Risk of lung disease in the PI*SS genotype of alpha-1 antitrypsin: an EARCO research project.

BACKGROUND: The PI*S variant is one of the most prevalent mutations within alpha-1 antitrypsin deficiency (AATD). The risk of developing AATD-related lung disease in individuals with the PI*SS genotype is poorly defined despite its substantial prevalence. Our study aimed to characterize this genotype and its risk for lung disease and compare it with the PI*ZZ and PI*SZ genotypes using data from the European Alpha-1 antitrypsin Deficiency Research Collaboration international registry. METHOD: Demographic, clinical, functional, and quality of life (QoL) parameters were assessed to compare the PI*SS characteristics with the PI*SZ and PI*ZZ controls. A propensity score with 1:3 nearest-neighbour matching was performed for the most important confounding variables. RESULTS: The study included 1007 individuals, with PI*SS (n = 56; 5.6%), PI*ZZ (n = 578; 57.4%) and PI*SZ (n = 373; 37.0%). The PI*SS population consisted of 58.9% men, with a mean age of 59.2 years and a mean FEV1(% predicted) of 83.4%. Compared to PI*ZZ individuals they had less frequent lung disease (71.4% vs. 82.2%, p = 0.037), COPD (41.4% vs. 60%, p = 0.002), and emphysema (23.2% vs. 51.9%, p < 0.001) and better preserved lung function, fewer exacerbations, lower level of dyspnoea, and better QoL. In contrast, no significant differences were found in the prevalence of lung diseases between PI*SS and PI*SZ, or lung function parameters, exacerbations, dyspnoea, or QoL. CONCLUSIONS: We found that, as expected, the risk of lung disease associated with the PI*SS genotype is significantly lower compared with PI*ZZ, but does not differ from that observed in PI*SZ individuals, despite having higher serum AAT levels. TRIAL REGISTRATION: www. CLINICALTRIALS: gov (ID: NCT04180319).

Predicting Exacerbations in Alpha-1 Antitrypsin Deficiency Using Clinical and Pulmonary Function Tests: Portuguese EARCO Registry.

INTRODUCTION: Exacerbations are common in individuals with alpha-1 antitrypsin deficiency (AATD)-related lung disease. This study intended to identify independent predictive factors for exacerbations in AATD using the Portuguese European Alpha-1 Research Collaboration (EARCO) registry. METHODS: This study includes patients from the Portuguese EARCO registry, a prospective multicenter cohort (NCT04180319). From October 2020 to April 2023, this registry enrolled 137 patients, 14 of whom were excluded for analysis for either missing 12 months of follow-up or baseline pulmonary function. RESULTS: Among the 123 AATD patients, 27 (22.0%) had at least one exacerbation in the last 12 months of follow-up. Patients with Pi*ZZ phenotype were three times more likely than the rest of the population to experience any exacerbation (32.7 vs. 14.1%, p = 0.014; OR 3.0). BODE index was significantly higher in exacerbators than in non-exacerbators (3.9 ± 2.4 vs. 1.3 ± 1.2; p < 0.001), including on multivariate analysis (p = 0.002). Similar results were found for BODEx (multivariate p < 0.001). DLCO was the only functional parameter independently associated with exacerbations (p = 0.024). CONCLUSIONS: DLCO, BODE, and BODEx were independent predictors of exacerbations at 12 months in AATD patients. Understanding these risk factors can aid decision-making on AATD-related lung disease management and improve patient outcomes.

PET-CT SUVmax and Endobronchial Ultrasound Features for Prediction of Malignancy: A Prospective Study.

