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Sara Cazorla-Rivero,1,2 Glorian Mura-Escorche,1,2 Francisca Gonzalvo-Hernández,3 Delia Mayato,1 Elizabeth Córdoba-Lanús,1,2,4,* Ciro Casanova1– 3,* 1Research Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; 2University of La Laguna, San Cristóbal de La Laguna, Tenerife, Spain; 3Pulmonary Department, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain; 4Instituto de Enfermedades Tropicales y Salud Pública de Canarias (IUETSPC), San Cristóbal de La Laguna, Tenerife, Spain*These authors contributed equally to this workCorrespondence: Elizabeth Córdoba-LanúsUniversity of La Laguna- IUETSPC, Av. Astrofísico Francisco Sanchez. Campus Anchieta, Apartado 456, San Cristobal de la Laguna CP 38200, Tenerife, SpainEmail acordoba@ull.edu.esBackground: COPD is characterized by a persistent inflammatory response, especially against cigarette smoke. COPD patients may develop varying degrees of emphysematous destruction of the lungs. A pathophysiological role for miRNAs in COPD has been suggested in several studies. We examined changes in microRNAs expression profile during 10 years follow-up in relation to COPD progression.Methods: Clinical and lung function parameters were registered from every subject included in the study. miRNAs expression was determined in 14 serum samples from 7 patients in two moments (4 smokers with COPD (BODE cohort) and 3 smokers without COPD) by next generation sequencing (NGS) at baseline and after 10 years follow-up. A validation study was performed by qPCR in 20 patients with COPD (13 emphysema-diagnosed by CTscan) and 10 smoker controls at baseline and after 10 years follow-up. hsa-miRNA-20a-5p and hsa-let-7d-5p were used as endogenous controls.Results: A total of 198 miRNAs (≥ 10TPM) were identified by NGS. Between these, hsa-miR-1246 was found significantly downregulated in COPD patients after 10 years when compared to baseline (p< 0.0001, FDR=0.05). Seventy-five percent of these patients had an emphysema diagnose. In the validation analysis, when analyzed longitudinally, hsa-miR-1246 was significantly downregulated in COPD patients with emphysema after 10 years (p= 0.019). However, no association was found between the expression of miR-1246 and any other lung function parameters (FEV1, PaO2, DLCO, IC/TLC) within the follow-up period. GO and KEGG enrichment analysis revealed miR-1246 to be associated with target genes in several pathways involved in COPD/emphysema development.Conclusion: Our findings suggest that hsa-miR-1246 may act as a biomarker of emphysema in COPD. Functional analysis is guaranteed to elucidate its role in COPD.Keywords: COPD progression, miRNAs, emphysema

Luis Pérez de Llano,1 Marc Miravitlles,2 Rafael Golpe,1 Francisco Javier Alvarez-Gutiérrez,3 Carolina Cisneros,4 Carlos Almonacid,5 Eva Martinez-Moragon,6 Francisco-Javier Gonzalez-Barcala,7 David Ramos-Barbón,8 Vicente Plaza,8 Jose Luis Lopez-Campos,3 Juan Pablo de-Torres,9 Ciro Casanova,10 Juan Luis Garcia Rivero,11 Juan Rodriguez Hermosa,12 Myriam Calle Rubio,12 Juan Jose Soler-Cataluña,13 Borja G Cosio14 1Pneumology Service, University Hospital Lucus Augusti, Lugo, EOXI Cervo, Lugo, Monforte, Spain; 2Pneumology Service, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBERES, Barcelona, Spain; 3Pneumology Service, Hospital Universitario Virgen del Rocio, Seville, Spain; 4Pneumology Service, La Princesa University Hospital, Madrid, Research Institute La Princesa IIP, Madrid, Spain; 5Pneumology Service, Ramón y Cajal Hospital (Ramon y Cajal Health Research Institute, IRYCIS), Madrid, Spain; 6Pneumology Service, Hospital Universitario Dr Peset, Valencia, Spain; 7Faculty of Medicine at the University of Santiago de Compostela, Pneumology Service of the University Clinical Hospital of Santiago de Compostela, CIBERES, Santiago de Compostela, Spain; 8Pneumology Service, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 9Division of Respirology and Sleep Medicine, Queen’s University, Canada, ON, Canada; 10Pneumology Service, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz De Tenerife, Spain; 11Pneumology Service, Hospital de Laredo, Laredo, Spain; 12Pneumology Service and Faculty of Medicine, Hospital Clínico San Carlos, Complutense University of Madrid, Madrid, Spain; 13Pneumology Service, Hospital Arnau de Vilanova, Valencia, Spain; 14Pneumology Service, Son Espases University Hospital, IdISBa, CIBERES, Clínica Quirón-Rotger, Palma, SpainCorrespondence: Borja G CosioPneumology Service, Hospital Universitario Son Espases, IdISBa, CIBERES, Clínica Quirón-Rotger, Ctra. de Valldemossa 79, Palma de Mallorca 07010, SpainTel +34 871 206714 Ext 76714Fax +34 871 909724Email borja.cosio@ssib.esAbstract: 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.Keywords: airflow obstruction, biomarker, personalised medicine, COPD asthma overlap

