Delegate Report from the 4th International Alpha-1 Patient Congress 2013

The 4th International Alpha-1 Patient Congress and International Research Conference on Alpha-1 Antitrypsin Deficiency took place in Barcelona in April this year.

We were privileged to be asked to attend as country delegate and patient representing the Alpha One Foundation in Ireland. This gave us the opportunity to mingle with patients, doctors and scientists with expertise in Alpha-1 Antitrypsin Deficiency. The Research Conference focussed on Alpha-1-related liver disease and invited expert scientists from some 20 countries worldwide to update and discuss their ongoing research. It was evident that much research is taking place in each country and the conference offered us the opportunity to hear about observations and findings through the various country representatives. In future, the conference will act as a forum for the exchange of ideas between researchers worldwide.

 Fourth International Alpha-1 Congress

As you are already aware, 2013 is the year in which the Alpha One Foundation celebrates 50 years since the discovery of Alpha-1 by scientist Sten Eriksson who was also present at the conference. Over the two days, we heard about the research carried out since its discovery and had some valuable feedback and perspective from patients on the various interventions and treatments they have undergone and the benefits they have derived from them. It was also clear that the Patient Groups in each country shared common goals and each had five key objectives, namely: 1. Raising Awareness, 2. Support and Information for Patients and Families, 3. Augmentation Therapy (clinical trial results and lobbying), 4. Early Diagnosis of Alpha-1, and 5. Scientific Research

For the purposes of this report, we would like to share with you a number of topics or messages that particularly resonated with us during the conference, namely Augmentation Therapy, Registries, and Alpha - Self Care.

Augmentation or Replacement Therapy: Consists of weekly infusions of a human plasma based product. In the United States replacement therapy became available in 1986 following small limited research studies. The biochemical efficacy of replacement therapy is still being investigated by European countries. It was also reassuring to learn that there are many more therapies being researched including Gene Therapy, Gene Correction, Cell Therapy and Inhaled and Intravenous Replacement therapy.

Registries: The challenge facing the Alpha One Foundation is to gather data to support the effectiveness of this expensive therapy and to lobby the various country Health representatives to gain support for the treatment. This is an on-going process. Trials and studies are taking place but take time. Countries also need to build up their registries of Alphas to be able to provide data on numbers of Alphas and demonstrate the occurrence of the disease within each country. Alpha One Foundation in Ireland is doing well in this area and has specifically targeted health providers to educate them on the importance of testing patients presenting with certain symptoms and in addition have encouraged Alphas to have family members tested which has added considerably to the registry.

Alpha – Self Care: Doctors at the conference provide some practical advice around patient self-care and nutrition. One of the key messages to all Alpha patients who currently smoke or passively smoke was to quit smoking and ensure that your living environment is free from smoke. They also highlighted the importance of exercise to maintain fitness and muscle strength and conditioning. This in turn contributes to improved breathing, positive mental health and quality of life.
We were also inspired by Dr. Fedon Lindberg’s talk on nutrition. He advocates the Mediterranean diet which is rich in vegetables, fruit, beans, nuts, seeds, healthy fats such as olive oil and low in salt and sugar (the main culprits which cause inflammation in the body).
We hope this short report serves to provide you with a brief insight into the conference this year. This conference was a wonderful opportunity for patients, doctors and scientists to come together to share first hand health experiences, observations, expertise and research about a disease close to their hearts and was a very definite step closer to achieving our common goal to discover a cure for Alpha-1 Antitrypsin Deficiency.

Report by: Fidelma Furey (Country Delegate), Martin Furey (Alpha-1 Patient). Also attended by Orla Keane and Josephine McGuirk (Alpha-1 patients).

 

Flora Women's Mini Marathon

Congratulations to all the ladies who took part in this year’s Flora Women’s Mini Marathon on the June Bank Holiday weekend. We are very grateful for every fundraising effort which helps us to continue our national screening programme for Alpha-1.

All fundraising events are much appreciated and we are happy to help you organise any event in your own local area.

Fourth International Alpha-1 Patient Congress April 11th 2013

Dear Friends of Alpha-1,

In April 1963, Swedish researchers Carl-Bertil Laurell and Sten Eriksson published their landmark research on the discovery of Alpha-1 Antitrypsin Deficiency. To commemorate the 50th anniversary of the discovery, the Fourth International Alpha-1 Patient Congress and an international Research Conference on Alpha-1 Antitrypsin Deficiency will be held in Barcelona, Spain, April 11th - 13th, 2013.

