Clinical and radiological clustering in patients with alpha1-antitrypsin deficiency caused by PI*SZ genotype

The PI*SZ genotype of Alpha 1-Antitrypsin Deficiency (AATD) is associated with Alpha 1-Antitrypsin (AAT) levels between 25% and 40% of those detected in subjects with the non-deficient PI*MM genotype. The risk attributable to SZ-AATD remains debated. The aim of the study is to evaluate the clinical and radiological characteristics, changes in respiratory function over time and quality of life in a large cohort of AATD patients with PI*SZ genotype, comparing these results with a cohort of AATD patients with severe PI* ZZ genotype. We analyzed 177 PI*SZ and 376 PI*ZZ subjects enrolled in the Italian Registry of Alpha1-AT (RIDA1). Among them 169 and 360, respectively, have at least three-years follow up of respiratory function performed after AATD diagnosis. In comparison to PI*ZZ, PI*SZ has higher frequency of healthy individuals (p<0.0001) and diagnosis of bronchial asthma (p=0.01). Centrilobular and bullous emphysema of the upper lobes was more common among PI*SZ, while basal panlobular emphysema was more common among PI*ZZ (p<0.05). FEV1 declined on average more rapidly in PI*ZZ than in PI*SZ. Cigarette smoking worsened obstruction, more so in PI*SZ than in PI*ZZ (p<0.0001). Overall quality of life, assessed by SGRQ, was better in PI*SZ than in PI*ZZ (11.7 and 29, respectively; p=0.0001). By considering relationships among age, smoke and lung function decline some clusters are more evident among PI*SZ subjects. In conclusion, the results showed clinical heterogeneity of the PI*SZ genotype, thus highlightning the need of a clinical follow-up similar to ZZ patients, in order to early identify possible pathological features