Triple Therapy and Clinical Control in B+ COPD Patients: A Pragmatic, Prospective, Randomized Trial.

INTRODUCTION: Treatment with LABA/LAMA is recommended in GOLD B patients. We hypothesized that triple therapy (LABA/LAMA/ICS) will be superior to LABA/LAMA in achieving and maintaining clinical control (CC), a composite outcome that considers both impact and disease stability in a subgroup of GOLD B patients (here termed GOLD B+ patients) characterized by: (1) remaining symptomatic (CAT≥10) despite regular LABA/LAMA therapy; (2) having suffered one moderate exacerbation in the previous year; and (3) having blood eosinophil counts (BEC) ≥150cells/µL. METHODS: The ANTES B+ study is a prospective, multicenter, open label, randomized, pragmatic, controlled trial designed to test this hypothesis. It will randomize 1028 B+ patients to continue with their usual LABA/LAMA combination prescribed by their attending physician or to begin fluticasone furoate (FF) 92µg/umeclidinium (UMEC) 55µg/vilanterol (VI) 22µg in a single inhaler q.d. for 12 months. The primary efficacy outcome will be the level of CC achieved. Secondary outcomes include the clinical important deterioration index (CID), annual rate of exacerbations, and FEV1. Exploratory objectives include the interaction of BEC and smoking status, all-cause mortality and proportion of patients on LABA/LAMA arm that switch therapy arms. Safety analysis include adverse events and incidence of pneumonia. RESULTS: The first patient was recruited on February 29, 2024; results are expected in the first quarter of 2026. CONCLUSIONS: The ANTES B+ study is the first to: (1) explore the efficacy and safety of triple therapy in a population of B+ COPD patients and (2) use a composite index (CC) as the primary result of a COPD trial.

Multidisciplinary Management of Patients With Chronic Obstructive Pulmonary Disease and Cardiovascular Disease.

Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist, increasing the prevalence of both entities and impacting on symptoms and prognosis. CVD should be suspected in patients with COPD who have high/very high risk scores on validated scales, frequent exacerbations, precordial pain, disproportionate dyspnea, or palpitations. They should be referred to cardiology if they have palpitations of unknown cause or angina pain. COPD should be suspected in patients with CVD if they have recurrent bronchitis, cough and expectoration, or disproportionate dyspnea. They should be referred to a pulmonologist if they have rhonchi or wheezing, air trapping, emphysema, or signs of chronic bronchitis. Treatment of COPD in cardiovascular patients should include long-acting muscarinic receptor antagonists (LAMA) or long-acting beta-agonists (LABA) in low-risk or high-risk non-exacerbators, and LAMA/LABA/inhaled corticosteroids in exacerbators who are not controlled with bronchodilators. Cardioselective beta-blockers should be favored in patients with CVD, the long-term need for amiodarone should be assessed, and antiplatelet drugs should be maintained if indicated.

Association between occupational exposure and chronic obstructive pulmonary disease and respiratory symptoms in the Spanish population.

INTRODUCTION: The aim of this study was to analyze the impact of occupational exposure on chronic obstructive pulmonary disease (COPD) and respiratory symptoms in the general Spanish population. METHODS: This was a study nested in the Spanish EPISCAN II cross-sectional epidemiological study that included participants who had completed a structured questionnaire on their occupational history, a questionnaire on respiratory symptoms, and forced spirometry. The data were analyzed using Chi-square and Student's t tests and adjusted models of multiple linear regression and logistic regression. RESULTS: We studied 7502 subjects, 51.1% women, with a mean age of 60±11 years. Overall, 53.2% reported some respiratory symptoms, 7.9% had respiratory symptoms during their work activity, 54.2% were or had been smokers, and 11.3% (851 subjects) met COPD criteria on spirometry. A total of 3056 subjects (40.7%) reported exposure to vapors, gases, dust or fumes (VGDF); occupational exposure to VGDF was independently associated with the presence of COPD (OR 1.22, 95% CI: 1.03-1.44), respiratory symptoms (OR 1.45, 95%: CI 1.30-1.61), and respiratory symptoms at work (OR 4.69, 95% CI: 3.82-5.77), with a population attributable fraction for COPD of 8.2%. CONCLUSIONS: Occupational exposure is associated with a higher risk of COPD and respiratory symptoms in the Spanish population. These results highlight the need to follow strict prevention measures to protect the respiratory health of workers.

