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BackgroundFew 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.MethodEPISCAN II was a multicentre, cross-sectional, population-based epidemiological study in individuals older than 40 years.ResultsA 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%versus45.5%, 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 pConclusionsApproximately 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 FEV1and low physical activity are also significantly associated with respiratory symptoms.

[EN]: The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD., [ES]: Los modelos de atención sanitaria actuales descritos en GesEPOC indican la mejor manera de hacer un diagnóstico correcto, la categorización de los pacientes, la adecuada selección de la estrategia terapéutica y el manejo y la prevención de las agudizaciones. Además, en la EPOC concurren diversos aspectos que resultan cruciales en una aproximación integrada de la atención sanitaria a estos pacientes. La evaluación de las comorbilidades en el paciente con EPOC representa un reto asistencial. Dentro de una valoración integral debe estudiarse la presencia de comorbilidades que tengan relación con la presentación clínica, con alguna técnica diagnóstica o con algunos tratamientos relacionados con la EPOC. Asimismo, son necesarias intervenciones en hábitos de vida saludables, la adhesión a tratamientos complejos, desarrollar capacidades para poder reconocer los signos y síntomas de la exacerbación, saber qué hacer para prevenirlos y tratarlos enmarcados en un plan de automanejo. Finalmente, los cuidados paliativos constituyen uno de los pilares en el tratamiento integral del paciente con EPOC, con los que se buscan prevenir o tratar los síntomas de una enfermedad, los efectos secundarios del tratamiento, y los problemas físicos, psicológicos y sociales de los pacientes y sus cuidadores. Por tanto, el objetivo principal de estos cuidados paliativos no es prolongar la esperanza de vida, sino mejorar su calidad. En este capítulo de GesEPOC 2021 se presenta una actualización sobre las comorbilidades más importantes, las estrategias de automanejo y los cuidados paliativos en la EPOC, y se incluye una recomendación sobre el uso de opiáceos para el tratamiento de la disnea refractaria en la EPOC.

[ES] En este artículo se presentan las recomendaciones sobre el diagnóstico y tratamiento del síndrome de agudización de la enfermedad pulmonar obstructiva crónica (EPOC) (SAE) de GesEPOC 2021. Como principales novedades, la guía propone una definición y aproximación sindrómica, una nueva clasificación de gravedad y el reconocimiento de diferentes rasgos tratables (RT), lo que supone un nuevo paso hacia la medicina personalizada. La evaluación de la evidencia se realiza mediante la metodología Grading of Recommendations Assessment, Development and Evaluation (GRADE), con la incorporación de seis nuevas preguntas con enfoque paciente, intervención, comparación y resultados (PICO). El proceso diagnóstico comprende cuatro etapas: 1) establecer el diagnóstico del SAE, 2) valorar la gravedad del episodio, 3) identificar el factor desencadenante y 4) abordar los RT. En este proceso diagnóstico se diferencia una aproximación ambulatoria, en la que se recomienda incluir una batería básica de pruebas y una hospitalaria, más exhaustiva, en la que se contempla el estudio de diferentes biomarcadores y pruebas de imagen. El tratamiento broncodilatador destinado al alivio inmediato de los síntomas se considera esencial para todos los pacientes, mientras que el uso de antibióticos, corticoides sistémicos, oxigenoterapia, ventilación asistida o el tratamiento de las comorbilidades variará en función de la gravedad y de los posibles RT. El empleo de antibióticos estará especialmente indicado ante un cambio en el color del esputo, cuando se requiera asistencia ventilatoria, en los casos que cursen con neumonía y también para aquellos con proteína-C reactiva elevada (≥ 20 mg/L). Los corticoides sistémicos se recomiendan en el SAE que necesita ingreso y se sugieren en el SAE moderado. La eficacia de estos fármacos es mayor en pacientes con recuento de eosinófilos en sangre ≥ 300 células/mm3. La ventilación mecánica no invasiva en fase aguda se establece fundamentalmente para pacientes con SAE que cursen con acidosis respiratoria, a pesar del tratamiento inicial., [EN] This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm3. Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment.

