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).

• Klíčová slova
• Alpha-1 antitrypsin, Lung disease, PI*SS, Registries,
• MeSH
• alfa-1-antitrypsin * genetika   MeSH
• deficit alfa1-antitrypsinu * genetika   epidemiologie   diagnóza   MeSH
• genotyp * MeSH
• kvalita života MeSH
• lidé středního věku MeSH
• lidé MeSH
• plicní nemoci genetika   epidemiologie   diagnóza   MeSH
• registrace MeSH
• rizikové faktory MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• Názvy látek
• alfa-1-antitrypsin * MeSH
• SERPINA1 protein, human MeSH Prohlížeč

BACKGROUND: Alpha-1 antitrypsin deficiency (AATD) is a rare disease that is associated with an increased risk of pulmonary emphysema. The European AATD Research Collaboration (EARCO) international registry was founded with the objective of characterising the individuals with AATD and investigating their natural history. METHODS: The EARCO registry is an international, observational and prospective study of individuals with AATD, defined as AAT serum levels < 11 μM and/or proteinase inhibitor genotypes PI*ZZ, PI*SZ and compound heterozygotes or homozygotes of other rare deficient variants. We describe the characteristics of the individuals included from February 2020 to May 2022. RESULTS: A total of 1044 individuals from 15 countries were analysed. The most frequent genotype was PI*ZZ (60.2%), followed by PI*SZ (29.2%). Among PI*ZZ patients, emphysema was the most frequent lung disease (57.2%) followed by COPD (57.2%) and bronchiectasis (22%). Up to 76.4% had concordant values of FEV1(%) and KCO(%). Those with impairment in FEV1(%) alone had more frequently bronchiectasis and asthma and those with impairment in KCO(%) alone had more frequent emphysema and liver disease. Multivariate analysis showed that advanced age, male sex, exacerbations, increased blood platelets and neutrophils, augmentation and lower AAT serum levels were associated with worse FEV1(%). CONCLUSIONS: EARCO has recruited > 1000 individuals with AATD from 15 countries in its first 2 years. Baseline cross sectional data provide relevant information about the clinical phenotypes of the disease, the patterns of functional impairment and factors associated with poor lung function. Trial registration www. CLINICALTRIALS: gov (ID: NCT04180319).

• Klíčová slova
• Alpha-1 antitrypsin, Phenotypes, Registry,
• MeSH
• alfa-1-antitrypsin genetika   MeSH
• bronchiektazie * diagnóza   epidemiologie   MeSH
• chronická obstrukční plicní nemoc * genetika   MeSH
• deficit alfa1-antitrypsinu * diagnóza   epidemiologie   genetika   MeSH
• genotyp MeSH
• lidé MeSH
• plicní emfyzém * diagnóza   epidemiologie   komplikace   MeSH
• prospektivní studie MeSH
• průřezové studie MeSH
• registrace MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• alfa-1-antitrypsin MeSH

Background: Adherence to inhaled medication constitutes a major problem in patients with chronic obstructive pulmonary disease (COPD) globally. However, large studies evaluating adherence in its entirety and capturing a large variety of potentially associated factors are still lacking. Objective: To study both elementary types of adherence to chronic inhaled COPD medication in "real-life" COPD patients and to assess relationships with a wide-ranging spectrum of clinical parameters. Methods: Data from the Czech Multicentre Research Database (CMRD) of COPD, an observational prospective study, were used. Overall adherence (OA) was evaluated with Morisky Medication Adherence Scale (©MMAS-4) and adherence to an application technique (A-ApplT) with the Five Steps Assessment. Mann-Whitney U test, Spearman's correlation, and logistic regression were used to explore relationships between variables. Results: Data of 546 participants (69.6% of all patients from the CMRD) were analyzed. Two-thirds self-reported optimal OA, but only less than one-third demonstrated A-ApplT without any error. OA did not correlate with A-ApplT. Next, better OA was associated with higher education, a higher number of inhalers, a lower rate of exacerbations, poorer lung function, higher degree of upper respiratory tract symptoms (SNOT-22), absence of depressive symptoms, ex-smoking status, regular mouthwash after inhaled corticosteroids (ICS), and flu vaccination. By contrast, better A-ApplT was associated with a lower number of inhalers, better lung function, and regular mouthwash after ICS. Independent predictors of nonoptimal OA included lower degree of education, absence of flu vaccination, anemia, depression, and peptic ulcer history, whereas independent predictors of lower A-ApplT were lower education, absence of regular mouthwash after ICS, and higher COPD Assessment Test score. Conclusions: Parameters associated with OA and A-ApplT differ, and those associated with both adherence domains are sometimes associated inversely. Based on this finding, we understand these as two separate constructs with an overlap.

