Despite recent improvements, α1-antitrypsin deficiency (AATD) remains a rarely diagnosed and treated condition. To assess the variability of AATD diagnosis/treatment in Europe, and to evaluate clinicians' views on methods to optimise management, specialist AATD clinicians were invited to complete a web-based survey. Surveys were completed by 15 physicians from 14 centres in 13 European countries. All respondents perceived the AATD diagnosis rate to be low in their country; 77% of physicians believed that ∼15% of cases were diagnosed. Low awareness was perceived as the greatest barrier to diagnosis. Spirometry was considered more practical than quantitative computed tomography (QCT) for monitoring AATD patients in clinical practice; QCT was considered more useful in trials. AAT therapy provision was reported to be highly variable: France and Germany were reported to treat the highest proportion (∼60%) of diagnosed patients, in contrast to the UK and Hungary, where virtually no patients receive AAT therapy. Most clinicians supported self-administration and extended dosing intervals to improve convenience of AAT therapy. This survey indicates that AATD diagnosis and management are highly heterogeneous in Europe; European cooperation is essential to generate data to support access to AAT therapy. Improving convenience of AAT therapy is an ongoing objective.

3rd Medical Dept Nuremberg General Hospital Paracelsus Medical University Nuremberg Germany

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

Dept of Internal Medicine 2 and Pneumology at Wilhelminenspital Wien Vienna Austria

Dept of Internal Medicine Respiratory Disease Unit Spedali Civili Brescia Italy

Dept of Pneumology and Lung Transplantation Bichat Hospital Paris France

Dept of Pneumology Hospital of Santo Andre Centro Hospitalar de Leiria Leiria Portugal

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

Dept of Pulmonology National Koranyi Institute for Pulmonology in Budapest Budapest Hungary

Dept of Respiratory Medicine Beaumont Hospital Royal College of Surgeons in Ireland Dublin Ireland

Dept of Respiratory Medicine Ghent University Hospital Ghent Belgium

Institute of Applied Health Research University of Birmingham Birmingham UK

Leiden University Medical Centre Dept of Pulmonology Leiden Netherlands

Pulmonology Dept Centro Hospitalar de São João Porto Portugal

Pulmonology Dept University Hospital Vall d'Hebron CIBER de Enfermedades Respiratorias Barcelona Spain

Pulmonology. 2020 Jul - Aug;26(4):181-183. doi: 10.1016/j.pulmoe.2020.01.003. PubMed

Zobrazit více v PubMed

American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med 2003; 168: 818–900. PubMed

Stoller JK, Sandhaus RA, Turino G, et al. . Delay in diagnosis of α1-antitrypsin deficiency: a continuing problem. Chest 2005; 128: 1989–1994. PubMed

Miravitlles M, Herr C, Ferrarotti I, et al. . Laboratory testing of individuals with severe α1-antitrypsin deficiency in three European centres. Eur Respir J 2010; 35: 960–968. PubMed

Greulich T, Ottaviani S, Bals R, et al. . Alpha1-antitrypsin deficiency – diagnostic testing and disease awareness in Germany and Italy. Respir Med 2013; 107: 1400–1408. PubMed

Esquinas C, Barrecheguren M, Sucena M, et al. . Practice and knowledge about diagnosis and treatment of alpha-1 antitrypsin deficiency in Spain and Portugal. BMC Pulm Med 2016; 16: 64.