Background: The concept of clinical control has been proposed as an instrument for evaluating patients with COPD. However, the possible association between clinical control, reduced symptom severity and HRQoL has yet to be confirmed. Methods: This multicentre, prospective and observational study was carried out in 15 pulmonology clinics in Spain. The patients were followed up for six months, with a baseline visit (V0), followed by visits at three months (V1) and six months (V2). Clinical control was determined at V1, with the application of both clinical criteria and the COPD assessment test (CAT). All patients reported their symptoms by a validated symptom diary (E-RS) using a portable device, and their HRQoL was assessed using the EQ5D questionnaire. The relationship between clinical control and E-RS and HRQoL during follow-up was assessed with t-test. Results: A total of 126 patients were screened. After application of the inclusion/exclusion criteria, 93 were finally included (mean age 66 +/- 8 years, 84.9% male), with a mean FEV1 predicted of 49.8% +/- 16.5%. Of these patients, 44 (47.3%) achieved clinical control at V1, according to CAT criteria, and 50 (53.8%), according to clinical criteria. The E-RS scores differed between controlled and uncontrolled patients at all time points, both according to CAT (mean differences of -4.6, -5.6 and -6.2 units at V0, V1 and V2, respectively, p, This study was funded by an unrestricted grant from Novartis Spain. This company did not intervene in the development of the study, data collection, analysis of results or drafting of the manuscript.

The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD.

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm3. Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment.

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.

Introduction: Control status may be a useful tool to assess response to treatment at each clinical visit in COPD. Control status has demonstrated to have long-term predictive value for exacerbations, but there is no information about the short-term predictive value of the lack of control and changes in control status over time. Method: Prospective, international, multicenter study aimed at describing the short-term (6 months) prognostic value of control status in patients with COPD. Patients with COPD were classified as controlled/uncontrolled at baseline and at 3,6-month follow-up visits using previously validated criteria of control. Moderate and severe exacerbation rates were compared between controlled and uncontrolled visits and between patients persistently controlled, uncontrolled and those changing control status over follow-up. Results: A total of 267 patients were analyzed: 80 (29.8%) were persistently controlled, 43 (16%) persistently uncontrolled and 144 (53.7%) changed control status during follow-up. Persistently controlled patients were more frequently men, with lower (not increased) body mass index and higher FEV1(%). During the 6 months following an uncontrolled patient visit the odds ratio (OR) for presenting a moderate exacerbation was 3.41 (95% confidence interval (CI) 2.47–4.69) and OR = 4.25 (95%CI 2.48–7.27) for hospitalization compared with a controlled patient visit. Conclusions: Evaluation of control status at each clinical visit provides relevant prognostic information about the risk of exacerbation in the next 6 months. Lack of control is a warning signal that should prompt investigation and action in order to achieve control status.

Eulogio Pleguezuelos,1,2 Amin Del Carmen,1 Eva Moreno,3 Pilar Ortega,4 Xavier Vila,4 Laura Ovejero,4 Mateu Serra-Prat,5 Elisabet Palomera,5 Manuel Vicente Garnacho-Castaño,6 Eduardo Loeb,7 Georgina Farago,7 Marc Miravitlles7 1Physical Medicine and Rehabilitation Department, Hospital de Mataró, Barcelona, Spain; 2Department of Experimental Science and Healthcare, Faculty of Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain; 3Physical Medicine and Rehabilitation Department, Hospitalet General Hospital, L´Hospitalet de Llobregat, Barcelona, Spain; 4Pneumology Department, Hospital de Mataró Mataró, Barcelona, Spain; 5Research Unit, Consorci Sanitari del Maresme, Barcelona, Spain; 6TGRI-AFIRS, Department of Physical Activity and Sports Science, School of Health Sciences, Tecno Campus, Universitat Pompeu Fabra, Barcelona, Spain; 7Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, SpainCorrespondence: Eulogio PleguezuelosHospital de Mataró, C/Cirera s/n 08302, Mataró, Barcelona, SpainTel +34 93.7417728Fax +34 93.7417717Email epleguezuelos@csdm.catPurpose: On March 16, 2020, the Spanish government declared a state of alarm due to the rapid spread of coronavirus disease 2019 (COVID-19). Patients with chronic obstructive pulmonary disease (COPD) were restricted to remain confined at home, and medical visits were cancelled for 3 months. The impact of this lockdown on the manifestations of COPD and the quality-of-life of these patients has not been explored.Patients and Methods: One hundred patients with COPD were interviewed by telephone from May 2– 18, 2020. The interviews included questions about the lockdown, missed medical appointments, fears of the disease, possible COVID-19 infection, and exacerbations of COPD suffered during this period and their management. In addition, the COPD Assessment Test, the Hospital Anxiety and Depression, and the 5-Dimension Euro Quality-of-Life questionnaires were administered.Results: Sixty-four (64%) patients claimed to have strictly complied with the lockdown, and only 42 (42%) stated they had left home at least once during lockdown. Only one patient (1%) was hospitalized due to COVID-19, and 13 (13%) patients presented an exacerbation of COPD self-managed at home with no admissions due to exacerbation of COPD during this period. A medical consultation or complementary test was cancelled in 90% of the patients, but 61% had a medical telephone visit with a high degree of satisfaction (mean 9.3/10). Most patients declared that their feeling regarding lung disease and general health was similar or even better during lockdown (82% and 81%, respectively).Conclusion: Our results indicate that in general lockdown had a low impact on COPD patients. Only one patient was affected by COVID-19, but moderate exacerbations of COPD were not infrequent. Although many medical visits and test were cancelled, patients were very satisfied with the medical telephone visits.Keywords: COPD, lockdown, COVID-19

