhesion molecule inhibitors, and phosphodiesterase inhibitors are being studied with the goal of inhibiting neutrophil activity. Surfactant replacement is also under investigation. Evidence suggests that the imbalance between proteases in COPD patients may be restored either by inhibiting proteolytic enzymes, such as neutrophil elastase inhibitors, cathepsin inhibitors, matrix metalloproteinase inhibitors, and secretory leukoprotease inhibitors, or by increasing antiproteases, such as a 1-antitrypsin. Evidence also exists that oxidative stress is increased in patients with COPD, and that reactive oxygen species are involved in the pathogenesis of COPD. Therefore, antioxidants such as N-acetyl cysteine and spin-trap antioxidants such as a-phenyl-N-tertbutyl nitrone may be useful. Pulmonary vasodilators, such as prostacyclin analogues, nitric oxide donors, endothelial antagonists, and angiotensin antagonists, are being studied in the hope of preventing the progression of pulmonary hypertension and cor pulmonale. Mucoregulators, such as tachykinin antagonists, sensory neuropeptide-release inhibitors, mediator and enzyme inhibitors, MUC gene suppressors, and mucolytic agents, may inhibit the hypersecretion of mucus, without affecting normal mucus secretion and normal mucociliary clearance.

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