Reliability of individual differences in distractor suppression driven by statistical learning.

A series of recent studies has demonstrated that attentional selection is modulated by statistical regularities, even when they concern task-irrelevant stimuli. Irrelevant distractors presented more frequently at one location interfere less with search than distractors presented elsewhere. To account for this finding, it has been proposed that through statistical learning, the frequent distractor location becomes suppressed relative to the other locations. Learned distractor suppression has mainly been studied at the group level, where individual differences are treated as unexplained error variance. Yet these individual differences may provide important mechanistic insights and could be predictive of cognitive and real-life outcomes. In the current study, we ask whether in an additional singleton task, the standard measures of attentional capture and learned suppression are reliable and stable at the level of the individual. In an online study, we assessed both the within- and between-session reliability of individual-level measures of attentional capture and learned suppression. We show that the measures of attentional capture, but not of distractor suppression, are moderately stable within the same session (i.e., split-half reliability). Test-retest reliability over a 2-month period was found to be moderate for attentional capture but weak or absent for suppression. RT-based measures proved to be superior to accuracy measures. While producing very robust findings at the group level, the predictive validity of these RT-based measures is still limited when it comes to individual-level performance. We discuss the implications for future research drawing on inter-individual variation in the attentional biases that result from statistical learning.

Comparison of Identification and Quantification of Polyphenolic Compounds in Skins and Seeds of Four Grape Varieties.

The aim of this study was to identify and quantify polyphenolic compounds in skin extracts from four Bulgarian grape varieties and compare them to those of seed extracts. The values of total phenolic contents, flavonoids, anthocyanins, procyanidins and an ascorbic acid in grape skin extracts were determined. The antioxidant capacities of skin extracts were evaluated using four different methods. The total phenolic content of skin extracts was 2-3 times lower than those of seed extracts. The significant difference between total parameter values of individual grape varieties were also found. According to the total phenolic content and antioxidant capacity of skin extracts, the different grape varieties were arranged in the following order: Marselan ≥ Pinot Noir ˃ Cabernet Sauvignon ˃ Tamyanka. The individual compounds in the grape skin extracts were determined using RP-HPLC and compared with those of the seed extracts. The determined composition of skin extracts was significantly different from the seed extracts' composition. Quantitative evaluation of the procyanidins and catechins in the skins was carried out. A correlation between phenolic contents, individual compounds and antioxidant capacity of different extracts was found. The studied grape extracts have a potential to be applied as natural antioxidants in the pharmaceutical and food industries.

Assessment of extrafine beclomethasone/formoterol for the treatment of chronic obstructive pulmonary disease: A non-interventional study in a Bulgarian population.

BACKGROUND: The beneficial effects of application of a fixed dose beclomethasone dipropionate (BDP) and formoterol fumarate (F) for the treatment of severe chronic obstructive disease (COPD) has been amply proven in well controlled clinical trials. Whether this also holds for real-world conditions and in such a heterogeneous patient population as is encountered in Bulgaria remained to be investigated. METHODS: In an observational, non-interventional study, 441 Bulgarian patients with severe COPD who were enrolled at 36 sites across the country received extrafine BDP/FF-combination therapy using the NEXThaler® DPI or the Foster® pMDI over a period of 16 weeks. At visits at the beginning, after 4 weeks and at the end of the study, alterations in lung function parameters FEV1 and FVC, disease symptoms, changes in CAT score, and patient distribution in GOLD 2017 categories A through D were assessed. RESULTS: A large share of the Bulgarian patients with severe COPD suffered from serious comorbidities, received additional medication, and about 2/3 were former or current smokers. Extrafine BDP/FF caused an increase in mean FEV1, FVC, a decrease of health impact as assessed by the CAT score, and a considerable shift of the share of category C and D patients towards A and B. In addition, the percentage of patients that were free of symptoms impacting everyday life such as fatigue and shortness of breath at rest increased throughout the study. A comparison of both application devices indicated that the NEXThaler® was superior in terms of lung functional aspects, as these parameters displayed a constant improvement over the observation period, whereas they plateaued at week 4 when using the pMDI. CONCLUSIONS: The therapeutic benefits of extrafine BDP/FF known from clinical trials could also be observed in a real-world setting, even in such a heterogenous patient population as the Bulgarian. The NEXThaler® appeared to be highly efficient in this setting, opening a new choice for the lung specialist and the patient to select the one device considered most suitable and practical.

