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Marc Miravitlles,1 Miguel Roman-Rodríguez,2,3 Xavier Ribera,4 John Ritz,5 José Luis Izquierdo6,7 On behalf of OPTI investigator’s group1Pneumology 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, Spain; 2Centro de Salud Dra. Teresa Pique, Mallorca, Spain; 3Instituto de Investigación Sanitaria de las Islas Baleares (IdISBa), Mallorca, Spain; 4Boehringer Ingelheim España, Sant Cugat del Vallés, Barcelona, Spain; 5Syneos Health - Boehringer Ingelheim Pharmaceuticals Inc., Ridgefield, CT, USA; 6Department of Medicine and Medical Specialties, Universidad de Alcalá, Madrid, Spain; 7Pneumology Department, Hospital Universitario de Guadalajara, Guadalajara, SpainCorrespondence: Marc Miravitlles,Pneumology Department, Hospital Universitari Vall d’Hebron, P. Vall d’Hebron 119-129, Barcelona, ES– 08035, Spain, Email marcm@separ.esPurpose: Inhaled corticosteroids (ICS) are frequently used to treat chronic obstructive pulmonary disease (COPD) outside the current recommendations. Our aim was to describe ICS use in COPD patients and to identify factors associated with ICS use among COPD patients treated within primary care in Spain.Patients and Methods: This was a cross-sectional, non-interventional and multicenter study of patients with COPD treated in primary care. Patient characteristics and exacerbations were described in terms of ICS use among the overall cohort, and among those with spirometry confirmed COPD (post-bronchodilator forced expiratory volume in 1 second [FEV1]/forced vital capacity [FVC] ratio < 70%). Multivariable logistic regression was used to identify factors associated with ICS use.Results: A total of 901 patients were included, of which 47.9% (n = 432) were treated with ICS. A total of 240 patients (26.6%) experienced moderate/severe exacerbations in the prior year, while 309 (34.3%) during the previous two years. History of asthma totaled 11.6% (n = 105). The most frequent phenotype was non-exacerbator (51.6%), and the proportion of patient with moderate or severe exacerbations was significantly higher among ICS treated patients compared to non-treated: 37.5% versus 16.6% during the previous year (p < 0.001), and 46.8% versus 22.8% during the previous 2-years (p < 0.001), respectively. Patient characteristics were similar among spirometry confirmed patients and the overall population. Factors significantly associated with ICS use were a history of asthma (OR = 4.39, 95% CI: 2.67– 7.26), the presence of moderate or severe exacerbations in the last year (OR = 2.52, 95% CI: 1.81– 3.49), followed by higher mMRC and higher CAT score.Conclusion: Nearly half of patients in primary care in Spain are treated with ICS, despite most of them being non-exacerbators. History of asthma, exacerbations, and worse dyspnea and CAT scores are associated with ICS use.Keywords: chronic obstructive pulmonary disease, primary care, inhaled corticosteroids, exacerbations

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.

Evgeni Mekov,1 Alexa Nuñez,2 Don D Sin,3 Masakazu Ichinose,4 Chin Kook Rhee,5 Diego Jose Maselli,6 Andréanne Coté,7 Charlotte Suppli Ulrik,8,9 François Maltais,7 Antonio Anzueto,6 Marc Miravitlles2 1Department of Occupational Diseases, Medical Faculty, Medical University of Sofia, Sofia, Bulgaria; 2Pneumology 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, Spain; 3Centre for Heart Lung Innovation, St. Paul’s Hospital, Department of Medicine (Respiratory Division), University of British Columbia, Vancouver, BC, Canada; 4Academic Center of Osaki Citizen Hospital, Miyagi, Japan; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; 6Division of Pulmonary Diseases & Critical Care, University of Texas Health, South Texas Veterans Health Care System, San Antonio, TX, USA; 7Institut Universitaire de Cardiologie et de Pneumologie de Québec, Université Laval, Québec, QC, Canada; 8Department of Pulmonary Medicine, Copenhagen University Hospital-Hvidovre, Hvidovre, Denmark; 9Institute of Clinical Medicine, University of Copenhagen, Copenhagen, DenmarkCorrespondence: Marc MiravitllesPneumology 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, SpainEmail marcm@separ.esAbstract: Although chronic obstructive pulmonary disease (COPD) and asthma are well-characterized diseases, they can coexist in a given patient. The term asthma–COPD overlap (ACO) was introduced to describe patients that have clinical features of both diseases and may represent around 25% of COPD patients and around 20% of asthma patients. Despite the increasing interest in ACO, there are still substantial controversies regarding its definition and its position within clinical guidelines for patients with obstructive lung disease. In general, most definitions indicate that ACO patients must present with non-reversible airflow limitation, significant exposure to smoking or other noxious particles or gases, together with features of asthma. In patients with a primary diagnosis of COPD, the identification of ACO has therapeutic implication because the asthmatic component should be treated with inhaled corticosteroids and some studies suggest that the most severe patients may respond to biological agents indicated for severe asthma. This manuscript aims to summarize the current state-of-the-art of ACO. The definitions, prevalence, and clinical manifestations will be reviewed and some innovative aspects, such as genetics, epigenetics, and biomarkers will be addressed. Lastly, the management and prognosis will be outlined as well as the position of ACO in the COPD and asthma guidelines.Keywords: ACO, asthma, COPD, epidemiology, genetics, biomarkers, prognosis, treatment

