PMID- 36707810 OWN - NLM STAT- MEDLINE DCOM- 20230131 LR - 20230202 IS - 1465-993X (Electronic) IS - 1465-9921 (Print) IS - 1465-9921 (Linking) VI - 24 IP - 1 DP - 2023 Jan 27 TI - The impact of diagnostic delay on survival in alpha-1-antitrypsin deficiency: results from the Austrian Alpha-1 Lung Registry. PG - 34 LID - 10.1186/s12931-023-02338-0 [doi] LID - 34 AB - BACKGROUND: Alpha-1-antitrypsin (AAT) deficiency (AATD) is a genetic disorder that can manifest as lung disease. A delay between onset of symptoms and diagnosis of AATD is common and associated with worse clinical status and more advanced disease stage but the influence on survival is unclear. OBJECTIVE: We aimed to investigate the impact of diagnostic delay on overall survival (OS) and transplant-free survival (TS) in AATD patients. METHODS: We analysed 268 AATD patients from the prospective multi-centre Austrian Alpha-1 Lung (AAL) Registry, employing descriptive statistics, Chi-square-test as well as univariable (Kaplan-Meier plots, log-rank test) and multivariable survival analysis (Cox regression). RESULTS: The predominant phenotype was Pi*ZZ (82.1%). At diagnosis, 90.2% had an AAT level below 0.6 g/L. At inclusion, 28.2% had never smoked, 68.0% had quit smoking and 3.8% continued to smoke. Lung disease was diagnosed in 98.5%, thereof most patients were diagnosed with emphysema (63.8%) and/or chronic obstructive pulmonary disease (44.0%). Median diagnostic delay was 5.3 years (inter-quartile range [IQR] 2.2-11.5 years). In multivariable analysis (n = 229), a longer diagnostic delay was significantly associated with worse OS (hazard ratio [HR] 1.61; 95% CI 1.09-2.38; p = 0.016) and TS (HR 1.43; 95% CI 1.08-1.89; p = 0.011), independent from age, smoking status, body mass index (BMI), forced expiratory volume in one second (FEV(1)) and long-term oxygen treatment. Furthermore, BMI, age and active smoking were significantly associated with worse OS as well as BMI, active smoking and FEV(1) were with worse TS. CONCLUSIONS: A delayed diagnosis was associated with significantly worse OS and TS. Screening should be improved and efforts to ensure early AATD diagnosis should be intensified. CI - (c) 2023. The Author(s). FAU - Meischl, Tobias AU - Meischl T AD - Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Ottakring, Montleartstrasse 37, 1160, Vienna, Austria. AD - Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria. FAU - Schmid-Scherzer, Karin AU - Schmid-Scherzer K AD - Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Ottakring, Montleartstrasse 37, 1160, Vienna, Austria. AD - Department of Medicine II With Pneumology, Klinik Ottakring, Vienna, Austria. FAU - Vafai-Tabrizi, Florian AU - Vafai-Tabrizi F AD - Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Ottakring, Montleartstrasse 37, 1160, Vienna, Austria. AD - Department of Medicine II With Pneumology, Klinik Ottakring, Vienna, Austria. FAU - Wurzinger, Gert AU - Wurzinger G AD - Center of Pulmology, LKH Graz II, Standort Enzenbach, Gratwein-Strassengel, Austria. FAU - Traunmuller-Wurm, Eva AU - Traunmuller-Wurm E AD - Department of Pulmology, Klinikum Wels-Grieskirchen, Wels, Austria. FAU - Kutics, Kristina AU - Kutics K AD - Department of Pulmology, Klinikum Wels-Grieskirchen, Wels, Austria. FAU - Rauter, Markus AU - Rauter M AD - Department of Pulmonology, Klinikum Klagenfurt Am Woerthersee, Klagenfurt, Austria. FAU - Grabcanovic-Musija, Fikreta AU - Grabcanovic-Musija F AD - Public Health Office, City of Salzburg, Salzburg, Austria. FAU - Muller, Simona AU - Muller S AD - Department of Pulmonology, Landeskrankenhaus Hohenems, Hohenems, Austria. FAU - Kaufmann, Norbert AU - Kaufmann N AD - Division of Gastroenterology, Infectiology and Pneumology, Department of Medicine, LKH Graz II, Graz, Austria. FAU - Loffler-Ragg, Judith AU - Loffler-Ragg J AD - Department of Medicine II, Medical University of Innsbruck, Innsbruck, Austria. FAU - Valipour, Arschang AU - Valipour A AD - Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Ottakring, Montleartstrasse 37, 1160, Vienna, Austria. AD - Department of Respiratory and Critical Care Medicine, Klinik Floridsdorf, Vienna, Austria. FAU - Funk, Georg-Christian AU - Funk GC AD - Karl Landsteiner Institute for Lung Research and Pulmonary Oncology, Klinik Ottakring, Montleartstrasse 37, 1160, Vienna, Austria. georg-christian.funk@gesundheitsverbund.at. AD - Department of Medicine II With Pneumology, Klinik Ottakring, Vienna, Austria. georg-christian.funk@gesundheitsverbund.at. LA - eng PT - Journal Article DEP - 20230127 PL - England TA - Respir Res JT - Respiratory research JID - 101090633 RN - 0 (alpha 1-Antitrypsin) SB - IM MH - Humans MH - Delayed Diagnosis MH - Prospective Studies MH - Austria/epidemiology MH - Lung MH - *alpha 1-Antitrypsin Deficiency/diagnosis/epidemiology/complications MH - *Pulmonary Disease, Chronic Obstructive/diagnosis/epidemiology MH - alpha 1-Antitrypsin MH - Registries PMC - PMC9881325 OTO - NOTNLM OT - Alpha-1-antitrypsin OT - Alpha-1-antitrypsin deficiency OT - Diagnostic delay COIS- TM received speaker fees from Chiesi and Janssen-Cilag; and travel support from CSL Behring, Chiesi, Jazz Pharmaceuticals and Janssen-Cilag. KSS received speaker fees from Chiesi, CSL Behring and Grifols. GW and AV received speaker fees and consultancy fees from Chiesi. NK received speaker fees from Chiesi. JLR received consultancy fees from CSL Behring. GCF received speaker fees and consultancy fees from Chiesi and CSL Behring. FVT, ETW, KK, MR, FGM, and SM declare no potential conflicts of interest. EDAT- 2023/01/29 06:00 MHDA- 2023/02/01 06:00 PMCR- 2023/01/27 CRDT- 2023/01/28 00:08 PHST- 2022/03/22 00:00 [received] PHST- 2023/01/18 00:00 [accepted] PHST- 2023/01/28 00:08 [entrez] PHST- 2023/01/29 06:00 [pubmed] PHST- 2023/02/01 06:00 [medline] PHST- 2023/01/27 00:00 [pmc-release] AID - 10.1186/s12931-023-02338-0 [pii] AID - 2338 [pii] AID - 10.1186/s12931-023-02338-0 [doi] PST - epublish SO - Respir Res. 2023 Jan 27;24(1):34. doi: 10.1186/s12931-023-02338-0.