Quantitative analysis of chest computed tomography in alpha-1-antitrypsin deficiency

Chest quantitative computed tomography (QCT) has been used in clinical trials to monitor patients with alpha-1 antitrypsin deficiency (AATD). There is limited data on the use of quantitative computed tomography (QCT) to phenotype emphysema in AATD.

Data from patients with a reduced AATD serum level and/or at least one deficiency mutation, who underwent a chest CT scan at the Thoraxklinik, University of Heidelberg, between 03/2012 and 02/2024, were retrospectively analyzed. The patients were categorized into three groups based on their AAT serum levels: reduced to normal (> 70 mg/dl), moderate (41-70 mg/dl), and severe (≤ 40 mg/dl). The QCT analyses were performed using a fully automated quantitative CT software package (YACTA v2.9.4.98).

In this retrospective cohort study, 75 AATD patients were analysed, including 13 with reduced-to-normal AATD, 16 with moderate AATD and 46 with severe AATD. The mean age was 54.3 ± 14.7 years with no differences between groups. Significant differences in pack-years (PY) were found: reduced to normal 14.9 ± 17.2, moderate 39.4 ± 31.9 and severe 15.1 ± 14.6 (p < 0.001). There were no differences in predicted FEV1% (54.1 ± 28.9%). QCT emphysema parameters showed a decrease in mean lung density and 15th percentile with lower serum levels (p < 0.05 for each), but no differences in global emphysema index (EI). A lobar-specific analysis, revealed that the reduced-to-normal and moderate AATD groups exhibited upper-lobe predominant emphysema. In contrast, the severe AATD group showed basal-predominant emphysema with maxima in the middle lobe and lingula. Additionally, a binary logistic regression analysis identified age (CI 1.01-1.12, p = 0,024) and lower of AATD serum levels (CI 0.92-0.98, p = < 0.001) as significant indicators for an emphysema pattern that was predominantly localized in the middle lobe and lingula.

The study provides new insights into the distribution of emphysema, with lobar-specific quantitative analysis challenging the existing paradigm that emphysema in severe AATD is most pronounced in the lower lobes.