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Objectives: There is a lack of evidence regarding the effectiveness of graphic health warning labels (GHWL) in different individuals, including patients with chronic obstructive pulmonary disease (COPD). Investigating knowledge and attitudes may allow better implementation of future public health policies. We hypothesised that differences in the impact of GHWL exist between non-smokers, smokers and patients with COPD, with decreased efficacy in those groups who are longer and more frequently exposed to them. Participants and setting: 163 participants (54% male, aged 21-80) including 60 non-smokers, 53 smokers and 50 patients with COPD (Gold stage II-IV), attending London respiratory outpatient clinics, participated in case-controlled surveys (50 items). Outcome measures: Ten different GHWL were shown and demographics, smoking history, plans to quit, smoking-risk awareness, emotional response, processing and impact of GHWL on behaviour were recorded. Patients were further asked to prioritise the hypothetical treatment or prevention of five specific smoking-related diseases. Results: Smokers, in particular those with COPD, were less susceptible to GHWL than non-smokers; 53.4% of all participants expressed fear when looking at GHWL, non-smokers (71.9%) more so than smokers (39.8%, p<0.001). COPD participants were less aware of the consequences than non-COPD participants (p<0.001), including an awareness of lung cancer (p=0.001). Lung cancer (95%), oral cancer (90.2%), heart disease (84.7%) and stroke (71.2%) were correctly associated with smoking, whereas blindness was least associated (23.9%). However, blindness was prioritised over oral cancer, stroke and in patients with COPD also over heart disease when participants were asked about hypothetical treatment or prevention. Conclusions: GHWL are most effective in nonsmokers and a desensitisation effect was observed in smokers and patients with COPD. As a consequence, a tailored and concerted public health approach to use such messages is required and 'blindness' deserves to be mentioned in this context because of an unexpectedly high-deterring impact. [ABSTRACT FROM AUTHOR]

This epidemiological study aimed to describe and compare the characteristics and outcomes of COPD patients starting treatment with a long-acting anti-muscarinic (LAMA) or a combination of a long-acting beta-2 agonist (LABA)/LAMA in primary care in Catalonia (Spain) over a one-year period. Data were obtained from the Information System for the Development in Research in Primary Care (SIDIAP), a population database containing information of 5.8 million inhabitants (80% of the population of Catalonia). Patients initiating treatment with a LAMA or LABA/LAMA in 2015 were identified, and information about demographic and clinical characteristics was collected. Then, patients were matched 1:1 for age, sex, FEV1%, history of exacerbations, history of asthma and duration of treatment, and the outcomes between the two groups were compared. During 2015, 5729 individuals with COPD started treatment with a LAMA (69.8%) or LAMA/LABA (30.2%). There were no remarkable differences between groups except for a lower FEV1 and more previous hospital admissions in individuals on LABA/LAMA. The number of tests and referrals was low and decreased in both groups during follow-up. For the same severity status, the evolution was similar with a reduction in exacerbations in both groups. Treatment was changed during follow-up in up to 34.2% of patients in the LABA/LAMA and 26.3% in the LAMA group, but adherence was equally good for both. Our results suggest that initial therapy with LAMA in monotherapy may be adequate in a significant group of mild to moderate patients with COPD and a low risk of exacerbations managed in primary care. A single rather than combined long-acting inhaler therapy may be adequate for most patients when treating mild to moderate chronic lung disease. Marc Miravitlles at the Hospital Universitari Vall d’Hebron, Barcelona, Spain, and co-workers have shown that, in the initial stages of chronic obstructive pulmonary disease (COPD), treatment with an inhaled drug called a long-acting anti-muscarinic agent (LAMA) is as effective as an alternative inhaler that combines LAMA with another drug (LABA). The researchers identified 5729 COPD patients from Catalonia starting on inhaled treatment in 2015 and followed up on their progress after 1 year. Patients starting on LAMA monotherapy were matched closely in terms of demographics and previous medical history to those starting on LAMA/LABA treatment. The team found no remarkable differences in clinical characteristics between the groups over the year. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. It is well established that patients with mild to moderate disease represent the majority of patients with COPD, and patients with mild COPD already have measurable physiological impairment with increased morbidity and a higher risk of mortality compared with healthy non-smoking individuals. However, this subpopulation is both underdiagnosed and undertreated. In addition, most clinical trials include cohorts of patients with worse lung function and quality of life, which are very different from the milder patients usually seen in primary care.Clinical trials have shown that mild-moderate COPD patients present an improvement in lung function after treatment with long-acting bronchodilators (LABD). Inhaled therapy has also shown benefits in terms of symptoms, health-related quality of life (HRQL) and exacerbation prevention in this population. Early intervention might have also a positive effect to prevent functional impairment. Nevertheless, there is scarce evidence from randomised clinical trials and real-life studies about the importance of pharmacological treatment in early stages of COPD to improve long-term outcomes. New concepts such as clinically important deterioration may help to investigate the impact of interventions on the natural history of the disease. [ABSTRACT FROM AUTHOR]

Background: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition that leads to decreased circulating alpha-1 antitrypsin (AAT) levels, significantly increasing the risk of serious lung and/or liver disease in children and adults, in which some aspects remain unresolved.Methods: In this review, we summarise and update current knowledge on alpha-1 antitrypsin deficiency in order to identify and discuss areas of controversy and formulate questions that need further research.Results: 1) AATD is a highly underdiagnosed condition. Over 120,000 European individuals are estimated to have severe AATD and more than 90% of them are underdiagnosed.Conclusions: 2) Several clinical and etiological aspects of the disease are yet to be resolved. New strategies for early detection and biomarkers for patient outcome prediction are needed to reduce morbidity and mortality in these patients; 3) Augmentation therapy is the only specific approved therapy that has shown clinical efficacy in delaying the progression of emphysema. Regrettably, some countries reject registration and reimbursement for this treatment because of the lack of larger randomised, placebo-controlled trials. 4) Alternative strategies are currently being investigated, including the use of gene therapy or induced pluripotent stem cells, and non-augmentation strategies to prevent AAT polymerisation inside hepatocytes. [ABSTRACT FROM AUTHOR]

Chronic Obstructive Pulmonary Disease (COPD) constitutes a major public health problem, and it is anticipated that its prevalence will continue to increase in the future. Its progressive nature requires a continuous and well-coordinated care approach. The follow-up for COPD should primarily focus on disease screening and control, which includes monitoring of pulmonary function, prevention of exacerbations, identification of aggravating factors and comorbidities, as well as ensuring treatment adequacy and adherence. However, existing clinical practice guidelines and consensus documents offer limited recommendations for the follow-up. In this context, we undertake a review of COPD treatment and the continuity of care recommendations endorsed by several scientific societies. Moreover, we underscore the importance of the involvement of nursing and community pharmacy in this process, as well as the utilization of quality indicators in the provision of care for the disease. [ABSTRACT FROM AUTHOR]

Introduction: Several studies mentioned parenchymal findings after SARS‐CoV‐2 pneumonia, but few studies have mentioned alterations in the airways. The aim of this study was to estimate the prevalence of tracheomalacia and to analyse the clinical characteristics in a cohort of patients with SARS‐CoV‐2. Methods: The study population consisted of all patients with SARS‐CoV‐2 admitted a hospital serving a population of 500 000 inhabitants. Patients were visited between 2 and 6 months after hospital discharge. In this visit, all patients were subjected to an exhaustive clinical questionnaire and underwent clinical examination, pulmonary function tests and chest CT. Results: From February 2020 to August 2021, 1920 patients were included in the cohort and tracheomalacia was observed in 15 (0.8%) on expiratory HRCT imaging. All patients with tracheomalacia also presented ground glass opacities in the CT scan and 12 patients had airway sequelae. Conclusions: Tracheomalacia is an exceptional sequela of SARS‐CoV‐2 survivors. [ABSTRACT FROM AUTHOR]

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 registrationwww.clinicaltrials.gov (ID: NCT04180319) [ABSTRACT FROM AUTHOR]

Background: Alpha-1 antitrypsin deficiency (AATD) is characterized by reduced serum levels of the AAT protein and predisposes to liver and lung disease. The characterization at structural level of novel pathogenic SERPINA1 mutants coding for circulating AAT could provide novel insights into the mechanisms of AAT misfolding. The present study aimed to provide a practical framework for the identification and analysis of new AAT mutations, combining structural simulations and clinical data. Methods: We analysed a total of five mutations (four not previously described) in a total of six subjects presenting moderate to severe AATD: Gly95Alafs*18, Val210Glu, Asn247Ser, Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile. Clinical data, genotyping and phenotyping assays, structural mapping, and conformational characterization through molecular dynamic (MD) simulations were developed and combined. Results: Newly discovered AAT missense variants were localized both on the interaction surface and the hydrophobic core of the protein. Distribution of mutations across the structure revealed Val210Glu at the solvent exposed s4C strand and close to the "Gate" region. Asn247Ser was located on the accessible surface, which is important for glycan attachment. On the other hand, Asp341His, Leu383Phe were mapped close to the "breach" and "shutter" regions. MD analysis revealed the reshaping of local interactions around the investigated substitutions that have varying effects on AAT conformational flexibility, hydrophobic packing, and electronic surface properties. The most severe structural changes were observed in the double- and triple-mutant (Pi*S + Asp341His and Pi*S + Leu383Phe + Lys394Ile) molecular models. The two carriers presented impaired lung function. Conclusions: The results characterize five variants, four of them previously unknown, of the SERPINA1 gene, which define new alleles contributing to the deficiency of AAT. Rare variants might be more frequent than expected, and therefore, in discordant cases, standardized screening of the S and Z alleles needs complementation with gene sequencing and structural approaches. The utility of computational modelling for providing supporting evidence of the pathogenicity of rare single nucleotide variations is discussed. [ABSTRACT FROM AUTHOR]

