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- Alpha-1 antitrypsin deficiency (AATD) is a highly underdiagnosed genetic condition1,2
- All patients with chronic obstructive pulmonary disease (COPD) should be tested for AATD per guidance from the American Thoracic Society (ATS), European Respiratory Society (ERS), Global Initiative for Chronic Obstructive Lung Disease (GOLD), and others2-4
- Managing AATD-associated COPD requires a combination of pharmacological, surgical, and nonpharmacological approaches4,5
AATD is highly underdiagnosed1
70,000 to 100,000
individuals in the United States are estimated to be severely AAT deficienta
>90%
of these cases are not diagnosed
a>11 µM.6
Guidelines recommend testing all patients with COPD for AATD2-4,7
ATS/ERS, CHEST/CTS, COPD Foundation, and GOLD recommend testing2-4,7:
- All patients with a diagnosis of COPD
- Symptomatic individuals (includes adult-onset asthma [persistent, incompletely reversible airflow obstruction], unexplained bronchiectasis, unexplained chronic liver disease, necrotizing panniculitis, granulomatosis with polyangiitis [GPA])
- Asymptomatic individuals (includes persistent obstruction on pulmonary function tests with identifiable risk factors [eg, cigarette smoking, occupational exposure])
-
First-degree relatives of patients diagnosed with AATD
| Guidelines | Core Testing Recommendation2-4 |
| ATS/ERS (2003 Statement) | Test all patients with COPD/emphysema |
| GOLD (2025) | Test all patients with COPD |
| COPD Foundation/Alpha-1 Foundation (2016 CPG) | Test all patients with COPD regardless of age/ethnicity |
Test all patients with COPD for AATD. Early detection and management is essential to reduce the potential for irreversible organ damage.2-4,8-10
What are the testing guidelines for AATD?
It is recommended that the diagnosis of AATD be confirmed through genetic testing and AAT protein level testing in parallel.11
| AAT Protein Level Testing11-13 | |
|
WHY: | Determine whether AAT protein deficiency is present and to assess severity |
|
WHAT: | Quantitative measure of AAT serum levels |
|
HOW: |
Whole blood, serum, dried blood spot sample Available methods include radial immunodiffusion, nephelometry, and latex-enhanced immunoturbidimetry |
| SERPINA1 Genetic Testing2,12 | |
|
WHY: | Confirm a diagnosis of AATD and determine patient’s specific genotype |
|
WHAT: | Identification of genetic alleles (M, S, Z, F, I, etc.) |
|
HOW: |
Whole blood, dried blood spot sample, cheek swab sample Detection via DNA sequencing or protease inhibitor (Pi) typing
|
AATD testing is widely available, including sponsored testing at no charge.b
bThis is not an endorsement of any specific lab. Testing options can be found at https://www.ncbi.nlm.nih.gov/gtr/. Sanofi does not review or control the content of non-Sanofi websites. Consult each laboratory for a full range of options. Content is current at time of publication, and testing may not be available in all states; please call laboratory to confirm test availability, sample shipping information, and all other logistics. This list does not constitute an endorsement by Sanofi.
AATD is caused by pathogenic variants of SERPINA1, the gene that encodes the AAT protein. Understanding risk begins with defining the underlying genetics of AATD.3,12,14
How is AATD-related COPD managed?
Managing AATD-associated COPD requires a combination of approaches4,5
Recommendations for management of chronic symptoms and acute exacerbations in patients with AATD typically follow those recommended for general COPD, as described in the guidelines from GOLD5
Pharmacological4,5
- Intravenous augmentation therapy:
- Weekly infusion of plasma-derived AAT (pdAAT)
- Raise and maintain serum AAT levels above 11 µM
- Bronchodilators
- Inhaled corticosteroids
- Biologics: eg, mepolizumab and dupilumab
- Roflumilast and ensifentrine
Bronchoscopic and surgical intervention3,4
- Lung transplant (AATD-associated end-stage lung disease)
- Possible bullectomy or LVRS in select patients
Nonpharmacological3-5,15
- Smoking cessation
- Vaccinations: SARS-CoV-2, RSV, influenza, pneumococcal, tetanus/diphtheria/pertussis, Hepatitis A and B
- Limit alcohol consumption and maintain ideal weight
- Pulmonary rehabilitation
- Exercise training: respiratory muscle training
- Disease education: occupational exposure (smoke, dust, fumes); risk occupation, such as farmers, firefighters, construction workers
- Oxygen therapy
Genotypes & AAT Levels
Understanding risk begins with defining the underlying genetics and potential deficiency of AAT protein.3,12
Frequently asked questions
Clinical guidelines (eg, ATS/ERS, GOLD, COPD Foundation) recommend testing2,4-7:
- All patients with a diagnosis of COPD
- Symptomatic individuals (includes adult-onset asthma [persistent, incompletely reversible airflow obstruction], unexplained bronchiectasis, unexplained chronic liver disease, necrotizing panniculitis, granulomatosis with polyangiitis [GPA])
- Asymptomatic individuals (includes persistent obstruction on pulmonary function tests with identifiable risk factors [eg, cigarette smoking, occupational exposure])
- First-degree relatives of patients diagnosed with AATD
Diagnosis typically involves11:
- Serum AAT level testing to assess quantitative deficiency
- Genotyping and/or phenotyping to confirm pathogenic variants and characterize disease risk
These tests are often performed in parallel for diagnostic accuracy.
