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.

COMET: a multicomponent home-based disease-management programme versus routine care in severe COPD.

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.

A proposal for the withdrawal of inhaled corticosteroids in the clinical practice of chronic obstructive pulmonary disease.

According to the current clinical practice guidelines for chronic obstructive pulmonary disease (COPD), the addition of inhaled corticosteroids (ICS) to long-acting ß2 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.

Variability in adherence to clinical practice guidelines and recommendations in COPD outpatients: a multi-level, cross-sectional analysis of the EPOCONSUL study.

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.

The Effect of Polymorphisms in DNA Repair Genes and Carcinogen Metabolizers on Leukocyte Telomere Length: A Cohort of Healthy Spanish Smokers.

INTRODUCTION: Smoking implies exposure to carcinogenic agents that causes DNA damage, which could be suspected to enhance telomere attrition. To protect and deal with DNA damage, cells possess mechanisms that repair and neutralize harmful substances. Polymorphisms altering DNA repair capacity or carcinogen metabolism may lead to synergistic effects with tobacco carcinogen-induced shorter telomere length independently of cancer interaction. The aim of this study was to explore the association between leukocyte telomere length (LTL) and several genetic polymorphisms in DNA repair genes and carcinogen metabolizers in a cohort of healthy smokers. METHODS: We evaluated the effect of six genetic polymorphisms in cytochrome P1A1 (Ile462Val), XRCC1 (Arg399Gln), APEX1 (Asp148Glu), XRCC3 (Thr241Met), and XPD (Asp312Asn; Lys751Gln) on LTL in a cohort of 145 healthy smokers in addition to smoking habits. RESULTS: Logistic regression analysis showed an association between XRCC1 399Gln allele and shorter telomere length (OR = 5.03, 95% CI = 1.08% to 23.36%). There were not association between the rest of polymorphisms analyzed and LTL. CONCLUSIONS: Continuous exposure to tobacco could overwhelm the DNA repair machinery, making the effect of the polymorphisms that reduce repair capacity more pronounced. Analyzing the function of smoking-induced DNA-repair genes and LTL is an important goal in order to identify therapeutic targets to treat smoking-induced diseases.

Effects of cigarette smoking and nicotine metabolite ratio on leukocyte telomere length.

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.

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.

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.

Unravelling young COPD and pre-COPD in the general population.

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 (FEV1/FVC) >0.70. Young COPD was defined as FEV1/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 FEV1/FVC <0.70, 65 (6.0%) were ≤50 years of age. Among the 8015 individuals with FEV1/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.

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.

Enhanced fatty acid oxidation through metformin and baicalin as therapy for COVID-19 and associated inflammatory states in lung and kidney.

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-ß-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-ß-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.

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.

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 and Determinants of COPD in Spain: EPISCAN II.

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.

Work Shift and Circadian Rhythm as Risk Factors for Poor Sleep Quality in Public Workers from Murcia (Spain).

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.

Reliability and Validity of a Stress Scale in Public Employees from Murcia (Spain).

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.

Association of HTR2A-1438G/A Genetic Polymorphism With Smoking and Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Cigarette smoking is a major risk factor in the development of chronic obstructive pulmonary disease (COPD). Serotonin levels have been associated with COPD and smoking has been as a significant modulator. Elevated levels of serotonin are responsible for bronchoconstriction and pulmonary vasoconstriction and also nicotine dependence, thus serotonin response could be affected by genetic polymorphisms in transporters and receptors of serotonin. OBJECTIVES: The aim of the current study was to analyze the effect of SLC6A4 (5HTT_LPR) (rs25531) and HTR2A-1438G/A (rs6311) genetic polymorphisms on the relation between smoking habits and COPD. METHODS: The association between SLC6A4 (5HTT_LPR) (rs25531), HTR2A-1438G/A (rs6311), smoking degree and COPD was analyzed in a total of 77 COPD patients (active smokers) and 90 control subjects (active healthy smokers). The DNA was extracted of peripheral leukocytes samples and genotyping was performed using an allele specific polymerase chain reaction. RESULTS: The distribution of SLC6A4 genotypes did not vary between healthy smokers and COPD patients (P=0.758). On the other hand, the A allele of HTR2A (rs6311) was significantly associated with COPD incidence in the trend model (P=0.02; 1.80 [1.04-3.11]). Among all smokers, this allele was also associated with the number of pack years smoked (P=0.02) and also, we observed a marginal association with FEV1/FVC values (P=0.06). CONCLUSION: Our results point a possible role of the A allele of HTR2A (rs6311) in COPD pathogenesis, suggesting that this effect depends partly on tobacco consumption due to a gene-by-environment interaction.