Background: Alpha-1 antitrypsin deficiency (AATD) is considered one of the most common genetic diseases and is characterised by the misfolding and polymerisation of the alpha-1 antitrypsin (AAT) protein within hepatocytes. The relevance of circulating polymers (CP) of AAT in the pathogenesis of lung and liver disease is not completely understood. Therefore, the main objective of our study was to determine whether there is an association between the levels of CP of AAT and the severity of lung and liver disease.Method: This was a cross-sectional study in patients with different phenotypes of AATD and controls. To quantify CP, a sandwich ELISA was performed using the 2C1 monoclonal antibody against AAT polymers. Sociodemographic data, clinical characteristics, and liver and lung parameters were collected.Results: A cohort of 70 patients was recruited: 32 Pi*ZZ (11 on augmentation therapy); 29 Z-heterozygous; 9 with other genotypes. CP were compared with a control group of 47 individuals (35 Pi*MM and 12 Pi*MS). ZZ patients had the highest concentrations of CP (p < 0.001) followed by Z heterozygous. The control group and patients with Pi*SS and Pi*SI had the lowest CP concentrations. Pi*ZZ also had higher levels of liver stiffness measurements (LSM) than the remaining AATD patients. Among patients with one or two Z alleles, two patients with lung and liver impairment showed the highest concentrations of CP (47.5 µg/mL), followed by those with only liver abnormality (n = 6, CP = 34 µg/mL), only lung (n = 18, CP = 26.5 µg/mL) and no abnormalities (n = 23, CP = 14.3 µg/mL). Differences were highly significant (p = 0.004).Conclusions: Non-augmented Pi*ZZ and Z-patients with impaired lung function and increased liver stiffness presented higher levels of CP than other clinical phenotypes. Therefore, CP may help to identify patients more at risk of developing lung and liver disease and may provide some insight into the mechanisms of disease. [ABSTRACT FROM AUTHOR]

In each box plot, the median value is indicated by the center horizontal black line, the 25th and 75th percentiles are indicated by the lower and upper box horizontal lines, and the mean value is indicated by the center horizontal white line. Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry. [Extracted from the article]

Visits to hospital emergency departments by patients with multimorbidity, complex chronic conditions, and frailty are becoming an increasing challenge. A territorial strategy has been developed, based on automated preselection lists, a nurse case manager with specialized experience, and a multi-level territorial referral consensus. The feasibility of this approach has been demonstrated, with 368 alerts detected, 85% of which were well-selected. Age, frailty, home care percentage, Barthel index, and cognition were progressively aligned with levels of care/referral (primary, intermediate, and specialized) according to previously agreed criteria. In 2024, there is extensive structured technical information, an expanding role for advanced nursing, and well-established inter-level service resources. Therefore, through automated selection, a consensual territorial protocol of pathways and clinical profiles, and autonomous nursing assessments managing multi-frequent cases, it would be possible to achieve, in a proactive, simple, and scalable manner, an appropriate distribution of alerts across levels, consistent with the social and healthcare needs of the patients., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Respiratory diseases exhibit diverse patterns in prevalence, clinical presentations, and outcomes between men and women. Historically, certain conditions were more prevalent in men, but trends have shifted, highlighting the need to understand sex disparities in respiratory health. Social, environmental, and healthcare changes have reshaped the landscape of respiratory diseases, complicating diagnosis and treatment. Moreover, the underrepresentation of women in clinical trials has limited our understanding of their specific needs. In this review, we explore the sex differences in the prevalence, clinical characteristics, and presentation of respiratory diseases, emphasizing the importance of tailored approaches to diagnosis and management. By recognizing and addressing these disparities, we can advance toward more equitable and effective respiratory healthcare for all individuals., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: The objective of this study was to investigate which of two short questionnaires, the Asthma Control Test (ACT) or the COPD Assessment Test (CAT), correlates better with severity variables and whether they share similar determinants in patients with asthma-COPD overlap. Method: This observational, cross-sectional, multicentric study included smokers and former smokers of more than 10 pack-years, with non-fully reversible airflow obstruction and either a concomitant diagnosis of asthma or signs of type 2 inflammation, from 15 centres in Spain. Results: A total of 157 patients were included, 109 (69.4%) were men, the mean age was 63.3 (SD: 9) years and the mean FEV1 (%) was 59.7% (SD: 20.5%). The mean CAT score was 14.5 (SD: 8.7), and the mean ACT score was 17.9 (SD: 5.2). Both scores showed good correlations (r = 0.717; p < 0.001). In the multivariate analysis, the Hospital Anxiety and Depression Scale and mMRC dyspnoea scores were independently and significantly associated with both the CAT and ACT scores; however, age was only significantly associated with the CAT, and the EQ-5D scores and the number of exacerbations in the previous year were only significantly associated with the ACT scores. The ACT had a slightly better predictive value for exacerbations than the CAT (AUC = 0.70 (95% CI: 0.62 to 0.79 vs. 0.65 (95% CI: 0.56 to 0.74))). Conclusions: There is a good correlation between ACT and CAT scores in patients with ACO. However, severe patients scored worse on the CAT than the ACT. Anxiety, depression and dyspnoea were significantly associated with both the CAT and ACT scores. The ACT was a slightly better predictor of exacerbations than the CAT in this population.

Background: Sex and gender influence many aspects of chronic obstructive pulmonary disease (COPD). Limited data are available on this topic in alpha-1 antitrypsin deficiency (AATD). We therefore aimed to investigate sex issues in the EARCO registry, a prospective, international, observational cohort study., Methods: Baseline data from PiZZ individuals, enrolled in the registry with complete data on sex and smoking history were analysed by group comparisons and binary logistic regression analyses., Results: 1283 patients with AATD, 49.3% women were analysed. Females reported less tobacco consumption (16.8±12.2 vs. 19.6±14.5 PY, p=0.006), occupational exposures towards gases, dusts or asbestos (p<0.005 each) and consumed less alcohol (5.5±7.6 vs. 8.4±10.3u/week, p<0.001). Females reported COPD (41% vs. 57%, p<0.001) and liver disease (11% vs. 20%, p<0.001) less often. However, they had a higher prevalence of bronchiectasis (24% vs. 13%, p<0.001). Despite better lung function (FEV 1 %pred. 73.6±29.9 vs. 62.7±29.5, p<0.001) females reported a similar symptom burden (CAT 13.4±9.5 vs. 12.5±8.9, p=ns) and exacerbation frequency (at least one in the previous year 30% vs. 26%, p=ns) compared to males. In multivariate analyses, female sex was an independent risk factor for exacerbations in the previous year OR 1.6 p=0.001 in addition to smoking history, COPD, asthma and bronchiectasis and was also identified as risk factors for symptom burden (CAT≥10) OR 1.4 p=0.014 besides age, BMI, COPD and smoking history., Conclusion: Men had higher rates of COPD and liver disease, women were more likely to have bronchiectasis. Women's higher symptom burden and exacerbation frequency suggest they may need tailored treatment approaches., (Copyright © 2024 The Author(s). Published by Elsevier España, S.L.U. All rights reserved.)

Severe alpha-1 antitrypsin deficiency (AATD) is associated with an increased risk of emphysema. However, the clinical manifestations are very heterogeneous, and an individual prognosis is very difficult to establish. Intravenous augmentation therapy with alpha-1 antitrypsin (AAT) from pooled blood donors is the only specific treatment available, but it requires weekly or biweekly administration for life. Several guidelines provide the indication criteria for the initiation of AAT augmentation therapy. However, in clinical practice, there are situations in which the decision as to when to start treatment becomes uncertain and some studies have shown great variability in the indication of this treatment even among specialists. The usual dilemma is between initiating augmentation therapy in individuals who may not develop significant lung disease or in whom disease will not progress or delaying it in patients who may otherwise rapidly and irreversibly progress. We illustrate this dilemma with five clinical cases: from the case of a patient with normal lung function who requests initiation of therapy to a moderately stable patient without augmentation or a mild patient who, after several years of remaining stable without treatment, deterioration in lung function initiated and, consequently, augmentation therapy was begun. All the nuances associated with the indication of augmentation justify a personalised approach and the decision about initiating augmentation therapy must be made after careful consideration of the pros and cons with the patient in reference centres with experience in treatment. These reference centres can work in collaboration with local hospitals where patients can be closely followed and augmentation therapy can be administered to avoid unnecessary travelling, making periodical administrations more comfortable for the patient.

Introduction: Physical activity (PA) has shown great benefits in patients with chronic obstructive pulmonary disease (COPD); however, their PA is below average. Motivational factors associated with PA in COPD have not been widely studied and could be a target for improving adherence to PA. The objective of our study was to identify and understand the different motivational and confidence factors related to low levels of PA in a COPD cohort., Method: Observational, prospective, multicenter study of COPD patients. Sociodemographic data, respiratory symptoms, comorbidities, spirometry, and exercise capacity were collected. PA was measured using the Dynaport accelerometer and patient motivation and confidence in PA were assessed by a questionnaire previously used in a COPD population in the USA., Results: Eighty six COPD patients were included, 68.6% being male, with a mean (SD) age of 66.6 (8.5) years and a mean forced expiratory volume in the first second (%) of 50.9% (17.3%). The mean walking time was 82.8 (37.8) minutes/day. Questions related to health benefits and enjoying exercise were ranked highest in the motivation questionnaire and statistically significant differences were found in PA measures between patients with low and high motivation. A lack of confidence regarding hot weather and health-related issues significantly influenced PA levels. Advice from third parties, including healthcare providers, was not associated with higher PA levels., Conclusions: Improving the health of COPD patients is their main motivation to perform PA. Lack of confidence when it is hot or when they fear for their health is related to low levels of PA. Advice from third parties, including healthcare professionals, is not associated with higher PA. These results are relevant for developing strategies to increase the adherence of COPD patients to PA programs., (© 2024 S. Karger AG, Basel.)