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5&times, 10&minus, 4) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10&minus, 3 to 3.77&times, 8). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.

Alexa Nuñez,1,2,* Viviana Marras,3,* Matevz Harlander,4 Evgeni Mekov,5 Cristina Esquinas,1 Matjaz Turel,4 David Lestan,4 Rosen Petkov,5 Nikolay Yanev,5 Pietro Pirina,3 Silvia Negri,3 Marc Miravitlles,1,2,6 Miriam Barrecheguren1 1Pneumology Department, Hospital Universitari Vall d´Hebron/Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain; 2Medicine Department, Autonomous University of Barcelona (UAB), Barcelona, Spain; 3Respiratory Unit, AOU Sassari, Sassari, Italy; 4Department of Pulmonary Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia; 5Department of Pulmonary Diseases, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria; 6CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain*These authors contributed equally to this workCorrespondence: Marc MiravitllesPneumology Department, Hospital Universitari Vall d´Hebron, P. Vall d’Hebron 119-129, Barcelona 08035, SpainTel +34 934893000Fax +34 93 274 82 08Email marcm@separ.esIntroduction: Chronic obstructive pulmonary disease (COPD) is associated with increased lung and systemic inflammation. We aimed to identify associations between easy-to-obtain blood biomarkers and the frequency and severity of exacerbations.Methods: Cross-sectional, multicentre study performed in four centres in Spain, Italy, Bulgaria, and Slovenia. Blood samples were obtained for blood cell count, C-reactive protein (CRP), alpha-1 antitrypsin (AAT) and fibrinogen analysis. The neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and eosinophil/basophil ratio (EBR) were calculated. Firstly, patients were divided into clinical phenotypes according to the Spanish guidelines of COPD, and secondly, patients were classified into 2 groups: non-exacerbators (≤ 1 ambulatory exacerbation in the previous year) and exacerbators (≥ 2 ambulatory exacerbations or 1 hospitalisation in the previous year). A multivariate stepwise logistic regression model was performed to identify laboratory parameters associated with exacerbators.Results: A total of 355 patients with a mean age 66 years (SD=8.9) were included, and 64% were male. The mean FEV1% (forced expiratory volume in the first second) was 55% (SD=20%), and the mean COPD Assessment Test (CAT) score was 15.6 (SD=7.9). One hundred ninety-six (55.2%) patients were classified in the non-exacerbator group, and 159 (44.8%) were exacerbators. Patients in the exacerbators group presented lower haemoglobin levels (p=0.019) and ERB (p= 0.023) but higher CRP levels (p=0.001). In the multivariate analysis, females, higher levels of CRP, lower FEV1% and low EBR were independently related to exacerbators.Conclusion: Female sex, having a more severe impairment of lung function, higher CRP levels and a lower EBR are associated with an exacerbator phenotype in COPD.Keywords: COPD, blood cells, biomarkers, exacerbation, phenotypes &nbsp

