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Background: An association of ABO blood group and COVID-19 remains controversial., Methods: Following STROBE guidance for observational research, we explored the distribution of ABO blood group in patients hospitalized for acute COVID-19 and in those with Long COVID. Contingency tables were made and risk factors were explored using crude and adjusted Mantle-Haentzel odds ratios (OR and 95% CI)., Results: Up to September 2022, there were a total of 5,832 acute COVID-19 hospitalizations in our hospital, corresponding to 5,503 individual patients, of whom blood group determination was available for 1,513 (27.5%). Their distribution by ABO was: 653 (43.2%) group 0, 690 (45.6%) A, 113 (7.5%) B, and 57 (3.8%) AB, which corresponds to the expected frequencies in the general population. In parallel, of 676 patients with Long COVID, blood group determination was available for 135 (20.0%). Their distribution was: 60 (44.4%) from group 0, 61 (45.2%) A, 9 (6.7%) B, and 5 (3.7%) AB. The distribution of the ABO system of Long COVID patients did not show significant differences with respect to that of the total group (p ≥ 0.843). In a multivariate analysis adjusting for age, sex, ethnicity, and severity of acute COVID-19 infection, subgroups A, AB, and B were not significantly associated with developing Long COVID with an OR of 1.015 [0.669-1.541], 1.327 [0.490-3.594] and 0.965 [0.453-2.058], respectively. The effect of the Rh+ factor was also not significant 1,423 [0.772-2,622] regarding Long COVID., Conclusions: No association of any ABO blood subgroup with COVID-19 or developing Long COVID was identified., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Soriano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Coronavirus-associated acute respiratory distress syndrome (CARDS) has limited effective therapy to date. NLRP3 inflammasome activation induced by SARS-CoV-2 in COVID-19 contributes to cytokine storm., Methods: This randomised, multinational study enrolled hospitalised patients (18-80 years) with COVID-19-associated pneumonia and impaired respiratory function. Eligible patients were randomised (1:1) via Interactive Response Technology to DFV890 + standard-of-care (SoC) or SoC alone for 14 days. Primary endpoint was APACHE II score at Day 14 or on day-of-discharge (whichever-came-first) with worst-case imputation for death. Other key assessments included clinical status, CRP levels, SARS-CoV-2 detection, other inflammatory markers, in-hospital outcomes, and safety., Findings: Between May 27, 2020 and December 24, 2020, 143 patients (31 clinical sites, 12 countries) were randomly assigned to DFV890 + SoC (n = 71) or SoC alone (n = 72). Primary endpoint to establish clinical efficacy of DFV890 vs. SoC, based on combined APACHE II score, was not met; LSM (SE), 8·7 (1.06) vs. 8·6 (1.05); p = 0.467. More patients treated with DFV890 vs. SoC showed ≥ 1-level improvement in clinical status (84.3% vs. 73.6% at Day 14), earlier clearance of SARS-CoV-2 (76.4% vs. 57.4% at Day 7), and mechanical ventilation-free survival (85.7% vs. 80.6% through Day 28), and there were fewer fatal events in DFV890 group (8.6% vs. 11.1% through Day 28). DFV890 was well tolerated with no unexpected safety signals., Interpretation: DFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS., Trial Registration: ClinicalTrials.gov, NCT04382053., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Smokefree laws are intended to protect against second-hand smoke (SHS) in outdoor areas. We examined if exposure to PM2.5 particles in outdoor smoking areas changed breathing rates in 60 patients with asthma ( n = 30) or with COPD ( n = 30), in an open, non-randomised, interventional study model in Czechia, Ireland and Spain. The patients wore a PM2.5 particle monitor (AirSpeck) and a breath monitor (RESpeck) for 24 h to determine changes in breathing rates (Br) at rest and during a visit to an outside smoking area. Spirometry and breath CO were measured before and the day after visiting an outdoor smoking area. The PM2.5 levels at the 60 venues were highly variable, ranging from ≥2000 µg/m 3 (in 4 premises) to ≤10 µg/m 3 (in 3 premises, which had only a single wall in the structure). At 39 venues, the mean PM 2.5 levels were ≥25 µg/m 3 . The breathing rate changed significantly in 57 of the 60 patients, resulting in an increase in some patients and a decrease in others. Comprehensive smokefree laws were ineffective in protecting asthma and COPD patients from exposure to high levels of SHS in outside areas of pubs and terraces, which should be avoided by these patients. These findings also support the extension of smokefree laws to outside areas.

Background: Urothelial cells exhibit increased expression of angiotensin-converting enzyme-2 receptor, which is the binding site of severe acute respiratory syndrome coronavirus 2 to cells. The frequency and distribution of genitourinary tract symptoms in patients diagnosed with coronavirus disease 2019 (COVID-19) is unknown., Objective: We explored trends in genitourinary tract symptoms by gender and each of six pandemic waves in patients admitted for COVID-19, and related them with severity, death and length of hospitalization., Design Setting and Participants: A retrospective study took place in our institution of COVID-19 admitted patients. Only patients with RT-PCR or antigen test confirmed SARS-CoV-2 infection were included. Demographic, clinical, and genitourinary symptoms were explored., Outcome Measurements and Statistical Analysis: COVID-19 patients with genitourinary tract symptoms were compared with those without. Statistical comparisons were conducted by parametric and nonparametric tests for quantitative variables, and χ 2 test for qualitative variables., Results and Limitations: Out of a total of 4,661 COVID-19 patients, genitourinary symptoms were found in 21,1%. These symptoms were more frequent in patients admitted for longer than 30 days, except for urinary incontinence (UI) and erectile dysfunction (ED). Acute kidney injury (AKI) and urinary tract infections (UTI) had a higher presence in the 5 th (16.7%; 12.8% respectively) and 3 rd wave (13.3%; 12.6% respectively). Genitourinary symptoms were higher for those patients admitted in critical care units. Frequency of AKI, UI, UTI and acute urinary retention (AUR) were higher for patients who were finally deceased (26.2%; 3.5%; 13.6% and 3.6% respectively)., Conclusions: A high frequency of genitourinary symptoms in patients admitted for COVID-19 was observed, whose frequency and distribution varied according to pandemic waves. Specific genitourinary conditions were associated with worse outcomes and poorer prognosis., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Author(s).)