Augmentation therapy with intravenous alpha-1 antitrypsin is the only specific treatment for alpha-1 antitrypsin deficiency (AATD)-associated emphysema. This treatment has been available and remained basically unchanged for more than 35 years, but many questions persist regarding its indications, regimen of administration and efficacy. Because AATD is a rare disease, it has not been possible to conduct randomised, placebo-controlled trials that are adequately powered for the usual outcomes analysed in non-AATD-related COPD, such as lung function decline, exacerbations, symptoms or quality of life. New outcomes such as lung densitometry measured by computed tomography are more sensitive for identifying emphysema progression but are not widely accepted by regulatory agencies. In addition, clinical manifestations, severity and the natural history of lung disease associated with AATD are very heterogeneous, which means that individual prediction of prognosis is challenging. Therefore, the indication for augmentation is sometimes a dilemma between initiating treatment in individuals who may not develop significant lung disease or in whom disease will not progress and delaying it in patients who will otherwise rapidly and irreversibly progress.Other areas of debate are the possible indication for augmentation in patients with severe AATD and respiratory diseases other than emphysema, such as bronchiectasis or asthma, and the use of therapy after lung transplant in AATD patients. All these uncertainties imply that the indication for treatment must be personalised in expert reference centres after in-depth discussion of the pros and cons of augmentation with the patient., Competing Interests: Conflict of interest: M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi, Zambon and Grifols; and research grants from Grifols. A. Anzueto has received consultant fees from AstraZeneca, Boehringer Ingelheim, Grifols, GlaxoSmithKline, Verona Pharma, TEVA and Mylan/Theravance. M. Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GSK and Boehringer Ingelheim; and consulting fees from GSK, Novartis, CSL Behring and Boehringer Ingelheim., (Copyright ©The authors 2023.)

Introduction: SARS-CoV-2 pneumonia can lead to several sequelae, among them, pulmonary fibrosis. The Enhanced Liver Fibrosis (ELF) score is a panel of serum markers of liver fibrosis. We aimed to describe the utility of the ELF score as a biomarker of pulmonary fibrosis secondary to COVID-19 pneumonia., Methods: Chest computed tomography (CT) scan, lung function tests (LFT) and blood analysis were obtained at three months after discharge. Data were analysed according to ELF scores and posteriorly divided into ELF tertiles., Results: One hundred twenty-nine patients were recruited; of these, 85.7% presented bilateral pneumonia at diagnosis of SARS-CoV2 infection. At 3 months after discharge, CT scan was available in 123 patients, 73 (59.3%) of whom presented parenchymal lung abnormalities (PLA) and LFT showed impairment in 28 (22.7%) patients. Globally, the most frequent PLA was ground glass opacities (50%), followed by bronchial thickening (26.8%), reticular pattern (19.5%), consolidation (10.5%) and air bronchogram sign (7.3%). Radiological findings were only significant in the higher tertile of ELF, with a reticular pattern as the predominant PLA (p = 0.002). Moreover, patients with both PLA and LFT impairment, presented a trend towards higher levels of ELF compared with patients with only PLA or LFT impairment, or no impairment (9.9 (0.7) vs 9.6 (0.8), 9.1 (1.1) and 9.3 (0.7); p = 0.054)., Conclusion: Patients with both PLA and LFT alteration at 3 months after SARS-CoV-2 pneumonia had higher ELF scores. The ELF score may be useful to identify patients with risk of fibrotic changes after SARS-CoV-2 pneumonia., Competing Interests: Declaration of competing interest Marc Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Menarini, Kamada, Takeda, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, CSL Behring, Inhibrx, Ferrer, Menarini, Mereo Biopharma, Spin Therapeutics, Specialty Therapeutics, ONO Pharma, Palobiofarma SL, Takeda, Novartis, Novo Nordisk, Sanofi, Zambon and Grifols and research grants from Grifols. Alexa Núñez has received speaker fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and CSL Behring, consulting fees from CSL Behring. Francisco Rodríguez-Frías has received speaker fees from CSL Behring. Galo Granados has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Zambon and GlaxoSmithKline. Cristina Esquinas has received speaker fees from CSL Behring. Cristina Aljama has received speaker fees from FAES farma and CSL Behring. Miriam Barrecheguren has received speaker fees from CSL Behring, Grifols, Chiesi, GlaxoSmithKline and Menarini, and consulting fees from CSL Behring and Boehringer Ingelheim. The remaining authors report no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Administration of exogenous alpha-1 antitrypsin (AAT) is the only specific therapy for the management of pulmonary morbidity in patients with AAT deficiency. It requires weekly or biweekly intravenous infusions, which may impact patient independence and quality of life. Self-administration of AAT therapy is an alternative to reduce the burden for patients who require AAT therapy. We presented herein experts' recommendations for the implementation of a program for the self-administration of AAT., Methods: This project was conducted using a modified nominal group technique and was undertaken in two online meetings involving the participation of 25 experts: specialists in pulmonology (n=17), nurses (n=5) and hospital pharmacists (n=3)., Results: The following issues were discussed, and several recommendations were agreed upon on the following topics: a) patient profile and clinical evaluation, establishing selection criteria that should include clinical as well as social criteria; b) role of health care professionals, suggested roles for specialists in pulmonology, nurses, and hospital pharmacists; c) training by the nurse, including recommendations before initiating the training and the content of the training sessions; and d) logistic issues and follow-up, adherence, and patient support., Conclusion: We expect this proposal to increase awareness of this therapeutic alternative and facilitate the implementation of self-administration programs, thus contributing to optimizing the patient experience with AAT therapy. Further research on the outcomes of these programs, especially from the patient perspective, will also help to improve their design and implementation., Competing Interests: MT-D: has received consulting fees from CSL Behring and Grifols; payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events from CSL Behring and Grifols; and support for attending meetings and/or travel from CSL Behring, Grifols and Chiesi. JLL-C: has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies or writing for publications from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, CSL Behring, Ferrer, Gebro, GlaxoSmithKline, Grifols, Menarini, Megalabs, Novartis and Rovi. MCR: has received speaker fees from AstraZeneca, Bial, Chiesi, CSL Behring, GlaxoSmithKline, Menarini, and Grifols; and consulting fees from GlaxoSmithKline, CSL Behring and Bial. CM-M: has received speaker fees and/or consulting fees and/or support to attend congresses from Astra-Zeneca, Boehringer-Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols and Menarini. APC: has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from CSL Behring. MB: has received speaker fees from Grifols, Menarini, CSL Behring, GSK, Boehringer Ingelheim and consulting fees from GSK, Novartis, CSL Behring and Boehringer Ingelheim. FJC-G: has received speaker honorarium from GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Mundipharma, Menarini, Pfizer, Novartis, Esteve, Teva Pharmaceutical, Ferrer, Rovi, Roche, Astra Zeneca, Bial, Actelion, Alter, CSL Behring, Faes Farma, Alter, Grifols, Sanofi Genzyme and Gebro Pharma; consulting honorarium from Chiesi, Boehringer Ingelheim, Teva Pharmaceutical, Astra Zeneca, Bial, CSL Behring and Sanofi Genzyme; and travel grants from GlaxoSmithKline, Chiesi, Boehringer Ingelheim, Teva Pharmaceutical, Astra Zeneca and CSL Behring. FC-M: has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Novartis, Sanofi, Vertex, CSL Behring and Grifols; and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, CSL Behring, and Grifols. JMH-P: Speaker honorarium from Grifols, CSL Behring, Astra-Zeneca, GSK, Bial laboratory, Teva laboratory and FAES Farma. Advisory honorarium from CSL Behring. Travel grants from Grifols and CSL Behring. LL-A: has received speaker honorarium from CSL Behring and Grifols SA; research grants from Grifols SA; consulting honorarium from CSL Behring; and travel grants from CSL Behring and Grifols SA. CMR: has received speaker honorarium from Astra Zeneca, CSL Behring CSL, Chiesi, Gebro, GSK, Mundipharma, TEVA and Sanofi; research grants from AstraZeneca, GSK and TEVA; and consulting and advisory honorarium from Astra Zeneca, CSL Behring, Chiesi, Mundipharma and TEVA. FJM: has received speaker fees and/or consulting fees and/or support to attend congresses from Astra-Zeneca, Boehringer-Ingelheim, Chiesi, CSL Behring, GlaxoSmithKline, Grifols, Menarini, Novartis, Sanofi Aventis and Teva. J-BM-R: has received speaker fees and/or consulting fees and/or support to attend congresses from CSL Behring and Grifols. RS: has received speaker fees and/or consulting fees and/or support to attend congresses from CSL Behring, Astra Zeneca, Chiesi, GlaxoSmithKline, Grifols, Teva, Novartis and Menarini. MO-P: has received speaker honorarium from Biogen, Novartis, Roche, Genzyme Sanofi and Takeda. JPQG: Advisory board member for CSL Behring. MM: has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Kamada, Takeda, Sandoz, Zambon, CSL Behring, Specialty Therapeutics, Janssen, Grifols and Novartis; consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Inhibrx, Laboratorios Esteve, Ferrer, Menarini, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols; and research grants from Grifols. RAR, MABG, LD-C, PGM, CM-G, IP, MRR-S-E and BT-G: have no conflict of interest., (© 2023 Torres-Durán et al.)

