Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Element of emphysema

Such sections confirmed the presence of a panacinar emphysema (Fig 7). It seemed that, as in other genetic entities, the degree of clinical manifestation in o^AT deficiency was highly variable, ranging from complete absence of symptoms to an early onset of an obstructive lung disease with severe dyspnea. In patients with lung disease the clinical picture was also variable but consistent in the sense that obstructive ventilatory insufficiency and radiologic emphysema were almost invariably present. I believe that the most important observation was the concept of the emphysema as the basic defect in these patients, who often had clinical diagnoses just reflecting secondary events such as bronchitis, asthmatic bronchitis or even bronchial asthma. I focused on the destructive element of emphysema when suggesting the so called proteolytic theory for development of emphysema. One should remember that general consensus on the destructive element of emphysema had been reached not so many years earlier (WHO, 1961). Two main sources of proteases, namely leukocytes which were known to be sequestered in the lungs, and macrophages were suggested. Figures 8, 9 and 10 illustrate some cases taken from this original series of patients.

Inheritance and Genetic Polymorphism
When studying TIC in a large number of relatives of deficient individuals, it was confirmed that three levels of axAT were found in family members: normal, intermediate (approximately 60 percent of normal) and a markedly low level (about 10 percent of the normal activity) (Fig 5 and 11). In other words, there were examples of an intermediate type of inheritance. My impression at that time from seeing many patients with intermediate levels (heterozygotes) was that they were not predisposed to any clinically important disease. Later on, there has been much controversy about the relationship of the heterozygous state to emphysema. There now seems to be general agreement on the small increased risk in heterozygous subjects.

Alpha1-antitrypsin Deficiency: Lessons Learned from the Bedside to the Gene and Back Again: Element of emphysema

Figure 7. Panacinar emphysema at autopsy. Mounted paper section according to Gough and Wentworth. (Reprinted from Eriksson by permission.)

Figure 8. Pulmonary angiogram (from the proband). The clinical diagnosis was chronic bronchitis and emphysema. The sister had bronchial asthma and emphysema.

Figure 8. Pulmonary angiogram (from the proband). The clinical diagnosis was chronic bronchitis and emphysema. The sister had bronchial asthma and emphysema.

Figure 9. Bronchogram. Chronic bronchitis with generalized bronchiectasis. The evidence for the presence of emphysema is equivocal.

Figure 9. Bronchogram. Chronic bronchitis with generalized bronchiectasis. The evidence for the presence of emphysema is equivocal.

Figure 10. Right lung at thoracotomy. Primary bullous emphysema.

Figure 10. Right lung at thoracotomy. Primary bullous emphysema.

Figure 11. Trypsin inhibitory capacity (TIC) in probands and relatives. Reprinted from Eriksson by permission.

Figure 11. Trypsin inhibitory capacity (TIC) in probands and relatives. Reprinted from Eriksson by permission.

Category: Health

Tags: emphysema, lung disease, trypsin inhibitory capacity