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El concepto de salud es mucho más difícil de definir que el concepto de enfermedad. Este trabajo resume la trayectoria histórica del concepto de salud desde las civilizaciones azteca y egipcia, hasta la definición de la Organización Mundial de la Salud en 1948: “Un estado de completo bienestar físico, mental y social, y no solamente la ausencia de afecciones o enfermedades”. Más recientemente, la definición de salud de la OMS se ha modificado y complementado con la cuarta dimensión: la salud espiritual. Implica un sentido de plenitud y satisfacción con la propia vida, sistema de valores, autoconfianza y autoestima, autoconciencia y presencia, paz y tranquilidad con equilibrio emocional dinámico, tanto interno como hacia el entorno, moralidad y veracidad, desinterés, emociones positivas, compasión y voluntad de ayudar y apoyar a los demás, responsabilidad y contribución al bien común y manejo exitoso de los problemas y demandas de la vida cotidiana, así como del estrés social. En definitiva, ‘salud’ es un concepto evolutivo y cambiante, que además es muy personal. Depende de la edad del individuo, sus condiciones y su entorno, y también del estado inicial de cada persona, entre otras variables. El transhumanismo y sus novedades aplicadas a la salud pueden revolucionar todos estos conceptos.

Elena García Castillo,1– 4 Tamara Alonso Pérez,1– 4 Adrián Peláez,1– 3 Patricia Pérez González,1,2,4 Joan B Soriano,1– 3 Julio Ancochea1– 4 1Pulmonary Department, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria La Princesa, Madrid, Spain; 2School of Medicine, Universidad Autónoma de Madrid (UAM), Madrid, Spain; 3Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain; 4Cátedra UAM-GSK “Respira Vida”, Madrid, SpainCorrespondence: Elena García Castillo, Pulmonology Department, Hospital Universitario La Princesa, C/ Diego de León, 62, Madrid, CP: 28006, Spain, Tel +34 91 520 22 77, Fax +91-520-26-72, Email elenagcs@gmail.comPurpose: The prevalence of Chronic obstructive pulmonary disease (COPD) in Spain has been evaluated in the last ten years by EPISCAN in 2007 and EPISCAN II in 2017. This study describes changes in the prevalence of COPD in an urban region of Spain in the last 10 years, its risk factors and underdiagnosis.Patients and Methods: Participants from the Autonomous Community of Madrid (Spain) were selected from both studies up to the age of 80 years. A descriptive analysis of their sociodemographic and clinical characteristics, as well as by gender, was conducted. COPD was defined by a post-bronchodilator ratio < 0.70.Results: The prevalence of COPD in the Autonomous Community of Madrid increased non-significantly from 11.0% (95% CI: 8.9– 13.5%) to 12.1% (95% CI: 9.6– 15.1, p=0.612). However, the prevalence by gender showed an increase in women (5.6% to 14.7%, p< 0.001) and a decrease in men (17.6% to 9.8%, p=0.08). Underdiagnosis was reduced from 81.0% to 67.9% (p=0.006), although with greater underdiagnosis in women (86.4% in EPISCAN and 100% in EPISCAN II). Smoking was higher in men than in women in EPISCAN (31.2% vs 23.0%, p< 0.01) but with no differences by gender in EPISCAN II (25.5% men vs 26.0% women, p=0.146). Age, smoking, low BMI, and a sedentary lifestyle were consistently associated with COPD.Conclusion: In 10 years in Madrid, there have been no changes in the global prevalence of COPD, but there have been important changes in women, with an increase in its prevalence, smoking habit and underdiagnosis.Keywords: COPD, prevalence, Madrid, spirometry

Background: Limited data on electronic cigarette prevalence, patterns and settings of use are available from several European countries. Methods: Within the TackSHS project, 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, 11,876 participants, representative of the population aged ≥15 years in each country, provided information on electronic cigarette. Findings: 2·4% (95% C.I. 2·2-2·7) of the subjects (2·5% men and 2·4% women; 0·4% never, 4·4% current- and 6·5% ex-smokers) reported current use of electronic cigarette, ranging from 0.6% in Spain to 7·2% in England. Of the 272 electronic cigarette users, 52·6% were dual users (i.e., users of both electronic and conventional cigarettes) and 58·8% used liquids with nicotine. In all, 65·1% reported using electronic cigarette in at least one indoor setting where smoking is forbidden, in particular in workplaces (34·9%) as well as bars and restaurants (41·5%). Multivariable logistic regression analysis showed that electronic cigarette use was lower among older individuals (p for trend

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.