Background: Initiation of treatment of COPD with a combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) is frequent irrespective of the risk of exacerbations., Method: We performed a retrospective, population-based, observational study aimed at comparing the effectiveness of a LABA/long-acting antimuscarinic agent (LAMA) and LABA/ICS in patients with COPD over a one-year follow-up. Data were obtained from an administrative healthcare claims database. The primary outcome was the risk of first exacerbation. A sensitivity analysis was conducted in a propensity-score matched population., Results: The population consisted of 14,046 COPD patients; 11,329 (80.6%) initiated LABA/ICS and 2717 (19.4%) LABA/LAMA. The matched population included 1650 patients in each arm. During follow-up, 69.6% patients in the LABA/ICS group and 64.4% in the LABA/LAMA group presented an exacerbation. The mean time to the first exacerbation was 6.03 months (95% confidence interval (CI): 5.94-6.12) for LABA/ICS and 6.4 months (95%CI: 6.21-6.59) for LABA/LAMA; p<0.001. The time to scalation to triple therapy was also significantly prolonged in LABA/LAMA. Similar results were obtained in the matched population. LABA/LAMA was associated with a significantly lower risk of exacerbations and escalation to triple therapy compared to LABA/ICS, except in patients with frequent exacerbations and high blood eosinophils in which no differences were observed in the time to first exacerbation., Conclusion: Initiation of treatment with LABA/LAMA was associated with a lower risk of exacerbation and escalation to triple therapy compared to LABA/ICS in the majority of patients with COPD in primary care., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The Spanish registry of α 1 -antitrypsin deficiency (AATD) integrated in the European Alpha-1 Research Collaboration (EARCO) provides information about the characteristics of patients, in particular those with the PI*SZ genotype, which is frequent in Spain., Method: Individuals with severe AATD defined as proteinase inhibitor (PI) genotypes PI*ZZ, PI*SZ and other rare deficient variants were included from February 1, 2020, to February 1, 2022. The analysis focused on a comparison of the characteristics of PI*ZZ and PI*SZ patients., Results: 409 patients were included (53.8% men) with a mean±sd age of 53.5±15.9 years. Genotypes were PI*ZZ in 181 (44.7%), PI*SZ in 163 (40.2%), PI*SS in 29 (7.2%) and other in 32 (7.9%). 271 (67.4%) had lung disease: 175 chronic obstructive pulmonary disease (43.5%), 163 emphysema (40.5%) and 83 bronchiectasis (20.6%). Patients with the PI*SZ genotype were younger, more frequently non-index cases and had a lower frequency of respiratory diseases except asthma compared with PI*ZZ patients. Among patients with respiratory diseases, PI*SZ individuals were significantly older both at onset of symptoms and at diagnosis; only asthma was more frequent in PI*SZ than in PI*ZZ individuals. Twelve PI*SZ patients (15.4%) received augmentation therapy compared with 94 PI*ZZ patients (66.2%; p<0.001)., Conclusions: There is a high prevalence of PI*SZ in Spain. Patients with the PI*SZ genotype were older at symptom onset and diagnosis and had less severe lung disease compared with PI*ZZ patients. The prevalence of asthma was higher in PI*SZ, and up to 15% of PI*SZ patients received augmentation therapy., Competing Interests: Competing interests: M. Torres-Durán has received speaker fees from Chiesi, CSL Behring, Grifols and Resmed, and consulting fees from CSL Behring and Grifols. J.L. López-Campos has received honoraria during the last 3 years for lecturing, scientific advice, participation in clinical studies or writing for publications for AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Esteve, Ferrer, Gebro, GlaxoSmithKline, Grifols, Menarini, Novartis, Rovi and Teva. J.L. Rodríguez-Hermosa has received speaker fees from Zambon, Bial, Gebro Pharma, GlaxoSmithKline, Chiesi, Boehringer Ingelheim, CSL Behring and Grifols. J.M. Hernández-Pérez has received speaker fees from Grifols, CSL Behring, AstraZeneca, GlaxoSmithKline, Bial laboratory and Teva laboratory, support for attending meetings from Grifols and CSL Behring, and consulting fees from CSL Behring. C. Rodríguez has received speaker fees from GlaxoSmithKline, AstraZeneca, Grifols, Chiesi, Ferrer, Menarini and Boehringer Ingelheim, has provided expert testimony for Chiesi, and has received support for attending meetings from FAES. A. Bustamante has received speaker fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Novartis and Ferrer, and funding for travelling or attending meetings from CSL Behring, AstraZeneca and Chiesi. F. Casas-Maldonado has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Gebro Pharma, GlaxoSmithKline, Laboratorios Esteve, Laboratorios Ferrer, Menarini, Novartis, Rovi, Teva, Vertex, Zambon, CSL Behring and Grifols, and consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, CSL Behring and Grifols. M. Barrecheguren has received speaker fees from Grifols, Menarini, CSL Behring, GlaxoSmithKline and Boehringer Ingelheim, and consulting fees from GlaxoSmithKline, Novartis, CSL Behring and Boehringer Ingelheim. C. González has received speaker fees from Menarini, GlaxoSmithKline, Novartis, Boehringer Ingelheim and Chiesi. M. Miravitlles has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, Kamada, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Teva, Spin Therapeutics, pH Pharma, Novartis, Sanofi and Grifols, and research grants from GlaxoSmithKline and Grifols. The remaining authors report no conflicts of interest., (Copyright ©The authors 2022.)

Introduction: Identifying the variables that guide decision-making in relation to the use of inhaled corticosteroids (ICS) can contribute to the appropriate use of these drugs. The objective of this study was to identify the clinical variables that physicians consider most relevant for prescribing or withdrawing ICS in COPD., Methods: A cross-sectional survey was conducted in Spain from November 2020 to May 2021. Therapeutic decisions on the use of ICS in 11 hypothetical COPD patient profiles were collected using an online survey answered by specialists with experience in the management of patients with COPD. Mixed-effects logistic regression was used to analyze the impact of patients' characteristics in the therapeutic decision for prescribing ICS or proceeding to its withdrawal., Results: A total of 74 pulmonologists agreed to collaborate in the survey and answered the questionnaire. The results showed great variability, with only 2 profiles achieving consensus for starting or withdrawing the treatment. The frequency and severity of exacerbations influenced the decision to prescribe ICS in a dose-response fashion (1 exacerbation odds ratio (OR) = 1.86, 95% confidence interval (CI) 1.02 to 3.43, two exacerbations OR = 11.6, 95% CI: 4.47 to 30.2 and three OR = 123, 95% CI: 25 to 601). Similarly, increasing blood eosinophils and history of asthma were associated with ICS use. On the other hand, pneumonia reduced the probability of initiating treatment with ICS (OR = 0.54 [0.29 to 0.98]). Lung function and dyspnea degree did not influence the clinician's therapeutic decision. The results for withdrawal of ICS were similar but in the opposite direction., Conclusion: In accordance with guidelines, exacerbations, blood eosinophils and history of asthma or pneumonia are the factors considered by pulmonologist for the indication or withdrawal of ICS. However, the agreement in prescription or withdrawal of ICS when confronted with hypothetical cases is very low, suggesting a great variability in clinical practice., Competing Interests: The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE). The authors did not receive payment related to the development of the manuscript. MM has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, Kamada, CSL Behring, Grifols and Novartis, consulting fees from AstraZeneca, Atriva Therapeutics, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, Spin Therapeutics, ONO Pharma, pH Pharma, Palobiofarma SL, Takeda, Novartis, Sanofi and Grifols and research grants from Grifols. FG has received economic compensation for consulting, lectures at various congresses and scientific training sessions, manuscript writing and support for attending meetings from Boehringer Ingelheim, GSK, Novartis, Astrazeneca, Chiesi, Pfizer, Esteve and Rovi. CRR reports no disclosure related to this paper. XP has received speaker fees from Boehringer Ingelheim, GlaxoSmithKline, Rovi and Chiesi. EMM has received economic compensation for consulting, lectures, presentations, manuscript writing, educational events, support for attending meetings, participation in data safety monitoring or advisory board from Boehringer Ingelheim, Glaxo Smith Kline, Novartis, Aflofarm, Bial, Chiesi, Meranini and GSK. CG has received economic compensation for consulting, support for attending meetings from Chiesi, Boehringer Ingelheim, Glaxo Smith Kline, Novartis, Meranini, Ferrer and Teva. CA has received speaker fees and/or consulting fees from Boehringer Ingelheim, Pfizer, AstraZeneca, Novartis, Chiesi, Faes farma, Esteve and GlaxoSmithKline. CF has received economic compensation by GOC Health Consulting for statistical analysis. SA has received economic compensation for support for attending meetings, other sessions and consulting from Novartis, Astra Zeneca, Menarini, GSK, Boeringer Ingelheim, Chiesi, Mundipharma, FAES, Pfizer and Teva. BA reports personal fees from GSK, grants, personal fees and non-financial support from Novartis, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Chiesi, grants, personal fees and non-financial support from Laboratorios BIAL, Menarini, personal fees from Gebro, Astra- Zeneca, and Gilead, outside the submitted work. In addition, has a patent P201730724 pending. EN has received economic compensation for consulting, lectures, presentations, manuscript writing and educational events from Novartis, Boehringer Ingelheim, Chiesi and Glaxo Smith Kline. MB reports personal fees from Grifols, Menarini, CSL Behring, GSK, Boehringer Ingelheim, and Novartis, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2022 Miravitlles et al.)

