Novel Lobe-based Transformer model (LobTe) to predict emphysema progression in Alpha-1 Antitrypsin Deficiency.

Emphysema, marked by irreversible lung tissue destruction, poses challenges in progression prediction due to its heterogeneity. Early detection is particularly critical for patients with Alpha-1 Antitrypsin Deficiency (AATD), a genetic disorder reducing ATT protein levels. Heterozygous carriers (PiMS and PiMZ) have variable AAT levels thus complicating their prognosis. This study introduces a novel prognostic model, the Lobe-based Transformer encoder (LobTe), designed to predict the annual change in lung density (ΔALD [g/L-yr]) using CT scans. Utilizing a global self-attention mechanism, LobTe specifically analyzes lobar tissue destruction to forecast disease progression. In parallel, we developed and compared a second model utilizing an LSTM architecture that implements a local subject-specific attention mechanism. Our methodology was validated on a cohort of 2,019 participants from the COPDGene study. The LobTe model demonstrated a small root mean squared error (RMSE=1.73 g/L-yr) and a notable correlation coefficient (ρ=0.61), explaining over 35% of the variability in ΔALD (R= 0.36). Notably, it achieved a higher correlation coefficient of 0.68 for PiMZ heterozygous carriers, indicating its effectiveness in detecting early emphysema progression among smokers with mild to moderate AAT deficiency. The presented models could serve as a tool for monitoring disease progression and informing treatment strategies in carriers and subjects with AATD. Our code is available at github.com/acil-bwh/LobTe.