General population
As AAT deficiency is incurable, and many patients (especially non-smokers) have normal lifespans, AAT deficiency is not routinely screened for.[6]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com
[38]Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis (Miami). 2016 Jun 6;3(3):668-82.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556762
http://www.ncbi.nlm.nih.gov/pubmed/28848891?tool=bestpractice.com
[58]Seersholm N, Kok-Jensen A, Dirksen A. Survival of patients with severe alpha-1 antitrypsin deficiency with special reference to non-index cases. Thorax. 1994;49:695-698.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC475060/pdf/thorax00299-0073.pdf
http://www.ncbi.nlm.nih.gov/pubmed/8066566?tool=bestpractice.com
Neonatal screening can improve modifiable risks such as smoking, but can also adversely affect parental stress and parent-child relationships.[8]Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α<sub>1</sub>-antitrypsin deficiency. Eur Respir J. 2017 Nov 30;50(5):1700610.
https://erj.ersjournals.com/content/50/5/1700610.long
http://www.ncbi.nlm.nih.gov/pubmed/29191952?tool=bestpractice.com
[10]Dummer J, Dobler CC, Holmes M, et al. Diagnosis and treatment of lung disease associated with alpha one-antitrypsin deficiency: a position statement from the Thoracic Society of Australia and New Zealand. Respirology. 2020 Mar;25(3):321-35.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078913
http://www.ncbi.nlm.nih.gov/pubmed/32030868?tool=bestpractice.com
Predispositional testing
Genetic counselling and screening is recommended for adult siblings of individuals with an abnormal AAT variant, whether heterozygous or homozygous.[38]Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis (Miami). 2016 Jun 6;3(3):668-82.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556762
http://www.ncbi.nlm.nih.gov/pubmed/28848891?tool=bestpractice.com
Children, parents, and distant relatives should receive genetic counselling and have screening discussed, but may reasonably accept or refuse screening.
Carrier testing in a reproductive setting
Genetic screening should be discussed with individuals at high risk of AAT deficiency, and with partners of those with AAT deficiency.[6]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com
Chronic obstructive pulmonary disease
Testing for AAT deficiency should be performed in all patients with COPD.[38]Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis (Miami). 2016 Jun 6;3(3):668-82.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556762
http://www.ncbi.nlm.nih.gov/pubmed/28848891?tool=bestpractice.com
[59]Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global strategy for prevention, diagnosis and management of COPD: 2024 report. 2024 [internet publication].
https://goldcopd.org/2024-gold-report
Asthma
The relationship between asthma and AAT deficiency is unclear, and screening recommendations vary.[8]Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α<sub>1</sub>-antitrypsin deficiency. Eur Respir J. 2017 Nov 30;50(5):1700610.
https://erj.ersjournals.com/content/50/5/1700610.long
http://www.ncbi.nlm.nih.gov/pubmed/29191952?tool=bestpractice.com
[9]Lopes AP, Mineiro MA, Costa F, et al. Portuguese consensus document for the management of alpha-1-antitrypsin deficiency. Pulmonology. 2018 Dec;24 Suppl 1:1-21.
https://www.doi.org/10.1016/j.pulmoe.2018.09.004
http://www.ncbi.nlm.nih.gov/pubmed/30473034?tool=bestpractice.com
[10]Dummer J, Dobler CC, Holmes M, et al. Diagnosis and treatment of lung disease associated with alpha one-antitrypsin deficiency: a position statement from the Thoracic Society of Australia and New Zealand. Respirology. 2020 Mar;25(3):321-35.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078913
http://www.ncbi.nlm.nih.gov/pubmed/32030868?tool=bestpractice.com
[38]Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis (Miami). 2016 Jun 6;3(3):668-82.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5556762
http://www.ncbi.nlm.nih.gov/pubmed/28848891?tool=bestpractice.com
[39]Marciniuk DD, Hernandez P, Balter M, et al. Alpha-1 antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society clinical practice guideline. Can Respir J. 2012;19:109-116.
https://www.hindawi.com/journals/crj/2012/920918
http://www.ncbi.nlm.nih.gov/pubmed/22536580?tool=bestpractice.com
The American Thoracic Society/European Respiratory Society recommendations suggest screening patients with asthma who have persistent airflow obstruction despite aggressive bronchodilator therapy.[6]American Thoracic Society/European Respiratory Society Statement. Standards for the diagnosis and management of individuals with alpha 1-antitrypsin deficiency. Am J Respir Crit Care Med. 2003 Oct 1;168(7):818-900.
https://www.atsjournals.org/doi/full/10.1164/rccm.168.7.818
http://www.ncbi.nlm.nih.gov/pubmed/14522813?tool=bestpractice.com
The WHO recommends all patients with adult-onset asthma be tested for AAT deficiency.[8]Miravitlles M, Dirksen A, Ferrarotti I, et al. European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α<sub>1</sub>-antitrypsin deficiency. Eur Respir J. 2017 Nov 30;50(5):1700610.
https://erj.ersjournals.com/content/50/5/1700610.long
http://www.ncbi.nlm.nih.gov/pubmed/29191952?tool=bestpractice.com
[43]World Health Organization. Alpha-1 antitrypsin deficiency: memorandum from a WHO meeting. Bull World Health Organ. 1997;75:397-415.
http://www.ncbi.nlm.nih.gov/pubmed/9447774?tool=bestpractice.com
One suggested algorithm for AAT deficiency screening in asthma recommends genotyping for S and Z alleles first. If either is detected, then serum AAT measurement should be performed.[60]Siri D, Farah H, Hogarth DK. Distinguishing alpha1-antitrypsin deficiency from asthma. Ann Allergy Asthma Immunol. 2013;111:458-464.
http://www.ncbi.nlm.nih.gov/pubmed/24267358?tool=bestpractice.com