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.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.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.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.Analizar las causas de muerte por enfermedades del aparato respiratorio en España durante el año 2020, con especial interés en COVID-19; también sus tendencias y determinantes, y compararlas con el año 2019.Estudio de cohortes retrospectivo. Se reagrupó la codificación de todas aquellas causas de muerte por enfermedades del aparato respiratorio. Se realizó un análisis descriptivo de todas las defunciones por sexo, edad en las 17 Comunidades Autónomas (CC. AA.). Además, se estimaron lasEn España en el año 2020 se atribuyeron 60.358 muertes a «COVID-19 virus identificado» y otras 14.481 a «COVID-19 virus no identificado (sospechoso)». Reagrupando las causas específicas de muerte, en el año 2020 las enfermedades del aparato respiratorio provocaron un total de 139.880 muertes, lo que corresponde al 28,3% de todas las muertes en España. En comparación con el año 2019, se observó un aumento del 68,5%. Por género, las defunciones por enfermedades del aparato respiratorio fueron mayores en los varones (32,0%) que en las mujeres (24,6%), aunque en causas específicas el porcentaje fue mayor en mujeres en COVID-19 sospechosa, asma, insuficiencia respiratoria y otras enfermedades del aparato respiratorio. Finalmente, las variables asociadas a la muerte por COVID-19 en el análisis multivariante fueron el género masculino, el aumento de la edad (máximo a los 80 años), estudios completados hasta secundaria y el estado civil soltero o viudo, aunque con una marcada variación por CC. AA.En España en el año 2020 la COVID-19 produjo un gran incremento (68,5%) de muertes por enfermedades del aparato respiratorio en comparación con el año anterior.

Graphical abstract, Introduction Impairment in pulmonary function tests and radiological abnormalities are a major concern in COVID-19 survivors. Our aim is to evaluate functional respiratory parameters, changes in chest CT, and correlation with peripheral blood biomarkers involved in lung fibrosis at two and six months after SARS-CoV-2 pneumonia. Methods COVID-FIBROTIC (clinicaltrials.gov NCT04409275) is a multicenter prospective observational cohort study aimed to evaluate discharged patients. Pulmonary function tests, circulating serum biomarkers, chest radiography and chest CT were performed at outpatient visits. Results In total, 313, aged 61.12 ± 12.26 years, out of 481 included patients were available. The proportion of patients with DLCO

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.

The Spanish COPD Guidelines (GesEPOC) were first published in 2012, and since then have undergone a series of updates incorporating new evidence on the diagnosis and treatment of COPD. GesEPOC was drawn up in partnership with scientific societies involved in the treatment of COPD and the Spanish Patients' Forum. Their recommendations are based on an evaluation of the evidence using GRADE methodology, and a narrative description of the evidence in areas in which GRADE cannot be applied. In this article, we summarize the recommendations on the pharmacological treatment of stable COPD based on 9 PICO questions. COPD treatment is a 4-step process: 1) diagnosis, 2) determination of the risk level, 3) initial and subsequent inhaled therapy, and 4) identification and management of treatable traits. For the selection of inhaled therapy, high-risk patients are divided into 3 phenotypes: non-exacerbator, eosinophilic exacerbator, and non-eosinophilic exacerbator. Some treatable traits are general and should be investigated in all patients, such as smoking or inhalation technique, while others affect severe patients in particular, such as chronic hypoxemia and chronic bronchial infection. COPD treatment is based on long-acting bronchodilators with single agents or in combination, depending on the patient's risk level. Eosinophilic exacerbators must receive inhaled corticosteroids, while non-eosinophilic exacerbators require a more detailed evaluation to choose the best therapeutic option. The new GesEPOC also includes recommendations on the withdrawal of inhaled corticosteroids and on indications for alpha-1 antitrypsin treatment. GesEPOC offers a more individualized approach to COPD treatment tailored according to the clinical characteristics of patients and their level of complexity.

