In a middle-aged man with hyperinflation and smoking history, which factor contributes to the pathogenesis of his lung disease?

• A. Impaired production of alpha1-antitrypsin
• B. Increased surfactant production
• C. Overproduction of mucus
• D. Enhanced ciliary motility

Answer: (A)

Emphysema develops from a protease–antiprotease imbalance in the lung. Alpha-1 antitrypsin normally keeps neutrophil elastase in check, protecting elastic tissue in the alveolar walls. Cigarette smoke drives neutrophil and macrophage recruitment and elastase release and, at the same time, oxidatively modifies alpha-1 antitrypsin, reducing its ability to inhibit elastase. The result is unchecked elastase activity that destroys elastic fibers in the alveolar septa, causing loss of elastic recoil, alveolar wall destruction, and the hyperinflation seen in smokers. So impaired alpha-1 antitrypsin activity contributes to the disease process.

Surfactant production upregulation would alter surface tension but isn’t the driver of smoker-related emphysema. Excess mucus production is more linked to chronic bronchitis, not the emphysematous destruction described here. Enhanced ciliary motility would improve clearance rather than promote lung destruction.