Innovative Molecular Testing Enhances Diagnosis of Genetic COPD

Researchers at National Jewish Health have developed a groundbreaking molecular diagnostic test that significantly improves the detection of Alpha-1 Antitrypsin Deficiency (AATD), a key genetic cause of chronic obstructive pulmonary disease (COPD). This new assay, described in a recent study published in CHEST Pulmonary, utilizes a 23-SNP multiplexed approach to identify multiple genetic mutations associated with AATD, providing a faster and more accurate diagnosis.

AATD is recognized as the second most common genetic lung disorder in the United States, affecting approximately 1 in 3,000 to 5,000 individuals and potentially impacting around 100,000 Americans. Despite its prevalence, it remains underdiagnosed, often delaying suitable treatment and leading to worsened health outcomes.

The novel test addresses previous limitations by detecting a wide range of mutations in the SERPINA1 gene, responsible for encoding the alpha-1 antitrypsin protein. Validation with 373 biological samples demonstrated the assay's ability to identify 20 pathogenic mutations, including rare alleles such as F, I, and some null variants, with 100% accuracy. This surpasses traditional methods like isoelectric focusing and previous molecular tests, which could only detect common S and Z alleles.

According to lead researcher Dr. Yongbao Wang, this assay offers a comprehensive and rapid genotyping solution that can be implemented as a frontline diagnostic tool. The test could also pave the way for newborn screening programs and at-home testing options, facilitating early detection and intervention.

Senior scientist Dr. Sharon Kuss-Duerkop emphasized that earlier and more reliable diagnosis enables better management and treatment outcomes, potentially preventing severe lung and liver complications associated with AATD. Since 2022, the 23-SNP AAT assay has been integrated into clinical practice at National Jewish Health, making it accessible for routine diagnostics.

The development marks a significant advancement in genetic testing for respiratory diseases, promising to enhance early diagnosis, personalized treatment, and overall patient care. This innovation underscores the ongoing progress in molecular diagnostics and targeted therapies in respiratory medicine.