Search

Chronic obstructive pulmonary disease (COPD) is a public health problem due to its high prevalence (11% in the adult population in Spain), increasing incidence, and great social and economic impact. Despite this, it is underdiagnosed (and, therefore, undertreated) at a rate of around 80%. In this paper, a group of respiratory physicians specializing in COPD discuss 7 fundamental problems ("cardinal sins") that contribute to this situation, with the explicit aim of proposing specific solutions that may help to improve this unfavorable state of affairs., (Copyright © 2022 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

In addition to recommendations for pharmacological treatment stratified for risk and phenotype, the new 2021 edition of the Spanish COPD Guidelines (GesEPOC 2021) proposes a personalized approach to treatable traits, defined as a characteristic (clinical, physiological, or biological) that can be identified by diagnostic tests or biomarkers, for which a specific treatment is available. Some treatable traits, such as malnutrition, sedentarism, emphysema or respiratory failure, can be treated with non-pharmacological therapies, and this was not covered in detail in the guidelines. This section of GesEPOC 2021 includes a narrative update with recommendations on dietary treatment, physical activity, respiratory rehabilitation, oxygen therapy, non-invasive ventilation, volume reduction, and lung transplantation. A PICO question with recommendations on the use of supplemental oxygen during exercise in COPD patients without severe hypoxemia is also included., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

The current health care models described in GesEPOC indicate the best way to make a correct diagnosis, the categorization of patients, the appropriate selection of the therapeutic strategy and the management and prevention of exacerbations. In addition, COPD involves several aspects that are crucial in an integrated approach to the health care of these patients. The evaluation of comorbidities in COPD patients represents a healthcare challenge. As part of a comprehensive assessment, the presence of comorbidities related to the clinical presentation, to some diagnostic technique or to some COPD-related treatments should be studied. Likewise, interventions on healthy lifestyle habits, adherence to complex treatments, developing skills to recognize the signs and symptoms of exacerbation, knowing what to do to prevent them and treat them within the framework of a self-management plan are also necessary. Finally, palliative care is one of the pillars in the comprehensive treatment of the COPD patient, seeking to prevent or treat the symptoms of a disease, the side effects of treatment, and the physical, psychological and social problems of patients and their caregivers. Therefore, the main objective of this palliative care is not to prolong life expectancy, but to improve its quality. This chapter of GesEPOC 2021 presents an update on the most important comorbidities, self-management strategies, and palliative care in COPD, and includes a recommendation on the use of opioids for the treatment of refractory dyspnea in COPD., (Copyright © 2021 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background and Objective: The availability of chest computed tomography (CT) imaging can help diagnose comorbidities associated with chronic obstructive pulmonary disease (COPD). Their systematic identification and relationship with all-cause mortality have not been explored. Furthermore, whether their CT-detected prevalence differs from clinical diagnosis is unknown., Methods: The prevalence of 10 CT-assessed comorbidities was retrospectively determined at baseline in 379 patients (71% men) with mild to severe COPD attending pulmonary clinics. Anthropometrics, smoking history, dyspnoea, lung function, exercise capacity, BODE (BMI, Obstruction, Dyspnoea and Exercise capacity) index and exacerbations rate were recorded. The prevalence of CT-determined comorbidities was compared with that recorded clinically. Over a median of 78 months of observation, the independent association with all-cause mortality was analysed. A 'CT-comorbidome' graphically expressed the strength of their association with mortality risk., Results: Coronary artery calcification, emphysema and bronchiectasis were the most prevalent comorbidities (79.8%, 62.7% and 33.9%, respectively). All were underdiagnosed before CT. Coronary artery calcium (hazard ratio [HR] 2.09; 95% CI 1.03-4.26, p = 0.042), bronchiectasis (HR 2.12; 95% CI 1.05-4.26, p = 0.036) and low psoas muscle density (HR 2.61; 95% CI 1.23-5.57, p = 0.010) were independently associated with all-cause mortality and helped define the 'CT-comorbidome'., Conclusion: This study of COPD patients shows that systematic detection of 10 CT-diagnosed comorbidities, most of which were not detected clinically, provides information of potential use to patients and clinicians caring for them., (© 2022 The Authors. Respirology published by John Wiley & Sons Australia, Ltd on behalf of Asian Pacific Society of Respirology.)