Currently, chronic obstructive pulmonary disease (COPD) patients and their physicians face a number of significant clinical challenges, one of which is the high degree of uncertainty related to chronic bronchial infection (CBI). By reviewing the current literature, several challenges can be identified, which should be considered as goals for research. One of these is to establish the bases for identifying the biological and clinical implications of the presence of potentially pathogenic microorganisms in the airways that should be more clearly elucidated according to the COPD phenotype. Another urgent area of research is the role of long-term preventive antibiotics. Clinical trials need to be carried out with inhaled antibiotic therapy to help clarify the profile of those antibiotics. The role of inhaled corticosteroids in patients with COPD and CBI needs to be studied to instruct the clinical management of these patients. Finally, it should be explored and confirmed whether a suitable antimicrobial treatment during exacerbations may contribute to breaking the vicious circle of CBI in COPD. The present review addresses the current state of the art in these areas to provide evidence which will enable us to progressively plan better healthcare for these patients. Yes

Introduction: The asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO) is a clinical condition that combines features of those two diseases, and that is difficult to define due to the lack of understanding of the underlying mechanisms. Determining systemic mediators may help clarify the nature of inflammation in patients with ACO. Objectives: We aimed at investigating the role and interaction of common markers of systemic inflammation (IL-6, IL-8, and tumor necrosis factor-alpha), Th2-related markers (periostin, IL-5, and IL-13), and IL-17 in asthma, COPD, and ACO. Methods: This is a cross-sectional study of patients aged >= 40 years with a post-bronchodilator forced expiratory volume in the first second/forced vital capacity < 0.70 recruited from out-patient clinics in tertiary hospitals with a clinical diagnosis of asthma, COPD, or ACO. ACO was defined by a history of smoking > 10 pack-years in a patient with a previous diagnosis of asthma or by the presence of eosinophilia in a patient with a previous diagnosis of COPD. Clinical, functional, and inflammatory parameters were compared between categories using discriminant and network analysis. Results: In total, 109 ACO, 89 COPD, and 94 asthma patients were included. Serum levels (median [interquartile range]) of IL-5 were higher in asthma patients than in COPD patients (2.09 [0.61-3.57] vs 1.11 [0.12-2.42] pg/mL, respectively; p=0.03), and IL-8 levels (median [interquartile range]) were higher in COPD patients than in asthma patients (9.45 [6.61-13.12] vs 7.03 [4.69-10.44] pg/mL, respectively; p < 0.001). Their values in ACO were intermediate between those in asthma and in COPD. Principal component and network analysis showed a mixed inflammatory pattern in ACO in between asthma and COPD. IL-13 was the most connected node in the network, with different weights among the three conditions. Conclusion: Asthma and COPD are two different inflammatory conditions that may overlap in some patients, leading to a mixed inflammatory pattern. IL-13 could be central to the regulation of inflammation in these conditions., The authors are grateful to all the patients who participated in the study. A number of investigators contributed to the study logistics and they are listed in the Supplementary materials. The project was endorsed by the COPD and Asthma Research Board (PII de EPOC y asma) of the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). The project was partially funded by the Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, Ministerio de Economia y Competitividad (FIS 15/01263) through European Union FEDER funds and by unrestricted grant from Chiesi Espana S.A.U.

RATIONALE: Adults may exhibit characteristics of both asthma and chronic obstructive pulmonary disease (COPD), a situation recently described as asthma-COPD overlap (ACO). There is a paucity of information about ACO in primary care. OBJECTIVES: 1) Estimate the prevalence and describe characteristics of individuals with ACO in primary care practices among patients currently diagnosed with asthma, COPD, or both; and 2) Compare the prevalence and characteristics of ACO between the three source populations. METHODS: The Respiratory Effectiveness Group (REG) conducted a cross-sectional study of individuals ≥40 years old and with ≥2 outpatient primary care visits over a 2-year period in the United Kingdom's Optimum Patient Care Research Database (OPCRD). Patients were classified into one of three source populations based on diagnostic codes: (A) COPD only; (B) both asthma and COPD; or (C) asthma only. ACO was defined as the presence of all of the following: (1) age ≥40 years; (2) current or former smoking, (3) post-bronchodilator (BD) airflow limitation (forced expired volume in the first second [FEV1] / forced vital capacity [FVC] < 0.7), and (4) ≥12% and ≥200 mL reversibility in post-BD FEV1. RESULTS: Among 2,165 individuals (1,015 COPD only, 395 with both asthma and COPD, and 755 asthma only), the overall prevalence of ACO was 20% (95% CI 18 to 23%). Patients with ACO had a mean age of 70 years (standard deviation 11 years), 60% were men, 73% were former smokers (rest were current smokers), and 66% were overweight or obese. Comorbid conditions were common in patients with ACO, including diabetes (53%), cardiovascular disease (36%), hypertension (30%), eczema (23%), and rhinitis (21%). The prevalence of ACO was higher in patients with a diagnosis of both asthma and COPD (32%) compared with a diagnosis of COPD only (20%, p

