Introduction:Chronic obstructive pulmonary disease (COPD) is a major public health problem. Research over the past few years has shown that COPD is the result of dynamic and cumulative gene-environment interactions starting early in life. This opens new opportunities for the Prediction, Prevention, Personalized and Precise management (P4) of COPD in young adults. The P4COPD study sought to: (1) investigate the genomic and environmental/lifestyle determinants of COPD in young adults (18-50 years); (2) contrast them with those determined in children, adolescent and older individuals; and (3) explore the feasibility and cost of implementing a P4 strategy for COPD in young adults in clinical practice. Materials and methods:The P4COPD study leverages from already existing cohorts (EarlyCOPD, INMA, LEVANTE, Aduheart) of young subjects (18-50 years) and de novo recruitment from primary care centers, in whom we: (1) analyzed demographic, epidemiological, clinical and physiologic information; (2) measured genetic, epigenetic and proteomic markers; (3) used analytical methods to identify endotypes, biomarkers and potential therapeutic targets associated with the presence of COPD, pre-COPD and/or low peak lung function. Results in young individuals: (4) were contrasted with healthy controls from the general population (IMPACT cohort) and COPD cohorts in older patients (BIOMEPOC, CHAIN and ECLIPSE). Besides, we (5) explored how to implement results in clinical practice; and (6) estimated its potential health cost implications. Results:First results are expected in the third and fourth quarters of 2026. Conclusions:Identifying young individuals at risk of COPD, in whom to establish a P4 strategy is highly relevant to promote healthy aging.

The Tajogaite volcano (La Palma, Canary Islands,Spain) first erupted on 19 September 2021, and remained active for 85 days, leading to the emergency evacuation of approximately 7,000 people (out of a total island population of approximately 84,000). To determine the impact of the Tajogaite volcanic eruption on the use of health care services during and after the eruption in an exposed and unexposed adult population, as well as its impact on quality of life and anxiolytic medication use. Ambispective cohort study. Healthy adults between the ages of 18 and 70 with no previous respiratory diseases were included and classified into three groups according to their level of exposure: highly exposed, moderately exposed and unexposed. The frequency of visits to health services during and after the eruption, the reasons for medical consultation and the consumption of anxiolytics were analyzed. In addition, perceived quality of life was assessed using the SF-12 questionnaire. A total of 472 participants were included. During the eruption, 37.5

The Spanish COPD Guidelines (GesEPOC) were first published in 2012, and since then, several updates have incorporated new evidence regarding the diagnosis and treatment of COPD. GesEPOC is a clinical practice guideline developed with the collaboration of the scientific societies involved in COPD management and the Spanish Patients' Forum. Its recommendations are based on an evaluation of the evidence using the GRADE methodology and on a narrative description of the evidence in those areas where application of this methodology is not feasible. This article summarizes the updated recommendations on the pharmacological treatment of stable COPD, derived from the development of 12 PICO questions. The COPD treatment process comprises five stages: (1) diagnosis; (2) risk stratification; (3) characterization; (4) initiation and continuation of treatment; and (5) follow-up. For inhaled treatment selection, high-risk patients are classified into three phenotypes: non-exacerbator, eosinophilic exacerbator, and non-eosinophilic exacerbator. Treatable traits include general aspects, applicable to all patients-such as smoking cessation and inhaler technique-and more specific conditions, mainly affecting severe patients, such as chronic hypoxemia or chronic bronchial infection. The cornerstone of COPD treatment is long-acting bronchodilators, either as monotherapy or in combination, depending on the patient's risk level. Eosinophilic exacerbators should receive inhaled corticosteroids, whereas non-eosinophilic exacerbators require a detailed evaluation to identify the most appropriate therapeutic option. GesEPOC 2025 also includes recommendations on inhaled corticosteroid withdrawal, the introduction of biologics, and the indication for alpha-1 antitrypsin therapy. GesEPOC 2025 represents a more individualized approach to COPD treatment, tailored to the clinical characteristics of patients and their level of risk or complexity.

