Chronic obstructive pulmonary diseas


Chronic obstructive pulmonary disease (COPD) refers broadly to a group of conditions that cause irreversible respiratory impairment by increasing obstruction to airflow through the bronchi of the lungs. This condition occurs most commonly in current or former regular cigarette smokers and is present in moderate to severe form in 80 million people worldwide. In 2005 the World Health Organization reported that 5 percent of all deaths around the world were due to COPD.

COPD typically has two components which may be present to varying degrees: chronic obstructive bronchitis and pulmonary emphysema. Individuals who predominantly have emphysema experience symptoms that differ in detail from those who predominantly have chronic bronchitis; however, both disorders contribute to shortness of breath during exercise and to general disability.

 

Chronic bronchitis

The chronic cough and sputum production of chronic bronchitis were once dismissed as nothing more than “smoker's cough,” without serious implications. But the striking increase in mortality from chronic bronchitis and emphysema that occurred after World War II in all Western countries indicated that the long-term consequences of chronic bronchitis could be serious. This common condition is characteristically produced by cigarette smoking. After about 15 years of smoking, significant quantities of mucus are coughed up in the morning, due to an increase in size and number of mucous glands lining the large airways. The increase in mucous cells and the development of chronic bronchitis may be enhanced by breathing polluted air (particularly in areas of uncontrolled coal burning). The changes are not confined to large airways, though these produce the dominant symptom of chronic sputum production. Changes in smaller bronchioles lead to obliteration and inflammation around their walls. All these changes together, if severe enough, can lead to disturbances in the distribution of ventilation and perfusion in the lung, causing a fall in arterial oxygen tension and a rise in carbon dioxide tension. By the time this occurs, the ventilatory ability of the patient, as measured by the velocity of a single forced expiration, is severely compromised; in a cigarette smoker, ventilatory ability has usually been declining rapidly for some years. It is not clear what determines the severity of these changes. Some people can smoke for decades without evidence of significant airway changes, whereas others may experience severe respiratory compromise after 15 years or less of exposure.

 

Pulmonary emphysema

This irreversible disease consists of destruction of alveolar walls. It occurs in two forms, centrilobular emphysema, in which the destruction begins at the centre of the lobule, and panlobular (or panacinar) emphysema, in which alveolar destruction occurs in all alveoli within the lobule simultaneously. In advanced cases of either type, this distinction can be difficult to make. Centrilobular emphysema is the form most commonly seen in cigarette smokers, and some observers believe it is confined to smokers. It is more common in the upper lobes of the lung (for unknown reasons). By the time the disease has developed, some impairment of ventilatory ability has probably occurred. Panacinar emphysema may also occur in smokers, but it is the type of emphysema characteristically found in the lower lobes of patients with a deficiency in the antiproteolytic enzyme known as alpha-1 antitrypsin. Like centrilobular emphysema, panacinar emphysema causes ventilatory limitation and eventually blood gas changes. Other types of emphysema, of less importance than the two major varieties, may develop along the dividing walls of the lung (septal emphysema) or in association with scars from other lesions.

A major step forward in understanding the development of emphysema followed the identification, in Sweden, of families with an inherited deficiency of alpha-1 antitrypsin, an enzyme essential for lung integrity. Members of affected families who smoked cigarettes commonly developed panacinar emphysema in the lower lobes, unassociated with chronic bronchitis but leading to ventilatory impairment and disability. Intense investigation of this major clue led to the “protease-antiprotease” theory of emphysema. It is postulated that cigarette smoking either increases the concentration of protease enzymes released in the lung (probably from white blood cells) or impairs the lung's defenses against these enzymes or both. Although many details of the essential biochemical steps at the cellular level remain to be clarified, this represents a major step forward in understanding a disease whose genesis was once ascribed to overinflation of the lung (like overdistending a bicycle tire).

