Clinical characteristics and outcomes among hospitalised COVID-19 patients across epidemic waves in Spain: An unCoVer analysis.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic had a significant impact in population health worldwide, and particularly in people with pre-existing chronic diseases. Early risk identification and stratification is essential to reduce the impact of future outbreaks of pandemic potential. This study aimed to comprehensively examine factors associated with COVID-19 mortality across the pandemic waves in Spain. METHODS: A retrospective study analyzed the characteristics of 13,974 patients admitted to Spanish hospitals due to SARS-CoV-2 infection from 2020-01-28 to 2022-12-31. The demographic and clinical features of patients during hospitalization on each pandemic waves were analyzed. MAIN FINDINGS: The findings highlight the heterogeneity of patient characteristics, comorbidities and outcomes, across the waves. The high prevalence of cardiometabolic diseases (53.9%) among COVID-19 patients emphasizes the importance of controlling these risk factors to prevent severe COVID-19 outcomes. CONCLUSIONS: In summary, the study associate hospital mortality with factors such as advanced age and comorbidities. The decline in mortality after the 4th wave indicates potential influences like vaccination, viral adaptation, or improved treatments. Notably, dementia and cancer metastases emerge as critical factors linked to higher mortality, highlighting the importance of addressing these conditions in COVID-19 management and preparing for future challenges.

Alpha-1 Antitrypsin Gene Variants in Patients without Severe Deficiency Diagnosed with Pulmonary Emphysema on Chest CT.

Introduction: Although pulmonary involvement due to alpha-1 antitrypsin (AAT) deficiency has been widely described, most studies focus on the genotypes causing severe deficiency (<60 mg/dL). Objective: The aim of this study was to analyze the prevalence of the different AAT gene variants that do not cause severe deficiency in patients with pulmonary emphysema diagnosed by thoracic computed tomography (CT). Furthermore, we assessed the risk associated with a non-severe decrease in AAT values in the pathogenesis of emphysema. Methods: Case-control study design that included patients who had a CT scan available of the entire thorax. In total, 176 patients with emphysema (cases) and 100 control subjects without emphysema were analyzed. Results: The prevalence of variants was higher among cases (25.6%; 45/176) than controls (22%; 22/100), although the difference was not statistically significant (P=0.504) when analyzed globally. In the control group, all the variants detected were MS. Excluding this variant, statistically significant differences were observed in the remaining variants (MZ, SS and SZ). Only 18% of the controls (all MS) presented values below our limit of normality, and all had values very close to the reference value (90 mg/dL). In contrast, 76% of patients with the other variants presented pathological levels. In a logistic regression model, both smoking and a non-severe reduction in AAT (60 to 90 mg/dL) increased the probability of emphysema. Conclusion: Our study confirms an association between certain variants in the alpha-1 antitrypsin gene that do not cause severe deficiency and the presence of pulmonary emphysema. This association with variants that are associated with reductions in serum AAT values is statistically significant and independent of smoking habit.

Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population.

INTRODUCTION: The aim of this study was to analyze the impact of occupational exposure on chronic obstructive pulmonary disease (COPD) and respiratory symptoms in the general Spanish population. METHODS: This was a study nested in the Spanish EPISCAN II cross-sectional epidemiological study that included participants who had completed a structured questionnaire on their occupational history, a questionnaire on respiratory symptoms, and forced spirometry. The data were analyzed using Chi-square and Student's t tests and adjusted models of multiple linear regression and logistic regression. RESULTS: We studied 7502 subjects, 51.1% women, with a mean age of 60±11 years. Overall, 53.2% reported some respiratory symptoms, 7.9% had respiratory symptoms during their work activity, 54.2% were or had been smokers, and 11.3% (851 subjects) met COPD criteria on spirometry. A total of 3056 subjects (40.7%) reported exposure to vapors, gases, dust or fumes (VGDF); occupational exposure to VGDF was independently associated with the presence of COPD (OR 1.22, 95% CI: 1.03-1.44), respiratory symptoms (OR 1.45, 95%: CI 1.30-1.61), and respiratory symptoms at work (OR 4.69, 95% CI: 3.82-5.77), with a population attributable fraction for COPD of 8.2%. CONCLUSIONS: Occupational exposure is associated with a higher risk of COPD and respiratory symptoms in the Spanish population. These results highlight the need to follow strict prevention measures to protect the respiratory health of workers.

Tobacco Patterns and Risk of Chronic Obstructive Pulmonary Disease: Results From a Cross-Sectional Study.

INTRODUCTION: There is still uncertainty about which aspects of cigarette smoking influence the risk of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to estimate the COPD risk as related to duration of use, intensity of use, lifetime tobacco consumption, age of smoking initiation and years of abstinence. METHODS: We conducted an analytical cross-sectional study based on data from the EPISCAN-II study (n=9092). All participants underwent a face-to-face interview and post-bronchodilator spirometry was performed. COPD was defined as post-bronchodilator FEV1/FVC<70%. Parametric and nonparametric logistic regression models with generalized additive models were used. RESULTS: 8819 persons were included; 858 with COPD and 7961 without COPD. The COPD risk increased with smoking duration up to ≥50 years [OR 3.5 (95% CI: 2.3-5.4)], with smoking intensity up to ≥39cig/day [OR 10.1 (95% CI: 5.3-18.4)] and with lifetime tobacco consumption up to >29 pack-years [OR 3.8 (95% CI: 3.1-4.8)]. The COPD risk for those who started smoking at 22 or later was 0.9 (95% CI: 0.6-1.4). The risk of COPD decreased with increasing years of cessation. In comparison with both never smokers and current smokers, the lowest risk of COPD was found after 15-25 years of abstinence. CONCLUSION: COPD risk increases with duration, intensity, and lifetime tobacco consumption and decreases importantly with years of abstinence. Age at smoking initiation shows no effect. After 15-25 years of cessation, COPD risk could be equal to that of a never smoker. This work suggests that the time it takes to develop COPD in a smoker is about 30 years.