Alphas from all over the world are welcome to attend the Congress, and Alpha-1 patient associations from many countries are expected to send delegates. The Research Conference will be held April 11-12, and there will be a joint session of patients and scientists on the afternoon of Friday, April 12.
National Patient Associations can name two delegates per country as guests of the meeting organizer for two nights, with travel, hotel and meals included.    
Please let me know who plans on attending from your Association. Log on to the conference website at www.alpha-1barcelona2013.org for further information.
Please also consider posting a story on your Associations website with a link to congress website.

Kind Regards,

Angela McBride
Steering Committee Barcelona Congress
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

 

Alpha-1 Patient Involved in Rare Disease Day 2012

The 29th of February 2012 is the 5th International Rare Disease Day, and to raise awareness of this day a promotional video was recorded featuring people who have a rare disease. The video was shot in Dublin and includes one of our Alpha-1 patients, Josephine McGuirk.

The rare disease awareness video can be seen here. You can also read Josephine's story in her own words here.

 

Report from Alpha-1 Patient Conference 2011

The Annual Alpha-1 Patient Conference for 2011 was a big success. Thanks to everyone that turned up on the day. The Alpha-1 Patient Support group had a successful meeting in the afternoon. They discussed future fundraising and awareness projects and got plenty of ideas from Angela McBride, Director of Development, Alpha-1 Foundation, USA. If anyone would like to get involved in further fundraising or has any ideas, please contact us at This email address is being protected from spambots. You need JavaScript enabled to view it. or Phone: 01-8093871.

Report from Alpha-1 Patient Conference 2010

Our annual Alpha-1 patient meeting for 2010 was held on the 8th of October in Marino Institute of Education on Griffith Avenue in Dublin.  It was a great success with numerous speakers, a question and answer session with Professor McElvaney, a patient support group meeting and a relaxation workshop.  Updates of the meeting have been sent in the post by Kitty and copies of the presentations are available below.

Our first speaker was Margaret Webb, CEO of Debra Ireland who discussed rare diseases and the importance of a national strategy for rare diseases. This was an illuminating talk, with Margaret keen to stress that newly diagnosed Alpha-1 patients should not feel isolated as over 150,000 people in Ireland suffer from some type of rare disease. Dr. Tomás Carroll followed with a discussion on Alpha-1 and its prevalence in Ireland. Research completed by the McElvaney group in Beaumont Hospital has shown that Alpha-1 is twice as prevalent as previously estimated, with 1 in 24 Irish individuals carriers for the Z mutation, which causes >98% of all cases of Alpha-1. This is one of the highest rates of Alpha-1 in Europe. Dr. Carroll also discussed the targeted detection programme for Alpha-1 which involves the majority of Irish Hospitals and how testing for Alpha-1 Deficiency is performed. Professor McElvaney followed up Dr. Carroll’s presentation with a lively question and answer sessions with plenty of questions provided by the Alpha-1 patients themselves. These questions covered the different Alpha-1 genes, genetic inheritance, disease symptoms and possible treatments. 

Two further presentations were given before lunch changing the focus of the meeting to patient entitlements. Elaine Bradley from the revenue online service (ROS) spoke about tax entitlements for chronic illness. Elaine then detailed what a patient can claim for including service of a practitioner, diagnostic procedures, supply of drugs and medical appliances, and nursing home fees. These claims can be made via the Med1 form or if the claim is for dental work the Med2 form. Self-employed people use Form 11. These forms are available on the following website:  http://www.revenue.ie/en/tax/it/leaflets/it6.html

The final talk before lunch was from Cristina Santamaria from Northside Citizen Information. She explained that her office was just one of 42 citizen information services located throughout the country. Their role is to provide appropriate information, advice and advocacy services for the needs of the local citizen. The majority of queries they deal with are related to social welfare and the health service. Cristina went through social welfare benefits which may be relevant for Alpha-1 patients such as illness benefit, invalidity pension, carer’s benefit, medical cards and the drug payment scheme. For any further help and advice on any of these benefits you can visit their website http://www.citizensinformation.ie/ or Lo-call 1890 777 121.To find your local service please see http://centres.citizensinformation.ie/. 

