Alpha-1 Is the #1 Known Genetic Risk Factor for COPD1

A clear connection between COPD and AAT deficiency

Alpha1-antitrypsin (AAT) deficiency, also called alpha-1 or genetic COPD, is a relatively common but widely underdiagnosed inherited condition that increases the risk of early onset COPD and of liver disease.2-4 AAT deficiency is the most common genetic risk factor for COPD, a highly prevalent, debilitating lung condition.1,5

COPD in the United States:

  • Affects 1 in 8 people aged 45 and older5
  • Prevalence of ~16 million6
  • 4th leading cause of death5

AAT deficiency is not rare; it is rarely diagnosed3

The estimated prevalence of AAT deficiency:

  • ~16 million Americans have COPD6
    • ~15% of patients have at least 1 abnormal allele and could be at increased risk of COPD and liver disease4,7
    • ~1 in 100 have a severe alpha-1 deficiency8
    • ~90% of people with AAT deficiency remain undiagnosed8

Patients with deficient alleles may be more common than you think9

Approximately 1 in 7 patients with COPD or treatment-resistant asthma have at least 1 deficient allele7

Pie charts showing the genetic variants of over 900,000 COPD patients screened for alpha-1.

~90% of patients with AAT deficiency are undiagnosed8

AAT deficiency is underrecognized10

Three lines of evidence demonstrate that AAT deficiency is widely underrecognized10:

~ 90% Undiagnosed

Despite a prevalence estimate of >100,000 individuals with severe AAT deficiency in the US, approximately 90% are undiagnosed3,8

Not Following the Guidelines

Low adherence to clinical guidelines that recommend screening all COPD and treatment-resistant asthma patients for AAT deficiency regardless of age, smoking history, ethnicity, or FEV1 status10,11

Delayed Diagnosis

Many patients experience 8 years of delay between onset of symptoms and accurate diagnosis2,3,10

Benefits of increasing detection and early diagnosis of AAT deficiency10

  • Identifies carriers of AAT-deficient alleles, which can be passed on to children10
  • Identifies those with severe AAT deficiency so available treatment options may be considered for appropriate patients10
  • Provides incentive for smoking cessation12
    • In a follow-up study, 59% of patients with severe alpha-1 attempted to quit smoking after receiving test results and minimal counseling12

There are lifestyle modifications and FDA-approved treatment options for patients with severe AAT deficiency

AlphaID genetic screening test that detects the 14 most prevalent alleles associated with AAT deficiency

Up Next: Pathophysiology of Alpha-1

FEV1, forced expiratory volume in 1 second.


  1. Silverman EK. Genetics of COPD. Annu Rev Physiol. 2020 February 2020;82:413-431. doi:10.1146/annurev-physiol-021317-121224.
  2. Campos MA, Wanner A, Zhang G. Sandhaus RA. Trends in the diagnosis of symptomatic patients with a1-antitrypsin deficiency between 1968 and 2003. CHEST. 2005;128(3):1179-1186.
  3. Stoller JK. Myths and misconceptions about a1-antitrypsin deficiency. Arch Intern Med. 2009; 169(6): 546-550.
  4. Stoller JK, Aboussouan LS. A review of alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med. 2012;185(3): 246-259.5. National Heart, Lung, and Blood Institute.
  5. National Heart, Lung, and Blood Institute. COPD National Action Plan. Accessed September 20, 2023.
  6. Centers for Disease Control and Prevention. Chronic Obstructive Pulmonary Disease (COPD). Accessed November 2, 2023.

  7. Data on file. Alpha-1 Genetics Laboratory.

  8. Brantly M, Campos M, Davis AM, D'Armiento J, et al. Detection of alpha-1 antitrypsin deficiency: the past, present and future. Orphanet J Rare Dis. 2020;96(15):1-10.

  9. de Serres FJ. Environ Health Perspect. 2003;111(16):1851-1854. 

  10. Stoller JK. Detecting alpha-1 antitrypsin deficiency. Ann Am Thorac Soc. 2016;13(Suppl3): S317-S325.
  11. 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.
  12. Carpenter MJ, Strange C, Jones Y, et al. Does genetic testing result in behavioral health change? Changes in smoking behavior following testing for alpha-1 antitrypsin deficiency. Ann Behav Med. 2007;33(1):22-28.