ABSTRACT
The modern era of COPD pathogenesis arose in the early 1960s following two seminal observations, one experimental and the other clinical. In 1963, Laurell and Eriksson reported an association of chronic airflow obstruction and emphysema with deficiency of serum a1-antitrypsin (a1-AT) (1), and in 1964 Gross et al. (2) described the first reproducible model of emphysema in experimental animals by injecting the lungs with the plant cysteine protease papain. Together, these two observations formed the basis for the proteinase-antiproteinase hypothesis of emphysema that has been the prevailing concept of the pathogenesis of emphysema ever since.