INTRODUCTION: Accurate and early staging of lung cancer has a critical impact on its prognosis. EBUS-TBNA is often the procedure of choice for mediastinal staging. Comprehension of the likelihood of malignancy of each lymph node (LN) can assist puncture decision-making during EBUS and offer insight of the procedure expected diagnostic yield. METHODS: Prospective analysis of mediastinal LN of patients undergoing EBUS-TBNA from April 2021 to May 2022. The relationship between PET-CT SUVmax levels, EBUS features, and malignancy on LN was investigated. For statistical analysis, patients were assigned to 3 groups: suspected malignancy (diagnosis and/or staging), confirmed malignancy (staging) or suspected benign disease. RESULTS: A total of 363 LN from 132 patients (71% male, mean 62 years old) were analyzed. Among those with suspected benign disease, no LN puncture resulted in a diagnosis of malignancy. PET-CT SUVmax and short axis size were independent factors for malignancy in LN of patients who underwent EBUS for suspected (p < .001 and p = .047, respectively) or confirmed malignancy (p < .001 and p < .001, respectively). All malignant LN presented SUVmax≥1.85 (≥2.85 for staging EBUS cases) and/or short axis size ≥4.28mm. Vascularized LN were more often malignant in either those with suspected (p = .087) or confirmed (p = .095) malignancy, although not statistically significant. LN that were simultaneously vascularized and lacked central hilar structure were also more commonly malignant (p = .013). CONCLUSION: LN that has higher SUVmax and are larger should be prioritized for puncture, followed by those vascularized and lacking central hilar structure. In staging EBUS cases, a systematic sampling (N3-N2-N1) is required and must precede any malignancy yield rationale.

Role of the one-minute sit-to-stand test in the diagnosis of post COVID-19 condition: a prospective cohort study.

OBJECTIVE: To analyze the relationship between one-minute sit-to-stand test (1MSTST) parameters and a diagnosis of post COVID-19 condition in a cohort of patients who previously had COVID-19. METHODS: This was a prospective cohort study of patients with post COVID-19 condition referred for body plethysmography at a tertiary university hospital. Post COVID-19 condition was defined in accordance with the current WHO criteria. RESULTS: Fifty-three patients were analyzed. Of those, 25 (47.2%) met the clinical criteria for post COVID-19 condition. HR was lower in the patients with post COVID-19 condition than in those without it at 30 s after initiation of the 1MSTST (86.2 ± 14.3 bpm vs. 101.2 ± 14.7 bpm; p < 0.001) and at the end of the test (94.4 ± 18.2 bpm vs. 117.3 ± 15.3 bpm; p < 0.001). The ratio between HR at the end of the 1MSTST and age-predicted maximal HR (HRend/HRmax) was lower in the group of patients with post COVID-19 condition (p < 0.001). An HRend/HRmax of < 62.65% showed a sensitivity of 78.6% and a specificity of 82.0% for post COVID-19 condition. Mean SpO2 at the end of the 1MSTST was lower in the patients with post COVID-19 condition than in those without it (94.9 ± 3.6% vs. 96.8 ± 2.4%; p = 0.030). The former group of patients did fewer repetitions on the 1MSTST than did the latter (p = 0.020). CONCLUSIONS: Lower SpO2 and HR at the end of the 1MSTST, as well as lower HR at 30 s after initiation of the test, were associated with post COVID-19 condition. In the appropriate clinical setting, an HRend/HRmax of < 62.65% should raise awareness for the possibility of post COVID-19 condition.

Expert Perspectives on the Management of Alpha 1-Antitrypsin Deficiency.

Alpha 1-antitrypsin deficiency is an inherited autosomal codominant disorder, which predisposes patients to lung and/or liver disease. Even though it is considered rare, it is one of the most frequent genetic disorders worldwide, albeit remaining underdiagnosed. Several organizations and societies, including the Portuguese Society of Pulmonology have been elaborating guidelines and recommendations for the diagnosis and management of alpha 1-antitrypsin deficiency. Nevertheless, some important matters are yet to be included in those, mainly due to lack of robust scientific evidence, and continue to represent a point of discussion. This article reviews some important scientific publications and expresses the perspectives of a group of Portuguese experts regarding the management of alpha 1-antitrypsin deficiency, namely in terms of the pre and neonatal diagnosis, the impact of the COVID-19 pandemic, the validity of replacement therapy in lung transplant-receiving, and finally, alternative strategies of alpha 1-antitrypsin deficiency treatment to improve the patients' quality of life.

