History and exam

Key diagnostic factors

common

productive cough

The National Heart, Lung, and Blood Institute (NHLBI) Registry of Individuals with Severe Deficiency of AAT reported 50% of patients with cough.[56] Many patients meet criteria for chronic bronchitis, manifested as chronic cough for 3 months in 2 successive years.[52]

shortness of breath on exertion

Patients with respiratory disease may present with shortness of breath on exertion.

current cigarette smoker

The greatest risk factor for emphysema in patients with the PI*ZZ phenotype is smoking. Lung function and survival are both affected.[24][46]​​​[47]​​ Some evidence suggests that ex-smokers and people who have never smoked have similar declines in lung function over time.[48] Some smokers may never develop pulmonary symptoms.[42]

uncommon

exposure to gas, fumes, and/or dust

Occupational or other exposure to inhaled toxins has been associated with decreased pulmonary function in patients with PI*ZZ AAT deficiency. This includes passive smoking and work with kerosene heaters.[49][50][51][52]

hepatomegaly

Patients with liver manifestations may present with hepatomegaly.

ascites

Patients with liver manifestations may present with ascites.

confusion

Patients with liver manifestations may present with hepatic encephalopathy.

Other diagnostic factors

common

ages 32-41 years

This is the mean age at which smokers with AAT deficiency typically present with symptomatic pulmonary disease.[24]

male sex

At least one study has shown an increase in symptomatic lung disease in PI*ZZ males.[20] However, this result is likely confounded by other variables, such as smoking and occupational exposure.[21][22][23]

wheezing

The NHLBI registry implies that bronchodilator-responsive wheezing is more prevalent in patients with deficient AAT than in patients with normal AAT and COPD.[56] However, it is neither sensitive nor specific for AAT-deficiency lung disease.[9]

Pulmonary function tests (PFTs) can differentiate between asthma and AAT deficiency disease because asthma is fully reversible with bronchodilation, whereas in AAT deficiency the reversibility is incomplete.[57]

chest hyperinflation

May indicate the presence of respiratory disease.

uncommon

scleral icterus/jaundice

AAT deficiency causing liver failure will normally present as jaundice, indicating hepatitis.[58] Liver disease will only occur in patients with phenotypes that are associated with intrahepatic polymerization of the AAT variant: notably the Z, Mmalton, and Siiyama.[12]

asterixis

May indicate the presence of liver disease.

Risk factors

strong

family history of AAT deficiency

The inheritance pattern of AAT deficiency is autosomal, and expression of the alleles is codominant. Knowledge that one or both parents are AAT deficient should increase suspicion of AAT deficiency, for example in an individual with early-onset emphysema.

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