ABSTRACT
Purpose: 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.
Subject(s)
Beclomethasone , Pulmonary Disease, Chronic Obstructive , Administration, Inhalation , Adrenergic beta-2 Receptor Agonists/adverse effects , Aged , Beclomethasone/adverse effects , Bronchodilator Agents/adverse effects , Cohort Studies , Formoterol Fumarate/adverse effects , Humans , Male , Muscarinic Antagonists/adverse effects , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/drug therapyABSTRACT
Background: COPD is a chronic disease traditionally associated with increased symptoms as lung function deteriorates. Follow-up times in previous cohort studies were limited to a few years. Interestingly, newer longer observational studies show a more comprehensive picture on disease progression over time. Therefore, the question on the relevancy of the follow-up time in cohort studies remains open. Methods: The ON-SINT study is an observational, retrospective, nationwide, real-life cohort study, in which patients diagnosed with COPD were recruited between December 2011 and April 2013 by primary care (PC) and secondary care (SC) physicians. Patients were evaluated at the inclusion visit and at the initial visit when the diagnosis of COPD was first established. Distribution of lung function decline over the years was studied comparing those cases with longer follow-up times, with the median of the distribution as the cutoff point. Results: The sample included 1214 patients of which 857 (70.6%) were recruited by PC and 357 (29.4%) by SC physicians. Median follow-up time was 6.26 years. Mean annual change in the complete cohort were -4.5 (222) ml year-1 for FVC and 5.5 (134) ml year-1 for FEV1. We confirm the variable distribution of FEV1 decline and found that longer follow-up periods reduce this variability. Of note, FEV1 decline was different between groups (shorter: 19.7 [180.4] vs longer: -9.7 [46.9]; p = 0.018). Further, our data revealed differences in the clinical presentation according to follow-up times, with special emphasis on dyspnea (OR: 1.035; 95%CI: 1.014-1.056), exacerbations (OR 1.172; 95%CI 1.045-1.315) and CAT scores (OR 1.047; 95%CI 1.019-1.075) being associated with longer follow-up times. Conclusions: This study describes the impact of follow-up periods on lung function variability, and reveals differences in clinical presentation according to follow-up times, with special emphasis on dyspnea, exacerbations and CAT scores.
ABSTRACT
Introducción: El presente trabajo describe el método y la organización del trabajo del estudio COPD History Assessment in Spain (CHAIN), cuyo objetivo principal es evaluar a largo plazo la historia natural de una cohorte de pacientes con enfermedad pulmonar obstructiva crónica (EPOC) desde un punto de vista multidimensional y la identificación de fenotipos clínicos comparándola con otra cohorte control sin EPOC. Pacientes y método: CHAIN es un estudio observacional multicéntrico de cohortes prospectivas realizado en 36 hospitales españoles. Ambas cohortes se seguirán durante un periodo de 5 años con visitas completas cada 12 meses y controles telefónicos cada 6 meses para valorar las exacerbaciones y el estado vital del sujeto. El periodo de reclutamiento de casos se realizó entre el 15 de enero de 2010 y el 31 de marzo de 2012. En cada visita anual se recoge información sobre: a) aspectos clínicos (situación socioeconómica, datos antropométricos, comorbilidades, tabaquismo, clínica respiratoria, exacerbaciones, calidad de vida, escala ansiedad-depresión, actividades de la vida diaria, tratamientos); b) función respiratoria (espirometría, gasometría arterial, hiperinsuflación, difusión, presiones respiratorias); c) índice BODE (variable principal del estudio); d) función muscular periférica, y e) analítica sanguínea (incluida IgE y factores de riesgo cardiovascular). Además, se creará una seroteca para la futura determinación de biomarcadores. Los datos de los pacientes son anonimizados en una base de datos con un acceso jerárquico para garantizar la seguridad en los accesos a la información. El estudio CHAIN aportará información sobre la progresión de la EPOC y establecerá una red de investigadores para futuros proyectos relacionados con la enfermedad(AU)
Introduction: This present paper describes the method and the organization of the study known as the COPD History Assessment In Spain (CHAIN), whose main objective is to evaluate the long-term natural history of a chronic obstructive pulmonary disease (COPD) patient cohort from a multidimensional standpoint and to identify clinical phenotypes, in comparison with another non-COPD control cohort. Patients and methods: CHAIN is a multicenter, observational study of prospective cohorts carried out at 36 Spanish hospitals. Both cohorts will be followed-up during a 5-year study period with complete office visits every 12 months and telephone interviews every 6 months in order to evaluate exacerbations and the vital state of the subjects. The recruitment period for cases was between 15 January 2010 and 31 March 2012. At each annual visit, information will be collected on: (i) clinical aspects (socio-economic situation, anthropometric data, comorbidities, smoking, respiratory symptoms, exacerbations, quality of life, anxiety-depression scale, daily life activities, treatments); (ii) respiratory function (spirometry, blood gases, hyperinflation, diffusion, respiratory pressures); (iii) BODE index (main study variable); (iv) peripheral muscle function, and (v) blood work-up (including IgE and cardiovascular risk factors). In addition, a serum bank will be created for the future determination of biomarkers. The data of the patients are anonymized in a database with a hierarchical access control in order to guarantee secure information access. The CHAIN study will provide information about the progression of COPD and it will establish a network of researchers for future projects related with COPD(AU)