Simultaneous enumeration of CD34+ and CD45+ cells using EasyCounter image cytometer.

Accurate counting of CD34-positive cells is important for successful hematopoietic stem cell transplantation that is applied to various diseases. The aim of this study was simultaneous counting of viable CD34+ (vCD34+) and CD45+ (vCD45+) cells in apheresis samples by automatic immunofluorescence counter - EasyCounter BC. CD34+ and CD45+ cells were counted using two conjugates anti-CD34 antibody - dR110 and anti-CD45 antibody - ATTO620, respectively. The conjugates were prepared by carbodiimide method. Dead nuclear cells were counted by using monomethine cyanine dye PO-TEDM 1. The linearity and reproducibility of EasyCounter BC for CD34+ cell counting were determined (R2 = 0.99; CV values for vCD34+ cells were 6.8 ÷ 8.5% and for vCD45+ cells 4.1 ÷ 7.2%). The obtained results by EasyCounter BC were compared with those by other two standard methods - flow cytometry (Guava easyCyte 8HT) and fluorescence microscopic method (Olympus BX51) with the same conjugates. Passing-Bablok regression was performed to determine the relationship between the results of the three methods, analyzing 43 apheresis samples. Correlation coefficients for vCD45+ and vCD34+ between EasyCounter BC and Olympus microscope were 0.987 and 0.982, respectively (P < 0.0001). Better results were obtained between EasyCounter BC and flow cytometer Guava, 0.998 for vCD45+ and 0.998 for vCD34+ (P < 0.0001).

The relationship of bovine milk somatic cell count to neutrophil level in samples of cow's milk assessed by an automatic cell counter.

This research communication describes the application of a fluorescent automatic cell counter Lactoscan SCC for simultaneous determination of somatic cell count and neutrophils in bovine milk. The obtained results were compared with results obtained by a flow cytometer and a light microscope. The Pearson correlations between the methods were calculated. A comparison between the main characteristics of the three kinds of analysis was made - the assay duration and the intra-assay precision. A relation between the SCC and neutrophil cells was observed in 55 milk samples. The obtained results confirm that the simultaneous determination of SCC and neutrophil analysis are necessary and support the early diagnosis of mastitis, the timely treatment of the animal and the avoidance of major economic losses.

CD34+ stem cell counting using labeled immobilized anti-CD34 antibody onto magnetic nanoparticles and EasyCounter BC image cytometer.

The ability of immobilized conjugate anti-CD34+ monoclonal antibody-dR110 and free conjugate anti-CD45+ monoclonal antibody-ATTO620 to precisely enumerate CD34+ stem cells and CD45+ cells in apheresis samples were evaluated. The conjugates anti-CD34+ antibody-dR110 and anti-CD45+- antibody-ATTO620 were prepared. Functionalized magnetic nanoparticles (MNPs) were synthesized. The anti-CD34+ antibody-dR110 conjugate was immobilized on the modified MNPs using a carbodiimide method. The stem cell count in thawed apheresis samples was determined using the free and the immobilized conjugate anti-CD34+ antibody-dR110 on MNPs and an image cell counter EasyCounter BC. A higher stem cell count and more accurate results were obtained with the immobilized conjugate, because a separation and concentration of the stem cells bound to antibody-dR110 on MNPs by external magnet were performed. Coefficients of variation of CD34+ cell count in apheresis samples, determined by EasyCounter BC, were ranged from 5.5 to 6.9% and those of CD45+ cell count from 3.8 to 4.7%. The viability of CD34+ cells was high from 98.5 to 99.6%. It was found that correlation coefficient between the flow cytometer and automatic cell counter, using free anti-CD34+ antibody-dR110 was 0.94, and when using immobilized anti-CD34+antibody-dR110 on MNPs, the correlation coefficient was 0.97.

Autofluorescence and White Light Bronchoscopy in the Diagnosis of Endobronchial Malignant Lesions.

