Report from Alpha-1 Conference 2019

Alpha-1 Conference 2019 took place in the Marino Institute of Education in Dublin on Friday, October 25th.  The theme for Conference 2019 was “How Can We Increase Awareness?” and a diverse range of speakers highlighted this important goal.

A large audience began to assemble from 9.30am, with many people up early and travelling from the four corners of the island. We are very grateful to all those who made the journey, and to our speakers – some of whom came from the USA and Saudi Arabia to take part.  A mix of familiar faces and first time attendees enjoyed tea, coffee and scones on arrival. 

Morning Session

Our first and special guest speaker was Miriam O’Day, CEO and President of the US Alpha-1 Foundation who opened the conference with a rousing presentation.  Miriam joked that despite the O’ it was her first time to visit Ireland but already hoped she would return again.  Miriam took us through the creation of the Foundation by three patient visionaries including the late, great Irish-American John W. Walsh.  The Foundation use a variety of methods to communicate with the Alpha-1 community in the US; traditional mail, magazine, webinars, podcasts, website articles on the Foundation website, educational events, and social media. Her organisation produces a fantastic Alpha-1-To-One magazine which can be accessed here. The goal is to provide support, information and also raise awareness.  

Miriam spoke about the many and diverse community fundraising efforts, both large and small, which raise awareness.  Public policy and advocacy was covered next, with a long list of collaborating organisations and government agencies testament to how influential the US Alpha-1 Foundation has become in 25 years.  A national network of over 80 support groups is a vital resource for over 7,000 Alphas and their families, and these groups are entirely volunteer-driven, but supported by the Foundation.  Another important driver of awareness is education.  Miriam outlined the Alpha-1 National Education Day Series which is composed of 6 Education Days across the country each year, in addition to the Annual Alpha-1 National Conference which took place in June in Orlando, Florida.  In addition to conferences, there is a wealth of online educational material and videos provided by the Foundation.  Other topics covered were scientific and medical research programmes that are funded by the Foundation, and the various efforts to increase detection rates.  Everything starts with a correct diagnosis and unfortunately the majority of people with Alpha-1 do not know they have it, yet.  Miriam finished with an uplifting message about how participation of patients in research programmes all over the globe means the field of Alpha-1 was finally getting close to a cure. 

Derick Mitchell Chief Executive Officer of IPPOSI was next to speak.  The Irish Platform for Patient Organisations, Science & Industry (IPPOSI) is unique in Europe as a body that brings together patients, scientific and medical researchers, and healthcare industry members on a 20 person board to discuss healthcare problems and propose solutions.  Since Derick assumed the role of CEO a key focus has been greater and more meaningful patient involvement in all aspects of healthcare research, policy, and innovation.  In their own words IPPOSI is “a patient-led organisation that works with patients, government, industry, & science to put patients at the heart of health innovation”.  Currently there are over 100 patient organisation members (including founder member Alpha-1 Foundation Ireland), over 200 science members, and 22 members from the healthcare industry.  

Derick posed many thought-provoking questions, such as “Is there equity in Irish healthcare?”, “What matters to patients?” and “Why educate patients?”  He explained how IPPOSI is developing a core of patient experts to help build a new vision for Irish healthcare and research where the patient voice is truly valued.  The IPPOSI “Patient Education Programme in Health Innovation” is a fantastic programme and we would love to see people from the Alpha-1 community sign up.  For more information about this programme visit https://www.ipposi.ie/our-work/education/patient-education-programme/

After a short coffee break the topic of new and emerging therapies was covered by Professor Gerry McElvaney, Lead Clinician at the National Centre of Expertise for AATD at Beaumont Hospital.  Professor McElvaney provided an overview of some of the exciting new therapies being developed for both the lung disease and the liver disease that can be caused by severe AATD.  He spoke first about the only specific therapy currently available to treat emphysema caused by severe AATD (usually for people who are ZZ phenotype).  This is called augmentation therapy.  It involves weekly intravenous infusions of alpha-1 antitrypsin protein, which is purified from the blood of health donors, and given to those patients born with the inherited deficiency.  Nineteen Irish people with ZZ AATD took part in a clinical trial called the “RAPID” study.  This study provided the best evidence to date that augmentation therapy slows down the loss of lung tissue, a key feature of emphysema.  Augmentation therapy has been available in the US for over 30 years, and is available today in many European countries.  Unfortunately, it is not available in Ireland due to its high cost.  Therefore, there is an urgent need for new therapies and thankfully there are several on the horizon.  