We aimed to compare clinical characteristics between Asian and Western chronic obstructive pulmonary disease (COPD) patients. This was a sub-analysis of an international, multicenter, prospective cohort study. Asian patients were enrolled in Singapore and South Korea. Western patients were enrolled in Spain, Poland, Ireland, the United Kingdom, and Malta. A total of 349 patients were analyzed. Among them, 110 (32%) patients were Asian and 239 (68%) Western. Male sex was more predominant in Asian than in Western (95% versus 63%, respectively; P, The study was designed and coordinated by the Respiratory Effectiveness Group (REG; www.effectivenessevaluation.org; Cambridge, UK) and delivered by Optimum Patient Care (OPC; www.optimumpatientcare.org).The following investigators participated in the study: Spain: Marc Miravitlles, Cristina Esquinas, Miriam Barrecheguren, Alexa Nunez, Hospital Universitari Vall d'Hebron, Barcelona. Bernardino Alcazar, Hospital de Alta Resolucion de Loja. Juan Luis Garcia-Rivero, Karina Hueso, Hospital Comarcal de Laredo, Cantabria. Miguel Roman-Rodriguez, Primary Health-care Center Son Pisa. IB-Salut. Palma de Mallorca. Poland: Pawel Sliwinsk Sliwinski, Katarzyna Iwan, Jacek Kolakowski, Institute of Tuberculosis and Lung Diseases, Warsaw. Korea: Chin Kook Rhee, Esther Ahn, St Mary's Hospital. Seoul. Singapore: Jessica Tan, Therese Lapperre, Karen Tan Li Leng, Nicole Chia, Ong Thun How, Syifa Binte Shamsuddin, Sherine Lim Shu Gim, Yap Chwee Bee, Soh Rui Ya, Singapore General Hospital. Augustine Tee, Jun Jie Yan, Samuel Hong, William Tan, Jessica Tan, Changi General Hospital. UK: Victoria Carter, Latife Hardaker, Andrew McLaughlin, Optimum Patient Care, Cambridge. Malta: Caroline Gouder, Mater Dei Hospital. Ireland: Richard W Costello, Royal College of Surgeons. Dublin. The study was funded by an unrestricted grant from Novartis AG.

Observational studies indicate that overutilization of inhaled corticosteroids (ICS) is common in patients with chronic obstructive pulmonary disease (COPD). Overprescription and the high risk of serious ICS-related adverse events make withdrawal of this treatment necessary in patients for whom the treatment-related risks outweigh the expected benefits. Elaboration of an optimal, universal, user-friendly algorithm for withdrawal of ICS therapy has been identified as an important clinical need. This article reviews the available evidence on the efficacy, risks, and indications of ICS in COPD, as well as the benefits of ICS treatment withdrawal in patients for whom its use is not recommended by current guidelines. After discussing proposed approaches to ICS withdrawal published by professional associations and individual authors, we present a new algorithm developed by consensus of an international group of experts in the field of COPD. This relatively simple algorithm is based on consideration and integrated assessment of the most relevant factors (markers) influencing decision-making, such a history of exacerbations, peripheral blood eosinophil count, presence of infection, and risk of community-acquired pneumonia.

We aimed to describe the differences and similarities between patients with chronic obstructive airway disease classified on the basis of classical diagnostic labels (asthma, chronic obstructive pulmonary disease (COPD), or asthma–COPD overlap (ACOS)) or according to the underlying inflammatory pattern (Th-2 signature, either Th-2-high or Th-2-low).We performed a cross-sectional study of patients aged ≥40 years and with a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio ≤0.7 with a previous diagnosis of asthma (non-smoking asthmatics (NSA)), COPD or ACOS, the latter including both smoking asthmatics (SA) and patients with eosinophilic COPD (COPD-e). Clinical, functional and inflammatory parameters (blood eosinophil count, IgE and exhaled nitric oxide fraction (FeNO)) were compared between groups. Th-2 signature was defined by a blood eosinophil count ≥300 cells·μL−1 and/or a sputum eosinophil count ≥3%.Overall, 292 patients were included in the study: 89 with COPD, 94 NSA and 109 with ACOS (44 SA and 65 with COPD-e). No differences in symptoms or exacerbation rate were found between the three groups. With regards the underlying inflammatory pattern, 94 patients (32.2%) were characterised as Th-2-high and 198 (67.8%) as Th-2-low. The Th-2 signature was found in 49% of NSA, 3.3% of patients with COPD, 30% of SA and 49.3% of patients with COPD-e. This classification yielded significant differences in demographic, functional and inflammatory characteristics.We conclude that a classification based upon the inflammatory profile, irrespective of the taxonomy, provides a more clear distinction of patients with chronic obstructive airway disease.

