Marion Wilkens, as appeared in Alpha1 Journal 1/2025.

A patient registry is an electronic database that collects medical information about patients with a specific disease. For rare diseases like alpha-1 antitrypsin deficiency (AATD), such a registry is particularly valuable: it enables the collection of large, long-term datasets that help improve care and treatment.

Why is this important?

Especially in the case of rare diseases, reliable data is often lacking – for example, on the natural course of the disease, the effects of therapy, or differences between individual patients. In AATD, for instance, we don't yet know exactly why patients with the same genotype (e.g., Pi*ZZ) show such different disease courses. We also know little about other gene variants. This is where the European EARCO registry comes in.

What is EARCO?

The European Alpha-1 Research Collaboration (EARCO) is a Europe-wide network of researchers, clinicians, and patient organizations. Its goals include:

• Establishment of an international registry for AATM patients
• Collection of high-quality long-term clinical data
• Better understanding of the disease progression
• Investigation of the effect of substitution therapy
• Development of standardized diagnostic and therapeutic recommendations

Who can participate?

All patients with an AAT serum level < 11 μM (50 mg/dl) and/or with genotypes PiZZ, PiSZ or other rare deficiency variants (homo- or compound heterozygous).

What data is collected? 

• Socioeconomic data (e.g. age, gender, origin, smoking status)
• Medical data (BMI, lung function, CT scan, liver function tests, AAT levels, genotype, treatment methods)
• Symptoms and disease progression (exacerbations, hospital stays, quality of daily life)
• annual follow-ups

Marion Wilkens, Alpha1 Germany eV, as published in Alpha1 Journal 1/2022.

After much advance announcement about how important EARCO is, we have finally reached a milestone: Germany has enrolled its first patients in the European registry.

The Thorax Clinic in Heidelberg, under the direction of senior physician Dr. Franziska Trudzinski, has taken over the coordination of registry entries in the EARCO registry with the support of Dr. Timm Greulich (Marburg) and has already entered the first patient data. Further centers in Germany will follow and have already applied for accreditation.

What does this mean for me as a patient? I will undergo even more thorough examinations, as a large amount of data is collected for the registry. Since data collection must also be carried out regularly, I will receive an annual appointment. These annual checkups allow my doctor and me to detect any deterioration in my health as early as possible. This gives me the opportunity to better manage the illness through increased knowledge.

Why is such a register generally so important?
We want to understand why the course of the disease varies so much. Why, for example, do some affected individuals never become ill despite severe deficiency? Which comorbidities influence the severity of the disease? What has a positive effect on its course? To find out about such things, we need valid (good) data, ideally covering a longer period – and that's what the European registry is for.

Join in and actively ask your doctor about EARCO!

Marion Wilkens, Chairwoman Alpha1 Germany eV.

The Department of Internal Medicine V of Saarland University Hospital (UKS), headed by Prof. Dr. med. Dr. rer. nat. Robert Bals, has been running the Alpha1 Registry in Germany since 2010 for both adults and children and adolescents.

It is not easy for researchers to obtain enough study participants or even data for a rare disease, which is why registries are extremely important. Every person affected by alpha-1 antitrypsin deficiency should actively participate in improving treatment options by registering in a registry.

Professor Bals compiled some interesting data from the registry for us (see blue box on the right). What we learn here is that we need to look not only among COPD patients, but also among asthmatics – we've always suspected this, but now it's been confirmed by data.

We are fortunate to have an Alpha-1 registry in Germany, although we would like to see more active participation. To be honest, children and adolescents were only included incidentally – their data was hardly analyzed. This is understandable, as the pulmonology department at Saarland University Hospital (UKS) is primarily an adult center. This is now set to change by transferring the children's and adolescents' registry to Bonn, under the direction of Professor Dr. Rainer Ganschow. We welcome this transfer to a dedicated children's center, which will undoubtedly expand the dataset for children and adolescents. Identifying early on what can influence the course of a disease offers us all an opportunity for more individualized and effective treatment.

It is important to ensure that the exchange of data between registries continues in the future, because, as we know, children grow into adults. We face this issue generally, as we also have a registry/study at the University Hospital RWTH Aachen. This study focuses on the liver, but it also collects a great deal of other valuable data from outside the liver.

But that's not all; a European EARCO registry will also be established in the future. Several countries are already actively collecting data from Alpha-1 patients, with more than 250 patients already included. Germany is currently in the approval process; the ethics committee still needs to give its consent.

The aim of the EARCO registry is to collect standardized longitudinal data at an international level in many different centers, which are needed to evaluate the following findings:

• The natural course of the disease
• The influence of risk factors
• Other genetic factors
• The role of substitution therapy in the
• Prognosis of the diseases

The main inclusion criterion is: severe AATD, defined by an AAT serum level < 50 mg/dl and/or a proteinase inhibitor; genotype ZZ, SZ and compound heterozygotes or homozygotes of other rare deficient variants (non-M).

This means that not all alphas are registered here either; for example, 'normal' MZs are not eligible. The data can only be entered by the center; the patient does not have the option to register themselves. The advantage: the data is secure and, due to the annual follow-up, scientifically very meaningful.

There are other registries, not exclusively focused on Alpha-1, that we could use for our condition, such as the Population Registry. This international registry aims to record as many people as possible affected by rare lung or respiratory diseases. Prof. Dr. Thomas OF Wagner, Medical Director of the Frankfurt Reference Center for Rare Respiratory Diseases and Coordinator of the ERN-LUNG Consortium, sees great potential in the registry: „Patient registries are important tools for supporting clinical research in the field of rare diseases and thus improving healthcare in the long term. With the help of the Population Registry, we are taking an important step towards providing better care for patients in the future.“. The Population Registry is available here in German and English.

Registers are extremely important; a lot of data can have a significant impact. From our perspective, the focus should absolutely be on ensuring that the collected data/registers can be interconnected. Far too little importance is currently attached to these interfaces!