Skip to content
How It Works
Explore
Ask a Question Resources Pricing
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Sign Up
PubMed This is a summary of 25 peer-reviewed journal articles Updated
Pulmonology · Alpha-1 Antitrypsin Deficiency

What Does a Low Alpha-1 Antitrypsin Test Mean for COPD?

At a Glance

A low alpha-1 antitrypsin blood test in someone with COPD does not confirm alpha-1 antitrypsin deficiency or predict disease severity. Follow-up blood, genetic, or protein testing, along with lung and liver checks, clarifies risk and guides care.

In this answer

4 sections

01

Confirming Your Diagnosis

02

Evaluating Your Lungs and Liver

03

Managing Your Care

04

What This Means for Your Family

If your initial screening test for alpha-1 antitrypsin (AAT) is low, it means you need further testing to find out if you have Alpha-1 Antitrypsin Deficiency (AATD). A single low blood level is not enough to make a diagnosis or determine your prognosis [1]. Your doctor will order follow-up tests to see exactly which genes you inherited and how much AAT your body is producing [2]. If AATD is confirmed, it provides crucial information that will help your care team tailor your COPD treatment, check for liver risks, and protect your family members.

Confirming Your Diagnosis

AAT is a protein made in the liver that protects the lungs from damage. It is an acute-phase protein, meaning its levels naturally rise when your body is experiencing inflammation, an infection, or a COPD exacerbation (a flare-up of symptoms) [3][4]. Because illness pushes AAT levels up, a low result while you are sick is still concerning and warrants follow-up. Conversely, if you are tested while sick and the result is normal, your doctor may still choose to repeat the test when you are well to ensure the inflammation wasn’t hiding a low baseline level [4].

To get an accurate diagnosis, your doctor will interpret your AAT blood level alongside specific genetic or protein tests [5]:

  • Quantitative AAT Level: A measure of how much AAT is in your blood.
  • Phenotype or Genotype Testing: A phenotype test looks at the specific AAT proteins in your blood, while a genotype test looks directly at your DNA to identify which AAT genes you inherited [6][7].

Understanding Your Genes

Alpha-1 Antitrypsin Deficiency is autosomal co-dominant. This means you inherit one AAT gene from each parent, and both genes affect how much AAT your body produces [8].

Genotype What It Means
Pi*MM The normal genetic combination [7].
Pi*MZ Having one normal “M” gene and one defective “Z” gene. While often called a “carrier,” people with Pi*MZ can have an increased risk of COPD, especially if they smoke or are exposed to lung irritants [9][10].
Pi*SZ An intermediate deficiency. Risk varies widely from person to person [7].
Pi*ZZ A severe deficiency that significantly increases the risk of early-onset emphysema and liver disease [10].

(Note: There are also other rare and “null” variants that your doctor will check for if needed [11]. Your individual prognosis depends on your specific genotype, smoking history, and lung function, not just your initial screening level [1][12].)

Evaluating Your Lungs and Liver

If AATD is confirmed, it can affect both your lungs and your liver [10]. A low test does not guarantee you will develop severe disease, but it means you need individualized monitoring.

  • Lung Risks: A lack of AAT protein leaves the lungs vulnerable to damage, accelerating emphysema (destruction of the air sacs in the lungs) and COPD [10]. Your doctor will likely order complete pulmonary function tests (breathing tests). A chest CT scan may be ordered if your symptoms or lung function suggest it is needed, but it is not automatically required for everyone [13].
  • Liver Risks: In some forms of AATD (especially Pi*ZZ), the abnormal AAT protein is produced but gets trapped inside the liver [10]. Over time, this buildup can cause liver injury, fibrosis (scarring of the liver), and eventually cirrhosis (severe, irreversible scarring) [14]. Your doctor will use blood tests (like liver enzymes or platelet counts) or an ultrasound to assess your liver health [15]. Surveillance for liver cancer is generally only necessary if you develop advanced fibrosis or cirrhosis [10].

