From the Guidelines
The primary lab test used to check for genetic Chronic Obstructive Pulmonary Disease (COPD) is a two-step process involving measuring serum A1AT protein levels and DNA sequencing of the coding exons of SERPINA1, with DNA sequencing being the gold standard for diagnosis. This approach is recommended due to the limitations of relying solely on measuring A1AT protein serum levels, which can fluctuate over time and have weak test-retest reproducibility 1. AAT deficiency is the most well-established genetic cause of COPD, accounting for about 1-2% of all COPD cases. If the initial blood test shows low levels of AAT, genetic testing through DNA sequencing of the SERPINA1 gene can identify specific mutations responsible for the deficiency.
Key points to consider in testing for genetic COPD include:
- A cutoff of <23mmol/L (<1.2 g/L) for A1AT protein serum levels can be used to reasonably exclude A1AT deficiency, but this may not be sufficient in all cases, particularly those with intermediate deficits or during episodes of acute inflammation 1.
- DNA sequencing allows for the testing of all genetic variants in the SERPINA1 gene, providing the most accurate diagnosis and facilitating cascade screening in families 1.
- Testing is particularly important for COPD patients who develop symptoms before age 40, have a family history of COPD, or have COPD despite minimal or no smoking history, as early detection can lead to specific treatments like augmentation therapy 1.
- The Canadian Thoracic Society guidelines recommend targeted testing and augmentation therapy for A1AT deficiency in patients with respiratory conditions potentially associated with A1AT deficiency, including COPD with emphysema 1.
In clinical practice, the ability to precisely classify individuals regarding their A1AT deficiency status through DNA sequencing can trigger important lifestyle interventions aimed at protecting respiratory health, and disease risk assessment may be more accurately made at the molecular rather than the protein level 1.
From the Research
Lab Tests for Genetic COPD
To check for genetic Chronic Obstructive Pulmonary Disease (COPD), several lab tests can be utilized. The primary focus is on identifying Alpha-1 Antitrypsin Deficiency (AATD), a genetic disorder associated with early onset COPD and liver disease.
- Alpha-1 Antitrypsin (AAT) Level Test: This test measures the level of AAT in the blood. Low levels of AAT can indicate AATD, which is a risk factor for COPD 2, 3.
- Genotyping: For individuals with low AAT levels, genotyping can be performed to determine the specific genetic mutation causing the deficiency. This can help confirm the diagnosis of AATD 2, 3.
- Phenotyping: This test determines the type of AAT protein in the blood, which can also help diagnose AATD 3.
Screening Guidelines
Several organizations, including the World Health Organization, European Respiratory Society, and American Thoracic Society, recommend screening for AATD in high-risk groups, such as:
- Individuals with COPD, especially those diagnosed before the age of 65 or with a smoking history of less than 20 pack years 4.
- Patients with nonresponsive asthma, bronchiectasis of unknown etiology, or unexplained liver disease 5, 6.
Diagnostic Approaches
The diagnosis of AATD is laboratory-based and can be performed by determining the AAT phenotype or genotype along with serum AAT levels 6. Primary care providers play a crucial role in the identification and early diagnosis of AATD patients, as they are often the first to encounter symptomatic individuals 6.
Treatment Options
Current treatment options for AATD include augmentation therapy with purified AAT for patients with deficient AAT levels and significant lung disease 5, 4. Other approaches include aggressive avoidance of smoking and biomass burning, vaccinations, antibiotics, exercise, good diet, COPD medications, and serial assessment 5.