What Are the Potential Clinical Impacts of Diagnostic Delays in AATD?
On this page you'll learn:
Every year of delayed diagnosis has measurable, lasting consequences for patients with AATD1
Longer diagnostic delay may lead to lung function decline, worsening QoL, and decreased survival1,2
Each additional year of diagnostic delay is associated with1,a:
1.6 pts worse SGRQ scoreb |
0.7 pts worse CAT scorec |
aData from 40 newly diagnosed patients with AATD.
bP<0.001.
cP=0.004.
Diagnostic delay is associated with lower 15-year survival rate2,d:
dThe majority of patients exhibited a ZZ genotype (n=220; 82.1%). At inclusion into the registry, 75 patients (28.2%) had never smoked, 181 patients (68.0%) had quit smoking, and 10 patients (3.8%) continued to smoke.
Patients with severe deficiency of AAT face an increased risk of early mortality, most often due to emphysema6
Of the 1129 registry enrollees, 204 subjects (18.1%) died over the course of follow-up. Of the 204 deaths, records were available for 120 subjects. Underlying cause of death was ascertained in 118 of the 120 subjects with records. In the overall cohort of 204 decedents, 13.7% were never-smokers and 86.3% were ever-smokers.6
Diagnostic delay of >10 years is associated with significantly more patients who have a history of pneumonia and exacerbations.2,e,f
eData from 268 patients with AATD from the prospective multicenter Austrian Alpha-1 Lung (AAL) Registry. The majority of patients exhibited a ZZ genotype (n=220; 82.1%). At inclusion into the registry, 75 patients (28.2%) had never smoked, 181 patients (68.0%) had quit smoking, and 10 patients (3.8%) continued to smoke.6
fP=0.008.2
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AATD disease progression is linked to increased disease burden3
Reduced lung capacity from AATD may impact daily life and make everyday activities more difficult7
A cross-sectional study evaluated 4694 participants enrolled in AlphaNet, a US health management organization for people with AATD and lung disease. The study found that AATD had its greatest impact on physical activities. The majority of the cohort had severe deficiency genotypes (ZZ, ZNull, or NullNull). Patients with AATD may struggle to participate in physical activities due to dyspnea, chronic bronchitis, and oxygen use.7
Patients with AATD can experience physical and emotional burdens3,7
Additionally, patients with AATD may face symptoms that affect daily activities, mobility, and emotional burden3,7,8:
- Exacerbations
- Breathlessness
- Fatigue
- Depression
- Anxiety
Timely detection of AATD can help to optimize patient outcomes4,5
Patients diagnosed with AATD can help prevent further disease worsening by avoiding smoking and environmental pollutants9,10
Taking a proactive approach to care is a strong catalyst for smoking cessation, which can lead to a lower decline in FEV1. Patients diagnosed at an early age (≤14 years) are more often never-smokers and have better lung function than those diagnosed after 14 years.11,12
>70% of patients quit smoking after AATD diagnosis.13
83% to 97% of patients maintained smoking cessation, with the highest proportion among ZZ genotypes.13
Timely diagnosis can also encourage adherence to preventative care (immunization and exercising) and help in avoidance of a high-risk occupation (eg, firefighter, farmer, construction worker).9,10,14
Don't let the risk of irreversible lung decline go unrecognized.
Frequently asked questions
Evidence suggests that diagnostic delay in AATD is associated with measurable clinical consequences. Patients diagnosed later in their disease course may experience greater lung function decline, increased symptom burden, reduced exercise capacity, and lower long-term survival compared with patients diagnosed earlier.1,2
AATD remains underrecognized despite being the best known genetic risk factor of COPD. Because symptoms often overlap with COPD, asthma, emphysema, and bronchiectasis, many patients experience multiple healthcare encounters before receiving an appropriate alpha-1 antitrypsin deficiency diagnosis.8,15-20
As AATD progresses, patients may experience increasing limitations in physical activity and daily functioning. Symptoms such as shortness of breath, fatigue, exacerbations, and reduced exercise tolerance can contribute to a growing disease burden and diminished quality of life.3,7,8
Definitions: AAT=alpha-1 antitrypsin; AATD=alpha-1 antitrypsin deficiency; CAT=COPD assessment test; COPD=chronic obstructive pulmonary disease; FEV1=forced expiratory volume in 1 second; QoL=quality of life; SGRQ=St. George's Respiratory Questionnaire.