Objective To measure, exposure to PM2.5 particles in outdoor smoking areas and changes in breathing rates in patients with asthma or chronic obstructive pulmonary disease (COPD). Setting Sixty venues in Czechia, Ireland and Spain, in an open, non-randomised, clinical trial. Participants We studied 60 patients-30 asthma patients (Female 63.3%), with a mean age (+/-standard deviation [SD]) of 47.4 (19.0 SD), and 30 COPD patients (Female 51.6%), mean age 63.5 (10.1 SD), smokers, non-smokers or ex-smokers, recruited through medical clinics. Intervention Patients wore a PM2.5 particle monitor (AirSpeck), and a breath monitor (RESpeck) for 24 hours 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. Results PM2.5 levels in the 60 venues were highly variable, in 1 premises levels of PM2.5 were sustained for at least 15 minutes at ≥ 2,000 µg/m3, in 4 premises, ≥ 500 (range 1,933-539) µg/m3, in 8 premises, ≥ 200(range 480-203) µg/m3, in 9 premises, ≥ 100 (range 170-108) µg/m3, in 8 premises, ≥ 40 (range 80.5- 40.1) µg/m3, in 9 premises, ≥ 25 µg/m3, in 10 premises, ≥ 10 µg/m3, in 8 premises, and ≤10 µg/m3 in only 3 premises, with a single wall. The overall breathing rates/minute (Br)did not change significantly but in 28 patients mean Br increased from 21.47 (1.74 SD) to 22.8 (2.29 SD), change of -1.35 (-1.80-0.91 C.I), p value 0.00 and mean in 29 patients Br decreased from 21.95(2.43 SD) to 20.38(2.79 SD), 1.57(1.03-2.12 C.I), p value 0.00. Conclusion Exposure to high levels of PM2.5, and associated alteration of patients’ breathing rates occurred in outdoor smoking areas despite national comprehensive smokefree laws. These exposure levels support the abolition of such areas. (Words 295) ClinicalTrials.gov ID: NCT03074734 Ethics: Approval Number: Ref: 15-103

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, PM2.5, and PM1.0 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 concentrations of seven-day 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/m3; 95 % CI: 0.01-0.02 μg/m3) and were all below the limit of quantification in control homes. Concentrations of seven-day PM2.5 and PM1.0 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. This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No 681040. BA received the support of a fellowship from “La Caixa” Foundation (ID 100010434; Fellowship code: LCF/BQ/IN17/11620013). The Tobacco Control Research Group at ICO-IDIBELL (BA, EF, MF, OT, MB, YC) is partly supported by the Ministry of Universities and Research, Government of Catalonia (2017SGR319) and thanks CERCA Programme Generalitat de Catalunya for the institutional support to IDIBELL. The work of SG is partially supported by an Investigation Grant from the Foundation AIRC for the Research on Cancer (AIRC IG 2021, ID 25987). The Laboratory of Toxicology University of Granada (FG, PO) is funded by the Spanish National Research Agency and the European Regional Development Fund (FEDER; Project UNGR15-CE-3380). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

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, The work is supported by a grant from the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreement (No 101016216)

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.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).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.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.

An innovative approach for the primary and definitive treatment of obstructive sleep apnea (OSA) in adult patients is presented: Bilateral Internal Ramus Distraction of the mandible (BIRD), which is a slow, progressive and more stable procedure to advance the mandibular bone. This study investigated whether this surgical approach is useful to cure OSA.Study design was of an interventional (surgical) one-arm trial of OSA patients assessed before and 12 months after BIRD. All patients were evaluated by pre- and post-operative polysomnography and three-dimensional scans. The amount of skeletal advancement, percentage of upper airway volume increase and postoperative value of mandibular occlusal plane were the predictor variables. Changes in the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI), and percentage of time with saturation under 90% (TC90) were the main outcome variables.Thirty-two subjects with a mean ± SD age of 41.9 ± 13.3 years and 87.5% male were included, and they were followed-up 32 ± 14.2 months. AHI was 47.9 ± 23.1 per hour before surgery and the Epworth Sleepiness Scale (ESS) was 13.4 ± 4.4. Postoperative AHI was 4.8 ± 5.6 per hour 12 months after surgery (P0.001), with 81.2% of the patients considered cured (AHI5) and 18.8% suffering from a mild-to-moderate residual OSA. ESS decreased to 1.9 ± 1.8 at the end of the surgical treatment (P0.001). 3D changes revealed an upper airway volume increase of 188.4% ± 73.5% (P0.001).Lengthening the mandibular ramus by distraction osteogenesis to cure OSA appears to be more effective and safer when compared to other surgical protocols, especially in very severe cases with initial AHI50/h. Titration of the mandibular advancement weekly using respiratory polygraphy allows better healing control and customization of the skeletal advancement, enhancing the aesthetic result.

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.