Introduction: We aim to describe the changes in prevalence and risk factors associated to chronic obstructive pulmonary disease (COPD) in Spain, comparing three population-based studies conducted in three timepoints., Methods: We compared participants from IBERPOC conducted in 1997, EPISCAN conducted in 2007 and EPISCAN II in 2017. COPD was defined as a postbronchodilator FEV 1 /FVC (forced expiratory volume in 1s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV 1 /FVC below the lower limit of normal (LLN)., Results: COPD prevalence in the population between 40 and 69 years decreased from 21.6% (95% CI 20.7%-23.2%) in 1997 to 8.8% (95% CI 8.2%-9.5%) in 2017, a 59.2% decline (p<0.001). In 2007, the prevalence was 7.7% (95% CI 6.8%-8.7%) with an upward trend of 1.1 percentage points in 2017 (p=0.073). Overall COPD prevalence decreased in men and women, although a significant increase was observed in the last decade in females (p<0.05). Current smokers significantly increased in the last decades (25.4% in 1997, 29.1% in 2007 and 23.4% in 2017; p<0.001). Regrettably, COPD underdiagnosis was constantly high, 77.6% in 1997, 78.4% in 2007, and to 78.2% in 2017 (p=0.95), higher in younger ages (40-49 yrs and 50-59 yrs) and also higher in women than in men in all three studies (p<0.05)., Conclusions: We report a significant reduction of 59.2% in the prevalence of COPD in Spain from 1997 to 2017 in subjects aged 40-69 years. Our study highlights the significant underdiagnosis of COPD, particularly sustained in women and younger populations., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) is commonly diagnosed when the airflow limitation is well established and symptomatic. We aimed to identify individuals at risk of developing COPD according to the concept of pre-COPD and compare their clinical characteristics with 1) those who have developed the disease at a young age, and 2) the overall population with and without COPD., Methods: The EPISCAN II study is a cross-sectional, population-based study that aims to investigate the prevalence of COPD in Spain in subjects ≥40 years of age. Pre-COPD was defined as the presence of emphysema >5% and/or bronchial thickening by computed chromatography (CT) scan and/or diffusing capacity of the lung for carbon monoxide ( D LCO ) <80% of predicted in subjects with respiratory symptoms and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV 1 /FVC) >0.70. Young COPD was defined as FEV 1 /FVC <0.70 in a subject ≤50 years of age. Demographic and clinical characteristics were compared among pre-COPD, young COPD and the overall population with and without COPD., Results: Among the 1077 individuals with FEV 1 /FVC <0.70, 65 (6.0%) were ≤50 years of age. Among the 8015 individuals with FEV 1 /FVC >0.70, 350 underwent both D LCO testing and chest CT scanning. Of those, 78 (22.3%) subjects fulfilled the definition of pre-COPD. Subjects with pre-COPD were older, predominantly women, less frequently active or ex-smokers, with less frequent previous diagnosis of asthma but with higher symptomatic burden than those with young COPD., Conclusions: 22.3% of the studied population was at risk of developing COPD, with similar symptomatic and structural changes to those with well-established disease without airflow obstruction. This COPD at-risk population is different from those that develop COPD at a young age., Competing Interests: Conflict of interest: B.G. Cosío has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Sanofi and TEVA, and research grants from Menarini, AstraZeneca and Boehringer Ingelheim. Conflict of interest: C. Casanova has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini and Novartis, and research grants from GlaxoSmithKline, Menarini and AstraZeneca. Conflict of interest: J.J. Soler-Cataluña has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GlaxoSmithKline, Menarini, Novartis and Teva, and consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, GlaxoSmithKline, Ferrer and Novartis. Conflict of interest: J.B. Soriano has nothing to disclose. F. García-Río has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Pfizer and Rovi, and research grants from Chiesi, Esteve, Gebro Pharma, GlaxoSmithKline, Menarini and TEVA. Conflict of interest: P. de Lucas has nothing to disclose. Conflict of interest: I. Alfageme has nothing to disclose. Conflict of interest: J.M. Rodríguez González-Moro has nothing to disclose. Conflict of interest: G. Sánchez is a GSK employee within the Medical Department. Conflict of interest: J. Ancochea has received speaker or consulting fees from Actelion, Air Liquide, Almirall, AstraZeneca, Boehringer Ingelheim, Carburos Médica, Chiesi, Faes Farma, Ferrer, GlaxoSmithKline, InterMune, Linde Healthcare, Menarini, MSD, Mundipharma, Novartis, Pfizer, Roche, Rovi, Sandoz, Takeda and Teva. Conflict of interest: M. Miravitlles has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Gebro Pharma, Kamada, GlaxoSmithKline, Grifols, Menarini, Mereo Biopharma, Novartis, pH Pharma, Palobiofarma SL, Rovi, TEVA, Spin Therapeutics, Verona Pharma and Zambon, and research grants from Grifols., (Copyright ©The authors 2023.)

Badkground: Physical capacity (PC) and daily physical activity (PA) are two crucial factors in the clinical course of COPD, although they do not always maintain a close relationship. The objectives were to evaluate the frequency of PC-PA dissociation in patients with COPD and subjects without airflow limitation (AL) and to identify its risk factors., Methods: A sample of 319 COPD patients and 399 subjects without AL was consecutively obtained from a population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, lung function testing, blood analysis and low-dose computed tomography (CT) scan with evaluation of lung density and airway wall thickness. A distance walked in 6 min > 70% predicted was considered an indicator of normal PC, while a Yale Physical Activity Survey summary index score <51 was used to identify with sedentary lifestyle., Results: 166 COPD patients (52.0%) reported a sedentary lifestyle with evidence of preserved PC, while this phenomenon was present in 188 (47.1%) subjects without AL. In the COPD group, symptoms of chronic bronchitis, depression and elevated hematocrit and blood eosinophil count were identified as independent risk factors for PC-PA dissociation. In turn, in the subjects without AL, the risk factors for PC-PA dissociation were low fat-free mass, obesity and anxiety, as well as reduced levels of HDL-cholesterol and the absence of osteoporosis., Conclusions: Almost half of COPD patients and subjects without airflow limitation with preserved PC maintain a sedentary lifestyle, with different risk factors for sedentarism between both groups., Competing Interests: Declaration of competing interest Francisco García-Río has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Pfizer and Rovi, and research grants from Chiesi, Esteve, Gebro Pharma, GlaxoSmithKline, Menarini and TEVA. Marc Miravitlles has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Gebro Pharma, Kamada, GlaxoSmithKline, Grifols, Menarini, Mereo Biopharma, Novartis, pH Pharma, Palobiofarma SL, Rovi, TEVA, Spin Therapeutics, Verona Pharma and Zambon, and research grants from Grifols. Joan B. Soriano has no conflict of interest. Borja G Cosio has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Sanofi, TEVA, and research grants from Menarini, AstraZeneca and Boehringer-Ingelheim. Juan José Soler-Cataluña has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GlaxoSmithKline, Menarini, Novartis and Teva, and consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, GlaxoSmithKline, Ferrer and Novartis. Ciro Casanova has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, and research grants from GlaxoSmithKline, Menarini and AstraZeneca. Pilar de Lucas has no conflict of interest. Inmaculada Alfageme has no conflict of interest. José Miguel Rodríguez González-Moro has no conflict of interest. María Guadalupe Sánchez Herrero is a GSK employee within the Medical Department. Julio Ancochea has received speaker or consulting fees from Actelion, Air Liquide, Almirall, AstraZeneca, Boehringer Ingelheim, Carburos Médica, Chiesi, Faes Farma, Ferrer, GlaxoSmithKline, InterMune, Linde Healthcare, Menarini, MSD, Mundipharma, Novartis, Pfizer, Roche, Rovi, Sandoz, Takeda y Teva, (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Prehospital Respiratory Early Warning Scores to estimate the requirement for advanced respiratory support is needed. To develop a prehospital Respiratory Early Warning Score to estimate the requirement for advanced respiratory support., Methods: Multicentre, prospective, emergency medical services (EMS)-delivered, longitudinal cohort derivationvalidation study carried out in 59 ambulances and five hospitals across five Spanish provinces. Adults with acute diseases evaluated, supported and discharged to the Emergency Department with high priority were eligible. The primary outcome was the need for invasive or non-invasive respiratory support (NIRS or IRS) in the prehospital scope at the first contact with the patient. The measures included the following: epidemiological endpoints, prehospital vital signs (respiratory rate, pulse oximetry saturation, fraction of inspired oxygen, systolic and diastolic mean blood pressure, heart rate, tympanic temperature and consciousness level by the GCS)., Results: Between 26 Oct 2018 and 26 Oct 2021, we enrolled 5793 cases. For NIRS prediction, the final model of the logistic regression included respiratory rate and pulse oximetry saturation/fraction of inspired oxygen ratio. For the IRS case, the motor response from the Glasgow Coma Scale was also included. The REWS showed an AUC of 0.938 (95% CI: 0.918-0.958), a calibration-in-large of 0.026 and a higher net benefit as compared with the other scores., Conclusions: Our results showed that REWS is a remarkably aid for the decision-making process in the management of advanced respiratory support in prehospital care. Including this score in the prehospital scenario could improve patients' care and optimise the resources' management., (© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background: Population distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications., Methods: A sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) >0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness., Results: In never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p<0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO., Conclusion: Reduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage., Trial Registration Number: NCT03028207., Competing Interests: Competing interests: FG-R has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Pfizer and Rovi, and research grants from Chiesi, Esteve, Gebro Pharma, GlaxoSmithKline, Menarini and TEVA. MM has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Gebro Pharma, Kamada, GlaxoSmithKline, Grifols, Menarini, Mereo Biopharma, Novartis, pH Pharma, Palobiofarma SL, Rovi, TEVA, Spin Therapeutics, Verona Pharma and Zambon, and research grants from Grifols. JBS has no conflict of interest. BGC has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Sanofi, TEVA and research grants from Menarini, AstraZeneca and Boehringer-Ingelheim. JJS-C has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GlaxoSmithKline, Menarini, Novartis and Teva, and and consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, GlaxoSmithKline, Ferrer and Novartis. CC has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, and research grants from GlaxoSmithKline, Menarini and AstraZeneca. PdL has no conflict of interest. IA has no conflict of interest. JMRG-M has no conflict of interest. MGSH is a GSK employee within the Medical Department. JA has received speaker or consulting fees from Actelion, Air Liquide, Almirall, AstraZeneca, Boehringer Ingelheim, Carburos Médica, Chiesi, Faes Farma, Ferrer, GlaxoSmithKline, InterMune, Linde Healthcare, Menarini, MSD, Mundipharma, Novartis, Pfizer, Roche, Rovi, Sandoz, Takeda y Teva., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: BRC reports being a speaker at meetings and advisory boards for GlaxoSmithKline; a consultant of advisory boards and a speaker for AstraZeneca; a consultant and speaker at meetings for Menarini; a consultant and advisory board member for Sanofi Aventis; and a consultant for Axios. BRC also reports consulting fees from GlaxoSmithKline, AstraZeneca, and Sanofi Aventis; payment or honoraria from GlaxoSmithKline, AstraZeneca, Menarini, Chiesi, and Regeneron; support for meeting attendance or travel from GlaxoSmithKline and Sanofi Aventis; and participation on data safety monitoring boards or advisory boards for AZ Therapeutics, Sanofi Aventis, and Vertex. JBS and JMM declare no competing interests.