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/mm 3 . Acute-phase non-invasive mechanical ventilation is specified primarily for patients with CES who develop respiratory acidosis despite initial treatment., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Rationale: Cigarette smoke (CS) inhalation triggers oxidative stress and inflammation, leading to accelerated lung aging, apoptosis, and emphysema, as well as systemic pathologies. Metformin is beneficial for protecting against aging-related diseases. Objectives: We sought to investigate whether metformin may ameliorate CS-induced pathologies of emphysematous chronic obstructive pulmonary disease (COPD). Methods: Mice were exposed chronically to CS and fed metformin-enriched chow for the second half of exposure. Lung, kidney, and muscle pathologies, lung proteostasis, endoplasmic reticulum (ER) stress, mitochondrial function, and mediators of metformin effects in vivo and/or in vitro were studied. We evaluated the association of metformin use with indices of emphysema progression over 5 years of follow-up among the COPDGene (Genetic Epidemiology of COPD) study participants. The association of metformin use with the percentage of emphysema and adjusted lung density was estimated by using a linear mixed model. Measurements and Main Results: Metformin protected against CS-induced pulmonary inflammation and airspace enlargement; small airway remodeling, glomerular shrinkage, oxidative stress, apoptosis, telomere damage, aging, dysmetabolism in vivo and in vitro ; and ER stress. The AMPK (AMP-activated protein kinase) pathway was central to metformin's protective action. Within COPDGene, participants receiving metformin compared with those not receiving it had a slower progression of emphysema (-0.92%; 95% confidence interval [CI], -1.7% to -0.14%; P  = 0.02) and a slower adjusted lung density decrease (2.2 g/L; 95% CI, 0.43 to 4.0 g/L; P  = 0.01). Conclusions: Metformin protected against CS-induced lung, renal, and muscle injury; mitochondrial dysfunction; and unfolded protein responses and ER stress in mice. In humans, metformin use was associated with lesser emphysema progression over time. Our results provide a rationale for clinical trials testing the efficacy of metformin in limiting emphysema progression and its systemic consequences.

Rationale: Poor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality., Methods: At baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65±8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48-119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality., Results: PsD was lower in COPD patients than in controls (40.5 vs 42.5, p=0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV 1 %, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02-1.12, p=0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94-0.99, p=0.023) were the variables independently associated with all-cause mortality., Conclusions: In COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD., (Copyright © 2021 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Background: The value of the single-breath diffusing capacity of the lungs for carbon monoxide (Dlco) relates to outcomes for patients with COPD. However, little is known about the natural course of Dlco over time, intersubject variability, and factors that may influence Dlco progression., Research Question: What is the natural course of Dlco in patients with COPD over time, and which other factors, including sex differences, could influence this progression?, Study Design and Methods: We phenotyped 602 smokers (women, 33%), of whom 506 (84%) had COPD and 96 (16%) had no airflow limitation. Lung function, including Dlco, was monitored annually over 5 years. A random coefficients model was used to evaluate Dlco changes over time., Results: The mean (± SE) yearly decline in Dlco % in patients with COPD was 1.34% ± 0.015%/y. This was steeper compared with non-COPD control subjects (0.04% ± 0.032%/y; P = .004). Sixteen percent of the patients with COPD, vs 4.3% of the control subjects, had a statistically significant Dlco % slope annual decline (4.14%/y). At baseline, women with COPD had lower Dlco values (11.37% ± 2.27%; P < .001) in spite of a higher FEV 1 % than men. Compared with men, women with COPD had a steeper Dlco annual decline of 0.89% ± 0.42%/y (P = .039)., Interpretation: Patients with COPD have an accelerated decline in Dlco compared with smokers without the disease. However, the decline is slow, and a testing interval of 3 to 4 years may be clinically informative. The lower and more rapid decline in Dlco values in women, compared with men, suggests a differential impact of sex in gas exchange function., Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov., (Copyright © 2021 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Hypovitaminosis D has been linked to deterioration in clinical parameters and lung function in COPD. As a response to low levels of vitamin D serum Parathyroid Hormone (iPTH) is increased in some, but not all, patients. The aim of this study was to determine whether COPD patients with elevated PTH levels are at higher risk of COPD exacerbations and hospitalizations., Methods: 166 COPD outpatients were randomly preselected. Clinical and analytical characteristics were assessed at baseline. After excluding patients with other conditions known to disturb calcium metabolism 141 patients were identified. Except one, all patients were prospectively followed for 12 months after obtaining the blood samples. Hypovitaminosis D was considered when serum 25(OH)D < 30 ng/mL. Secondary hyperparathyroidism was considered when serum iPTH