• α1-Protease (α1-antitrypsin) inhibitor deficiency fi leads to early onset emphysema • α1-Protease inhibits several types of proteases, including neutrophil elastase, which is implicated in the genesis of emphysema
• Autosomal dominant mutations, especially in northern Europeans, produce abnormally low serum and tissue levels of this inhibitor, altering the balance of connective tissue synthesis and proteolysis • A homozygous mutation (the ZZ genotype) results in inhibitor levels 10–15% of normal, leading to a very high risk of emphysema, particularly in smokers
3. Defi ficiency of which protein increases the risk of early onset emphysema? • Chronic bronchitis is characterized by chronic airway injury and narrowing with infl flammation, particularly of small airways, and by hypertrophy of large airway mucous glands, increased mucus secretion, and mucus obstruction of airways • Emphysema is a disease of the surrounding lung parenchyma and not the airways
• Emphysema results from (1) destruction of terminal respiratory units, (2) loss of alveolar capillary bed, and (3) loss of the supporting structures of the lung, including elastic connective tissue • Loss of elastic connective tissue reduces normal support of noncartilaginous airways, leading to diminished elastic recoil and increased compliance and premature collapse of the airways during expiration
2. What are the pathophysiologic changes in emphysema vs chronic bronchitis?
Pulmonary Disease (COPD), B
44 Obstructive Lung Disease: Chronic Obstructive