Key Points
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Chronic obstructive pulmonary disease (COPD) is one of the most common causes of death and morbidity in the world, and is rising in prevalence throughout the world.
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Current drug therapy concentrates on bronchodilators to reduce symptoms, and the new long-acting anticholinergic tiotropium bromide seems to be the most effective bronchodilator to date.
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No treatment is available at present that stops the relentless progression of the disease.
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A better understanding of the cellular and molecular mechanisms that underlie the inflammatory and destructive disease process is now pointing to several new therapeutic targets.
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Antagonists that block inflammatory mediators that are involved in the recruitment of neutrophils, monocytes and cytotoxic T-lymphocytes are in development, including leukotriene B4 and CXC-chemokine antagonists and inhibitors of tumour-necrosis factor-α.
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Oxidative stress is an important component of COPD, and new antioxidants and peroxynitrite inhibitors are in development.
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Corticosteroids have little or no anti-inflammatory effect in COPD patients, so that new broad-spectrum anti-inflammatory drugs are needed. Drugs in development include phosphodiesterase-4 inhibitors, p38 mitogen-activated-protein-kinase inhibitors, and NF-κB inhibitors.
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Proteases are responsible for the destruction of lung parenchyma that is seen in emphysema, and several elastase inhibitors are now in development.
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The possibility of reversing emphysema with retinoic-acid-receptor agonists is also being explored.
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New delivery systems are needed to optimize the new therapies that need to be delivered to small airways and lung parenchyma.
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New ways to monitor the inflammation in COPD are needed to assess these new therapies in clinical studies.
Abstract
COPD is one of the most common diseases in the world, and there is a global increase in prevalence, but there are no drugs available at present that halt the relentless progression of this disease. However, a better understanding of the cellular and molecular mechanisms that are involved in the underlying inflammatory and destructive processes has revealed several new targets for which drugs are now in development, and the prospects for finding new treatments are good.
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Glossary
- EMPHYSEMA
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The destruction of the lung parenchyma by proteolytic enzymes (proteases).
- LUNG PARENCHYMA
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The part of the lungs beyond the airways (alveoli) at which gas exchange takes place.
- NEUTROPHIL
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A white cell (granulocyte) that is recruited into the lungs from the circulation in COPD. Through the release of proteolytic enzymes, these cells might contribute to emphysema.
- MACROPHAGE
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An inflammatory cell in the lung that is derived from monocytes in the circulation. They are the scavengers of the lungs, and can produce many inflammatory mediators.
- CYTOTOXIC (CD8+) T-LYMPHOCYTE
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An immune cell that is recruited from the circulation that has the ability to kill infectious organisms and, also, epithelial cells in the lung.
- DYSPNOEA
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Shortness of breath and discomfort of breathing.
- EXACERBATIONS
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Worsening of COPD with increased breathlessness and sputum, which is usually caused by bacterial or viral infections.
- MONOCYTE
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A white blood cell in the circulation that is recruited to the lungs to differentiate into a macrophage.
- CHEMOTAXIS
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The movement of cells in response to a chemical gradient that is provided by chemotactic agents, such as interleukin-8 and leukotriene B4, which attract neutrophils.
- BRONCHOALVEOLAR LAVAGE
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The procedure that is used to obtain inflammatory cells from the lungs, which involves injecting saline down a bronchoscope and recovering the fluid, which contains inflammatory mediators and cells, such as alveolar macrophages and neutrophils, the function of which can then be studied.
- ELASTOLYTIC ACTIVITY
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The breakdown of elastin fibres by enzymes (elastases).
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Barnes, P. New treatments for copd. Nat Rev Drug Discov 1, 437–446 (2002). https://doi.org/10.1038/nrd820
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DOI: https://doi.org/10.1038/nrd820
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