BACKGROUND: This study aims to evaluate the clinical characteristics of COPD patients with AATD according to their age at diagnosis. METHODS: Data was obtained from the European Alpha-1 Research Collaboration (EARCO) registry, an international prospective cohort study. AATD patients with COPD registered between February 2020 and October 2024 were analysed. Clinical charateristics were compared between groups, stratified by age of AATD diagnosis as follows; <45, 45-65 and ≥65 years. A multivariable logistic regression model explored factors associated with age at diagnosis. RESULTS: A total of 1,565 AATD-COPD patients were included, with 18.2% receiving an AATD diagnosis at age ≥ 65. In univariate comparisons according to diagnosis age revealed that the prevalence of patients with Pi*ZZ mutation was lower in the ≥ 65 age group (47.1%) compared to the 45-65 (65.5%) and < 45 (78.5%) age groups. In contrast, the prevalence of Pi*SZ and Pi*SS were higher in the ≥ 65 group compared to the younger age groups. The proportion of never-smokers was highest in the ≥ 65 group (39.5%), whereas only 15.3% of patients under 45 were never-smokers. Multivariate analysis showed that; compared to never-smokers, former smoking (OR: 0.08; 95% CI: 0.03-0.23) and current smoking (OR: 0.43; 95% CI: 0.27-0.70) were negatively associated with a diagnosis at age ≥ 65 in all sample. Compared to the Pi*ZZ genotype, among all sample, Pi*SS was associated with more than a 3-fold increased likelihood of diagnosis at age ≥ 65 and when considering only index cases Pi*SZ was associated with diagnosis age of ≥ 65 (OR: 2.01, 95%CI: 1.01-4.04). Among patients with the Pi*ZZ, current smoking was negatively associated (OR:0.24,95%CI: 0.13-0.47) with a diagnosis at age ≥ 65, whereas higher FEV1% and serum AAT levels were positively associated with later diagnosis. CONCLUSION: Patients diagnosed at an older age had lower tobacco exposure and less severe disease. This suggests that subclinical symptoms may contribute to delays in diagnosis, as COPD features can be subtle or under-recognised until later in life. Our findings highlight the importance of considering AATD in all COPD patients, regardless of age, to avoid missed or delayed diagnoses.

Asthma and Airway Centre Division of Respiratory Medicine Department of Medicine University Health Network Toronto Western Hospital University of Toronto Toronto ON Canada

Centro de Investigación Biomédica en Red de Enfermedades Respiratorias Instituto de Salud Carlos 3 Madrid Spain

Department of Chest Diseases Faculty of Medicine Recep Tayyip Erdoğan University Rize Türkiye

Department of Chest Diseases Hamidiye Faculty of Medicine Süreyyapaşa Chest Diseases and Surgery Education and Training Hospital University of Health Sciences İstanbul Türkiye

Department of Chest Diseases Hamidiye Faculty of Medicine Yedikule Chest Diseases and Surgery Education and Training Hospital University of Health Sciences İstanbul Türkiye

Department of Chest Diseases İzmir Faculty of Medicine Dr Suat Seren Chest Diseases and Surgery Education and Training Hospital University of Health Sciences İzmir Türkiye

Department of Clinical Medicine Faculty of Health Sciences University of Copenhagen Copenhagen Denmark

Department of Internal Medicine and Medical Therapeutics University of Pavia Pavia 27100 Italy

Department of Pneumology 1st Faculty of Medicine Thomayer Hospital Charles University Prague Czech Republic

Department of Public Health Faculty of Medicine Recep Tayyip Erdoğan University Rize Türkiye

Department of Respiratory Medicine and Allergology Skåne University Hospital Lund University Malmö Sweden

Division of Pulmonology University Hospital Zurich Zurich Switzerland

Division of Respiratory Diseases IRCCS Policlinico San Matteo Pavia 27100 Italy

Pulmonology Department Centro Hospitalar Universitário de Santo António Porto Portugal

Pulmonology Department Department of Medicine School of Medicine Hospital Clínico San Carlos Universidad Complutense de Madrid Instituto de Investigación Sanitaria del Hospital Clínico San Carlos Madrid Spain

Pulmonology Department Hospital da Senhora da Oliveira Unidade Local de Saúde Alto Ave Guimarães Portugal

Pulmonology Department Nuestra Señora de Candelaria University Hospital Santa Cruz de Tenerife Spain

School of Health Sciences University of Birmingham Birmingham UK

Section of Respiratory Medicine Department of Medicine Herlev and Gentofte Hospital University of Copenhagen Hellerup Denmark

Servicio de Neumología Complejo Hospitalario Clínico Universitario de Santiago Santiago de Compostela Spain

Servicio de Neumología Hospital Álvaro Cunqueiro NeumoVigo 1 i Research Group IIS Galicia Sur Vigo Spain

Unidad Médico Quirúrgica de Enfermedades Respiratorias Instituto de Biomedicina de Sevilla Hospital Universitario Virgen del Rocío Universidad de Sevilla Sevilla Spain

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