45 Emphysema
Pulmonary emphysema is defined in morphological rather than clinical terms. The 1958 Ciba Symposium defined emphysema as an “increase beyond the normal of air spaces, distal to the terminal bronchiole, either from dilation or from destruction of their walls.” The subsequent American Thoracic Society statement in 1962 made anatomic destruction a part of the definition: “Emphysema is an anatomic alteration of the lung characterized by an abnormal enlargement of the air spaces distal to the terminal, nonrespiratory bronchiole, accompanied by destructive changes of the alveolar walls.”
The definition was refined in 1985 in a workshop report of the National Heart, Lung, and Blood Institute: “Emphysema is defined as a condition of the lung characterized by abnormal, permanent enlargement of airspaces distal to the terminal bronchiole, accompanied by the destruction of their walls, and without obvious fibrosis.”
Emphysema can also be subclassified in anatomic terms.
The acinus is the gas-exchanging unit of the lung served by a single terminal bronchiole. Within the acinus, the terminal bronchiole is succeeded by three orders of branching respiratory bronchioles that are subsequently succeeded by alveolar ducts and terminal alveolar sacs, all of which bear alveoli. If emphysematous changes predominate in the region of respiratory bronchioles, the condition is termed centriacinar or centrilobular emphysema. More uniform involvement constitutes panacinar or panlobular emphysema. Emphysema located predominantly in the periphery of the acinus along lobular septa is paraseptal emphysema. Occasionally, emphysema may occur adjacent to a scar or fibrotic process and is called paracicatricial emphysema. be a universal finding in elderly adults if properly prepared lungs are carefully examined.Distribution and Incidence
Because emphysema is, by definition, a morphological diagnosis, its presence and prevalence depend on the interpretation of an examination of the lungs during an autopsy.
Obvious emphysema is likely to be found in at least 50 percent of an average autopsy population, with a frequency of about 65 percent in men and 15 percent in women. Incidence increases with age, reaching 30 percent by the fourth decade and 60 percent by the seventh decade of life. It has been suggested that at least some emphysema mayEpidemiology
Whereas most epidemiological studies are based on information elicited by questionnaires or physiological tests, emphysema is a morphological diagnosis and epidemiological studies must be confined to autopsy data. Furthermore, the lungs must be properly fixed on inflation and examined using comparable techniques and emphysema grading methods. Perhaps because of a younger average age of the population examined and a lower prevalence of cigarette smoking, studies from Africa reveal a lower frequency of emphysema than elsewhere. Yet even when populations are of the same age, and the lungs are examined by the same investigators, there appear to be some national and even regional differences. For example, the frequency of emphysema is greater in parts of the United Kingdom than in Sweden or some parts of North America, and lower in some North American cities than in others. The frequency differences may reflect different patterns of cigarette smoking or levels of air pollution, or the selection of people autopsied. The various studies do agree that the amount and severity of emphysema increase with advancing age, and cigarette smoking is a primary cause of the disease. In the various studies, emphysema is found, and in more severe form, at least twice as often in men as in women. The greater incidence of emphysema in males may reflect the greater prevalence of smoking in men; if that is the case, then as more women take up cigarette smoking, this sex preference may change. Although emphysema is remarkably common, it is a cause of, or contributes to, death in only a small percentage of cases.
Etiology
The disruption of alveolar architecture characteristic of emphysema appears to be the result of tissue destruction caused by elastolytic proteases derived from polymorphonuclear leukocytes and alveolar macrophages.