Study Objectives: To investigate the association between moderate or severe obstructive sleep apnea treated with home continuous positive airway pressure (CPAP) and severe coronavirus disease 2019 (COVID-19)., Methods: Retrospective study of patients admitted for COVID-19. Patients with obstructive sleep apnea treated with home CPAP were identified and for each of them we selected 5 patients admitted consecutively in the following hours. The main outcome of the study was the development of severe COVID-19, defined as 1) death or 2) a composite outcome of death or the presence of severe hypoxemic respiratory failure at or during admission. The association between CPAP-treated obstructive sleep apnea and these outcomes was estimated by logistic regression analysis after applying inverse probability of treatment weighting using a propensity score-weighting approach., Results: Of the 2,059 patients admitted, 81 (3.9%) were receiving treatment with home CPAP. Among the 486 patients included in the study, 19% died and 39% presented the composite outcome. The logistic regression analysis did not show an association of CPAP treatment either with death (odds ratio [OR]: 0.684; 95% confidence interval [CI]: 0.332-1.409; P = .303) or with the composite outcome (OR: 0.779; 95% CI: 0.418-1.452; P = .432). Death was associated with age (OR: 1.116; 95% CI: 1.08-1.152; P < .001) and number of comorbidities (OR: 1.318; 95% CI: 1.065-1.631; P = .012), and the composite outcome was associated with male sex (OR: 2.067; 95% CI: 1.19-3.589; P = .01) and number of comorbidities (OR: 1.241; 95% CI: 1.039-1.484; P = .018)., Conclusions: In hospitalized patients with COVID-19, prior obstructive sleep apnea treated with home CPAP is not independently associated with worse outcomes., Citation: Sampol J, Sáez M, Martí S, et al. Impact of home CPAP-treated obstructive sleep apnea on COVID-19 outcomes in hospitalized patients. J Clin Sleep Med . 2022;18(7):1857-1864., (© 2022 American Academy of Sleep Medicine.)

The aim of this observational, retrospective study was to describe characteristics, treatment patterns, and adherence among patients with asthma who initiated multiple-inhaler triple therapy (MITT) in Catalonia, Spain. This study used data of patients initiating MITT in 2016 from the SIDIAP (Information System for Research in Primary Care) database, which covers ~80% of the Catalonian population (5.8 million). Of 1,204 patients initiating MITT, 361 (30.0%) stepped down (discontinued ≥ 1 and continued ≥1 MITT component) and 89 (7.4%) stopped all three components of MITT for a period of 60 days during the following 12 months. In the follow-up period, 196 (16.3%) patients were considered adherent to MITT (>0.8 proportion of days covered [PDC]), with a mean (standard deviation) PDC of 0.52 (0.51) days. Given the low adherence and substantial rates of step down/discontinuation among patients initiating MITT, there is an urgent need to implement strategies to improve treatment adherence/persistence., (© 2022. The Author(s).)

Background: Venous thromboembolism (VTE) is a major complication after lung transplantation (LT). However, its pathophysiology remains unknown, and coagulation profiles have yet to be described., Objective: The aim of this study was to longitudinally assess coagulation status after LT., Methods: We performed a prospective study and described the coagulation profiles of 48 patients at 5 different time-points: before LT and at 24-72 h, 2 weeks, 4 months, and 1 year after LT., Results: At baseline, almost all analyzed coagulation factors were within the normal range, except for FVIII, which was above the normal range. Von Willebrand factor (vWF) and FVIII were increased after LT and remained high at 1 year after transplantation. The cumulative incidence of VTE was 22.9%. Patients who developed VTE had higher FVIII activity 2 weeks after LT., Conclusions: This is the first study to describe coagulation profiles up to 1 year after LT. We show that most markers of a procoagulant state normalize at 2 weeks after LT, but that values of FVIII and vWF remain abnormal at 1 year. This problem has received little attention in the literature. Larger studies are necessary to confirm the results and to design appropriate prophylactic strategies., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: In lung transplantation (LT), the length of ischemia time is controversial as it was arbitrarily stablished. We ought to explore the impact of extended cold-ischemia time (CIT) on ischemia-reperfusion injury in an experimental model., Methods: Experimental, randomized pilot trial of parallel groups and final blind analysis using a swine model of LT. Donor animals (n=8) were submitted to organ procurement. Lungs were subjected to 6h (n=4) or 12h (n=4) aerobic hypothermic preservation. The left lung was transplanted and re-perfused for 4h. Lung biopsies were obtained at (i) the beginning of CIT, (ii) the end of CIT, (iii) 30min after reperfusion, and (iv) 4h after reperfusion. Lung-grafts were histologically assessed by microscopic lung injury score and wet-to-dry ratio. Inflammatory response was measured by determination of inflammatory cytokines. Caspase-3 activity was determined as apoptosis marker., Results: We observed no differences on lung injury score or wet-to-dry ratio any given time between lungs subjected to 6h-CIT or 12h-CIT. IL-1β and IL6 showed an upward trend during reperfusion in both groups. TNF-α was peaked within 30min of reperfusion. IFN-γ was hardly detected. Caspase-3 immunoexpression was graded semiquantitatively by the percentage of stained cells. Twenty percent of apoptotic cells were observed 30min after reperfusion., Conclusions: We observed that 6 and 12h of CIT were equivalent in terms of microscopic lung injury, inflammatory profile and apoptosis in a LT swine model. The extent of lung injury measured by microscopic lung injury score, proinflammatory cytokines and caspase-3 determination was mild., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

This study describes the clinical presentation, treatment, and outcomes of SARS-CoV-2 infection in lung transplant recipients (LTRs). This is a multicenter, retrospective study of all adult LTRs with confirmed SARS-CoV-2 infection from March 4 until April 28, 2020 in six Spanish reference hospitals for lung transplantation. Clinical and radiological data, treatment characteristics, and outcomes were reviewed. Forty-four cases were identified in that period. The median time from transplantation was 4.2 (interquartile range: 1.11-7.3) years. Chest radiography showed acute parenchymal abnormalities in 32 (73%) cases. Hydroxychloroquine was prescribed in 41 (93%), lopinavir/ritonavir (LPV/r) in 14 (32%), and tocilizumab in 19 (43%) patients. There was a strong interaction between tacrolimus and LPV/r in all cases. Thirty-seven (84%) patients required some degree of respiratory support and/or oxygen therapy, and 13 (30%) were admitted to intermediate or intensive critical care units. Seventeen (39%) patients had died and 20 (45%) had been discharged at the time of the last follow-up. Deceased patients had a worse respiratory status and chest X-ray on admission and presented with higher D-dimer, interleukin-6, and lactate dehydrogenase levels. In this multicenter LTR cohort, SARS-CoV-2 presented with high mortality. Additionally, the severity of disease on presentation predicted subsequent mortality., (© 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.)

There is limited information about the initiation of triple therapy (TT) in patients with chronic obstructive pulmonary disease (COPD) in primary care. This was an observational, population-based study in patients identified from a primary care electronic medical records database in Catalonia from 2011 to 2015 aimed to identify the use of TT in patients with newly diagnosed COPD. A total of 69,668 newly diagnosed patients were identified of whom 11,524 (16.5%) initiated TT, of whom 8626 initiated TT at or immediately after COPD diagnosis. Among them, 72.3% were GOLD A/B, 14.6% were frequent exacerbators, and 7.1% had asthma-COPD overlap (ACO). Variables associated with TT initiation were: male sex, older age, previous exacerbations, ACO, a previous treatment regimen containing an inhaled corticosteroid, previous pneumonia, and history of lung cancer. A significant number of COPD patients in Primary Care initiated TT shortly after or even before an established COPD diagnosis.

Background: Recent data from real world clinical practices on the use of Triple Therapy (TT) in patients with COPD are scarce., Methods: Observational population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical records database in Catalonia, covering 80% of the general population. The aims were to characterize COPD patients who initiated TT and to describe treatment pathways before and after TT initiation. Time to and probability of step down or complete discontinuation of TT was described using restricted mean survival time and Kaplan-Meier analysis., Results: A total of 34,018 COPD patients initiated TT during the study period. Of them, 23,867 (70.1%) were GOLD A/B. 18,453 (54.2%) were non-exacerbators, 9931 (29.2%) infrequent exacerbators, 5634 (16.5%) frequent exacerbators and 1923 (5.6%) had asthma-COPD overlap. Drugs most frequently used prior to initiation of TT were long-acting antimuscarinics (22.5%) and combination of long-acting beta2 agonists/inhaled corticosteroids (15.2%). A total of 11,666 (34.3%) stepped down and 1091 (3.2%) discontinued TT during follow-up. Step down following TT was more likely in patients with severe COPD, especially during the first year; however, discontinuation was more common among patients with mild COPD., Conclusion: Most patients initiating treatment with TT were non exacerbators and continued on the same treatment over time regardless severity of disease. Stepping down was more frequent in severe patients, while discontinuation was more common among mild patients. Overall, it appears that TT is extensively used in primary care for treatment of patients with COPD., (Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

