A study published in the journal Respiratory Research describes characteristics of individuals included in the international alpha-1 antitrypsin deficiency (AATD) registry of the European Alpha-1 Research Collaboration (EARCO).

EARCO, a project of the European Respiratory Society, aims to characterize patients’ different genotypes, as well as to evaluate the natural history and impact of various treatments for the disorder, including augmentation therapy.

The EARCO registry is an observational, prospective study (NCT04180319) of individuals with AATD, which is defined as alpha-1 antitrypsin (AAT) serum levels of less than 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ or compound heterozygotes or homozygotes of other rare deficient variants. Results of the current study are from the EARCO registry’s launch in February 2020 through May 2022.


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Although it was designed as a European initiative, the EARCO registry has extended beyond European boundaries to become a global registry. As of May 2022, it had 47 recruiting centers in 15 countries.

“EARCO is a prospective study that will provide relevant information about the natural history of AATD in the future and is the platform for the development of other clinical studies in the field,” the authors wrote.

The database at the time comprised 1079 individuals, of whom 35 were excluded, leaving 1044 participants for analysis. The most common genotype observed was PI*ZZ in 629 individuals; PI*SZ was found in 305 patients, PI*SS in 41 participants, and rare variants in 69 individuals. Among the participants with the PI*ZZ genotype, 51.5% were male.

The mean patient age in this group was 55.6±13.2 years, and the mean age at diagnosis was 44.7±16.7 years. Among PI*ZZ participants, the most common lung disease reported was emphysema in 57.2%, followed by chronic obstructive pulmonary disease in 55.9% and bronchiectasis in 22.0%.

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Of 449 individuals with the PI*ZZ genotype who had valid measurements of forced expiratory volume in 1 second/ forced vital capacity ratio (FEV1%) and carbon monoxide transfer coefficient (KCO%), 76.4% (343 of 449) of them had concordant values. Participants with an impairment in FEV1% alone experienced bronchiectasis and asthma more often, whereas those with an impairment in KCO% alone experienced emphysema and liver disease more frequently.

Per multivariate analysis, male sex, advanced age, exacerbations, increased blood platelets and neutrophils, augmentation, and lower AAT serum levels were all associated with worse FEV1%. A total of 190 individuals in the
PI*ZZ group had received augmentation at the time of enrollment in the EARCO registry.

Reference

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