The Cause of COPD You Don't Know: Alpha-1 Antitrypsin Deficiency
Imagine a daily reality in which every breath is a struggle and fatigue a constant companion. For many people living with alpha-1 antitrypsin deficiency (also known as “AATD”), a rare genetic condition, this is their lived experience. These aren’t just surface-level symptoms; they’re critical signs of progressive underlying lung and liver damage that often go undiagnosed, as the manifestation of AATD shares the same symptoms of better-known respiratory conditions such as chronic obstructive pulmonary disease (COPD).1,2 While AATD can cause COPD, it’s the COPD you don’t know—the version with a genetic cause, resulting from when a person’s blood serum does not have enough or any detectable alpha-1 antitrypsin (AAT), an important protective protein.2 In short, the COPD caused by AATD.
The Missing Protein
The AAT protein is produced in the liver and helps protect the lungs from inflammation and damage. But for individuals with AATD, a genetic mutation means this vital protein is either insufficient or not detectable in the lungs.2,3 What’s more, abnormally shaped AAT can get trapped in the liver, causing damage there, while simultaneously the lungs can be left vulnerable and unprotected because not enough AAT gets into circulating blood serum.2 The result? Consistently low or absent levels of AAT leading ultimately to irreversible deterioration of lung function.2,4 The goal of treatment is to raise these AAT levels in an individual’s lungs and bloodstream.5
Alpha-1 Antitrypsin Deficiency (AATD) Is an Inherited Condition ²,³
The Challenge of Diagnosis
The insidious nature of AATD lies in its 'nonspecific' symptoms— most commonly shortness of breath and wheezing—which are easily overlooked in early stages.2 This ambiguity means the genetic underpinnings of AATD can be missed and individuals are diagnosed with and treated for other conditions—such as environmental COPD, emphysema, asthma and chronic bronchitis.2,4 It is recommended that all COPD patients be screened for AATD, but all too often, that doesn’t happen.1 And the treatments for these other lung conditions do nothing to address the lack of AAT.
The staggering numbers? An estimated 90% of individuals with severe AATD remain undiagnosed.6 Globally, 235,000 people worldwide live with AATD and represent 1-3% of the global COPD population.7,8 This means no matter how much they seek to manage their COPD with medication, oxygen therapy or lifestyle changes, it won’t address the true underlying cause.
The Urgency of Early Intervention
Early and accurate identification of AATD is crucial. Time is literally lung health. This is especially true for early-onset cases of AATD in younger people aged 20-50 years old, when intervention could lead to better health outcomes.9,10 Yet, people living with AATD wait an average of eight years for a diagnosis from the time they first experience symptoms.11 Delays in diagnosis compound into delays in receiving treatment, which can put those living with AATD at risk for irreversible lung damage.9,10
Addressing the Unmet Need
There is a twofold unmet need in AATD: more comprehensive screening and diagnosis and—for those who are diagnosed—additional options to manage the disease. The AATD community is eager for innovations that aim to address the underlying cause of AATD—treatments that increase AAT levels and offer convenient dosing schedules, helping to reduce the burden on patients.
At Sanofi, we are leveraging our extensive experience in rare respiratory diseases to take action in pursuing recognition and innovation for conditions like AATD. We strive to deliver support and solutions for people managing rare diseases that persist with unmet needs.
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References
- Alpha-1 Antitrypsin Deficiency Symptoms and Diagnosis. American Lung Association website. https://www.lung.org/lung-health-diseases/lung-disease-lookup/alpha-1-antitrypsin-deficiency/symptoms-diagnosis. Updated October 2024. Accessed October 2025.
- Alpha-1 antitrypsin deficiency. MedlinePlus Genetics website. https://medlineplus.gov/genetics/condition/alpha-1-antitrypsin-deficiency/. Accessed October 2025.
- Learn About Alpha-1 Antitrypsin Deficiency. American Lung Association website. https://www.lung.org/lung-health-diseases/lung-disease-lookup/alpha-1-antitrypsin-deficiency/learn-about-alpha-1-antitrypsin-defiency. Updated March 2025. Accessed October 2025.
- Cazzola M, Stolz D, Rogliani R, et al. α1-Antitrypsin deficiency and chronic respiratory disorders. Eur Respir Rev. February 2020;29(155):190073.
- Wells AD, Woods A, Hilleman DE, et al. Alpha-1 Antitrypsin Replacement in Patients With COPD. PT.July 2019;44(7):412–415.
- Aboussouan L, Stoller JK. Detection of alpha-1 antitrypsin deficiency: a review. Respir Med.2009;103(3):335-41.
- Smith G, Singh K. Alpha-1 Antitrypsin Deficiency: Navigating Challenges Through Collaborative Innovation. Chest. December 2024;166(6):1288-1290.
- Pfeffer DN, Dhakne R, El Massad O, et al. Improving the Likelihood of Identifying Alpha-1 Antitrypsin Deficiency Among Patients With COPD: A Novel Predictive Model Using Real-World Data. Chronic Obstr Pulm Dis. 2025;12(1):1-11.
- Brantly M, Campos M, Davis AM, et al. Detection of alpha-1 antitrypsin deficiency: the past, present and future. Orphanet J Rare Dis. April 2020;15:96.
- Turner AM, Ficker JH, Vianello A, et al. Advancing the understanding and treatment of lung pathologies associated with alpha 1 antitrypsin deficiency. Ther Adv Respir Dis. February 2025;19:17534666251318841.
- Campos MA, Wanner A, Zhang G, et al. Trends in the diagnosis of symptomatic patients with alpha1-antitrypsin deficiency between 1968 and 2003. Chest. September 2005;128(3):1179-86