Alpha-1 Antitrypsin Deficiency
This page is intended for Healthcare Professionals and Persons Qualified to Prescribe or Supply.
What is Alpha-1 Antitrypsin Deficiency-Lung Disease?1,2,3
Alpha-1 Antitrypsin Deficiency (AATD) is a rare, genetic condition that results in a deficiency of alpha-1 antitrypsin, a protein that protects the lungs and liver against environmental damage, as well as against attack by neutrophil elastase, a key enzyme that the body releases during inflammation. Without this protein, or with defective proteins, inflammation has both acute and long-term effects.
People living with Alpha-1 Antitrypsin Deficiency-associated Lung Disease (AATD-LD) experience gradual, irreversible loss of lung function due to the permanent destruction of the lungs’ supportive elastic tissues. This can result in early onset emphysema or chronic obstructive pulmonary disease (COPD), even in the absence of smoking. This often starts in early adulthood.
AATD-LD treatment approaches include avoidance of cigarette smoke, use of inhalers to help control symptoms, and in some cases intravenous infusion of alpha-1 antitrypsin protein. These do not halt disease progression, and AATD-LD can be life-threatening and lead to the need for a lung transplant. However, a lung transplant does not remove the underlying cause of the disease, and the replacement lungs continue to experience progressive damage and consequent loss of function.
Assessing the impact of Alpha-1 Antitrypsin Deficiency-associated Lung Disease
To date, there is limited research on patients’ direct experiences of AATD-LD and, until recently, no clinical outcome assessment measures have been developed or validated specifically for this population.4
The St. George’s Respiratory Questionnaire for COPD (SGRQ-C) is well established in assessing health related quality of life across different chronic respiratory conditions, but had not been validated for use with AATD-LD.4
A recent study has evaluated the content validity of SGRQ-C for people living with the condition, as well as identified important symptoms and impacts that patients with AATD-LD experience.4
Participants reported a broad range of symptoms and impacts, with shortness of breath (dyspnea) and cough being the most common. Shortness of breath was endorsed by most as being the most relevant and important symptom. All participants reported experiencing some activity limitation due to AATD-LD, with physical activity limitations considered most important by just over half of participants.4
The study shows for the first time that the SGRQ-C is a valid measure of outcomes in this condition. It concluded that it is suitable as a clinical outcomes assessment endpoint in its current form.4
How many people are affected by Alpha-1 Antitrypsin Deficiency?
AATD is a genetic condition, which runs in families and can be passed on from parents to their children.2,5 The most severe form of AATD is found in people who have the Pi*ZZ or NULL genetic types, which mean that they produce either very low blood levels of abnormal protein or no protein at all. There are an estimated 50,000 people with severe deficiency (e.g., Pi*ZZ or NULL) in North America and some 60,000 in Europe.2,5
AbbreviationsÂ
AATD, Alpha-1 Antitrypsin Deficiency; AATD-LD, Alpha-1 Antitrypsin Deficiency-associated Lung Disease; SGRQ-C, St. George’s Respiratory Questionnaire for COPD.
References
- Chen CH et al. Front Pharmacol. 2024;15:1421598.
- Blanco I et al. Int J COPD. 2017;12:561–569.
- Silverman E et al. NEJM. 2009;360:2749-2757.
- Wells JM et al. Am J Respir Crit Care Med. 2025;211:A3677.
- Rodriguez-Frias F et al. Ther Adv Respir Dis. 2012;6(2):79-85.