BACKGROUND: Autofluorescence bronchoscopy (AFB) allows a more sensitive approach to the diagnosis of premalignant and malignant endobronchial lesions than white light bronchoscopy (WLB) can do. AIM: To assess the autofluorescence bronchoscopy and white light bronchoscopy in diagnosing malignant endobronchial lesions. MATERIALS AND METHODS: The design of the study is a retrospective case-control study. Thirty-two parameters were entered into an Excel file and analysed with SPSS v. 21 for Mac book Pro. Endoscopy findings were graded in 4 options and morphological results - in 9 options according to WHO classification. The results are presented using McNemar's test and sensitivity, specificity and positive and negative predictive values as well. RESULTS: Three hundred and three patients were included in the study. Lung cancer was found in 38.3% of the patients using histology and in 35.6% - using cytology. McNemar's test for AFB finding for suspected and malignant lesions OR was 8.333 (95% CI 3.571-23.784) while for WLB OR was 0.128 (95% CI 0.045-0.299). For cytological results OR was 3.800 (95% CI 2.123-7.227) and 3.471 (95% CI 1.996-6.351), respectively. P value was <0.0001 for all tests. Sensitivity for AFB and WLB was 94.83% but specificity was 52.83% and 55.66% if histology was used. For cytology these numbers were respectively 86.11% and 84.26% for sensitivity, and 63.69% and 62.42% for specificity. CONCLUSION: AFB has an advantage over WLB in diagnosing endobronchial malignant lesions. Biopsying suspicious, not only visible malignant lesions, increased diagnostic sensitivity.

Diagnosis and Treatment of Three Cases of Bronchial Carcinoma In Situ.

As part of a retrospective study on bronchoscopies performed at the Clinic of Pneumonology and Phthisiatry of the University Hospital - Pleven by autofluorescence bronchoscopy we found 3 cases diagnosed with carcinoma in situ. They were treated in different ways - endobronchial electrocoagulation, extraction by forceps biopsy and open surgery, but the result was the same - clinical healing. The paper presents the three clinical cases and the analysis of the treatment.

Impact of Air Pollution and Outdoor Temperature on the Rate of Chronic Obstructive Pulmonary Disease Exacerbations.

BACKGROUND: Environmental pollution can be one of the main risk factors for acute exacerbations of chronic obstructive pulmonary disease (COPD). AIM: To study the relationship between air pollution, outdoor temperature and exacerbations of COPD. MATERIALS AND METHODS: COPD patients (n=1432) were followed up for one year. The levels of particulate matter up to 10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2) and outside temperatures were collected from the Environmental Agency database. RESULTS: A total of 309 acute COPD exacerbations (AECOPD) were recorded in the analysis. The daily mean concentrations of PM10 were found to correlate significantly with the daily mean concentrations of NO2 and SO2 (ρ 0.34 and ρ 0.49, respectively; p=0.0001). The negative correlations between the daily mean temperature and the daily mean levels of PM10, NO2 and SO2 were also significant (ρ -0.44, ρ -0.11, and ρ -0.37, respectively; p=0.0001). The daily number of AECOPD correlated with the mean levels of PM10 in the previous six days (ρ 0.14; p=0.02) and the lower outdoor temperature (ρ -0.2; p=0.001). The negative correlation between the daily number of AECOPD and the mean daily temperature was stronger in days with levels of PM10 above 50 µg/m3 (ρ -0.3 p=0.02 vs. ρ -0.18 p= 0.01). CONCLUSION: Lower daily mean temperatures were associated with the levels of air pollutants. The level of PM10 correlated with the levels of the other air pollutants. The daily number of AECOPD was found to correlate weakly, but signifi cantly with the mean level of PM10 in the previous six days.

Efficacy and safety of AZD3199 vs formoterol in COPD: a randomized, double-blind study.

