New Irish Study Shows carriers of the Z Alpha-1 Gene who smoke are at Increased Risk of COPD

Researchers from the Alpha One Foundation, the Royal College of Surgeons in Ireland and Harvard University have made a major breakthrough in identifying people who have an increased risk of developing COPD (chronic obstructive pulmonary disease) due to a combination of 1 copy of the Z Alpha-1 gene (MZ carriers) and exposure to cigarette smoke.

The research published in January in the American Journal of Respiratory and Critical Care Medicine, clarifies the risk of COPD linked to alpha-1 antitrypsin deficiency (Alpha-1), an inherited condition affecting almost 250,000 on the island of Ireland.

The research provides the strongest evidence yet that the estimated 1 in 25 people on the island of Ireland, who have inherited a combination of one normal (M) and one abnormal (Z) alpha-1 antitrypsin gene have an increased risk of the debilitating lung condition COPD. Cigarette smoke is the most influential factor in determining whether these individuals who carry this combination of genes (MZ) are at a greater risk of COPD compared to those who have two normal Alpha-1 genes (MM).

Given the very large number of people in Ireland who have the MZ combination of genes (one normal and one abnormal Alpha-1 gene), doctors leading the research stress that it is even more important than ever that people who have been diagnosed with COPD should be tested for Alpha-1. To date, approximately 1,500 people of an estimated 250,000 people on the island of Ireland have been identified with the (MZ) gene combination.

Professor Gerry McElvaney, Professor of Medicine at RCSI, principal investigator and chairman of the Alpha One Foundation Ireland, said "This research signals a major breakthrough in understanding the heightened risk of COPD for people who have the combination of one normal and one abnormal alpha-1 antitrypsin gene. If people know that they have a genetic predisposition to developing COPD, it allows intervention at an earlier age, encourages smoking cessation and prevents a further decline in lung function in a disease that is otherwise preventable. It also provides an opportunity for other family members to get tested for Alpha-1."

"Funded by the Department of Health and Children, the Alpha One Foundation provides a free national screening programme for Alpha-1, the only national screening programme in the world. We strongly urge people to avail of this service, particularly if they have COPD. Also as Alpha-1 is a hereditary disease, we recommend that all first degree family members of individuals with Alpha-1 should be tested. Alpha-1 can be easily diagnosed by a simple blood test. For more information on how to be tested, contact the National Centre for Alpha-1 based at Beaumont Hospital, Dublin." added Professor McElvaney.

Dr. Kevin Molloy, Royal College of Surgeons in Ireland, the lead author of the study said "Alpha-1 is a common inherited condition that is massively under-diagnosed both in Ireland and internationally. As this research has an impact on a large number of people who have the MZ gene combination, the research will greatly increase awareness and diagnosis of Alpha-1. Knowing that you have a genetic predisposition to developing COPD should encourage people to avoid exposure to cigarette smoke if they definitively know they have a higher risk of developing this debilitating lung condition."

"250 individuals from 51 Irish families took part in the research which set out to determine the risk of COPD for people who carry one normal and abnormal Alpha-1 gene. The participants were first degree family members of individuals with the confirmed MZ gene combination. The research used a unique study design which removed a lot of uncertainty from previous attempts to assess the risk of developing COPD for people who have the MZ gene combination." added Dr. Molloy 

This piece has featured in a variety of local and national newspapers (for example Irish Times, Irish Independent, and Irish Examiner) and radio stations around the country and was featured on a segment on TV3 news.


Research Breakthrough in Understanding Alpha-1 by Irish Scientists

The Irish Times, the Irish Examiner, the RTE website, the Evening Herald and several other newspapers have this week (January 13th) reported a new discovery by scientists based at the Royal College of Surgeons of Ireland and Beaumont Hospital.  These scientists have discovered how a protein, known as alpha-1 antitrypsin (AAT), which is produced by the liver, plays a significant role in reducing inflammation from white blood cells and its overall importance for good health. Their research findings were published in this month's edition of Science Translational Medicine, a prestigious journal that highlights medical advances resulting from scientific research.

The study revealed for the first time how a lack of Alpha-1 protein leads to increased levels of white blood cell proteins, which in turn cause an autoimmune response that produces harmful oxidants and can lead to the development of the lung disease COPD.

The scientists, including RCSI Professor of Medicine Gerry McElvaney, Dr David Bergin and Dr Emer Reeves from the Respiratory Research Division of RCSI's Department of Medicine, also revealed how a treatment, known as augmentation therapy where Alpha-1 protein purified from blood is given intravenously, can ease the autoimmunity leading to the disease. As a result, Prof McElvaney said the research gives new hope for a better quality of life for sufferers of this chronic condition and may also be applied to other autoimmune associated diseases, such as rheumatoid arthritis.

The research was funded by the Medical Research Charities Group/ Health Research Board, the Alpha One Foundation (Ireland) and the Alpha-1 Foundation (USA).


International Collaborative Study To Establish The 1st International (WHO) Standard for Alpha-1 Antitrypsin

Irish scientists based at Beaumont Hospital have been involved in a multicentre study to determine the first ever international standard for alpha-1 antitrypsin. This study will make it easier for research groups and pharmaceutical companies to assess the activity and potency of different preparations of alpha-1 antitrypsin being used as a therapeutic agent.

International Collaborative Study To Establish The 1st International (WHO) Standard For Alpha-1 Antitrypsin

Craig Thelwell1, Peter Rigsby2 and Colin Longstaff1
1Biotherapeutics Group, Haemostasis Section and 2Biostatistics Division, National Institute for Biological Standards and Control, South Mimms, Herts EN6 3QG, England.

An international collaborative study was organised to establish the 1st International Standard (IS) for Alpha-1-Antitrypsin (AAT) as agreed at the Alpha-1 Foundation Workshop in April 2005, Cincinnati, USA. The study involved 15 laboratories from 10 different countries. Laboratories were provided with detailed methods and critical reagents and were asked to measure the potency of four candidate standards (A, 05/150; B, 05/152; C, 05/162 and D, 05/172). In addition laboratories with relevant experience were invited to carry out extended characterisation of the materials, including total protein and antigen content for which an additional reference preparation was provided. Analysis of the data indicated that any of the candidates would be suitable based on potency determination; however candidate C had a slight advantage based on filling data. It is therefore proposed that candidate C (05/162) be adopted as the 1st International Standard for Alpha-1-Antitrypsin with a potency of 243 nmoles (12.4 mg) active AAT per ampoule.

A copy of the full publication can be viewed here.

What is Alpha-1 Antitrypsin?
Alpha-1 antitrypsin is a vital protein produced by the liver to protect the lungs. It provides protection from the harmful effects of infections and inhaled irritants, particularly tobacco smoke. It can be easily measured by a simple blood test. 
What is Alpha-1 Antitrypsin Deficiency?
Alpha-1 antitrypsin deficiency (Alpha-1) is a genetic condition which, after cystic fibrosis, is the commonest genetic disorder in Ireland. It severely affects more than 15,000 people, with another 250,000 carriers also at risk of lung and liver disease on the island of Ireland. It is a proven genetic risk factor for chronic obstructive pulmonary disease (COPD).
How Do I Get Tested?
The Alpha One Foundation provides free testing for Alpha-1 as part of a national screening programme which is funded by the HSE. For more details ring 01-8093871 or email