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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., (Copyright © 2023 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Progressive respiratory failure is the primary cause of death in the coronavirus disease 2019 (COVID-19) pandemic. It is the final outcome of the acute respiratory distress syndrome (ARDS), characterized by an initial exacerbated inflammatory response, metabolic derangement and ultimate tissue scarring. A positive balance of cellular energy may result crucial for the recovery of clinical COVID-19. Hence, we asked if two key pathways involved in cellular energy generation, AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling and fatty acid oxidation (FAO) could be beneficial. We tested the drugs metformin (AMPK activator) and baicalin (CPT1A activator) in different experimental models mimicking COVID-19 associated inflammation in lung and kidney. We also studied two different cohorts of COVID-19 patients that had been previously treated with metformin. These drugs ameliorated lung damage in an ARDS animal model, while activation of AMPK/ACC signaling increased mitochondrial function and decreased TGF-β-induced fibrosis, apoptosis and inflammation markers in lung epithelial cells. Similar results were observed with two indole derivatives, IND6 and IND8 with AMPK activating capacity. Consistently, a reduced time of hospitalization and need of intensive care was observed in COVID-19 patients previously exposed to metformin. Baicalin also mitigated the activation of pro-inflammatory bone marrow-derived macrophages (BMDMs) and reduced kidney fibrosis in two animal models of kidney injury, another key target of COVID-19. In human epithelial lung and kidney cells, both drugs improved mitochondrial function and prevented TGF-β-induced renal epithelial cell dedifferentiation. Our results support that favoring cellular energy production through enhanced FAO may prove useful in the prevention of COVID-19-induced lung and renal damage., Competing Interests: Declaration of competing interest The authors have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (Copyright © 2023 The Authors. Published by Elsevier España, S.L.U. All rights reserved.)

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.)

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.)

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.)

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).)

Lower respiratory tract infections, including chronic obstructive pulmonary disease exacerbations (COPD-E) and community acquired pneumonia (CAP), are one of the most frequent reasons for consultation in primary care and hospital emergency departments, and are the cause of a high prescription of antimicrobial agents. The selection of the most appropriate oral antibiotic treatment is based on different aspects and includes to first consider a bacterial aetiology and not a viral infection, to know the bacterial pathogen that most frequently cause these infections and the frequency of their local antimicrobial resistance. Treatment should also be prescribed quickly and antibiotics should be selected among those with a quicker mode of action, achieving the greatest effect in the shortest time and with the fewest adverse effects (toxicity, interactions, resistance and/or ecological impact). Whenever possible, antimicrobials should be rotated and diversified and switched to the oral route as soon as possible. With these premises, the oral treatment guidelines for mild or moderate COPD-E and CAP in Spain include as first options beta-lactam antibiotics (amoxicillin and amoxicillin-clavulanate and cefditoren), in certain situations associated with a macrolide, and relegating fluoroquinolones as an alternative, except in cases where the presence of Pseudomonas aeruginosa is suspected., (©The Author 2022. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

COPD (chronic obstructive pulmonary disease) includes patients with chronic bronchitis and / or emphysema who have in common the presence of a chronic and progressive airflow obstruction, with symptoms of dyspnea and whose natural history is modified by acute episodes of exacerbations. Exacerbation (EACOPD) is defined as an acute episode of clinical instability characterized by a sustained worsening of respiratory symptoms. It is necessary to distinguish a new EACOPD from a previous treatment failure or a relapse. EACOPD become more frequent and intense over time, deteriorating lung function and quality of life. The diagnosis of EACOPD consists of 3 essential steps: a) differential diagnosis; b) establish the severity, and c) identify its etiology. The main cause of exacerbations is infection, both bacterial and viral. Antibiotics are especially indicated in severe EACOPD and the presence of purulent sputum. Beta-lactams (amoxicillin-clavulanate and cefditoren) and fluoroquinolones (levofloxacin) are the most widely used antimicrobials. This review updates the problem of acute exacerbation with infectious origin from the perspective of etiology, antimicrobial resistance, microbiological studies, risk stratification, and antimicrobial management. The risk, prognosis and characteristics of COPD patients who develop COVID19 are analyzed., (©The Author 2021. Published by Sociedad Española de Quimioterapia. This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)(https://creativecommons.org/licenses/by-nc/4.0/).)

