Researchers from 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.

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. The impact on the individual who develops this disease is significant and, according to medical literature, the average lifespan of an Alpha-1 is 54 years. The research being carried out by Professor 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.

The research has additionally been recognised as being in the top 2% of published articles in biology and medicine by the distinguished Faculty of 1,000. 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.

The research was also supported by 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 and Children.