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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

Luis Pérez de Llano,1,* Borja G Cosío,2,3,* Amanda Iglesias,3 Natividad de las Cuevas,4 Juan Jose Soler-Cataluña,3,5 Jose Luis Izquierdo,6 Jose Luis López-Campos,3,7 Carmen Calero,7 Vicente Plaza,3,8–10 Marc Miravitlles,3,11 Alfons Torrego,8–10 Eva Martinez-Moragon,12 Joan B Soriano,13 Antolin Lopez Viña,14 Irina Bobolea15 On behalf of the CHACOS Study Group 1Department of Respiratory Medicine, Hospital Lucus Augusti, Lugo, Spain; 2Department of Respiratory Medicine, Hospital Universitario Son Espases-IdISBa, Palma de Mallorca, Spain; 3CIBER de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; 4Department of Allergy, Hospital 12 de Octubre, Madrid, Spain; 5Department of Respiratory Medicine, Hospital Arnau de Vilanova, Valencia, Spain; 6Department of Respiratory Medicine, Hospital Universitario de Guadalajara, Guadalajara, Spain; 7Department of Respiratory Medicine, Hospital Virgen del Rocío, Sevilla, Spain; 8Department of Respiratory Medicine, Hospital de la Santa Creu y Sant Pau, Barcelona, Spain; 9Institut d’Investigació Biomédica Sant Pau, IIB Sant Pau, Barcelona, Spain; 10Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain; 11Department of Respiratory Medicine, Hospital Universitari Vall d’Hebron, Barcelona, Spain; 12Department of Respiratory Medicine, Hospital Dr Peset, Valencia, Spain; 13Instituto de Investigación Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain; 14Department of Respiratory Medicine, Hospital Puerta de Hierro, Madrid, Spain; 15Servei de Pneumologia i Alergia, Hospital Clinic, Barcelona, Spain *These authors contributed equally to this work 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-α), 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 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

To assess the cost-effectiveness of benralizumab (benra) vs. mepolizumab (mepo) and dupilumab (dupi) for the treatment of patients with severe uncontrolled asthma from the Spanish Health System perspective. Exacerbations avoided, quality-adjusted life years (QALYs) gained and costs in a 5-year period were estimated with a Markov model for a cohort of 1,000 patients in which, based on published evidence, 31% of the patients received biologics + oral corticosteroids (OCS) and 69% received only biologics. Efficacy data (exacerbation reduction and OCS elimination) were derived from a matching-adjusted indirect comparison. Published EQ-5D utilities per health state (biologic alone, biologic + OCS, standard of care + OCS, exacerbations, and post-exacerbations) were used for QALY estimation. Utility decrements associated with exacerbation management [-0.1 (OCS or emergency visits), −0.2 (hospitalization)] derived from the literature were applied. Costs (€, 2022) included drug acquisition (ex-factory price), administration and disease management. An expert panel (2 pneumologists and 1 pharmacist) validated all inputs. Benra was more effective (52.21 QALYs) than mepo (51.39 QALYs) and dupi (51.30 QALYs). Benra avoided more exacerbations (2.87 exacerbations) compared to mepo (4.70 exacerbations) and dupi (5.11 exacerbations) for the 5-year horizon. Total costs/patient were €56,093.77 (benra), €59,280.45 (mepo) and €62,991.76 (dupi), resulting in benra dominating (more QALYs with lower costs) vs. mepo and dupi. Benralizumab can be considered as a dominant treatment alternative vs. other biologic drugs for the treatment of uncontrolled severe eosinophilic asthma patients in Spain. [ABSTRACT FROM AUTHOR]

Luis Pérez de Llano,1 David Dacal Rivas,1 Nuria Marina Malanda,2 Vicente Plaza Moral,3 José Antonio Gullón Blanco,4 Mariana Muñoz-Esquerre,5 Ismael García-Moguel,6 Rocío M Díaz Campos,7 Eva Martínez-Moragón,8 Alicia Harbenau Mena,9 Borja G Cosío,10 Alicia Padilla Galo,11 Carolina Cisneros Serrano12 1Pneumology Service, Hospital Lucus Augusti, EOXI Lugo, Cervo e Monforte, Lugo, Spain; 2Pneumology Service, Hospital Universitario de Cruces, Barakaldo, Bizkaia, Spain; 3Pneumology Service, Hospital Sta Creu i Sant Pau, Barcelona, Spain; 4Pneumology Service, University Hospital San Agustín, Avilés, Spain; 5Pneumology Service, Hospital Bellvitge-IDIBELL, Barcelona, Spain; 6Allergy Service, Hospital 12 de Octubre, Madrid, Spain; 7Pneumology Service, Institute for Health Research (i+12), Hospital Universitario 12 de Octubre, Madrid, Spain; 8Pneumology Service, Hospital Doctor Peset, Valencia, Spain; 9Allergy Service, Hospital de Mérida, Badajoz, Spain; 10Pneumology Service, Hospital Universitario Son Espases-IdISBa-CIBERES, Palma de Mallorca, Spain; 11Pneumology Service, Hospital Costa del Sol, Marbella, Málaga, Spain; 12Pneumology Service, Hospital Universitario de La Princesa, Madrid, SpainCorrespondence: David Dacal Rivas, Pneumology Service, University Hospital Lucus Augusti, Lugo, Spain, Tel +34982296000, Email daviddacalrivas@hotmail.comAbstract: Although biologics have demonstrated to be effective in T2-high asthma patients, there is little experience with these drugs in asthma–COPD overlap (ACO). The aim of this study was to compare the effectiveness of biologics in these two conditions. We included 318 patients (24 ACO and 297 asthma) treated with monoclonal antibodies and followed for at least 12 months. Omalizumab was the most frequently employed biologic agent both in patients with ACO and asthma. Asthma control test (ACT) scores after at least 12 months of biologic therapy were not significantly different between groups. The percentage of patients with ≥ 1 exacerbation and ≥ 1 corticosteroid burst was significantly higher in ACO patients (70.8 vs 27.3 and 83.3% vs 37.5%, respectively), whereas the percentage of “controlled” patients (with no exacerbations, no need for corticosteroids and ACT ≥ 20) was significantly lower (16.7% vs 39.7%). In conclusion, this report suggests that patients with ACO treated with biologics reach worse outcomes than asthma patients.Keywords: asthma, asthma–COPD overlap, COPD

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