Uninhibited digestion of tissue is observed in patients with alpha-l-antitrypsin deficiency. This genetically determined protease inhibitor phenotype Z (PiZ) occurs in no more than 1 in 1,000 individuals in a general population, however, and thus can account for only a small proportion of emphysema cases. Evidence suggests that cigarette smoke can enhance accumulation of leukocytes and macrophages in the lung with release of elastolytic enzymes, and can also inhibit antiprotease activity by mechanisms still under study. Although some forms of mild emphysema are quite common and can occur in nonsmokers, there is nonetheless a strong association between cigarette smoking and emphysema. Thus, although the precise mechanisms remain to be elucidated, cigarette smoking is the most important cause of the moderate to severe forms of emphysema, causing clinical symptoms, respiratory impairment, disability, and death.Clinical Manifestations
The patient with clinically significant emphysema is typically an older male smoker who gives a history of breathing difficulties that increase in severity over time. On physical examination, he is usually thin, with a thoracic configuration (barrel chested) suggesting hyperinflation, and has markedly diminished breath sounds when listened to on ausculation. Airflow obstruction can be demonstrated by slowing of forced expiration. The chest radiograph confirms hyperinflation with a relatively small heart and decreased peripheral lung markings. However, this “typical” clinical picture is more often the exception than the rule. In several reported series of autopsies, moderate to severe forms of emphysema were found in a significant proportion of individuals who did not exhibit clinical evidence of the disease. In addition, chest radiographs are not reliable in either diagnosing or ruling out emphysema. Most often, emphysema OCCtu-S in conjunction with chronic bronchitis and is accompanied by a chronic productive cough.
The presumptive diagnosis of emphysema cannot be made without pulmonary function tests. Chronic airflow obstruction manifested by slowing of forced expiration is characteristic of moderate to severe emphysema, although even this finding may not be universal. When emphysema increases in severity, hyperinflation is reflected by an increase in total lung capacity and residual volume, and the carbon monoxide diffusing capacity is reduced. Loss of lung elastic recoil is commonly associated with emphysema. Such physiological data provide more sensitive indicators of the presence of emphysema than do clinical signs and symptoms or radiological findings.
History
In a postscript to his 1698 Treatise of the Asthma, John Floyer described bullous emphysema, together with hyperinflation and loss of lung elastic recoil, from his dissection of a broken winded mare. In his 1793 book on Morbid Anatomy, Matthew Baillie described the morphology of human emphysema with tissue destruction leading to airspace enlargement. There is good evidence that the lung used as an illustration in Baillie’s book was that of Samuel Johnson, whose lungs, at autopsy, were found to be permanently distended and failed to collapse on opening the chest. Rene Laennec’s classic Treatise on the Diseases of the Chest first appeared in 1819 and was expanded in a subsequent edition in 1826, the year of his death. In it, Laennec provided the first description of pulmonary emphysema, the destructive nature of the disease, and its association with chronic bronchitis. James Jackson, Jr., accumulated a series of cases of emphysema and noted that the disease exhibited a familial predisposition. Though he died in 1834, his work was published in a paper by his mentor Pierre Louis in 1837. It was not until 1963 that the genetically determined alpha-1- antitrypsin deficiency associated with emphysema was described. The physiological changes associated with emphysema have attracted the attention of many investigators over the years.
The loss of lung recoil associated with emphysema was inferred from early observations. It was noted by Fritz Rohrer in 1916 and studied by K. von Neergaard and K. Wirz in 1927 and Ronald Christie in 1934 among others. Recent advances in the pathological anatomy of emphysema stem from the work of J. Gough in 1952 using techniques developed by him and by J. E. Wentworth. The precise mechanisms leading to the lung destruction characteristic of emphysema are under current investigation.Ronald J. Knudson
Bibliography
American Thoracic Society. 1962. Definitions and classifications of chronic bronchitis, asthma, and pulmonary emphysema: A statement by the American Thoracic Society. American Review OfRespiratory Diseases 85: 762-8.
Ciba Symposium. 1959. Terminology, definitions, and classification of chronic pulmonary emphysema and related conditions: A report of the conclusions of a Ciba guest symposium. Thorax 14: 289—99.
Report of a National Heart, Lung, and Blood Institute, Division of Lung Diseases Workshop. 1985. The definition of emphysema. American Review of Respiratory Diseases 132: 182—5.
Snider, Gordon L., ed. 1983. Clinics in chest medicine, Vol. 4, No. 3.
Thurlbeck, William M. 1976. Chronic airflow obstruction in lung disease. Philadelphia.
1982. The anatomical pathology of chronic airflow obstruction. In Current pulmonology, ed. D. H. Simmons, 1—24. New York.