Alpha-1 Antitrypsin Deficiency and COPD
Authors: Tomás Carroll and Anne Marie O’Dowd
Address: Alpha-1 Foundation Ireland, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9.
Introduction
Alpha-1 antitrypsin deficiency (AATD or more simply known as “Alpha-1”) is one of the most common genetic conditions in Ireland but surprisingly few people have heard of it. Before we talk about the condition, let us talk a little about the protein that can cause so much damage when it is missing.
Alpha-1 antitrypsin (AAT) is a protein made by our liver that has a very important job. It protects our lungs from damage caused by things we breathe in, such as cigarette smoke. In a sense, AAT acts like a protective shield for our delicate lungs. Alpha-1 antitrypsin deficiency is a genetic condition that leads to low amounts of faulty AAT in the blood. The knock on effect is that not enough AAT reaches the lungs and this can lead to lung damage and chronic obstructive pulmonary disease (COPD), especially if the person is a smoker (see Figure 1). Of note, people with Alpha-1 are also at risk of liver disease because the faulty AAT protein gets stuck inside the liver and can causes problem there. So the 2 main organs that can be affected in Alpha-1 are the lungs and the liver.
Figure 1. The alpha-1 antitrypsin protein and what happens when not enough is present in the body.
How common is Alpha-1?
Alpha-1 is hugely under-diagnosed in Ireland and the rest of Europe. This is because the lung symptoms are similar to asthma and COPD, for example, shortness of breath, wheezing, coughing, and regular chest infections. Many people with Alpha-1 have to wait many years before getting a proper diagnosis – a story that will be very familiar to people with COPD. People with lung problems caused by Alpha-1 will be often told at first “you must have been a smoker” and doctors may assume they smoked more heavily than is actually the case. People with COPD who have smoked very little or never may actually have undiagnosed Alpha-1. In the same way, people with liver disease caused by Alpha-1 are often told at first “you must have been a heavy drinker” when this may not be the case.
In the past Alpha-1 was considered very rare and so not many people were ever tested. Now we know that large numbers of people in Ireland are affected by both severe and moderate Alpha-1 (see Figure 2), with around 265,000 people estimated on the island of Ireland. The severe form of Alpha-1 is linked to high risk of COPD, even in never smokers. The moderate form of Alpha-1 means you have 1 copy of a faulty AAT gene (for example MZ or SZ genotype). For COPD to develop, someone with moderate Alpha-1 must have smoked or been exposed to fumes, dusts or gases for long periods, for example in a workplace like construction or farming. The positive is that if you have moderate Alpha-1 and never smoke or vape, you have no increased risk of lung problems.
Figure 2. The estimated numbers of people with severe AATD (ZZ) and moderate AATD (SZ and MZ) on the island of Ireland.
The continuing under-diagnosis of Alpha-1 is frustrating. We know that people with Alpha-1 who never smoke are unlikely to develop lung disease. So the earlier the diagnosis of Alpha-1 is made the better so smoking or vaping can be stopped before lung damage happens. An early diagnosis is also important to allow family screening to occur. This can identify more people at risk, particularly those who may be smokers, among siblings, children, and the wider family.
Alpha-1 Foundation Ireland has made efforts to tackle the continuing problem of under-diagnosis. For example, we have lobbied for better National COPD Guidelines that recommend testing for Alpha-1. This is not a new idea. Guidelines from the World Health Organisation way back in 1997 stated every person diagnosed with COPD should be offered the test for Alpha-1. Unfortunately, Alpha-1 seems to be the elephant in the COPD room that many doctors do not notice. Given the high rate of AATD in Ireland, we are hopeful that new COPD guidelines will recommend testing for Alpha-1 in all people with COPD, regardless of their age, or whether they smoked or not. This would lead to more people getting a correct diagnosis, and getting the right medical care and advice.
How Do I Get Tested for Alpha-1?
The test for Alpha-1 is a simple blood test. Your GP can take a blood sample and send it to the nearest hospital. The hospital will then send the sample to the Alpha-1 Foundation laboratory in the RCSI Centre at Beaumont Hospital who carry out the lab test for free as part of a HSE-funded national targeted detection programme for Alpha-1.
Of note, if you have a relative who has been diagnosed with Alpha-1, you should consider getting tested. This is because you will share many of the same genes as your relative, so you could be affected by Alpha-1 too. A good example can be seen in Figure 3 below. A phrase sometimes used is “the roots of COPD are in your family tree”. If COPD runs in your family, this could be a clue that Alpha-1 is involved.
Figure 3. A Large Irish Family Affected by AATD. 4 of the 10 children were born with severe AATD (ZZ) and 2 with moderate AATD (MZ).
How to Contact Us?
If you or anyone you know is affected by Alpha-1, you can find out more information at www.alpha1.ie, by ringing us on 01-8093871, or by sending us an email at alpha1@rcsi.ie. If you would like to be tested, Alpha-1 Foundation Ireland can provide you with a letter for your GP explaining the test in detail.