Stress is common in all work environments. Technostress and the difficulty of separating the family arena from the work environment are some of the new and emerging risks faced by companies, employees and society in general. Most of the available instruments for measuring stress in workers have been focused on education professionals and healthcare workers. Therefore, it is necessary to validate simple and friendly-use tools to detect stress levels in public workers. The aim of this study was to determine the internal consistency of an adapted version of the Student Stress Inventory-Stress Manifestations (SSI-SM) for public employees and to determine if high-stress levels are related to personal and work-related factors. A cross-sectional and descriptive study was conducted from October 2016 to February 2019 including 468 Spanish public workers based in Murcia. An adapted version of the SSI-SM was administered and data on personal and work-related factors were collected. Results showed that all of the factors had Cronbach's α over 0.700, and no items need to be deleted due to correlations with the factor exceeding 0.300. Factor 1, "Self-concept", has a Cronbach's α of 0.868, with values of 15.62 ± 4.99; factor 2, "Sociability", Cronbach's α: 0.853, with mean values of 13.33 ± 4.17; factor 3, "Somatization" , Cronbach's α: 0.704, mean value of 5.35 ± 1.90 and: factor 4, "Uncertainty", Cronbach's α: 0.746, with a mean value of 8.19 ± 2.51. In conclusion, the internal consistency of the adapted SSI-SM for public employees with different work positions and shifts has been validated and determined. This study provides a useful tool for the early detection of stress in public employees and may be potentially useful for preventing the harmful consequences of stress.

The purpose of this study was to determine the prevalence of sleep quality and to investigate variables predicting the risk of poor sleep quality in public workers from Murcia (Spain). A cross-sectional and prospective study was conducted from October 2013 to February 2016 in 476 public workers. The Pittsburgh Sleep Quality Index was used to measure the quality of sleep, and the reduced scale of the Horne and Österberg Morningness-Eveningness Questionnaire was applied to analyze the circadian typology. The predictive variables of self-reported poor sleep quality were identified by multivariate logistic regression. No significant differences were found according to sex in the overall sleep quality scores (5 ± 2.9 versus 5.1 ± 3, p = 0.650), but there were in the duration of sleep. Three percent of females slept <5 hours compared to 2% of men ( p = 0.034). Fixed morning shifts (OR = 1.9, 95% CI 1.3-3.1; p = 0.007) and evening chronotypes (OR = 1.6, 95% CI 1.0-2.3; p = 0.017) were independent predictors of suffering from poor sleep quality. In conclusion, the frequency of self-reported poor sleep quality among public workers from Murcia was 37.4%. Being a public worker with a fixed morning shift and having an evening chronotype demonstrated to be associated with the quality of sleep.

Background: The incidence of papillary thyroid microcarcinoma (PTMC) is increasing., Objective: To analyze the long-term prognosis of PTMC., Method: Study population: patients with a histopathological diagnosis of PTMC (size ≤ 1 cm) treated according to the risk of recurrence of the Latin American Thyroid Society. Inclusion criteria: minimum follow-up of 2 years, availability of histopathological samples, and treatment compliance. Exclusion criteria: previous thyroid surgery, other synchronous malignancies or ectopic location of the PTMC. Study variables: persistences, recurrences and mortality., Results: Based on the risk of recurrence, PTMC has very low risk in 65.2% (n = 105), low risk in 17.4% (n = 28) and high risk in 17.4% (n = 28). In high risk patients, total thyroidectomy was performed in all cases, cervical lymphadenectomy in 57,1% (n = 16) and metabolic therapy with I 131 in all cases. During a mean follow-up of 119,8 ± 65 months, 0.6% (n = 1) of recurrences took place. Risk factors associated to recurrence were not identified. No patient died due to MCPT., Conclusions: PTMC treated based on its risk of recurrence has a good long-term prognosis, without persistences, with a low number of recurrences and absence of disease-associated mortality., (Copyright: © 2020 Permanyer.)

