Irreversible lung damage may lead to chronic pulmonary conditions^1,2

In alpha-1 antitrypsin deficiency (AATD), progressive decline in lung function can lead to chronic obstructive pulmonary disease (COPD) and emphysema^1,2
This functional decline can also reduce quality of life and shorten life expectancy^1-5

Patients with AATD are predisposed to developing COPD and emphysema¹

COPD exacerbations in patients with AATD can be triggered by respiratory infection, air pollution, and environmental irritants⁶
The severity and frequency of COPD exacerbations can accelerate the progression of lung disease in patients with AATD⁷
People with AATD-related COPD experience more emphysema, COPD exacerbations, and cirrhosis compared to those with COPD without AATD⁸

Emphysema is reported in 47% of Medicare patients with AATD-related COPD⁸

Bar chart showing rates of emphysema, COPD exacerbations, and cirrhosis in patients with COPD, with and without AATD

Data from Khandelwal N et al. J Health Econ Outcomes Res. 2025;12(1):66-74.
Retrospective analysis of 742 Medicare patients with AATD with emphysema, COPD exacerbations, and cirrhosis, compared with matched individuals with COPD without AATD (2015-2021).⁸

Severe AAT deficiency is associated with a poor prognosis with increased exacerbations and shorter lifespan^5,7,9-11

Exacerbation burden is significantly higher in AATD^7,9,10,12

2x

Median annualized exacerbation rates in AATD are double that observed in COPD without AATD^9,10,a

61%

Of 584 patients with AATD-COPD, 61% experienced one or more severe exacerbations, including hospitalization⁷

14 Days

Median duration exacerbation was 14 days (interquartile range 7-21)¹²

^aComparison of 2 different studies. Study 1: 19 patients with AATD-related COPD. Average age was 52 years. Study 2: 132 patients with moderate-to-severe COPD without AATD.

Patients with AATD have decreased life expectancy compared to the general population¹³

58% to 72%

of deaths in patients with severe deficiency of AAT are caused by respiratory disease such as emphysema^5,11

34%

10-year survival in patients with AATD-associated COPD who received a lung transplant (1025 deceased patients)¹⁴

Patients with severe deficiency of AAT face an increased risk of early mortality, most often due to emphysema⁵

Mortality increases as % predicted FEV₁ decreases⁵

Kaplan-Meier mortality analysis by % predicted FEV₁

Kaplan-Meier curve showing mortality rates in AATD stratified by FEV1

Adapted from Stoller JK et al. Chest. 2005;127(4):1196-1204.
Of the 1,129 registry enrollees, 204 subjects (18.1%) died over the course of follow-up. 7.8% (n=16/204) were never-smokers in whom emphysema was still deemed the underlying cause of death in the majority (56%, n=9/16) (National Heart, Lung, and Blood Institute Registry 1989-1992).⁵

Highest mortality is in patients with FEV₁ <15%⁵
Patients with FEV₁ ≥50% show the lowest mortality⁵

Severe AAT deficiency, defined as a serum level <11 μM.⁵

Emphysema is the most common cause of mortality in patients with severe deficiency of AAT⁵

Ring graph showing underlying causes of death in patients with severe AAT deficiency

Data from Stoller JK et al. Chest. 2005;127(4):1196-1204.
Underlying causes of death among 118 patients with severe deficiency of AAT (defined as serum level <11 µmol/L). Of the 118 patients, 13.7% were never-smokers and 86.3% were ever-smokers (National Heart, Lung, and Blood Institute Registry 1989-1992).⁵

Up to 72% of deaths in patients with severe deficiency of AAT are caused by emphysema⁵
Other causes include cirrhosis, malignancy, diverticulitis, sepsis/infection, trauma/accidents, and other cases⁵

Progression of AATD leads to worsening COPD burden and quality of life¹⁵

The annual decline in quality of life is significantly greater for patients with AATD-associated COPD compared with AATD (no COPD) (P=0.025)³

Bar chart showing annual decline in quality of life in patients with COPD, with and without AATD