A deficiência de alfa 1-antitripsina é uma doença hereditária autossómica codominante que aumenta a predisposição para o desenvolvimento de doença pulmonar e/ou hepática. Esta doença, embora seja considerada rara, é um dos distúrbios genéticos mais comuns em todo o mundo. Contudo, atualmente ainda constitui uma doença subdiagnosticada. Várias organizações e sociedades, incluindo a Sociedade Portuguesa de Pneumologia, elaboraram recomendações e diretrizes para o diagnóstico e gestão da deficiência de alfa 1-antitripsina. Porém, estes documentos ainda não abordam alguns temas relevantes associados à gestão da deficiência de alfa 1-antitripsina, principalmente devido à falta de robustez na evidência científica, que continuam a representar um ponto de discussão entre a comunidade médica. Neste artigo é feita a revisão de publicações científicas relevantes acerca da deficiência de alfa 1-antitripsina, e são descritas as perspetivas de especialistas portugueses sobre a gestão da deficiência de alfa 1-antitripsina, nomeadamente ao nível do diagnóstico pré e neonatal, do impacto da pandemia COVID-19, da validação da terapêutica de aumento em doentes que receberam um transplante pulmonar e, por fim, estratégias alternativas para a melhoria do tratamento da deficiência de alfa 1-antitripsina de modo a promover a qualidade de vida dos doentes.

European pathways of care in Alpha-1 Antitrypsin deficiency.

BACKGROUND: Despite initiatives to improve awareness and treatment of alpha-1 antitrypsin deficiency (AATD), country-level processes for AATD management remain unclear. OBJECTIVES: We conducted a pan-European physician survey to clarify the pathways for AATD care. METHOD: Professionals involved in AATD diagnosis and/or management completed a web-based survey on the detection, evaluation, monitoring and treatment of AATD and the utilisation of European reference network centres for rare lung diseases (ERN-LUNG). RESULTS: Surveys were completed by 166 physicians from 18 European countries. Overall, 25 % of respondents were unaware of local specific AATD testing guidelines, and most (72 %) had referred <10 patients to a specialist. However, there was general agreement regarding reasons for referral and the types of patient referred. Approaches to AATD testing are heterogenous, with significant between-country differences in the sample testing and collection methods used. Alpha-1 antitrypsin therapy is most frequently monitored using spirometry (98 %), gas transfer (79 %) or symptoms (82 %). Overall, 28 % of respondents were unfamiliar with ERN-LUNG centres, with Portugal and Spain reporting the lowest familiarity, and use of these centres for patient evaluation varied widely. However, engagement with ERN-LUNG centres was widely agreed to be useful when it did occur (especially in Italy and Poland). Little cross-border use of ERN-LUNG centres for patient testing/evaluation was reported. CONCLUSIONS: European care pathways for AATD are largely uniform, but with notable heterogeneity in testing approaches and a need for education and standardisation. Familiarity with and use of ERN-LUNG AATD services is variable, and increased awareness of these services is warranted.

Role of the one-minute sit-to-stand test in the diagnosis of post COVID-19 condition: a prospective cohort study / Papel do teste de se sentar e levantar durante um minuto no diagnóstico de síndrome pós-COVID-19: estudo prospectivo de coorte

