Alpha-1 Lung Disease: Diagnosis

Reviewed by Karina A. Serban, MD, Robert A. Sandhaus, MD, PhD, FCCP

What tests diagnose Alpha-1?

Alpha-1 antitrypsin blood level, Pi-type or phenotype (structure of the protein made by the Alpha-1 gene), and genotype (testing the Alpha-1 DNA)

In people with Alpha-1 lung disease, the blood level of alpha-1 antitrypsin will often be very low, less than 20 percent of the normal level. The phenotype (Pi-type) of the alpha-1 antitrypsin protein in a person is determined by identifying how the protein moves on an electrified gel. A normal protein is referred to as an M protein. A person with normal alpha-1 antitrypsin proteins is referred to as Pi MM. The most common abnormal proteins are S, Z and F. Sometimes a gene will make no protein; this a “null” gene. When you have two Z genes, you are Pi ZZ, and a person that is most likely to get Alpha-1 lung and/or liver disease. 


Chest radiograph or Chest CT scan

A chest x-ray may reveal that the lungs are hyperinflated due to emphysema. A chest CT will show a pattern of emphysema specific to Alpha-1. When the normal small air sacs (alveoli) of the lungs break down and consolidate, they look like large holes in the lung, like the holes in Swiss cheese. In those who smoke but don’t have Alpha-1, emphysema will occur more frequently in the upper part of the lung. In those with Alpha-1 emphysema, the lower parts of the lung are most commonly affected. Bronchiectasis can occur in those with Alpha-1 lung disease. This is the permanent dilation and thickening of the bronchial tubes from chronic inflammation.


Pulmonary function tests

Breathing tests that test for abnormal airflow are called pulmonary function tests (PFTs). In people with emphysema, the volume of air expelled from the lungs in one second will be diminished relative to the total amount of air expelled. Air can get out, but at a slower rate. People with emphysema will also tend to have hyperinflated lungs, and they will trap air in their lungs. This hyperinflation and air trapping tends to worsen with exercise. This is one reason that people with emphysema feel short of breath soon after starting exercise. Finally, complete PFTs measure how well the lungs can exchange oxygen (O2), which we want to get into our body. This is referred to as the diffusion capacity. When the small air sacs of the lung break down to form larger air sacs, or emphysema, the capacity of the lungs to exchange oxygen with the blood is impaired.


How does Alpha-1 lung disease affect my life expectancy?

People who continue to smoke and have Alpha-1 lung disease, have an average life expectance of about 60 years of age. People who quit smoking or never smoked and have Alpha-1, can still develop Alpha-1 lung disease but they have a better prognosis, and many will have similar life expectancy compared to those who don’t have Alpha-1. It is important to discover whether you have Alpha-1 early in life, since this could affect your choice to smoke or not. Some advocate screening for the abnormal Alpha-1 antitrypsin genes at birth.

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