What lies ahead? Future research and treatment for chronic obstructive pulmonary disease

The morphologic basis for airflow obstruction in chronic obstructive pulmonary disease is extremely complex and consists of heterogeneous lesions. Emphysema seems to be the single most important lesion in this disorder. Abnormalities of the peripheral conducting airways, including inflammation, fibrosis, smooth muscle hypertrophy, and hyperplasia of mucus-secreting elements, are also of functional importance. Low-grade inflammation involving both airways and parenchyma occurs after only short-term exposure to cigarette smoke. This chronic inflammatory reaction may initiate other, largely irreversible, tissue responses that are responsible for airflow function. In the case of emphysema, tissue obstruction is thought to be due to an elastase-antielastase imbalance, leading to accelerated destruction of elastic fibers in the alveolar walls. Logical strategies for controlling the development of emphysema might include measures to prevent the influx of phagocyte-borne elastases into the lung as well as efforts to supplement the antiprotease shield of the lower airways. Anti-inflammatory drugs might also be effective in suppressing cigarette-smoke--induced reactions in the conducting airways. Other agents might be effective by preventing bronchoconstriction and the proliferation of smooth muscle elements in airway walls.
Over the last two decades, the incidence of chronic obstructive pulmonary disease (COPD) has been increasing. COPD is a major cause of mortality and new methods of preventing and treating COPD are needed. Cigarette smoking is the leading known cause of COPD. The physiological changes that occur in the lungs of patients with COPD include lung tissue inflammation, destruction of the elastic fibers that allow the lungs to expand, fibrosis (the formation of dense, nonelastic tissue), excessive growth of smooth muscle cells, and excessive mucus production. Emphysema is the most serious form of COPD, which occurs when enzymes called proteases, such as elastase, destroy the lung tissue. Cigarette smoking causes emphysema by causing inflammation in the lungs, which increases the amount of proteases and tissue damage. Under normal circumstances, the lung tissue makes a substance called alpha-1 proteinase inhibitor (alpha1-PI), which inactivates proteases so that they do not damage the lung tissue. However, during chronic cigarette smoking large amounts of proteases are made and there is not enough alpha1-PI to prevent tissue damage. Emphysema can also be caused by an inherited deficiency of alpha1-PI. Infusions of alpha1-PI have been used to treat patients with alpha1-PI deficiency, but this form of treatment is very expensive. Corticosteroids reduce tissue inflammation and may be effective in slowing the progression of COPD. Clinical studies are needed to determine if drugs such as ipratropium, which that dilate the lung air passages, can help slow the progression of COPD in cigarette smokers. At the present time, the best method of preventing COPD is preventing or stopping cigarette smoking. (Consumer Summary produced by Reliance Medical Information, Inc.)