ABSTRACT Objective: To analyze the relationship between one-minute sit-to-stand test (1MSTST) parameters and a diagnosis of post COVID-19 condition in a cohort of patients who previously had COVID-19. Methods: This was a prospective cohort study of patients with post COVID-19 condition referred for body plethysmography at a tertiary university hospital. Post COVID-19 condition was defined in accordance with the current WHO criteria. Results: Fifty-three patients were analyzed. Of those, 25 (47.2%) met the clinical criteria for post COVID-19 condition. HR was lower in the patients with post COVID-19 condition than in those without it at 30 s after initiation of the 1MSTST (86.2 ± 14.3 bpm vs. 101.2 ± 14.7 bpm; p < 0.001) and at the end of the test (94.4 ± 18.2 bpm vs. 117.3 ± 15.3 bpm; p < 0.001). The ratio between HR at the end of the 1MSTST and age-predicted maximal HR (HRend/HRmax) was lower in the group of patients with post COVID-19 condition (p < 0.001). An HRend/HRmax of < 62.65% showed a sensitivity of 78.6% and a specificity of 82.0% for post COVID-19 condition. Mean SpO2 at the end of the 1MSTST was lower in the patients with post COVID-19 condition than in those without it (94.9 ± 3.6% vs. 96.8 ± 2.4%; p = 0.030). The former group of patients did fewer repetitions on the 1MSTST than did the latter (p = 0.020). Conclusions: Lower SpO2 and HR at the end of the 1MSTST, as well as lower HR at 30 s after initiation of the test, were associated with post COVID-19 condition. In the appropriate clinical setting, an HRend/HRmax of < 62.65% should raise awareness for the possibility of post COVID-19 condition.

RESUMO Objetivo: Analisar a relação entre parâmetros do teste de se sentar e levantar durante um minuto (TSL1) e o diagnóstico de síndrome pós-COVID-19 em uma coorte de pacientes que anteriormente apresentaram COVID-19. Métodos: Estudo prospectivo de coorte de pacientes com síndrome pós-COVID-19 encaminhados para realizar pletismografia corporal em um hospital universitário terciário. A síndrome pós-COVID-19 foi definida conforme os critérios atuais da OMS. Resultados: Foram analisados 53 pacientes. Destes, 25 (47,2%) preencheram os critérios clínicos de síndrome pós-COVID-19. A FC foi menor nos pacientes com síndrome pós-COVID-19 do que naqueles sem a síndrome 30 s após o início do TSL1 (86,2 ± 14,3 bpm vs. 101,2 ± 14,7 bpm; p < 0,001) e no fim do teste (94,4 ± 18,2 bpm vs. 117,3 ± 15,3 bpm; p < 0,001). A relação entre a FC no fim do TSL1 e a FC máxima prevista para a idade (FCfim/FCmáx) foi menor nos pacientes com síndrome pós-COVID-19 (p < 0,001). A relação FCfim/FCmáx < 62,65% apresentou sensibilidade de 78,6% e especificidade de 82,0% para síndrome pós-COVID-19. A média da SpO2 no fim do TSL1 foi menor nos pacientes com síndrome pós-COVID-19 do que naqueles sem a síndrome (94,9 ± 3,6% vs. 96,8 ± 2,4%; p = 0,030). Os pacientes com síndrome pós-COVID-19 realizaram menos repetições durante o TSL1 do que os sem a síndrome (p = 0,020). Conclusões: SpO2 e FC mais baixas no fim do TSL1 e FC mais baixa 30 s após o início do teste apresentaram relação com síndrome pós-COVID-19. No contexto clínico apropriado, a relação FCfim/FCmáx < 62,65% deve alertar para a possibilidade de síndrome pós-COVID-19.

Alpha 1 Antitrypsin Therapy in Patients with Alpha 1 Antitrypsin Deficiency: Perspectives from a Registry Study and Practical Considerations for Self-Administration During the COVID-19 Pandemic.