Background: Chronic obstructive pulmonary disease (COPD) is one of the main reasons for healthcare appointments and use of healthcare resources. In recent years, clinics specializing in COPD have been developed to offer improved care and optimization of recourses for patients with high complexity and frequent decompensations. However, little is known about the clinical practice in this clinical model specializing in COPD. The objectives of this study were to assess the prevalence, characteristics of specialized COPD outpatient respiratory clinics and to evaluate clinical practice in this healthcare model., Methods: EPOCONSUL is a Spanish nationwide, observational, cross-sectional, clinical audit with prospective case recruitment including the clinical records for 4508 COPD cases from outpatient respiratory clinics over a 12-month period (May 2014-May 2015). The study evaluated clinical practice in 2378 cases from 28 hospitals with both general and specialized COPD outpatient respiratory clinics., Results: Only 28 (47.5%) centers had an outpatient clinic specializing in COPD, which was characterized by longer patient visits and a higher prevalence of written protocols compared to a general clinic. Patients treated in a specialized clinic had greater obstruction severity, a higher degree of dyspnea and also suffered from more comorbidities. The majority of patients at both types of clinic were classified as high risk (81.1% versus 83%, p = 0.384) according to GesEPOC criteria. Clinical control of COPD was more frequent at specialized clinics, with significant differences in non-severe patients (70.5% versus 56.1%, p < 0.001). Testing was done more frequently in specialized clinics, with better adherence to good clinical practice recommendations., Conclusion: A specialized COPD outpatient clinic is a healthcare model found in few pulmonology departments that treats more severe patients and those with increased comorbidities. The COPD patients treated in a specialized clinic had a better clinical control, as defined by impact and clinical stability. It is a healthcare model to offer improved care with a higher degree of adherence to guidelines., Competing Interests: This study was partly funded by Boehringer Ingelheim. Myriam Calle Rubio has received speaker fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Menarini, and Novartis and consulting fees from GlaxoSmith¬Kline, Gebro Pharma and Novartis. Juan José Soler-Cataluña has received speaker fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GSK, Menarini, Mundipharma, Novartis and and consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, GSK, Mundipharma and Novartis. Jose Luis Lopez Campos has received fees for giving conferences, scientific advising, participation in clinical studies or draft of publications for (alphabetical order): Almirall, AstraZeneca, Bayer, Boehringer Ingelheim, Cantabria Pharma, Chiesi, Esteve, Faes, Ferrer, Gebro Pharma, GlaxoSmithKline, Grifols, Menarini, MSD, Novartis, Pfizer, Rovi, Teva y Takeda. Bernardino Alcázar Navarrete reports personal fees from GSK, grants, personal fees and non-financial support from Novartis AG, personal fees and non-financial support from Boehringer Ingelheim, personal fees and non-financial support from Chiesi, grants, personal fees and nonfinancial support from Laboratorios Menarini, personal fees from Gebro, personal fees from Astra- Zeneca, outside the submitted work. None of these are related to this work. José Miguel Rodríguez González- Moro has received fees for giving conferences from Astra-Zeneca, GSK, Boehringer Ingelheim, Teva, Novartis and Chiesi. J.B. Soriano declares having received grants from 2014 to date from Linde via Hospital Universitario de La Princesa, and has participated in speaking activities, advisory committees and consultancies during the period 2014−2018 sponsored by Almirall, AstraZeneca, Boehringer Ingelheim, CHEST, Chiesi, ERS, Esteve, GEBRO, Grifols, GSK, Linde, Lipopharma, Mundipharma, Novartis, Pfizer, RiRL, Rovi, Sandoz, SEPAR and Takeda, outside the submitted work. Manuel E. Fuentes Ferrer does not have conflicts of interest Juan Luis Rodriguez Hermosa has received speaker fees from Boehringer Ingelheim and Gebro Pharma. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Alpha-1 antitrypsin deficiency (AATD) is the most common hereditary disorder in adults, but is under-recognized. In Spain, the number of patients diagnosed with AATD is much lower than expected according to epidemiologic studies. The objectives of this study were to assess the frequency and determinants of testing serum α1-antitrypsin (AAT) levels in COPD patients, and to describe factors associated with testing., Methods: EPOCONSUL is a cross-sectional clinical audit, recruiting consecutive COPD cases over one year. The study evaluated serum AAT level determination in COPD patients and associations between individual, disease-related, and hospital characteristics., Results: A total of 4,405 clinical records for COPD patients from 57 Spanish hospitals were evaluated. Only 995 (22.5%) patients had serum AAT tested on some occasion. A number of patient characteristics (being male [OR 0.5, p < 0.001], ≤55 years old [OR 2.38, p<0.001], BMI≤21 kg/m2 [OR 1.71, p<0.001], FEV1(%)<50% [OR 1.35, p<0.001], chronic bronchitis [OR 0.79, p < 0.001], Charlson index ≥ 3 [OR 0.66, p < 0.001], or history or symptoms of asthma [OR 1.32, p<0.001]), and management at a specialized COPD outpatient clinic [OR 2.73,p<0.001] were identified as factors independently associated with ever testing COPD patients for AATD. Overall, 114 COPD patients (11.5% of those tested) had AATD. Of them, 26 (22.8%) patients had severe deficiency. Patients with AATD were younger, with a low pack-year index, and were more likely to have emphysema (p<0.05)., Conclusion: Testing of AAT blood levels in COPD patients treated at outpatient respiratory clinics in Spain is infrequent. However, when tested, AATD (based on the serum AAT levels ≤100 mg/dL) is detected in one in five COPD patients. Efforts to optimize AATD case detection in COPD are needed., Competing Interests: Boehringer Ingelheim gave financial support with a donation for to carry out the study. The financing entity did not participate in the design of the study, data collection, analysis, publication or preparation of this manuscript. Myriam Calle Rubio received speaker fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Menarini, and Novartis and consulting fees from GlaxoSmithKline, Gebro Pharma and Novartis. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