Greulich T, Averyanov A, Borsa L, et al. . European screening for alpha-antitrypsin deficiency in subjects with lung disease. Clin Respir J 2017; 11: 90–97. PubMed

Piitulainen E, Mostafavi B, Tanash HA. Health status and lung function in the Swedish alpha 1-antitrypsin deficient cohort, identified by neonatal screening, at the age of 37–40 years. Int J Chron Obstruct Pulmon Dis 2017; 12: 495–500. PubMed PMC

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

Chorostowska-Wynimko J. Disease modification in emphysema related to alpha-1 antitrypsin deficiency. COPD 2016; 13: 807–815. PubMed

Corda L, Bertella E, La Piana GE, et al. . Inhaled corticosteroids as additional treatment in alpha-1-antitrypsin-deficiency-related COPD. Respiration 2008; 76: 61–68. PubMed

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. PubMed

McElvaney NG, Burdon J, Holmes M, et al. . Long-term efficacy and safety of α1 proteinase inhibitor treatment for emphysema caused by severe α1 antitrypsin deficiency: an open-label extension trial (RAPID-OLE). Lancet Respir Med 2017; 5: 51–60. PubMed

Sandhaus RA, Turino G, Brantly ML, et al. . The diagnosis and management of alpha-1 antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis 2016; 3: 668–682. PubMed 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. PubMed

Stockley RA, Miravitlles M, Vogelmeier C, et al. . Augmentation therapy for alpha-1 antitrypsin deficiency: towards a personalised approach. Orphanet J Rare Dis 2013; 8: 149. PubMed PMC

Soy D, de la Roza C, Lara B, et al. . Alpha-1-antitrypsin deficiency: optimal therapeutic regimen based on population pharmacokinetics. Thorax 2006; 61: 1059–1064. PubMed PMC

Blanco I, de Serres FJ, Fernandez-Bustillo E, et al. . Estimated numbers and prevalence of PI*S and PI*Z alleles of α1-antitrypsin deficiency in European countries. Eur Respir J 2006; 27: 77–84. PubMed

Blanco I, Bueno P, Diego I, et al. . Alpha-1 antitrypsin Pi*Z gene frequency and Pi*ZZ genotype numbers worldwide: an update. Int J Chron Obstruct Pulmon Dis 2017; 12: 561–569. PubMed PMC

de Serres FJ. Alpha-1 antitrypsin deficiency is not a rare disease but a disease that is rarely diagnosed. Environ Health Perspect 2003; 111: 1851–1854. PubMed PMC

Bradi AC, Audisho N, Casey DK, et al. . Alpha-1 antitrypsin deficiency in Canada: regional disparities in diagnosis and management. COPD 2015; 12: Suppl. 1, 15–21. PubMed

Barrecheguren M, Monteagudo M, Simonet P, et al. . Diagnosis of alpha-1 antitrypsin deficiency: a population-based study. Int J Chron Obstruct Pulmon Dis 2016; 11: 999–1004. PubMed PMC

Bals R, Koczulla R, Kotke V, et al. . Identification of individuals with alpha-1-antitrypsin deficiency by a targeted screening program. Respir Med 2007; 101: 1708–1714. PubMed

Carroll TP, O'Connor CA, Floyd O, et al. . The prevalence of alpha-1 antitrypsin deficiency in Ireland. Respir Res 2011; 12: 91. PubMed PMC

de la Roza C, Rodríguez-Frías F, Lara B, et al. . Results of a case-detection programme for α1-antitrypsin deficiency in COPD patients. Eur Respir J 2005; 26: 616–622. PubMed

Molina J, Flor X, García R, et al. . The IDDEA project: a strategy for the detection of alpha-1 antitrypsin deficiency in COPD patients in the primary care setting. Ther Adv Respir Dis 2011; 5: 237–243. PubMed

Corda L, Medicina D, La Piana GE, et al. . Population genetic screening for alpha1-antitrypsin deficiency in a high-prevalence area. Respiration 2011; 82: 418–425. PubMed

Chorostowska-Wynimko J, Bakuła A, Kulus M, et al. . Standards for diagnosis and care of patients with inherited alpha-1 antitrypsin deficiency Recommendations of the Polish Respiratory Society, Polish Society of Pediatric Pulmonology and Polish Society of Pediatric Gastroenterology. Pneumonol Alergol Pol 2016; 84: 193–202. PubMed

Casas F, Blanco I, Martinez MT, et al. . Indications for active case searches and intravenous alpha-1 antitrypsin treatment for patients with alpha-1 antitrypsin deficiency chronic pulmonary obstructive disease: an update. Arch Bronconeumol 2015; 51: 185–192. PubMed

