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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.

Resumen Objetivo El objetivo de este estudio es analizar los datos actuales del nivel de conocimiento de la poblacion sobre la EPOC y evaluar algunas actuaciones diagnosticas, como el uso de espirometria. Material y metodos Estudio epidemiologico, observacional y transversal mediante entrevista telefonica, con marcacion aleatoria de numeros de telefono fijos, realizado en noviembre del 2019, con una muestra representativa a nivel nacional en adultos mayores de 40 anos. Resultados De un total de 51.079 contactos telefonicos se obtuvo un total de 1.920 encuestados. La edad media era 61,9 anos, con 31,6% de hombres. El 19,4% de ellos eran fumadores actuales y un 13,4% referia tener alguna enfermedad respiratoria (5% referia una EPOC). El 27,9% tenia conocimiento espontaneo sobre la EPOC, lo que supone un aumento relativo respecto al 17% observado en el 2011. El canal de informacion mas frecuente eran los medios de comunicacion (35,5%), con importante presencia de redes sociales e Internet (25,7%). Un 18,1% tenia sintomas respiratorios cronicos. De ellos, un 59,3% solicito atencion medica y un 66,2% se realizo la espirometria. La espirometria era realizada con menor frecuencia en sujetos atendidos en Atencion Primaria respecto a Neumologia (51,9% vs. 79,1%; p Conclusiones El conocimiento de la EPOC es todavia escaso y son necesarias estrategias para aumentar la concienciacion y la importancia de evaluar los sintomas respiratorios y el mayor uso de la espirometria.

Background The value of the single-breath diffusing capacity of the lungs for carbon monoxide (D lco ) relates to outcomes for patients with COPD. However, little is known about the natural course of D lco over time, intersubject variability, and factors that may influence D lco progression. Research Question What is the natural course of D lco in patients with COPD over time, and which other factors, including sex differences, could influence this progression? Study Design and Methods We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including D lco, was monitored annually over 5 years. A random coefficients model was used to evaluate D lco changes over time. Results The mean (± SE) yearly decline in D lco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant D lco % slope annual decline (4.14%/y). At baseline, women with COPD had lower D lco values (11.37% ± 2.27%; P lco annual decline of 0.89% ± 0.42%/y (P = .039). Interpretation Patients with COPD have an accelerated decline in D lco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in D lco values in women, compared with men, suggests a differential impact of sex in gas exchange function. Trial Registry ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov

Although the chronic presence of microorganisms in the airways of patients with stable chronic obstructive pulmonary disease (COPD) confers a poor outcome, no recommendations have been established in disease management guidelines on how to diagnose and treat these cases. In order to guide professionals, the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR) has prepared a document which aims to answer questions on the clinical management of COPD patients in whom microorganisms are occasionally or habitually isolated. Since the available scientific evidence is too heterogeneous to use in the creation of a clinical practice guideline, we have drawn up a document based on existing scientific literature and clinical experience, addressing the definition of different clinical situations and their diagnosis and management. The text was drawn up by consensus and approved by a large group of respiratory medicine experts with extensive clinical and scientific experience in the field, and has been endorsed by the SEPAR Scientific Committee.

Chronic airflow obstruction affects a wide range of airway diseases, the most frequent of which are asthma, COPD, and bronchiectasis; they are clearly identifiable in their extremes, but quite frequently overlap in some of their pathophysiological and clinical characteristics. This has generated the description of new mixed or overlapping disease phenotypes with no clear biological grounds. In this special article, a group of experts provides their perspective and proposes approaching the treatment of chronic airway disease (CAD) through the identification of a series of therapeutic goals (TG) linked to treatable traits (TT) - understood as clinical, physiological, or biological characteristics that are quantifiable using biomarkers. This therapeutic approach needs validating in a clinical trial with the strategy of identification of TG and treatment according to TT for each patient independently of their prior diagnosis.

[Background]: The relationship between cancer and venous thromboembolic disease (VTD) are complex because the activated coagulation factors are not only involved in thrombosis but also in malignant processes, such as angiogenesis and metastasis., [Objective]: To compare phenotypes of extracellular vesicles (EVs), and levels of D-dimer, soluble P-selectin (sP-selectin) and antigenic tissue factor (TF) between unprovoked VTD patients, who did not develop cancer during one-year follow-up, and those with advanced stage of cancer but not associated with VTD., [Methods]: A prospective study in which we included 138 unprovoked VTD patients and 67 advanced cancer patients, who did not develop thrombosis. Levels of EVs of different cellular origin (platelet, endothelium and leukocyte), EVs positive for tissue factor (TF) and P-selectin glycoprotein ligand 1 were quantified by flow cytometry. D-dimer, soluble P-selectin (sP-selectin) and antigenic TF were determined by ELISA., [Results]: TF-positive EVs, D-dimer, and sP-selectin were markedly elevated in unprovoked VTD patients compared to cancer patients without association with thrombosis., [Conclusions]: Levels of TF-positive EVs, D-dimer and sP-selectin are able to discriminate between unprovoked VTD patients not related to cancer and cancer patients not associated with VTD. These results could lead to the application of EVs as biomarkers of both diseases., This work was supported by research grants from the Plan Nacional de Investigacion Cient ıfica, Desarrollo e Innovacion Tecnologica (Instituto de Salud Carlos III, Fondo de Investigacion Sanitaria [PI11/02308], Red RIC [RD12/0042/ 0029], Junta de Andalucıa [CVI-6654] and by the Fundacion Investigacion Hospital La Fe, Spain.

Introduction Despite the evidence provided by clinical trials, there are some uncertainties and controversies regarding the use of triple inhaled therapy. With the aim of evaluating clinical practice in specialized respiratory units, a Delphi consensus document was implemented on the use of single-inhaler fixed-dose triple therapies after 1 year of use in Spain. Methods A scientific committee of COPD experts defined a thematic index, guided a systematic literature review and helped design the Delphi questionnaire. This was sent to the other 45 COPD experts between April and June 2019. Agreement/disagreement on 58 statements was tested in two rounds using a Likert scale. Replies were classified as a consensus when ≥80% of the panelists agreed; a majority when a degree of agreement of ≥66% was reached; and divergence if agreement was Results After two rounds, 44.44% of the statements reached consensus, 14.81% reached majority and 40.74% were divergent. Panelists agreed that escalating from double bronchodilation should be phenotype-based and aim to prevent exacerbations but not for improving symptoms. The addition of an antimuscarinic to inhaled corticosteroids combinations achieves improvement in lung function, symptoms and exacerbation prevention. Main safety concerns included the increased risk of pneumonia as compared to bronchodilator therapies, with similar cardiovascular effects. There was no consensus agreement on patient type response based on blood eosinophil counts or obstruction severity. Conclusion The low degree of consensus among panelists may reflect the complexity of severe COPD management. The information provided here may be useful to clinicians implementing personalized medicine for COPD patients.