was higher than normal (50 pg/mL) in patients with hypovitaminosis D. COPD exacerbations and hospital admissions were recorded during the follow-up., Results: Prevalence of hypovitaminosis D in COPD patients was 89.3%, prevalence of secondary hyperparathyroidism associated with hypovitaminosis D was 22,9%. Cox proportional risk analysis showed that patients belonging to the high iPTH-low 25(OH)D group were at a higher risk of moderate COPD exacerbations (HR 1.81 (CI95% 1.043-3.127), p = 0.035) and hospital admissions (HR 5.45 (CI95% 2.018-14.720), p = 0.002) as compared with those with normal iPTH-low 25(OH)D levels., Conclusions: COPD patients with hypovitaminosis D and elevated iPTH have higher risk of moderate exacerbations and hospitalizations than those with hypovitaminosis D and normal iPTH., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Two previous national epidemiological studies, IBERPOC in 1997 and EPISCAN in 2007, determined the COPD burden in Spain. Changes in demographics and exposure to risk factors demand the periodic update of COPD prevalence and its determinants., Methods: EPISCAN II aimed to estimate the prevalence of COPD in the general population aged 40 years or older in all 17 regions of Spain. A random population screening sample, requiring 600 participants per region performed a questionnaire plus post-bronchodilator (post-BD) spirometry., Results: A total of 12,825 subjects were initially contacted, and 9433 (73.6%) agreed to participate, of whom 9092 performed a valid spirometry. Baseline characteristics were: 52.6% women, mean±SD age 60±11 years, 19.8% current- and 34.2% former-smokers. The prevalence of COPD measured by post-BD fixed ratio FEV 1 /FVC<0.7 was 11.8% (95% C.I. 11.2-12.5) with a high variability by region (2.4-fold). Prevalence was 14.6% (95% C.I. 13.5-15.7) in males and 9.4% (95% C.I. 8.6-10.2) in females; according to the lower limit of normal (LLN) was 6.0% (95% C.I. 5.5-6.5) overall, by sex being 7.1% (95% C.I. 6.4-8.0) in males and 4.9% (95% C.I. 4.3-5.6) in females. Underdiagnosis of COPD was 74.7%. Cases with COPD were a mean of seven years older, more frequently male, of lower attained education, and with more smokers than the non-COPD population (p<0.001). However, the number of cigarettes and pack-years in non-COPD participants was substantial, as it was the reported use of e-cigarettes (7.0% vs. 5.5%) (p=0.045). There were also significant social and clinical differences including living alone, previous respiratory diagnoses, more comorbidities measured with the Charlson index, greater BODE and COTE scores, cognitive impairment, and depression (all p<0.001)., Conclusions: COPD remains prevalent in Spain and frequently underdiagnosed., (Copyright © 2020 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: 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 (FEV 1 , PaO 2 , DL CO , 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., Competing Interests: Sara Cazorla-Rivero, Glorian Mura-Escorche, Francisca Gonzalvo-Hernández, Delia Mayato, and Elizabeth Córdoba-Lanús, declare not to have any financial or personal conflict of interests. Ciro Casanova Macario reports grants from Astra-Zeneca, GSK, and Menarini, advisory board for Astra-Zeneca and GSK, financial support for congress from Boehringer, Novartis and Menarini, personal fees from Bial, and lectures for Novartis, outside the submitted work; and declares to have received lectures and/or scientific advice from Laboratorios Bial, Boehringer-Ingelheim, AstraZeneca, GSK, Esteve, Menarini, Novartis and Rovi in the last three years. The authors report no other potential conflicts of interest for this work., (© 2020 Cazorla-Rivero 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., Competing Interests: Luis Perez de Llano declares to have received grants and/or fees for consultancy or speeches from Novartis, Astra-Zeneca, GSK, Teva, Boehringer-Ingelheim, Chiesi, Sanofi, Menarini, Mundipharma, and Esteve, and reports grants, personal fees, and non-financial support from AstraZeneca, TEVA, and Chiesi, personal fees and non-financial support from GSK, Novartis, Mundipharma and Boehringer, personal fees from Sanofi, other from Menarini, and personal fees from Esteve, BIAL, TECHDOW PHARMA, MSD, and ROVI S.A., outside the submitted work; Marc Miravitlles has received speaking fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, AstraZeneca, Menarini, Rovi, Bial, Zambon, CSL Behring, Grifols, and Novartis; consulting fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Ferrer, GlaxoSmithKline, Bial, Gebro Pharma, CSL Behring, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, pH Pharma, Novartis, and Grifols; and aid for research from GlaxoSmithKline and Grifols, and reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, Menarini, Rovi, Bial, Sandoz, Zambon, CSL Behring, Novartis, GlaxoSmithKline, Gebro Pharma, Kamada, Laboratorios Esteve, Ferrer, Mereo Biopharma, Verona Pharma, TEVA, Spin Therapeutics, pH Pharma, Sanofi and Grifols, and grants from GlaxoSmithKline and Grifols, outside the submitted work. Rafael Golpe declares that he has received speaking or advisory fees, or economic aid to attend congresses from Astra-Zeneca, GSK, Novartis, Chiesi, Mundipharma, Menarini, TEVA, Grifols, Ferrer, Boehringer-Ingelheim, Rovi, and Gebro. Borja G Cosío declares he has received speaking or advisory fees, or economic aid to attend congresses from Astra-Zeneca, GSK, Novartis, Chiesi, Mundipharma, Menarini, TEVA, Boehringer-Ingelheim, and Rovi and reports personal fees from AstraZeneca, GlaxoSmithKline, Rovi, Boehringer-Ingelheim, Chiesi, Menarini, Rovi, Zambon, Grifols, Novartis, Ferrer, Gebro