Chronic bronchitis and emphysema are distinct processes. Both may follow cigarette smoking, however, and they commonly occur together, so determination of the extent of each during life is not easy. In general, significant emphysema is more likely if ventilatory impairment is constant, gas transfer in the lung (usually measured with carbon monoxide) is reduced, and the lung volumes are abnormal. Development of high-resolution computerized tomography has greatly improved the accuracy of detection of emphysema. Some people with emphysema suffer severe incapacity before the age of 60; thus, emphysema is not a disease of the elderly only. An accurate diagnosis can be made from pulmonary function tests, careful radiological examination, and a detailed history. The physical examination of the chest reveals evidence of airflow obstruction and overinflation of the lung, but the extent of lung destruction cannot be reliably gauged from these signs, and therefore laboratory tests are required. (For more information about the methods of detection of lung diseases, see above Methods of investigation.)

The prime symptom of emphysema, which is always accompanied by a loss of elasticity of the lung, is shortness of breath, initially on exercise only, and associated with loss of normal ventilatory ability and increased obstruction to expiratory airflow. The expiratory airflow from a maximum inspiration is measured by the “forced expiratory volume in one second,” or FEV1, and is a predictor of survival of emphysema. Chronic hypoxemia (lowered oxygen tension) often occurs in severe emphysema and leads to the development of increased blood pressure in the pulmonary circulation, which in turn leads to failure of the right ventricle of the heart. The symptoms and signs of right ventricular failure include swelling of the ankles (edema) and engorgement of the neck veins. These are portents of advanced lung disease in this condition. The hypoxemia may also lead to an increase in total hemoglobin content and in the number of circulating red blood cells, as well as to psychological depression, irritability, loss of appetite, and loss of weight. Thus, the advanced syndrome of chronic obstructive lung disease may cause such shortness of breath that the afflicted person has difficulty walking, talking, and dressing, as well as numerous other symptoms.

The slight fall in ventilation that normally accompanies sleep may exacerbate the failure of lung function in chronic obstructive lung disease, leading to a further fall in arterial oxygen tension and an increase in pulmonary arterial pressure.

Unusual forms of emphysema also occur. In one form the disease appears to be unilateral, involving one lung only and causing few symptoms. Unilateral emphysema is believed to result from a severe bronchiolitis in childhood that prevented normal maturation of the lung on that side. “Congenital lobar emphysema” of infants is usually a misnomer, since there is no alveolar destruction. It is most commonly caused by overinflation of a lung lobe due to developmental malformation of cartilage in the wall of the major bronchus. Such lobes may have to be surgically removed to relieve the condition. Bullous emphysema can occur in one or both lungs and is characterized by the presence of one or several abnormally large air spaces surrounded by relatively normal lung tissue. This disease most commonly occurs between the ages of 15 and 30 and usually is not recognized until a bullous air space leaks into the pleural space, causing a pneumothorax.

 

Lung cancer

Up to the time of World War II, cancer of the lung was a relatively rare condition. The increase in its incidence in Europe after World War II was at first ascribed to better diagnostic methods, but by 1956 it had become clear that the rate of increase was too great to be accounted for in this way. At that time the first epidemiological studies began to indicate that a long history of cigarette smoking was associated with a great increase in risk of death from lung cancer. By 1965 cancer of the lung and bronchus accounted for 43 percent of all cancers in the United States in men, an incidence nearly three times greater than that of the second most common cancer (of the prostate gland) in men, which accounted for 16.7 percent of cancers. In 1964 Smoking and Health: Report of the Advisory Committee to the Surgeon General of the Public Health Service (United States) concluded categorically that cigarette smoking is causally related to lung cancer in men. Since then, many further studies in diverse countries have confirmed this conclusion.

The incidence of lung cancer in women began to rise in 1960 and continued rising through the mid-1980s. This is believed to be explained by the later development of heavy cigarette smoking in women compared with men, since women greatly increased their cigarette consumption during World War II. By 1988 there was evidence suggesting that the peak incidence of lung cancer due to cigarette smoking in men may have been passed. The incidence of lung cancer mortality in women, however, is increasing.