Electronic cigarette (e-cigarette) use emits potentially hazardous compounds and deteriorates indoor air quality. Home is a place where e-cigarettes may frequently be used amid its increasing prohibition in public places. This study assessed the real-life scenario of bystanders' exposure to secondhand e-cigarette aerosol (SHA) at home. A one-week observational study was conducted within the TackSHS project in four countries (Greece, Italy, Spain, and the United Kingdom) in 2019 including: 1) homes of e-cigarette users living together with a non-user/non-smoker; and 2) control homes with no smokers nor e-cigarette users. Indoor airborne nicotine, PM 2.5 , and PM 1.0 concentrations were measured as environmental markers of SHA. Biomarkers, including nicotine and its metabolites, tobacco-specific nitrosamines, propanediol, glycerol, and metals were measured in participants' saliva and urine samples. E-cigarette use characteristics, such as e-cigarette refill liquid's nicotine concentration, e-cigarette type, place of e-cigarette use at home, and frequency of ventilation, were also collected. A total of 29 e-cigarette users' homes and 21 control homes were included. The results showed that the seven-day concentrations of airborne nicotine were quantifiable in 21 (72.4 %) out of 29 e-cigarette users' homes; overall, they were quite low (geometric mean: 0.01 μg/m 3 ; 95 % CI: 0.01-0.02 μg/m 3 ) and were all below the limit of quantification in control homes. Seven-day concentrations of PM 2.5 and PM 1.0 in e-cigarette and control homes were similar. Airborne nicotine and PM concentrations did not differ according to different e-cigarette use characteristics. Non-users residing with e-cigarette users had low but significantly higher levels of cotinine, 3'-OH-cotinine and 1,2-propanediol in saliva, and cobalt in urine than non-users living in control homes. In conclusion, e-cigarette use at home created bystanders' exposure to SHA regardless of the e-cigarette use characteristics. Further studies are warranted to assess the implications of SHA exposure for smoke-free policy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

This study aimed to report mortality, risk factors, and burden of diseases in Spain. The Global Burden of Disease, Injuries, and Risk Factors 2019 estimates the burden due to 369 diseases, injuries, and impairments and 87 risk factors and risk factor combinations. Here, we detail the updated Spain 1990-2019 burden of disease estimates and project certain metrics up to 2030. In 2019, leading causes of death were ischaemic heart disease, stroke, chronic obstructive pulmonary disease, Alzheimer's disease, and lung cancer. Main causes of disability adjusted life years (DALYs) were ischaemic heart disease, diabetes, lung cancer, low back pain, and stroke. Leading DALYs risk factors included smoking, high body mass index, and high fasting plasma glucose. Spain scored 74/100 among all health-related Sustainable Development Goals (SDGs) indicators, ranking 20 of 195 countries and territories. We forecasted that by 2030, Spain would outpace Japan, the United States, and the European Union. Behavioural risk factors, such as smoking and poor diet, and environmental factors added a significant burden to the Spanish population's health in 2019. Monitoring these trends, particularly in light of COVID-19, is essential to prioritise interventions that will reduce the future burden of disease to meet population health and SDG commitments., (© 2022. The Author(s).)

Background: Few large epidemiological studies have analysed the prevalence of respiratory symptoms and their determinants in the general adult population. We investigated the prevalence and determinants of respiratory symptoms and compared their prevalence with that of two previous studies conducted in 1999 and 2009., Method: EPISCAN II was a multicentre, cross-sectional, population-based epidemiological study in individuals older than 40 years., Results: A total of 9092 individuals were included. Up to 47.5% reported at least one respiratory symptom, being more frequent in women than in men (49.4% versus 45.5%, p=0.0002) and with wheezing being the most frequent (33.7%) followed by dyspnoea (26.8%). The presence of any symptom was associated with female sex, higher body mass index (BMI), lower forced expiratory volume in 1 s (FEV 1 % pred), reduced physical activity, a higher Charlson index and the presence of anxiety and depression. Smoking was also significantly associated with having at least one respiratory symptom in a dose-response fashion (OR: 1.415, 1.916, 2.192 and 2.987 for 0-10, 10-20, 20-30 and >30 pack-years, respectively, all p<0.0001). The prevalence of symptoms remained quite similar over the last 20 years (wheezing 40%, 36% and 33.7% and dyspnoea 10.4%, 9.9% and 13.1% in 1999, 2009 and 2019, respectively)., Conclusions: Approximately half of the adult Spanish population have respiratory symptoms and this prevalence has remained quite stable over the last 20 years. Smoking remains the main factor associated with respiratory symptoms, but female sex, comorbidities, high BMI and low FEV 1 and low physical activity are also significantly associated with respiratory symptoms., Competing Interests: Conflict of interest: M. Miravitlles has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Cipla, CSL Behring, Laboratorios Esteve, Gebro Pharma, Kamada, GlaxoSmithKline, Grifols, Menarini, Mereo Biopharma, Novartis, pH Pharma, Palobiofarma SL, Rovi, TEVA, Spin Therapeutics, Verona Pharma and Zambon, and research grants from Grifols. J.J. Soler-Cataluña has received speaker fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GlaxoSmithKline, Menarini, Novartis and Teva, and consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, GlaxoSmithKline, Ferrer and Novartis. F. García-Río has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Pfizer and Rovi, and research grants from Chiesi, Esteve, Gebro Pharma, GlaxoSmithKline, Menarini and TEVA. J. Ancochea has received speaker or consulting fees from Actelion, Air Liquide, Almirall, AstraZeneca, Boehringer Ingelheim, Carburos Médica, Chiesi, Faes Farma, Ferrer, GlaxoSmithKline, InterMune, Linde Healthcare, Menarini, MSD, Mundipharma, Novartis, Pfizer, Roche, Rovi, Sandoz, Takeda and Teva. C. Casanova has received speaker or consulting fees from AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini and Novartis, and research grants from GlaxoSmithKline, Menarini and AstraZeneca. J.M.R. González-Moro has recieved research grants from GSK and Grifols, outside the submitted work; and speaker or consulting fees from AstraZeneca, Chiesi, GlaxoSmithKline, Meiji, and Orion pharma, outside the submitted work. G. Sanchez is a GlaxoSmithKline employee within the Medical Dept. B.G. Cosio has received speaker or consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Menarini, Novartis, Sanofi and TEVA, and research grants from Menarini, AstraZeneca and Boehringer Ingelheim. J.B. Soriano, P. de Lucas and I. Alfageme have no conflicts of interest., (Copyright ©The authors 2022.)