BACKGROUND: We investigated the efficacy and safety of AZD3199, a novel inhaled ultra-LABA, with the main aim of establishing a dose that would maintain 24-hour bronchodilation in patients with COPD. METHODS: Patients (n = 329) were randomized to AZD3199 (200, 400 or 800 µg o.d.), formoterol (9 µg b.i.d.) or placebo via Turbuhaler® in a parallel group study. The primary objective of the study was to compare the clinical efficacy of three doses of AZD3199 inhaled once daily with 9 µg formoterol twice daily and placebo, over a 4-week treatment period in adults with moderate-to-severe COPD. After 4 weeks, peak (0-4 h) and trough (24-26 h) forced expiratory volume in 1 second (FEV1) were assessed as the primary efficacy outcome variables. RESULTS: All AZD3199 doses significantly increased mean peak and trough FEV1 versus placebo (106-171 ml and 97-110 ml increases, respectively), but with no clear dose-response; the level of bronchodilation was comparable to or greater than that achieved with formoterol. Forced vital capacity (FVC) at peak bronchodilation also significantly increased with AZD3199 versus placebo (153-204 ml). COPD symptom scores and reliever use were reduced with AZD3199, while FEV1 reversibility was unaltered. Adverse events were mild-to-moderate, with no safety concerns identified. Drug exposure was dose-proportional, but lower than predicted from healthy volunteers. CONCLUSIONS: All three doses of AZD3199 produced 24-hour bronchodilation, but with no clear dose-response, suggesting that doses of 200 µg or less may be sufficient to maintain bronchodilation over 24 hours in patients with COPD. No safety concerns were identified. Further studies are required to determine the once-daily AZD3199 dose for COPD. TRIAL REGISTRATION: Clinicaltrials.gov, NCT00929708.

Regional advisory board position statement on optimal pneumococcal vaccination in adults. Update to 2011 consensus on adult pneumococcal disease: update on optimal pneumococcal vaccination in adults.

BACKGROUND: An important development in the field of adult pneumococcal vaccination since the last Consensus Statement, published by the Expert Panel of Central and Eastern Europe and Israel (the Region) in September 2012, was the licensure of the 13-valent pneumococcal conjugate vaccine (PCV13) for adults aged 50 years and older. DISCUSSION: The Expert Panel has developed this Position Statement as an update to its previous Consensus to address the following topics which are likely to be on the agenda of national scientific societies during the ongoing updates of vaccination recommendations in the Region: the availability of a pneumococcal conjugate vaccine for adults over 50 years of age, the available clinical evidence on its use in adults, and the future place of conjugate vaccines in adult pneumococcal vaccination. The Expert Panel concluded that there is sufficient epidemiologic immunogenicity and safety evidence to use PCV 13 in adults over 50 years of age. RESULTS: The use of conjugate vaccine induces immunological memory and can overcome some limitations associated with the plain polysaccharide vaccine (PPV). It was also agreed that, if the use of PPV is considered appropriate, PCV13 should be administered first, regardless of prior pneumococcal vaccination status.

Antimicrobial Potential, Antioxidant Activity, and Phenolic Content of Grape Seed Extracts from Four Grape Varieties.

The aim of this study was to evaluate the total phenolic content, composition, and antioxidant and antibacterial activities of four grape seed extracts (Cabernet Sauvignon, Marselan, Pinot Noir, and Tamyanka). The total phenolic content (TPC) and flavonoid, anthocyanin, procyanidin, ascorbic acid, DPPH, and ABTS antioxidant capacities of the grape seed extracts (GSEs) were determined. The extracts showed high TPC values (79.06-111.22 mg GAE/g). The individual components in the GSEs were determined using HPLC. High contents of catechin, epicatechin, and procyanidin B1 were found in the extracts. The antimicrobial activity of the obtained GSEs against Staphylococcus aureus, Bacillus cereus, and Escherichia coli was evaluated using the agar diffusion test and a test to determine the minimum inhibitory concentration (MIC). According to the effect on the growth of pathogens, the extracts were ranked in the following order: Pinot Noir > Marselan > Cabernet Sauvignon > Tamyanka. The tested bacteria showed high sensitivity to the extracts (MIC = 0.12-0.50 mg/mL). According to the MIC values, the bacteria were in the following order: S. aureus > B. cereus > E. coli. A correlation was found between the phenolic content of the GSEs and their antibacterial potential. The obtained results show that the studied GSEs have good potential as antioxidant and antimicrobial agents.

Characteristics of patients with severe asthma in primary and secondary care settings considered eligible for biological therapy - the Bulgarian RECOGNISE study.