After lunch there was a patient support group meeting more of which is discussed in the patient support group section. The final presentation of the day was on stress management and relaxation techniques. In this workshop Michelle McGettigan and Olive Gibson from the Health Promotion Unit in Beaumont Hospital described to a captive audience what exactly stress is, how it can be managed, and more importantly how we can eliminate it from our lives. One of these techniques was a 20 minute meditation period that everyone participated in leaving us all relaxed and revived for the journey home.

Thanks again to everyone who attended,

The Alpha One Foundation.

 

Annual Alpha-1 Patient Meeting 2009

The annual Alpha-1 patient meeting will be held on Saturday 10th October at 10.30am in Marino Institute of Education on Griffith Avenue, Dublin 9. All Alpha-1 patients and their families are invited to attend this forum. Invited speakers will be discussing issues relevant to Alpha-1 patients, including disease management, current research, and ongoing clinical trials in Beaumont Hospital.

 Alpha-1 affects the lungs and liver, causing emphysema in the lungs and cirrhosis of the liver. These can be life threatening conditions in both adults and children. Recent research from our group has shown that over 2,100 Irish people have severe Alpha-1, which is usually undiagnosed or misdiagnosed as something else e.g. chronic obstructive pulmonary disease (COPD) or asthma.

•    It is vital to highlight that Alpha-1 is not a rare disease, but a disease that is rarely diagnosed.
•    Our national targeted detection programme screens all COPD, asthma, liver disease patients and relatives of Alphas. Early diagnosis is essential. We show Alpha-1 individuals diagnosed early have fewer symptoms and significantly better lung function.
•    The Foundation’s research demonstrates a much higher incidence of Alpha-1 in Ireland than previously thought, with over 2,100 individuals at risk of developing severe disease.
•    In addition we have shown there are over 200,000 Alpha-1 carriers in Ireland who possess one copy of the harmful gene.  These patients are also at increased risk of developing emphysema, particularly if they smoke.
•    Identification of patients from a targeted detection programme should include aggressive family screening and allow the initiation of preventative measures before significant lung disease has occurred.

Prof. Gerry McElvaney, Professor of Medicine RCSI and consultant respiratory physician in Beaumont Hospital states;
“Our research and experience with Alpha-1 patients and other respiratory diseases point to the fact that there is a great need for a National Respiratory Strategy to co-ordinate the proper diagnosis and treatment of Alpha-1 and other respiratory conditions. Our studies clearly show it is vital for the health and welfare of our patients that they are diagnosed as early as possible, before they develop symptoms.”

For further information contact: Kitty O’Connor, CEO Alpha One Foundation on 01-8093871 or This email address is being protected from spambots. You need JavaScript enabled to view it..

The Alpha One Foundation supports the Irish Donor Network - Always carry a Donor Card.

Flora Women's Mini Marathon 2009

The Flora Women's Mini Marathon takes place on Monday 1st June 2009. This is a unique opportunity for Alphas and their families in alliance with the Patient Support Group and the Alpha One Foundation to raise funds for research and increased awareness into alpha-1 antitrypsin deficiency (Alpha-1).

This year we are raising funds for equipment used in our research laboratory. This vital piece of equipment costs €10,000. Sponsorship cards and T-shirts are available from the Alpha One Foundation at 01-8093871 or www.florawomensminimarathon.ie. Members of the Patient Support Group and Alpha One Foundation are participating in the event, meaning patients can raise funds by collecting money on behalf of these participants. We understand many patients may not be able to take part in this event themselves. For further details contact Kitty on 01-8093871 or log on to www.florawomensminimarathon.ie.

Alpha-1 can cause life threatening conditions in both adults and children. It is estimated that 3,000 people on the island of Ireland have Alpha-1 which is either undiagnosed or misdiagnosed as something else e.g. COPD or asthma. Our research demonstrates a much higher incidence of Alpha-1 on the island of Ireland than previously thought, with an estimated 3,000 individuals at risk of developing this severe disease. Alpha-1 individuals identified as a result of family screening have significantly increased lung function when compared to Alphas identified by targeted symptomatic screening. Our results emphasize the need for increased awareness and early detection of asymptomatic Alpha-1. Identification of patients from a targeted detection programme includes thorough family screening and this allows the initiation of preventative measures before significant lung disease has occurred. 