References: 1. Tejwani V, Nowacki AS, Fye E, Sanders C, Stoller JK. The impact of delayed diagnosis of alpha-1 antitrypsin deficiency: the association between diagnostic delay and worsened clinical status. Respir Care. 2019;64(8):915-922. 2. Meischl T, Schmid-Scherzer K, Vafai-Tabrizi F, et al. The impact of diagnostic delay on survival in alpha-1-antitrypsin deficiency: results from the Austrian Alpha-1 Lung Registry. Respir Res. 2023;24(1):34. doi:10.1186/s12931-023-02338-0 3. Choate R, Holm KE, Sandhaus RA, Mannino DM, Strange G. 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 4. 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. 5. Wells AD, Woods A, Hilleman DE, Malesker MA. Alpha-1 antitrypsin replacement in patients with COPD. P T. 2019;44(7):412-415. 6. Stoller JK, Tomashefski J Jr, Crystal RG, et al. Mortality in individuals with severe deficiency of α1-antitrypsin: findings from the National Heart, Lung, and Blood Institute Registry. Chest. 2005;127(4):1196-1204. 7. Choate R, Holm KE, Sandhaus RA, Mannino DM. Health-related quality of life in alpha-1 antitrypsin deficiency-associated chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2023;208(10):1132-1134. 8. 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. 9. Craig TJ, Corbett ML, Meadows JA. Improving detection of alpha-1 antitrypsin deficiency: role of the allergist. J Allergy Clin Immunol Pract. 2023;11(8):2348-2354. 10. Beiko T, Strange C. Anxiety and depression in patients with alpha-1 antitrypsin deficiency: current insights and impact on quality of life. Ther Clin Risk Manag. 2019;15:959-964. 11. Fähndrich S, Bernhard N, Lepper PM, et al. Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV1 in individuals with PiZZ alpha-1-antitrypsin deficiency. Respir Med. 2017;129:8-15. 12. Hiller AM, Piitulainen E, Tanash H. The clinical course of severe alpha-1-antitrypsin deficiency in patients identified by screening. Int J Chron Obstruct Pulmon Dis. 2022;17:43-52. 13. Franciosi AN, Alkhunaizi MA, Woodsmith A, et al. Alpha-1 antitrypsin deficiency and tobacco smoking: exploring risk factors and smoking cessation in a registry population. COPD. 2021;18(1):76-82. 14. Barjaktarevic I, Campos M. Management of lung disease in alpha-1 antitrypsin deficiency: what we do and what we do not know. Ther Adv Chronic Dis. 2021;12:49-63. 15. COPD Foundation. Genetic COPD. Reviewed April 17, 2025. Accessed August 19, 2026. https://www.copdfoundation.org/Learn-More/I-am-a-Healthcare-Provider/Genetic-COPD.aspx 16. Craig TJ, Henao MP. Advances in managing COPD related to α1-antitrypsin deficiency: an under-recognized genetic disorder. Allergy. 2018;73(11):2110-2121. 17. Quinn M, Ellis P, Pye A, Turner AM. Obstacles to early diagnosis and treatment of alpha-1 antitrypsin deficiency: current perspectives. Ther Clin Risk Manag. 2020;16:1243-1255. 18. Global Initiative for Chronic Obstructive Lung Disease (GOLD). GOLD Report. Accessed August 19, 2026. https://goldcopd.org/2026-gold-report-and-pocket-guide/ 19. Campos MA, Wanner A, Zhang G, Sandhaus RA. Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003. Chest. 2005;128(3):1179-1186. 20. Stoller JK, Brantly M. The challenge of detecting alpha-1 antitrypsin deficiency. COPD. 2013;10(suppl 1):26-34.