The COPD Patient Management European Trial (COMET) investigated the efficacy and safety of a home-based COPD disease management intervention for severe COPD patients.The study was an international open-design clinical trial in COPD patients (forced expiratory volume in 1 s <50% of predicted value) randomised 1:1 to the disease management intervention or to the usual management practices at the study centre. The disease management intervention included a self-management programme, home telemonitoring, care coordination and medical management. The primary end-point was the number of unplanned all-cause hospitalisation days in the intention-to-treat (ITT) population. Secondary end-points included acute care hospitalisation days, BODE (body mass index, airflow obstruction, dyspnoea and exercise) index and exacerbations. Safety end-points included adverse events and deaths.For the 157 (disease management) and 162 (usual management) patients eligible for ITT analyses, all-cause hospitalisation days per year (mean±sd) were 17.4±35.4 and 22.6±41.8, respectively (mean difference -5.3, 95% CI -13.7 to -3.1; p=0.16). The disease management group had fewer per-protocol acute care hospitalisation days per year (p=0.047), a lower BODE index (p=0.01) and a lower mortality rate (1.9% versus 14.2%; p<0.001), with no difference in exacerbation frequency. Patient profiles and hospitalisation practices varied substantially across countries.The COMET disease management intervention did not significantly reduce unplanned all-cause hospitalisation days, but reduced acute care hospitalisation days and mortality in severe COPD patients., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

Background: Clinical audits have reported considerable variability in COPD medical care and frequent inconsistencies with recommendations. The objectives of this study were to identify factors associated with a better adherence to clinical practice guidelines and to explore determinants of this variability at the the hospital level., Methods: EPOCONSUL is a Spanish nationwide clinical audit that evaluates the outpatient management of COPD. Multilevel logistic regression with two levels was performed to assess the relationships between individual and disease-related factors, as well as hospital characteristics., Results: A total of 4508 clinical records of COPD patients from 59 Spanish hospitals were evaluated. High variability was observed among hospitals in terms of medical care. Some of the patient's characteristics (airflow obstruction, degree of dyspnea, exacerbation risk, presence of comorbidities), the hospital factors (size and respiratory nurses available) and treatment at a specialized COPD outpatient clinic were identified as factors associated with a better adherence to recommendations, although this only explains a small proportion of the total variance., Conclusion: To be treated at a specialized COPD outpatient clinic and some intrinsic patient characteristics were factors associated with a better adherence to guideline recommendations, although these variables were only explaining part of the high variability observed among hospitals in terms of COPD medical care.