Pharma, and Laboratorios Esteve, during the conduct of the study. Francisco Javier Alvarez-Gutiérrez declares that in the last 3 years he has received fees for advisory work, lectures, or subsidies to attend congresses and scientific meetings from ALK, AstraZeneca, BIal, Boehringer-Ingelheim, Chiesi, GSK, Menarini, Mundipharma, Novartis, and TEVA. Carolina Cisneros has received speaking fees from AstraZeneca, GSK, TEVA, Menarini, Mundipharma, and Novartis; aid to attend congresses from Chiesi, TEVA, Menarini, and Mundipharma; and fees for advisory work from ALK, AstraZeneca, MundiPharma, TEVA, GSK, and Novartis, and reports grants, personal fees, and non-financial support from AstraZeneca, grants and personal fees from GSK and Novartis, personal fees and non-financial support from TEVA, Menarini, Chiesi and Mundipharma, and personal fees from ALK, outside the submitted work. Carlos Almonacid declares to have received funding in the last 5 years from Astra-zeneca, GSK, Novartis, Chiesi, Mundipharma, Menarini, and TEVA, by way of aid to attend congresses, or as speaking or consulting fees, and reports grants and personal fees from GSK and AstraZeneca, personal fees from ALK, Novartis, Chiesy, and Mundipharma, and non-financial support from Menarini, outside the submitted work. Eva Martinez-Moragon declares to have received funding in the last 5 years from Astra-zeneca, GSK, ALK, Novartis, Chiesi, Mundipharma, Menarini, and TEVA, by way of aid to attend congresses, as speaking fees, or participation in scientific consultancy. Francisco-Javier Gonzalez-Barcala has received speaking fees or research grants from ALK, AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Gebro Pharma, GlaxoSmithKline, Laboratorios Esteve, Menarini, Mundipharma, Novartis, Rovi, Roxall, Stallergenes-Greer, and Teva, and reports speaker fees, consulting fees or research grants from ALK, Astra-Zeneca, Bial, Boehringer Ingelheim, Chiesi, Gebro Pharma, GlaxoSmithKline, Laboratorios Esteve, Menarini, Mundipharma, Novartis, Rovi, Roxall, Stallergenes-Greer and Teva. David Ramos-Barbón reports personal fees from GlaxoSmithKline, AstraZeneca, TEVA Pharmaceuticals, personal fees and non-financial support from Novartis and Chiesi, non-financial support from Boehringer-Ingelheim, and personal fees from BIAL Pharmaceuticals, outside the submitted work. Vicente Plaza declares to have received, in the last 3 years, fees for participating as speaker at meetings sponsored by AstraZeneca, Chiesi, and Novartis, and as a consultant from ALK, AstraZeneca, Bial, Boehringer, MundiPharma, and Sanofi; he received economic aid to attend congresses from AZ, Chiesi, and Novartis; and he received subsidies for research projects from AZ, Chiesi, and Menarini; and reports grants and personal fees from AstraZeneca and Chiesi, grants from Menarini, and personal fees from Sanofi, Mundipharma, Boehringer-Ingelheim, GlaxoSmithKline, and Merck, outside the submitted work. Jose Luis López-Campos has received fees, in the last 3 years, for giving lectures, scientific consultancy, participation in clinical studies, or writing papers for (alphabetical order): AstraZeneca, Boehringer Ingelheim, Chiesi, CSL Behring, Esteve, Ferrer, Gebro, GlaxoSmithKline, Grifols, Menarini, Novartis, Rovi, and Teva, and reports personal fees and non-financial support from AstraZeneca, grants, personal fees, and non-financial support from Boehringer, Chiesi, GSK, Grifols, Menarini, and Novartis, personal fees from CSL Behring, Esteve, and Ferrer, grants and personal fees from GebroPharma, and personal fees from Rovi and Teva, outside the submitted work. Ciro Casanova has received fees for giving lectures, scientific consultancy, participation in clinical studies, or writing papers for (alphabetical order): AstraZeneca, Bial, Boehringer Ingelheim, Chiesi, Esteve, Gebro, GlaxoSmithKline, Menarini, Novartis, Rovi, and Teva, and reports non-financial support from Astra-Zeneca, personal fees from Bial, Boehringer-Ingelheim, Chiesi, Esteve, and Novartis, personal fees and non-financial support from GSK, and grants and non-financial support from Menarini, outside the submitted work. Juan Luis Rodriguez Hermosa has received speaking fees from Boehringer Ingelheim and Gebro Pharma and reports personal fees from Boehringer Ingelheim, Grifols, Gebro, and Glaxo, outside the submitted work. Myriam Calle Rubio has received speaking fees from Boehringer Ingelheim, AstraZeneca, GlaxoSmithKline, Menarini, and Novartis; and consulting fees from GlaxoSmith¬Kline, Gebro Pharma, and Novartis, and reports personal fees from Boehringer Ingelheim, Menarini, Novartis, Gebro, Glaxo, and AstraZeneca, outside the submitted work. JJ Soler-Cataluña declares to have received fees for giving lectures, scientific consultancy, or participation in clinical studies on behalf of Air Liquide, AstraZeneca, Boehringer Ingelheim, Chiesi, Esteve, Ferrer, GSK, Menarini, Mundipharma, Novartis, Rovi, Sandoz, and Teva and reports grants and personal fees from AstraZeneca, Chiesi, and GSK, grants, personal fees, and non-financial support from Boehringer-Ingelheim and Novartis, and personal fees from Bial, Ferrer, Rovi, and Teva, outside the submitted work. Borja G Cosio reports grants and personal fees from AstraZeneca, Chiesi, and GSK, personal fees from Novartis, personal fees and non-financial support from Mundipharma, and grants from Menarini, Teva, Boehringer-Ingelheim, and Rovi, outside the submitted work. The rest of the authors declare they have no conflict of interests for this work. The rest of the authors declare they have no conflict of interests for this work., (© 2020 Pérez de Llano et al.)

