ABSTRACT
Since the first description of alpha 1-antitrypsin (a l AT) deficiency by Laurell and Eriksson in 1963 (1), major advances have been made in understanding the basic scientific aspects of this disorder. As discussed in another chapter, the structures of the protein and the gene for a 1 AT have been elucidated, the gene has been cloned, and transfer of the gene to animal host cells has been accomplished both in vitro and in vivo (2,3). Although these strides are especially impressive for having occurred in the short span of 32 years, they highlight a paradox that the basic scientific understanding of a 1 AT deficiency far outstrips clinical understanding. Specifically, basic clinical questions about clinical features of affected individ uals, risk factors for airflow obstruction, and the natural history of alAT defi ciency remain unanswered, largely because of the difficulty of assembling a large cohort for study. Indeed, estimates of the rate of decline of FEVj in affected individuals vary greatly in available series (i.e., from as low as 42 ml/year to as high as 317 ml/year) (4-9). Furthermore, until the recent publication of experi ence from the Danish Registry (10) (with n = 565 participants) and from the NIHsponsored Registry of Patients with Severe Deficiency of Alpha 1 -Antitrypsin
(11) (with n = 1129 participants)— the subject of this chapter-the largest avail able series consisted of 264 enrollees (12).