According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting β 2 agonist therapy is recommended in patients with moderate-to-severe disease and an increased risk of exacerbations. However, ICS are largely overprescribed in clinical practice, and most patients are unlikely to benefit from long-term ICS therapy.Evidence from recent randomized-controlled trials supports the hypothesis that ICS can be safely and effectively discontinued in patients with stable COPD and in whom ICS therapy may not be indicated, without detrimental effects on lung function, health status, or risk of exacerbations. This article summarizes the evidence supporting the discontinuation of ICS therapy, and proposes an algorithm for the implementation of ICS withdrawal in patients with COPD in clinical practice.Given the increased risk of potentially serious adverse effects and complications with ICS therapy (including pneumonia), the use of ICS should be limited to the minority of patients in whom the treatment effects outweigh the risks.

Few studies have investigated the variability of COPD-related symptoms or factors related to symptom variability. This observational, prospective, multicentre study was conducted to describe the number and intensity of morning and night-time respiratory symptoms and their variability over one week using the Night-time and Early Morning Symptoms of COPD Instruments (NiSCI and EMSCI) to evaluate stable COPD patients. Logistic regression analyses were performed to investigate factors associated with symptom variability. A total of 2669 patients were evaluated (mean age, 67.7 years; 80.9% men; mean FEV1 50.6%). Of these, 48% reported night-time symptoms and 71% reported morning symptoms. Of the 2293 patients who completed the NiSCI and EMSCI, 90% showed variability in either symptom number (89.6%) or symptom intensity (15.8%). More severe dyspnoea, more exacerbations during the previous year and the exacerbator or mixed COPD-asthma phenotypes were associated with variability in symptom number or intensity. Anxiety was significantly associated with variability in symptom number and intensity. Most COPD patients showed symptom variability over a weeklong period, especially in terms of symptom number. Several COPD-related factors, mainly factors related to more severe disease and more frequent exacerbations, were associated with increased symptom variability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Chronic obstructive pulmonary disease (COPD) outpatients account for a large burden of usual care by respirologists. EPOCONSUL is the first national clinical audit conducted in Spain on the medical care for COPD patients delivered in outpatient respiratory clinics. We aimed to evaluate the clinical interventions and the degree of adherence to recommendations in outpatients of current COPD clinical practice guidelines., Methodology: This is an observational study with prospective recruitment (May 2014-May 2015) of patients with a COPD diagnosis as seen in outpatient respiratory clinics. The information collected was historical in nature as for the clinical data of the last and previous consultations, and the information concerning hospital resources was concurrent., Results: A total of 17,893 clinical records of COPD patients in outpatient respiratory clinics from 59 Spanish hospitals were evaluated. Of the 5,726 patients selected, 4,508 (78.7%) were eligible. Overall, 12.1% of COPD patients did not fulfill a diagnostic spirometry criteria. Considerable variability existed in the available resources and work organization of the hospitals, although the majority were university hospitals with respiratory inpatient units. There was insufficient implementation of clinical guidelines in preventive and educational matters. In contrast, quantitative evaluation of dyspnea grade (81.9%) and exacerbation history (70.9%) were more frequently performed. Only 12.4% had COPD severity calculated according to the Body mass index, airflow Obstruction, Dyspnoea and Exercise capacity (BODE) index. Phenotype characteristics according to Spanish National Guideline for COPD were determined in 46.3% of the audited patients, and the risk evaluation according to Global initiative for chronic Obstructive Lung Disease was estimated only in 21.9%., Conclusion: The EPOCONSUL study reports the current situation of medical care for COPD patients in outpatient clinics in Spain, revealing its variability, strengths, and weaknesses. This information has to be accounted for by health managers to define corrective strategies and maximize good clinical practice., Competing Interests: The authors report no conflicts of interest in this work.