[Background] The global prevalence of chronic obstructive pulmonary disease (COPD) has increased markedly in recent decades. Given the scarcity of resources available to address global health challenges and respiratory medicine being relatively under-invested in, it is important to define research priorities for COPD globally. In this paper, we aim to identify a ranked set of COPD research priorities that need to be addressed in the next 10 years to substantially reduce the global impact of COPD., [Methods] We adapted the Child Health and Nutrition Research Initiative (CHNRI) methodology to identify global COPD research priorities., [Results] 62 experts contributed 230 research ideas, which were scored by 34 researchers according to six pre-defined criteria: answerability, effectiveness, feasibility, deliverability, burden reduction, and equity. The top-ranked research priority was the need for new effective strategies to support smoking cessation. Of the top 20 overall research priorities, six were focused on feasible and cost-effective pulmonary rehabilitation delivery and access, particularly in primary/community care and low-resource settings. Three of the top 10 overall priorities called for research on improved screening and accurate diagnostic methods for COPD in low-resource primary care settings. Further ideas that drew support involved a better understanding of risk factors for COPD, development of effective training programmes for health workers and physicians in low resource settings, and evaluation of novel interventions to encourage physical activity., [Conclusions] The experts agreed that the most pressing feasible research questions to address in the next decade for COPD reduction were on prevention, diagnosis and rehabilitation of COPD, especially in low resource settings. The largest gains should be expected in low- and middle-income countries (LMIC) settings, as the large majority of COPD deaths occur in those settings. Research priorities identified by this systematic international process should inform and motivate policymakers, funders, and researchers to support and conduct research to reduce the global burden of COPD., National Institute for Health Research (NIHR), Health Data Research UK.

Background: The study of hematic concentrations of alpha1 antitrypsin (AAT) is currently one step in the diagnosis of AAT deficiency. To try to clarify the relevance of the laboratory techniques, we carried out a systematic review of the literature. Methods: Studies evaluating the quantification of AAT in peripheral blood were searched in PubMed in July 2021. The selection criteria included (1) any type of study design that included a quantification of AAT in peripheral blood; (2) studies written in English or Spanish; (3) studies evaluating human beings; and (4) studies involving adults. Results: Out of 207 studies, the most frequently used techniques were nephelometry (43.9%), followed by ELISA (19.8%) and turbidimetry (13.5%). Altogether, 182 (87.9%) cases expressed their results in units of gram, while 16 (7.7%) articles expressed them in units of mole. Only 2.9% articles referred to the standard used, 43.5% articles indicated the commercial kit used, and 36.2% indicated the analyzer used. Conclusions: The technical aspects of these determinations are not always reported in the literature. Journals should be attentive to these technical requirements and ensure that they are included in the works in which AAT is determined in order to ensure a correct interpretation of the study findings.

Borja G Cosio,1,2 Hanaa Shafiek,1,3 Nuria Toledo-Pons,1,2 Amanda Iglesias,1,2 Margalida Barcelo,1 Cristina Represas-Represas,4 Lorena Comeche,5 Pablo Catalan,6 Alberto Fernandez-Villar,4 Jose Luis Lopez- Campos,7 Jose Echave-Sustaeta,5 Juan Jose Soler-Cataluna8 1Respiratory Medicine, Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Spain; 2CIBERES-IDISBa, Palma de Mallorca, Spain; 3Chest Diseases Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt; 4Respiratory Medicine, Hospital Alvaro Cunqueiro, Vigo, Spain; 5Respiratory Medicine, Hospital Universitario Quironsalud Madrid, Madrid, Spain; 6Respiratory Medicine, Hospital General de Castellón, Castellón, Spain; 7Respiratory Medicine, Hospital Virgen del Rocio-CIBERES, Sevilla, Spain; 8Respiratory medicine, Hospital Arnau de Vilanova-CIBERES, Valencia, SpainCorrespondence: Borja G CosioHospital Universitario Son Espases, Ctra de Valldemossa 79, Palma de Mallorca, 07010, SpainTel +34 871 20 6714Email borja.cosio@ssib.esPurpose: Exacerbations of COPD (ECOPD) are a frequent cause of hospitalization that seemed to ameliorate during the COVID outbreak. We aimed to evaluate the clinical characteristics of COPD-related hospital admissions and mortality in relation to the presence of COVID-19.Patients and Methods: We conducted a case–control study of patients admitted in four teaching hospitals throughout Spain between March 15 and April 30, 2020. Hospital admissions of respiratory cause with and without PCR-proven SARS-CoV-2 infection in patients with COPD were evaluated. Baseline and episode-related clinical characteristics were analyzed. Logistic regression analysis was performed to evaluate the risk for mortality.Results: During the study period, 2101 patients were admitted for respiratory worsening, 1200 (57.1%) with COVID-19. A total of 228 (10.8%) were admitted due to COPD worsening, of whom 52 (22.8%) tested positive for COVID-19. COPD patients with COVID-19, when compared to those without COVID-19, were more frequently males with better lung function (FEV1 postbronchodilator 71% vs 46% respectively, p< 0.001) and had higher mortality (44.9% vs 13.6% respectively, p< 0.001) despite similar age, comorbidities, total days of hospitalization and admission to intensive care unit. COVID-19 and eosinopenia were the strongest risk factors for mortality in the multivariate analysis in the overall COPD population. Inhaled corticosteroid use was not associated to mortality.Conclusion: Hospitalizations for ECOPD without COVID-19 were more frequent than COPD with COVID-19 during the first outbreak, but the latter were associated with higher mortality and low eosinophil counts that warrant further analysis.Keywords: COPD exacerbation, mortality, inhaled corticosteroids, hospitalization