Altres ajuts: A. Schötzau performed data management of PROMISE for which he received financial compensation.Thermo Scientific Biomarkers (Hennigsdorf, Germany) provided all the reagents for copeptin measurements. Several composite markers have been proposed for risk assessment in chronic obstructive pulmonary disease (COPD). However, choice of parameters and score complexity restrict clinical applicability. Our aim was to provide and validate a simplified COPD risk index independent of lung function. The PROMISE study (n=530) was used to develop a novel prognostic index. Index performance was assessed regarding 2-year COPD-related mortality and all-cause mortality. External validity was tested in stable and exacerbated COPD patients in the ProCOLD, COCOMICS and COMIC cohorts (total n=2988). Using a mixed clinical and statistical approach, body mass index (B), severe acute exacerbations of COPD frequency (AE), modified Medical Research Council dyspnoea severity (D) and copeptin (C) were identified as the most suitable simplified marker combination. 0, 1 or 2 points were assigned to each parameter and totalled to B-AE-D or B-AE-D-C. It was observed that B-AE-D and B-AE-D-C were at least as good as BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity), ADO (age, dyspnoea, airflow obstruction) and DOSE (dyspnoea, obstruction, smoking, exacerbation) indices for predicting 2-year all-cause mortality (c-statistic: 0.74, 0.77, 0.69, 0.72 and 0.63, respectively; Hosmer-Lemeshow test all p>0.05). Both indices were COPD specific (c-statistic for predicting COPD-related 2-year mortality: 0.87 and 0.89, respectively). External validation of B-AE-D was performed in COCOMICS and COMIC (c-statistic for 1-year all-cause mortality: 0.68 and 0.74; c-statistic for 2-year all-cause mortality: 0.65 and 0.67; Hosmer-Lemeshow test all p>0.05). The B-AE-D index, plus copeptin if available, allows a simple and accurate assessment of COPD-related risk. The B-AE-D indices allow a simple and accurate assessment of COPD-related risk in the absence of lung function

Salud Santos,1,2 Alicia Marin,2,3 Joan Serra-Batlles,4 David de la Rosa,5 Ingrid Solanes,6 Xavier Pomares,7 Marta López-Sánchez,1 Mariana Muñoz-Esquerre,1 Marc Miravitlles2,81Pneumology Department, Hospital Universitari de Bellvitge, Universidad de Barcelona, Bellvitge Biomedical Research Institute (IDIBELL), Hospitaletde Llobregat, Barcelona, 2Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Madrid, 3Pneumology Department, Hospital Universitari Germans Trias i Pujol, Badalona, 4Pneumology Department, Hospital Universitari de Vic, 5Pneumology Unit, Hospital Plató, 6Pneumology Department, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau, Universidad Autónoma, Barcelona, 7Pneumology Department, Hospital Universitari Parc Taulí, Sabadell, 8Pneumology Department, Hospital Universitari Vall d’Hebron, Barcelona, SpainAbstract: Exacerbations of COPD represent an important medical and health care problem. Certain susceptible patients suffer recurrent exacerbations and as a consequence have a poorer prognosis. The effects of bronchial infection, either acute or chronic, and of the inflammation characteristic of the disease itself raise the question of the possible role of antibiotics and anti-inflammatory agents in modulating the course of the disease. However, clinical guidelines base their recommendations on clinical trials that usually exclude more severe patients and patients with more comorbidities, and thus often fail to reflect the reality of clinicians attending more severe patients. In order to discuss aspects of clinical practice of relevance to pulmonologists in the treatment and prevention of recurrent exacerbations in patients with severe COPD, a panel discussion was organized involving expert pulmonologists who devote most of their professional activity to day hospital care. This article summarizes the scientific evidence currently available and the debate generated in relation to the following aspects: bacterial and viral infections, chronic bronchial infection and its treatment with cyclic oral or inhaled antibiotics, inflammatory mechanisms and their treatment, and the role of computerized tomography as a diagnostic tool in patients with severe COPD and frequent exacerbations.Keywords: COPD exacerbation, treatment, bronchial infection, anti-inflammatory treatment, antibiotics