Background: There is partial evidence that COPD is expressed differently in women than in men, namely on symptoms, pulmonary function, exacerbations, comorbidities or prognosis. There is a need to improve the characterization of COPD in females., Methods: We obtained and pooled data of 17 139 patients from 22 COPD cohorts and analysed the clinical differences by sex, establishing the relationship between these characteristics in women and the prognosis and severity of the disease. Comparisons were established with standard statistics and survival analysis, including crude and multivariate Cox-regression analysis., Results: Overall, 5355 (31.2%) women were compared with men with COPD. Women were younger, had lower pack-years, greater FEV 1 %, lower BMI and a greater number of exacerbations (all p < 0.05). On symptoms, women reported more dyspnea, equal cough but less expectoration (p < 0.001). There were no differences in the BODE index score in women (2.4) versus men (2.4) (p = 0.5), but the distribution of all BODE components was highly variable by sex within different thresholds of BODE. On prognosis, 5-year survival was higher in COPD females (86.9%) than in males (76.3%), p < 0.001, in all patients and within each of the specific comorbidities that we assessed. The crude and adjusted RR and 95% C.I. for death in males was 1.82 (1.69-1.96) and 1.73 (1.50-2.00), respectively., Conclusions: COPD in women has some characteristic traits expressed differently than compared to men, mainly with more dyspnea and COPD exacerbations and less phlegm, among others, although long-term survival appears better in female COPD patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Introduction: The EPISCAN study, published in 2007, was an update of the results of the 1997 IBERPOC study. Changes in demographics and exposure to risk factors demand the periodic update of prevalence and determining factors in COPD. This article is a summary of the protocol and tools used in EPISCAN II., Materials and Methods: The primary objective of EPISCAN II is to estimate the prevalence of COPD among the general population aged 40 years or more in the 17 autonomous communities of Spain. The sample size requires 600 participants (300 men and 300 women) per center, selected by screening 10,200 participants in a short visit (questionnaire plus forced post-bronchodilator spirometry). Of these, 800 (400 with COPD and 400 without COPD) will also perform a long visit (including a walking test, blood tests, determination of diffusion, pulse oximetry and bioimpedance, and low radiation CT)., Results: The first participant was recruited on 28 February 2017. As of 22 November 2017, a total of 3,581 participants had been included, of whom 422 had already performed the long visit. It is estimated that the field work will be completed by December 2018. The new imaging data, biomarkers, and information on new exposures, such as electronic cigarettes and environmental pollution, will help us re-quantify the burden of COPD., Conclusions: EPISCAN II will provide updated information on prevalence and determinants of COPD in Spain, allowing for the comparison of spirometric results and other factors associated with COPD among the 17 autonomous communities., (Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The objective of this study was to analyze the clinical characteristics of COPD patients attending general respiratory clinics, adherence to clinical guidelines, classification accuracy, and therapeutic management., Method: Multicenter, cross-sectional study, with the primary objective of describing the number, intensity, and variability of symptoms in COPD patients. Data were collected in 2015 by 300 pulmonologists who evaluated a total of 3,010 patients, of which 2,669 (88.6%) were eligible for analysis., Results: A total of 22% were active smokers, notably 21% and 17% of GOLD groups C and D, and 17% and 19% of exacerbators in the GesEPOC classification; 62.3% had associated comorbidities. The diagnostic process was characterized by limited use of tests such as diffusion capacity or lung volumes, even in the more severe GOLD groups or the GesEPOC exacerbator phenotypes. The use of multidimensional scales, such as BODE (12%), and specific rehabilitation protocols was also rare. Treatment was based on different combinations of bronchodilators and inhaled corticosteroids. Methylxanthines were used in very few patients (7%)., Conclusions: A large proportion of COPD patients seen in respiratory clinics have non-complex disease and pulmonology tests are rarely performed. Our study confirms a slight change in treatments and the frequent association with comorbidities that can modify the clinical presentation of the patient., (Copyright © 2018 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Background: The stability of the new GOLD 2017 COPD staging is unknown, as well as the frequency of individual transitions in COPD stages beyond one year., Methods: All COPD participants in the CHAIN cohort were re-analysed according to GOLD 2017 up to five years of follow-up. Their individual changes within COPD stages were aggregated into cohort-wide Markov chains; group stability was evaluated using joinpoint regression., Results: At baseline, 959 COPD patients were distributed according to GOLD 2017 stages as 37.7% in A, 38.3% B, 8.2% C, and 15.7% D. The group proportion of patients in each stage was maintained from years one to five. However, we found significant changes between stages at the individual patient level, especially in the more severe stages. The probability of a patient remaining in the same GOLD 2017 COPD stage for two consecutive years ranged during the five years of follow-up for stage C from 16% to 31% per year, while for D from 23% to 43% per year, indicating substantial variation either increasing or decreasing severity for the vast majority of patients., Conclusions: We conclude that group stability observed in COPD staging according to GOLD 2017 recommendations is paired with a large variability at the individual patient level., (Copyright © 2018. Published by Elsevier Ltd.)