Alpha 1 Antitrypsin deficiency (AATD) is a hereditary condition characterized by low serum Alpha 1 Antitrypsin (AAT) levels and a predisposition towards early-onset emphysema. Infusion of AAT is the only disease-modifying therapy that can sufficiently raise plasma AAT levels above the putative protective threshold and reduce the decline in lung density loss. Several randomized controlled trials (RCTs) and registry studies support the clinical efficacy of AAT therapy in slowing the progression of AATD-related emphysema and improving survival outcomes. The COVID-19 pandemic has prompted physicians to develop additional strategies for delivering AAT therapy, which are not only more convenient for the patient, but are "COVID-19 friendly", thereby reducing the risk of exposing these vulnerable patients. Intravenous (IV) self-administration of AAT therapy is likely to be beneficial in certain subgroups of patients with AATD and can remove the need for weekly hospital visits, thereby improving independence and well-being. Increasing the awareness of self-administration in AATD through the development of formal guidelines and training programs is required among both physicians and patients and will play an essential role, especially post-COVID-19, in encouraging physicians to consider self-administration for AATD in suitable patients. This review summarizes the benefits of AAT therapy on the clinical endpoints of mortality and quality of life (QoL) and discusses the benefits of self-administration therapy compared with conventional therapy administered by a healthcare professional. In addition, this review highlights the challenges of providing AAT therapy during the COVID-19 pandemic and the potential considerations for its implementation thereafter.

Treatable Traits in COPD - A Proposed Approach.

The well-recognized individual heterogeneity within COPD patients has led to a growing interest in greater personalization in the approach of these patients. Thus, the treatable traits strategy has been proposed as a further step towards precision medicine in the management of chronic airway disease, both in stable phase and acute exacerbations. The aim of this paper is to perform a critical review on the treatable traits strategy and propose a guide to approach COPD patients in the light of this new concept. An innovative stepwise approach is proposed - a multidisciplinary model based on two distinct phases, with the potential to be implemented in both primary care and hospital settings. The first phase is the initial and focused assessment of a selected subset of treatable traits, which should be addressed in all COPD patients in both settings (primary care and hospital). As some patients may present with advanced disease at diagnosis or may progress despite this initial treatment requiring a more specialized assessment, they should progress to a second phase, in which a broader approach is recommended. Beyond stable COPD, we explore how the treatable traits strategy may be applied to reduce the risk of future exacerbations and improve the management of COPD exacerbations. Since many treatable traits have already been related to exacerbation risk, the strategy proposed here represents an opportunity to be proactive. Although it still lacks prospective validation, we believe this is the way forward for the future of the COPD approach.

Comparative analysis of the bronchoalveolar microbiome in Portuguese patients with different chronic lung disorders.

The lung is inhabited by a diverse microbiome that originates from the oropharynx by a mechanism of micro-aspiration. Its bacterial biomass is usually low; however, this condition shifts in lung cancer (LC), chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD). These chronic lung disorders (CLD) may coexist in the same patient as comorbidities and share common risk factors, among which the microbiome is included. We characterized the microbiome of 106 bronchoalveolar lavages. Samples were initially subdivided into cancer and non-cancer and high-throughput sequenced for the 16S rRNA gene. Additionally, we used a cohort of 25 CLD patients where crossed comorbidities were excluded. Firmicutes, Proteobacteria and Bacteroidetes were the most prevalent phyla independently of the analyzed group. Streptococcus and Prevotella were associated with LC and Haemophilus was enhanced in COPD versus ILD. Although no significant discrepancies in microbial diversity were observed between cancer and non-cancer samples, statistical tests suggested a gradient across CLD where COPD and ILD displayed the highest and lowest alpha diversities, respectively. Moreover, COPD and ILD were separated in two clusters by the unweighted UniFrac distance (P value = 0.0068). Our results support the association of Streptoccocus and Prevotella with LC and of Haemophilus with COPD, and advocate for specific CLD signatures.

Reduction of Severe Exacerbations of COPD during COVID-19 Pandemic in Portugal: A Protective Role of Face Masks?

