Characteristics of Patients with Alpha-1 Antitrypsin Deficiency – Two-Year Data from the EARCO Registry

The International EARCO Registry and Collected Data

AATD is a rare disease associated with an increased risk of pulmonary emphysema in adults and liver and panniculitis involvement in children and adults. It is estimated that severe AATD in homozygous form affects 1 in 3,500–6,000 Europeans, and every 800th patient with chronic obstructive pulmonary disease (COPD).

The international EARCO registry (European Alpha-1 antitrypsin Deficiency Research Collaboration) was initiated by the European Respiratory Society (ERS) with the goal of describing AATD in individual genotypes, its natural progression, and the impact of therapy, including augmentation therapy. Although it was established as a European project, it has expanded into a global registry.

The registry represents an international observational study in which any physician caring for patients with AATD can participate. Individuals with a diagnosis of AATD or with an alpha-1 antitrypsin (AAT) level < 11 µM (< 0.5 g/l) or genotypes PI*ZZ, PI*SZ, and other rare variants of the AAT gene leading to its deficiency are included. The collected data include demographic characteristics, genotype, comorbidities, lung function, respiratory symptoms, liver ultrasound elastography findings, respiratory disease exacerbations, quality of life, physical activity, chest CT, and treatment.

Characteristics of Patients with AATD

In the following published work, data from 1,044 individuals with AATD from 15 countries were analyzed. The most common genotype was PI*ZZ, found in 60.2% of cases, followed by PI*SZ in 29.2% and PI*SS in 3.9%. The average age of patients with the PI*ZZ genotype was 56 years, the age at diagnosis was 45 years, 51.5% were men, and only 1.8% of these patients were employed. AATD was identified based on the presence of symptoms in 72.8% of cases.

Lung disease was reported in 81.4% of these individuals: most commonly emphysema (57.2%), COPD (55.9%), and bronchiectasis (22%). Liver involvement was present in 16% of patients with the PI*ZZ genotype. In more than 76% of patients, corresponding values of forced expiratory volume in one second (FEV₁) and diffusion coefficient (K_CO) were found. Patients with only FEV₁ impairment had more frequent bronchiectasis and asthma, whereas patients with only K_CO impairment had more frequent emphysema and liver involvement. Multivariate analysis indicated that a decline in FEV₁ was associated with older age, male gender, exacerbations, an increased number of platelets and neutrophils, augmentation therapy use, and lower serum AAT levels.

Augmentation Therapy

Only 30% of individuals with severe PI*ZZ deficiency received augmentation therapy. However, patients from countries where this therapy is not covered were also included. Patients receiving augmentation therapy were more likely to have AATD identified due to symptoms and demonstrated greater lung function impairment and more frequent exacerbations than those not receiving augmentation therapy.

The most common augmentation therapy regimen was 120 mg/kg every 2 weeks (48.9%), followed by 180 mg/kg every 3 weeks (28.9%), and 60 mg/kg every week (18.4%). Treatment was mostly administered in the hospital (88.9% of cases), less frequently at the general practitioner (9.5%), or at home (1.5%).

Conclusion

The EARCO registry has provided new information on the clinical and functional characteristics of patients with AATD. It is a prospective registry that will continue to collect data on the natural course of the disease and serves as a basis for the preparation of further clinical studies in this field.

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Source: Miravitlles M., Turner A. M., Torres-Duran M. et al. Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry. Respir Res 2022 Dec 16; 23 (1): 352, doi: 10.1186/s12931-022-02275-4.