Am. J. Respir. Crit. Care Med.,
Volume 160, Number 5, November 1999, S72-S79
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S79.There is a driving need to develop new and effective treatments for COPD. Bronchodilators are now
the mainstay of symptomatic therapy and a new long-acting anticholinergic bronchodilator, tiotropium bromide, is now in advanced clinical trials as a once daily dry powder inhaler. Several inflammatory mediators are involved in the chronic neutrophilic inflammation that typifies COPD, including leukotriene B4 and interleukin 8, for which specific receptor antagonists have been developed.
Since the inflammatory process in COPD is essentially steroid resistant, new antiinflammatory treatments are needed. Drugs that may be effective include phosphodiesterase 4 inhibitors, NF-
B inhibitors, and interleukin 10. Inhibition of proteases is another approach and inhibitors of neutrophil
elastase, cathepsins, and matrix metalloproteases are now in clinical development. Supply of endogenous antiproteases, such as 
1-antitrypsin and secretory leukocyte protease inhibitors as recombinant proteins or by gene transfer, is also being explored. In future drugs that may stimulate alveolar
repair might be developed, including retinoid receptor agonists and hepatic growth factor. Future
directions will include earlier detection of disease, gene profiling to identify which smokers are at risk
of COPD, and the development of noninvasive surrogate markers to monitor disease activity in order
to monitor new therapies. Identification of genes that confer a risk for COPD in smokers may identify
novel targets for drug development. Barnes PJ. Novel approaches and targets for treatment of
chronic obstructive pulmonary disease.
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  J. O. Cantor and G. M. Turino Can Exogenously Administered Hyaluronan Improve Respiratory Function in Patients With Pulmonary Emphysema? Chest, January 1, 2004; 125(1): 288 - 292. [Abstract] [Full Text] [PDF]
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R. I. Cohen, K. Marzouk, P. Berkoski, C. P. O'Donnell, V. Y. Polotsky, and S. M. Scharf Body Composition and Resting Energy Expenditure in Clinically Stable, Non-Weight-Losing Patients With Severe Emphysema Chest, October 1, 2003; 124(4): 1365 - 1372. [Abstract] [Full Text] [PDF]
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 P J Barnes Chronic obstructive pulmonary disease * 12: New treatments for COPD Thorax, September 1, 2003; 58(9): 803 - 808. [Full Text] [PDF]
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 N. Mukaida Pathophysiological roles of interleukin-8/CXCL8 in pulmonary diseases Am J Physiol Lung Cell Mol Physiol, April 1, 2003; 284(4): L566 - L577. [Abstract] [Full Text] [PDF]
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 M. Decramer, P.N.R. Dekhuijzen, T. Troosters, C. van Herwaarden, M. Rutten-van Molken, C.P.O. van Schayck, D. Olivieri, I. Lankhorst, and A. Ardia The Bronchitis Randomized On NAC Cost-Utility Study (BRONCUS): hypothesis and design Eur. Respir. J., March 1, 2001; 17(3): 329 - 336. [Abstract] [Full Text] [PDF]
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 A. Tung Perioperative Ventilation of the Vascular Surgery Patient Seminars in Cardiothoracic and Vascular Anesthesia, November 1, 2000; 4(4): 265 - 274. [Abstract] [PDF]
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D. C. Underwood, R. R. Osborn, S. Bochnowicz, E. F. Webb, D. J. Rieman, J. C. Lee, A. M. Romanic, J. L. Adams, D. W. P. Hay, and D. E. Griswold SB 239063, a p38 MAPK inhibitor, reduces neutrophilia, inflammatory cytokines, MMP-9, and fibrosis in lung Am J Physiol Lung Cell Mol Physiol, November 1, 2000; 279(5): L895 - L902. [Abstract] [Full Text] [PDF]
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 P. J. Barnes Chronic Obstructive Pulmonary Disease N. Engl. J. Med., July 27, 2000; 343(4): 269 - 280. [Full Text] [PDF]
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