Prof Gerry McElvaney, Prof of Medicine, RCSI and Beaumont Hospital states “our research and experience with Alpha-1 patients and other respiratory diseases, point to the fact that there is a great need for a National Respiratory Strategy to co-ordinate the proper diagnosis and treatment of Alpha-1 and other respiratory conditions. Our studies clearly show it is vital for the health and welfare of our patients that they are diagnosed as early as possible, before they develop symptoms.”

Alpha One Foundation supports the Irish Donor Network - Always carry a Donor Card.

 

Patient Report from 3rd Alfa Europe Alliance Meeting 2008

An Irish Alpha-1 patient Orla Keane had the opportunity to attend the 3rd Alfa Europe Alliance Meeting in Prague from May 9th to 10th.

Irish Delegate Report from the Third Alfa Europe Meeting, May 2008

Agenda
Dr. Thomas Köhnlein MD, Hannover Medical School
Ongoing researches into alpha1-antirypsin deficiency
Dr. Pawel Kuca MD, National TB and Lung Diseases Research Institute,
Epidemiology and detection program in Poland MU
Dr. Jan Chlumský Ph.D., Department of Pneumonology, Thomayer Teaching Hospital, Prague
Situation of alpha-1 patients in the Czech Republic
Klaus Schäfer, Talecris Biotherapeutics GmbH
Replacement therapy and Europe

Topics
1. Lung rehabilitation
2. Access to therapies
3. Access to insurance, mortgage, pension
4. Genetic discrimination within Europe

All delegates gathered at the Hotel Don Giovanni on the afternoon of Friday 9th May. We were welcomed to Prague by the Federation President, Larry Warren CEO of the Alpha One Foundation Ireland and Silke Horakava from the Czech Alpha Group who were our hosts for the Conference. The AGM, initially consisted of voting and legal formalities, Larry Warren presented his President’s Report; in this he outlined events of the Conference in Rome last year.  

    * The alliance of the Alfa Europe Federation & the European Alpha-1 Foundation, has given the Federation a more stable footing and financial backing to run the Organisation and develop
    * The Federation membership is growing, with France and the Czech Republic joining this year and Poland, UK, Scotland and Portugal soon to be joining
    * It is important that The Federation is recognised by the EU Commission as a patient support partner, in order that Alpha Europe becomes recognised in the EU, this will eventually be for the benefit of all Alpha patients and their families
    * Larry Warren reported that the Federation already
          o Is a member of the Plasma and Protein Users group, which meets 4 times a year to look at the supply of produce etc
          o Has been accepted as a member of EURORDIS, the European Alliance for patients with rare diseases
          o Has applied for membership of EPPOSI, which is an alliance of patient groups, science and industry
          o Intends to build a working relationship with AIR, the Alpha-1 International Registry.
          o The above will ensure that the Federation is part of the planning for therapies, registries or any other matters that will affect Alpha sufferers
    * This year France has the EU Presidency and they have already given notice to the Federation that the French Government wishes to raise the profile of rare diseases (such as Alpha-1) in the EU and look at how they are tackled and will hopefully draw up directives and recommendations to the Parliament and Commission, these will then be passed down to National Governments
    * In order to raise the awareness of Alpha-1 within the EU, delegates were asked to take back to their various groups and associations a request that Alpha patients right to their local MEPs telling them about Alpha-1 as an illness, how it affects them personally and their families lives and the problems they encounter with receiving treatments, therapies and reimbursements.

Nuccia Gatta, who has been Vice President and last year hosted the Rome Conference, explained how Italy along with Holland and Germany, have been doing the PAAIR (a collaboration between Patient Associations - PA - and the Alpha-1 International Registry - AIR), this will give the EU an example of how individuals involved in a rare disease can organise themselves to improve the diagnosis, care and treatment of a disease and the impact this has on patient care. We next went on to the Treasurers report, given by Juergen Schultz, explained that the Federation now had finance coming in from the Foundation, this apart from the 50euros membership fee paid by each member country, is, at present, the Federation’s main source of income. Conferences are funded by the Foundation, although the World Conference in Rome was funded by outside organisation. After discussion of the reports, the meeting moved on to electing officers

    * President - Larry Warren
    * Vice President - Sandrine Lefrancois (nominated from the floor, Nuccia Gatta stood down)
    * Treasurer -  Juergen Schultz
    * Auditor - Elke Sadtler-Lison

By Orla Keane,
May 2008.

