Alpha 1 MZ Lungs
In this section we provide more information about the effect of an Alpha 1 Antitrypsin Deficiency on the Lungs.
Because this effect is well known and described in other literature, we will limit the information to the key elements.
In simple terms, Alpha 1 Antitrypsin protects the lungs from inflammation and damage caused by inhaling irritants such as tobacco smoke, and/or other air pollution particles.
The way it works, is that Alpha 1 Antitrypsin provides an antiprotease protective screen throughout the body, but most importantly in the lung, where it can neutralize the activity of the serine protease neutrophil elastase. It’s effectively the off switch” for the enzyme called neutrophil elastase. Neutrophil elastase is important for fighting infections in the lungs, but it can also destroy your healthy lung tissue. After neutrophil elastase has had time to fight an infection, AAT shuts it off (inhibits) so it won’t damage your lungs.
The result of an Alpha 1 Antitrypsin deficiency results in unbalanced (i.e., relatively unopposed) rapid breakdown of proteins (protease activity), especially in the supporting elastic structures of the lungs which are found in the walls of the air sacs of the lung, also called alveoli. Over years, this destruction can lead to progressive breakdown of the walls of the air sacs which is emphysema and is accelerated by smoking, and/or occupational exposures.
Bronchiectasis is characterized by dilatation of the bronchial wall and the clinical syndrome are a cough, sputum production and frequent respiratory exacerbations.
The association between Alpha 1 Antitrypsin deficiency and bronchiectasis is still under debate, however there are studies indicating that there is a relation between AAT and bronchiectasis.
The protective role of AAT on bronchial inflammation is supported by two studies, one in mice and the other in humans. The first one shows that in AAT+/+ transgenic mice that express human AAT in lungs, the mortality of Pseudomonas aeruginosa-induced pneumonia was reduced by 90% compared to non-transgenic control animals. Moreover, exogenous human AAT given to non-transgenic mice also significantly reduced P. aeruginosa pneumonia mortality. P. aeruginosa-infected AAT+/+ mice demonstrated reduced lung tissue damage, decreased bacterial concentrations in the lungs and blood, and diminished circulating cytokine concentrations compared to infected non-transgenic mice. The second study, instead, shows that among subjects with humoral immunodeficiencies requiring gamma–globulin replacement therapy, patients with bronchiectasis were found to have lower median levels of AAT than those without bronchiectasis, suggesting that a deficiency of AAT could promote the development of bronchiectasis.