Data from Stockley RA et al. Respir Res. 2018;19(1):137.
Mean (IQR) annual decline in SGRQ total a slope in a UK retrospective database study in patients with AATD genotype ZZ (n=454).
^bThe SGRQ is a commonly used measure of QoL specifically designed for patients with obstructive airway diseases.¹⁷

More frequent COPD exacerbations are associated with worsening quality of life⁴

Line graph showing increase in SGRQ score (worsening quality of life) as exacerbation frequency increases

Line graph showing decrease in SF-36 score (worsening quality of life) as exacerbation frequency increases

Data from Campos MA et al. Respir Med. 2009;103(10):1532-1539.
SGRQ and SF-36 scores from a noninterventional baseline follow-up of patients with AATD (N=922). Ninety-four percent (94%) of patients had genotype ZZ.⁴

Patients with AATD have more COPD exacerbations per year than patients with non-AATD COPD⁸
COPD exacerbations become more frequent as AATD progresses¹⁶
More frequent COPD exacerbations are associated with worsening quality of life¹⁵

^cSGRQ scores range from 0 to 100, with higher scores indicating worse quality of life.¹⁷
^dSF-36 scores range from 0 to 100, with lower scores indicating worse quality of life.¹⁸

AATD cannot be deduced based on age, smoking history, or severity of FEV₁ decline¹⁹

FEV₁ % predicted by age for 378 ZZ patients stratified by smoking status

Scatterplot showing FEV1 in smokers and non-smokers with severe genotype (ZZ)

Adapted with permission from: Demeo DL et al. Thorax. 2007;62(9):806-813.
Clinical presentation alone is not enough to determine which patients with COPD may be living with less of the AAT protein.^19,20
^dStage III severe COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines.⁶

Clickable image to learn more about testing for AATD

AAT protein icon with a downward arrow representing lower levels

Mechanism of Disease

AATD is an inherited disease that may cause protease-induced lung damage.^1,24

Learn more →

Genotypes & AAT Levels

Understanding risk begins with defining the underlying genetics and potential deficiency of AAT protein.^21,25

Review the data →

AAT=alpha-1 antitrypsin; AATD=alpha-1 antitrypsin deficiency; COPD=chronic obstructive pulmonary disease; FEV₁=forced expiratory volume in 1 second; IQR=interquartile range; QoL=quality of life; SF-36=36-Item Short Form Health Survey; SGRQ=St. George’s Respiratory Questionnaire.

