Intraindividual variability in serum alpha-1 antitrypsin levels

Background: Measuring alpha-1 antitrypsin (AAT) serum levels is often the first step when investigating for alpha-1 antitrypsin deficiency (AATD). The purpose of this study was to determine the test-retest reproducibility of AAT serum levels and to determine if between-measurements variability was associated with acute phase markers of inflammation. Methods: We retrospectively analyzed a sample of 255 patients from a community respirology practice with chronic obstructive pulmonary disease (COPD) in whom AAT serum levels were measured twice, on separate visits. White blood cell count and fibrinogen were also measured at the time of the second blood sampling as markers of acute phase inflammation. Intraclass correlation coefficient (ICC), Pearson correlation coefficient, and Bland-Altman analysis were used to document test-retest reproducibility. Regression analyses were used to identify potential correlates of test-retest AAT level differences. Results: Although the 2 AAT serum levels were significantly correlated, the between-measurement agreement was weak (ICC of 0.38 [95% confidence interval (CI), 0.27 to 0.48]; Pearson correlation coefficient of 0.34 [95% CI, 0.23 to 0.44]) and Bland-Altman analysis revealed wide 95% limits of agreement. Considering that an AAT serum level below 1.13g/L should trigger further investigations to confirm the AAT status, discrepancies between the test-retest AAT levels resulted in reconsidering requirement for further investigation in 22% of patients. A significant correlation between the fibrinogen value and the second AAT level was found (r=0.21, p=0.004 [n=173]). Conclusions: Serum AAT levels showed weak intra-individual reproducibility which could lead to AATD status misclassification and potentially a missed diagnosis of AATD.