Despite the wide application of adherence as a concept, the definition, evaluation and improvement of the adherence to treatment by patients with chronic obstructive pulmonary disease (COPD) still present some challenges. First, it is necessary to clearly define the concepts of treatment adherence, compliance and persistence. Second, it is critical to consider the various methods of evaluating and quantifying adherence when interpreting adherence studies. In addition, the advantages and disadvantages of the different ways of measuring treatment adherence should be taken into account. Another subject of some debate is the number of variables associated with COPD treatment adherence. Adherence is a complex concept that goes beyond the dosage or the use of inhalation devices, and a number of variables are involved in determining adherence, from the clinical aspects of the disease to the patient's confidence in the doctor's expertise and the level of social support experienced by the patient. Notably, despite these challenges, the importance of adherence has been well established by clinical trials and routine clinical practice. The available evidence consistently shows the substantial impact that a lack of adherence has on the control of the disease and its long-term prognosis. For these reasons, the correct evaluation of therapeutic adherence should be a key objective in clinical interviews of patients. In recent years, various initiatives for improving adherence have been explored. All these initiatives have been based on patient education. Therefore, health care professionals should be aware of the issues pertaining to adherence and take the opportunity to educate patients each time they contact the health care system.

[Background] Previous studies have shown that the arterial wall is a potential source of inflammatory markers in COPD. Here, we sought to compare the expression of acute phase reactants (APRs) in COPD patients and controls both at the local (pulmonary arteries and lung parenchyma) and systemic (peripheral blood leukocytes and plasma) compartments., [Methods] Consecutive patients undergoing elective surgery for suspected primary lung cancer were eligible for the study. Patients were categorized either as COPD or control group based on the spirometry results. Pulmonary arteries and lung parenchyma sections, peripheral blood leukocytes, and plasma samples were obtained from all participants. Gene expression levels of C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2, and SAA4) were evaluated in tissue samples and peripheral blood leukocytes by reverse transciption-PCR. Plasma CRP and SAA protein levels were measured by enzyme-linked immunosorbent assays. Proteins were evaluated in paraffin-embedded lung tissues by immunohistochemistry., [Results]A total of 40 patients with COPD and 62 controls were enrolled. We did not find significant differences in the gene expression between COPD and control group. Both CRP and SAA were overexpressed in the lung parenchyma compared with pulmonary arteries and peripheral blood leukocytes. The expression of SAA was significantly higher in the lung parenchyma than in the pulmonary artery (2-fold higher for SAA1 and SAA4, P=0.015 and P, [Conclusions] The expression of SAA in lung parenchyma is higher than in pulmonary artery and peripheral blood leukocytes. Notably, no associations were noted between lung expression of APRs and their circulating plasma levels, making the leakage of inflammatory proteins from the lung to the bloodstream unlikely. Based on these results, other potential sources of systemic inflammation in COPD (eg, the liver) need further scrutiny., The authors thank the HUVR-IBiS Biobank (Andalusian Public Health System Biobank and ISCIII-Red de Biobanco PT13/0010/0056) for the assessment and technical support provided. This study was financially supported by grants from Fundación de Neumología y Cirugía Torácica del Sur (Neumosur) No. 4/2012 and from the Instituto de Salud Carlos III, Ministerio de Economía (PI12/01576).

Introduction and objectives: Determinants of chronic obstructive pulmonary disease (COPD) in the early stages of its natural history are not well known. Improving our knowledge of these factors will help to design interventions that can modify prognosis. Study objectives are: a) to characterize a COPD population of young adults aged 35-50 years from a multidimensional point of view; b) to compare these patients with smokers with normal lung function: and c) to create a cohort of young adults aged 35-50 years (smokers or former smokers), with and without COPD, who will be followed in the future to improve understanding of the natural history of the disease. Participants and method: This is a case-control multicenter study aimed at establishing a well characterized cohort of young adults, smokers or former-smokers, with and without COPD, for subsequent follow-up. A total of 311 participants (101 cases and 210 controls) were selected from approximately 30 primary care settings and 12 hospitals in 8 Spanish regions. Subjects were smokers or former smokers (> 10 pack-years) aged 35-50 years. Diagnosis of COPD was based on a post-bronchodilator result of FEV1/FVC < 70%. The main study variables were: questionnaires on health, symptoms, exacerbations and daily physical activity, lung function tests, blood and sputum samples, and low-dose computed tomography. In the statistical analysis, COPD patient characteristics will be described and compared with control subjects using a logistic regression analysis. (C) 2018 SEPAR. Published by Elsevier Espana, S.L.U. All rights reserved.

Background: Inaccurate diagnosis in COPD is a current problem with relevant consequences in terms of inefficient health care, which has not been thoroughly studied in primary care medicine. The aim of the present study was to evaluate the degree of inaccurate diagnosis in Primary Care in Spain and study the determinants associated with it. Methods: The Community Assessment of COPD Health Care (COACH) study is a national, observational, randomized, non-interventional, national clinical audit aimed at evaluating clinical practice for patients with COPD in primary care medicine in Spain. For the present analysis, a correct diagnosis was evaluated based on previous exposure and airway obstruction with and without the presence of symptoms. The association of patient-level and center-level variables with inaccurate diagnosis was studied using multivariate multilevel binomial logistic regression models. Results: During the study 4,307 cases from 63 centers were audited. The rate of inaccurate diagnosis was 82.4% (inter-regional range from 76.8% to 90.2%). Patient-related interventions associated with inaccurate diagnosis were related to active smoking, lung function evaluation, and specific therapeutic interventions. Center-level variables related to the availability of certain complementary tests and different aspects of the resources available were also associated with an inaccurate diagnosis. Conclusions: The prevalence data for the inaccurate diagnosis of COPD in primary care medicine in Spain establishes a point of reference in the clinical management of COPD. The descriptors of the variables associated with this inaccurate diagnosis can be used to identify cases and centers in which inaccurate diagnosis is occurring considerably, thus allowing for improvement.