Patient Report from the European Alpha-1 Conference, Rome 2007

The Alpha One Foundation had two representatives, Josephine McGuirk and John Hannan, attending the European Alpha-1 Conference which was held in Rome in September 2007. This was a great opprtunity for Irish Alphas to meet other Alphas from all over Europe and to learn about the latest developments in the field of Alpha-1.

Patient Report from the European Alpha-1 Conference, Rome 2007
Delegates from 21 countries world wide gathered with fellow patients, carers, medical experts and pharmaceutical company representatives in the Eternal City for the 3rd Alpha-1 Patient Congress, hosted by the Italian Alpha-1 Association, on the weekend of 28th-30th September, 2007. The Alpha One Foundation had two representatives present at the congress, myself and John Hannan.

The Conference began on the evening of the 28th, when the assembled delegates and guests were welcomed by Larry Warren, our own CEO and President of Alfa Europe and Nuccia Gatta, President of the Italian Alpha-1 Association and Vice President of Alfa Europe.  At this stage Larry gave a warm welcome and thanks to the Medical Professionals, who were attending the Conference, for their continued care and support, also to the Pharmaceutical Companies for their support.
Larry Warren reported that the Alfa Europe Federation was now a legally recognised and registered organisation. It will be an organisation of many languages and cultures, and it is hoped will prove to be a voice in the EU that will increase awareness of Alpha-1 and promote more, much needed research into the illness. To open the Conference all the Delegates we asked to give a brief presentation to show how their individual patient groups were working and how they were moving forward. 21 countries were represented, including for the first time the Czech Republic, who have only recently set up an AATD centre. In addition to European countries there were delegates from the USA, Puerto Rico, Argentina, Australia and New Zealand. Some countries have had patient groups for a number of years while others have only recently been formed. Patient groups were proactive in many aspects of their organizations, such as the setting up of support networks for patients, regional groups, supporting research programmes, advocating for clinical trials, working closely with the medical professionals, and producing leaflets and newsletters explaining about Alpha-1. Saturday began at 9am, with a presentation from John Walsh, Irish-American Alpha-1 patient and President of the Alpha-1 Foundation in the USA, entitled “Patients Empowerment”. This talk proved to be very motivating. John first said how encouraging it was to see so many countries sending delegates to the conference. He said that patient groups give Alpha-1 patients  

    * Inspiration through collective and shared experience
    * Courage to do things
    * Empowerment to take action, through frustration and desperation
    * Self confidence and power
    * Alphas serving Alphas

Patients groups involve not only patients but loved ones, wider groups, communities, medical professionals, scientists, and also challenge patients to get up and become involved, and can encourage healthcare industries to aid research into therapies. Continuing with his presentation, John said how he had picked up common themes from all the delegates-

    * Lack of awareness, low detection rates and diagnosis
    * Lack of resources
    * Limitation on access to therapies in some countries
    * Start up Charities
    * Limited or no support for patients
    * Transplant issues
    * The more aware the better the cure
    * Quest for a cure(s) to conquer or eradicate the illness

The one message that came through is that there is under diagnosis, mis-diagnosis, and a lack of awareness and understanding amongst the medical profession and the general public of Alpha-1. It is patient groups who can change this, by making sure hospital consultants, GPs, nurses, family and friends know about the illness and the effect it has on people’s lives, not just sufferers, but their carers and families.  

Josephine McGuirk, October 2007.