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

© 2020 Pérez de Llano et al., 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.

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

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.

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.

Sergey Avdeev,1,2 Zaurbek Aisanov,3 Vladimir Arkhipov,4 Andrey Belevskiy,3 Igor Leshchenko,5 Svetlana Ovcharenko,6 Evgeny Shmelev,7 Marc Miravitlles81Department of Pulmonology, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation; 2Clinical Department, Federal Pulmonology Research Institute, Federal Medical and Biological Agency of Russia, Moscow, Russian Federation; 3Department of Pulmonology, N.I. Pirogov Russian State National Research Medical University, Moscow, Russian Federation; 4Department of Clinical Pharmacology and Therapy, Russian Medical Academy of Continuous Professional Education, Moscow, Russian Federation; 5Department of Phthisiology, Pulmonology and Thoracic Surgery, Ural State Medical University, Ekaterinburg, Russian Federation; 6Department of Internal Diseases No.1, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation; 7Department of Differential Diagnostics, Federal Central Research Institute of Tuberculosis, Moscow, Russian Federation; 8Pneumology Department, University Hospital Vall d’Hebron/Vall d’Hebron Research Institute (VHIR), Ciber de Enfermedades Respiratorias (CIBERES), Barcelona, SpainAbstract: 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.Keywords: COPD, exacerbation, inhaled corticosteroid, patient follow-up, guideline adherence, treatment algorithm

Casas A, Montes de Oca M, Menezes AMB, Wehrmeister FC,Lopez Varela MV, Mendoza L, Ramírez L, Miravitlles M.Int J Chron Obstruct Pulmon Dis. 2018;13:1545–1556.Page 1552, Disclosure, the text “AM has been paid forher work as a statistician for the LASSYC study. LR isan employee of AstraZeneca. The other authors report noconflicts of interest in this work” should read “AMM hasbeen paid by AstraZeneca and GlaxoSmithKline for herwork as a statistician for the LASSYC and PLATINIOstudies, respectively. LR is an employee of AstraZeneca.MM has received speaker fees from Boehringer Ingelheim,Chiesi, Cipla, Menarini, Rovi, Bial, CSL Behring, Grifolsand Novartis; consultancy fees from Boehringer Ingelheim,Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring,Laboratories Esteve, Mereo BioPharm, Verona Pharma, pHPharma, Novartis and Grifols; and research grants fromGlaxoSmithKline and Grifols. The authors report no otherconflicts of interest in this work”. Read the original article

Bronchiectasis in COPD patients: more than a comorbidity?[Corrigendum]Martinez-Garcia MA, Miravitlles M. Int J Chron ObstructPulmon Dis. 2017;12:1401–1411.Page 1409, Disclosure, the text “The authors report noconflicts of interest in this work” should read “MM has received speaker fees from Boehringer Ingelheim, Chiesi,Cipla, Menarini, Rovi, Bial, CSL Behring, Grifols andNovartis; consultancy fees from Boehringer Ingelheim,Chiesi, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratories Esteve, Mereo BioPharma, Verona Pharma, pHPharma, Novartis and Grifols; and research grants fromGlaxoSmithKline and Grifols. MAM has received speakerfees from Chiesi, Grifols, Novartis, TEVA and Zambon;onsultancy fees from Zambon and TEVA; and researchgrants from Zambon”.Read the original article &nbsp