Jose Luis López-Campos,1,2 Laura Carrasco Hernández,1,2 Borja Ruiz-Duque,1 Rocio Reinoso-Arija,1 Candelaria Caballero-Eraso1,2 1Unidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/Universidad de Sevilla, Seville, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, SpainCorrespondence: Jose Luis López-CamposUnidad Médico-Quirúrgica de Enfermedades Respiratorias, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot, s/n, Seville, 41013, SpainTel +34 955013166Email lopezcampos@separ.esAbstract: Recent advances in inhaled drugs and a clearer definition of the disease have made the task of managing COPD more complex. Different proposals have been put forward which combine all the available treatments and the different clinical presentations in an effort to select the best therapeutic options for each clinical context. As COPD is a chronic progressive disease, the escalation of therapy has traditionally been considered the most natural way to tackle it. However, the notion of COPD as a constantly progressing disease has recently been challenged and, in specific areas, this points to the possibility of a de-escalation in treatment. In this context, the clinician requires simple, specific recommendations to guide these changes in treatment in their daily clinical practice. To accomplish this, the first step must be a correct evaluation and an accurate initial preliminary diagnosis of the patient’s condition. Thereafter, the first escalation in therapy must be introduced with caution as the disease progresses, since clinical trials are not designed with clinical decision-making in mind. During this escalation, three possibilities are open to change the current treatment for a different one within the same family, to increase non-pharmacological interventions or to increase the pharmacological therapies. Beyond that point, a patient with persistent symptoms represents a complex clinical scenario which requires a specialized approach, including the evaluation of different respiratory and non-respiratory comorbidities. Unfortunately, there are few de-escalation studies available, and these are mainly observational in nature. The debate on de-escalation in pharmacological treatment, therefore, involves two main discussion points: the withdrawal of bronchodilators and the withdrawal of inhaled steroids. Altogether, the scheme for modifying treatment must be more personalized than just adding molecules, and the therapeutic response and its conditioning factors should be evaluated at each step before proceeding further.Keywords: COPD, escalation of treatment, pharmacological therapies, precision medicine

Chronic obstructive pulmonary disease (COPD) patients constitute a heterogeneous population in terms of treatment response. Our objective was to identify possible predictive factors of response to treatment with single bronchodilation monotherapy in patients diagnosed with COPD. The Time-based Register and Analysis of COPD Endpoints (TRACE, clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients who have been attending annual visits since 2012. Patients who were kept on a single bronchodilator during the first year of follow-up were selected. The responders were defined according to all of the following variables: any improvement in morning post-dose forced expiratory volume in 1 s or deterioration &lt, 100 mL, no change or improvement in dyspnea score, and no occurrence of exacerbations. Significant and plausible variables were analyzed using a proportional hazard Cox regression for single bronchodilator responders. We analyzed 764 cases, of whom 128 (16.8%) were receiving monotherapy with one bronchodilator. Of these, 85 patients (66.4%) were responders. Factors affecting responder status were: female gender (hazard ratio (HR) 0.276, 95% confidence interval (CI) 0.089–0.858), dyslipidemia (HR 0.436, 95%CI 0.202–0.939), not performing regular exercise (HR 0.523, 95%CI 0.254–1.076), active smoking (HR 0.413, 95%CI 0.186–0.920), and treatment adherence (HR 2.527, 95%CI 1.271–5.027). The factors associated with a single bronchodilation response are mainly non-pharmacological interventions and comorbidities.

CHAIN Study Investigators., [Background] Control in COPD is a dynamic concept that can reflect changes in patients’ clinical status that may have prognostic implications, but there is no information about changes in control status and its long-term consequences., [Methods] We classified 798 patients with COPD from the CHAIN cohort as controlled/uncontrolled at baseline and over 5 years. We describe the changes in control status in patients over long-term follow-up and analyze the factors that were associated with longitudinal control patterns and related survival using the Cox hazard analysis., [Results] 134 patients (16.8%) were considered persistently controlled, 248 (31.1%) persistently uncontrolled and 416 (52.1%) changed control status during follow-up. The variables significantly associated with persistent control were not requiring triple therapy at baseline and having a better quality of life. Annual changes in outcomes (health status, psychological status, airflow limitation) did not differ in patients, regardless of clinical control status. All-cause mortality was lower in persistently controlled patients (5.5% versus 19.1%, p = 0.001). The hazard ratio for all-cause mortality was 2.274 (95% CI 1.394–3.708; p = 0.001). Regarding pharmacological treatment, triple inhaled therapy was the most common option in persistently uncontrolled patients (72.2%). Patients with persistent disease control more frequently used bronchodilators for monotherapy (53%) at recruitment, although by the end of the follow-up period, 20% had scaled up their treatment, with triple therapy being the most frequent therapeutic pattern., [Conclusions] The evaluation of COPD control status provides relevant prognostic information on survival. There is important variability in clinical control status and only a small proportion of the patients had persistently good control. Changes in the treatment pattern may be relevant in the longitudinal pattern of COPD clinical control. Further studies in other populations should validate our results., [Trial registration] Clinical Trials.gov: identifier NCT01122758., This study has been funded by AstraZeneca.

Objective There is controversy regarding the significance of radiological consolidation in the context of COPD exacerbation (eCOPD). While some studies into eCOPD exclude these cases, consolidation is a common feature of eCOPD admissions in real practice. This study aims to address the question of whether consolidation in eCOPD is a distinct clinical phenotype with implications for management decisions and outcomes. Patients and Methods The European COPD Audit was carried out in 384 hospitals from 13 European countries between 2010 and 2011 to analyze guideline adherence in eCOPD. In this analysis, admissions were split according to the presence or not of consolidation on the admission chest radiograph. Groups were compared in terms of clinical and epidemiological features, existing treatment, clinical care utilized and mortality. Results 14,111 cases were included comprising 2,714 (19.2%) with consolidation and 11,397 (80.8%) without. The risk of radiographic consolidation increased with age, female gender, cardiovascular diseases, having had two or more admissions in the previous year, and sputum color change. Previous treatment with inhaled steroids was not associated. Patients with radiographic consolidation were significantly more likely to receive antibiotics, oxygen and non-invasive ventilation during the admission and had a lower survival from admission to 90-day follow-up. Conclusions Patients admitted for COPD exacerbation who have radiological consolidation have a more severe illness course, are treated more intensively by clinicians and have a poorer prognosis. We recommend that these patients be considered a distinct subset in COPD exacerbation.