Managing Your Care

Finding out you have AATD does not replace your standard COPD care—you still need to use your prescribed inhalers, get respiratory vaccinations, and consider pulmonary rehabilitation [16][17]. However, AATD requires some specialized management:

  • Strict Avoidance of Smoking and Pollutants: Tobacco smoke is incredibly dangerous with AATD and speeds up lung damage [9]. You must stop smoking and avoid secondhand smoke. You should also work to minimize occupational exposures to dust, fumes, and chemicals, using practical protections like better ventilation or appropriate protective equipment [16][18].
  • Specialist Care: Consider a referral to a pulmonologist or a specialized AATD reference center to help coordinate your care [19].
  • Augmentation Therapy: For certain patients with a severe AAT deficiency (like Pi*ZZ) and documented emphysema/abnormal lung function, doctors may prescribe augmentation therapy [5][20]. This involves intravenous (IV) infusions (often weekly) of AAT protein purified from donor blood [21]. It is not a cure and does not treat liver disease. Clinical trials suggest it may slow the loss of lung tissue (measured by CT scans), but its impact on symptoms or survival is less certain [21][22]. It is generally only prescribed for non-smokers with severe deficiency [23][20].

What This Means for Your Family

Because AATD is genetic, your blood relatives could also have the condition or be carriers [8]. Medical guidelines recommend that all first-degree relatives (parents, siblings, and children) be offered genetic counseling and testing [24][25].

A genetic counselor can explain what your specific genotype means for each family member. Testing is a personal choice, but knowing their status allows your family to make informed decisions about smoking, occupational hazards, and family planning [25].

Common questions in this guide

Does a low alpha-1 antitrypsin result confirm AAT deficiency?
No. A single low blood level suggests that further evaluation is needed, but it does not by itself confirm alpha-1 antitrypsin deficiency or show how severe the condition will be. Doctors usually combine the level with genetic or protein testing.
Can illness change my alpha-1 antitrypsin test result?
Yes. Alpha-1 antitrypsin rises during inflammation, infection, or a COPD flare, so a normal result obtained while you are sick may hide a lower usual level. Your clinician may repeat the test after you recover; a low result during illness still deserves follow-up.
Which tests are used to confirm alpha-1 antitrypsin deficiency?
Confirmation may include a quantitative blood test, a phenotype test that identifies the AAT protein pattern, and a genotype test that examines inherited genes. The results help identify combinations such as Pi*ZZ or Pi*MZ and guide risk assessment.
Does a low AAT level mean I will develop emphysema or liver disease?
No. A low result does not guarantee severe lung or liver disease; risk depends on the inherited genotype, smoking and pollutant exposure, and lung function. If deficiency is confirmed, clinicians may monitor breathing with pulmonary function tests and assess the liver with blood tests or ultrasound.
What treatment is available if AAT deficiency is confirmed?
You still need standard COPD care, including prescribed inhalers, recommended respiratory vaccinations, and pulmonary rehabilitation when appropriate. Strictly avoiding smoking and harmful fumes is important, and selected nonsmokers with severe deficiency, emphysema, and abnormal lung function may be considered for often-weekly intravenous augmentation therapy; it is not a cure and does not treat liver disease.
Should my relatives be tested for alpha-1 antitrypsin deficiency?
Because AAT deficiency is inherited, parents, siblings, and children may have the condition or carry an altered gene. Guidelines recommend offering first-degree relatives genetic counseling and testing so they can make informed choices about smoking, workplace exposures, and family planning.

Related questions

When Are Oral Steroids Used for COPD? Side Effects Explained What Does a Low DLCO Indicate in COPD? Causes Explained When Are Antibiotics Needed for a COPD Exacerbation? What Does FEV1 Percent Predicted Mean for COPD Prognosis? What Is a Mild, Moderate, or Severe COPD Exacerbation?
Show more
Why Do COPD Flare-Ups Keep Happening? How to Prevent Them How Often Should Spirometry Be Repeated for COPD Monitoring? Is COPD Reversible? Can Treatment Restore Lung Function? Should COPD Patients Get Low-Dose CT Lung Cancer Screening? How Is the BODE Index Calculated and Interpreted in COPD? How Is a Severe COPD Exacerbation Treated in the Hospital? Can You Get COPD If You Have Never Smoked? Causes Explained What Happens If I Have Asthma and COPD Together? Explained Why Can COPD Be GOLD Grade 2 and Still Be Group E? Can Borderline Spirometry Confirm COPD? When to Repeat? What Are COPD-Related PH and Cor Pulmonale Symptoms? What Should a Written COPD Exacerbation Action Plan Include? Do I Need a Chest CT, Chest X-ray, or DLCO Test for COPD? What Comorbidities Should COPD Checkups Screen For?