INTRODUCTION: Asthma is a major non-communicable disease. It affects both children and adults, but is the most common chronic condition among the former. While inhaled controller drugs stabilize the disease in most asthma patients, there are a certain number of people who suffer from severe asthma, which requires treatment escalation. Oral corticosteroids are usually added, but they are associated with various side effects that may limit their application. The introduction of biologicals targeting inflammatory mediators has opened a new era of asthma treatment highlighting the importance of patient characterization.

Opportunity for healthy ageing: lessening the burden of adult pneumococcal disease in Central and Eastern Europe, and Israel.

The population of the Region (Central Europe, Eastern Europe, and Israel) is ageing, necessitating preventative programmes to maintain a healthy and active lifestyle in older age groups. Invasive pneumococcal disease (including bacteremic pneumonia, bacteremia without a focus, and meningitis) has higher incidence, morbidity and mortality in older adults and is a substantial public health burden in the ageing population. Surveillance in the Region establishes a significant burden in older adults of invasive pneumococcal disease (IPD), which still appears to be under-estimated as compared with other countries, and this warrants an improvement in surveillance systems. The largest proportion of IPD in adults is bacteremic pneumonia. Community-acquired pneumonia (CAP), largely attributable to S. pneumoniae, can be bacteremic or non-bacteremic; the non-bacteremic forms of CAP also represent a significant burden in the Region. The burden of pneumococcal disease can be reduced with programmes of effective vaccination. Recommendations on pneumococcal vaccination in adults vary widely across the Region. The main barrier to implementation of vaccination programmes is low awareness among healthcare professionals on serious heatlh consequences of adult pneumococcal disease and of vaccination options. The Expert Panel calls on healthcare providers in the Region to improve pneumococcal surveillance, optimize and disseminate recommendations for adult vaccination, and support awareness and education programmes about adult pneumococcal disease.

Reactivation of tuberculosis in patient treated with the antifibrotic drug nintedanib.

The novel antifibrotic drugs for idiopathic pulmonary fibrosis give us an opportunity for change the course of the disease. Their usages are expected to rise with the widening of their indications. We report a case of a patient who complains of fatigue breathlessness on exertion, dry cough, and fever up to 38°C while on the antifibrotic drug nintedanib treatment. We proved the reactivation of latent tuberculosis (TB) by microbiology of bronchial lavage. The outpatient died from massive hemoptysis. To our knowledge, we present the first case in the world for reactivation of TB in a patient on treatment with nintedanib. We suggest closer follow-up for patients with a history of TB or living in countries with higher TB prevalence during treatment with antifibrotic drugs.

Biodegradation of bisphenols with immobilized laccase or tyrosinase on polyacrylonitrile beads.

The biodegradation of waters polluted by some bisphenols, endowed with endocrine activity, has been studied by means of laccase or tyrosinase immobilized on polyacrylonitrile (PAN) beads. Bisphenol A (BPA), Bisphenol B (BPB), Bisphenol F (BPF) and Tetrachlorobisphenol A (TCBPA) have been used. The laccase-PAN beads system has been characterized as a function of pH, temperature and substrate concentration. The biochemical parameters so obtained have been compared with those of the free enzyme to evidence the modification induced by the immobilization process. Once characterized, the laccase-PAN beads have been employed in a fluidized bed reactor to determine for each of the four bisphenols the degradation rate constant (k); the τ(50), i.e., the time to obtain the 50% of degradation, and the removal efficiency (RE(90)) after 90 min of enzyme treatment. The same parameters have been measured for each of the four pollutants with the same fluidized bed bioreactor loaded with tyrosinase-PAN beads. The internal comparison, i.e., in each of the two catalytic systems, has shown that both enzymes exhibit a removal efficiency in the following order BPF>BPA>BPB>TCBPA. The external comparison, i.e., the comparison between the two catalytic system, has shown that the catalytic power of laccase were higher than that of tyrosinase. The operational stability of both catalytic systems resulted excellent, since they maintained more than 80% of the initial activity after 30 days of work.

Distractor suppression leads to reduced flanker interference.