Campos MA, Diaz AA. The role of computed tomography for the evaluation of lung disease in alpha-1 antitrypsin deficiency. Chest 2018; 153: 1240–1248. PubMed PMC

Green CE, Parr DG, Edgar RG, et al. . Lung density associates with survival in alpha 1 antitrypsin deficient patients. Respir Med 2016; 112: 81–87. PubMed

Edgar RG, Patel M, Bayliss S, et al. . Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review. Int J Chron Obstruct Pulmon Dis 2017; 12: 1295–1308. PubMed PMC

Ficker JH, Chapman KR, Turner AM, et al. . Alpha 1 antitrypsin (A1-PI) treatment slows emphysema progression independent of baseline FEV1 Eur Respir J 2017; 50: Suppl. 61, OA3416.

Rahaghi FF, Miravitlles M. Long-term clinical outcomes following treatment with alpha 1-proteinase inhibitor for COPD associated with alpha-1 antitrypsin deficiency: a look at the evidence. Respir Res 2017; 18: 105. PubMed PMC

Campos M, Geraghty P, Holt G, et al. . The biological effects of double dose augmentation therapy for subjects with alpha-1 antitrypsin deficiency. Am J Respir Crit Care Med 2017; 195: A6315. PubMed PMC

Greulich T, Chlumsky J, Wencker M, et al. . Safety of bi-weekly intravenous therapy with alpha-1 antitrypsin. Eur Respir J 2017; 50: Suppl. 61, PA710.

European Parliament Directorate-General for Internal Policies EU Options for Improving Access to Medicines. www.europarl.europa.eu/RegData/etudes/STUD/2016/587304/IPOL_STU(2016)587304_EN.pdf Date last updated: August 2016. Date last accessed: October 24 2017.

European Patients Forum Directive on Patients' Rights in Cross-Border Healthcare – EPF Position Statement. April 2016 www.eu-patient.eu/globalassets/policy/cross-borderhealthcare/epf_position_statement_cbhc_220416.pdf Date last updated: April 2016. Date last accessed: February 18, 2019.

Gøtzsche PC, Johansen HK. Intravenous alpha-1 antitrypsin augmentation therapy for treating patients with alpha-1 antitrypsin deficiency and lung disease. Cochrane Database Syst Rev 2016; 9: CD007851. PubMed PMC

Gauvain C, Mornex JF, Pison C, et al. . Health-related quality of life in patients with alpha-1 antitrypsin deficiency: the French experience. COPD 2015; 12: Suppl. 1, 46–51. PubMed

Wilke A, Semper H, Gross C, et al. . Langzeit-Augmentationstherapie von Patienten mit Alpha-1-Antitrypsin-Mangel in der häuslichen Pflege. [Longterm Homecare Augmentation Program in Alpha-1-Antitrypsin Deficient Patients]. Pneumologie 2018; 72: 590–597. PubMed

Piitulainen E, Bernspång E, Bjorkman S, et al. . Tailored pharmacokinetic dosing allows self-administration and reduces the cost of IV augmentation therapy with human α1-antitrypsin. Eur J Clin Pharmacol 2003; 59: 151–156. PubMed

Schrijvers LH, Beijlevelt-van der Zande M, Peters M, et al. . Learning intravenous infusion in haemophilia: experience from the Netherlands. Haemophilia 2012; 18: 516–520. PubMed

Ochs HD, Gupta S, Kiessling P, et al. . Safety and efficacy of self-administered subcutaneous immunoglobulin in patients with primary immunodeficiency diseases. J Clin Immunol 2006; 26: 265–273. PubMed

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

Research priorities in α1-antitrypsin deficiency: results of a patients' and healthcare providers' international survey from the EARCO Clinical Research Collaboration

Protocol for the EARCO Registry: a pan-European observational study in patients with α1-antitrypsin deficiency