New treatments for AATD lung disease include a neutrophil elastase (NE) inhibitor in oral tablet form to be taken daily.  NE is a key driver of inflammation and lung destruction in AATD lung disease, and if we can stop its effects, it could improve symptoms and slow disease progression.  The company producing this drug will start recruiting for a clinical trial to test this new therapy in mid-2020 and we are hopeful that Irish patients will have the opportunity to join this trial.  New treatments for AATD liver disease include a gene silencing approach.  The root cause of the liver disease in AATD is the misshapen Z AAT protein which builds up in the liver with toxic effects, sometimes requiring liver transplantation.  Luckily the numbers affected by serious liver disease are small, with a lifetime risk in severe (ZZ) AATD of between 10-15% for liver cirrhosis.  Nevertheless, this will be the first ever specific treatment for AATD-induced liver disease and represents a huge step forward for the AATD community.  The new drug targets the AAT gene, switching it off and preventing the rogue Z AAT protein from damaging the liver.  Professor McElvaney was hopeful that Irish AATD patients with liver disease will be eligible to join this study from mid-2020.  Finally, there is one other exciting new therapy in development that aims to repair the underlying defect in severe AATD (ZZ type) at the protein level.  The company involved will begin recruitment in mid-2020 for a phase I study to test the safety of the drug for the first time in human volunteers.  It could represent a cure as it corrects the problem in both the liver and the lung.  Professor McElvaney finished up by stating the three studies offer great promise for the future and are all close to recruitment stage. 

Our next special guest speaker was Niamh Kelly who gave a wonderful presentation on behalf of her family.  In a powerful and moving tribute to her late sister Marion, Niamh discussed Marion’s battle with lung disease caused by Alpha-1 and how her quality of life had slowly deteriorated.  Marion opened up her own hairdressing business some years ago which was a source of great pride, but little did Marion realise that the fumes in many hair products were damaging her lungs.  After being accepted on to a clinical trial Marion’s condition did improve but then tragically in late 2017 Marion passed away suddenly after supply of the drug was controversially stopped. 

Following an emotional but successful battle to restore supply of the drug for the remaining Alpha-1 patients, and appearances on TV and radio, Niamh recalled being asked to represent Ireland at the Alpha-1 Global conference in Croatia in April 2019.  She attended the conference with Marion’s daughter Aideen, Orla Keane and Geraldine Kelly and admitted it was a huge eye opener and a turning point in her understanding of Alpha-1.  For example, she had not fully realised the genetic aspect and that other family members could also have inherited the condition and be at risk.  Since attending this conference in Croatia, she has discussed testing for Alpha-1 with other family members, and is working hard at changing the rules and laws around how clinical trials are operated.  She has had high level meetings with European officials and her goal is to develop a code of conduct for clinical trials, in particular how they finish and what happens to patients in the aftermath.  Niamh’s final thoughts returned to her late, dearly departed sister Marion, and how she would want the family to continue to work to help others with Alpha-1.  After a prolonged round of applause a lively question and answer session followed.

Following Niamh's powerful talk, the group heard an update from the national targeted detection programme for Alpha-1.  In May 2004, Alpha-1 Foundation Ireland launched the national AATD targeted detection programme, with financial support from the HSE and Department of Health.  In October of 2019 a milestone was reached: 20,000 people with chronic obstructive pulmonary disease (COPD), asthma, and liver disease, as well as first-degree relatives of people known to have AATD, had been tested.  Dr. Tomás Carroll, Chief Scientist at Alpha-1 Foundation Ireland, working on this testing programme since it began, provided an overview of the progress to date.  Of the 20,000 tested, over 4,200 people have been found to have some form of alpha-1 antitrypsin deficiency.  Of note, 400 were found to have the ZZ genotype – the most severe form of Alpha-1.  The detection programme has provided valuable data on the number of people affected by Alpha-1 in Ireland.

  • A total of 358 ZZ individuals (severe deficiency) have been diagnosed so far.
  • 350 people have been diagnosed with the SZ genotype (all significantly at risk of liver disease, and lung disease if they are smokers).
  • 3,425 MZ genotypes have been found (representing moderate deficiency – carriers are significantly at risk of lung disease if they smoke).

Research from Alpha-1 Foundation Ireland and the Royal College of Surgeons in Ireland (RCSI) has shown that 1 in 25 people in Ireland have the MZ phenotype, yet the vast majority are unaware and remain undiagnosed.  Tomás stressed that a goal of the foundation was to ensure testing for Alpha-1 should automatically be carried out in everyone diagnosed with COPD.  This is a recommendation first made by the World Health Organisation in 1997, but which still is not standard practice in Ireland and many other European countries. 

While Alpha-1 can cause lung, liver, and rarely skin disease, the symptoms people can develop varies hugely, with some remaining healthy and leading long and productive lives.  A lot depends on lifestyle factors, especially smoking.  Tomás repeated that everything starts with a correct diagnosis and that is the goal of the detection programme, to find all those at risk of health problems due to Alpha-1.  A correct diagnosis of Alpha-1 means accurate intervention which can postpone or even prevent disease and added motivation to stop smoking.  It also allows for closer medical surveillance and the opportunity for patients to participate in clinical trials.  Tomás also discussed the importance of the National AATD Registry, a database of more than 540 people diagnosed with Alpha-1.  He outlined how the registry is being used to increase our knowledge of Alpha-1 and quickly identify who might be eligible for new treatments as part of clinical trial assessments.  Tomás finished by detailing other foundation activities including educational seminars for health professionals and COPD support groups (more details here at copd.ie), and suggested people visit the Alpha-1 Foundation Ireland website www.alpha1.ie, as well as our Facebook Alpha-1 Foundation Ireland and Twitter @Alpha_Ireland channels.  Wrapping up Tomás thanked former colleague Dr. Laura Fee for her dedication and hard work during her seven years with the foundation.