Early kinetics of SARS-CoV-2 viral load (VL) in plasma determined by quantitative reverse-transcription polymerase chain reaction (RT-PCR) was evaluated as a predictor of poor clinical outcome in a prospective study and assessed in a retrospective validation cohort. Prospective observational single-center study including consecutive adult patients hospitalized with COVID-19 between November 2020 and January 2021. Serial plasma samples were obtained until discharge. Quantitative RT-PCR was performed to assess SARS-CoV-2 VL. The main outcomes were in-hospital mortality, admission to the Intensive Care Unit (ICU), and their combination (Poor Outcome). Relevant viremia (RV), established in the prospective study, was assessed in a retrospective cohort including hospitalized COVID-19 patients from April 2021 to May 2022, in which plasma samples were collected according to clinical criteria. Prospective cohort: 57 patients were included. RV was defined as at least a twofold increase in VL within ≤2 days or a VL > 300 copies/ml, in the first week. Patients with RV (N = 14; 24.6%) were more likely to die than those without RV (35.7% vs. 0%), needed ICU admission (57% vs. 0%) or had Poor Outcome (71.4% vs. 0%), (p < 0.001 for the three variables). Retrospective cohort: 326 patients were included, 18.7% presented RV. Patients with RV compared with patients without RV had higher rates of ICU-admission (odds ratio [OR]: 5.6 [95% confidence interval [CI]: 2.1-15.1); p = 0.001), mortality (OR: 13.5 [95% CI: 6.3-28.7]; p < 0.0001) and Poor Outcome (OR: 11.2 [95% CI: 5.8-22]; p < 0.0001). Relevant SARS-CoV-2 viremia in the first week of hospitalization was associated with higher in-hospital mortality, ICU admission, and Poor Outcome. Findings observed in the prospective cohort were confirmed in a larger validation cohort., (© 2022 The Authors. Journal of Medical Virology published by Wiley Periodicals LLC.)

Importance: Some individuals experience persistent symptoms after initial symptomatic SARS-CoV-2 infection (often referred to as Long COVID)., Objective: To estimate the proportion of males and females with COVID-19, younger or older than 20 years of age, who had Long COVID symptoms in 2020 and 2021 and their Long COVID symptom duration., Design, Setting, and Participants: Bayesian meta-regression and pooling of 54 studies and 2 medical record databases with data for 1.2 million individuals (from 22 countries) who had symptomatic SARS-CoV-2 infection. Of the 54 studies, 44 were published and 10 were collaborating cohorts (conducted in Austria, the Faroe Islands, Germany, Iran, Italy, the Netherlands, Russia, Sweden, Switzerland, and the US). The participant data were derived from the 44 published studies (10 501 hospitalized individuals and 42 891 nonhospitalized individuals), the 10 collaborating cohort studies (10 526 and 1906), and the 2 US electronic medical record databases (250 928 and 846 046). Data collection spanned March 2020 to January 2022., Exposures: Symptomatic SARS-CoV-2 infection., Main Outcomes and Measures: Proportion of individuals with at least 1 of the 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after SARS-CoV-2 infection in 2020 and 2021, estimated separately for hospitalized and nonhospitalized individuals aged 20 years or older by sex and for both sexes of nonhospitalized individuals younger than 20 years of age., Results: A total of 1.2 million individuals who had symptomatic SARS-CoV-2 infection were included (mean age, 4-66 years; males, 26%-88%). In the modeled estimates, 6.2% (95% uncertainty interval [UI], 2.4%-13.3%) of individuals who had symptomatic SARS-CoV-2 infection experienced at least 1 of the 3 Long COVID symptom clusters in 2020 and 2021, including 3.2% (95% UI, 0.6%-10.0%) for persistent fatigue with bodily pain or mood swings, 3.7% (95% UI, 0.9%-9.6%) for ongoing respiratory problems, and 2.2% (95% UI, 0.3%-7.6%) for cognitive problems after adjusting for health status before COVID-19, comprising an estimated 51.0% (95% UI, 16.9%-92.4%), 60.4% (95% UI, 18.9%-89.1%), and 35.4% (95% UI, 9.4%-75.1%), respectively, of Long COVID cases. The Long COVID symptom clusters were more common in women aged 20 years or older (10.6% [95% UI, 4.3%-22.2%]) 3 months after symptomatic SARS-CoV-2 infection than in men aged 20 years or older (5.4% [95% UI, 2.2%-11.7%]). Both sexes younger than 20 years of age were estimated to be affected in 2.8% (95% UI, 0.9%-7.0%) of symptomatic SARS-CoV-2 infections. The estimated mean Long COVID symptom cluster duration was 9.0 months (95% UI, 7.0-12.0 months) among hospitalized individuals and 4.0 months (95% UI, 3.6-4.6 months) among nonhospitalized individuals. Among individuals with Long COVID symptoms 3 months after symptomatic SARS-CoV-2 infection, an estimated 15.1% (95% UI, 10.3%-21.1%) continued to experience symptoms at 12 months., Conclusions and Relevance: This study presents modeled estimates of the proportion of individuals with at least 1 of 3 self-reported Long COVID symptom clusters (persistent fatigue with bodily pain or mood swings; cognitive problems; or ongoing respiratory problems) 3 months after symptomatic SARS-CoV-2 infection.