Impact of comorbidities in COPD clinical control criteria. The CLAVE study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) frequently coexists with other chronic diseases, namely comorbidities. They negatively impact prognosis, exacerbations and quality of life in COPD patients. However, no studies have been performed to explore the impact of these comorbidities on COPD clinical control criteria. RESEARCH QUESTION: Determine the relationship between individualized comorbidities and COPD clinical control criteria. STUDY DESIGN AND METHODS: Observational, multicenter, cross-sectional study performed in Spain involving 4801 patients with severe COPD (< 50 predicted forced expiratory volume in the first second [FEV1%]). Clinical control criteria were defined by the combination of COPD assessment test (CAT) scores (≤16 vs ≥17) and exacerbations in the previous three months (none vs ≥1). Binary logistic regression adjusted by age and FEV1% was performed to identify comorbidities potentially associated with the lack of control of COPD. Secondary endpoints were the relationship between individualized comorbidities with COPD assessment test and exacerbations within the last three months. RESULTS: Most frequent comorbidities were arterial hypertension (51.2%), dyslipidemia (36.0%), diabetes (24.9%), obstructive sleep apnea-hypopnea syndrome (14.9%), anxiety (14.1%), heart failure (11.6%), depression (11.8%), atrial fibrillation (11.5%), peripheral arterial vascular disease (10.4%) and ischemic heart disease (10.1%). After age and FEV1% adjustment, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; all p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; all p < 0.001), sleep disorders (p < 0.0001), anemia (p = 0.015) and gastroesophageal reflux (p < 0.0001). These comorbidities were also related to previous exacerbations and COPD assessment test scores. INTERPRETATION: Comorbidities are frequent in patients with severe COPD, negatively impacting COPD clinical control criteria. They are related to health-related quality of life measured by the COPD assessment test. Our results suggest that comorbidities should be investigated and treated in these patients to improve their clinical control. TAKE-HOME POINTS: Study question: What is the impact of comorbidities on COPD clinical control criteria? RESULTS: Among 4801 patients with severe COPD (27.5% controlled and 72.5% uncontrolled), after adjustment by age and FEV1%, comorbidities related to lack of clinical control were cardiovascular diseases (heart failure, peripheral vascular disease and atrial fibrillation; p < 0.0001), psychologic disorders (anxiety and depression; p < 0.0001), metabolic diseases (diabetes, arterial hypertension and abdominal obesity; p < 0.001), obstructive sleep apnea-hypopnea syndrome (p < 0.0001), anaemia (p = 0.015) and gastroesophageal reflux (p < 0.0001), which were related to previous exacerbations and COPD assessment test scores. INTERPRETATION: Comorbidities are related to health-related quality of life measured by the COPD assessment test scores and history of exacerbations in the previous three months.

Inhaled Maintenance Therapy in the Follow-Up of COPD in Outpatient Respiratory Clinics. Factors Related to Inhaled Corticosteroid Use. EPOCONSUL 2021 Audit.

OBJECTIVE: The aim of this analysis was to describe the patterns of inhaled maintenance therapy according to risk level and to explore the determinants associated with the decision to prescribe inhaled corticosteroids (ICS) in addition to bronchodilator therapy according to risk level as strategy in the follow-up of COPD in daily clinical practice. METHODS: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021 and January 31, 2022. RESULTS: 4225 patients from 45 hospitals in Spain were audited. Risk levels were analyzed in 2678 patients. 74.5% of patients were classified as high risk and 25.5% as low risk according to GesEPOC criteria. Factors associated with the prescription of ICS in low-risk COPD were symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p<0.001], peripheral blood eosinophilia>300mm3 [OR: 2.16 (1.10-4.24), p=0.025], and having a predicted FEV1%<80% [OR: 2.17 (1.15-4.08), p=0.016]. In high-risk COPD, factors associated with triple therapy versus dual bronchodilator therapy were a mMRC dyspnea score of ≥2 [OR: 1.97 (1.41-2.75), p<0.001], symptoms suggestive of asthma [OR: 6.70 (3.14-14.29), p<0.001], and a predicted FEV1%<50% [OR: 3.09 (1.29-7.41), p<0.011]. CONCLUSIONS: Inhaled therapy in the follow-up of COPD does not always conform to the current guidelines. Few changes in inhaled therapy are made at follow-up visits. The use of ICS is common in COPD patients who meet low-risk criteria in their follow-up and triple therapy in high-risk COPD patients is used as an escalation strategy in patients with high clinical impact. However, a history of exacerbations and eosinophil count in peripheral blood were not factors predicting triple therapy.

