PiSZ alpha-1 antitrypsin deficiency (AATD): pulmonary phenotype and prognosis relative to PiZZ AATD and PiMM COPD

INTRODUCTION: The PiSZ genotype results in less severe deficiency of alpha-1 antitrypsin (AAT) than PiZZ. Less is known about phenotypic and prognostic features.

METHODS: We studied 699 PiZZ, 126 PiSZ and 316 PiMM patients. All AAT deficiency (AATD) patients were augmentation naive. PiSZ were compared with PiZZ patients for clinical phenotype at baseline including CT findings, smoke exposure, progression of lung disease and survival. Similarly, PiSZ patients diagnosed as a result of investigation for possible lung disease (lung index cases) were compared with PiMM. Multivariable analytical techniques and matching (PiSZ to PiZZ) were employed to account for demographic differences.

RESULTS: Pack-years smoked and FEV1 exhibited a negative correlation in PiSZ and ZZ patients (both r=-0.43), with emphysema and COPD occurring more commonly in PiZZ patients at <20 pack-year exposure. In multivariable analyses, PiSZ patients were less likely to have emphysema (p<0.01) and had better survival than PiZZ (p=0.017), but lung function decline did not differ significantly. 42% of PiSZ patients had upper-zone-dominant emphysema on CT scan. Analyses of AAT level confirmed a critical threshold at 11 μM, particularly with regard to phenotypes classical of PiZZ AATD.Significant baseline differences suggested that PiSZ had presented earlier to health services than PiMM. Once this was accounted for, risk of emphysema did not differ between PiSZ and PiMM although survival was lower in PiMM patients (p<0.01).

CONCLUSIONS: PiSZ patients are less susceptible to cigarette smoke than PiZZ. The pattern of emphysema may be similar at diagnosis to usual COPD.