Get notified when new evidence is published on chronic obstructive pulmonary disease.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References

References (25)
  1. 1

    Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective threshold.

    Franciosi AN, Fraughen D, Carroll TP, McElvaney NG

    The European respiratory journal 2022; (59(2)) doi:10.1183/13993003.01410-2021.

    PMID: 34172471
  2. 2

    Indications for active case searches and intravenous alpha-1 antitrypsin treatment for patients with alpha-1 antitrypsin deficiency chronic pulmonary obstructive disease: an update.

    Casas F, Blanco I, Martínez MT, et al.

    Archivos de bronconeumologia 2015; (51(4)):185-92.

    PMID: 25027067
  3. 3

    Beyond the lungs: Alpha-1 antitrypsin's potential role in human gestation.

    Jezela-Stanek A, Chorostowska-Wynimko J

    Advances in clinical and experimental medicine : official organ Wroclaw Medical University 2019; (28(9)):1257-1261 doi:10.17219/acem/103668.

    PMID: 30929319
  4. 4

    Prevalence of alpha-1 antitrypsin deficiency in patients with acute exacerbation of chronic obstructive pulmonary disease: Insights from a prospective study.

    Rayees AK, Chetambath R, Ibrahim R, Kumar A

    Journal of family medicine and primary care 2024; (13(6)):2354-2356 doi:10.4103/jfmpc.jfmpc_1357_23.

    PMID: 39027845
  5. 5

    Spanish Clinical Practice Guidelines for the Diagnosis and Management of Alpha-1 Antitrypsin Deficiency: 2026 Update.

    Calle Rubio M, López-Campos JL, Casas Maldonado F, et al.

    Archivos de bronconeumologia 2026; doi:10.1016/j.arbres.2026.06.004.

    PMID: 42392940
  6. 6

    State-of-the-art testing for alpha-1 antitrypsin deficiency.

    Kueppers F, Sanders C

    Allergy and asthma proceedings 2017; (38(2)):108-114 doi:10.2500/aap.2017.38.4031.

    PMID: 28120746
  7. 7

    A Novel Detection Method to Identify Individuals with Alpha-1 Antitrypsin Deficiency: Linking Prescription of COPD Medications with the Patient-Facing Electronic Medical Record.

    Lam SW, Strange C, Brantly ML, Stoller JK

    Chronic obstructive pulmonary diseases (Miami, Fla.) 2022; (9(1)):26-33 doi:10.15326/jcopdf.2021.0260.

    PMID: 34784453
  8. 8

    Alpha-1 Antitrypsin Deficiency: Principles of Care.

    Rodrigues JF, Mineiro A, Reis A, et al.

    Acta medica portuguesa 2020; (33(6)):433-439 doi:10.20344/amp.12950.

    PMID: 32504520
  9. 9

    Alpha-1 Antitrypsin PiMZ Genotype Is Associated with Chronic Obstructive Pulmonary Disease in Two Racial Groups.

    Foreman MG, Wilson C, DeMeo DL, et al.

    Annals of the American Thoracic Society 2017; (14(8)):1280-1287 doi:10.1513/AnnalsATS.201611-838OC.

    PMID: 28380308
  10. 10

    Amelioration of Alpha-1 Antitrypsin Deficiency Diseases with Genome Editing in Transgenic Mice.

    Shen S, Sanchez ME, Blomenkamp K, et al.

    Human gene therapy 2018; (29(8)):861-873 doi:10.1089/hum.2017.227.

    PMID: 29641323
  11. 11

    PiComplutense (p.Pro393Thr): A novel SERPINA1 variant in Alpha-1 antitrypsin deficiency identified in two siblings.

    Rodríguez Hermosa JL, Esmaili S, Ayat Ortiz S, et al.

    Respiratory medicine case reports 2025; (58()):102285 doi:10.1016/j.rmcr.2025.102285.

    PMID: 41070050
  12. 12

    Individualized lung function trends in alpha-1-antitrypsin deficiency: a need for patience in order to provide patient centered management?

    Stockley RA, Edgar RG, Pillai A, Turner AM

    International journal of chronic obstructive pulmonary disease 2016; (11()):1745-56 doi:10.2147/COPD.S111508.