Studies of the effects of smoking on leukocyte telomere length (LTL) using cigarettes smoked per day or pack years smoked (PYS) present limitations. Reported high levels of smoking may not increase toxin exposure levels proportionally. Nicotine metabolism ratio (NMR) predicts total cigarette puff volume and overall exposure based on total N-nitrosamines, is highly reproducible and independent of time since the last cigarette. We hypothesized that smokers with higher NMRs will exhibit increased total puff volume, reflecting efforts to extract more nicotine from their cigarettes and increasing toxin exposure. In addition, higher levels of smoking could cause a gross damage in LTL. The urinary cotinine, 3-OH cotinine and nicotine levels of 147 smokers were analyzed using a LC/MS system Triple-Q6410. LTL and CYP2A6 genotype was determined by PCR in blood samples. We found a significant association between NMR and CYP2A6 genotype. Reduction in LTL was seen in relation to accumulated tobacco consumption and years smoking when we adjusted for age and gender. However, there were no significant differences between NMR values and LTL. In our study the higher exposure was associated with lower number of PYS. Smokers with reduced cigarette consumption may exhibit compensatory smoking behavior that results in no reduced tobacco toxin exposure. Our results suggest that lifetime accumulated smoking exposure could cause a gross damage in LTL rather than NMR or PYS. Nevertheless, a combination of smoking topography (NMR) and consumption (PYS) measures may provide useful information about smoking effects on health outcomes., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Variations in tobacco-related cancers, incidence and prevalence reflect differences in tobacco consumption in addition to genetic factors. Besides, genes related to lung cancer risk could be related to smoking behavior. Polymorphisms altering DNA repair capacity may lead to synergistic effects with tobacco carcinogen-induced lung cancer risk. Common problems in genetic association studies, such as presence of gene-by-environment (G x E) correlation in the population, may reduce the validity of these designs. The main purpose of this study was to evaluate the independence assumption for selected SNPs and smoking behaviour in a cohort of 320 healthy Spanish smokers. We found an association between the wild type alleles of XRCC3 Thr241Met or KLC3 Lys751Gln and greater smoking intensity (OR = 12.98, 95% CI = 2.86-58.82 and OR=16.90, 95% CI=2.09-142.8; respectively). Although preliminary, the results of our study provide evidence that genetic variations in DNA-repair genes may influence both smoking habits and the development of lung cancer. Population-specific G x E studies should be carried out when genetic and environmental factors interact to cause the disease.

Some controversy exists on the specific genetic variants that are associated with nicotine dependence and smoking-related phenotypes. The purpose of this study was to analyse the association of smoking status and smoking-related phenotypes (included nicotine dependence) with 17 candidate genetic variants: CYP2A6*1×2, CYP2A6*2 (1799T>A) [rs1801272], CYP2A6*9 (-48T>G) [rs28399433], CYP2A6*12, CYP2A13*2 (3375C>T) [rs8192789], CYP2A13*3 (7520C>G), CYP2A13*4 (579G>A), CYP2A13*7 (578C>T) [rs72552266], CYP2B6*4 (785A>G), CYP2B6*9 (516G>T), CHRNA3 546C>T [rs578776], CHRNA5 1192G>A [rs16969968], CNR1 3764C>G [rs6928499], DRD2-ANKK1 2137G>A (Taq1A) [rs1800497], 5HTT LPR, HTR2A -1438A>G [rs6311] and OPRM1 118A>G [rs1799971]. We studied the genotypes of the aforementioned polymorphisms in a cohort of Spanish smokers (cases, N = 126) and ethnically matched never smokers (controls, N = 80). The results showed significant between-group differences for CYP2A6*2 and CYP2A6*12 (both P<0.001). Compared with carriers of variant alleles, the odds ratio (OR) for being a non-smoker in individuals with the wild-type genotype of CYP2A6*12 and DRD2-ANKK1 2137G>A (Taq1A) polymorphisms was 3.60 (95%CI: 1.75, 7.44) and 2.63 (95%CI: 1.41, 4.89) respectively. Compared with the wild-type genotype, the OR for being a non-smoker in carriers of the minor CYP2A6*2 allele was 1.80 (95%CI: 1.24, 2.65). We found a significant genotype effect (all P≤0.017) for the following smoking-related phenotypes: (i) cigarettes smoked per day and CYP2A13*3; (ii) pack years smoked and CYP2A6*2, CYP2A6*1×2, CYP2A13*7, CYP2B6*4 and DRD2-ANKK1 2137G>A (Taq1A); (iii) nicotine dependence (assessed with the Fagestrom test) and CYP2A6*9. Overall, our results suggest that genetic variants potentially involved in nicotine metabolization (mainly, CYP2A6 polymorphisms) are those showing the strongest association with smoking-related phenotypes, as opposed to genetic variants influencing the brain effects of nicotine, e.g., through nicotinic acetylcholine (CHRNA5), serotoninergic (HTR2A), opioid (OPRM1) or cannabinoid receptors (CNR1).

