Researchers have found that serum alpha-1 antitrypsin (AAT) levels demonstrate weak intraindividual reproducibility in subsequent determinations, thus calling into question the reliability of AAT testing as the main diagnostic test for alpha-1 antitrypsin deficiency (AATD), according to a study published in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. 

The best approach to diagnosing AATD is still under debate, with proposed diagnostic algorithms sometimes depending on methods that are inconclusive. Hence, testing for AAT levels remains the favored approach to diagnosing AATD, despite the fact that AAT levels can appear normal in some forms of AATD. In addition, AAT levels fluctuate; they are known to rise in the presence of injury, inflammation, and infection. 

Another potential problem with using AAT levels to diagnose AATD is that little is known about their intraindividual variability. Researchers therefore set out to investigate the test-retest reproducibility of AAT levels. They retrospectively analyzed the serum AAT levels of 255 patients with COPD from a community respiratory practice. These patients had their serum AAT levels measured twice during separate visits. 

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Researchers discovered that although there was a statistically significant correlation between the 2 serum AAT levels, the between-measurement agreement was poor; the intraclass correlation (ICC) was 0.38 (95% CI, 0.27-0.48). In addition, the results demonstrated a large coefficient of variation (17%) between the 2 measurements.

“Discrepancies between the test-retest AAT levels would have led to reconsidering the requirement for further investigation in 22% of the subjects at the second AAT level measurement when using the 1.13 g/L threshold to determine the need for additional testing,” the authors stated.

Researchers believe that factors such as smoking status, chronobiological fluctuations, and different methodologies between labs could have influenced AAT levels. Regardless of the factors that contribute to fluctuating AAT levels, the results of this study question the common clinical practice of excluding a diagnosis of AATD based purely on AAT testing. 

Which other diagnostic tests can be performed to reach a more accurate diagnosis (or exclusion) of AATD? The authors of the study have a proposal: “Along these lines, we submit that testing patients at the molecular level with DNA sequencing would provide complementary information regarding their AAT status and thus help resolve the uncertainties associated with the traditional diagnostic approach.”


Haillot A, Pelland AA, Bossé Y, Carroll TP, Maltais F, Dandurand RJ. Intra-individual variability in serum alpha-1 antitrypsin levels. Chronic Obstr Pulm Dis. Published online August 17, 2021. doi:10.15326/jcopdf.2021.0228