This results over time in parenchymal lung destruction due to increased connective tissue breakdown, and the development of panlobular emphysema, especially in the presence of smoking.22 Z-AAT polymers also co-localise with neutrophils in the lung tissue, which increases the local proteinase release thereby contributing to further interstitial damage, as previously reviewed.23,24 Recently, AAT polymers have been identified in both monocytes25 and macrophages26 from AATD patients and evidence is building that these cells may also play a role in the development of AATD lung disease. This evidence concerns the gene SERPINA1 and pulmonary emphysema.