α1-antitrypsin deficiency (AATD) is a rare and under-recognised genetic condition. Owing to its low prevalence, international initiatives are key for conducting high-quality research in the field. From July 2018 to December 2019, the European Alpha-1 Research Collaboration (EARCO) developed and conducted two surveys, one for healthcare providers and one for patients and caregivers, aiming to identify research priorities and barriers in access to treatment for AATD. A survey on 164 research questions was electronically sent to 230 AATD experts in Europe, and 94 completed surveys from 24 countries were received. The top research areas identified by healthcare providers were causes of variable progression and poor outcomes, improvement in diagnosis, initiation and optimal dosing of augmentation therapy and effectiveness of self-management interventions. During the same period, 438 surveys were completed by patients and caregivers from 26 countries. The top research areas identified were improving knowledge about AATD, in particular among general practitioners, access to AATD specialised centres and access to reliable, easy to understand information about living with AATD. Regarding barriers to treatment, participants from countries where augmentation therapy was reimbursed prioritised improving knowledge in AATD, while respondents in non-reimbursed countries regarded access to AATD augmentation therapy and to specialised centres as the most relevant. The main research and management priorities identified by healthcare providers and patients included understanding the natural history of AATD, improving information to physicians, improving access to specialised reference centres, personalising treatment and having equal opportunities for access to existing therapies.

Alpha 1 UK Support Group Droitwich UK

Alpha1 Deutschland e 5 Gernsheim Germany

Dept of Genetics and Clinical Immunology National Institute of Tuberculosis and Lung Diseases Warsaw Poland

Dept of Internal Medicine and Therapeutics Pneumology Unit IRCCS San Matteo Hospital Foundation University of Pavia Pavia Italy

Dept of Medicine Pulmonary and Critical Care Medicine University Medical Centre Giessen and Marburg Philipps University Member of the German Centre for Lung Research Marburg Germany

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

Dept of Respiratory Medicine Allergology and Pulmonary Oncology Poznań University of Medical Sciences Poznan Poland

Dept of Respiratory Medicine University Hospitals of Coventry and Warwickshire Coventry UK

Division of Pulmonology University Hospital Zurich Zurich Switzerland

European Lung Foundation Sheffield UK

Pneumology Dept Hospital Universitari Vall d'Hebron Vall d'Hebron Institut de Recerca Vall d'Hebron Barcelona Hospital Campus Barcelona Spain

Pulmonology Dept Centro Hospitalar do Porto Porto Portugal

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Blanco I, Bueno P, Diego I, et al. . α1-antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update. Int J Chron Obstruct Pulmon Dis 2017; 12: 561–569. doi:10.2147/COPD.S125389 PubMed DOI PMC

Miravitlles M, Dirksen A, Ferrarotti I, et al. . European Respiratory Society statement: diagnosis and treatment of pulmonary disease in α1-antitrypsin deficiency. Eur Respir J 2017; 50: 1700610. doi:10.1183/13993003.00610-2017 PubMed DOI

Miravitlles M, Chorostowska-Wynimko J, Ferrarotti I, et al. . The European Alpha-1 Research Collaboration (EARCO): a new ERS Clinical Research Collaboration to promote research in α1-antitrypsin deficiency. Eur Respir J 2019; 53: 1900138. doi:10.1183/13993003.00138-2019 PubMed DOI

Brightling C, Genton C, Bill W, et al. . ERS Clinical Research Collaborations: underpinning research excellence. Eur Respir J 2018; 52: 1801534. doi:10.1183/13993003.01534-2018 PubMed DOI

Eriksson S. Pulmonary emphysema and α1-antitrypsin deficiency. Acta Med Scand 1964; 175: 197–205. doi:10.1111/j.0954-6820.1964.tb00567.x PubMed DOI

Blanco I, Diego I, Bueno P, et al. . Prevalence of α1-antitrypsin genotypes in patients with COPD in Europe: a systematic review. Eur Respir Rev 2020; 29: 200014. doi:10.1183/16000617.0014-2020 PubMed DOI PMC

Schluchter MD, Stoller JK, Barker AF, et al. . Feasibility of a clinical trial of augmentation therapy for α1-antitrypsin deficiency. Am J Respir Crit Care Med 2000; 161: 796–801. doi:10.1164/ajrccm.161.3.9906011 PubMed DOI

Greulich T, Altraja A, Barrecheguren M, et al. . Protocol for the EARCO Registry: a pan-European observational study in patients with α1-antitrypsin deficiency. ERJ Open Res 2020; 6: 00181-2019. doi:10.1183/23120541.00181-2019 PubMed DOI PMC

Seersholm N, Kok-Jensen A, Dirksen A. Survival of patients with severe α1-antitrypsin deficiency with special reference to non-index cases. Thorax 1994; 49: 695–698. doi:10.1136/thx.49.7.695 PubMed DOI PMC

