Although tremendous improvements have been made in the understanding of the pathophysiology of the disease in recent years, many questions remain unanswered, and AATD poses several important challenges:
- The natural history and prognosis of AATD patients is not well known, and there is a lack of prognostic tools to support medical decision making (early referral for a lung transplantation for instance).
- Although the vast majority of patients with severe deficiency share the same genetic disorder (ZZ genotype), the prevalence and severity of liver and respiratory disease vary markedly. Genetic/environmental cofactors have been suspected, but the majority have yet to be identified.
- Augmentation therapy has been shown to slow, but not stop, the progression of emphysema, as assessed by CT densitometry. However, its impact on FEV1, quality of life and mortality has not been definitively established. Consequently, augmentation therapy is not reimbursed in all European countries.
- Most studies on AATD have focused on the ZZ population. The impact of other rarer variants on outcomes is unknown.
The answer to these questions requires the access to large cohorts of patients and cannot be addressed solely at individual country level. This was the main reason to initiate an European Alpha-1 Clinical Research Collaboration (EARCO). This will enable an international group of experienced researchers to answer fundamental questions about epidemiology, genetics, pathophysiology, clinical management and prognosis of lung disease associated with AATD. Furthermore, the initiative brings together multiple stakeholders including researchers, healthcare providers and patients with the aim of advancing understanding through clinical and scientific research and improving the quality of life of patients with the deficiency.
EARCO takes advantage of existing AATD registries that have been developed at the national level. Several countries have established registries in which AATD patients are included and followed-up with clinical and biological data collected. However, these registries differ in terms of inclusion criteria, data collected and frequency and extent of follow-up. Within EARCO, we will harmonize the data collection process and assess the quality of the data within a short time frame after the data are generated and entered into the database.