References: 1. Kalfopoulos M, Wetmore K, ElMallah MK. Pathophysiology of alpha-1 antitrypsin lung disease. In: Borel F, Mueller C, eds. Alpha-1 Antitrypsin Deficiency: Methods in Molecular Biology. Humana Press; 2017:9-20. 2. Meseeha M, Sankari A, Attia M. Alpha-1 antitrypsin deficiency. In: StatPearls [Internet]. StatPearls Publishing; August 17, 2024. Accessed April 14, 2026. https://www.ncbi.nlm.nih.gov/books/NBK442030/ 3. Stockley RA, Edgar RG, Starkey S, Turner AM. Health status decline in α-1 antitrypsin deficiency: a feasible outcome for disease modifying therapies? Resp Res. 2018;19(1):137. 4. Campos MA, Alazemi S, Zhang G, et al. Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy. Respir Med. 2009:103(10)1532-1539. 5. Stoller JK, Tomashefski J Jr, Crystal RG, et al. Mortality in individuals with severe deficiency of alpha1-antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry. Chest. 2005;127(4):1196-1204. 6. Global Initiative for Chronic Obstructive Lung Disease. GOLD Report. Accessed April 14, 2026. https://goldcopd.org 7. Hiller AM, Piitulainen E, Jehpsson L, Tanash H. Decline in FEV₁ and hospitalized exacerbation in individuals with severe alpha-1 antitrypsin deficiency. Int J Chron Obstruct Pulm Dis. 2019;14:1075-1083. 8. Khandelwal N, Hinson J, Nguyen T, et al. Clinical and economic outcomes in patients with alpha-1 antitrypsin deficiency in a US Medicare advantage population. J Health Econ Outcomes Res. 2025;12(1):66-74. 9. Vijayasaratha K, Stockley RA. Reported and unreported exacerbations of COPD: analysis by diary cards. Chest. 2008;133(1):34-41. 10. Donaldson GC, Seemungal TA, Patel IS, Lloyd-Owen SJ, Wilkinson TM, Wedzicha JA. Longitudinal changes in the nature, severity and frequency of COPD exacerbations. Eur Respir J. 2003;22(6):931-936. doi:10.1183/09031936.03.00038303 11. Tanash HA, Nilsson PM, Nilsson JA, Piitulainen E. Survival in severe alpha-1-antitrypsin deficiency (PiZZ). Respir Res. 2010;11(1):44. doi:10.1186/1465-9921-11-44 12. Needham M, Stockley RA. Exacerbations in α₁-antitrypsin deficiency. Eur Respir J. 2005;25(6):992-1000. 13. Wahlin S, Widman L, Hagström H. Epidemiology and outcomes of alpha-1 antitrypsin deficiency in Sweden 2002-2020: a population-based cohort study of 2286 individuals. J Intern Med. 2025;297(3):300-311. 14. Riley L, Lascano J. Clinical outcomes and survival following lung transplantation in patients with Alpha-1 antitrypsin deficiency. Respir Med. 2020;172:106145. doi:10.1016/j.rmed.2020.106145 15. Choate R, Holm KE, Sandhaus RA, Mannino DM, Strange C. Characteristics associated with SF-36 in alpha-1 antitrypsin deficiency-associated COPD: a cross-sectional analysis. BMC Pulm Med. 2024;24(1):138. doi:10.1186/s12890-024-02953-7 16. Miravitlles M, Herepath M, Priyendu A, et al. Disease burden associated with alpha-1 antitrypsin deficiency: systematic and structured literature reviews. Eur Respir Rev. 2022;31(163):210262. doi:10.1183/16000617.0262-2021 17. Jones P. St. George’s Respiratory Questionnaire Manual. St. George’s, University of London; March 2022. Accessed March 11, 2026. https//www.citystgeorges.ac.uk/__data/assets/pdf_file/0009/899631/SGRQ-Manual-March-2022.pdf 18. Ware JE, Snow KK, Kosinski M, Gandek B. SF-36 Health Survey Manual and Interpretation Guide. The Health Institute, New England Medical Center; 1993. Accessed April 16, 2026. https://www.researchgate.net/profile/John-Ware-6/publication/313050850_SF-36_Health_Survey_Manual_Interpretation_Guide/links/594a5b83aca2723195de5c3d/SF-36-Health-Survey-Manual-Interpretation-Guide.pdf 19. Demeo DL, Sandhaus RA, Barker AF, et al. Determinants of airflow obstruction in severe alpha-1-antitrypsin deficiency. Thorax. 2007;62(9):806-813. 20. Molloy K, Hersh CP, Morris VB, et al. Clarification of the risk of chronic obstructive pulmonary disease in α₁-antitrypsin deficiency PiMZ heterozygotes. Am J Respir Crit Care Med. 2014;189(4):419-427. 21. 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;168(7):818-900. 22. Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chron Obstr Pulm Dis. 2016;3(3):668-682. 23. Abboud RT, Nelson TN, Jung B, Mattman A. Alpha1-antitrypsin deficiency: a clinical-genetic overview. Appl Clin Genet. 2011;4:55-65. 24. Mazzuca C, Vitiello L, Travaglini S, et al. Immunological and homeostatic pathways of alpha-1 antitrypsin: a new therapeutic potential. Front Immunol. 2024;15:1443297. doi:10.3389/fimmu.2024.1443297 25. Feitosa PHR, de Oliveira Castellano MVC, da Costa CH, et al. Recommendations for the diagnosis and treatment of alpha-1 antitrypsin deficiency. J Bras Pneumol. 2024;50(5):e20240235. doi:10.36416/1806-3756/e20240235

Irreversible lung damage may lead to chronic pulmonary conditions1,2

Patients with AATD are predisposed to developing COPD and emphysema1

Severe AAT deficiency is associated with a poor prognosis with increased exacerbations and shorter lifespan5,7,9-11

Exacerbation burden is significantly higher in AATD7,9,10,12

2x

61%

14 Days

Patients with AATD have decreased life expectancy compared to the general population13