An alpha-1 antitrypsin concentration is ordered to help diagnose the cause of early onset emphysema, especially when a person does not have obvious risk factors such as smoking or exposure to lung irritants such as dust and fumes.

Alpha-1 antitrypsin is also ordered to help diagnose the cause of persistent jaundice and other signs of liver dysfunction. This is done primarily in infants and young children but may also be done in patients of any age.

Alpha-1 antitrypsin phenotype testing may be ordered if the alpha-1 antitrypsin concentration is lower than normal. It looks at the amount and type of AAT being produced and compares it to normal patterns.

DNA testing may be done as a follow-up to an alpha-1 antitrypsin level and phenotype. Once it has been established that an abnormality exists, then the DNA genetic testing can be ordered to establish which Pi gene alleles are present. This test does not test for every variant, just the most common ones (M, S, and Z, as well as any that may be common in a particular geographical area or family). Once the affected person’s Pi gene alleles have been determined, other family members may be tested to establish their own possible risk of developing emphysema and/or liver involvement as well as the likelihood that their children might inherit it.

Alpha-1 antitrypsin testing may be ordered when a newborn or infant has jaundice that lasts for an extended period of time (more than a week or two), an enlarged spleen, ascites, pruritus (itching), and other signs of liver injury. It may be ordered when a person under 40 years of age develops wheezing, a chronic cough or bronchitis, is short of breath after exertion and/or shows other signs of emphysema. This is especially true when the patient is not a smoker, has not been exposed to known lung irritants, and when the lung damage appears to be located low in the lungs. AAT testing may also be done when you have a close relative with alpha-1 antitrypsin deficiency.

Alpha-1 antitrypsin phenotype testing is ordered when a patient has a decreased level of AAT. DNA testing is performed when the AAT test indicates that the patient has lower than normal level of AAT and when the alpha-1 antitrypsin phenotype test indicates that some or all of the AAT protein being produced appears to be a variant. It may also be ordered in the rare case when no AAT is being produced. AAT DNA testing may be done on close relatives when there is an affected family member, and when a patient wants to determine their risk of having an affected child.

AAT concentrations are primarily important when they are lower than normal and/or indicate that the AAT being produced is abnormal. The lower the level of normal AAT, the greater the risk of developing emphysema.

With abnormal AAT it depends on how much is produced and how abnormal it is. Low concentrations of abnormal AAT in the blood may lead to both emphysema (because of the lack of lung protection) and to liver disease because of the buildup of dysfunctional AAT inside the liver cells producing it.

When DNA testing indicates the presence of one or two abnormal copies of the Pi gene, less AAT and/or abnormal AAT will be produced and the variant copies can be passed on to the patient’s children. The degree of AAT deficiency and the degree of lung and/or liver damage experienced is very variable. Two people with the same gene copies may have very different disease courses.

AAT is an acute phase reactant. This means that it will be elevated in acute and chronic inflammatory conditions, infections, and with some cancers. Increased levels of AAT may also be seen with infections, oral contraceptives, pregnancy, stress, and thyroid infections. Although an increased amount of AAT may be present, this test is not usually measured or used as a monitoring tool in these situations. This may cause levels to be "normal" in persons with mild to moderate AAT deficiency when they also have another condition that increases AAT.

AAT concentrations may be decreased with neonatal respiratory distress syndrome, and with conditions that decrease serum proteins such as kidney disease (nephrotic syndrome), malnutrition, and some cancers.