Impact of the COVID-19 pandemic in mortality due to respiratory diseases: A comparative analysis of 2021 and 2020 vs 2019 in Spain.

INTRODUCTION: We previously reported an increase in respiratory mortality in 2020 in Spain after COVID-19. It is unclear if this rise is sustained in the longer-term. We aimed to determine whether respiratory mortality in 2021 in Spain returned to pre-pandemic levels. MATERIAL AND METHODS: In an observational, large study using official National Institute of Statistics data, we explored deaths due to respiratory diseases, that is, all causes of death by the standard WHO list of diseases of the respiratory system plus COVID-19, tuberculosis and lung cancer. Using the latest available official data of Spain, we analyzed changes in the mortality pattern in Spain from January 2019 to December 2021. We endorsed STROBE guidance for observational research. RESULTS: There were 98,714 deaths due to respiratory diseases in 2021 in Spain, corresponding to 21.9% of all deaths, becoming second in the ranking of causes of death. Respiratory diseases mortality in Spain has not returned to pre-pandemic levels in 2021, still with an increase of 30.3% (95% CI 30.2-30.4) compared to rates in 2019. All respiratory-specific causes of death decreased in 2021, except for lung cancer, that increased in women and decreased in men compared to 2019 (both p<0.05). In a multivariate analysis some established risk factors for respiratory diseases mortality were confirmed, such as male gender and older age; further, an association with reduced mortality in rural Spain was observed, still with a large geographical variability. CONCLUSIONS: The COVID-19 pandemic has had a lasting impact on deaths due to respiratory diseases and certain specific causes of death in 2021, and it has disproportionately affected certain regions.

Particle Exposure Hazards of Visiting Outdoor Smoking Areas for Patients with Asthma or COPD Even in EU Countries with Comprehensive Smokefree Laws.

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/m3 (in 4 premises) to ≤10 µg/m3 (in 3 premises, which had only a single wall in the structure). At 39 venues, the mean PM 2.5 levels were ≥25 µg/m3. 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.

Prevalence of reduced lung diffusing capacity and CT scan findings in smokers without airflow limitation: a population-based study.

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.

Electronic Cigarette Use in 12 European Countries: Results From the TackSHS Survey.

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. RESULTS: 2.4% (95% confidence interval [CI], 2.2-2.7%) of the subjects (2.5% among men and 2.4% among women; 0.4% among never, 4.4% among current- and 6.5% among 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 (ie, 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, at workplaces (34.9%) and bars and restaurants (41.5%). Multivariable logistic regression analysis showed that electronic cigarette use was lower among older individuals (P for trend <0.001) and higher among individuals with high level of education (P for trend = 0.040). Participants from countries with higher tobacco cigarette prices more frequently reported electronic cigarette use (odds ratio 3.62; 95% CI, 1.80-7.30). CONCLUSION: Considering the whole adult population of these 12 European countries, more than 8.3 million people use electronic cigarettes. The majority of users also smoked conventional cigarettes, used electronic cigarettes with nicotine, and consumed electronic cigarettes in smoke-free indoor areas.

Trends of COPD in Spain: Changes Between Cross Sectional Surveys 1997, 2007 and 2017.

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 FEV1/FVC (forced expiratory volume in 1s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV1/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.

Exposure to secondhand aerosol from electronic cigarettes at homes: A real-life study in four European countries.

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 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/m3; 95 % CI: 0.01-0.02 µg/m3) and were all below the limit of quantification in control homes. Seven-day concentrations of 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.

A GBD 2019 study of health and Sustainable Development Goal gains and forecasts to 2030 in Spain.

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.

Respiratory symptoms and their determinants in the general Spanish population: changes over 20 years.

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 (FEV1 % 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 FEV1 and low physical activity are also significantly associated with respiratory symptoms.

Prevalence of Chronic Obstructive Pulmonary Disease in an Urban Area. Changes in COPD Ten Years on.

Purpose: 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.

Determinants of blood eosinophil levels in the general population and patients with COPD: a population-based, epidemiological study.

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 FEV1/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.

Safety and Efficacy of Devices Delivering Inhaled Antibiotics among Adults with Non-Cystic Fibrosis Bronchiectasis: A Systematic Review and a Network Meta-Analysis.

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, FEV1% 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.

Critical appraisal of international adult bronchiectasis guidelines using the AGREE II tool.

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.

Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19.

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.

Spanish COPD Guidelines (GesEPOC) 2021: Updated Pharmacological treatment of stable COPD. / Actualización 2021 de la Guía Española de la EPOC (GesEPOC). Tratamiento farmacológico de la EPOC estable.

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.