People with COVID-19 might have sustained postinfection sequelae. Known by a variety of names, including long COVID or long-haul COVID, and listed in the ICD-10 classification as post-COVID-19 condition since September, 2020, this occurrence is variable in its expression and its impact. The absence of a globally standardised and agreed-upon definition hampers progress in characterisation of its epidemiology and the development of candidate treatments. In a WHO-led Delphi process, we engaged with an international panel of 265 patients, clinicians, researchers, and WHO staff to develop a consensus definition for this condition. 14 domains and 45 items were evaluated in two rounds of the Delphi process to create a final consensus definition for adults: post-COVID-19 condition occurs in individuals with a history of probable or confirmed SARS-CoV-2 infection, usually 3 months from the onset, with symptoms that last for at least 2 months and cannot be explained by an alternative diagnosis. Common symptoms include, but are not limited to, fatigue, shortness of breath, and cognitive dysfunction, and generally have an impact on everyday functioning. Symptoms might be new onset following initial recovery from an acute COVID-19 episode or persist from the initial illness. Symptoms might also fluctuate or relapse over time. A separate definition might be applicable for children. Although the consensus definition is likely to change as knowledge increases, this common framework provides a foundation for ongoing and future studies of epidemiology, risk factors, clinical characteristics, and therapy., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2022 World Health Organization. Published by Elsevier Ltd.All rights reserved. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyze the causes of death by diseases of the respiratory system in Spain in 2020, with special interest in COVID-19; also its trends and determinants, and compare them with 2019., Material and Methods: Retrospective cohort study. The coding of all those causes of death by diseases of the respiratory system were regrouped. A descriptive analysis of all deaths and by gender, age, and the 17 Autonomous Communities (CC.AA.) was performed. Also, odds ratios of death in crude and multivariate analysis by logistic regression were estimated., Results: In Spain in 2020, 60,358 deaths were attributed to "COVID-19 virus identified" and another 14,481 to "COVID-19 virus not identified (suspicious)". Regrouping the specific causes of death, in 2020 the diseases of the respiratory system caused a total of 139,880 deaths, which corresponds to 28.3% of all deaths in Spain. Compared to 2019, an increase of 68.5% was observed. By gender, deaths by diseases of the respiratory system were higher in men (32.0%) than in women (24.6%), although in specific causes the percentage was higher in women with suspected COVID-19, asthma, respiratory insufficiency and other diseases of the respiratory system. Finally, the variables associated with death from COVID-19 in the multivariate analysis were being male, increasing age (maximum at 80 years), completed studies up to secondary level, employed, and single or widowed marital status, although with a marked variation by CC.AA., Conclusions: In Spain in 2020, COVID-19 produced a large increase (68.5%) in deaths by diseases of the respiratory system compared to the previous year., (© 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: Guidelines aim to standardize and optimize diagnosis and management. We evaluated the quality of evidence supporting recommendations from different international adult guidelines on bronchiectasis, and classified with the GRADE system., Methods: Quality of eligible clinical practice guidelines was assessed for six domains using the AGREE II tool, with ≥ 80% rating as excellent., Results: Seven guidelines (283 recommendations) were analyzed, and four of them were considered "recommended for use" (three reported after 2017 as excellent). Overall, 144 (50.9%) recommendations were based on low-quality evidence, representing 81.5% in diagnosis and 36.2% in therapy. In contrast, 5/92 (5.4%) and 40/191 (20.9%) recommendations regarding diagnostic and treatment (respectively) were based on high-quality evidence. Quality agreement ratings were significantly (p< 0.05) higher for guidelines delivered after 2015, progressing from 27.7% to 58.3%, qualifying as excellent. Highest scores were documented in the domains of "scope and purpose" followed by "clarifying of presentation" and "editorial independence"., Conclusion: Updated guidelines reported after 2017 improved quality, although well-designed randomized clinical trials remain an unmet need. AGREE II quality assessment identified four guidelines qualified as recommended for use. Improvements are required in stakeholder involvement and applicability., (Copyright © 2022 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Blood eosinophils are considered a biomarker for the treatment of chronic obstructive pulmonary disease (COPD). Population-based studies are needed to better understand the determinants of the blood eosinophil count (BEC) in individuals with and without COPD., Methods: EPISCAN II is a multicentre, cross-sectional, population-based epidemiological study aimed at investigating the prevalence and determinants of COPD in Spain. Study subjects were randomly selected from the general population, and COPD was defined by a post-bronchodilator FEV 1 /FVC < 0.7. For the pre-specified outcomes related to BEC, the first 35 COPD and 35 non-COPD subjects were consecutively recruited in 12 of the participating centres with the objective of analysing 400 individuals in each group. Baseline BEC and its association with demographic, clinical and functional variables were analysed., Results: A total of 326 COPD and 399 non-COPD subjects were included in the analysis. The mean age (standard deviation [SD]) was 63.2 years (11.0), 46.3% were male, and 27.6% were active smokers. BEC was significantly higher in individuals with COPD [192 cells/μL (SD: 125) vs. 160 cells/μL (SD: 114); p = 0.0003]. In a stepwise multivariate model, being male, active smoker and having a previous diagnosis of asthma were independently associated with having a higher BEC., Conclusions: This population-based study estimated the distribution of eosinophils in the healthy adult population and concluded that COPD patients have a significantly higher BEC. Male sex, active smoking and concomitant asthma were significantly associated with a higher BEC., (© 2022. The Author(s).)

Introduction: Obstructive sleep apnea (OSA) increases the risk of type 2 diabetes, and hyperinsulinemia. Pregnancy increases the risk of OSA; however, the relationship between OSA and gestational diabetes mellitus (GDM) is unclear. We aimed (1) to evaluate OSA prevalence in GDM patients; (2) to assess the association between OSA and GDM; and (3) to determine the relationships between sleep parameters with insulin resistance (IR)., Methods: A total of 177 consecutive women (89 with GDM, 88 controls) in the third trimester of pregnancy underwent a hospital polysomnography. OSA was defined when the apnea-hypopnea index (AHI) was ≥5h -1 ., Results: Patients with GDM had higher pregestational body mass index (BMI) and neck circumference than controls, but no differences in snoring or OSA-symptoms, or AHI (3.2±6.0 vs. 1.9±2.7h -1 , p=.069). OSA prevalence was not significantly different in both groups. We did not identify OSA as a GDM risk factor in the crude analysis 1.65 (95%CI: 0.73-3.77; p=.232). Multiple regression showed that total sleep time (TST), TST spent with oxygen saturation<90% (T90), and maximum duration of respiratory events as independent factors related with homeostasis model assessment of IR, while T90 was the only independent determinant of quantitative insulin sensitivity check index., Conclusion: OSA prevalence during the third trimester of pregnancy was not significantly different in patients with GDM than without GDM, and no associations between OSA and GDM determinants were found. We identified T90 and obstructive respiratory events length positive-related to IR, while TST showed an inverse relationship with IR in pregnant women., (Copyright © 2021. Publicado por Elsevier España, S.L.U.)

Background: European countries differ considerably in the scope and the extent of their policies to protect people from the harms of secondhand smoke exposure. Public opinion may have a substantial influence on several stages of policy development, implementation, and compliance. For this reason, we aimed to evaluate the population level of support for smoke-free policies and its correlates., Methods: We used data from the TackSHS Survey (2017-2018), a cross-sectional study with representative samples of the general population aged ≥15 years from 12 European countries. We described the proportion of non-smokers' and smokers' support for the implementation of smoke-free legislation in 14 indoor and outdoor settings and the country-level characteristics associated with it., Results: In the total sample (n = 11,902), support for smoke-free legislation were the lowest for restaurants/bar patios (non-smokers = 53.0%; smokers = 29.2%) and the highest for workplaces (non-smokers = 78.5%; smokers = 66.5%). In the country-level analysis, the highest support among non-smokers was for workplaces in Bulgaria (93.1%) and the lowest for restaurants/bars patios in Greece (39.4%). Among smokers, the corresponding estimates were for children's playgrounds in Latvia (88.9%) and for cars in Portugal (21%). For most settings, support for smoke-free legislation was directly related with the countries' prevalence of secondhand smoke presence and reported smoking in each setting., Discussion: Our results show that the majority of European adults (including a large proportion of smokers) are supportive of implementing smoke-free legislation in indoor settings and extending it to selected outdoor settings. Such expressive support can be seen as an opportunity to advance legislation and protect the European population from secondhand smoke exposure., (Copyright © 2021. Published by Elsevier Inc.)

It remains unknown whether the type of aerosol generating device is affecting efficacy and safety among non-cystic fibrosis bronchiectasis (NCFB) adults. The proposal of this network meta-analysis (NMA) is to evaluate effectiveness and safety of inhaled antibiotics administered via dry powder inhaler (DPI) and via nebulizers (SVN) among adult patients with NCFB. Inclusion criteria were randomized-controlled trials, adults (≥18 years) with NCFB, and inhaled antibiotics administered via DPI as intervention. Search strategy was performed in PubMed, Web of Science, and Cochrane Library from 2000 to 2019. Sixteen trials (2870 patients) were included. Three trials (all ciprofloxacin) used DPIs and thirteen used SVN (three ciprofloxacin). Both DPI and SVN devices achieved similar safety outcomes (adverse events, antibiotic discontinuation, severe adverse events, and bronchospasm). Administration of ciprofloxacin via DPI significantly improved time to first exacerbation (87 days, 95% CI 34.3-139.7) and quality of life (MD -7.52; 95% CI -13.06 to -1.98) when compared with via SVN. No other significant differences were documented in clinical efficacy (at least one exacerbation, FEV 1 % predicted) and microbiologic response (bacterial eradication, emergence of new potential pathogens, and emergence of antimicrobial resistance) when comparing devices. Our NMA documented that time to first exacerbation and quality of life, were more favorable for DPIs. Decisions on the choice of devices should incorporate these findings plus other criteria, such as simplicity, costs or maintenance requirements.