Background: Two previous national epidemiological studies, IBERPOC in 1997 and EPISCAN in 2007, determined the COPD burden in Spain. Changes in demographics and exposure to risk factors demand the periodic update of COPD prevalence and its determinants. Methods: EPISCAN II aimed to estimate the prevalence of COPD in the general population aged 40 years or older in all 17 regions of Spain. A random population screening sample, requiring 600 participants per region performed a questionnaire plus post-bronchodilator (post-BD) spirometry. Results: A total of 12,825 subjects were initially contacted, and 9433 (73.6%) agreed to participate, of whom 9092 performed a valid spirometry. Baseline characteristics were: 52.6% women, mean ± SD age 60 ± 11 years, 19.8% current- and 34.2% former-smokers. The prevalence of COPD measured by post-BD fixed ratio FEV1/FVC < 0.7 was 11.8% (95% C.I. 11.2–12.5) with a high variability by region (2.4-fold). Prevalence was 14.6% (95% C.I. 13.5–15.7) in males and 9.4% (95% C.I. 8.6–10.2) in females; according to the lower limit of normal (LLN) was 6.0% (95% C.I. 5.5–6.5) overall, by sex being 7.1% (95% C.I. 6.4–8.0) in males and 4.9% (95% C.I. 4.3–5.6) in females. Underdiagnosis of COPD was 74.7%. Cases with COPD were a mean of seven years older, more frequently male, of lower attained education, and with more smokers than the non-COPD population (p < 0.001). However, the number of cigarettes and pack-years in non-COPD participants was substantial, as it was the reported use of e-cigarettes (7.0% vs. 5.5%) (p = 0.045). There were also significant social and clinical differences including living alone, previous respiratory diagnoses, more comorbidities measured with the Charlson index, greater BODE and COTE scores, cognitive impairment, and depression (all p < 0.001). Conclusions: COPD remains prevalent in Spain and frequently underdiagnosed.

SARS-CoV-2 is responsible for the development of coronavirus disease 2019 (COVID-19) in infected individuals, who can either exhibit mild symptoms or progress toward a life-threatening acute respiratory distress syndrome (ARDS). Exacerbated inflammation and dysregulated immune responses involving T and myeloid cells occur in COVID-19 patients with severe clinical progression. However, the differential contribution of specific subsets of dendritic cells and monocytes to ARDS is still poorly understood. In addition, the role of CD8+ T cells present in the lung of COVID-19 patients and relevant for viral control has not been characterized. Here, we have studied the frequencies and activation profiles of dendritic cells and monocytes present in the blood and lung of COVID-19 patients with different clinical severity in comparison with healthy individuals. Furthermore, these subpopulations and their association with antiviral effector CD8+ T cell subsets were also characterized in lung infiltrates from critical COVID-19 patients. Our results indicate that inflammatory transitional and nonclassical monocytes and CD1c+ conventional dendritic cells preferentially migrate from blood to lungs in patients with severe COVID-19. Thus, this study increases the knowledge of specific myeloid subsets involved in the pathogenesis of COVID-19 disease and could be useful for the design of therapeutic strategies for fighting SARS-CoV-2 infection.

Background Guidelines are critical for facilitating cost-effective COPD care. Development and implementation in low-and middle-income countries (LMICs) is challenging. To guide future strategy, an overview of current global COPD guidelines is required. Research Question We systematically reviewed national COPD guidelines, focusing on worldwide availability and identification of potential development, content, context, and quality gaps that may hamper effective implementation. Study Design and Methods Scoping review of national COPD management guidelines. We assessed: (1) global guideline coverage; (2) guideline information (authors, target audience, dissemination plans); (3) content (prevention, diagnosis, treatments); (4) ethical, legal, and socio-economic aspects; and (5) compliance with the eight Institute of Medicine (IOM) guideline standards. LMICs guidelines were compared with those from high-income countries (HICs). Results Of the 61 national COPD guidelines identified, 30 were from LMICs. Guidelines did not cover 1.93 billion (30.2%) people living in LMICs, whereas only 0.02 billion (1.9%) in HICs were without national guidelines. Compared with HICs, LMIC guidelines targeted fewer health-care professional groups and less often addressed case finding and co-morbidities. More than 90% of all guidelines included smoking cessation advice. Air pollution reduction strategies were less frequently mentioned in both LMICs (47%) and HICs (42%). LMIC guidelines fulfilled on average 3.37 (42%) of IOM standards, compared with 5.29 (66%) in HICs (P < .05). LMICs scored significantly lower compared with HICs regarding conflicts of interest management, updates, articulation of recommendations, and funding transparency (all, P < .05). Interpretation Several development, content, context, and quality gaps exist in COPD guidelines from LMICs that may hamper effective implementation. Overall, COPD guidelines in LMICs should be more widely available and should be transparently developed and updated. Guidelines may be further enhanced by better inclusion of local risk factors, case findings, and co-morbidity management, preferably tailored to available financial and staff resources.