[Chronic Bronchial Infection in Stable COPD]. / Infección bronquial crónica en EPOC estable.

Classically, the role of pulmonary infection in patients with chronic obstructive pulmonary disease (COPD) has focused on periods of exacerbation. However, in a clinically stable situation, little attention has been paid to the role play by the presence of potentially pathogenic micro-organisms (especially when they are repeatedly isolated, which is known as chronic bronchial infection [CBI]) in the pathogenesis, prognosis and disease treatment. In recent years, however, some evidence has been published on the deleterious effect of CBI in COPD since it has been associated to greater local inflammation, greater disease severity, poorer health-related quality of life, greater number and severity of exacerbations and cardiovascular events, presence of bronchiectasis, rapid decline of lung function, and even higher mortality (especially related to Pseudomonas aeruginosa infection). It is not known, however, what is the role of anti-inflammatory or antibiotic treatments on CBI in stable COPD patients. This review focused on the scientific evidence on this topic that exists up to now, from the very definition of IBC in COPD to the possible treatments that this situation entails, as well as the numerous future challenges it generates, especially the development of knowledge of the pulmonary microbiome, its alterations and its consequences.

[Health-Related Quality of Life and Therapeutic Adherence to Continuous Positive Airway Pressure (CPAP) in Patients with Obstructive Sleep Apnea (OSA)]. / Calidad de vida relacionada con la salud y adhesión terapéutica a la presión positiva continua en la vía aérea (CPAP) en pacientes con apnea obstructiva del sueño (AOS).

Introduction: The benefits of CPAP in patients with obstructive sleep apnea (OSA) are not achieved without therapeutic adherence (TA). The perception of benefit is one of the main predictors of adherence. However, it is unknown whether the impact of CPAP on health-related quality of life (HRQoL) is related to TA. Objective: 1) To evaluate whether changes in HRQoL after initiating CPAP are associated with AT. 2) To analyze the influence of various TA determinants, including baseline HRQoL. Methods: Prospective observational and longitudinal study on a cohort of patients with moderate-severe OSA and indication of CPAP. Baseline and after-therapy HRQoL were evaluated using the Quebec Sleep Questionnaire (QSQ), as well as other possible AT determinants. A multivariate analysis was performed. Results: A total of 364 patients (78% men) were included, with mean age of 55 ± 11 years and apnea-hypopnea index of 42 ± 19/hour. 33.3% without TA. There was no association between HRQoL changes after 3 months of CPAP and AT and between QSQ baseline score and AT. A higher ODI4%, a global improvement and social interactions (QSQ), were associated with AT. Baseline anxiety-depressive symptoms, worsening anxiety, and side effects with CPAP were associated with worse AT. Conclusions: The impact of CPAP on HRQoL with respect to the perception of social interactions seems to condition TA. The basal impact of the disease, in terms of HRQoL, is not associated with AT.

Tobacco Patterns and Risk of Chronic Obstructive Pulmonary Disease: Results From a Cross-Sectional Study.