Objective: Although the importance of assessing inspiratory flow in the selection of treatments for chronic obstructive pulmonary disease (COPD) is understood, evaluation of this factor is not yet widespread or standardized. The objective of the present work was to evaluate the peak inspiratory flow (PIF) of patients with COPD and to explore the variables associated with a suboptimal PIF. Methods: An observational, cross-sectional study was carried out at specialized nursing consultations over a period of 6 months. We collected clinical data as well as data on symptoms, treatment adherence, and patient satisfaction with their inhalers via questionnaires. PIF was determined using the In-Check Dial G16&reg, device (Clement Clarke International, Ltd., Harlow, UK). In each case, the PIF was considered suboptimal when it was off-target for any of the prescribed inhalers. The association with suboptimal PIF was evaluated using multivariate logistic regression and the results were expressed as the odds ratio (OR) with 95% confidence interval (CI). Results: A total of 122 COPD patients were included in this study, of whom 34 (27.9%) had suboptimal PIF. A total of 229 inhalers were tested, of which 186 (81.2%) were dry powder devices. The multivariate analysis found an association between suboptimal PIF and age (OR = 1.072, 95% CI (1.019, 1.128), p = 0.007) and forced vital capacity (OR = 0.961, 95% CI (0.933, 0.989), p = 0.006). Conclusions: About a third of patients in complex specialized COPD care have suboptimal PIFs, which is related to age and forced vital capacity.

In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A–4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66–0.68) for GOLD 2015 and 0.65 (95% CI 0.63–0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system., GOLD 2019 staging system created 16 subgroups. GOLD 2015 and GOLD 2019 are not strong predictors of mortality, and do not have sufficient discriminatory power to be used as a tool for risk classification of mortality in patients with COPD. https://bit.ly/3idBuaN

Jaco Voorham,1,2 Simonetta Baldi,3 Luigi Santoro,4 Marjan Kerkhof,1,5 Marco Contoli,6 Leonardo M Fabbri,6 Huib AM Kerstjens,7 Jose Luis López-Campos,8 Nicolas Roche,9 Dave Singh,10 Claus F Vogelmeier,11 David B Price1,12 1Observational & Pragmatic Research Institute Pte Ltd, Singapore, Singapore; 2Data to Insights Research Solutions, Lisbon, Portugal; 3Department of Global Clinical Development, Chiesi SAS, Bois Colombes Cedex, France; 4Department of Global Clinical Development, Chiesi Farmaceutici S.p.A, Parma, Italy; 5Mescio Research, Blauwestad, The Netherlands; 6Section of Respiratory Medicine, Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, Italy; 7Department of Pulmonary Diseases, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands; 8Respiratory Diseases Unit, University Hospital Virgen Del Rocío, Seville, Spain; 9Service de Pneumologie, Hôpital Cochin, APHP, Centre-Université de Paris, Paris, France; 10University of Manchester, Manchester University NHS Foundation Trust, Manchester, UK; 11Department of Internal Medicine, Pulmonary and Critical Care Medicine, University of Marburg, Member of the German Centre for Lung Research (DZL), Marburg, Germany; 12Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B PriceAcademic Primary Care, Division of Applied Health Sciences University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen AB25 2ZD 198785, UKTel +65 6962 3627Email dprice@opri.sgPurpose: This study aimed to evaluate the non-inferiority of initiating extrafine beclometasone dipropionate/formoterol fumarate (BDP/FF) versus double bronchodilation (long-acting beta-agonists [LABA]/long-acting muscarinic antagonists [LAMA]) among patients with a history of chronic obstructive pulmonary disease (COPD) exacerbations.Patients and Methods: A historical cohort study was conducted using data from the UK’s Optimum Patient Care Research Database. Patients with COPD ≥ 40 years at diagnosis were included if they initiated extrafine BDP/FF or any LABA/LAMA double therapy as a step-up from no maintenance therapy or monotherapy with inhaled corticosteroids (ICS), LAMA, or LABA and a history of ≥ 2 moderate/severe exacerbations in the previous two years. The primary outcome was exacerbation rate from therapy initiation until a relevant therapy change or end of follow-up. Secondary outcomes included rate of acute respiratory events, acute oral corticosteroids (OCS) courses, and antibiotic prescriptions with lower respiratory indication, modified Medical Research Council score (mMRC) ≥ 2, and time to first pneumonia diagnosis. The non-inferiority boundary was set at a relative difference of 15% on the ratio scale. Five potential treatment effect modifiers were investigated.Results: A total of 1735 patients initiated extrafine BDP/FF and 2450 patients initiated LABA/LAMA. The mean age was 70 years, 51% were male, 41% current smokers, and 85% had FEV1 < 80% predicted. Extrafine BDP/FF showed non-inferiority to LABA/LAMA for rate of exacerbations (incidence rate ratio [IRR] = 1.01 [95% CI 0.94– 1.09]), acute respiratory events (IRR = 0.98 [0.92– 1.04]), acute OCS courses (IRR = 1.01 [0.91– 1.11]), and antibiotic prescriptions (IRR = 0.99 [0.90– 1.09]), but not for mMRC (OR = 0.93 [0.69– 1.27]) or risk of pneumonia (HR = 0.50 [0.14– 1.73]). None of the a priori defined effect modifier candidates affected the comparative effectiveness.Conclusion: This study found that stepping up to extrafine BDP/FF from no maintenance or monotherapy was not inferior to stepping up to double bronchodilation therapy in patients with a history of exacerbations.Keywords: real-world, electronic health records, observational, comparative effectiveness, heterogeneity, chronic obstructive pulmonary disease

The phenotypic characteristics of chronic obstructive pulmonary disease (COPD) in individuals younger than 50 years of age (early COPD) are not well defined. This prospective, multi-centre, case-control study sought to describe these characteristics and compare them with those of smokers (>= 10 pack-years) of similar age with normal spirometry (controls). We studied 92 cases (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), In part, by CIBERES, SEPAR, FIS (CP16/00039, PI17/00369, PI18/01008) and an unrestricted grant from Boehringer-Ingelheim. Funding information for this article has been deposited with the Crossref Funder Registry.

