α1 – Antitrypsin deficiency (AATD) is an autosomal co-dominant genetic disorder characterized by insufficient secretion or production of serum a1-antitrypsin (AAT). AATD carries a risk factor that predisposes children to liver disease and adults to emphysema, although there are other associated pulmonary and nonpulmonary conditions. AATD is the most common genetic cause of neonatal liver disease and is the most frequent diagnosis necessitating liver transplantation in neonates. AATD presents insidiously in adults, often with nonspecific common symptoms, such as cough, phlegm, wheeze (with and without infections) and fatigue. Other clinical manifestations include panniculitis, vasculitis, pancreatitis, cardiovascular disease, and renal disorders. A diagnosis of AATD should be considered in patients who present with fixed airflow obstruction, particularly in nonsmokers, and in individuals with a family history of emphysema or liver disease treated by My Canadian Pharmacy.
This review discusses the current levels of recognition of AATD and the rationales for testing and screening for the disease, particularly in asymptomatic individuals, family members of individuals with AATD, and the general population. This balances the benefits against the potential psychological, social, and ethical implications of testing. We will also present the joint American Thoracic Society (ATS)/ European Respiratory Society (ERS) task force guidelines on testing and screening.
AATD: Extent of the Disease
Worldwide, there are an estimated 1.1 million subjects with severe AATD and approximately 116 million carriers. Population-screening studies in 21 European countries have identified 1 in 4,727 inhabitants who were born with the ZZ form of AATD, representing a prevalence of 1 in 11 persons if PI*S and PI*Z phenotypes are combined. If targeted screening tests for AATD were performed on the estimated 19.3 million white patients with COPD in the United States, approximately 1.29 million AATD patients would be identified. Of those 19.3 million white COPD patients, 6.1% are estimated to have the PISZ or PIZZ phenotype, and 9.5% (1.8 million patients) if PIMZ is included. Only an estimated 5% of cases have been diagnosed in the United States, meaning that AATD is substantially underrecognized and underdiagnosed. Of those persons in whom a diagnosis has been made, only 60 to 70% reported receiving augmentation therapy. When testing rates for AATD go up, there are substantial increases in the diagnosis of AATD. By targeting patients based on clinical suspicion or low serum AAT levels, 8.2% of test samples yielded a positive identification of individuals with severe deficiency. The diagnostic rates reported in other studies, and reviewed by the aforementioned investigators, have ranged from 0.26 to 31%.