INTRODUCTION: There is still uncertainty about which aspects of cigarette smoking influence the risk of Chronic Obstructive Pulmonary Disease (COPD). The aim of this study was to estimate the COPD risk as related to duration of use, intensity of use, lifetime tobacco consumption, age of smoking initiation and years of abstinence. METHODS: We conducted an analytical cross-sectional study based on data from the EPISCAN-II study (n=9092). All participants underwent a face-to-face interview and post-bronchodilator spirometry was performed. COPD was defined as post-bronchodilator FEV1/FVC<70%. Parametric and nonparametric logistic regression models with generalized additive models were used. RESULTS: 8819 persons were included; 858 with COPD and 7961 without COPD. The COPD risk increased with smoking duration up to ≥50 years [OR 3.5 (95% CI: 2.3-5.4)], with smoking intensity up to ≥39cig/day [OR 10.1 (95% CI: 5.3-18.4)] and with lifetime tobacco consumption up to >29 pack-years [OR 3.8 (95% CI: 3.1-4.8)]. The COPD risk for those who started smoking at 22 or later was 0.9 (95% CI: 0.6-1.4). The risk of COPD decreased with increasing years of cessation. In comparison with both never smokers and current smokers, the lowest risk of COPD was found after 15-25 years of abstinence. CONCLUSION: COPD risk increases with duration, intensity, and lifetime tobacco consumption and decreases importantly with years of abstinence. Age at smoking initiation shows no effect. After 15-25 years of cessation, COPD risk could be equal to that of a never smoker. This work suggests that the time it takes to develop COPD in a smoker is about 30 years.

Lack of Clinical Control in COPD Patients Depending on the Target and the Therapeutic Option.

Introduction: According to the Global Initiative for chronic obstructive lung disease (GOLD), when a treatment is not achieving an appropriate response it should be switched taking into account the predominant treatable trait to target (dyspnea or exacerbations). The objective of the present study was to investigate the lack of clinical control according to the target and medication groups. Materials and Methods: This was a post-hoc analysis of the CLAVE study, an observational, cross-sectional, multicenter study which evaluated the clinical control, and related-factors, in a cohort of 4801 patients with severe chronic obstructive pulmonary disease (COPD). The primary endpoint was the percentage of uncontrolled patients defined as COPD Assessment Test (CAT) >16 or presence of exacerbations in the last 3 months despite receiving long-acting beta2-agonist (LABA) and/or long-acting antimuscarinic antagonist (LAMA) with or without inhaled corticosteroids (ICS). Secondary objectives included the description of sociodemographic and clinical characteristics of patients by therapeutic group and the identification of characteristics potentially associated with the lack of control of COPD including low adherence measured by the test to adherence to inhalers (TAI). Results: In the dyspnea pathway, lack of clinical control was of 25.0% of patients receiving LABA or LAMA in monotherapy, 29.5% by those with LABA + LAMA, 38.3% with LABA + ICS and 37.0% with triple therapy (LABA + LAMA + ICS). In the exacerbation pathway, percentages were 87.1%, 76.7%, 83.3%, and 84.1%, respectively. Low physical activity and high Charlson comorbidity index were independent factor of non-control in all therapeutic groups. Additional factors were lower post-bronchodilator FEV1 and poor adherence to inhalers. Conclusion: There are still room for improvement in COPD control. From the pharmacological perspective, every step in treatment have a pool of uncontrolled patients in which a step-up could be considered according to a trait to target strategy.

Impact of COPD Exacerbations and Burden of Disease in Spain: AVOIDEX Study.

Purpose: Chronic obstructive pulmonary disease (COPD) is characterized by high morbidity and mortality, with a considerable consumption of healthcare resources (HRU). This study aims to obtain real world evidence regarding the consequences of COPD exacerbations and to provide updated data on the burden of this disease and its treatment. Patients and Methods: A retrospective study in seven Spanish regions was conducted among COPD patients diagnosed between 1/01/2010 and 31/12/2017. The index date was the diagnosis of COPD and patients were followed until lost to follow-up, death or end of the study, whichever occurred first. Patients were classified by patient pattern (incident or prevalent), type and severity of exacerbations, and treatments prescribed. Demographic and clinical characteristics were evaluated, together with the incidence of exacerbations, comorbidities, and the use of HRU, during the baseline (12 months before the index date) and the follow-up periods by incident/prevalent and treatment prescribed. Mortality rate was also measured. Results: The study included 34,557 patients with a mean age of 70 years (standard deviation: 12). The most frequent comorbidities were diabetes, osteoporosis, and anxiety. Most patients received inhaled corticosteroids (ICS) with long-acting beta agonists (LABA), or long-acting muscarinic agonists (LAMA), followed by LABA with LAMA. Incident patients (N=8229; 23.8%) had fewer exacerbations than prevalent patients (N=26328; 76.2%), 0.3 vs 1.2 exacerbations per 100 patient-years. All treatment patterns present a substantial disease burden, which seems to increase with the evolution of the disease (ie moving from initial treatments to combination therapies). The overall mortality rate was 40.2 deaths/1000 patient-years. General practitioner visits and tests were the HRU most frequently required. The frequency and severity of exacerbations positively correlated with the use of HRU. Conclusion: Despite receiving treatment, patients with COPD suffer a considerable burden mainly due to exacerbations and comorbidities, which require a substantial use of HRU.