In 2019, the Global Initiative for Chronic Obstructive Lung Disease (GOLD) proposed a clinical grading system for patients with chronic obstructive pulmonary disease (COPD) with 4 categories (A-D) based on symptoms and exacerbation history.As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare mortality prediction of 2015 and 2019 COPD GOLD staging systems.We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems and we compared the predictive ability for 5-year mortality of both classifications.17 139 patients with COPD were enrolled in 22 cohorts of 11 countries; 8823 of them had complete data and were analyzed. Mean age was 63.9 years(SD 9.8); 5 552(62.9%) were male and mean FEV1 was 54.8%(SD 22.3). Compared with 2015, the GOLD 2019 classified the patients in milder degrees of COPD:groups C and D decreased from 13.6% to 5.8% and 40% to 17.8% respectively (p

This article belongs to the Special Issue Current Perspectives in Management of Chronic Obstructive Pulmonary Disease., Despite recent notable innovations in the management of chronic obstructive pulmonary disease (COPD), no major advances in patient-centered medicine have been achieved. Current guidelines base their proposals on the average results from clinical trials, leading to what could be termed ‘means-based’ medical practice. However, the therapeutic response is variable at the patient level. Additionally, the variability of the clinical presentation interacts with comorbidities to form a complex clinical scenario for clinicians to deal with. Consequently, no consensus has been reached over a practical approach for combining comorbidities and disease presentation markers in the therapeutic algorithm. In this context, from the patients’ first visit, the clinician faces four major dilemmas: (1) establishing the correct diagnosis of COPD as opposed to other airway diseases, such as bronchial asthma; (2) deciding on the initial therapeutic approach based on the clinical characteristics of each case; (3) setting up a study strategy for non-responding patients; (4) pursuing a follow-up strategy with two well-defined periods according to whether close or long-term follow-up is required. Here, we will address these major dilemmas in the search for a patient-centered approach to COPD management and suggest how to combine them all in a single easy-to-use strategy., This manuscript has received a grant from Instituto de Salud Carlos III, FIS project PI18/00682 included in the Acción Estratégica en Salud, Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2013–2016, Instituto de Salud Carlos III, Fondos FEDER.

This article belongs to the Special Issue Rare Respiratory Diseases: A Personal and a Public Health Problem., Ever since the first studies, restoring proteinase imbalance in the lung has traditionally been considered as the main goal of alpha1 antitrypsin (AAT) replacement therapy. This strategy was therefore based on ensuring biochemical efficacy, identifying a protection threshold, and evaluating different dosage regimens. Subsequently, the publication of the results of the main clinical trials showing a decrease in the progression of pulmonary emphysema has led to a debate over a possible change in the main objective of treatment, from biochemical efficacy to clinical efficacy in terms of lung densitometry deterioration prevention. This new paradigm has produced a series controversies and unanswered questions which face clinicians managing AAT deficiency. In this review, the concepts that led to the approval of AAT replacement therapy are reviewed and discussed under a new prism of achieving clinical efficacy, with the reduction of lung deterioration as the main objective. Here, we propose the use of current knowledge and clinical experience to face existing challenges in different clinical scenarios, in order to help clinicians in decision-making, increase interest in the disease, and stimulate research in this field.

Chronic obstructive pulmonary disease (COPD) is an entity with a heterogeneous presentation. For this reason, attempts have been made to characterize different phenotypes and endotypes to enable a more individualized approach. The aim of the Biomarkers in COPD (BIOMEPOC) project is to identify useful biomarkers in blood to improve the characterization of patients. Clinical data and blood samples from a group of patients and healthy controls will be analyzed. The project will consist of an exploration phase and a validation phase. Analytical parameters in blood will be determined using standard techniques and certain 'omics' (transcriptomics, proteomics, and metabolomics). The former will be hypothesis-driven, whereas the latter will be exploratory. Finally, a multilevel analysis will be conducted. Currently, 269 patients and 83 controls have been recruited, and sample processing is beginning. Our hope is to use the results to identify new biomarkers that, alone or combined, will allow a better characterization of patients.

Introduction: The objective of this study was to analyze the clinical characteristics of COPD patients attending general respiratory clinics, adherence to clinical guidelines, classification accuracy, and therapeutic management. Method: Multicenter, cross-sectional study, with the primary objective of describing the number, intensity, and variability of symptoms in COPD patients. Data were collected in 2015 by 300 pulmonologists who evaluated a total of 3,010 patients, of which 2,669 (88.6%) were eligible for analysis. Results: A total of 22% were active smokers, notably 21% and 17% of GOLD groups C and D, and 17% and 19% of exacerbators in the GesEPOC classification; 62.3% had associated comorbidities. The diagnostic process was characterized by limited use of tests such as diffusion capacity or lung volumes, even in the more severe GOLD groups or the GesEPOC exacerbator phenotypes. The use of multidimensional scales, such as BODE (12%), and specific rehabilitation protocols was also rare. Treatment was based on different combinations of bronchodilators and inhaled corticosteroids. Methylxanthines were used in very few patients (7%). Conclusions: A large proportion of COPD patients seen in respiratory clinics have non-complex disease and pulmonology tests are rarely performed. Our study confirms a slight change in treatments and the frequent association with comorbidities that can modify the clinical presentation of the patient.

Background Despite the existing evidence-based smoking cessation interventions, chances of achieving that goal in real life are still low among patients with COPD. We sought to evaluate the clinical consequences of changes in smoking habits in a large cohort of patients with COPD. Methods CHAIN (COPD History Assessment in Spain) is a Spanish multicenter study carried out at pulmonary clinics including active and former smokers with COPD. Smoking status was certified by clinical history and co-oximetry. Clinical presentation and disease impact were recorded via validated questionnaires, including the London Chest Activity of Daily Living (LCADL) and the Hospital Anxiety and Depression Scale (HADS). No specific smoking cessation intervention was carried out. Factors associated with and clinical consequences of smoking cessation were analyzed by multivariate regression and decision tree analyses. Results One thousand and eighty-one patients with COPD were included (male, 80.8%; age, 65.2 [SD 8.9] years; FEV1, 60.2 [20.5]%). During the 2-year follow-up time (visit 2, 906 patients; visit 3, 791 patients), the majority of patients maintained the same smoking habit. Decision tree analysis detected chronic expectoration as the most relevant variable to identify persistent quitters in the future, followed by an LCADL questionnaire (cutoff 9 points). Total anxiety HADS score was the most relevant clinical impact associated with giving up tobacco, followed by the LCADL questionnaire with a cutoff value of 10 points. Conclusions In this real-life prospective COPD cohort with no specific antismoking intervention, the majority of patients did not change their smoking status. Our study also identifies baseline expectoration, anxiety, and dyspnea with daily activities as the major determinants of smoking status in COPD. Trial Registry ClinicalTrials.gov; No. NCT01122758; URL: www.clinicaltrials.gov.