The reason for the carcinogenicity of tobacco smoke is not known. Tobacco smoke contains more than 60 carcinogenic compounds, including harmful nitrosamines and polycyclic aromatic hydrocarbons. In addition to its single-agent effects, cigarette smoking greatly potentiates the cancer-causing proclivity of asbestos fibres, increases the risk of lung cancer due to inhalation of radon daughters (products of the radioactive decay of radon gas), and possibly also increases the risk of lung cancer due to arsenic exposure. People who do not smoke but who live or work with smokers and who therefore are exposed to secondhand tobacco smoke have an increased risk for lung cancer.

Because lung cancer is characterized by different types of tumours, because it may be located in different parts of the lung, and because it may spread beyond the lungs at an early stage, the first symptoms noted by the patient vary. These symptoms may include a persistent cough, blood staining of the sputum, a pneumonia that does not resolve fully with antibiotics, or shortness of breath due to a pleural effusion. A physician may discover distant metastases in bone tissues or in the brain that cause symptoms unrelated to the lung. Lymph nodes may be involved early, and enlargement of the lymph nodes in the neck may lead to a chest examination and the discovery of a tumour. In some cases a small tumour metastasis in the skin, abnormal mental function or behaviour, jaundice from liver dysfunction, or sensory changes in the legs from peripheral neuropathy (damage to nerves outside the central nervous system) may be the first sign of the disease. In other cases, only a general feeling of malaise, unusual fatigue, or seemingly minor symptoms may serve as the first indication. In addition, some affected individuals experience clubbing (swelling) of the fingers and toes, an unusual sign that may disappear after surgical removal of the tumour. Lung cancer may develop in an individual who already has chronic bronchitis and who therefore has had a cough for many years.The diagnosis often depends on securing tissue for histological examination, although in some cases this entails removal of the entire neoplasm before a definitive diagnosis can be made.

Survival from lung cancer has improved only slightly since the mid-1970s, when the U.S. government greatly increased funding for cancer research in an effort to find a cure for the disease. Early detection with routine chest radiographs has been attempted, and large-scale trials of routine sputum examination for the detection of malignant cells have been conducted, but neither screening method has been shown thus far to affect long-term mortality. Attention has been turned to prevention by every means possible. Foremost among them are efforts to inform the public of the risk and to limit the advertising of cigarettes. Steps have been taken to reduce asbestos exposure, both in the workplace and in public and private buildings, and to control air pollution. The magnitude of the contribution of air pollution to the incidence of lung cancer is not known with certainty.

Persons exposed to radon are at risk for lung cancer. The hazard from exposure was formerly thought to be confined to uranium miners, who, by virtue of their work underground, encounter high levels of these radioactive materials. However, significant levels of radon have been detected in houses built over natural sources, and, with increasingly efficient insulation of houses, radon may reach concentrations high enough to place the occupants at risk for lung cancer. Major regional variations in the natural distribution of radon occur, and it is not yet possible to quantify precisely the actual magnitude of the risk. In some regions of the world (such as the Salzburg region of Austria), levels are high enough that radon exposure is believed to account for the majority of cases of lung cancer in nonsmokers.

Workers exposed to arsenic in metal-smelting operations, and the community around the factories from which arsenic is emitted, have an increased risk for lung cancer. Arsenic is widely used in the electronics industry in the manufacture of various products, including microchips and semiconductors, and careful surveillance of this industry has helped prevent future disease.

Some types of lung cancer are unrelated to cigarette smoking. Alveolar cell cancer is a slowly spreading condition that affects men and women in equal proportion and is not related to cigarette smoking. Pulmonary adenocarcinoma of the lung also has a more equal sex incidence than other types; although its incidence is increased in smokers, it may also be caused by other factors.

It is common to feel intuitively that one should be able to apportion cases of lung cancer among discrete causes, on a percentage basis. But in multifactorial disease, this is not possible. Although the incidence of lung cancer would probably be far lower without cigarette smoking, the contribution of neither this factor nor any of the other factors mentioned can be precisely quantified. Treatment of most forms of lung cancer may involve chemotherapy, radiation therapy, or surgery (see Lung cancer: Treatment).

 

Occupational lung disease