The clinical course of lung transplantation (LT) is diverse: some patients present chronic lung allograft dysfunction (CLAD) and progressive decline in pulmonary function, but others maintain normal spirometric values and active lives., Objectives: The aim of this study was to elucidate whether long-term LT survivors with normal spirometry achieve normal exercise capacity, and to identify predictive factors of exercise capacity., Methods: This was a cross-sectional multicentre study, where bilateral LT recipients who survived at least 10 years after LT, with normal spirometry, no diagnosis of CLAD and modified Medical Research Council dyspnoea degree ≤2 underwent cardiopulmonary exercise testing (CPET)., Results: 28 LT recipients were included with a mean±sd age of 48.7±13.6 years. Oxygen uptake ( V' O 2 ) had a mean±sd value of 21.49±6.68 mL·kg -1 ·min -1 (75.24±15.6%) and the anaerobic threshold was reached at 48.6±10.1% of the V' O 2 max predicted. The mean±sd heart rate reserve at peak exercise was 17.56±13.6%. The oxygen pulse increased during exercise and was within normal values at 90.5±19.4%. The respiratory exchange ratio exceeded 1.19 at maximum exercise. The median (25-75 th percentile) EuroQol-5D score was 1 (0.95-1), indicating a good quality of life. The median (25-75 th percentile) International Physical Activity Questionnaire score was 5497 (4007-9832) MET-min·week -1 with 89% of patients reporting more than 1500 MET-min·week -1 . In the multivariate regression models, age, sex and diffusing capacity of the lung for carbon monoxide remained significantly associated with V' O 2 max (mL·kg -1 ·min -1 ); haemoglobin and forced expiratory volume in 1 s were significantly associated with maximum work rate (watts), after adjusting for confounders., Conclusion: We report for the first time near-normal peak V' O 2 values during CPET and normal exercise capacity in long-term LT recipients without CLAD., Competing Interests: Conflict of interest: B. Saez-Gimenez reports lecture fees from GlaxoSmithKline, and travel grants from Actelion Pharmaceuticals, Bial, Mundipharma, Novartis and Astellas Pharma, during the conduct of the study. Conflict of interest: M. Barrecheguren has nothing to disclose. Conflict of interest: M.A. Ramon has nothing to disclose. Conflict of interest: A. Gomez-Garrido has nothing to disclose. Conflict of interest: C. Bravo has nothing to disclose. Conflict of interest: V. Monforte has nothing to disclose. Conflict of interest: M. López-Meseguer has nothing to disclose. Conflict of interest: C. Berastegui has nothing to disclose. Conflict of interest: E. Revilla has nothing to disclose. Conflict of interest: C. Romero has nothing to disclose. Conflict of interest: R. Laporta has nothing to disclose. Conflict of interest: S. Fernández-Rozas has nothing to disclose. Conflict of interest: J. Redel-Montero has nothing to disclose. Conflict of interest: A. Solé has nothing to disclose. Conflict of interest: M. de la Torre has nothing to disclose. Conflict of interest: L. Puente has nothing to disclose. Conflict of interest: A. Roman has nothing to disclose. Conflict of interest: S. Gómez-Ollés reports travel grants from Teva and Actelion Pharmaceuticals during the conduct of the study. Conflict of interest: I. Ojanguren reports personal fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi and GlaxoSmithKline, grants and personal fees from Mindipharma, personal fees from Novartis and Teva, grants from Menarini, and personal fees from MSD, during the conduct of the study., (Copyright ©ERS 2021.)

α 1 -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., Competing Interests: Conflict of interest: M. Barrecheguren reports speaker fees from Grifols, Menarini, CSL Behring, Boehringer Ingelheim and GlaxoSmithKline, and consulting fees from GSK and Novartis, outside the submitted work. Conflict of interest: K. O'Hara reports non-financial support from the European Lung Foundation/European Respiratory Society and Mereo BioPharma Group PLC, personal fees and non-financial support from NICE, and non-financial support from Alpha-1 Global; the Alpha-1 UK Support Group has received grants from CSL Behring, and receives donations from individuals/companies as a result of fundraising activities. Conflict of interest: M. Wilkens reports reimbursement of travel costs by the European Lung Foundation during the conduct of the study; as chairman of the patient organisation Alpha1 Deutschland e.V., he does not personally receive any donations, but the organisation receives money from public funds and the pharmaceutical industry (grants as well as, e.g. travel costs). Conflict of interest: J. Boyd is an employee of the European Lung Foundation. Conflict of interest: E. Kolda has nothing to disclose. Conflict of interest: B. Lara has nothing to disclose. Conflict of interest: J. Chorostowska-Wynimko reports grants, personal fees and non-financial support from Grifols, AstraZeneca and Pfizer, personal fees and non-financial support from MSD and BMS, personal fees from GlaxoSmithKline, Novartis, Chiesi and Roche, grants and personal fees from Boehringer Ingelheim, grants, personal fees and non-financial support from CSL Behring and CelonPharma, and personal fees from Amgen and Lekam, outside the submitted work. Conflict of interest: I. Ferrarotti has received speaker and consulting fees from CSL Behring and Grifols Conflict of interest: J. Chlumsky reports personal fees and non-financial support from CSL Behring, personal fees from AstraZeneca, personal fees and non-financial support from GlaxoSmithKline, and personal fees and non-financial support from Boehringer Ingelheim, Actelion and Takeda, during the conduct of the study. Conflict of interest: C. Clarenbach reports personal fees from Roche, Novartis, Boehringer, GlaxoSmithKline, AstraZeneca, Sanofi, Vifor and Mundipharma, outside the submitted work. Conflict of interest: T. Greulich reports grants from CSL-Behring, Grifols and Kamada during the conduct of the study; personal fees for lectures and advisory boards from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, CSL-Behring, Grifols, GlaxoSmithKline and Novartis, and grants from Grifols and the German Centre for Lung Research (DZL), Marburg, Germany (Deutsches Zentrum für Lungenforschung), outside the submitted work. Conflict of interest: M. Miravitlles reports speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Zambon, Sandoz, 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, Kamada, TEVA, Sanofi, pH Pharma, Novartis and Grifols, and grants from GlaxoSmithKline and Grifols, outside the submitted work. Conflict of interest: M. Sucena reports speaker or consulting fees from Boehringer Ingelheim, CSL Behring, Grifols and Novartis, and personal fees from Bial, Boehringer Ingelheim, CSL Behring, DarSaúde, Gasoxmed, Grifols, Linde, Menarini, Novartis and VitalAire, outside the submitted work., (Copyright ©ERS 2020.)

Background: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research., Methods: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion., Results: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder., Conclusions: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities., Competing Interests: Conflict of interest: C. Bai has nothing to disclose. Conflict of interest: S.H. Chotirmall has nothing to disclose. Conflict of interest: J. Rello has nothing to disclose. Conflict of interest: G.A. Alba has nothing to disclose. Conflict of interest: L.C. Ginns has nothing to disclose. Conflict of interest: J.A. Krishnan reports grants from National Institutes of Health, Regeneron/Department of Health and Human Services, and Verily for COVID-19 studies outside the submitted work. Conflict of interest: R. Rogers has nothing to disclose. Conflict of interest: E. Bendstrup reports grants and personal fees from Hofmann la Roche and Boehringer Ingelheim, outside the submitted work. Conflict of interest: P-R. Burgel reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Insmed, Novartis, Pfizer, Teva and Zambon, and grants and personal fees from Vertex and GSK, outside the submitted work. Conflict of interest: J.D. Chalmers reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Glaxosmithkline, Insmed and Novartis, personal fees from Chiesi and Zambon, and grants from Gilead, outside the submitted work. Conflict of interest: A. Chua has nothing to disclose. Conflict of interest: K.A. Crothers has nothing to disclose. Conflict of interest: A. Duggal has nothing to disclose. Conflict of interest: Y.W. Kim has nothing to disclose. Conflict of interest: J.G. Laffey has nothing to disclose. Conflict of interest: C.M. Luna has nothing to disclose. Conflict of interest: M.S. Niederman reports other funding from Abbvie and Merck, outside the submitted work. Conflict of interest: G. Raghu reports consultant fees from Boerhinger Ingelheim, Roche-Genentech, Blade therapeutics, PureTech Health and Humanetics corporation. Conflict of interest: J.A. Ramirez has nothing to disclose. Conflict of interest: J. Riera has nothing to disclose. Conflict of interest: O. Roca provides consultancy to Hamilton Medical but did not receive any personal fees. All compensations were received by the Institute of Research of his institution. He also reports personal fees from Air Liquide, outside the submitted work. Conflict of interest: M. Tamae-Kakazu has nothing to disclose. Conflict of interest: A. Torres has nothing to disclose. Conflict of interest: R.R. Watkins has nothing to disclose. Conflict of interest: M. Barrecheguren reports speaker fees from Grifols, Menarini, CSL Behring, Boehringer Ingelheim and GSK, and consulting fees from GSK and Novartis, outside the submitted work. Conflict of interest: M. Belliato has nothing to disclose. Conflict of interest: H.A. Chami reports grants, personal fees and non-financial support from Pfizer, and personal fees from Boehringer Ingelheim, MSD, Novartis, Mundipharma and AstraZeneca, outside the submitted work. Conflict of interest: R. Chen has nothing to disclose. Conflict of interest: G.A. Cortes Puentes has nothing to disclose. Conflict of interest: C. Delacruz has nothing to disclose. Conflict of interest: M.M. Hayes has nothing to disclose. Conflict of interest: L.M.A. Heunks reports grants from Liberate medical, USA, personal fees from Getinge Critical Care, Sweden, and grants and personal fees from Orion Pharma, Finland, outside the submitted work. Conflict of interest: S.R. Holets has nothing to disclose. Conflict of interest: C.L. Hough has nothing to disclose. Conflict of interest: S. Jagpal was a sub-investigator for the RWJ New Brunswick Remdesivir study. Conflict of interest: S. Jeon has nothing to disclose. Conflict of interest: K. Johkoh has nothing to disclose. Conflict of interest: M.M. Lee has nothing to disclose. Conflict of interest: J. Liebler has nothing to disclose. Conflict of interest: G.N. McElvaney has nothing to disclose. Conflict of interest: A. Moskowitz has nothing to disclose. Conflict of interest: R.A. Oeckler has nothing to disclose. Conflict of interest: I. Ojanguren reports grants and personal fees from AstraZeneca and Chiesi, personal fees from Boehringer Ingelheim, Novartis, GSK, MSD, BIAL, Mundipharma and TEVA, and grants from Menarini, outside the submitted work. Conflict of interest: A. O'Regan has nothing to disclose. Conflict of interest: M.W. Pletz has nothing to disclose. Conflict of interest: C.K. Rhee reports personal fees from MSD, AstraZeneca, GSK Novartis, Takeda, Mundipharma, Boehringer-Ingelheim, Teva, Sanofi and Bayer, outside the submitted work. Conflict of interest: M.J. Schultz's institution and department participated, and participates in, international studies of remdisivir. Participation was without financial compensations, etc., and also did not and will not lead to authorships on manuscripts from these studies. Conflict of interest: E. Storti has nothing to disclose. Conflict of interest: C. Strange has nothing to disclose. Conflict of interest: C.C. Thomson has nothing to disclose. Conflict of interest: F.J. Torriani has nothing to disclose. Conflict of interest: X. Wang has nothing to disclose. Conflict of interest: W. Wuyts has nothing to disclose. Conflict of interest: T. Xu has nothing to disclose. Conflict of interest: D. Yang has nothing to disclose. Conflict of interest: Z. Zhang has nothing to disclose. Conflict of interest: K.C. Wilson has nothing to disclose., (Copyright ©ERS 2020.)