The implementation of potential new step-up or step-down treatment recommendations in response to current guidelines is one of the main challenges currently faced in actual daily practice settings. In the present narrative review, we aim to discuss the relevance of these step-up and step-down proposals at the patient level in daily clinical practice. In particular, we aim to review the challenges associated with inhaled maintenance therapy for chronic obstructive pulmonary disease (COPD) in four clinical scenarios. First, we discuss the step up from single to double bronchodilation, including current controversies regarding the addition of a second bronchodilator versus initial treatment with two bronchodilators. Second, we discuss the step up from double bronchodilation to triple therapy while challenging current indications for inhaled steroid therapy and discussing triple therapy designs. Third, we discuss the step down from triple therapy to double bronchodilation while evaluating the effect of this downshift in risk categories on the patient according to the new classifications. Finally, we discuss the step down from double to single bronchodilation, with a special focus on safety. We believe this review will help to highlight the most relevant discussion points regarding the treatment of COPD in a manner that will stimulate and guide related clinical research.

The cardiovascular effects of biomass smoke exposure in patients with chronic obstructive pulmonary disease are not well characterized, and few studies have assessed the possible differences between patients with disease caused by biomass smoke and tobacco. The aim of this study was to search for differences in cardiovascular variables between both types of the disease. Twenty subjects (15 men, 5 women) with chronic obstructive pulmonary disease caused by tobacco were matched one to one for sex, age, and forced expiratory volume in 1 s to 20 patients with biomass-related disease. Echocardiography and carotid ultrasound studies were performed. Flow-mediated endothelium-dependent vasodilatation and endothelium-independent vasodilatation were also measured. There were no significant differences between groups in any of the echocardiographic variables, nor in the intima–media carotid thickness, the number of carotid plaques, or the percentage of endothelium-dependent or endothelium-independent vasodilation. A high percentage of patients in both groups showed an abnormal flow-mediated endothelium-dependent vasodilatation pattern. The study does not support the hypothesis of a different cardiovascular effect of biomass or tobacco smoke exposure in patients with chronic obstructive pulmonary disease. Cardiovascular comorbidity should be assessed in patients with biomass-associated disease, similarly to subjects with tobacco-related disease.

Javier Mohigefer,1 Carmen Calero-Acuña,2,3 Eduardo Marquez-Martin,2 Francisco Ortega-Ruiz,2,3 Jose Luis Lopez-Campos2,3 1Faculty of Medicine, 2Medical-Surgical Unit of Respiratory Diseases, Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Seville, 3CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain Objective: Several previous studies have shown a suboptimal level of understanding of COPD among different population groups. Students in their final year of Medicine constitute a population that has yet to be explored. The evaluation of their understanding provides an opportunity to establish strategies to improve teaching processes. The objective of the present study is to determine the current level of understanding of COPD among said population.Methods: A cross-sectional observational study was done using digital surveys given to medical students in their final year at the Universidad de Sevilla. Those surveyed were asked about demographic data, smoking habits as well as the clinical manifestation, diagnosis and treatment of COPD.Results: Of the 338 students contacted, responses were collected from 211 of them (62.4%). Only 25.2% had an accurate idea about the concept of the disease. The study found that 24.0% of students were familiar with the three main symptoms of COPD. Tobacco use was not considered a main risk factor for COPD by 1.5% of students. Of those surveyed, 22.8% did not know how to spirometrically diagnose COPD. Inhaled corticosteroids were believed to be part of the main treatment for this disease among 51.0% of the students. Results show that 36.4% of respondents believed that home oxygen therapy does not help COPD patients live longer. Only 15.0% considered the Body-mass index, airflow Obstruction, Dyspnea, and Exercise (BODE) index to be an important parameter for measuring the severity of COPD. Giving up smoking was not believed to prevent worsening COPD among 3.4% of students surveyed. Almost half of students (47.1%) did not recommend that those suffering from COPD undertake exercise.Conclusion: The moderate level of understanding among the population of medical students in their final year shows some strengths and some shortcomings. Teaching intervention is required to reinforce solid knowledge among this population. Keywords: COPD, knowledge, surveys and questionnaires, students, medical

Jose Luis Lopez-Campos,1,2 Carmen Calero-Acuña,1,2 Eduardo Márquez-Martín,1 Esther Quintana Gallego,1,2 Laura Carrasco-Hernández,1 Maria Abad Arranz,1 Francisco Ortega Ruiz1,2 1Virgen del Rocio University Hospital, Biomedicine Institute of Seville (IBiS), Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Sevilla, Spain; 2Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain Objective: The combination of a long-acting muscarinic antagonist (LAMA) and a long-acting β2-agonist (LABA) in a single inhaler is a viable treatment option for patients with chronic obstructive pulmonary disease (COPD). Here, we systematically review the current knowledge on double bronchodilation for the treatment of COPD, with a specific focus on its efficacy versus placebo and/or monotherapy bronchodilation. Methods: A systematic review of clinical trials investigating LABA/LAMA combination therapies was conducted. Articles were retrieved from PubMed, Embase, and Scopus on June 26, 2016. We specifically selected clinical trials with a randomized controlled or crossover design published in any scientific journal showing the following characteristics: 1) comparison of different LABA/LAMA combinations in a single inhaler for patients with COPD, 2) dose approved in Europe, and 3) focus on efficacy (versus placebo and/or bronchodilator monotherapy) in terms of lung function, respiratory symptoms, or exacerbations. Results: We analyzed 26 clinical trials conducted on 24,338 patients. All LABA/LAMA combinations were consistently able to improve lung function compared with both placebo and bronchodilator monotherapy. Improvements in symptoms were also consistent versus placebo, showing some lack of correlation for some clinical end points and combinations versus monotherapy bronchodilation. Albeit being an exploratory end point, exacerbations showed an improvement with LABA/LAMA combinations over placebo in some trials; however, scarce information was available in comparison with bronchodilator monotherapy in most studies. Conclusion: Our data show consistent improvements for LABA/LAMA combinations, albeit with some variability (depending on the clinical end point, the specific combination, and the comparison group). Clinicians should be aware that these are average differences. All treatments should be tailored at the individual level to optimize clinical outcomes. Keywords: COPD, bronchodilators, efficacy, systematic review

