α₁-Antitrypsin deficiency and chronic respiratory disorders

Abstract

α1-antitrypsin deficiency (AATD) is a hereditary disorder associated with a risk of developing liver disease and pulmonary emphysema, and other chronic respiratory disorders (mainly asthma and bronchiectasis); Z variant is the commonest deficient variant of AAT. Determining AAT concentration in serum or plasma and identifying allelic variants by phenotyping or genotyping are fundamental in the diagnosis of AATD. Initial evaluation and annual follow-up measurement of lung function, including post-bronchodilator forced expiratory volume in 1 s and gas transfer inform on disease progression. Lung densitometry is the most sensitive measure of emphysema progression, but must not be use in the follow-up of patients in routine clinical practice. The exogenous administration of purified human serum-derived AAT is the only approved specific treatment for AATD in PiZZ. AAT augmentation therapy is not recommended in PiSZ, PiMZ or current smokers of any protein phenotype, or in patients with hepatic disease. Lung volume reduction and endoscopic bronchial valve placement are useful in selected patients, whereas the survival benefit of lung transplant is unclear. There are several new lines of research in AATD to improve the diagnosis and evaluation of the response to therapy and to develop genetic and regenerative therapies and other treatments.

Proteins associated with neutrophil degranulation are upregulated in nasopharyngeal swabs from SARS-CoV-2 patients

“…CD2, CD4, and CD8 can be cleaved on the surface of T-cells by ELANE and CTSG that dysregulate T-cell function [ 25 ]. It was reported that patients that lack alpha-1 antitrypsin (α1-Pi) which is the physiological inhibitor of PRTN3 and ELANE carries a high risk of developing emphysema [ 26 ]. Azurophil granules also carry Cathepsin D which was reported to be up-regulated in the pulmonary macrophages in a mouse model of cigarette smoking [ 27 ].…”

ALTERED MOLECULAR PATHWAYS OBSERVED IN NASO-OROPHARYNGEAL SAMPLES OF SARS-CoV-2 PATIENTS

“…CD2, CD4, and CD8 can be cleaved on the surface of T-cells by ELANE and CTSG that dysregulate T-cell Function [29]. It was reported that patients that lack alpha-1 antitrypsin (α1-Pi) which s the physiological inhibitor of PRTN3 and ELANE carries a high risk of developing emphysema [30]. Azurophil granules also carry Cathepsin D which was reported to be up-regulated in the pulmonary macrophages in a mouse model of cigarette smoking [31].…”

Is it Time to Look Beyond Bronchodilators and Corticosteroids in Treating COPD?

“…Circulating protein α 1 -antitrypsin (AAT) effectively inhibits proteases and also controls neutrophilic inflammation [14]. In the presence of AAT deficiency, augmentation therapy with i.v.…”

“…purified AAT becomes central. However, one of the main disadvantages of AAT therapy is that intravenous AAT arrives at the lung in a relatively inactive state [14]. To improve AAT replacement therapy, new intravenous formulations have been developed.…”