This epidemiological study aimed to describe and compare the characteristics and outcomes of COPD patients starting treatment with a long-acting anti-muscarinic (LAMA) or a combination of a long-acting beta-2 agonist (LABA)/LAMA in primary care in Catalonia (Spain) over a one-year period. Data were obtained from the Information System for the Development in Research in Primary Care (SIDIAP), a population database containing information of 5.8 million inhabitants (80% of the population of Catalonia). Patients initiating treatment with a LAMA or LABA/LAMA in 2015 were identified, and information about demographic and clinical characteristics was collected. Then, patients were matched 1:1 for age, sex, FEV1%, history of exacerbations, history of asthma and duration of treatment, and the outcomes between the two groups were compared. During 2015, 5729 individuals with COPD started treatment with a LAMA (69.8%) or LAMA/LABA (30.2%). There were no remarkable differences between groups except for a lower FEV1 and more previous hospital admissions in individuals on LABA/LAMA. The number of tests and referrals was low and decreased in both groups during follow-up. For the same severity status, the evolution was similar with a reduction in exacerbations in both groups. Treatment was changed during follow-up in up to 34.2% of patients in the LABA/LAMA and 26.3% in the LAMA group, but adherence was equally good for both. Our results suggest that initial therapy with LAMA in monotherapy may be adequate in a significant group of mild to moderate patients with COPD and a low risk of exacerbations managed in primary care., Chronic lung disease: Simple and effective treatment A single rather than combined long-acting inhaler therapy may be adequate for most patients when treating mild to moderate chronic lung disease. Marc Miravitlles at the Hospital Universitari Vall d’Hebron, Barcelona, Spain, and co-workers have shown that, in the initial stages of chronic obstructive pulmonary disease (COPD), treatment with an inhaled drug called a long-acting anti-muscarinic agent (LAMA) is as effective as an alternative inhaler that combines LAMA with another drug (LABA). The researchers identified 5729 COPD patients from Catalonia starting on inhaled treatment in 2015 and followed up on their progress after 1 year. Patients starting on LAMA monotherapy were matched closely in terms of demographics and previous medical history to those starting on LAMA/LABA treatment. The team found no remarkable differences in clinical characteristics between the groups over the year.

Pere Almagro,1 Sergi Yun,1 Ana Sangil,1 Mónica Rodríguez-Carballeira,1 Meritxell Marine,1 Pedro Landete,2 Juan José Soler-Cataluña,3 Joan B Soriano,4 Marc Miravitlles5 1Multimorbidity Patients Unit, Internal Medicine Department, Hospital Universitario Mutua de Terrassa, Universidad de Barcelona, Terrassa, Barcelona, 2Department of Pneumology, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Madrid, 3Department of Pneumology, Hospital Arnau de Vilanova-Lliria, Valencia, 4Instituto de Investigación Hospital Universitario de la Princesa (IISP), Universidad Autónoma de Madrid, Madrid, 5Department of Pneumology, Vall d’Hebron University Hospital, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain Abstract: Current recommendations to consider initiation of palliative care (PC) in COPD patients are often based on an expected poor prognosis. However, this approach is not evidence-based, and which and when COPD patients should start PC is controversial. We aimed to assess whether current suggested recommendations for initiating PC were sufficiently reliable. We identified prognostic variables proposed in the literature for initiating PC; then, we ascertained their relationship with 1-year mortality, and finally, we validated their utility in our cohort of 697 patients hospitalized for COPD exacerbation. From 24 articles of 499 screened, we selected 20 variables and retrieved 48 original articles in which we were able to calculate the relationship between each of them and 1-year mortality. The number of studies where 1-year mortality was detailed for these variables ranged from 9 for previous hospitalizations or FEV1 ≤30% to none for albumin ≤25mg/dL. The percentage of 1-year mortality in the literature for these variables ranged from 5% to 60%. In the validation cohort study, the prevalence of these proposed variables ranged from 8% to 64%; only 10 of the 18 variables analyzed in our cohort reached statistical significance with Cox regression analysis, and none overcame an area under the curve ≥0.7. We conclude that none of the suggested criteria for initiating PC based on an expected poor vital prognosis in COPD patients in the short or medium term offers sufficient reliability, and consequently, they should be avoided as exclusive criteria for considering PC or at least critically appraised. Keywords: COPD, palliative care, prognosis, mortality, survival, end of life