    PMID: 27536086
  13. 13

    Imaging in alpha-1 antitrypsin deficiency: a window into the disease.

    Huang YT, Wencker M, Driehuys B

    Therapeutic advances in chronic disease 2021; (12_suppl()):20406223211024523 doi:10.1177/20406223211024523.

    PMID: 34408834
  14. 14

    Review article: New developments in biomarkers and clinical drug development in alpha-1 antitrypsin deficiency-related liver disease.

    Loomba R, Clark G, Teckman J, et al.

    Alimentary pharmacology & therapeutics 2024; (59(10)):1183-1195 doi:10.1111/apt.17967.

    PMID: 38516814
  15. 15

    Clinical and histologic features of adults with alpha-1 antitrypsin deficiency in a non-cirrhotic cohort.

    Clark VC, Marek G, Liu C, et al.

    Journal of hepatology 2018; (69(6)):1357-1364 doi:10.1016/j.jhep.2018.08.005.

    PMID: 30138687
  16. 16

    Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know.

    Barjaktarevic I, Campos M

    Therapeutic advances in chronic disease 2021; (12_suppl()):20406223211010172 doi:10.1177/20406223211010172.

    PMID: 34408831
  17. 17

    Improving the Lives of Patients with Alpha-1 Antitrypsin Deficiency.

    Sandhaus RA, Strange C, Zanichelli A, et al.

    International journal of chronic obstructive pulmonary disease 2020; (15()):3313-3322 doi:10.2147/COPD.S276773.

    PMID: 33328731
  18. 18

    [Alpha-1-antitrypsin deficiency - an update].

    Bernhard N, Bals R, Fähndrich S

    Deutsche medizinische Wochenschrift (1946) 2016; (141(20)):1467-1469 doi:10.1055/s-0042-112096.

    PMID: 27701692
  19. 19

    Personalised indication of augmentation therapy for emphysema associated with severe alpha-1 antitrypsin deficiency: a case series.

    Aljama C, Martin T, Granados G, et al.

    Therapeutic advances in respiratory disease 2024; (18()):17534666241271917 doi:10.1177/17534666241271917.

    PMID: 39132722
  20. 20

    Alpha-1-Antitrypsin Deficiency: Disease Management and Learning from Studies.

    Greulich T

    COPD 2017; (14(sup1)):S8-S11 doi:10.1080/15412555.2017.1286166.

    PMID: 28306355
  21. 21

    Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review.

    Edgar RG, Patel M, Bayliss S, et al.

    International journal of chronic obstructive pulmonary disease 2017; (12()):1295-1308 doi:10.2147/COPD.S130440.

    PMID: 28496314
  22. 22

    Alpha 1 antitrypsin augmentation therapy for alpha 1 antitrypsin deficiency-associated lung disease.

    Glaister P, Hindle Robinson N, Woods A, et al.

    The Cochrane database of systematic reviews 2026; (8()):CD015930 doi:10.1002/14651858.CD015930.pub2.

    PMID: 42626936
  23. 23

    Alpha-1 antitrypsin (AAT) augmentation therapy in individuals with the PI*MZ genotype: a pro/con debate on a working hypothesis.

    Barjaktarevic I, Miravitlles M

    BMC pulmonary medicine 2021; (21(1)):99 doi:10.1186/s12890-021-01466-x.

    PMID: 33757485
  24. 24

    The Diagnosis and Management of Alpha-1 Antitrypsin Deficiency in the Adult.

    Sandhaus RA, Turino G, Brantly ML, et al.

    Chronic obstructive pulmonary diseases (Miami, Fla.) 2016; (3(3)):668-682 doi:10.15326/jcopdf.3.3.2015.0182.

    PMID: 28848891
  25. 25

    Variants of SERPINA1 and the increasing complexity of testing for alpha-1 antitrypsin deficiency.

    Foil KE

    Therapeutic advances in chronic disease 2021; (12_suppl()):20406223211015954 doi:10.1177/20406223211015954.

    PMID: 34408833

This page explains what a low alpha-1 antitrypsin result may mean for someone with COPD for informational purposes only and does not constitute medical advice. Your clinician should interpret your result and decide which confirmatory tests, monitoring, and treatments are appropriate.