The Alpha-1 Antitrypsin Deficiency Registry Study Group Survival and FEV1 decline in individuals with severe deficiency of α1-antitrypsin. Am J Respir Crit Care Med 1998; 158: 49–59. doi:10.1164/ajrccm.158.1.9712017 PubMed DOI

Demeo DL, Sandhaus RA, Barker AF, et al. . Determinants of airflow obstruction in severe α1-antitrypsin deficiency. Thorax 2007; 62: 806–813. doi:10.1136/thx.2006.075846 PubMed DOI PMC

Wood AM, Needham M, Simmonds MJ, et al. . Phenotypic differences in α1-antitrypsin-deficient sibling pairs may relate to genetic variation. COPD 2008; 5: 353–359. doi:10.1080/15412550802522320 PubMed DOI

Tanash HA, Ekström M, Rönmark E, et al. . Survival in individuals with severe α1-antitrypsin deficiency (PiZZ) in comparison to a general population with known smoking habits. Eur Respir J 2017; 50: 1700198. doi:10.1183/13993003.00198-2017 PubMed DOI

Chapman KR, Burdon JG, Piitulainen E, et al. . Intravenous augmentation treatment and lung density in severe α1-antitrypsin deficiency (RAPID): a randomised, double-blind, placebo-controlled trial. Lancet 2015; 386: 360–368. doi:10.1016/S0140-6736(15)60860-1 PubMed DOI

Wewers MD, Casolaro MA, Sellers SE, et al. . Replacement therapy for α1-antitrypsin deficiency associated with emphysema. N Engl J Med 1987; 316: 1055–1062. doi:10.1056/NEJM198704233161704 PubMed DOI

Stockley RA, Miravitlles M, Vogelmeier C. Augmentation therapy for α1-antitrypsin deficiency: towards a personalised approach. Orphanet J Rare Dis 2013; 8: 149. doi:10.1186/1750-1172-8-149 PubMed DOI PMC

Campos MA, Geraghty P, Holt G, et al. . The biological effects of double-dose α1-antitrypsin augmentation therapy. A pilot clinical trial. Am J Respir Crit Care Med 2019; 200: 318–326. doi:10.1164/rccm.201901-0010OC PubMed DOI PMC

Sorrells S, Camprubi S, Griffin R, et al. . SPARTA clinical trial design: exploring the efficacy and safety of two dose regimens of α1-proteinase inhibitor augmentation therapy in α1-antitrypsin deficiency. Respir Med 2015; 109: 490–499. doi:10.1016/j.rmed.2015.01.022 PubMed DOI

Stolk J, Tov N, Chapman KR, et al. . Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of chronic obstructive pulmonary disease. Eur Respir J 2019; 54: 1900673. doi:10.1183/13993003.00673-2019 PubMed DOI

Chorostowska-Wynimko J. Targeted screening programmes in COPD: how to identify individuals with α1-antitrypsin deficiency. Eur Respir Rev 2015; 24: 40–45. doi:10.1183/09059180.00010614 PubMed DOI PMC

Meira L, Boaventura R, Seixas S, et al. . α1-antitrypsin deficiency detection in a Portuguese population. COPD 2018; 15: 4–9. doi:10.1080/15412555.2017.1414779 PubMed DOI

Campos MA, Wanner A, Zhang G, et al. . Trends in the diagnosis of symptomatic patients with α1-antitrypsin deficiency between 1968 and 2003. Chest 2005; 128: 1179–1186. doi:10.1378/chest.128.3.1179 PubMed DOI

Greulich T, Ottaviani S, Bals R, et al. . α1-antitrypsin deficiency - diagnostic testing and disease awareness in Germany and Italy. Respir Med 2013; 107: 1400–1408. doi:10.1016/j.rmed.2013.04.023 PubMed DOI

Esquinas C, Barrecheguren M, Sucena M, et al. . Practice and knowledge about diagnosis and treatment of α1-antitrypsin deficiency in Spain and Portugal. BMC Pulm Med 2016; 16: 64. doi:10.1186/s12890-016-0222-4 DOI

The Council of the European Union; Council recommendation of 8 June 2009 on an action in the field of rare diseases, 2009/C 151/02 http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:C:2009:151:0007:0010:EN:PDF Date last accessed: May 22, 2020.

Luisetti M, Balfour-Lynn IM, Johnson S, et al. . Perspectives for improving the evaluation and access of therapies for rare lung diseases in Europe. Respir Med 2012; 106: 759–768. doi:10.1016/j.rmed.2012.02.016 PubMed DOI

Horváth I, Canotilho M, Chlumský J, et al. . Diagnosis and management of α1-antitrypsin deficiency in Europe: an expert survey. ERJ Open Res 2019; 5: 00171-2018. doi:10.1183/23120541.00171-2018 PubMed DOI PMC

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