Background: There is partial evidence that COPD is expressed differently in women than in men, namely on symptoms, pulmonary function, exacerbations, comorbidities or prognosis. There is a need to improve the characterization of COPD in females. Methods: We obtained and pooled data of 17 139 patients from 22 COPD cohorts and analysed the clinical differences by sex, establishing the relationship between these characteristics in women and the prognosis and severity of the disease. Comparisons were established with standard statistics and survival analysis, including crude and multivariate Cox-regression analysis. Results: Overall, 5355 (31.2%) women were compared with men with COPD. Women were younger, had lower pack-years, greater FEV1%, lower BMI and a greater number of exacerbations (all p < 0.05). On symptoms, women reported more dyspnea, equal cough but less expectoration (p < 0.001). There were no differences in the BODE index score in women (2.4) versus men (2.4) (p = 0.5), but the distribution of all BODE components was highly variable by sex within different thresholds of BODE. On prognosis, 5-year survival was higher in COPD females (86.9%) than in males (76.3%), p < 0.001, in all patients and within each of the specific comorbidities that we assessed. The crude and adjusted RR and 95% C.I. for death in males was 1.82 (1.69–1.96) and 1.73 (1.50–2.00), respectively. Conclusions: COPD in women has some characteristic traits expressed differently than compared to men, mainly with more dyspnea and COPD exacerbations and less phlegm, among others, although long-term survival appears better in female COPD patients.

Alpha-1 antitrypsin deficiency (AATD) is a rare and underdiagnosed disease that is associated with the development of liver disease in adults and children and pulmonary emphysema in adults. Several studies have shown that there is limited knowledge about the disease and its diagnosis among health care providers, and there is an important inequity in the access to specialized care and appropriate treatment across Europe. The European Commision and the European Respiratory Society (ERS) recommend that the care of patients with AATD must be organized in reference centers at national or regional levels. These reference centers must provide optimal clinical care in terms of adequate diagnostic techniques, such as phenotyping and genotyping, and ensure access to treatment according to guidelines. Reference centers should also provide continuous medical education for health care professionals, genetic counseling, collaboration with patient associations and promote collaborative research and clinical trials with new and existing treatments for the disease. These centers must have a registry of their activity and collaborate with large, international, multicenter registries, such as the European Alpha-1 antitrypsin Deficiency Research Collaboration (EARCO) international registry, which is endorsed by the ERS, and aims to recruit up to 3,000 patients over a period of three years and prospectively follow them to better understand the natural history of the disease and the impact of different treatments on outcomes in a real life setting. International collaboration and standardized collection of high-quality prospective data will provide new insights into the clinical manifestations and prognosis of AATD., Alexa Núñez is the recipient of a Rio Hortega contract in the 2019 Strategic Action Health Call from the Instituto de Salud Carlos III for the years 2020-2022. Miriam Barrecheguren is the recipient of a Rio Hortega contract in the 2017 Strategic Action Health Call from the Instituto de Salud Carlos III for the years 2018-2019. The Spanish centers for Alpha-1 antitrypsin Deficiency are funded by unrestricted research grants from Grifols.

[EN]: [Introduction]: The objective of this analysis was the evaluation of a new national circuit used for diagnosing alpha1 antitrypsin deficiency (AATD) based on multiplex technology using online registration and mail posted samples from dried blood spots (DBS) and buccal swabs. [Methods]: This is an observational, ongoing study conducted in Spain since March 2018. Samples are coded on a web platform and sent by postal mail to the central laboratory. Allele-specific genotyping for the 14 most common mutations was done with the Luminex 200 Instrument System. Gene sequencing was done if none of the mutations were found and the AAT serum level was, [ES]: [Introducción]: El objetivo de este análisis fue la evaluación de un nuevo circuito nacional utilizado para diagnosticar la deficiencia de alfa-1 antitripsina (DAAT) basado en tecnología multiplex con muestras de manchas de sangre seca (DBS, por sus siglas en inglés) y frotis bucales enviados por correo postal tras un registro previo en línea. [Métodos]: Este es un estudio observacional en curso que se está llevando a cabo en España desde marzo de 2018. Las muestras se codifican en una plataforma web y se envían por correo postal al laboratorio central. El genotipado de un alelo específico buscando las 14 mutaciones más comunes se realizó con el sistema Luminex® 200. Se realizó secuenciación génica si no se encontraba ninguna de las mutaciones y el nivel sérico de AAT era < 60 mg/dl, o por solicitud del médico responsable. [Resultados]: En el momento del presente informe se habían procesado 5.803 (92,9%) muestras, 4.984 (85,9%) de frotis bucal y 819 (14,1%) de DBS. La prevalencia de las combinaciones frecuentes de alelos fue: MS 19,0%, MZ 14,4%, SS 2,9%, SZ 3,7% y ZZ 1,4%. Globalmente, los portadores de Z representaron el 20,0% y los portadores de S el 26,6% de esta población, observándose diferencias entre las regiones. Se identificaron 209 (3,6%) portadores de alelos raros, 12 (0,2%) portadores de alelos nulos y se describieron 14 (0,3%) nuevas mutaciones. Otras enfermedades respiratorias que no eran EPOC, incluyendo el asma mal controlado o las bronquiectasias, también presentaron mutaciones DAAT. [Conclusiones]: La disponibilidad de un sistema de diagnóstico con registro web basado en el análisis simultáneo de 14 variantes genéticas de frotis bucales o DBS enviados por correo postal ha demostrado ser útil, y el sistema puede mejorar el diagnóstico temprano de DAAT.

We systematically reviewed the current knowledge on fixed-dose triple therapies for the treatment of chronic obstructive pulmonary disease (COPD), with a specific focus on its efficacy versus single bronchodilation, double fixed dose combinations, and open triple therapies. Articles were retrieved from PubMed, Embase, and Scopus up to 3 August 2018. We selected articles with randomized controlled or crossover design conducted in patients with COPD and published as full-length articles or scientific letters, evaluating triple therapy combinations in a single or different inhaler, and with efficacy data versus monocomponents, double combinations, or open triple therapies. Our systematic search reported 108 articles, of which 24 trials were finally selected for the analysis. A total of 7 studies with fixed dose triple therapy combinations, and 17 studies with open triple therapies combinations. Triple therapy showed improvements in lung function [trough forced expiratory volume (FEV1) ranging from not significant (NS) to 147 ml], health status using the St. George’s Respiratory Questionnaire [(SGRQ) from NS to 8.8 points], and exacerbations [risk ratio (RR) from NS to 0.59 for all exacerbations] versus single or double therapies with a variability in the response, depending the specific combination, and the comparison group. The proportion of adverse effects was similar between study groups, the exception being the increase in pneumonia for some inhaled corticosteroid (ICS) containing groups. The reviews of this paper are available via the supplementary material section.