Rationale: The prevalence of obstructive sleep apnea (OSA) or nocturnal hypoxemia without OSA (i.e., isolated nocturnal hypoxemia [iNH]) and its impact on the natural history of chronic obstructive pulmonary disease (COPD) are unclear. Objective: We determined the prevalences of OSA and iNH in patients with COPD and their contribution to all-cause mortality and COPD exacerbations. Methods: At baseline, we performed home sleep apnea testing in the CHAIN (COPD History Assessment in Spain) study cohort. OSA was defined by an apnea-hypopnea index of ⩾15 events per hour, and iNH was defined by an oxygen saturation as measured by pulse oximetry <90% for >30% of the nocturnal recording time. During an observation time of 6.5 years, we evaluated the association of OSA or iNH with all-cause mortality using multivariable Cox regression models and with COPD exacerbations using negative binomial models. Results: Among 428 patients with COPD, OSA and nocturnal hypoxemia were ruled out in 41%, whereas 27% had iNH and 32% had OSA (i.e., COPD/OSA "overlap syndrome" [OVS]). OVS was independently associated with obesity as defined by a body mass index ⩾30 kg/m2 and with severe COPD exacerbations (P < 0.01), whereas iNH was associated with lower forced expiratory volume in 1 second and lower resting arterial oxygen saturation. Compared with patients with COPD without OSA or iNH, those with untreated OVS had greater risks of mortality (hazard ratio, 1.74; 95% confidence interval, 1.03-2.94) and COPD exacerbations (incidence rate ratio, 1.44; 95% confidence interval, 1.05-2.03). Conclusions: OSA and iNH are frequent in patients with COPD, and the prevalences decrease or increase, respectively, with disease severity. Patients with COPD with untreated OVS but not with iNH had a greater risk of all-cause mortality and COPD exacerbations.

The analysis of blood metabolites may help identify individuals at risk of having COPD and offer insights into its underlying pathophysiology. This study aimed to identify COPD-related metabolic alterations and generate a biological signature potentially useful for screening purposes. Plasma metabolomic profiles from 91 COPD patients and 91 controls were obtained using complementary semi-targeted and untargeted LC-MS approaches. Univariate analysis identified metabolites with significant differences between groups, and enrichment analysis highlighted the most affected metabolic pathways. Multivariate analysis, including ROC curve assessment and machine learning algorithms, was applied to assess the discriminatory capacity of selected metabolites. After adjustment for major potential confounders, 56 metabolites showed significant differences between COPD patients and controls. The enrichment analysis revealed that COPD-associated metabolic alterations primarily involved lipid metabolism (especially fatty acids and acylcarnitines), followed by amino acid pathways and xenobiotics. A panel of 10 metabolites, mostly related to lipid metabolism, demonstrated high discriminatory performance for COPD (ROC-AUC: 0.916; 90.1% sensitivity and 89% specificity). These findings may contribute to improving screening strategies and a better understanding of COPD-related metabolic changes. However, our findings remain exploratory and should be interpreted with caution, needing further validation and mechanistic studies.

BACKGROUND:Patients with COPD are at high risk of major adverse cardiovascular events (MACEs) developing. Existing clinical tools for risk stratification in these patients have underperformed in predicting the outcomes. RESEARCH QUESTION:Does a combination of cardiovascular risk score (CVRS) and coronary artery calcium score (CACS) improve risk assessment of MACEs in patients with COPD? STUDY DESIGN AND METHODS:This was an observational cohort of patients with COPD (n = 529). They underwent a chest CT scan, and clinical, functional, and laboratory data were recorded. The CACS and CVRS (Systematic Coronary Risk Evaluation [SCORE] 2, SCORE2-Older People [OP], SCORE2-Diabetes, and Secondary Manifestations of Arterial Disease [SMART] risk scores) were calculated. Using a threshold of CVRS of ≥ 10% or CACS score of > 3, patients were divided into 4 groups-group I, CVRS < 10% and CACS ≤ 3; group II, CVRS ≥ 10% and CACS ≤ 3; group III, CVRS < 10% and CACS > 3; and group IV, CVRS ≥ 10% and CACS > 3-who were followed up for a median of 98 months. Regression analysis and Kaplan Meier curves were used to compare the risks among groups. Receiver operating characteristic (ROC) curve analysis determined the performance of CACS and CVRS and their combination to predict MACEs. RESULTS:Most patients were male (80%) with moderate COPD. Over time, 131 patients (24%) experienced a MACE. Compared with group I, the hazard ratios for MACEs were: group IV, 7.6 (95% CI, 4.9-11.9; P < .001); group III, 3.1 (95% CI, 1.8-8.5; P < .001); and group II, 2.6 (95% CI, 1.6-4.2; P < .001). The areas under the ROC curve for predicting MACEs were 0.72 (P < .01) for CACS plus CVRS compared with 0.69 for CVRS and 0.66 for CACS. CONCLUSIONS:The combination of cardiovascular risk and coronary artery calcification scores were shown to provide a complementary role in MACE risk stratification in patients with COPD.

