Researchers from the Royal College of Surgeons in Ireland (RCSI) and Beaumont Hospital have made a breakthrough in understanding the mechanisms behind the most severe form of hereditary emphysema (alpha-1 antitrypsin deficiency, or Alpha-1) and how protein treatments can improve the condition. Please see our news & events section for the full article. You can also view articles on this research in the Irish Times and the Irish Health websites. This research was also described in the Irish Daily Mail and the Irish Daily Star. 

 

Researchers from the Royal College of Surgeons in Ireland (RCSI) and Beaumont Hospital have made a breakthrough in understanding the mechanisms behind the most severe form of hereditary emphysema and how protein treatments can improve the condition. The findings of this study may also lead to new treatments for patients with smoker’s emphysema.

The inherited condition, known as Alpha-1 Antitrypsin Deficiency (Alpha-1), results in the most severe form of hereditary emphysema.  Alpha-1 Antitrypsin is an important protein produced by the liver, from where it is released into the bloodstream and travels to the lungs to protect the lungs from disease.

In patients with the Alpha-1 condition, excessive amounts of white blood cells (neutrophils) enter the lungs and cause inflammation and chronic lung disease. Until now the cause of this was not fully understood but the researchers involved in this study have now uncovered the mechanisms behind the influx of white blood cells which causes the inflammation.

The condition is more common in Ireland than in most other countries with severe deficiency occurring in 1 in 2,000 of the population and 1 in 24 people carry the gene for the disease. After cystic fibrosis, Alpha-1 is the most common fatal inherited lung condition in Ireland and in its most severe form is estimated to affect more than 2,000 people nationally. The less severe form may affect as many as 300,000 individuals in Ireland. (1)

Professor Gerry McElvaney, Professor of Medicine at RCSI and senior author on the study commented: “Our study is the first to reveal the mechanisms by which a lack of the Alpha-1 protein causes an increase in white blood cells entering the lungs, leading to the development of lung disease. Our research also reveals how a treatment known as augmentation therapy, where the natural Alpha-1 protein is given intravenously, leads to a decrease in the white blood cells going into the lungs thereby decreasing inflammation. This research gives new hope for a better quality of life for sufferers of this chronic condition.”

The research may also be applied to those with smoker’s emphysema. Smokers render themselves deficient in the alpha-1 protein as chemicals in cigarette smoke destroys this important protein which protects their lungs.

“We are now exploring the possibility of treating smoker’s emphysema with the Alpha-1 protein” Professor McElvaney concluded.

Mr. John Walsh is President of the Alpha-1 Foundation, the US patient advocate group which provided research funding for this project. He was in Dublin recently to attend the Annual Chopin Recital in the Mansion House which aims to increase awareness of the condition and commented: “Typically Alpha-1 patients present with early onset emphysema somewhere between 35 and 45 years old (2). The impact on the individual who develops disease is significant and, according to medical literature in the US, the average lifespan of an Alpha-1 is 54 years (3). The research being carried out by Prof McElvaney and his team at RCSI Beaumont has really advanced the understanding of Alpha-1”.

 

In 2004, the Alpha One Foundation initiated the first national screening programme for Alpha-1 in the world with funding from the Department of Health and Children. So far this programme has tested over 5,000 individuals and found over 25% are at risk. 

The joint lead authors on the study are Dr David Bergin and Dr Emer Reeves from the Respiratory Research Division of RCSI’s Department of Medicine based in the Education and Research Centre at Beaumont Hospital in Dublin who worked with a team at the Centre and also collaborated with researchers at Dublin City University.

The study was published in the prestigious Journal of Clinical Investigation in December 2010. (4)

The research has additionally been recognised as being in the top 2% of published articles in biology and medicine by the distinguished Faculty of 1000. In their assessment, this study is a major contribution towards understanding the mechanism underlying excessive white blood cell (neutrophil) migration to the lungs of patients with hereditary alpha-1-antitrypsin deficiency. (5)

The research was also supported by the The Medical Research Charities Group/ Health Research Board, the Programme for Research in Third-Level Institutions (PRTLI) administered by the Higher Education Authority, the Alpha One Foundation (Ireland), Alpha-1 Foundation (USA) and the Department of Health & Children.

 

ENDS

(1)  Source: Alpha One Foundation (Ireland).

(2)  This figure refers to homozygote individuals (carry two defective genes)

(3)  Based on the largest longitudinal study which was done at the National Institute of Health in the United States

(4)  Reference: David A. Bergin, Emer P. Reeves, Paula Meleady, Michael Henry, Oliver J. McElvaney, Tomás P. Carroll, Claire Condron, Sanjay H. Chotirmall, Martin Clynes, Shane J. O’Neill and Noel G. McElvaney. α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8. Journal of Clinical Investigation. Vol. 20. No. 12. December 2010.

(5)   Faculty of 1000 Biology and Medicine: Evaluations for Bergin DA & Reeves EP et al., J Clin Invest 2010 Dec 1: http://f1000.com/7766956#eval8111055

 

 

 

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.

 

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 alpha1@rcsi.ie.