Although asthma is very common affecting 5-10% of the population, the diagnosis of asthma in adults remains a challenge in the real world that results in both over- and under-diagnosis. A task force (TF) was set up by the European Respiratory Society to systematically review the literature on the diagnostic accuracy of tests used to diagnose asthma in adult patients and provide recommendation for clinical practice.The TF defined eight PICO (Population, Index, Comparator, and Outcome) questions that were assessed using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) approach, The TF utilised the outcomes to develop an evidenced-based diagnostic algorithm, with recommendations for a pragmatic guideline for everyday practice that was directed by real-life patient experiences.The TF support the initial use of spirometry followed, and if airway obstruction is present, by bronchodilator reversibility testing. If initial spirometry fails to show obstruction, further tests should be performed in the following order: FeNO, PEF variability or in secondary care, bronchial challenge. We present the thresholds for each test that are compatible with a diagnosis of asthma in the presence of current symptoms.The TF reinforce the priority to undertake spirometry and recognise the value of measuring blood eosinophils and serum IgE to phenotype the patient. Measuring gas trapping by body plethysmography in patients with preserved FEV 1 /FVC ratio deserves further attention. The TF draw attention on the difficulty of making a correct diagnosis in patients already receiving inhaled corticosteroids, the comorbidities that may obscure the diagnosis, the importance of phenotyping, and the necessity to consider the patient experience in the diagnostic process., Competing Interests: Conflict of interest: Dr. LOUIS reports grants and personal fees from GSK, grants and personal fees from AZ, grants and personal fees from Chiesi, grants and personal fees from Novartis, personal fees from Sanofi, outside the submitted work; . Conflict of interest: Dr. Satia reports grants and personal fees from GSK, personal fees from AstraZeneca, grants and personal fees from Merck, grants from ERS Respire 3 Marie Curie Fellowship, grants from E.J. Moran Campbell Early Career Award, outside the submitted work; . Conflict of interest: Dr. OJANGUREN reports grants and personal fees from ASTRAZENECA, personal fees and non-financial support from BOEHRINGUER-INGELHEIM, personal fees and non-financial support from CHIESI, grants, personal fees and non-financial support from NOVARTIS, personal fees from MSD, personal fees from PURETECH, grants and personal fees from SANOFI, personal fees from BIAL, personal fees from TEVA, grants and personal fees from GSK, outside the submitted work. Conflict of interest: Dr. SCHLEICH reports grants and personal fees from GSK, grants and personal fees from AstraZeneca, personal fees from Chiesi, outside the submitted work. Conflict of interest: Dr. Bonini has nothing to disclose. Conflict of interest: Ms Tonia reports acting as ERS Methodologist . Conflict of interest: Dr. Rigau reports and declares he worked as ERS methodologist until February 2020. Conflict of interest: Dr. ten Brinke reports institutional fees from Research Advisory Boards: GSK, Sanofi, TEVA, AstraZeneca, Boehringer Ingelheim , institutional fees from Lectures AstraZeneca, GSK ,TEVA, SanofiGenzyme, grants from AstraZeneca, GSK ,TEVA, outside the submitted work. Conflict of interest: Dr. Buhl reports personal fees from AstraZeneca, Berlin-Chemie, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Novartis, Sanofi, Roche and Teva, and grants to Mainz University Hospital from Boehringer Ingelheim, GlaxoSmithKline, Novartis and Roche, all outside the submitted work. Conflict of interest: Dr. Loukides has nothing to disclose. Conflict of interest: Dr. Kocks reports grants, personal fees and non-financial support from AstraZeneca, grants, personal fees and non-financial support from Boehringer Ingelheim, grants and personal fees from Chiesi Pharmaceuticals, grants and personal fees from GSK, grants and personal fees from Novartis, personal fees from MSD, grants and personal fees from TEVA, personal fees from COVIS, outside the submitted work; and Janwillem Kocks holds 72.5% of shares in the General Practitioners Research Institute. Conflict of interest: Dr. Boulet reports grants from Amgen, AstraZeneca, GlaxoSmithKline, Merck, Novartis, Sanofi-Regeneron, grants from AstraZeneca, GlaxoSmithKline. Merck, personal fees from Astra Zeneca, Novartis, GlaxoSmithKline, Merck, Sanofi-Regeneron, personal fees from AstraZeneca, Covis, GlaxoSmithKline, Novartis, Merck, Sanofi, grants and non-financial support from AstraZeneca, Covis, GlaxoSmithKline, Merck, Novartis, non-financial support from Chair of Global Initiative for Asthma (GINA) Board of Directors, President of the Global Asthma Organisation (Interasma) Conflict of interest: Dr. Bourdin reports grants, personal fees, non-financial support and other from GSK, grants, personal fees, non-financial support and other from Astra Zeneca, grants, personal fees, non-financial support and other from Boeringher Ingelheim, personal fees, non-financial support and other from Novartis, personal fees, non-financial support and other from Chiesi Farma, non-financial support and other from Teva, personal fees, non-financial support and other from Sanofi Regeneron, grants, personal fees, non-financial support and other from Actelion / Jansen, other from United Therapeutics, other from Pulsar, personal fees, non-financial support and other from Roche, from null, outside the submitted work. Conflict of interest: Courtney Coleman is an employee of European Lung Foundation. Conflict of interest: Dr. Needham has nothing to disclose. Conflict of interest: Dr. Thomas reports personal fees from GSK, personal fees from Boehringer Ingelheim , personal fees from Chiesi, outside the submitted work; . Conflict of interest: Dr. Idzko has nothing to disclose. Conflict of interest: Dr. Papi reports grants, personal fees, non-financial support and other from GlaxoSmithKline, grants, personal fees and non-financial support from AstraZeneca, grants, personal fees, non-financial support and other from Boehringer Ingelheim, grants, personal fees, non-financial support and other from Chiesi Farmaceutici, grants, personal fees, non-financial support and other from TEVA, personal fees, non-financial support and other from Mundipharma, personal fees, non-financial support and other from Zambon, personal fees, non-financial support and other from Novartis, grants, personal fees and non-financial support from Menarini, personal fees, non-financial support and other from Sanofi/Regeneron, personal fees from Roche, grants from Fondazione Maugeri, grants from Fondazione Chiesi, personal fees from Edmondpharma, outside the submitted work. Conflict of interest: Dr. Porsbjerg reports grants and personal fees from Astra Zeneca, grants and personal fees from GSK, grants and personal fees from Novartis, grants and personal fees from TEVA, grants and personal fees from Sanofi, grants and personal fees from Chiesi, grants from Pharmaxis, outside the submitted work; . Conflict of interest: Dr. Schuermans reports non-financial support from Free University of Brussels, outside the submitted work; . Conflict of interest: Dr. B. Soriano Conflict of interest: Dr. Usmani reports grants and personal fees from astra zeneca, grants and personal fees from boehringer ingelheim, grants and personal fees from chiesi, grants and personal fees from glaxosmithkline, personal fees from napp, personal fees from mundipharma, personal fees from sandoz, personal fees from takeda, grants from edmond pharma, personal fees from cipla, personal fees from covis, personal fees from novartis, personal fees from mereo biopharma, personal fees from orion, personal fees from menarini, personal fees from ucb, personal fees from trudell medical, personal fees from deva, personal fees from kamada, personal fees from covis, outside the submitted work., (Copyright ©The authors 2022. For reproduction rights and permissions contact permissions@ersnet.org.)

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm 3 . Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Infection by SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) can be associated with serious and life-threatening conditions, including acute respiratory distress syndrome (ARDS). Severity and mortality have been related to a cytokine storm, an imbalance of oxidative stress, and a pro-thrombotic state.We conducted an observational retrospective cohort study from a community-based large population of hospitalized COVID-19 PCR + patients admitted from March 01, 2020, to January 24, 2021, with integrated primary to tertiary care information in Castilla la Mancha, Spain. We explored the potential benefits of the antioxidant, anti-inflammatory and anti-thrombotic drug N-acetylcysteine (NAC) administered orally in high doses (600 mg every 8 h), added to standard of care in COVID-19 patients by using the free text information contained in their electronic health records (EHRs).Out of 19,208 patients with a diagnosis of COVID-19 hospitalized, we studied 2071 (10.8%) users of oral NAC at high doses. COVID-19 patients treated with NAC were older, predominantly male, and with more comorbidities such as hypertension, dyslipidemia, diabetes, and COPD when compared with those not on NAC (all p  < 0.05). Despite greater baseline risk, use of NAC in COVID-19 patients was associated with significantly lower mortality (OR 0.56; 95%CI 0.47-0.67), a finding that remained significant in a multivariate analysis adjusting by baseline characteristics and concomitant use of corticosteroids. There were no significant differences with the use of NAC on the mean duration of hospitalization, admission to the intensive care unit or use of invasive mechanical ventilation. The observed association signaling to better relevant outcomes in COVID-19 patients treated with NAC at high doses should be further explored in other settings and populations and in randomized controlled trials.

