Understanding alpha-1 antitrypsin deficiency: A review with an allergist's outlook

Alpha-1 antitrypsin (AAT) is the prototypical protease inhibitor from the serine protease inhibitor (serpin) superfamily that protects lung tissue from proteolytic damage by inhibiting neutrophil elastase. Approximately 1 in 2750 to 1 in 4500 individuals have an autosomal codominant condition that leads to a deficiency of circulating AAT. In individuals with AAT deficiency (AATD), AAT is retained in liver cells, which predisposes them to liver disease, and does not reach lung tissues through circulation, where it normally acts as the primary natural regulator of proteolytic activity in the pulmonary tissues, which thus leads to lung disease. Despite being commonly labeled as a rare disease, AATD is one of the most common autosomal genetic disorders and is considered highly underrecognized, with ≤10% of individuals suspected with AATD identified. Screening guidelines have been established, and the diagnosis is easy to confirm when the condition is suspected. Early recognition is key to prevent morbidity and mortality associated with the disease. For this reason, all patients with chronic obstructive pulmonary disease and patients with asthma and fixed obstruction should be tested to exclude the diagnosis of AATD. Augmentation therapy of the deficient protein is available for those with significant lung disease and protein deficiency, and analysis of recent data supported preservation of lung tissue with this treatment. In this review, oriented toward specialists in allergy and immunology, we focused our discussion on the presentation, diagnosis, and treatment of pulmonary symptoms of AATD.