Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry

Background: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. Methods: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. Results: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). Conclusions: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function.Funding: The International EARCO registry is funded by unrestricted grants of Grifols, CSL Behring, Kamada, pH Pharma and Takeda to the European Respiratory Society (ERS). Acknowledgements: The authors would like to thank the patients who participated in this study and the EARCO study investigators (listed below). We wish to acknowledge Elise Heuvelin from the ERS ofce (Lausanne, Switzterland) for her support in the management of EARCO, and Gemma Vilagut and Christina Founti (Bioclever, Barcelona, Spain) for their support in EARCO data monitoring. We also acknowledge the participation of Eduardo Loeb (Barcelona, Spain) in the development of the database and the monitoring of the data. List of EARCO study investigators: Georg-Christian Funk (Austria), Wim Jans sens, Silvia Pérez-Bogerd (Belgium), Leidy Prada (Colombia), Ana Hecomovic (Croatia), Eva Bartosovska, Jan Chlumsky, (Czech Republic), Alan Altraja, Jaanus Martti (Estonia), Angelo G. Corsico, Ilaria Ferrarotti, Simone Scarlata, Mario Malerba (Italy), Jan Stolk, Emily F van’t Wout (Netherlands), Joanna Chorowstoska-Wyminko (Poland), Catarina Guimaraes, Maria Sucena, Ana Caldas Raquel Marçoa, Isabel Ruivo dos Santos, Bebiana Conde, Maria Joana Reis Amado Maia Da Silva, Rita Boaventura (Portugal), Ruxandra Ulmeanu (Romania), María Torres-Duran, Marc Miravitlles, Miriam Barrecheguren, Juan Luis Rodriguez-Hermosa, Myriam Calle-Rubio, José María Hernández-Pérez, José Luis López-Campos, Francisco Casas-Maldonado, Ana Bustamante, Carlota Rodriguez-García, Cristina Martinez-González, Cruz González, Eva Tabernero, Lourdes Lázaro, Virginia Almadana, Mar Fernández-Nieto, Francisco Javier Michel de la Rosa, Carlos Martíez-Rivera, Layla Diab, María Isabel Parra (Spain), Hanan Tanash, Eeva Piitulainen (Sweden), Christian F. Clarenbach (Switzerland), Serap Argun Baris, Dilek Karadogan, Sebahat Genç (Turkey), Alice M. Turner, Beatriz Lara, David G. Parr (United Kingdom). EARCO Steering committee: Christian F Clarenbach and Marc Miravitlles (Co-chairs), Robert Bals, Jan Stolk, Joanna Chorostowska-Wynimko, Karen O’Hara, Marion Wilkens, José Luis López-Campos, Alice M. Turner, Ilaria Ferrarotti, Gerry McElvaney and Robert A. Stockle