Introduction: Using data from the TackSHS survey, we aim to provide updated estimates on the prevalence and determinants of overweight and obesity in Europe., Methods: A face-to-face survey was conducted in 2017-2018 in 12 European countries (Bulgaria, England, France, Germany, Greece, Ireland, Italy, Latvia, Poland, Portugal, Romania, and Spain). Overall, 10,810 participants, representative in each country of the general adult population, provided information on self-reported height and weight., Results: Almost half of participants (48.1%; 95% confidence interval, CI: 47.2-49.1) reported to be overweight or obese (54.1% in men and 42.5% in women) and 12.6% (95% CI: 12.0-13.2) obese (11.3% in men and 13.8% in women). Obesity prevalence was lowest in Italy (7.5%) and France (8.8%) and highest in Greece (19.7%) and Romania (21.1%). Multilevel logistic random-effects analyses showed that prevalence of obesity was related with higher age and lower level of education and socioeconomic status. As compared to northern European countries, Western and Southern European ones showed a significantly lower obesity prevalence. When compared to a companion study conducted in 2010, Eastern and Northern European countries showed an increased trend in obesity prevalence. Conversely, countries with the lowest obesity prevalence (less than 10%), such as Italy and France, showed a decreased trend., Conclusions: Despite a large heterogeneity across countries, overweight and obesity prevalence estimates in Europe are alarming, with most of the countries reporting obesity prevalence approaching 20% or more, particularly in Eastern and Northern Europe. Since 2010, obesity prevalence increased in most of these countries., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition that requires a comprehensive and coordinated response across sectors and disciplines., Aims: In the absence of a multisectoral framework to tackle this condition, we developed one using the sustainable development goals (SDGs) as the basis for converging thinking about the design and delivery of public health responses., Methods: A multidisciplinary group identified the SDG targets and indicators for inclusion in the new framework through a two-stage process. Firstly, a core team of three researchers independently reviewed the 169 targets and 231 indicators of the SDGs to select a shortlist. Over two Delphi rounds, a multidisciplinary group of 12 experts selected which of the shortlisted targets and indicators to include. Respondents also provided written feedback on their selection. Targets and indicators with 75% or greater agreement were included in the final framework., Results: The final framework comprises 16 targets-representing 9% of all targets and 62% (16/26) of the shortlisted targets-and seven indicators, accounting for 50% (7/14) of the shortlisted indicators and 3% of all indicators. The selected targets and indicators cover a broad range of factors, from health, food and nutrition to education, the economy, and the built environment., Conclusions: Addressing the challenge of NAFLD will require a re-envisioning of the liver health landscape, with greater focus on joined-up systems thinking and action. This new framework can help guide this process, including by outlining the stakeholders with whom the liver health community needs to engage., (© 2021 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd.)

Introduction: unCoVer-Unravelling data for rapid evidence-based response to COVID-19-is a Horizon 2020-funded network of 29 partners from 18 countries capable of collecting and using real-world data (RWD) derived from the response and provision of care to patients with COVID-19 by health systems across Europe and elsewhere. unCoVer aims to exploit the full potential of this information to rapidly address clinical and epidemiological research questions arising from the evolving pandemic., Methods and Analysis: From the onset of the COVID-19 pandemic, partners are gathering RWD from electronic health records currently including information from over 22 000 hospitalised patients with COVID-19, and national surveillance and screening data, and registries with over 1 900 000 COVID-19 cases across Europe, with continuous updates. These heterogeneous datasets will be described, harmonised and integrated into a multi-user data repository operated through Opal-DataSHIELD, an interoperable open-source server application. Federated data analyses, without sharing or disclosing any individual-level data, will be performed with the objective to reveal patients' baseline characteristics, biomarkers, determinants of COVID-19 prognosis, safety and effectiveness of treatments, and potential strategies against COVID-19, as well as epidemiological patterns. These analyses will complement evidence from efficacy/safety clinical trials, where vulnerable, more complex/heterogeneous populations and those most at risk of severe COVID-19 are often excluded., Ethics and Dissemination: After strict ethical considerations, databases will be available through a federated data analysis platform that allows processing of available COVID-19 RWD without disclosing identification information to analysts and limiting output to data aggregates. Dissemination of unCoVer's activities will be related to the access and use of dissimilar RWD, as well as the results generated by the pooled analyses. Dissemination will include training and educational activities, scientific publications and conference communications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Obstructive sleep apnea (OSA) is prevalent in pregnancy and it is associated with adverse pregnancy-related outcomes such as gestational diabetes, pre-eclampsia, and low birth weight. Maternal systemic inflammation is proposed to be one of the main intermediate mechanisms. However, the effects of OSA on systemic inflammation are unknown in normal pregnancy. Methods: Women in the 3rd trimester underwent hospital polysomnography to evaluate whether OSA increases systemic inflammation in normal pregnancy and its potential association with adverse fetal outcomes. OSA was defined as an apnea-hypopnea index (AHI) of ≥ 5 h -1 . Plasma cytokines levels (TNF-α, IL-1β, IL-6, IL-8, and IL-10) were determined by multiple immunoassays. Results: We included 11 patients with OSA and 22 women with AHI < 5 h -1 , who were homogeneous in age, and body mass index (BMI). Women with OSA had significant higher levels of TNF-α, IL-1β, IL-8, and IL-10. We found significant correlations between AHI during REM and TNF-α ( r = 0.40), IL-1β ( r = 0.36), IL-6 ( r = 0.52), IL-8 ( r = 0.43), between obstructive apnea index and TNF-α ( r = 0.46) and between AHI and IL-1β ( r = 0.43). We also found that CT90% was related to IL-8 ( r = 0.37). There were no significant differences in neonatal characteristics; however, we found inverse correlations between TNF-α and IL-8 with birth weight (both r = -0.48), while IL-8 showed a significant inverse relationship with neonatal gestational age ( r = -0.48). Conclusions: OSA in our normal pregnancy population was associated with higher systemic inflammation, which was related to obstructive events, especially during REM sleep. Moreover, systemic inflammation was inversely correlated with neonatal birth weight and age., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alonso-Fernández, Ribot Quetglas, Herranz Mochales, Álvarez Ruiz De Larrinaga, Sánchez Barón, Rodríguez Rodríguez, Gil Gómez, Pía Martínez, Cubero Marín, Barceló Nicolau, Cerdà Moncadas, Codina Marcet, De La Peña Bravo, Barceló Bennasar, Iglesias Coma, Morell-Garcia, Peña Zarza, Giménez Carrero, Durán Cantolla, Marín Trigo, Piñas Cebrian, Soriano and García-Río.)