Background: Understanding the risk factors for exacerbations of COPD may help provide a more personalised approach to exacerbation prevention., Method: Observational, prospective, international, multicentre study aimed at identifying risk factors for exacerbations of COPD. Clinical variables, lung function and CAT scores were collected at baseline. In addition, routine blood biomarkers were also obtained, and patients were followed for 12 months., Results: A total of 326 patients were included. Of these, 155 (47.5%) presented at least one exacerbation. The median time to the first exacerbation was 147 days. Exacerbators had more respiratory symptoms, more impairment in FEV1(%), FVC(%) and a worse CAT score. Regarding biomarkers, only C-reactive protein was significantly higher in exacerbators (2.8 (standard deviation (SD):3.8) mg/dL vs. 1.9 (SD:2.6) mg/dL; p = 0.037). In multivariate analysis, only CAT scores, FEV1(%) and previous exacerbations were significantly associated with having an exacerbation during follow-up. In the equation of risk, patients with a CAT score ≥15, FEV1(%) <55% and at least one exacerbation the previous year had a probability of 76% of having an exacerbation during the next year, compared with 17% in patients who had none of the previous variables. No biomarkers showed a significant association in multivariate analysis., Conclusions: Less than half of the patients presented an exacerbation during the one-year follow-up. CAT scores, FEV1(%) and previous exacerbations were the only variables associated with increased risk of exacerbations. Routine biomarkers did not provide additional information to evaluate the risk of exacerbations., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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., Competing Interests: Conflict of interest: T. Greulich reports grants from CSL-Behring, Grifols and Kamda during the conduct of the study; 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), outside the submitted work. Conflict of interest: A. Altraja reports travel support to attend the EARCO stakeholder board meeting on 17 June 2019 from EARCO during the conduct of the study; support for clinical trials and honoraria for advisory board meetings from CSL Behring, honoraria for lectures/chairmanships and advisory board meetings and travel support from Shire Pharmaceuticals, AstraZeneca, Boehringer Ingelheim, Chiesi (Norameda), GlaxoSmithKline, MSD, Novartis, Roche, Bayer and Actelion (Johnson & Johnson), research support from Pfizer, travel support from Teva, Sanofi and United Therapeutics (AOP Orphan), honoraria for lectures and travel support from Berlin-Chemie Menarini Group, and honoraria for lectures from Orion, outside the submitted work. Conflict of interest: M. Barrecheguren reports speaker fees from Menarini, Grifols, CSL Behring, Boehringer Ingelheim, Gebro Pharma and GlaxoSmithKline, and consulting fees from Novartis and GlaxoSmithKline, outside the submitted work. Conflict of interest: R. Bals reports grants and personal fees from AstraZeneca and Boehringer Ingelheim, personal fees from GlaxoSmithKline and Grifols, grants and personal fees from Novartis, personal fees from CSL Behring, grants from the German Federal Ministry of Education and Research (BMBF) Competence Network Asthma and COPD (ASCONET), Sander Stiftung, Schwiete Stiftung, Krebshilfe and Mukoviszidose e.V., outside the submitted work. Conflict of interest: J. Chlumsky reports personal fees for lectures and consultation from CSL Behring, and travel support from CSL Behring, outside the submitted work. Conflict of interest: J. Chorostowska-Wynimko reports grants, personal fees and nonfinancial support from Grifols, personal fees from Kamada, grants, personal fees and nonfinancial support from AstraZeneca, personal fees and nonfinancial support from Pfizer, MSD and BMS, personal fees from GSK, Novartis amd Chiesi, personal fees and nonfinancial support from Roche, grants and personal fees from Boehringer Ingelheim, personal fees and nonfinancial support from Abbvie, grants, personal fees and nonfinancial support from CSL Behring, personal fees from Lekam, grants, personal fees and nonfinancial support from CelonPharma, and personal fees from Takeda, outside the submitted work. Conflict of interest: C. Clarenbach reports consulting fees and travel support from Vifor Pharma, and consulting or speaker fees from Boehringer, Novartis, GSK, AstraZeneca and Sanofi, outside the submitted work. Conflict of interest: L. Corda has nothing to disclose. Conflict of interest: A.G. Corsico has nothing to disclose. Conflict of interest: I. Ferrarotti has nothing to disclose. Conflict of interest: C. Esquinas has nothing to disclose. Conflict of interest: C. Gouder has nothing to disclose. Conflict of interest: A. Hećimović reports speaker fees from Roche, Boehringer Ingelheim, Novartis and MSD, outside the submitted work. Conflict of interest: A. Ilic has nothing to disclose. Conflict of interest: Y. Ivanov has nothing to disclose. Conflict of interest: S. Janciauskiene has nothing to disclose. Conflict of interest: W. Janssens reports receiving research grants and money for consultancy activities from Behring, AstraZeneca, Boerhinger Ingelheim, GSK, Chiesi, outside the submitted work. He is co-founder of ArtiQ, a spinoff company in healthcare. Conflict of interest: M. Kohler reports advisor fees from Novartis, Boehringer Ingelheim, AstraZeneca, GSK and Bayer, outside the submitted work. Conflict of interest: A. Krams reports personal fees and nonfinancial support from AstraZeneca, Berlin-Chemie/Menarini and Boehringer Ingelheim, personal fees from GlaxoSmithKline and Merck Serono, personal fees and nonfinancial support from Norameda (represents Chiesi in Baltic countries), personal fees from Novartis, and nonfinancial support from Mylan, outside the submitted work. Conflict of interest: B. Lara has nothing to disclose. Conflict of interest: R. Mahadeva reports personal fees from Chiesi, Astra Zeneca and Boehringer Ingelheim, and grants from Pfizer Open Air, outside the submitted work. Conflict of interest: G. McElvaney has sat on advisory boards for CSL Behring, Grifols, Vertex and Chiesi. Conflict of interest: J-F. Mornex reports nonfinancial support from ADAAT, grants, personal fees and nonfinancial support from LFB and CSL Behring, nonfinancial support from Grifols, personal fees and nonfinancial support from Polyphor, during the conduct of the study; personal fees and nonfinancial support from Actelion, GSK, Roche and Novartis, nonfinancial support from Bayer, personal fees and nonfinancial support from BMS, nonfinancial support from Pfizer and MSD, personal fees from Ellivie, and nonfinancial support from Boehringer, outside the submitted work. Conflict of interest: K. O'Hara reports nonfinancial support from ELF/ERS and Mereo BioPharma Group PLC, grants from CSL Behring, and also receives donations from individuals/companies as a result of fundraising activities; personal fees and nonfinancial support from NICE and nonfinancial support from Alpha-1 Global, outside the submitted work. Conflict of interest: D. Parr reports advisory board and consultancy fees from CSL Behring and Kamada, outside the submitted work. Conflict of interest: E. Piitulainen has nothing to disclose. Conflict of interest: K. Schmid-Scherzer has nothing to disclose. Conflict of interest: N. Seersholm has nothing to disclose. Conflict of interest: R.A. Stockley reports a grant for a small, investigator-lead project and personal fees for a trial steering board from CSL Behring; a lecture fee from GSK; advisory board fees from Vertex, inhbrix, Mereobiopharma and Novartis; and lecture fees from Grifols, during the conduct of the study. He acts in an advisory manner for several companies with an interest in α1-antitrypsin deficiency. Conflict of interest: J. Stolk has nothing to disclose. Conflict of interest: M. Sucena reports lecture fees and travel pay from Grifols and CSL Behring, outside the submitted work. Conflict of interest: H. Tanash has nothing to disclose. Conflict of interest: A. Turner reports grants and personal fees from CSL Behring; personal fees and nonfinancial support from Boehringer Ingelheim; nonfinancial support from GSK; grants, personal fees and nonfinancial support from AstraZeneca; grants, personal fees and nonfinancial support from Chiesi; grants from Grifols biotherapeutics, outside the submitted work. Conflict of interest: R. Ulmeanu has nothing to disclose. Conflict of interest: M. Wilkens reports that as chairman of the patient organisation Alpha1 Deutschland e.V., he does not receive personally any donations but his organisation receives money from public funds as well as from the pharmaceutical industry, including grants and travelling costs. Conflict of interest: A. Yorgancıoğlu reports grants from MSD, and personal fees from GSK, AstraZeneca, Abdi Ibrahim, Chiesi, Novartis and Sandoz, outside the submitted work. Conflict of interest: A. Zaharie has nothing to disclose. Conflict of interest: M. Miravitlles reports speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, AstraZeneca, 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 to his institution from GlaxoSmithKline and Grifols, outside the submitted work., (Copyright ©ERS 2020.)