Background: Cross-sectional and longitudinal studies describe shorter telomeres in patients with chronic obstructive pulmonary disease (COPD) compared to matched non-COPD controls, but the relationship is confounded by tobacco consumption. We hypothesized that telomere shortening would be similar between non-smoking and smoking individuals with airflow limitation and shorter than non-obstructed controls., Methods: Telomere length (T/S) was measured by qPCR in blood leukocytes of 80 non-smoking patients and 80 age-matched smokers with airflow limitation. Forty non-smoker healthy individuals served as controls. Anthropometrics, lung function, previous and current comorbidities were recorded in all individuals. Relationship between telomere length and clinical and functional variables were explored in the three groups., Results: Telomeres length was similar in non-smokers and smoker individuals with airflow limitation (T/S = 0.61 ± 0.19 vs. 0.60 ± 0.23, p > 0.05) respectively. Telomere length was significantly shorter in both groups compared to healthy controls (T/S 0.79 ± 0.40; p = 0.01) independent from age and sex. No significant association was found between the telomere length and clinical or lung function parameters., Conclusions: Telomere shortening is associated with airflow limitation independent of smoking status. Weather premature ageing or biologically determined shorter telomeres are responsible for this finding remain to be determined., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To describe the evidence- and experience-based expert consensus on the use of single-agent bronchodilators in patients with stable mild-moderate chronic obstructive pulmonary disease (COPD)., Methods: Using Delphi methodology, a panel of 7 respiratory medicine experts was established, who, in the first nominal group meeting defined the scope, users, and document sections. The panel drew up 14 questions on the use of single-agent bronchodilators in patients with mild-moderate stable COPD to be answered with a systematic review of the literature. The results of the review were discussed in a second nominal group meeting and 17 statements were generated. Agreement/disagreement with the statements was tested among16 different experts including respiratory medicine experts and primary care physicians. Statements were scored from1 (total disagreement) to10 (total agreement). Agreement was considered if at least 70% voted ≥7. The level of evidence and grade of recommendation of the systematic literature review was assessed using the Oxford Centre for Evidence-based Medicine levels., Results: A total of 12 of the 17 statements were selected. Specific statements were generated on different profiles of patients with stable mild-moderate COPD in whom single-agent bronchodilators could be prescribed., Conclusions: These statements on the use of single-agent bronchodilators might improve the outcomes and prognosis of patients with stable mild-moderate COPD., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Few studies have investigated the variability of COPD-related symptoms or factors related to symptom variability. This observational, prospective, multicentre study was conducted to describe the number and intensity of morning and night-time respiratory symptoms and their variability over one week using the Night-time and Early Morning Symptoms of COPD Instruments (NiSCI and EMSCI) to evaluate stable COPD patients. Logistic regression analyses were performed to investigate factors associated with symptom variability. A total of 2669 patients were evaluated (mean age, 67.7 years; 80.9% men; mean FEV1 50.6%). Of these, 48% reported night-time symptoms and 71% reported morning symptoms. Of the 2293 patients who completed the NiSCI and EMSCI, 90% showed variability in either symptom number (89.6%) or symptom intensity (15.8%). More severe dyspnoea, more exacerbations during the previous year and the exacerbator or mixed COPD-asthma phenotypes were associated with variability in symptom number or intensity. Anxiety was significantly associated with variability in symptom number and intensity. Most COPD patients showed symptom variability over a weeklong period, especially in terms of symptom number. Several COPD-related factors, mainly factors related to more severe disease and more frequent exacerbations, were associated with increased symptom variability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Following a proposal by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), sponsor of the Spanish COPD Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma (GEMA), authors of both papers have unified the criteria for the diagnosis of asthma-COPD overlap syndrome (ACOS). This consensus defines ACOS as the presence in a given patient of three elements: significant smoking exposure, chronic airflow limitation and asthma. Diagnosis is confirmed when a patient (35years of age or older), smoker or ex-smoker of more than 10 pack-years, presents airflow limitation (post-bronchodilator FEV1/FVC<0.7) that persists after treatment with bronchodilators and inhaled corticosteroids (even after systemic corticosteroids in selected cases), and an objective current diagnosis of asthma (according to GEMA criteria). In cases in which the diagnosis of asthma cannot be demonstrated, marked positive results on a bronchodilator test (FEV 1 ≥15% and ≥400mL) or elevated blood eosinophil count (≥300eosinophils/μL) will also be diagnostic of ACOS. The opinion of another 33 experts who had not participated in the consensus was sought using a modified Delphi survey. Up to 80% of respondents gave a very positive opinion of the consensus, and declared that it was better than other previous proposals. The GesEPOC-GEMA consensus on ACOS provides a unique perspective of the diagnostic problem, using a simple proposal and a pragmatic diagnostic algorithm that can be applied at any healthcare level., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