 

A Selection of Abstracts from Rome Conference 2007  

ALPHA-1 ANTITRYPSIN DEFICIENCY: WHERE WE ARE, WHERE WE ARE GOING TO

Maurizio Luisetti, Center for Diagnosis of Inherited Alpha-1 antitrypsin Deficiency, Laboratory of Biochemistry and Genetics, Institute of Respiratory Disease, University of Pavia, Fondazione IRCCS, Policlinico San Matteo, Pavia, Italy

At the beginning of the 1960s, two scientists in Sweden, Laurell & Eriksson, associated missing bands on paper electrophoresis in sera with subjects suffering from pulmonary emphysema and chronic liver disease. This was the first report of a disorder since then referred to as “Alpha-1 antitrypsin Deficiency” (AATD). Now, 44 years after the discovery, AATD is in its middle age, and an astonishing amount of data have accumulated during four decades. We have currently a satisfactory view of the AATD epidemiology, at least in western countries; we have gained a good level of knowledge about the pathogenesis of lung and liver disease. We have developed suitable methods for laboratory identification of protein and molecular abnormalities linked to AATD. A number of national registries for AATD have been established, as well as national patient support groups, and their federations work together for a better awareness of the disorder. Replacement therapy is available in a growing number of countries, and several hundreds of AATD subjects with lung disease are currently treated. But a number of relevant questions are still unanswered, and we hope we are able to offer satisfactory answers to these question in the next future. Basic questions, such as the definition of the exact ratio between asymptomatic individuals affected by AATD and individuals affected by AATD which develop lung/liver disease (and, more importantly, what differentiates the latter from the former), and clinical questions, such as the development of more effective “replacement” therapies, are among the questions AATD patients ask the scientific community. This is a commitment for the future.
 
PATHOGENESIS OF LIVER INJURY IN ALPHA-1-ANTITRYPSIN DEFICIENCY
F. Callea, Department of Pathology, Children’s Hospital Bambino Gesù, Rome, Italy.

Liver pathology is a major manifestation of Alpha-1-antitrypsin deficiency (AAT), restricted to the AAT mutations causing misfolding of the protein and accumulation in the Endoplasmic Reticulum (ER) of hepatocytes. So far three such mutations have been identified, Z, Mmalton, Siiyama, the Z variant being the most frequent. The spectrum of the associated liver pathology comprises neonatal cholestasis, chronic hepatitis, cirrhosis and HCC. The mechanism of the liver damage is not fully understood. There are two major lines of thinking: 1) the storage is toxic per se, 2) additional factors are required for the development of the liver damage. The main argument favouring the second opinion is mainly based upon the observation that only a minority of AAT deficient individuals develop liver disease. I would like to emphasize the point that the accumulation of the mutant AAT represents per se the elementary lesion of the disease and that is an unavoidable process. In this context I will be reviewing the patho-morphogenesis of the storage phenomenon and the main morphological alterations with special regard to new electron microscopic findings. The epidemiological and clinical relevance of the morphological alterations are discussed also in view of the new experimental data on the pathways for degradation of the mutant proteins that accumulate in the ER.

PATHOGENESIS OF LUNG DISEASE
David A. Lomas, University of Cambridge, Cambridge, UK.

Alpha-1 Antitrypsin is produced from the liver and bathes all the tissues of the body. Its role is to protect against tissue damage from enzymes released from neutrophils. The genetic deficiency of alpha-1 antitrypsin that results from the Z mutation causes the protein to form polymers that are retained within the cells of the liver. This retention of protein causes liver disease. The resulting lack of plasma alpha-1 antitrypsin (10-15% of normal levels) leaves the lungs exposed to attack by neutrophil enzymes and so results in emphysema. We have recently shown that some of the alpha-1 antitrypsin that enters the lung can change shape and form chains of polymers. These polymers are unable to function as inhibitors of neutrophil enzymes and so exacerbate the tissues damage. Moreover the polymers are themselves inflammatory and cause further attraction of neutrophils into the lungs. This in turn accelerates the inflammation and emphysema. All these factors are exacerbated by smoking. My laboratory has defined the pathway by which polymers form and is currently developing strategies to block the polymerisation of Z alpha-1 antitrypsin. Such a strategy will prevent the accumulation of Z alpha-1 antitrypsin within hepatocytes thereby treating the associated liver disease. The release of alpha-1 antitrypsin from the liver will increase the circulating levels of alpha-1 antitrypsin and hence provide protection for the lungs against emphysema.  

THE NEED OF STANDARDIZATION OF DIAGNOSIS
Ilaria Ferrarotti, Fondazione IRCCS, Policlinico S. Matteo, Pavia, Italy.

