Alpha-1 Is the #1 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 States5:

  • Affects 1 in 8 people aged 45 and older
  • Prevalence of ~16 million
  • 4th leading cause of death

AAT deficiency is not rare; it is rarely diagnosed3

The estimated prevalence of AAT deficiency3:

  • Population-based screening studies estimate a prevalence of ~100,000 (or 1 in 1600-5000) individuals in the US with severe AAT deficiency3
    • However, targeted screening of diagnosed COPD patients could yield a much higher detection rate of 1 in 1006
  • By contrast, case-finding studies found that AAT deficiency is a contributing cause in ~3% (or 480,000) of the ~16 million cases of COPD in the US 3,5

Deficient AAT alleles are common8

Of more than 900,000 patients screened for alpha-1 over 10 years, 15% (>140,000 patients) had at least 1 deficient allele.

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

>90% of patients with AAT deficiency are undiagnosed2,8

AAT deficiency is underrecognized9

Three lines of evidence demonstrate that AAT deficiency is widely underrecognized9:

>90% Undiagnosed

Despite a prevalence estimate of >100,000 individuals with severe AAT deficiency in the US, more than 90% are undiagnosed2,8

Not Following the Guidelines

Low adherence to clinical guidelines that recommend screening all COPD patients for AAT deficiency regardless of age, smoking history, ethnicity, or FEV1 status9,10

Delayed Diagnosis

Many patients experience 8 years of delay between onset of symptoms and accurate diagnosis2,3,9

Benefits of increasing detection and early diagnosis of AAT deficiency9,10

  • Identifies carriers of AAT-deficient alleles, which can be passed on to children9
  • Identifies those with severe AAT deficiency so available treatment options may be considered for appropriate patients9
  • Provides incentive for smoking cessation10
    • In a follow-up study, 59% of patients with severe alpha-1 attempted to quit smoking after receiving test results and minimal counseling11

There are FDA-approved treatment options for severe AAT deficiency

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

Up Next: Pathophysiology of Alpha-1

Learn More

FEV1, forced expiratory volume in 1 second.

References:

  1. Alpha-1 Foundation. Lung disease. https://www.alpha1.org/Newly-Diagnosed/Learning-about-Alpha-1/Lung-Disease. Accessed April 27, 2023.
  2. Campos MA, Wanner A, Zhang G, Sandhaus RA. Trends in the diagnosis of symptomatic patients with α1-antitrypsin deficiency between 1968 and 2003. CHEST. 2005;128(3):1179-1186.
  3. Stoller JK. Myths and misconceptions about ⍺1-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. COPD National Action Plan. https://www.nhlbi.nih.gov/health-topics/education-and-awareness/COPD-national-action-plan. Accessed April 27, 2023.
  6. 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. 
  7. Data on file, Alpha-1 Genetics Laboratory.
  8. Lascano JE, Campos MA. The important role of primary care providers in the detection of alpha-1 antitrypsin deficiency. Postgrad Med. 2017;129(8):889-895.
  9. Stoller JK. Detecting alpha-1 antitrypsin deficiency. Ann Am Thorac Soc. 2016;13(Suppl.3): S317-S325.
  10. 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.
  11. 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.