Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project.
Martín, Teresa Guimarães, Catarina Esquinas, Cristina Torres-Duran, Maria Turner, Alice M Tanash, Hanan Rodríguez-García, Carlota Corsico, Angelo López-Campos, José Luis Bartošovská, Eva
Martín, Teresa
Guimarães, Catarina
Esquinas, Cristina
Torres-Duran, Maria
Turner, Alice M
Tanash, Hanan
Rodríguez-García, Carlota
Corsico, Angelo
López-Campos, José Luis
Bartošovská, Eva
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2024-06-26
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Abstract
Background: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry.
Method: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables.
Results: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL.
Conclusions: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels.
Trial registration: www.
Clinicaltrials: gov (ID: NCT04180319).
Keywords: Alpha-1 antitrypsin; Lung disease; PI*SS; Registries.
Citation
Martín T, Guimarães C, Esquinas C, Torres-Duran M, Turner AM, Tanash H, Rodríguez-García C, Corsico A, López-Campos JL, Bartošovská E, Stæhr Jensen JU, Hernández-Pérez JM, Sucena M, Miravitlles M. Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project. Respir Res. 2024 Jun 26;25(1):260. doi: 10.1186/s12931-024-02879-y. PMID: 38926693; PMCID: PMC11210092.
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