Background & Aims: Alpha-1 antitrypsin deficiency (AATD) is among the most common genetic disorders. Severe AATD is caused by a homozygous mutation in the SERPINA1 gene that encodes the Glu342Lys substitution (called the Pi*Z mutation, Pi*ZZ genotype). Pi*ZZ carriers may develop lung and liver diseases. Mutation-associated lung disorders have been well studied, but less is known about the effects in liver. We assessed the liver disease burden and associated features in adults with this form of AATD., Methods: We collected data from 554 Pi*ZZ adults (403 in an exploratory cohort, 151 in a confirmatory cohort), in 9 European countries, with AATD who were homozygous for the Pi*Z mutation, and 234 adults without the Pi*Z mutation (controls), all without pre-existing liver disease. We collected data on demographic parameters, comorbidities, lung- and liver-related health, and blood samples for laboratory analysis. Liver fibrosis was assessed non-invasively via the serum tests Aspartate Aminotransferase to Platelet Ratio Index and HepaScore and via transient elastography. Liver steatosis was determined via transient elastography-based controlled attenuation parameter. We performed histologic analyses of livers from transgenic mice that overexpress the AATD-associated Pi*Z variant., Results: Serum levels of liver enzymes were significantly higher in Pi*ZZ carriers vs controls. Based on non-invasive tests for liver fibrosis, significant fibrosis was suspected in 20%-36% of Pi*ZZ carriers, whereas signs of advanced fibrosis were 9- to 20-fold more common in Pi*ZZ carriers compared to non-carriers. Male sex; age older than 50 years; increased levels of alanine aminotransferase, aspartate aminotransferase, or γ-glutamyl transferase; and low numbers of platelets were associated with higher liver fibrosis burden. We did not find evidence for a relationship between lung function and liver fibrosis. Controlled attenuation parameter ≥280 dB/m, suggesting severe steatosis, was detected in 39% of Pi*ZZ carriers vs 31% of controls. Carriers of Pi*ZZ had lower serum concentrations of triglyceride and low- and very-low-density lipoprotein cholesterol than controls, suggesting impaired hepatic secretion of lipid. Livers from Pi*Z-overexpressing mice had steatosis and down-regulation of genes involved in lipid secretion., Conclusions: In studies of AATD adults with the Pi*ZZ mutation, and of Pi*Z-overexpressing mice, we found evidence of liver steatosis and impaired lipid secretion. We identified factors associated with significant liver fibrosis in patients, which could facilitate hepatologic assessment and counseling of individuals who carry the Pi*ZZ mutation. ClinicalTrials.gov Number NCT02929940., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: Self-management has gained increased relevance in the management of chronic obstructive pulmonary disease patients. The heterogeneity in self-management interventions has complicated the development of recommendations for clinical practice. In this review, we present the latest findings regarding conceptual definition, effectiveness of self-management interventions and self-management strategies in chronic obstructive pulmonary disease as a first step toward personalized medicine: what, how and to whom?, Recent Findings: Self-management interventions have shown benefits in improving health-related quality of life and reducing hospital admissions. Favorable outcomes can only be achieved if patients have an ultimate goal, that is their desired achievements in their life. In the continuum of care, the components of the self-management program will vary to adapt to the condition of the patient (disease severity, comorbidities) and to factors such as patient motivation, confidence (self-efficacy), access to health care, family and social support. A combination of education, case management and patient-centric action plan has shown the best chance of success., Summary: The individual patient's needs, own preferences and personal goals should inform the design of any intervention with a behavioral component. A continuous loop process has to be implemented to constantly assess what work and does not work, aiming at achieving the desired outcomes for a given patient.

Background: α1-Antitrypsin deficiency (AATD) is associated with a high risk of developing lung and liver disease. Despite being one of the most common hereditary disorders worldwide, AATD remains under-diagnosed and prolonged delays in diagnosis are usual. The aim of this study was to validate the use of buccal swab samples and serum circulating DNA for the complete laboratory study of AATD., Methods: Sixteen buccal swab samples from previously characterized AATD patients were analyzed using an allele-specific genotyping assay and sequencing method. In addition, 19 patients were characterized by quantification, phenotyping and genotyping using only serum samples., Results: The 16 buccal swab samples were correctly characterized by genotyping. Definitive results were obtained in the 19 serum samples analyzed by quantification, phenotyping and genotyping, thereby performing the complete AATD diagnostic algorithm., Conclusions: Buccal swab samples may be useful to expand AATD screening programs and family studies. Genotyping using DNA from serum samples permits the application of the complete diagnostic algorithm without delay. These two methods will be useful for obtaining more in depth knowledge of the real prevalence of patients with AATD.

Background: Insufficient epidemiological data are available on bronchiectasis in southern European populations. The aim of this study was to determine the prevalence and incidence of bronchiectasis in Catalonia, Spain and describe the characteristics of patients with an active diagnosis of bronchiectasis in 2012., Methods: This study used data from a population database containing information from 5.8 million people (80% of the population of Catalonia). Patients with bronchiectasis were identified using International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) codes, and information on clinical characteristics and treatment was extracted., Results: A total of 20895 patients with bronchiectasis were identified in 2012. The prevalence of bronchiectasis was 36.2 cases per 10 000 inhabitants, with an incidence of 4.81 cases per 10 000 inhabitants. Prevalence and incidence increased with age and were highest in men over 65 years of age. Among the whole bronchiectasis population in Primary Care, 48.6% of patients had had blood tests, 11.2% had undergone spirometry, only 2.1% had a chest X-ray, and 0.9% had undergone high-resolution computed tomography or sputum culture. 56% had at least one exacerbation and 12.5% had been admitted to hospital during the year of the study. The drugs most frequently used were inhaled corticosteroids (in 37.4% of patients) and long-acting β 2 agonists (in 36%); half of the patients received no treatment (51.8%)., Conclusions: The prevalence and incidence of bronchiectasis increases with age. The management of bronchiectasis in primary care was not optimal, and the disease continues to represent an important clinical burden., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: Alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite initiatives developed to increase awareness. The objective was to describe the current situation of the diagnosis of AATD in primary care (PC) in Catalonia, Spain., Methods: We performed a population-based study with data from the Information System for Development in Research in Primary Care, a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). We collected the number of alpha-1 antitrypsin (AAT) determinations performed in the PC in two periods (2007-2008 and 2010-2011) and described the characteristics of the individuals tested., Results: A total of 12,409 AAT determinations were performed (5,559 in 2007-2008 and 6,850 in 2010-2011), with 10.7% of them in children. As a possible indication for AAT determination, 28.9% adults and 29.4% children had a previous diagnosis of a disease related to AATD; transaminase levels were above normal in 17.7% of children and 47.1% of adults. In total, 663 (5.3%) individuals had intermediate AATD (50-100 mg/dL), 24 (0.2%) individuals had a severe deficiency (<50 mg/dL), with a prevalence of 0.19 cases of severe deficiency per 100 determinations. Nine (41%) of the adults with severe deficiency had a previous diagnosis of COPD/emphysema, and four (16.7%) were diagnosed with COPD within 6 months., Conclusion: The number of AAT determinations in the PC is low in relation to the prevalence of COPD but increased slightly along the study period. The indication to perform the test is not always clear, and patients detected with deficiency are not always referred to a specialist.

Introduction: Treatment for COPD is tailored based on clinical characteristics and severity. However, prescription patterns in COPD patients newly diagnosed in primary care may differ from guideline recommendations., Method: We performed an epidemiological study with data obtained from the Information System for the Development in Research in Primary Care (SIDIAP), a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). Patients newly diagnosed with COPD from 2007 to 2012 were identified and information about the initial treatment patterns was collected. The initial treatment was also described by phenotype and severity., Results: During the study period 41,492 patients were newly diagnosed with COPD. Patients were classified as non exacerbators (28,552 patients, 69%), asthma-COPD overlap syndrome (ACOS) (2152 patients, 5.2%) and frequent exacerbators (10,888 patients, 27.6%). Among the patients in whom FEV1 was available, 13.9% were GOLD stage 1, 55.2% stage 2, 26% stage 3 and 4.8% stage 4. Globally, the most frequently prescribed treatment patterns were short-acting bronchodilators (SABD) in monotherapy (17.7%), long-acting β-2 agonists (LABA) + inhaled corticosteroids (ICS) (17.3%) and triple therapy (12.2%). The frequency of patients treated with a SABD increased from 15.9% to 19.5% during the study period, while the number of untreated patients decreased from 24.4% to 15.1%. Up to 45.2% of patients were initially treated with ICS, which were frequently prescribed in the ACOS (69.2%) and in the exacerbator phenotype patients (52.4%) while ICS use has decreased from 43.8% in 2007 to 35.8% in 2012 in non exacerbator patients. Up to 13.6% and 14.8% of GOLD 4 patients received no treatment or only SABD after diagnosis., Conclusions: Initial treatment patterns in newly diagnosed COPD patients often do no comply with guidelines. The use of ICS is excessive but has decreased mainly in non exacerbator patients. Many COPD patients still remain untreated after diagnosis, although this has decreased. Some GOLD 4 patients are still receiving SABD or no treatment at all after diagnosis., (Copyright © 2015 Elsevier Ltd. All rights reserved.)