Management typically involves a combination of4,5:
- Pharmacologic therapies
- Nonpharmacologic interventions
- Procedural or surgical approaches (in select cases)
Treatment is generally aligned with COPD management principles, with additional consideration of AAT-specific therapies.
Pharmacologic management may include4,5:
- Intravenous AAT augmentation therapy (in appropriate patients)
- Inhaled bronchodilators
- Inhaled corticosteroids (as indicated)
- Biologic therapies for select phenotypes
- Preventive therapies (eg, vaccinations)
Definitions: AAT=alpha-1 antitrypsin; AATD=alpha-1 antitrypsin deficiency; ATS=American Thoracic Society; COPD=chronic obstructive pulmonary disease; CTS=Canadian Thoracic Society; ERS=European Respiratory Society; GOLD=Global Initiative for Chronic Obstructive Lung Disease; LVRS=lung volume reduction surgery; Pi=protease inhibitor; RSV=respiratory syncytial virus; SARS-CoV-2=severe acute respiratory syndrome coronavirus 2.
References: 1. Lopez MA. Alpha-1 antitrypsin deficiency (AATD). Accessed March 25, 2026. https://www.rarediseaseadvisor.com/disease-info-pages/alpha-1-antitrypsin-deficiencyepidemiology-aatd/ 2. 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. 3. American Thoracic Society; European Respiratory Society. 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. 4. Global Initiative for Chronic Obstructive Lung Disease. GOLD Report. Accessed February 3, 2026. https://goldcopd.org 5. Barjaktarevic I, Campos M. Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know. Ther Adv Chron Dis. 2021;12:49-63. 6. Barjaktarevic I, Miravitlles M. Alpha-1 antitrypsin (AAT) augmentation therapy in individuals with the PI*MZ genotype: a pro/con debate on a working hypothesis. BMC Pulm Med. 2021;21(1):99. doi:10.1186/s12890-021-01466-x 7. Hernandez P, Bossé Y, Bush P, et al. Alpha-1-antitrypsin deficiency targeted testing and augmentation therapy: a Canadian Thoracic Society meta-analysis and clinical practice guideline. Chest. 2025;167(4):1044-1063. 8. 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 9. Seçinti E, Schantz K, Delbecque L, et al. Patient-centered assessment of treatment for alpha-1 antitrypsin deficiency: literature review to identify concepts and measures for people with alpha1-antitrypsin deficiency. Orphanet J Rare Dis. 20(1):83. doi:10.1186/s13023-025-03592-9 10. Meseeha M, Sankari A, Attia M. Alpha-1 antitrypsin deficiency. In: StatPearls [Internet]. StatPearls Publishing; August 17, 2024. Accessed March 4, 2026. https://www.ncbi.nlm.nih.gov/books/NBK442030/ 11. Abboud RT, Nelson TN, Jung B, et al. Alpha1-antitrypsin deficiency: a clinical-genetic overview. Appl Clin Genet. 2011;4:55-65. 12. 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 13. Craig TJ, Henao MP. Advances in managing COPD related to α1–antitrypsin deficiency: an under-recognized genetic disorder. Allergy. 2018;73(11):2110-2121. 14. Cazzola M, Stolz D, Rogliani P, Matera MG. α1-Antitrypsin deficiency and chronic respiratory disorders. Eur Respir Rev. 2020;29(155):190073. doi:10.1183/16000617.0073-2019 15. Stoller JK, Aboussouan LS. A review of α1-antitrypsin deficiency. Am J Respir Crit Care Med. 2012;185(3):246-259.