Viral infections are known to be the main trigger for Chronic obstructive pulmonary disease (COPD) exacerbations. Face masks are acknowledged for effective viral aerosol shedding reduction. COVID-19 pandemic generated an opportunity to study the impact of face masks and confinement on droplet transmission diseases, usually implicated in acute exacerbations of COPD (AECOPD). We aimed to evaluate the variation on severe AECOPD (sAECOPD) rate in a Portuguese COPD cohort during the first COVID-19 lockdown and following months. This retrospective self-controlled study enrolled 322 adult patients followed at COPD-specialized consultation in a tertiary hospital from February 2016 to July 2020, of whom 286 met inclusion criteria. Severe AECOPD events were registered from March 2020 (beginning of state of emergency) until July 2020. From 2016 to 2019 there was a mean of 38 patients per year with sAECOPD. During 2020, 11 patients experienced sAECOPD. Over the course of 2020 there was a 73.4% (p < 0.001) decrease in sAECOPD events comparing with previous years' average. After the end of State of Emergency, the rate of sAECOPD events also declined by 74.6% (p < 0.001) comparing with the same timeline of previous years. Results were consistent and statistically significant when comparing 2020 with each of previous years for every period of analysis. Our findings suggest a sustained decrease in the rate of sAECOPD during confinement and in the following months. The widespread use of face mask and social distancing during COVID-19 pandemic may play an important role in preventing the transmission of respiratory infections and consequently reducing sAECOPD.

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

RATIONALE AND OBJECTIVES: Alpha-1 antitrypsin deficiency (AATD) is a genetic condition that leads to an increased risk of emphysema and liver disease. Despite extensive investigation, there remain unanswered questions concerning the natural history, pathophysiology, genetics and the prognosis of the lung disease in association with AATD. The European Alpha-1 Clinical Research Collaboration (EARCO) is designed to bring together researchers from European countries and to create a standardised database for the follow-up of patients with AATD. STUDY DESIGN AND POPULATION: The EARCO Registry is a non-interventional, multicentre, pan-European, longitudinal observational cohort study enrolling patients with AATD. Data will be collected prospectively without interference/modification of patient's management by the study team. The major inclusion criterion is diagnosed severe AATD, defined by an AAT serum level <11 µM (50 mg·dL-1) and/or a proteinase inhibitor genotype ZZ, SZ or compound heterozygotes or homozygotes of other rare deficient variants. Assessments at baseline and during the yearly follow-up visits include lung function testing (spirometry, body plethysmography and diffusing capacity of the lung), exercise capacity, blood tests and questionnaires (symptoms, quality of life and physical activity). To ensure correct data collection, there will be designated investigator staff to document the data in the case report form. All data will be reviewed by the EARCO database manager. SUMMARY: The EARCO Registry aims to understand the natural history and prognosis of AATD better with the goal to create and validate prognostic tools to support medical decision-making.

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

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.

Profiling of lung microbiota discloses differences in adenocarcinoma and squamous cell carcinoma.

The lung is a complex ecosystem of host cells and microbes often disrupted in pathological conditions. Although bacteria have been hypothesized as agents of carcinogenesis, little is known about microbiota profile of the most prevalent cancer subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC). To characterize lung cancer (LC) microbiota a first a screening was performed through a pooled sequencing approach of 16S ribosomal RNA gene (V3-V6) using a total of 103 bronchoalveaolar lavage fluid samples. Then, identified taxa were used to inspect 1009 cases from The Cancer Genome Atlas and to annotate tumor unmapped RNAseq reads. Microbial diversity was analyzed per cancer subtype, history of cigarette smoking and airflow obstruction, among other clinical data. We show that LC microbiota is enriched in Proteobacteria and more diverse in SCC than ADC, particularly in males and heavier smokers. High frequencies of Proteobacteria were found to discriminate a major cluster, further subdivided into well-defined communities' associated with either ADC or SCC. Here, a SCC subcluster differing from other cases by a worse survival was correlated with several Enterobacteriaceae. Overall, this study provides first evidence for a correlation between lung microbiota and cancer subtype and for its influence on patient life expectancy.

Diagnosis and management of α1-antitrypsin deficiency in Europe: an expert survey.

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.