Variations in Chronic Obstructive Pulmonary Disease Outpatient Care in Respiratory Clinics: Results From the 2021 EPOCONSUL Audit.

INTRODUCTION: The aim of our work has been to describe the results of the clinical audit carried out in 2021 and to compare the results with 2015 EPOCONSUL audit. METHODS: EPOCONSUL 2021 is a cross-sectional audit that evaluated the outpatient care provided to patients with a diagnosis of chronic obstructive pulmonary disease (COPD) in respiratory clinics in Spain with prospective recruitment between April 15, 2021, and January 31, 2022. RESULTS: A total of 45 hospitals participated in the 2021 audit and 4.225 clinical records of patients were evaluated. Clinical phenotype according to the Spanish National Guidelines for COPD care (GesEPOC) was reported in 63.1% of the audited patients, and the COPD type assessment for the Global initiative for chronic Obstructive Lung Disease (GOLD) was present in 38.3%. There was an improved compliance with clinical practice guideline (CPG) recommendations in the 2021 audit with respect to the 2015 audit. There was an increase in the proportion of cases with alfa-1-antitrypsin serum level testing available (audit 1: 18.9%; audit 2: 38.7%, p<0.001) and 6-min walk test carried out (audit 1: 24%; audit 2: 45.2%, p<0.001). However, these significant variations adherence to CPG recommendations were not reached for the clinical evaluation and therapeutic intervention category when adjusting for patient and resource variables. CONCLUSIONS: The 2021 EPOCONSUL audit showed increased adherence to recommendations although they seem to be related to the availability of resources for care. These results should be taken into account in order to establish improvements in resources to achieve a better quality of care.

Unravelling young COPD and pre-COPD in the general population.

Background: Chronic obstructive pulmonary disease (COPD) is commonly diagnosed when the airflow limitation is well established and symptomatic. We aimed to identify individuals at risk of developing COPD according to the concept of pre-COPD and compare their clinical characteristics with 1) those who have developed the disease at a young age, and 2) the overall population with and without COPD. Methods: The EPISCAN II study is a cross-sectional, population-based study that aims to investigate the prevalence of COPD in Spain in subjects ≥40 years of age. Pre-COPD was defined as the presence of emphysema >5% and/or bronchial thickening by computed chromatography (CT) scan and/or diffusing capacity of the lung for carbon monoxide (D LCO) <80% of predicted in subjects with respiratory symptoms and post-bronchodilator forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC) >0.70. Young COPD was defined as FEV1/FVC <0.70 in a subject ≤50 years of age. Demographic and clinical characteristics were compared among pre-COPD, young COPD and the overall population with and without COPD. Results: Among the 1077 individuals with FEV1/FVC <0.70, 65 (6.0%) were ≤50 years of age. Among the 8015 individuals with FEV1/FVC >0.70, 350 underwent both D LCO testing and chest CT scanning. Of those, 78 (22.3%) subjects fulfilled the definition of pre-COPD. Subjects with pre-COPD were older, predominantly women, less frequently active or ex-smokers, with less frequent previous diagnosis of asthma but with higher symptomatic burden than those with young COPD. Conclusions: 22.3% of the studied population was at risk of developing COPD, with similar symptomatic and structural changes to those with well-established disease without airflow obstruction. This COPD at-risk population is different from those that develop COPD at a young age.

Dissociation between physical capacity and daily physical activity in COPD patients. A population-based approach.

