Competing Interests: Conflict of interest: M. Miravitlles reports speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo BioPharma, Verona Pharma, TEVA, pH Pharma, Novartis and Grifols, and research grants from GlaxoSmithKline and Grifols, all outside the submitted work. Conflict of interest: J. Chorostowska-Wynimko reports grants, personal fees and non-financial support from Grifols, AstraZeneca and CSL Behring, personal fees from Kamada, GSK, Novartis, Chiesi and Lekam, personal fees and non-financial support from Pfizer, MSD, BMS, Roche, Abbvie and CelonPharma, and grants and personal fees from Boehringer Ingelheim, all outside the submitted work. Conflict of interest: I. Ferrarotti has received speaker and consulting fees from CSL Behring and Grifols. Conflict of interest: N.G. McElvaney reports grants from Grifols (support for Irish Registry), personal fees from CSL Behring (for advisory board), and grants and personal fees from Chiesi, all outside the submitted work. Conflict of interest: K. O'Hara reports non-financial support from the ELF/ERS and from Mereo BioPharma Group plc, grants from CSL Behring (for the Alpha-1 UK Support Group, which also receives donations from individuals/companies as a result of fundraising activities), personal fees and non-financial support from NICE, and non-financial support from Alpha-1 Global, outside the submitted work. Conflict of interest: J. Stolk reports grants from CSL Behring and Kamada Ltd, personal fees from pH Pharma, and non-financial support from Mereo BioPharma, outside the submitted work; J. Stolk is also consultant to CSL Behring, Kamada Ltd and pH Pharma Inc. Conflict of interest: R.A. Stockley reports personal fees from AstraZeneca (advisory board membership and for lectures), Nycomed (for lectures), Boehringer Ingelheim and CSL Behring (advisory board membership, for lectures and travel to meetings), and from Shire, Chiesi, Polyphor, GlaxoSmithKline, Mereo BioPharma, Vertex Pharmaceuticals Inc and Akari Therapeutics plc (all for advisory board membership), outside the submitted work. Conflict of interest: A. Turner reports grants (to assess prevalence of AATD) and personal fees (for consultancy work) from CSL Behring, grants from Grifols biotherapeutics (to look at the role of CT scanning in AATD disease progression), grants from the Alpha 1 Foundation (examining phenotypes and progression after exacerbations in AATD lung disease), grants (for usual COPD) and non-financial support (to attend conferences) from AstraZeneca and Chiesi, grants from the ATS foundation (examining the role of augmentation on health status), and personal fees and non-financial support from Boehringer Ingelheim (speaker fees and support to attend conferences), all outside the submitted work. Conflict of interest: M. Wilkens reports non-financial support to reimburse travel costs from the ELF (European Lung Foundation), during the conduct of the study; as chairman of the patient organisation Alpha1 Deutschland e.V., M. Wilkens personally does not receive any donations, but the organisation receives money from public funds as well as from the pharmaceutical industry, e.g. grants as well as travelling costs. Conflict of interest: T. Greulich reports grants from CSL Behring and Grifols, during the conduct of the study; as well as personal fees for lectures and advisory boards from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL Behring, GSK and Novartis, grants and personal fees for lectures and advisory boards from Grifols, and grants from the German Centre for Lung Research (DZL), Marburg, Germany (Deutsches Zentrum für Lungenforschung), outside the submitted work.