According to the current guidelines from the Global Initiative for Chronic Obstructive Lung Disease (GOLD), all individuals with chronic obstructive pulmonary disease (COPD) should be tested for alpha-1 antitrypsin deficiency (AATD) to improve the clinical management of the disease.

AATD, a rare autosomal recessive disorder, is observed in 1% to 3% of individuals who develop COPD. AATD can be classified according to protease inhibitor (PI*) types (ie, variations in alleles). Mammen and Lee explained, “PI*M is the predominant (normal) AAT allele, whereas PI*Z is the most common pathologic allele, followed by variants PI*S, PI*I, and PI*F.”

Since AATD is an autosomal recessive disorder, the disease occurs when an individual inherits 2 abnormal genes. Therefore, an individual with AATD could present with PI*MZ, PI*ZS, ZS, or any other combination of 2 disease alleles.

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AATD treatment involves the intravenous infusion of plasma-purified α1-antitrypsin (AAT) proteins. This aims to promote the proper functioning of the immune system, as well as to slow the progression of emphysema.

AAT proteins are key mediators in AATD pathogenesis. In AATD, a point mutation at the SERPINA1 allele on chromosome 14 results in misfolded AAT proteins. These aberrantly formed proteins are dysfunctional and can accumulate in the liver. This, in turn, causes cirrhosis and progressive lung damage as a result of the loss of neutrophil elastase inhibition.

This contrasts to normal conditions, in which AAT proteins have protective effects on lung tissues. They prevent lung damage by cytotoxic enzymes secreted by mobile neutrophils.


Mammen JR, Lee JE. Understanding the genetics of chronic obstructive pulmonary disease, α1-antitrypsin deficiency, and implications for clinical practice. J Am Assoc Nurse Pract. 2021;33(8):576-579. doi:10.1097/JXX.0000000000000627