Recent studies using the additional singleton paradigm have shown that regularities in distractor locations can cause biases in the spatial priority map, such that attentional capture by salient singletons is reduced for locations that are likely to contain distractors. It has been suggested that this type of suppression is proactive (i.e., occurring before display onset). The current study replicated the original findings using an online version of the task. To further assess the suppression of high-probability locations, we employed a congruence manipulation similar to the traditional flanker effect, where distractors could be either congruent or incongruent with the response to the target. Experiment 1 shows that through statistical learning distractor suppression reduces the interference from incongruent distractors, as participants made less errors in high-probability versus low-probability conditions. In Experiment 2, participants were forced to search for a specific target feature (the so-called feature-search mode), which is assumed to allow participants to ignore distractors in a top-down manner. Yet even when this "top-down" search mode was employed, there was still a congruence effect when the distractor singleton was presented at the low-probability but not at the high-probability location. The absence, but not reversal, of a congruence effect at the high-probability location also further indicates that this distractor suppression mechanism is proactive. The results indicate that regardless of the search mode used, there is suppression of the high-probability location indicating that this location competes less for attention within the spatial priority map than all other locations.

Simultaneous determination of ochratoxin A and enterotoxin A in milk by magnetic nanoparticles based fluorescent immunoassay.

Ochratoxin A (OTA) and staphylococcus enterotoxin A (SEA) are highly toxic contaminants and have induced human health problems. They commonly occur in milk and milk products. A competitive fluorescent immunoassay was developed for rapid and simultaneous determination of these toxins in milk samples. The procedure was based on the competitive immunoreactions between antigens in sample and antigen-fluorescent dye conjugates with immobilised antibodies on magnetic nanoparticles (MNPs). Each monoclonal antibody specifically recognises its corresponding toxin (antigen), and there is no cross-reactivity in the assay. First, monoclonal antibodies against OTA and SEA were produced. The activity of the obtained antibodies was determined by fluorescent-linked immunosorbent assay. Then, the monoclonal antibodies were immobilised on MNPs. The amounts of immobilised anti-OTA antibody and anti-SEA antibody were determined to be 20 and 22 µg mL-1, respectively. The antigen-fluorescent dye conjugates OTA-OVA-ATTO620 and SEA-FITC were prepared. The optimal amount of immobilised antibodies for competitive immunoassay was determined. It was found that the linear range of OTA in buffer was larger (0.001-100 ng mL-1) than the linear range of SEA (0.001-20 ng mL-1). The results for simultaneous determination of OTA and SEA in sixfold diluted milk were almost the same in buffer; the linear range for OTA was from 0.005  to 100 ng mL-1 and for SEA from 0.005  to 20 ng mL-1. The detection limit for both OTA and SEA in milk was 0.004 ng mL-1. The developed method took half the time of the individual assays (20 min). The assay was evaluated using spiked milk samples. The influences of somatic cell count, fat, pH and protein concentration in milk on immunoassay were studied. In summary, this developed immunoassay could provide an effective and rapid approach for detecting multi-toxins in milk samples.

Free-viewing multi-stimulus eye tracking task to index attention bias for alcohol versus soda cues: Satisfactory reliability and criterion validity.

Cognitive -motivational models point to attention bias (AB) as an important factor in the persistence of problematic drinking behavior. Unfortunately, the measures that have been used to examine AB in addiction typically showed poor psychometric properties. To bring research on AB a critical step further it would be crucial to develop tasks with acceptable reliability and construct validity. Recently, Lazarov and colleagues (2016) developed a multi-stimulus free-viewing task (participants were free to look at any part of the screen and there was no secondary task involved) that showed excellent psychometric properties in the context of social anxiety as well as depression. We, therefore, adapted this task and examined its psychometric quality within the context of alcohol use. Participants with varying levels of alcohol use (N = 100) were presented with 54 matrices each containing 8 alcoholic and 8 non-alcoholic drinks. Each matrix was presented for 6 s. First fixation (100 ms) location and latency and total dwell time were assessed for alcohol and soda pictures. Assessment of AB, craving, and alcohol use (problems) was repeated after 3-8 days. Specifically, the dwell-time based AB-measure showed excellent internal reliability and considerable stability. Supporting the validity of the current AB-measures, it was found that participants with higher scores on craving and alcohol problems (i) dwelt longer on alcohol stimuli, and (ii) more often showed a first fixation on alcohol, whereas (iii) stronger craving was associated with shorter latency of first alcohol fixations. The AB-measure showed promising psychometric properties. Thus, this free-viewing eye-tracking task seems a welcome new tool for being used in future research on AB in addiction.

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.