Patients with Chronic Obstructive Pulmonary Disease Exacerbations: Recommendations for Diagnosis, Treatment and Care. / Paciente exacerbador con enfermedad pulmonar obstructiva crónica: recomendaciones en procesos diagnósticos, terapéuticos y asistenciales.

OBJECTIVE: To describe an evidence- and experience-based expert consensus on the most relevant issues of patients with COPD exacerbations. METHODS: The Delphi technique was used. Evidence was reviewed by a scientific committee and 60 experts. A questionnaire was prepared containing 3 sections: diagnosis of the exacerbator; treatment, and healthcare processes. The survey was answered in 2 rounds by 60 pneumologists on an online platform. Statements were scored on a Likert scale from 1 (total disagreement) to 9 (total agreement). Agreement and disagreement were defined as a score of 7-9 or 1-3, respectively, given by more than two thirds of the participants. RESULTS: A total of 48 statements were included, one of which was added in the second round. Consensus was reached in 37 items (78.7%) after the first round (agreement), and in 43 (89.5%) after the second round (42 agreement, 1 disagreement). The statements with the highest proportion of experts agreeing were as follows: in exacerbators, chronic bronchial infection favors lung function decline (93.1%); long-acting bronchodilators should not be withdrawn (93.1%); treatment must be personalized if new exacerbations occur despite optimal bronchodilator treatment (96.6%); management must be coordinated between primary care and the respiratory medicine department (93.1%), and patients must be followed up in specific integrated multicomponent programs (94.8%). CONCLUSIONS: The findings of this study could assist in the diagnosis and treatment of COPD exacerbators in our area.

Assessing the clinical practice in specialized outpatient clinics for chronic obstructive pulmonary disease: Analysis of the EPOCONSUL clinical audit.

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.

10 Years After EPISCAN: A New Study on the Prevalence of COPD in Spain -A Summary of the EPISCAN II Protocol. / Nuevo estudio sobre la prevalencia de la EPOC en España: resumen del protocolo EPISCAN II, 10 años después de EPISCAN.

INTRODUCTION: The EPISCAN study, published in 2007, was an update of the results of the 1997 IBERPOC study. Changes in demographics and exposure to risk factors demand the periodic update of prevalence and determining factors in COPD. This article is a summary of the protocol and tools used in EPISCAN II. MATERIALS AND METHODS: The primary objective of EPISCAN II is to estimate the prevalence of COPD among the general population aged 40 years or more in the 17 autonomous communities of Spain. The sample size requires 600 participants (300 men and 300 women) per center, selected by screening 10,200 participants in a short visit (questionnaire plus forced post-bronchodilator spirometry). Of these, 800 (400 with COPD and 400 without COPD) will also perform a long visit (including a walking test, blood tests, determination of diffusion, pulse oximetry and bioimpedance, and low radiation CT). RESULTS: The first participant was recruited on 28 February 2017. As of 22 November 2017, a total of 3,581 participants had been included, of whom 422 had already performed the long visit. It is estimated that the field work will be completed by December 2018. The new imaging data, biomarkers, and information on new exposures, such as electronic cigarettes and environmental pollution, will help us re-quantify the burden of COPD. CONCLUSIONS: EPISCAN II will provide updated information on prevalence and determinants of COPD in Spain, allowing for the comparison of spirometric results and other factors associated with COPD among the 17 autonomous communities.