BADKGROUND: Physical capacity (PC) and daily physical activity (PA) are two crucial factors in the clinical course of COPD, although they do not always maintain a close relationship. The objectives were to evaluate the frequency of PC-PA dissociation in patients with COPD and subjects without airflow limitation (AL) and to identify its risk factors. METHODS: A sample of 319 COPD patients and 399 subjects without AL was consecutively obtained from a population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, lung function testing, blood analysis and low-dose computed tomography (CT) scan with evaluation of lung density and airway wall thickness. A distance walked in 6 min > 70% predicted was considered an indicator of normal PC, while a Yale Physical Activity Survey summary index score <51 was used to identify with sedentary lifestyle. RESULTS: 166 COPD patients (52.0%) reported a sedentary lifestyle with evidence of preserved PC, while this phenomenon was present in 188 (47.1%) subjects without AL. In the COPD group, symptoms of chronic bronchitis, depression and elevated hematocrit and blood eosinophil count were identified as independent risk factors for PC-PA dissociation. In turn, in the subjects without AL, the risk factors for PC-PA dissociation were low fat-free mass, obesity and anxiety, as well as reduced levels of HDL-cholesterol and the absence of osteoporosis. CONCLUSIONS: Almost half of COPD patients and subjects without airflow limitation with preserved PC maintain a sedentary lifestyle, with different risk factors for sedentarism between both groups.

Prevalence of reduced lung diffusing capacity and CT scan findings in smokers without airflow limitation: a population-based study.

BACKGROUND: Population distribution of reduced diffusing capacity of the lungs for carbon monoxide (DLCO) in smokers and main consequences are not properly recognised. The objectives of this study were to describe the prevalence of reduced DLCO in a population-based sample of current and former smoker subjects without airflow limitation and to describe its morphological, functional and clinical implications. METHODS: A sample of 405 subjects aged 40 years or older with postbronchodilator forced expiratory volume in 1 s/forced vital capacity (FVC) >0.70 was obtained from a random population-based sample of 9092 subjects evaluated in the EPISCAN II study. Baseline evaluation included clinical questionnaires, exhaled carbon monoxide (CO) measurement, spirometry, DLCO determination, 6 min walk test, routine blood analysis and low-dose CT scan with evaluation of lung density and airway wall thickness. RESULTS: In never, former and current smokers, prevalence of reduced DLCO was 6.7%, 14.4% and 26.7%, respectively. Current and former smokers with reduced DLCO without airflow limitation were younger than the subjects with normal DLCO, and they had greater levels of dyspnoea and exhaled CO, greater pulmonary artery diameter and lower spirometric parameters, 6 min walk distance, daily physical activity and plasma albumin levels (all p<0.05), with no significant differences in other chronic respiratory symptoms or CT findings. FVC and exhaled CO were identified as independent risk factors for low DLCO. CONCLUSION: Reduced DLCO is a frequent disorder among smokers without airflow limitation, associated with decreased exercise capacity and with CT findings suggesting that it may be a marker of smoking-induced early vascular damage. TRIAL REGISTRATION NUMBER: NCT03028207.

Trends of COPD in Spain: Changes Between Cross Sectional Surveys 1997, 2007 and 2017.

INTRODUCTION: We aim to describe the changes in prevalence and risk factors associated to chronic obstructive pulmonary disease (COPD) in Spain, comparing three population-based studies conducted in three timepoints. METHODS: We compared participants from IBERPOC conducted in 1997, EPISCAN conducted in 2007 and EPISCAN II in 2017. COPD was defined as a postbronchodilator FEV1/FVC (forced expiratory volume in 1s/forced vital capacity) ratio <0.70, according to GOLD criteria; subsequently, also as the FEV1/FVC below the lower limit of normal (LLN). RESULTS: COPD prevalence in the population between 40 and 69 years decreased from 21.6% (95% CI 20.7%-23.2%) in 1997 to 8.8% (95% CI 8.2%-9.5%) in 2017, a 59.2% decline (p<0.001). In 2007, the prevalence was 7.7% (95% CI 6.8%-8.7%) with an upward trend of 1.1 percentage points in 2017 (p=0.073). Overall COPD prevalence decreased in men and women, although a significant increase was observed in the last decade in females (p<0.05). Current smokers significantly increased in the last decades (25.4% in 1997, 29.1% in 2007 and 23.4% in 2017; p<0.001). Regrettably, COPD underdiagnosis was constantly high, 77.6% in 1997, 78.4% in 2007, and to 78.2% in 2017 (p=0.95), higher in younger ages (40-49 yrs and 50-59 yrs) and also higher in women than in men in all three studies (p<0.05). CONCLUSIONS: We report a significant reduction of 59.2% in the prevalence of COPD in Spain from 1997 to 2017 in subjects aged 40-69 years. Our study highlights the significant underdiagnosis of COPD, particularly sustained in women and younger populations.

