Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project
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...
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BMC
2024-06-01
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| Series: | Respiratory Research |
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| Online Access: | https://doi.org/10.1186/s12931-024-02879-y |
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| author | Teresa Martín Catarina Guimarães Cristina Esquinas Maria Torres-Duran Alice M. Turner Hanan Tanash Carlota Rodríguez-García Angelo Corsico José Luis López-Campos Eva Bartošovská Jens-Ulrik Stæhr Jensen José María Hernández-Pérez Maria Sucena Marc Miravitlles |
| author_facet | Teresa Martín Catarina Guimarães Cristina Esquinas Maria Torres-Duran Alice M. Turner Hanan Tanash Carlota Rodríguez-García Angelo Corsico José Luis López-Campos Eva Bartošovská Jens-Ulrik Stæhr Jensen José María Hernández-Pérez Maria Sucena Marc Miravitlles |
| author_sort | Teresa Martín |
| collection | DOAJ |
| description | 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). |
| format | Article |
| id | doaj-art-0c03cbec06a64a27b9085b09ac59ffb5 |
| institution | Kabale University |
| issn | 1465-993X |
| language | English |
| publishDate | 2024-06-01 |
| publisher | BMC |
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| series | Respiratory Research |
| spelling | doaj-art-0c03cbec06a64a27b9085b09ac59ffb52025-01-26T12:48:54ZengBMCRespiratory Research1465-993X2024-06-0125111110.1186/s12931-024-02879-yRisk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research projectTeresa Martín0Catarina Guimarães1Cristina Esquinas2Maria Torres-Duran3Alice M. Turner4Hanan Tanash5Carlota Rodríguez-García6Angelo Corsico7José Luis López-Campos8Eva Bartošovská9Jens-Ulrik Stæhr Jensen10José María Hernández-Pérez11Maria Sucena12Marc Miravitlles13Pneumology Department, Hospital Beatriz ÂngeloPneumology Department, Hospital Senhora da OliveiraFaculty of Medicine and Health Sciences, University of BarcelonaPneumology Department, NeumoVigo I+i Research Group, Hospital Álvaro Cunqueiro, IIS Galicia SurRespiratory Medicine, University Hospitals Birmingham NHS Foundation TrustDepartment of Respiratory Medicine and Allergology, Skåne University Hospital, Lund UniversityPneumology Department, Complejo Hospitalario Clínico-Universitario de SantiagoPneumology Unit, IRCCS San Matteo Hospital FoundationUnidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS). Hospital Universitario Virgen del Rocío, Universidad de SevillaDepartment of Pneumology, Thomayer Hospital, First Faculty of Medicine, Charles UniversitySection of Respiratory Medicine, Department of Medicine, Herlev and Gentofte Hospital, University of CopenhagenPneumology Department, Hospital Universitario Nuestra Señora de La CandelariaPneumology Department, Centro Hospitalar Universitário de Santo AntónioPneumology Department, Hospital Universitari Vall d’Hebron/Vall d’Hebron Research Institute (VHIR), Vall d’Hebron Barcelona Hospital Campus. CIBER de Enfermedades Respiratorias (CIBERES)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).https://doi.org/10.1186/s12931-024-02879-yAlpha-1 antitrypsinLung diseaseRegistriesPI*SS |
| spellingShingle | Teresa Martín Catarina Guimarães Cristina Esquinas Maria Torres-Duran Alice M. Turner Hanan Tanash Carlota Rodríguez-García Angelo Corsico José Luis López-Campos Eva Bartošovská Jens-Ulrik Stæhr Jensen José María Hernández-Pérez Maria Sucena Marc Miravitlles Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project Respiratory Research Alpha-1 antitrypsin Lung disease Registries PI*SS |
| title | Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project |
| title_full | Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project |
| title_fullStr | Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project |
| title_full_unstemmed | Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project |
| title_short | Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project |
| title_sort | risk of lung disease in the pi ss genotype of alpha 1 antitrypsin an earco research project |
| topic | Alpha-1 antitrypsin Lung disease Registries PI*SS |
| url | https://doi.org/10.1186/s12931-024-02879-y |
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