Emphysema is characterized by destruction of respiratory bronchioles, alveolar ducts, and alveoli leaving enlarged airspaces. There are several types of emphysema, but the most common type is centrilobular (also known as centriacinar or proximal acinar) emphysema caused by tobacco smoking that involves primarily the respiratory bronchioles. It is most prominent in the upper lung zones. Panacinar emphysema, like that seen with α₁-antitrypsin deficiency, involves alveolar ducts as well as the respiratory bronchioles.

The destruction of lung parenchyma in emphysema leaves residual fragments of tissue, including islands of fibrovascular tissue. Although it has been emphasized that emphysema is not the same as diffuse interstitial fibrosis, remodeling of lung tissue also appears to have a role in emphysema, and there may be mild fibrosis. Additional histopathologic changes related to tobacco smoking, including respiratory and membranous bronchiolitis, respiratory bronchiolitis-associated interstitial lung disease, and desquamative and related findings, may be seen in association with emphysema from tobacco smoking. Anthracotic pigment and/or macrophages containing smoker’s pigment may be present. Bullae are cystic spaces that are found in the lung apices, subpleurally, and elsewhere in emphysematous lungs.