Cost-Effectiveness of Once-Daily Single-Inhaler COPD Triple Therapy in Spain: IMPACT Trial.

Purpose: Given between-country differences in healthcare systems, treatment costs, and disease management guidelines, country-specific cost-effectiveness analyses are important. This study evaluated the cost-effectiveness of once-daily fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI and UMEC/VI among patients with symptomatic chronic obstructive pulmonary disease (COPD) at risk of exacerbations from a Spanish healthcare system perspective. Patients and Methods: Baseline data and treatment effects from the IMPACT trial were populated into the validated GALAXY COPD progression model. Utilities were estimated using Spanish observational data. Direct healthcare costs (2019 €) were informed by Spanish public sources. A 3% discount rate for costs and benefits was applied. The time horizon and treatment duration were 3 years (base case). One-way sensitivity, scenario, and probabilistic sensitivity analyses were performed. Results: FF/UMEC/VI treatment resulted in fewer exacerbations over 3 years (4.130 vs 3.648) versus FF/VI, with a mean (95% confidence interval [CI]) incremental cost of €444 (€149, €713) per patient and benefit of 0.064 (0.053, 0.076) quality-adjusted life years (QALYs), resulting in an incremental cost-effectiveness ratio (ICER) of €6887 per QALY gained. FF/UMEC/VI was a dominant treatment strategy versus UMEC/VI, resulting in fewer exacerbations (4.130 vs 3.360), with a mean (95% CI) incremental cost of -€450 (-€844, -€149) and benefit of 0.054 (0.043, 0.064) QALYs. FF/UMEC/VI was cost-effective versus FF/VI and UMEC/VI across all analyses. Conclusion: FF/UMEC/VI was predicted to be a cost-effective treatment option versus FF/VI or UMEC/VI in symptomatic COPD patients at risk of exacerbations in Spain, across all scenarios and sensitivity analyses.

Discriminant Validity of a Single Clinical Question for the Screening of Inactivity in Individuals Living with COPD.

Introduction: Quantifying physical activity in chronic obstructive pulmonary disease (COPD) with questionnaires and activity monitors in clinical practice is challenging. The aim of the present study was to analyse the discriminant validity of a single clinical question for the screening of inactive individuals living with COPD. Methods: A multicentre study was carried out in stable COPD individuals both in primary and tertiary care. Patients wore the Dynaport accelerometer for 8 days and then answered 5 physical activity questions developed for the study, referring to the week in which their physical activity was monitored. Receiver operating characteristic (ROC) curve analysis with physical activity level (PAL) as the gold standard reference was used to determine the best cut-off point for each of the 5 clinical physical activity questions tested. Results: A total of 86 COPD participants were analysed (males 68.6%; mean (SD) age 66.6 (8.5) years; FEV1 50.9 (17.3)% predicted; mean of 7305 (3906) steps/day). Forty-two (48.8%) participants were considered physically inactive (PAL ≤1.69). Answers to 4 out of 5 questions significantly differed in active vs inactive patients. The Kappa index and ROC curves showed that the answer to the question "On average, how many minutes per day do you walk briskly?" had the best discriminative capacity for inactivity, with an area under the curve (AUC) (95% Confidence interval (CI)) of 0.73 (0.63-0.84) and 30 min/day was identified as the best cut-off value (sensitivity (95% CI): 0.75 (0.60-0.87); specificity: 0.76 (0.61-0.88)). Conclusion: The present results indicate that self-reported brisk walk time lower than 30 min/day may be a valid tool for the screening of inactivity in individuals living with COPD in routine care, if more detailed physical activity measures are not feasible.

Respiratory symptoms and their determinants in the general Spanish population: changes over 20 years.

