Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype

Research output: Contribution to journalReviewpeer-review

Harvard

McElvaney, GN, Sandhaus, RA, Miravitlles, M, Turino, GM, Seersholm, N, Wencker, M & Stockley, RA 2020, 'Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype', The European respiratory journal, vol. 55, no. 6. https://doi.org/10.1183/13993003.02410-2019

APA

McElvaney, G. N., Sandhaus, R. A., Miravitlles, M., Turino, G. M., Seersholm, N., Wencker, M., & Stockley, R. A. (2020). Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype. The European respiratory journal, 55(6). https://doi.org/10.1183/13993003.02410-2019

CBE

MLA

Vancouver

Author

McElvaney, Gerard N ; Sandhaus, Robert A ; Miravitlles, Marc ; Turino, Gerard M ; Seersholm, Niels ; Wencker, Marion ; Stockley, Robert A. / Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype. In: The European respiratory journal. 2020 ; Vol. 55, No. 6.

Bibtex

@article{76015360c4804b8f951e3ea5d556ed46,
title = "Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype",
abstract = "α1-Antitrypsin deficiency (AATD), characterised by reduced levels or functionality of α1-antitrypsin (AAT), is a significantly underdiagnosed genetic condition that predisposes individuals to lung and liver disease. Most of the available data on AATD are based on the most common, severe deficiency genotype (PI*ZZ); therefore, treatment and monitoring requirements for individuals with the PI*SZ genotype, which is associated with a less severe AATD, are not as clear. Recent genetic data suggest the PI*SZ genotype may be significantly more prevalent than currently thought, due in part to less frequent identification in the clinic and less frequent reporting in registries. Intravenous AAT therapy, the only specific treatment for patients with AATD, has been shown to slow disease progression in PI*ZZ individuals; however, there is no specific evidence for AAT therapy in PI*SZ individuals, and it remains unclear whether AAT therapy should be considered in these patients. This narrative review evaluates the available data on the PI*SZ genotype, including genetic prevalence, the age of diagnosis and development of respiratory symptoms compared with PI*ZZ individuals, and the impact of factors such as index versus non-index identification and smoking history. In addition, the relevance of the putative 11 µM {"}protective threshold{"} for AAT therapy and the risk of liver disease in PI*SZ individuals is explored. The purpose of this review is to identify open research questions in this area, with the aim of optimising the future identification and management of PI*SZ individuals.",
author = "McElvaney, {Gerard N} and Sandhaus, {Robert A} and Marc Miravitlles and Turino, {Gerard M} and Niels Seersholm and Marion Wencker and Stockley, {Robert A}",
note = "Copyright {\textcopyright}ERS 2020.",
year = "2020",
month = jun,
doi = "10.1183/13993003.02410-2019",
language = "English",
volume = "55",
journal = "European Respiratory Journal",
issn = "0903-1936",
publisher = "European Respiratory Society",
number = "6",

}

RIS

TY - JOUR

T1 - Clinical considerations in individuals with α1-antitrypsin PI*SZ genotype

AU - McElvaney, Gerard N

AU - Sandhaus, Robert A

AU - Miravitlles, Marc

AU - Turino, Gerard M

AU - Seersholm, Niels

AU - Wencker, Marion

AU - Stockley, Robert A

N1 - Copyright ©ERS 2020.

PY - 2020/6

Y1 - 2020/6

N2 - α1-Antitrypsin deficiency (AATD), characterised by reduced levels or functionality of α1-antitrypsin (AAT), is a significantly underdiagnosed genetic condition that predisposes individuals to lung and liver disease. Most of the available data on AATD are based on the most common, severe deficiency genotype (PI*ZZ); therefore, treatment and monitoring requirements for individuals with the PI*SZ genotype, which is associated with a less severe AATD, are not as clear. Recent genetic data suggest the PI*SZ genotype may be significantly more prevalent than currently thought, due in part to less frequent identification in the clinic and less frequent reporting in registries. Intravenous AAT therapy, the only specific treatment for patients with AATD, has been shown to slow disease progression in PI*ZZ individuals; however, there is no specific evidence for AAT therapy in PI*SZ individuals, and it remains unclear whether AAT therapy should be considered in these patients. This narrative review evaluates the available data on the PI*SZ genotype, including genetic prevalence, the age of diagnosis and development of respiratory symptoms compared with PI*ZZ individuals, and the impact of factors such as index versus non-index identification and smoking history. In addition, the relevance of the putative 11 µM "protective threshold" for AAT therapy and the risk of liver disease in PI*SZ individuals is explored. The purpose of this review is to identify open research questions in this area, with the aim of optimising the future identification and management of PI*SZ individuals.

AB - α1-Antitrypsin deficiency (AATD), characterised by reduced levels or functionality of α1-antitrypsin (AAT), is a significantly underdiagnosed genetic condition that predisposes individuals to lung and liver disease. Most of the available data on AATD are based on the most common, severe deficiency genotype (PI*ZZ); therefore, treatment and monitoring requirements for individuals with the PI*SZ genotype, which is associated with a less severe AATD, are not as clear. Recent genetic data suggest the PI*SZ genotype may be significantly more prevalent than currently thought, due in part to less frequent identification in the clinic and less frequent reporting in registries. Intravenous AAT therapy, the only specific treatment for patients with AATD, has been shown to slow disease progression in PI*ZZ individuals; however, there is no specific evidence for AAT therapy in PI*SZ individuals, and it remains unclear whether AAT therapy should be considered in these patients. This narrative review evaluates the available data on the PI*SZ genotype, including genetic prevalence, the age of diagnosis and development of respiratory symptoms compared with PI*ZZ individuals, and the impact of factors such as index versus non-index identification and smoking history. In addition, the relevance of the putative 11 µM "protective threshold" for AAT therapy and the risk of liver disease in PI*SZ individuals is explored. The purpose of this review is to identify open research questions in this area, with the aim of optimising the future identification and management of PI*SZ individuals.

U2 - 10.1183/13993003.02410-2019

DO - 10.1183/13993003.02410-2019

M3 - Review

C2 - 32165400

VL - 55

JO - European Respiratory Journal

JF - European Respiratory Journal

SN - 0903-1936

IS - 6

ER -

ID: 62429844