Background: In-hospital mortality in patients with coronavirus disease 2019 (COVID-19) is high. Simple prognostic indices are needed to identify patients at high-risk of COVID-19 health outcomes. We aimed to determine the usefulness of the CONtrolling NUTritional status (CONUT) index as a potential prognostic indicator of mortality in COVID-19 patients upon hospital admission., Methods: Our study design is of a retrospective observational study in a large cohort of COVID-19 patients. In addition to descriptive statistics, a Kaplan-Meier mortality analysis and a Cox regression were performed, as well as receiver operating curve (ROC)., Results: From February 5, 2020 to January 21, 2021, there was a total of 2969 admissions for COVID-19 at our hospital, corresponding to 2844 patients. Overall, baseline (within 4 days of admission) CONUT index could be scored for 1627 (57.2%) patients. Patients' age was 67.3 ± 16.5 years and 44.9% were women. The CONUT severity distribution was: 194 (11.9%) normal (0-1); 769 (47.2%) light (2-4); 585 (35.9%) moderate (5-8); and 79 (4.9%) severe (9-12). Mortality of 30 days after admission was 3.1% in patients with normal risk CONUT, 9.0% light, 22.7% moderate, and 40.5% in those with severe CONUT (P < 0.05). An increased risk of death associated with a greater baseline CONUT stage was sustained in a multivariable Cox regression model (P < 0.05). An increasing baseline CONUT stage was associated with a longer duration of admission, a greater requirement for the use of non-invasive and invasive mechanical ventilation, and other clinical outcomes (all P < 0.05). The ROC of CONUT for mortality had an area under the curve (AUC) and 95% confidence interval of 0.711 (0.676-0746)., Conclusion: The CONUT index upon admission is potentially a reliable and independent prognostic indicator of mortality and length of hospitalization in COVID-19 patients., (Copyright © 2022 The Chinese Medical Association, produced by Wolters Kluwer, Inc. under the CC-BY-NC-ND license.)

Objective: Due to partial or poorly enforced restrictions secondhand tobacco smoke (SHS) is still present in outdoor hospitality venues in many European countries. This study aimed to assess SHS concentrations in outdoor hospitality venues across Europe and identify contextual exposure determinants., Methods: Cross-sectional study. We measured airborne nicotine and evidence of tobacco use in terraces of bars, cafeterias, and pubs from 11 European countries in 2017-2018. Sites were selected considering area-level socioeconomic indicators and half were visited during nighttime. We noted the smell of smoke, presence of smokers, cigarette butts, ashtrays, and number of physical covers. Contextual determinants included national smoke-free policies for the hospitality sector, the Tobacco Control Scale score (2016), and the national smoking prevalence (2017-2018). We computed medians and interquartile ranges (IQR) of nicotine concentrations and used multivariate analyses to characterize the exposure determinants., Results: Nicotine was present in 93.6% of the 220 sites explored. Overall concentrations were 0.85 (IQR:0.30-3.74) μg/m 3 and increased during nighttime (1.45 IQR:0.65-4.79 μg/m 3 ), in enclosed venues (2.97 IQR:0.80-5.80 μg/m 3 ), in venues with more than two smokers (2.79 IQR:1.03-6.30 μg/m 3 ), in venues in countries with total indoor smoking bans (1.20 IQR:0.47-4.85 μg/m 3 ), and in venues in countries with higher smoking prevalence (1.32 IQR:0.49-5.34 μg/m 3 ). In multivariate analyses, nicotine concentrations were also positively associated with the observed number of cigarette butts. In venues with more than two smokers, SHS levels did not significantly vary with the venues' degree of enclosure., Conclusions: Our results suggest that current restrictions in outdoor hospitality venues across Europe have a limited protective effect and justify the adoption of total smoking bans in outdoor areas of hospitality venues., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Further evidence is needed on the effects that short- and long-term exposure to secondhand smoke (SHS) have on the respiratory health of patients with lung disease. Within the TackSHS project we aimed to assess the acute respiratory effects in lung function that result from short-term SHS exposure among patients with asthma and chronic obstructive pulmonary disease (COPD)., Methods: The study design was an intervention trial with measurements before/after exposure to SHS in legal outdoor smoking areas. We studied patients with asthma or COPD from Czechia, Ireland, and Spain. Forced spirometry, peak flow and carbon monoxide (CO) measurements were performed pre- and 24 h post- exposure., Results: Overall, 60 patients were studied, 30 with asthma, and 30 with COPD; 35 (58.3%) were female. There were no significant differences observed in exhaled CO between pre- and 24 h post-exposure neither in women ( p  = 0.210), nor in men ( p  = 0.169).A statistically significant decrease in forced vital capacity (FVC) was seen, overall, in asthma participants ( p  = 0.02) and in forced expiratory volume in the first second (FEV 1 ), ( p  = 0.02), FVC ( p  = 0.04) and peak expiratory flow rate (PEFR) ( p  = 0.04) in female asthmatic participants. The observed decreases in respiratory measurements in COPD were not significant. There were no reported increases in symptoms, respiratory medication, or use of health services 24 h after the exposure., Conclusion: We conclude that acute, short-term SHS exposure had a statistically significant effect on spirometry in female asthma patients but did not significantly modify spirometric indices 24 h later in COPD patients.

Background: Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations., Methods: We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154., Results: Twelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70-5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81-18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28-1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82-0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV 1 , mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35-3.27) at the end of therapy, with a number needed to treat of 6., Conclusions: IA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes., (Copyright © 2021 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Background: Secondhand smoke (SHS) exposure at home and fetal SHS exposure during pregnancy are a major cause of disease among children. The aim of this study is quantifying the burden of disease due to SHS exposure in children and in pregnancy in 2006-2017 for the 28 European Union (EU) countries., Methods: Exposure to SHS was estimated using a multiple imputation procedure based on the Eurobarometer surveys, and SHS exposure burden was estimated with the comparative risk assessment method using meta-analytical relative risks. Data on deaths and disability-adjusted life years (DALYs) were collected from National statistics and from the Global Burden of Disease Study., Results: Exposure to SHS and its attributable burden stalled in 2006-2017; in pregnant women, SHS exposure was 19.8% in 2006, 19.1% in 2010, and 21.0% in 2017; in children it was 10.1% in 2006, 9.6% in 2010, and 12.1% in 2017. In 2017, 35,633 DALYs among children were attributable to SHS exposure in the EU, mainly due to low birth weight., Conclusions: Comprehensive smoking bans up to 2010 contributed to reduce SHS exposure and its burden in children immediately after their implementation; however, SHS exposure still occurs, and in 2017, its burden in children was still relevant., Impact: Exposure to secondhand smoke at home and in pregnancy is a major cause of disease among children. Smoking legislation produced the adoption of voluntary smoking bans in homes; however, secondhand smoke exposure at home still occurs and its burden is substantial. In 2017, the number of deaths and disability-adjusted life years in children attributable to exposure to secondhand smoke in the European Union countries were, respectively, 335 and 35,633. Low birth weight caused by secondhand smoke exposure in pregnancy showed the largest burden. Eastern European Union countries showed the highest burden., (© 2020. International Pediatric Research Foundation, Inc.)

Objectives: The aim of this study was to systematically describe the findings of lung ultrasound (US) in patients with coronavirus 2019 (COVID-19) pneumonia and to analyze its prognostic value., Methods: Lung US examinations were performed in 63 patients with COVID-19 pneumonia admitted to a university hospital. Lung involvement was evaluated on a 4-point scale with a 12-area pulmonary division, obtaining a lung score (LS). Ultrasound findings and clinical characteristics were recorded., Results: All patients showed US involvement in at least 1 area (mean ± SD, 8 ± 3.5). The total LS was 15.3 ± 8.1, without differences between left and right lungs. Most affected regions were the lower region (95.2%) and the posterior region (73.8%). The total LS showed a strong correlation (r = -0.765) with the oxygen pressure-to-fraction of inspired oxygen ratio; by lung region, those with a higher correlation were the LS of the anterior region (r = -0.823) and the LS of the upper region (r = -0.731). In total, 22.2% of patients required noninvasive respiratory support (NIRS). A multivariate analysis showed that the anterior region LS, adjusted for age and sex, was significant (odds ratio, 2.159; 95% confidence interval, 1.309-3.561) for the risk of requiring NIRS. An anterior region LS of 4 or higher and a total LS of 19 or higher had similar characteristics to predict the need for NIRS., Conclusions: Ultrasound involvement in COVID-19 pneumonia is bilateral and heterogeneous. Most affected regions are the posterior and the lower regions. The anterior region has prognostic value because its involvement strongly correlates with the risk of requiring NIRS, and an anterior region LS of 4 or higher has high sensitivity and specificity for predicting the need for NIRS., (© 2020 American Institute of Ultrasound in Medicine.)