and modulation of NADPH oxidase activity and reactive oxygen species production in human neutrophils by α-antitrypsin.

Oxidative stress from innate immune cells is a driving mechanism that underlies COPD pathogenesis. Individuals with α-1 antitrypsin (AAT) deficiency (AATD) have a dramatically increased risk of developing COPD. To understand this further, the aim of this study was to investigate whether AATD presents with altered neutrophil NADPH oxidase activation, due to the specific lack of plasma AAT.

α Antitrypsin therapy modulates the neutrophil membrane proteome and secretome.

Obstructive pulmonary disease in patients with α antitrypsin (AAT) deficiency (AATD) occurs earlier in life compared with patients without AATD. To understand this further, the aim of this study was to investigate whether AATD presents with altered neutrophil characteristics, due to the specific lack of plasma AAT, compared with non-AATD COPD.This study focussed on the neutrophil plasma membrane and, by use of label-free tandem mass spectrometry, the proteome of the neutrophil membrane was compared in forced expiratory volume in 1 s (FEV)-matched AATD, non-AATD COPD and in AATD patients receiving weekly AAT augmentation therapy (n=6 patients per cohort).

The impact of alpha-1 antitrypsin augmentation therapy on neutrophil-driven respiratory disease in deficient individuals.

Alpha-1 antitrypsin (AAT) is the most abundant serine protease inhibitor circulating in the blood. AAT deficiency (AATD) is an autosomal codominant condition affecting an estimated 3.4 million individuals worldwide.

Alpha-1 proteinase inhibitors for the treatment of alpha-1 antitrypsin deficiency: safety, tolerability, and patient outcomes.

Alpha-1 antitrypsin (AAT) deficiency remains an underrecognized genetic disease with predominantly pulmonary and hepatic manifestations. AAT is derived primarily from hepatocytes; however, macrophages and neutrophils are secondary sources. As the natural physiological inhibitor of several proteases, most importantly neutrophil elastase (NE), it plays a key role in maintaining pulmonary protease-antiprotease balance.