Chest
Volume 117, Issue 2, Supplement, February 2000, Pages 10S-14S
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Mechanisms in COPD: Differences From Asthma

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Although considerable progress has been made in understanding the cellular and molecular mechanisms of asthma, much less attention has been paid to COPD. The inflammatory process in COPD is very different from that in asthma, with different inflammatory cells, mediators, inflammatory effects, and response to therapy. Airway inflammation in asthma, characterized by an eosinophilic inflammation affecting all the airways but not lung parenchyma, is linked to airway hyperresponsiveness. In COPD, there is a predominantly neutrophilic inflammation in the airways. Parenchymal destruction is an important irreversible feature and leads to airflow obstruction through dynamic compression. The eosinophilic inflammation in asthma is markedly suppressed by corticosteroids, but they have no appreciable effect on the inflammation in COPD, consistent with a failure of long-term corticosteroids to alter the progression of COPD.

Section snippets

Inflammatory Cells and Pathology

Airway inflammation in asthma is characterized by an eosinophilic inflammation, with an increase in activated and degranulating eosinophils in bronchial biopsies, BAL, and in induced sputum.12 There is also an increase in CD4+ T lymphocytes (T-helper type 2 cells) that appear to orchestrate the eosinophilic inflammation and degranulated mast cells that underlie the rapid and episodic bronchoconstrictor responses that are so characteristic of asthma. Epithelial shedding is a common feature of

Inflammatory Mediators

More than 50 inflammatory mediators have been implicated in asthma.11 Cysteinyl-leukotrienes are prominent bronchoconstrictors in asthma and are derived from mast cells and eosinophils. Histamine, prostaglandins, and kinins may also contribute to bronchoconstriction in asthma. Cholinergic reflexes may be activated by these inflammatory mediators, particularly kinins. β2-Agonists are by far the most effective bronchodilators in asthma, as they act as functional antagonists and counteract the

Enzymes

Several inflammatory enzymes are involved in asthma.11 Mast cell tryptase may play an important role in AHR and in some aspects of airway remodeling in asthma. In COPD, there is excessive activity of proteases, and an imbalance between proteases and endogenous antiproteases. Several proteases are likely to be involved in lung parenchymal destruction. Neutrophil elastase, a neutral serine protease, is a major constituent of lung elastolytic activity and also potently stimulates mucus secretion.

Response to Anti-inflammatory Treatment

The response to treatment differs markedly between asthma and COPD. The eosinophilic inflammation in asthma is markedly suppressed by corticosteroids, which inhibit almost every aspect of the inflammatory process.25 There is a disappearance of eosinophils from the airways and sputum, with a reduction in AHR. In contrast, corticosteroids do not appear to have any effect on the inflammation in COPD, with no changes in neutrophilic inflammation, reduction in inflammatory mediators, or proteases.26

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