AATD is a largely under-recognized condition and one of the most common severe hereditary disorders in the world. To improve the diagnostic yield and to address the discrepancy between expected and diagnosed AATD cases, the recently published ATS/ERS Statement (2003) recommends diagnostic testing for all symptomatic adults with emphysema, COPD or asthma with incomplete reversible airflow obstruction, individuals with unexplained liver disease, asymptomatic individuals with persistent obstruction on pulmonary function tests with identifiable risk factors (cigarette smoking, occupational exposure) and adults with necrotizing panniculitis. The laboratory diagnosis of AATD has evolved from the initial description of the condition in 1963 based on paper electrophoresis – agarose-gel electrophoresis – immunoelectrophoresis to the currently used methodology, that is a combination of serum AAT level determination, isoelectric focusing (IEF), genotyping, and sequencing. The availability of matrices such as the dried blood spot have facilitated the implementation of laboratory analyses for alpha-1 antitrypsin deficiency, but have also challenged laboratories to develop more reliable and reproducible techniques starting from dried blood.

THE IMPORTANCE OF SCREENING
Luciano Corda, Centro Riferimento Deficit Alfa1-Antitripsina, Medicina Respiratoria/Prima Medicina, Spedali Civili, Brescia, Cattedra di Malattie dell’Apparato Respiratorio, Università di Brescia, Italy.

Screening is performed to identify the presence of a disease or a risk factor for a disease, typically among asymptomatic persons. In this way, a disease, or risk factors for a disease, can be detected early, allowing either early treatment or prevention. Screening tests are widely used by clinicians as part of the periodic health examination, as well as by public health officials. Examples of screening tests are as varied as blood tests to detect lead poisoning in young children, mammography to detect breast cancer and questionnaires to identify persons with alcohol or other drug problems. Even if alpha-1 antitrypsin deficiency (AATD) is considered a rare disease, it is probably the most common widespread genetic abnormality. AATD is rarely diagnosed, both because of poor awareness by health workers and lack of implemented screening programs. An underrecognition of AATD diagnosis persists in spite of an effort to enhance clinicians’ awareness. From the clinical point of view the under-recognition might be explained by the facts that most of clinical phenotypes associated with AATD are not exclusive to this condition and that the abnormal genes have an incomplete penetrance (the relationship between genotype and clinical phenotype is not strong). The availability of alpha-1 antitrypsin replacement therapy for individuals with pulmonary emphysema associated with AATD encouraged the scientific community to establish and reinforce AATD screening. Screening for AATD has been recommended by the World Health Organization (WHO) in 1997. The American Thoracic Society (ATS) together with the European Respiratory Society (ERS) in 2003 advise population screening when three main conditions occur: 1) high prevalence of AATD (more than 1/1500), 2) high prevalence of smokers or of people exposed to toxic inhalants 3) availability of adequate genetic “counselling”. A population screening programme might be very innovative making use of new genetic techniques. An adequate screening program and an early diagnosis of AATD may permit to apply primary (i.e. smoking cessation for lung disease or alcohol abstention for liver disorders) or secondary (i.e. treatment of related lung diseases) prevention measures. At the moment there are evidences of neonatal screening, patient oriented detection (case-finding) and so called “targeted screening”. Recently, the Italian Association of “Alphas” coordinated a screening for AATD in the entire population of a small village in a high risk area.   

ONGOING RESEARCH AND DEVELOPMENT
Robert Stockley, University Hospital, Birmingham, U.K.

From the first recognition of alpha-1 antitrypsin deficiency in 1963 the research field became very active exploring the deficiency as a cause of all COPD. In the early 1980s augmentation therapy was introduced and with the understanding that this was “a cure” research activity waned. However in recent years a more inquisitive approach to the condition has emerged. Why do some AATD patients remain well? How does the lung disease present? How does it develop? How should patients be treated? What is the effect of chest infections? Can we prevent deterioration? Can we repair the damage? These and many other questions challenge us for the next few years. Of importance clinical trials of old or new treatments will emerge and be delivered through the extensive collaboration of researchers and the developments of the AIR and AOF registries. However it is critical that these are co-ordinated and not replicated merely to appease regulatory bodies. Close collaboration between medical registries, pharmaceutical companies and patient groups will be essential if we are to assess future therapies adequately.