Toward the Formulation of a Theory of Asthma

TOWARD THE FORMULATION OF A THEORY OF ASTHMA ALAN R. LEFF* Early Conceptualizations: Defining Asthma Asthma is a Greek word meaning panting or short-drawn breath. It was described by Hippocrates and recognized as a disease entity by Egyptian and Hebrew physicians. A close approximation of a modern theory of asthma was formulated by Thomas Willis in 1678. Willis believed asthma was caused by ". . . cramps of the moving fibre of the bronchi" [I]. A reasonable description of the symptoms of asthma was given by Sir John Floyer in 1698; Floyer also proposed that bronchospasm was the underlying cause [2]. At the same time that asthma was being described clinically, other forms of obstructive airways disease were being elucidated. Floyer described the morphology of emphysema in a mare [2], and Laennec later corroborated his observations. Emphysema was first conceived as a pathological entity in humans in the seventeenth century, and the first detailed descriptions were made 100 years later by Watson [3] and Morgagni [4]. These descriptions provided the modern basis for the understanding of emphysema, which since then has been identified as the destruction and disappearance of the gas exchange units of the lung— the alveoli. Because the symptoms are similar, many physicians confused asthma with other forms of obstructive pulmonary disease. Osier characterized asthma as a "nervous condition," and this view has persisted in various forms into the twentieth century. At the turn of the twentieth century, emphysema or type A chronic obstructive pulmonary disease (COPD), chronic bronchitis (type B COPD), and asthma came to be regarded as Work supported by the National Heart, Lung, and Blood Institute, grants HL-32495 and HL-0 1398. *Section of Pulmonary and Critical Care Medicine, Department of Medicine, Box 98, University of Chicago, 5481 South Maryland Avenue, Chicago, Illinois 60637.© 1990 by The University of Chicago. All rights reserved. 003 1 -5982/90/3302-0674$0 1 .00 292 I Alan R. Leff ¦ A Theory ofAsthma separate entities. The practice of cigarette smoking has vastly increased the prevalence of COPD in Western civilization. Furthermore, as asthma may occur initially in adults even in advanced life, diagnoses of these three entities are still confused and interchanged. With the introduction of quantitative measurements of pulmonary function- testing in the early 1950s, a new dimension was added to the definition of asthma. This related to the concept of airway hyperreactivity —the notion of dynamic oscillations in airflow obstruction. These studies quantified the clinical impression that lung function in asthma changed, often within minutes, from near normal to severe obstruction and often was reversible as readily. These extreme gyrations in physiological function were nonetheless accompanied by a paucity of pathological findings. As patients rarely die of acute asthma, there has been limited study of its pathology in the acute state. Those limited studies that have been performed in patients dying of severe, relentless asthma (status asthmaticus) have shown minimal pathological changes. In contrast to the widespread destruction of alveoli characteristic of emyphysema (type A COPD) or permanent occlusive changes, loss of structural cartilage , and marked mucous gland proliferation characteristic of chronic bronchitis (type B COPD), the pathological findings of fatal asthma are relatively scant—mucous plugging of small airways, some airway edema, and inflammation and smooth muscle hypertrophy. None of these are irreversible changes. The observation of smooth muscle hypertrophy in early pathological studies suggested that the acute narrowing of airways in asthma was the result of airway smooth muscle hypercontractility—a notion that has been the nidus of most modern theories of the pathogenesis of asthma. This paucity of pathophysiological findings also led to a "dual" definition of airway obstructive diseases. While types A and B COPD are defined as pathological entities, asthma has been defined as a physiological entity in terms of oscillations in pulmonary function. In the 1959 Ciba International Symposium, emphysema was defined as an "increase beyond normal in the size of airspaces distal to the terminal bronchiole either from dilatation or from destruction of their walls" [5]. Chronic bronchitis was defined in that same symposium as "chronic or recurrent excessive mucous secretion in the bronchial tree," whereas asthma was defined as reversible airways obstruction with a compatible history. The linkage of...