Carlos Cabrera,1 Ciro Casanova,2 Yolanda Martín,3 Virginia Mirabal,3 María del Carmen Sánchez,4 Felisa Álvarez,5 Gabriel Juliá,1 Pedro Cabrera-Navarro,1 Miguel Ángel García-Bello,6 José María Marín,7 Juan Pablo de-Torres,8 Miguel Divo,9 Bartolomé Celli9 1University Hospital of Gran Canaria Dr Negrín, Respiratory Service, Las Palmas de Gran Canaria, Spain; 2University Hospital Nuestra Señora de la Candelaria, Respiratory Service, Santa Cruz de Tenerife, Spain; 3Arucas Health Center, Primary Care Las Palmas de Gran Canaria, Spain; 4Cueva Torres Health Center, Primary Care Las Palmas de Gran Canaria, Spain; 5La Feria Health Center, Primary Care Las Palmas de Gran Canaria, Spain; 6University Hospital of Gran Canaria Dr Negrín, Investigation Unit, Las Palmas de Gran Canaria, Spain; 7University Hospital Miguel Servet, Respiratory Service, Zaragoza, Spain; 8Navarra University Clinic, Respiratory Service, Pamplona, Spain; 9Brigham and Women’s Hospital, Pulmonary and Critical Care Service, Boston, MA, USA Introduction: Guidelines recommendations for the treatment of COPD are poorly followed. This could be related to the complexity of classification and treatment algorithms. The purpose of this study was to validate a simpler dyspnea-based treatment algorithm for inhaled pharmacotherapy in stable COPD, comparing its concordance with the current Global Initiative for Obstructive Lung Disease (GOLD) guideline.Methods: We enrolled patients who had been diagnosed with COPD in three primary care facilities and two tertiary hospitals in Spain. We determined anthropometric data, forced expiratory volume in the 1st second (percent), exacerbations, and dyspnea based on the modified Medical Research Council scale. We evaluated the new algorithm based on dyspnea and exacerbations and calculated the concordance with the current GOLD recommendations.Results: We enrolled 100 patients in primary care and 150 attending specialized care in a respiratory clinic. There were differences in the sample distribution between cohorts with 41% vs 26% in grade A, 16% vs 12% in grade B, 16% vs 22% in grade C, and 27% vs 40% in grade D for primary and respiratory care, respectively (P=0.005). The coincidence of the algorithm with the GOLD recommendations in primary care was 93% and 91.8% in the respiratory care cohort.Conclusion: A simple dyspnea-based treatment algorithm for inhaled pharmacotherapy of COPD could be useful in the management of COPD patients and concurs very well with the recommended schema suggested by the GOLD initiative. Keywords: COPD, treatment, algorithm, primary care

Marc Miravitlles,1,2 Bernardino Alcázar,3 Francisco Javier Alvarez,4 Teresa Bazús,5 Myriam Calle,6 Ciro Casanova,7 Carolina Cisneros,8 Juan P de-Torres,9 Luis M Entrenas,10 Cristóbal Esteban,11 Patricia García-Sidro,12 Borja G Cosio,13 Arturo Huerta,14 Milagros Iriberri,15 José Luis Izquierdo,16 Antolín López-Viña,17 José Luis López-Campos,2,4 Eva Martínez-Moragón,18 Luis Pérez de Llano,19 Miguel Perpiñá,20 José Antonio Ros,21 José Serrano,22 Juan José Soler-Cataluña,23 Alfons Torrego,24 Isabel Urrutia,11 Vicente Plaza24 1Pneumology Department, Hospital Universitari Vall d’Hebron, Barcelona, 2CIBER de Enfermedades Respiratorias (CIBERES), Madrid, 3Respiratory Department, Hospital de Alta Resolucion de Loja, Granada, 4Medical-Surgical Unit of Respiratory Diseases, Virgen del Rocio University Hospital, Biomedicine Institute of Seville (IBiS), Seville, 5Department of Pneumology, Hospital Universitario Central de Asturias, Oviedo, 6Department of Pneumology, Hospital Clínico San Carlos, Madrid, 7Department of Pneumology, Hospital Nuestra Señora de la Candelaria, Santa Cruz de Tenerife, 8Department of Pneumology, Hospital Universitario de La Princesa/Instituto de Investigación Sanitaria (IIS-IP), Madrid, 9Pulmonary Department, Clínica Universidad de Navarra, Pamplona, 10Department of Pneumology, Hospital Universitario Reina Sofia, Córdoba, 11Department of Pneumology, Hospital Galdakao-Usansolo, Galdakao, 12Department of Pneumology, Hospital Universitario de La Plana, Vila-real, 13Department of Pneumology, Hospital Universitario Son Espases IdISPa, Palma de Mallorca, 14Sección Urgencias Medicina – Neumología, Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Hospital Clinic de Barcelona, Barcelona, 15Department of Pneumology, Hospital Universitario de Cruces, Bilbao, 16Department of Pneumology, Hospital Universitario de Guadalajara, Guadalajara, 17Department of Pneumology, Hospital Universitario Puerta de Hierro Majadahonda, Madrid, 18Department of Pneumology, Hospital Universitario Dr Peset, Valencia, 19Department of Pneumology, Hospital Universitario Lucus Augusti, Lugo, 20Department of Pneumology, Hospital Universitario y Politécnico La Fe, Valencia, 21Department of Pneumology, Hospital Clínico Universitario Virgen de la Arrinxaca, Murcia, 22Department of Pneumology, Hospital Comarcal de Inca, Inca, 23Pneumology Department, Hospital Arnau de Vilanova-Lliria, Valencia, 24Department of Respiratory Medicine, Hospital de la Santa Creu i Sant Pau, Institut d’Investigació Biomédica Sant Pau (IIB Sant Pau), Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain 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

A study of the agonistic buffering behavior among chimpanzees and the status of the buffers used, either an infant of the alpha female or the social rank of the male, are described. The chimpanzees adapt to new social conditions by changing behavior.