Aisanov Z, Avdeev S, Arkhipov V, Belevskiy A, Chuchalin A,Leshchenko I, Ovcharenko S, Shmelev E, Miravitlles M.Int J Chron Obstruct Pulmon Dis. 2018;13:183–187.Page 186, Disclosure, the text “The authors report no conflictsof interest in this work” should read “SA has receivedspeaker/consultancy fees from Boehringer Ingelheim,AstraZeneca, Chiesi, Teva and Novartis; non-financialsupport from Boehringer Ingelheim, Chiesi and Novartis;and research grants from AstraZeneca, GlaxoSmithKline andNovartis. MM has received speaker fees from BoehringerIngelheim, Chiesi, Cipla, Menarini, Rovi, Bial, CSL Behring,Grifols and Novartis; consultancy fees from BoehringerIngelheim, Chiesi, GlaxoSmithKline, Bial, Gebro Pharma,CSL Behring, Laboratories Esteve, Mereo BioPharm, VeronaPharma, pH Pharma, Novartis and Grifols; and research grantsfrom GlaxoSmithKline and Grifols. ZA has received speaker/consultancy fees from Boehringer Ingelheim, AstraZeneca,Chiesi, Teva and Novartis, GlaxoSmithKline; non-financialsupport from Boehringer Ingelheim, GSK and Novartis; andresearch grants from AstraZeneca, GlaxoSmithKline andNovartis. The authors report no other conflicts of interestin this work”.Read the original article

David MG Halpin,1 Marc Miravitlles,2 Norbert Metzdorf,3 Bartolomé Celli4 1Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK; 2Pneumology Department, Hospital Universitari Vall d’Hebron, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 3Respiratory Medicine, Boehringer Ingelheim Pharma GmBH & Co KG, Ingelheim am Rhein, Germany; 4Pulmonary Division, Brigham and Women’s Hospital, Boston, MA, USA Abstract: Severe exacerbations of COPD, ie, those leading to hospitalization, have profound clinical implications for patients and significant economic consequences for society. The prevalence and burden of severe COPD exacerbations remain high, despite recognition of the importance of exacerbation prevention and the availability of new treatment options. Severe COPD exacerbations are associated with high mortality, have negative impact on quality of life, are linked to cardiovascular complications, and are a significant burden on the health-care system. This review identified risk factors that contribute to the development of severe exacerbations, treatment options (bronchodilators, antibiotics, corticosteroids [CSs], oxygen therapy, and ventilator support) to manage severe exacerbations, and strategies to prevent readmission to hospital. Risk factors that are amenable to change have been highlighted. A number of bronchodilators have demonstrated successful reduction in risk of severe exacerbations, including long-acting muscarinic antagonist or long-acting β2-agonist mono- or combination therapies, in addition to vaccination, mucolytic and antibiotic therapy, and nonpharmacological interventions, such as pulmonary rehabilitation. Recognition of the importance of severe exacerbations is an essential step in improving outcomes for patients with COPD. Evidence-based approaches to prevent and manage severe exacerbations should be implemented as part of targeted strategies for disease management. Keywords: severe COPD exacerbations, hospitalization, prevention, treatment, bronchodilators, long-acting muscarinic antagonist

Mike Thomas,1 David MG Halpin,2 Marc Miravitlles3 1Primary Care and Population Sciences, University of Southampton, Southampton, 2Department of Respiratory Medicine, Royal Devon and Exeter Hospital, Exeter, UK; 3Pneumology Department, Hospital Universitari Vall d’Hebron, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Barcelona, Spain Abstract: Inhaled bronchodilator medications are central to the management of COPD and are frequently given on a regular basis to prevent or reduce symptoms. While short-acting bronchodilators are a treatment option for people with relatively few COPD symptoms and at low risk of exacerbations, for the majority of patients with significant breathlessness at the time of diagnosis, long-acting bronchodilators may be required. Dual bronchodilation with a long-acting β2-agonist and long-acting muscarinic antagonist may be more effective treatment for some of these patients, with the aim of improving symptoms. This combination may also reduce the rate of exacerbations compared with a bronchodilator-inhaled corticosteroid combination in those with a history of exacerbations. However, there is currently a lack of guidance on clinical indicators suggesting which patients should step up from mono- to dual bronchodilation. In this article, we discuss a number of clinical indicators that could prompt a patient and physician to consider treatment escalation, while being mindful of the need to avoid unnecessary polypharmacy. These indicators include insufficient symptomatic response, a sustained increased requirement for rescue medication, suboptimal 24-hour symptom control, deteriorating symptoms, the occurrence of exacerbations, COPD-related hospitalization, and reductions in lung function. Future research is required to provide a better understanding of the optimal timing and benefits of treatment escalation and to identify the appropriate tools to inform this decision. Keywords: COPD, dual bronchodilation, monobronchodilation, ICS, triple therapy