• Klíčová slova
• COPD, adherence, application technique, compliance, inhalation systems,
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Subjects with COPD frequently develop considerable weakness and deconditioning of the inspiratory musculature, which can be corrected with inspiratory muscle training (IMT). While rehabilitation centers may be able to provide IMT as part of the rather complex management of COPD, there is currently a lack of rehabilitation services in the Czech Republic. Remote IMT may then benefit subjects with COPD who are unable to attend or do not have access to rehabilitation programs. We aim at evaluating the utility of the test of incremental respiratory endurance (TIRE) as an at-home IMT method in subjects with COPD, while comparing the effectiveness of this novel training approach to the outcomes of traditional, threshold loading IMT protocols. METHODS/DESIGN: This prospective, randomized controlled trial will comprise 8 weeks of at-home IMT sessions with remote supervision followed by 4 months of unsupervised, independent IMT. Eligible subjects will be randomly assigned to one of the following three distinct home-based IMT protocols: (1) TIRE, (2) Threshold loading, and (3) Sham training. Subjects allocated to the TIRE group will train once daily using an advanced IMT electronic system (PrO2), while the other two groups will receive threshold devices. Study outcomes will include measures of inspiratory muscle strength and endurance, pulmonary function, COPD-specific symptomatology, functional exercise capacity, surrogate markers of mortality risk, mental health status and health-related quality of life. DISCUSSION: While we acknowledge the value of threshold loading IMT protocols, we believe that the TIRE training method has the potential to provide additional clinical benefits in COPD given its sophisticated remote tracking system and ability to modulate all aspects of muscular performance, including not only strength but also endurance, power and work capacity, allowing users to achieve considerably higher inspiratory pressures throughout the full range of inspiration when compared to other more traditionally used IMT methods.

• Klíčová slova
• chronic obstructive pulmonary disease, inspiratory muscle training, pulmonary rehabilitation, quality of life, telemedicine, test of incremental respiratory endurance,
• MeSH
• chronická obstrukční plicní nemoc * diagnóza   terapie   MeSH
• dechová cvičení * MeSH
• dýchací svaly * MeSH
• kvalita života * MeSH
• lidé MeSH
• prospektivní studie MeSH
• randomizované kontrolované studie jako téma MeSH
• tolerance zátěže MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Česká republika MeSH

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.

• Publikační typ
• časopisecké články MeSH

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) constitutes a major health challenge in Central and Eastern European (CEE) countries. However, clinical phenotypes, symptom load, and treatment habits of patients with COPD in CEE countries remain largely unknown. This paper provides a rationale for phenotyping COPD and describes the methodology of a large study in CEE. METHODS/DESIGN: The POPE study is an international, multicenter, observational cross-sectional survey of patients with COPD in CEE. Participation in the study is offered to all consecutive outpatients with stable COPD in 84 centers across the CEE region if they fulfill the following criteria: age >40 years, smoking history ≥10 pack-years, a confirmed diagnosis of COPD with postbronchodilator FEV1/FVC <0.7, and absence of COPD exacerbation ≥4 weeks. Medical history, risk factors for COPD, comorbidities, lung function parameters, symptoms, and pharmaceutical and nonpharmaceutical treatment are recorded. The POPE project is registered in ClinicalTrials.gov with the identifier NCT02119494. OUTCOMES: The primary aim of the POPE study was to phenotype patients with COPD in a real-life setting within CEE countries using predefined classifications. Secondary aims of the study included analysis of differences in symptoms, and diagnostic and therapeutic behavior in participating CEE countries. CONCLUSION: There is increasing acceptance toward a phenotype-driven therapeutic approach in COPD. The POPE study may contribute to reveal important information regarding phenotypes and therapy in real-life CEE.

• Klíčová slova
• COPD, Central Europe, Eastern Europe, GOLD, comorbidity, phenotypes, study,
• MeSH
• chronická obstrukční plicní nemoc genetika   MeSH
• fenotyp * MeSH
• lidé MeSH
• průřezové studie MeSH
• výzkumný projekt MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• pozorovací studie MeSH
• Geografické názvy
• Evropa MeSH