What causes COPD?

Smoking is responsible for 90% of COPD in the United States. Although not all cigarette smokers will develop COPD, it is estimated that 15% will. Smokers with COPD have higher death rates than nonsmokers with COPD. They also have more frequent respiratory symptoms (coughing, shortness of breath, etc.) and more deterioration in lung function than non-smokers.

Effects of passive smoking or "second-hand smoke" on the lungs are not well-known; however, evidence suggests that respiratory infections, asthma, and symptoms are more common in children who live in households where adults smoke.

Cigarette smoking damages the lungs in many ways. For example, the irritating effect of cigarette smoke attracts cells to the lungs that promote inflammation. Cigarette smoke also stimulates these inflammatory cells to release elastase, an enzyme that breaks down the elastic fibers in lung tissue.

Air pollution can cause problems for persons with lung disease, but it is unclear whether outdoor air pollution contributes to the development of COPD. However, in the non-industrialized world, the most common cause of COPD is indoor air pollution. This is usually due to indoor stoves used for cooking.

Some occupational pollutants such as cadmium and silica do increase the risk of COPD. Persons at risk for this type of occupational pollution include coal miners, construction workers, metal workers, cotton workers, etc. (Most of this risk is associated with cigarette smoking and these occupations, an issue not well controlled for. These occupations are more often associated with interstitial lung diseases, especially the pneumoconioses) Nevertheless, the adverse effects of smoking cigarettes on lung function are far greater than occupational exposure.

Another well-established cause of COPD is a deficiency of alpha-1 antitrypsin (AAT). AAT deficiency is a rare genetic (inherited) disorder that accounts for less than 1% of the COPD in the United States.

As discussed previously, normal function of the lung is dependent on elastic fibers surrounding the airways and in the alveolar walls. Elastic fibers are composed of a protein called elastin. An enzyme called elastase that is found even in normal lungs (and is increased in cigarette smokers) can break down the elastin and damage the airways and alveoli. Another protein called alpha-1 antitrypsin (AAT) (produced by the liver and released into the blood) is present in normal lungs and can block the damaging effects of elastase on elastin.

The manufacture of AAT by the liver is controlled by genes which are contained in DNA-containing chromosomes that are inherited. Each person has two AAT genes, one inherited from each parent. Individuals who inherit two defective AAT genes (one from each parent) have either low amounts of AAT in the blood or AAT that does not function properly. The reduced action of AAT in these individuals allows the destruction of tissue in the lungs by elastase to continue unopposed. This causes emphysema by age 30 or 40. Cigarette smoking accelerates the destruction and results in an even earlier onset of COPD.

Individuals with one normal and one defective AAT gene have AAT levels that are lower than normal but higher than individuals with two defective genes. These individuals MAY have an increased risk of developing COPD if they do not smoke cigarettes; however, their risk of COPD probably is higher than normal if they smoke. Though their Alpha-1 antitrypsin blood levels may be in the normal range, the function of this enzyme is impaired to relative to normals.