Operationally, intermediate AATD candidates for future trials could be classified by (i) exacerbation burden (e.g., ≥2 moderate or ≥1 severe event in the prior year) given its prognostic weight [44,45,46,47,48,49,50,51]; (ii) HRCT evidence of emphysema distribution/airway involvement in capturing structural disease; and (iii) exploratory biomarkers of neutrophil-driven inflammation and AAT functional adequacy to refine risk stratification. This evidence concerns the gene SERPINA1 and pulmonary emphysema.