Emphysema Causes. Cigarette smoking is by far the most dangerous behavior that causes people to develop emphysema, and it is also the most preventable cause. Other risk factors include a deficiency of an enzyme called alpha-1-antitrypsin, air pollution, airway reactivity, heredity, male sex, and age. The pollutants cause inflammation in the airways, leading to lung tissue destruction. 2  Close relatives of people with emphysema are more likely to develop the disease themselves. 3  This is probably because the tissue sensitivity or response to smoke and other irritants may be inherited.