Aim: To analyze the accuracy of diagnosis in a population receiving inhaled therapies due to respiratory diseases in a primary care setting., Method: Noninterventional, multicenter, cross-sectional, observational epidemiologic study methodology., Results: A total of 9752 subjects were evaluated. Of these, 4188 (42.9%) patients were diagnosed with asthma, 4175 (42.8%) with chronic obstructive pulmonary disease (COPD), and 1389 had a diagnosis of disease of unknown origin. Of those over the age of 40 years, 4079 (50.9%) had COPD and 2877 (35.9%) had asthma. Sixty percent of the subjects were men, and the proportion of men was higher in patients with COPD (83.2%) than in the group with asthma (39.8%, P < 0.0001). Of subjects with COPD, 17.3% had mild, 55.3% had moderate, 24.1% had severe, and 3.2% had very severe disease. With regard to the level of severity of asthma, 34.9% of subjects had intermittent, 34.6% had mild persistent, 27.1% had moderate persistent, and 3.5% had severe persistent disease. Only 13.9% of patients in the COPD group had all the characteristics of COPD based on the Global Initiative for Chronic Obstructive Lung Disease criteria and an absence of the characteristics of asthma., Conclusions: The majority of patients receiving inhaled therapy in primary care did not have an accurate diagnosis according to current international guidelines for COPD and asthma. More initiatives for improving diagnostic accuracy in respiratory diseases must be implemented in primary care.

Aims: A cross-sectional multicenter study was designed to assess health-related quality of life (HRQL) in women with chronic obstructive pulmonary disease (COPD) who were attended in the outpatient setting in actual conditions of the daily practice., Methods: A total of 1786 women with COPD (mean age of 66.5 years) and 1661 pairs of men and women matched by age and COPD severity participated in a cross-sectional study. HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12)., Results: The mean PCS-12 and MCS-12 scores were 36.5+/-10.3 and 44.1+/-11.8, respectively. General health and physical functioning domains were those with the lowest scores, whereas role emotional and social functioning were those with the highest scores. The percentage of women with low HRQL increased according to age, whereas the percentage of women with high or normal HRQL decreased significantly. In relation to COPD severity, more women rated HRQL as low in the physical component than in the mental component. HRQL correlated significantly with FEV(1) in both PCS-12 and MCS-12 scales. As expected, an inverse significant correlation between HRQL and degree of dyspnea in the PCS-12 and the MCS-12 scales was observed. Women had also a significantly worse HRQL than men in all physical and mental domains., Conclusions: In outpatient women with COPD, HRQL was impaired especially the physical component of the SF-12. For the same age and severity of COPD, women showed significantly lower scores in all physical and mental domains of the SF-12 than men.

Background: The objective of this study was to measure health-related quality of life (HRQL) in outpatients with chronic obstructive pulmonary disease (COPD) and to assess differences in HRQL according to age, gender, and severity of COPD., Methods: A total of 9405 patients (79% men, mean age 68 years) participated in a cross-sectional study. HRQL was measured with the Short Form 12 Health Survey Questionnaire (SF-12). Severity of COPD was graded into three levels according to forced expiratory volume in one second value., Results: COPD severity was mild in 33.8% of cases, moderate in 49.3% and severe in 16.8%. The mean physical component summary (PCS-12) and mental component summary (MCS-12) scores were 36.8 +/- 10.4 and 47.2 +/- 11.2, respectively. General health and physical functioning domains were those with the lowest scores. The mean MCS-12 scores were significantly higher in men (47.9 +/- 10.9) than in women (44.1 +/- 11.8) (P < 0.001). Patients older than 60 years rated HRQL worse than patients aged 40-59 years. There were statistically significant differences according to severity of disease in the mean scores of all domains of the PCS-12 and MCS-12 scales., Conclusions: The present findings show the influence of female gender, older age and moderate-to-severe of airflow limitation on HRQL in outpatients with COPD attended in daily practice.