Background: Few large epidemiological studies have analysed the prevalence of respiratory symptoms and their determinants in the general adult population. We investigated the prevalence and determinants of respiratory symptoms and compared their prevalence with that of two previous studies conducted in 1999 and 2009. Method: EPISCAN II was a multicentre, cross-sectional, population-based epidemiological study in individuals older than 40 years. Results: A total of 9092 individuals were included. Up to 47.5% reported at least one respiratory symptom, being more frequent in women than in men (49.4% versus 45.5%, p=0.0002) and with wheezing being the most frequent (33.7%) followed by dyspnoea (26.8%). The presence of any symptom was associated with female sex, higher body mass index (BMI), lower forced expiratory volume in 1 s (FEV1 % pred), reduced physical activity, a higher Charlson index and the presence of anxiety and depression. Smoking was also significantly associated with having at least one respiratory symptom in a dose-response fashion (OR: 1.415, 1.916, 2.192 and 2.987 for 0-10, 10-20, 20-30 and >30 pack-years, respectively, all p<0.0001). The prevalence of symptoms remained quite similar over the last 20 years (wheezing 40%, 36% and 33.7% and dyspnoea 10.4%, 9.9% and 13.1% in 1999, 2009 and 2019, respectively). Conclusions: Approximately half of the adult Spanish population have respiratory symptoms and this prevalence has remained quite stable over the last 20 years. Smoking remains the main factor associated with respiratory symptoms, but female sex, comorbidities, high BMI and low FEV1 and low physical activity are also significantly associated with respiratory symptoms.

Validation of the Spanish Activity Questionnaire in COPD (SAQ-COPD) in Patients with Chronic Obstructive Pulmonary Disease.

Purpose: The Spanish Activity Questionnaire in COPD (SAQ-COPD) is a short, simple physical activity (PA) measurement instrument for patients with chronic obstructive pulmonary disease (COPD). In this study, we analyzed its validity and sensitivity to change. Methods: Prospective scale validation study. An accelerometer (DynaPort MoveMonitor®) and the Yale Physical Activity Survey (YPAS) were used as reference standards. The analyses examined the criterion validity (Spearman correlations), internal consistency (Cronbach's alpha), factorial structure, test-retest reliability (intraclass correlation coefficient, ICC), sensitivity to change and receiver operating characteristic (ROC) curve to classify patients with low PA. Results: A total of 300 patients diagnosed with COPD were analyzed (73% males, mean age 66 ± 8 years, 40.3% with severe airflow limitation). Cronbach's alpha was 0.60 and Spearman's correlations with accelerometer measurements of PA [number of steps, metabolic equivalents (MET), physical activity level (PAL)] and YPAS ranged from 0.37 to 0.53 (all p < 0.001). ICC was 0.69 (95% CI 0.61-0.74) and the area under the ROC curve to identify low PA was 0.65 (95% confidence interval: 0.58-0.73). Significant variations in SAQ-COPD scores were found between groups defined by YPAS for change. Conclusion: The SAQ-COPD questionnaire is a valid instrument for classifying PA in patients with COPD. Correlations with other instruments provide criterion validity and also demonstrate good sensitivity to change.

[Translated article] Spanish COPD Guidelines (GesEPOC) 2021 Update. Diagnosis and Treatment of COPD Exacerbation Syndrome.

This article details the GesEPOC 2021 recommendations on the diagnosis and treatment of COPD exacerbation syndrome (CES). The guidelines propose a definition-based syndromic approach, a new classification of severity, and the recognition of different treatable traits (TT), representing a new step toward personalized medicine. The evidence is evaluated using GRADE methodology, with the incorporation of 6 new PICO questions. The diagnostic process comprises four stages: 1) establish a diagnosis of CES, 2) assess the severity of the episode, 3) identify the trigger, and 4) address TTs. This diagnostic process differentiates an outpatient approach, that recommends the inclusion of a basic battery of tests, from a more comprehensive hospital approach, that includes the study of different biomarkers and imaging tests. Bronchodilator treatment for immediate relief of symptoms is considered essential for all patients, while the use of antibiotics, systemic corticosteroids, oxygen therapy, and assisted ventilation and the treatment of comorbidities will vary depending on severity and possible TTs. The use of antibiotics will be indicated particularly if sputum color changes, when ventilatory assistance is required, in cases involving pneumonia, and in patients with elevated C-reactive protein (≥ 20 mg/L). Systemic corticosteroids are recommended in CES that requires admission and are suggested in moderate CES. These drugs are more effective in patients with blood eosinophil counts ≥ 300 cells/mm3. Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment.