Variability of Pulmonary Function in Alpha-1-Antitrypsin Deficiency: Clinical Correlates

Abstract

Many persons with alpha-1-antitrypsin deficiency do not have clinically significant lung function impairment: the perceived natural history of antitrypsin deficiency has been distorted by ascertainment bias. In addition to cigarette smoking, it appears that asthma, lower respiratory infections, and possibly some familial factors contribute to a severe clinical course. Follow-up of our cohort with widely varying lung function will provide insights into the natural history of the emphysema associated with alpha-1-antitrypsin deficiency.

α; 1 -Antitrypsin Protease Inhibitor MZ Heterozygosity Is Associated With Airflow Obstruction in Two Large Cohorts

“…24 PI ZZ subjects show signifi cant variability in the development of lung disease, 25 and IL-10 has been identifi ed as a potential genetic modifi er for airfl ow obstruction in severe AAT defi ciency. 26 Gene-advisory boards and medical educational activities for CSL Behring; and served as a consultant to Talecris Biotherapeutics.…”

Clinical phenotypes of Italian and Spanish patients with α1-antitrypsin deficiency

“…According to the predominance of symptoms, AATD is a very heterogeneous disease [29], and patients may be classified into different clinical phenotypes [30,31]. Most of the patients were classified by their physicians as having pulmonary emphysema, whereas a smaller number presented a predominance of other phenotypes.…”

Polymerization and Oxidation of Alpha-1-Antitrypsin in Pathogenesis of Emphysema

“…According to this hypothesis, emphysema in A1ATD arises from an imbalance of neutrophil elastase and A1AT as antielastase, which leads to inappropriate antielastase defense and the relatively excessive activity of neutrophil elastase and consequent degradation of elastin and other extracellular matrix components of the lower respiratory tract. However, only 1% of patients with COPD are A1ATD (Lieberman, et al, 1986), indicating that A1ATD alone is not sufficient to induce emphysema (Silverman, et al, 1989). The additional factor which may induce emphysema in A1ATD is inflammation, when elastin repair mechanisms are overwhelmed by a massive attack of elastase from triggered neutrophils and cigarette smoke.…”