Future directions in the pharmacologic therapy of chronic obstructive pulmonary disease.
Current therapy for chronic obstructive pulmonary disease (COPD) fails to alter its relentless progression. This remains a significant challenge and unmet need. A recent advance is the demonstration that treatment with a fixed dose of an inhaled corticosteroid and a long-acting beta2-agonist in COPD improves lung function and quality of life, and reduces exacerbation more effectively than either drug alone. Other improvements include the introduction of tiotropium, a once-daily anticholinergic. In advanced clinical development are other once-daily bronchodilators and combinations of anticholinergic drugs and beta2-agonists. Increased understanding of the pathogenesis of COPD has led to novel drugs aimed at inhibiting targets, including phosphodiesterase 4, proteases, and various inflammatory mediators. Furthermore, COPD is increasingly seen as a systemic disorder or, indeed, may be a pulmonary manifestation of a complex pathophysiologic response to chronic inhalation of toxic irritants and associated with aging. Future therapy may involve better understanding of how best to target existing drugs used to treat cardiovascular disorders associated with smoking, such as atherosclerosis and hypercoagulability, and the development of new drugs that target systemic and metabolic manifestations that either result from or coexist with chronic lung inflammation, hypoxia, and cardiovascular disease in COPD.
Buhl
Roland
R
Mainz University Hospital, Langenbeckstrasse 1, Mainz, D-55131, Germany. r.buhl@3-med.klinik.uni-mainz.de
Farmer
Stephen G
SG
D000280:Administration, Inhalation; D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000975:Antioxidants / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000627:therapeutic use; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011480:Protease Inhibitors / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology; D011788:Quality of Life; D016540:Smoking Cessation
D000318:Adrenergic beta-Agonists; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D000975:Antioxidants; D001993:Bronchodilator Agents; D005938:Glucocorticoids; D010726:Phosphodiesterase Inhibitors; D011480:Protease Inhibitors