Introduction: Down syndrome(DS), due to the anatomy of their upper airways, have a high prevalence of obstructive sleep apnea-hypopnea(OSA), this relation has been little studied. We aimed to determine the prevalence, clinical and polygraphic features ofOSA, and their changes after the start of treatment. Material and methods: Observational study design, consecutive DSpatients with suspectedOSA were included, being referred because of excessive daytime sleepiness and cognitive impairment. A complete sleep history assesment and either polygraphy(PG) or polysomnography(PSG) were conducted. Results: 47 patients were studied,60% male, age of35±10 years, BMI30±6 kg/m2, neck circumference41±4 cm. The Epworth score was13±5. PG was performed in92%, andPSG in the other8%, resulting 7% normal, 7% mild,41% moderate and45% severe OSA, with an AHI of38±31h-1, dominated by events in supine position(56±33), ODI33.6±28h-1, minimum oxygen saturation79±10%, shorter than90% of saturation22±24%. Treatment was started withCPAP in 25(53.2%), with a pressure of7±2 cmH2O, 72% of them had good adaptation and compliance, resulting with improvement in52% after6 months. Conclusions: OSA was diagnosed in93%;42% of them had severe OSA, with a high prevalence of respiratory events in supine position. CPAP treatment was started in more than half, with an objective improvement in52% of patients.

ImportanceWhile much of the attention on the COVID-19 pandemic was directed at the daily counts of cases and those with serious disease overwhelming health services, increasingly, reports have appeared of people who experience debilitating symptoms after the initial infection. This is popularly known as long COVID.ObjectiveTo estimate by country and territory of the number of patients affected by long COVID in 2020 and 2021, the severity of their symptoms and expected pattern of recoveryDesignWe jointly analyzed ten ongoing cohort studies in ten countries for the occurrence of three major symptom clusters of long COVID among representative COVID cases. The defining symptoms of the three clusters (fatigue, cognitive problems, and shortness of breath) are explicitly mentioned in the WHO clinical case definition. For incidence of long COVID, we adopted the minimum duration after infection of three months from the WHO case definition. We pooled data from the contributing studies, two large medical record databases in the United States, and findings from 44 published studies using a Bayesian meta-regression tool. We separately estimated occurrence and pattern of recovery in patients with milder acute infections and those hospitalized. We estimated the incidence and prevalence of long COVID globally and by country in 2020 and 2021 as well as the severity-weighted prevalence using disability weights from the Global Burden of Disease study.ResultsAnalyses are based on detailed information for 1906 community infections and 10526 hospitalized patients from the ten collaborating cohorts, three of which included children. We added published data on 37262 community infections and 9540 hospitalized patients as well as ICD-coded medical record data concerning 1.3 million infections. Globally, in 2020 and 2021, 144.7 million (95% uncertainty interval [UI] 54.8–312.9) people suffered from any of the three symptom clusters of long COVID. This corresponds to 3.69% (1.38–7.96) of all infections. The fatigue, respiratory, and cognitive clusters occurred in 51.0% (16.9–92.4), 60.4% (18.9–89.1), and 35.4% (9.4–75.1) of long COVID cases, respectively. Those with milder acute COVID-19 cases had a quicker estimated recovery (median duration 3.99 months [IQR 3.84–4.20]) than those admitted for the acute infection (median duration 8.84 months [IQR 8.10–9.78]). At twelve months, 15.1% (10.3–21.1) continued to experience long COVID symptoms.Conclusions and relevanceThe occurrence of debilitating ongoing symptoms of COVID-19 is common. Knowing how many people are affected, and for how long, is important to plan for rehabilitative services and support to return to social activities, places of learning, and the workplace when symptoms start to wane.Key PointsQuestionWhat are the extent and nature of the most common long COVID symptoms by country in 2020 and 2021?FindingsGlobally, 144.7 million people experienced one or more of three symptom clusters (fatigue; cognitive problems; and ongoing respiratory problems) of long COVID three months after infection, in 2020 and 2021. Most cases arose from milder infections. At 12 months after infection, 15.1% of these cases had not yet recovered.MeaningThe substantial number of people with long COVID are in need of rehabilitative care and support to transition back into the workplace or education when symptoms start to wane.

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.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.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.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.ClinicalTrials.gov, NCT04382053.