The clinical presentation of chronic obstructive pulmonary disease (COPD) varies widely, so treatment must be tailored according to the level of risk and phenotype. In 2012, the Spanish COPD Guidelines (GesEPOC) first established pharmacological treatment regimens based on clinical phenotypes. These regimens were subsequently adopted by other national guidelines, and since then, have been backed up by new evidence. In this 2017 update, the original severity classification has been replaced by a much simpler risk classification (low or high risk), on the basis of lung function, dyspnea grade, and history of exacerbations, while determination of clinical phenotype is recommended only in high-risk patients. The same clinical phenotypes have been maintained: non-exacerbator, asthma-COPD overlap (ACO), exacerbator with emphysema, and exacerbator with bronchitis. Pharmacological treatment of COPD is based on bronchodilators, the only treatment recommended in low-risk patients. High-risk patients will receive different drugs in addition to bronchodilators, depending on their clinical phenotype. GesEPOC reflects a more individualized approach to COPD treatment, according to patient clinical characteristics and level of risk or complexity., (Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.)

Chronic obstructive pulmonary disease (COPD), although frequent in older individuals, can also occur at younger age; this latter population has not been well described. We reviewed the functional progression of 1708 patients with COPD attending pulmonary clinics. Those with three or more annual spirometries were divided into those who, at enrolment, were ≤ 55 (n = 103) or ≥ 65 (n = 463) years of age (younger and older COPD, respectively). Baseline and annual changes in lung function (forced expiratory volume in 1 s (FEV1)) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) score were recorded and compared between both groups. Severity distribution by Global Initiative for Chronic Obstructive Lung Disease and BODE scores were similar in both groups, except for mild obstruction, which was higher in the younger group. Mean FEV1 decline was 38.8 and 40.6 mL · year(-1), while BODE scores increased 0.19 and 0.23 units per year, for younger and older COPD, respectively. Both groups had similar proportion of FEV1 rapid decliners (42% and 46%, respectively). The severity distribution and progression of disease in younger patients with COPD is similar to that of patients of older age. This observation suggests that younger individuals presenting with COPD develop the disease from an already compromised pulmonary and systemic status, complementing the model of steeper decline of lung function proposed by Fletcher and Peto., (©ERS 2014.)

Objective: The COPD Assessment Test (CAT) has been proposed for assessing health status in COPD, but little is known about its longitudinal changes. The objective of this study was to evaluate 1-year CAT variability in patients with stable COPD and to relate its variations to changes in other disease markers., Methods: We evaluated the following variables in smokers with and without COPD at baseline and after 1 year: CAT score, age, sex, smoking status, pack-year history, BMI, modified Medical Research Council (mMRC) scale, 6-min walk distance (6MWD), lung function, BODE (BMI, obstruction, dyspnea, exercise capacity) index, hospital admissions, Hospital and Depression Scale, and the Charlson comorbidity index. In patients with COPD, we explored the association of CAT scores and 1-year changes in the studied parameters., Results: A total of 824 smokers with COPD and 126 without COPD were evaluated at baseline and 441 smokers with COPD and 66 without COPD 1 year later. At 1 year, CAT scores for patients with COPD were similar (± 4 points) in 56%, higher in 27%, and lower in 17%. Of note, mMRC scale scores were similar (± 1 point) in 46% of patients, worse in 36%, and better in 18% at 1 year. One-year CAT changes were best predicted by changes in mMRC scale scores (β-coefficient, 0.47; P < .001). Similar results were found for CAT and mMRC scale score in smokers without COPD., Conclusions: One-year longitudinal data show variability in CAT scores among patients with stable COPD similar to mMRC scale score, which is the best predictor of 1-year CAT changes. Further longitudinal studies should confirm long-term CAT variability and its clinical applicability., Trial Registry: ClinicalTrials.gov; No.: NCT01122758; URL: www.clinicaltrials.gov.

The value and timing of multidimensional assessments in chronic obstructive pulmonary disease (COPD) remains unclear because there is little information about their variability and relationship to outcome. The aim of this study was to determine the progression of COPD using clinical and spirometric variability over time with mortality as the outcome. We determined the annual intra-individual variability of forced expiratory volume in 1 s (FEV1) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index in 403 patients with at least five measurements. The pattern was defined as "stable" if the annual change remained constant in ≥66% of the observations and "unstable" if it did not meet that threshold. We explored the minimum number of yearly observations that related to mortality in the 704 patients of the cohort. The "unstable" pattern of FEV1 was seen in 53% and 40% of patients using a threshold of 40 mL·year(-1) and 100 mL·year(-1), respectively. There was a slightly more "stable" pattern in the BODE index (62% for 1 point). A profile associated with mortality was defined by a baseline measurement followed by annual measurements for 2 years of the BODE index, but not its individual components, including FEV1 (p<0.001). Progression of COPD measured using FEV1 is inconsistent and relates poorly to outcome. Monitoring the more stable BODE index better assesses disease progression.