Miriam Barrecheguren,1,2 Mónica Monteagudo,3 Pere Simonet,3–5 Carl Llor,6 Esther Rodriguez,1,7 Jaume Ferrer,1,2,7 Cristina Esquinas,1 Marc Miravitlles1,2,7 1Department of Pneumology, Vall d´Hebron University Hospital, 2Medicine Department, Autonomous University of Barcelona (UAB), 3IDIAP Jordi Gol, 4Departament Ciències Clíniques, Universitat de Barcelona, Barcelona, 5Primary Care Centre Viladecans-2, Viladecans, 6Primary Care Centre Via Roma, Barcelona, 7CIBER of Respiratory Diseases (CIBERES), Spain Introduction: Alpha-1 antitrypsin deficiency (AATD) remains an underdiagnosed condition despite initiatives developed to increase awareness. The objective was to describe the current situation of the diagnosis of AATD in primary care (PC) in Catalonia, Spain.Methods: We performed a population-based study with data from the Information System for Development in Research in Primary Care, a population database that contains information of 5.8 million inhabitants (80% of the population of Catalonia). We collected the number of alpha-1 antitrypsin (AAT) determinations performed in the PC in two periods (2007–2008 and 2010–2011) and described the characteristics of the individuals tested.Results: A total of 12,409 AAT determinations were performed (5,559 in 2007–2008 and 6,850 in 2010–2011), with 10.7% of them in children. As a possible indication for AAT determination, 28.9% adults and 29.4% children had a previous diagnosis of a disease related to AATD; transaminase levels were above normal in 17.7% of children and 47.1% of adults. In total, 663 (5.3%) individuals had intermediate AATD (50–100mg/dL), 24 (0.2%) individuals had a severe deficiency (

Background: Some patients with COPD may share characteristics of asthma; this is the so-called asthma-COPD overlap syndrome (ACOS). There are no universally accepted criteria for ACOS, and most treatments for asthma and COPD have not been adequately tested in this population. Materials and methods: We performed a survey among pulmonology specialists in asthma and COPD aimed at collecting their opinions about ACOS and their attitudes in regard to some case scenarios of ACOS patients. The participants answered a structured questionnaire and attended a face-to-face meeting with the Metaplan methodology to discuss different aspects of ACOS. Results: A total of 26 pulmonologists with a mean age of 49.7 years participated in the survey (13 specialists in asthma and 13 in COPD). Among these, 84.6% recognized the existence of ACOS and stated that a mean of 12.6% of their patients might have this syndrome. In addition, 80.8% agreed that the diagnostic criteria for ACOS are not yet well defined. The most frequently mentioned characteristics of ACOS were a history of asthma (88.5%), significant smoking exposure (73.1%), and postbronchodilator forced expiratory volume in 1 second/forced vital capacity,0.7 (69.2%). The most accepted diagnostic criteria were eosinophilia in sputum (80.8%), a very positive bronchodilator test (69.2%), and a history of asthma before 40 years of age (65.4%). Up to 96.2% agreed that first-line treatment for ACOS was the combination of a long-acting beta(2)-agonist and inhaled steroid, with a long-acting antimuscarinic agent (triple therapy) for severe ACOS. Conclusion: Most Spanish specialists in asthma and COPD agree that ACOS exists, but the diagnostic criteria are not yet well defined. A previous history of asthma, smoking, and not fully reversible airflow limitation are considered the main characteristics of ACOS, with the most accepted first-line treatment being long-acting beta(2)-agonist/inhaled corticosteroids., The authors want to thank Montserrat Falgueras, Maria Fontanals, Laura Molina, Rosa Palomino, and Sonia Pisa (GOC Networking, Barcelona, Spain) for their help in the organization of the study, data entry and analysis of the questionnaires, and the facilitation of the Metaplan session. This study was funded by Chiesi Spain.