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

Abstract

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. Trial registrationwww.clinicaltrials.gov (ID: NCT04180319)

Characteristics of Patients With Alpha-1 Antitrypsin Deficiency From Rural Appalachia: A Retrospective Single-Center Study

“…Another study by Xue et al demonstrated high levels of correlation between obesity and AAT levels [ 12 ]. Another observational study of the international registry demonstrated COPD in 57.2% and bronchiectasis in 22% of patients [ 13 ].…”

Cardiovascular disease in Alpha 1 antitrypsin deficiency: an observational study assessing the role of neutrophil proteinase activity and the suitability of validated screening tools

“…Previous studies assessing CVD risk in AATD have shown contradictory results, but most studies have been small or have included patients on augmentation therapy [ 29 ]. The European AATD Research Collaboration international registry suggested that in untreated homozygous Z patients’ the prevalence of cardiovascular was 20.9%, which was even higher in augmented patients (38.5%) [ 19 ]. Although the reasons are currently unknown, this could reflect differences in disease severity, progression rates or co-morbidities [ 19 ] which were main factors in deciding on augmentation therapy.…”

“…The European AATD Research Collaboration international registry suggested that in untreated homozygous Z patients’ the prevalence of cardiovascular was 20.9%, which was even higher in augmented patients (38.5%) [ 19 ]. Although the reasons are currently unknown, this could reflect differences in disease severity, progression rates or co-morbidities [ 19 ] which were main factors in deciding on augmentation therapy. A Danish study of only 6 ZZ homozygotes and 39 MZ heterozygotes described lower blood pressure with MZ patients having a lower risk of coronary vascular disease compared to non-AATD controls [ 15 ].…”

The prevalence of bronchiectasis in patients with alpha-1 antitrypsin deficiency: initial report of EARCO

“…The recent establishment of EARCO (European Alpha1 Research Collaboration) International Registry, a deep phenotyping data base of AAT deficiency patients sponsored by the European Respiratory Society (ERS) enables us to estimate the prevalence of Bx in AAT deficiency as a baseline to understanding its nature, impact and management. The current article presents the initial findings of patients recruited to EARCO up to December 2021 [ 18 ].…”