Guidelines recommend defining chronic obstructive pulmonary disease (COPD) by airflow obstruction and other factors, but no studies have evaluated the ability of existing multicomponent indices to predict mortality up to 10 years. We conducted a patient-based pooled analysis. Survival analysis and C statistics were used to determine the best COPD index/indices according to several construct variables and by varying time-points. Individual data of 3633 patients from 11 COPD cohorts were collected, totalling the experience of 15 878 person-years. Overall, there were 1245 death events within our cohorts, with a Kaplan-Meier survival of 0.963 at 6 months, which was reduced to 0.432 at 10 years. In all patients, ADO (age, dyspnoea and forced expiratory volume in 1 s), BODE (body mass index, airflow obstruction, dyspnoea and exercise capacity) and e-BODE (BODE plus exacerbations) were the best indices to predict 6-month mortality. The ADO index was the best to predict 12-month (C statistic 0.702), 5-year (C statistic 0.695) and 10-year mortality (C statistic 0.698), and was significantly better than BODE (all p<0.05). The best indices to predict death by C statistics when adjusting by age were e-BODE, BODEx (substitution of exacerbations for exercise capacity) and BODE. No index predicts short-term survival of COPD well. All BODE modifications scored better than ADO after age adjustment. The ADO and BODE indices are overall the most valid multicomponent indices to predict time to death in all COPD patients.

Background: The 6-minute walk distance (6MWD) has been useful in the evaluation of men with COPD. Little is known about 6MWD in women with the disease., Objectives: Using healthy women as a reference, to evaluate the factors that help determine 6MWD in women with COPD. To explore if the 350 meters threshold differentiates survival in women as it does in men., Methods: Healthy women (n = 164) and with COPD (n = 223) were included in the study. Age, pack-years history, smoking status, comorbidities (Charlson Index), BMI, MRC dyspnea, spirometry and 6MWD were recorded in all participants and PaO(2) and IC/TLC in COPD women. The patients were prospectively followed and deaths registered. Factors predicting 6MWD were determined by multiple regression analysis. ROC analysis was used to calculate the best threshold value for the 6MWD with mortality as gold standard. Kaplan-Meier curves compared survival of patients that walked more or less than 350 m by age categories., Results: The 6MWD is decreased in women with COPD. Values decrease with age and GOLD stages. Age, BMI, smoking status, comorbidities, MRC and FEV(1%) are statistical significant predictors of 6MWD. A 350 m cut-off value has a good sensitivity and specificity to predict (73% and 80% respectively) and differentiate survival (p < 0.001 for log rank comparisons) in these patients., Conclusions: In women with COPD, the 6MWD decreases with age and GOLD stages. A 350 m distance is a valid threshold to differentiate survival. Further studies in different settings should confirm our findings.

Background: The relationship of diurnal desaturations (oximetry-measured blood oxygen saturation [S(pO(2))] < 90%) during activities of daily living and clinical aspects in patients with chronic obstructive pulmonary disease (COPD) and moderate hypoxemia has not been systematically evaluated., Methods: We prospectively studied 88 patients with stable COPD (forced expiratory volume in the first second [FEV(1)] < 80% of predicted, ratio of FEV(1) to forced vital capacity < 70% of predicted, and P(aO(2)) 60-70 mm Hg) with 24 hours of ambulatory oximetry. Desaturators were defined as those who spent >/= 30% of the time with S(pO(2)) < 90%. Patients engaged in their usual activities of daily living. We correlated these desaturations with the following variables, measured immediately before the 24 hours of oximetry: body mass index, dyspnea (measured with the modified Medical Research Council dyspnea scale), gas exchange, pulmonary function, quality of life (measured with the Saint George's respiratory questionnaire), and comorbidity (measured with the Charlson index)., Results: Thirty-three (38%) of the patients were desaturators: 50% nocturnal and 22% diurnal. We also measured daytime arterial blood gas values from arterial blood samples and found that the desaturators had higher P(aCO(2)) (p = 0.001) and lower P(aO(2)) (p = 0.007) than the nondesaturators. There were no differences in the other variables. The correlation between nocturnal and diurnal time with S(pO(2)) < 90% was r(2) = 0.67, and the concordance was low (Cohen's kappa 0.43, p < 0.001)., Conclusions: Patients with stable COPD and moderate hypoxemia have frequent and potentially important desaturations during activities of daily living and at night. In addition, there is a big difference in the profile and degree of nocturnal and diurnal desaturations. Twenty-four hours of oximetry provides valuable information for comprehensive evaluation of patients with COPD.