Afternoon Session

After an enjoyable lunch kindly sponsored by A. Menarini we heard from Mansour Alkhunaizi, a final year medical student at RCSI.  Mansour took time out from his busy schedule to travel to Dublin from his home in Saudi Arabia to talk about the research he carried out with Alpha-1 Foundation Ireland in summer 2019.  Mansour explored smoking rates in those diagnosed with Alpha-1. 

His study showed a 70-92% smoking cessation rate (across ZZ, SZ, and MZ phenotypes) for those who were smoking at the time of AATD diagnosis. The highest cessation rates were found among the ZZ group, with only 2% continuing to smoke.  Importantly, this suggests that awareness of increased risk due to Alpha-1 can lead to positive changes in behaviour, namely stopping smoking.  From a behaviour point of view, he found that having a parent who smoked made it more likely that the child would become an adult smoker.  Smokers with parent(s) who smoked consumed more cigarettes (on average 23.47 pack years vs. 14.87 for smokers with non-smoking parent).  Mansour’s final message was that when you smoke, you are doing harm to yourself, to those passively inhaling the smoke, and you risk passing on the habit of smoking to your children.  These findings are very important – showing that people diagnosed with moderate (MZ, SZ) and severe (ZZ) Alpha-1 stop smoking soon after their diagnosis, and the majority do not restart smoking once they have stopped.  Explaining the significance of his study, Mansour said that in the typical COPD population, only about 30% of people manage to quit smoking.  Interestingly, a diagnosis of Alpha-1 appears to be a bigger motivation to quit smoking than a diagnosis of lung disease or lung cancer – in one US study, 42.9% of patients continued smoking following surgery for lung cancer.

The next topic for discussion was “Answering the SZ Question - An Irish Family Study”, presented by Dr. Alex Franciosi, a medical doctor and PhD student from RCSI, a familiar face to many in the audience.  Alex explained how there are an estimated 12,000 people on the island of Ireland who are SZ, and so far 350 have been detected in the national detection programme.  He described how people with the SZ genotype have been classified as having severe deficiency in some countries and guidelines despite a lack of good evidence for SZ deficiency directly causing disease.  

In a project funded by the US Alpha-1 Foundation, Alex travelled to every corner of Ireland for more than 2 years studying families with at least one SZ member.  This family approach helped to more carefully understand the risk of lung disease for this type of Alpha-1.   His research results show that people who are SZ Alpha-1 and don’t smoke, have little to no risk of lung disease.  On the other hand SZ smokers do have an increased risk of COPD, but this is comparable to MZ Alpha-1.  In light of this, SZ Alpha-1 should be classified as moderate deficiency and not severe, which is an important positive message for those affected and the medical profession.  Alex finished by thanking all the participants who generously took part in his study and helped to advance our knowledge of SZ.  

Another familiar face to many in the audience Eóin Durkan from the School of Health and Human Performance in Dublin City University (DCU), was next to present on pulmonary rehabilitation and Alpha-1.  Eóin is a final year PhD student in DCU in collaboration with Alpha-1 Foundation Ireland and the Irish Research Council.  A strong believer in exercise really is the best medicine, Eóin has been examining exercise as a treatment for lung disease caused by Alpha-1 for almost 3 years. 

He found that both fitness and quality of life can be improved with pulmonary rehabilitation in people with Alpha-1.  Eóin also stressed that exercise capacity has been shown to be a better predictor of quality of life score than pulmonary function score, further underlining its potential to improve health.  His take home message was that if we don’t use our muscle, we lose it, and any exercise (no matter how small) is better than none.  Something is better than nothing and more is better than something! 

The final speaker of the day was Dr. Oliver McElvaney, a medical doctor and researcher at the Irish Centre for Genetic Lung Disease at RCSI.  Oliver discussed a number of promising clinical trials on the horizon, as well as the upcoming ZZ research study which is going to look at families affected by the most severe form of Alpha-1.  The aim is to find out more about the risk factors that influence lung and liver disease, as well as identifying additional affected relatives, previously untested, who may be at risk.  Oliver wrapped up conference 2019 by thanking all those who had taken part in previous research studies, and looked forward to continued high participation rates in research which would help this and future generations of people affected by Alpha-1. 

A big thank you to all of our speakers who kindly took time out of their busy schedules.  Thank you to A. Menarini who sponsored lunch with an unrestricted educational grant.  Thank you to Eóin Durkan and Mansour Alkhunaizi for helping with the smooth running of the conference.  Thank you to Orla Keane who helped out with registration, Josephine McGuirk with Christmas cards, and Seamus O’Donnell with poetry books.  Their help was much appreciated by our small team of two.  If you would like to get a copy of “Window to my World” which is the beautiful collection of poetry written by the late John O’Donnell, click here.  

If you would like to suggest topics or ideas for next year’s conference we would be delighted to hear from you.  Please let us know (phone 01-8093871 or email us at This email address is being protected from spambots. You need JavaScript enabled to view it.).

See you all in October for conference 2020!