Antitrypsin deficiency is associated with- (a) (b)
Restrictive lung pathology
Cystric fibrosis
Emphysema
Carcinoma
Pathogenesis of Emphysema

The most accepted theory in the pathogenesis of emphysema is protease - antiprotease mechanism which is responsible in the pathogenesis of two common forms of emphysema, i.e. centriacinar and panacinar.
The alveolar wall destruction results from an imbalance between proteases (mainly elastase) and antiproteases in the lung.
Proteases (elastase) cause the destruction of alveolar wall, while antiproteases prevent this damage.
α1 - antitrypsin is the major antiprotease (anti elastase) secreted by neutrophils during inflammation

A. Pathogenesis of panacinar emphysema

Panacinar emphysema is associated with congenital deficiency of α1 - antitrypsin.
This results in unchecked overactivity of neutrophil elastase that causes the destruction of alveolar wall.
As α1 - antitrypsin is deficient throughout the acinus, the acini are uniformly involved from the respiratory bronchiole to the terminal blind alveoli.
Neutrophils are the major cells in the pathogenesis of panacinar emphysema

B. Pathogenesis of centriacinar emphysema

Centriacinar emphysema is associated with smoking.
Nicotine acts as a direct chemoattractant for neutrophils and macrophages.
So, in centriacinar emphysema, both neutrophils and macrophages play a central role.
Smoking enhances the activity of neutrophil and macrophage elastase.
Macrophage elastase is not inhibited by a1 - antitrypsin and indeed can proteolytically digest this antiprotease.
Beside protease - antiprotease mechanism, oxidant-antioxidant imbalance also plays an important role in the pathogenesis of smoking-related emphysema.
Normally, the lung contains a healthy complement of antioxidants (superoxide dismutase, glutathione).
Tobacco smoke contains abundant reactive oxygen species (free radicals) which deplete these antioxidant mechanisms.
Free radicals cause tissue damage, as well as they, inactivate α1 - antitrypsin, resulting in functional α1 - antitrypsin deficiency even in patients without enzyme deficiency.

Why smoking-related emphysema involves centriacinar portion?
The impaction of smoke particles occurs predominantly at the bifurcation of respiratory bronchioles, resulting in the influx of neutrophils and macrophages, both of which secrete proteases. An increase in protease activity localized in the centriacinar region, together with the smoke-induced oxidative damage, causes the centriacinar pattern of emphysema that is seen in smokers.