RATIONALE:The lung diffusing capacity for carbon monoxide (DLco), a metric of gas transfer, provides physiological information distinct from spirometry. While DLco independently predicts mortality in COPD, its integration into the GOLD spirometric staging (% FEV1) to improve risk assessment, remains unexplored. OBJECTIVES:To determine if DLco enhances the predictive power of GOLD spirometric classification for all-cause and respiratory mortality. METHODS:We followed 469 patients (mean age 64 years, 58% FEV1) with complete lung function tests in the Spanish multicenter CHAIN study for up to 10 years, with mortality as the main outcome. Patients were dichotomized based on DLco impairment (<50% cutoff). A Cox proportional hazard model evaluated the added value of DLco to GOLD FEV1 spirometric staging for all-cause and respiratory mortality. Validation of the results was conducted in the Kingston COPD Canadian cohort (N=300 patients). RESULTS:Over time, 184 (39.2%) patients died, 84 (17.9%) from respiratory causes. Adjusted analyses showed DLco<50% independently predicted all-cause [HR=1.83 (95%CI 1.32-2.54, p<0.001)] and respiratory [HR=2.27 (95%CI 1.43-3.60, p<0.001)] mortality. Incorporating DLco<50% increased mortality risk compared to FEV1 alone, particularly in GOLD stages 3 and 4, where survival time decreased by 1.23 years (p=0.002) and 1.25 years (p=0.004) for all-cause and respiratory deaths, respectively. These findings were validated in the Canadian cohort. CONCLUSIONS:Adding DLco to FEV1 enhances the prognostic accuracy of the GOLD spirometric severity classification, especially for patients in GOLD stages 3-4 at higher risk of adverse outcomes. CLINICALTRIALS:gov Identifier: NCT01122758.

Lung cancer (LC) constitutes an important cause of death among patients with Chronic Obstructive Pulmonary Disease (COPD). Both diseases may share pathobiological mechanisms related to oxidative damage and cellular senescence. In this study, the potential value of leucocyte telomere length, a hallmark of aging, and 8-OHdG concentrations, indicative of oxidative DNA damage, as risk biomarkers of LC was evaluated in COPD patients three years prior to LC diagnosis. Relative telomere length measured using qPCR and serum levels of 8-OHdG were determined at the baseline in 99 COPD smokers (33 with LC and 66 age-matched COPD without LC as controls). Of these, 21 COPD with LC and 42 controls had the biomarkers measured 3 years before. Single nucleotide variants (SNVs) in TERT, RTEL, and NAF1 genes were also determined. COPD cases were evaluated, which showed greater telomere length (p < 0.001) and increased serum 8-OHdG levels (p = 0.004) three years prior to LC diagnosis compared to the controls. This relationship was confirmed at the time of LC diagnosis. No significant association was found between the studied SNVs in cases vs. controls. In conclusion, this preliminary study shows that longer leucocyte telomere length and increased 8-OHdG serum levels can be useful as early biomarkers of the risk for future lung cancer development among COPD patients.

Background Not all hypercapnic COPD patients benefit from home noninvasive ventilation (NIV), and mechanisms through which NIV improves clinical outcomes remain uncertain. We aimed to identify “responders” to home NIV, denoted by a beneficial effect of NIV on arterial partial pressure of carbon dioxide (PaCO2), health-related quality of life (HRQoL) and survival, and investigated whether NIV achieves its beneficial effect through an improved PaCO2. Methods We used individual patient data from previous published trials collated for a systematic review. Linear mixed-effect models were conducted to compare the effect of NIV on PaCO2, HRQoL and survival, within subgroups defined by patient and treatment characteristics. Secondly, we conducted a causal mediation analysis to investigate whether the effect of NIV is mediated by a change in PaCO2. Findings Data of 1142 participants from 16 studies were used. Participants treated with lower pressure support (<14 versus ≥14 cmH2O) and with lower adherence (<5 versus ≥5 h·day−1) had less improvement in PaCO2 (mean difference (MD) −0.30 kPa, p<0.001 and −0.29 kPa, p<0.001, respectively) and HRQoL (standardised MD 0.10, p=0.002 and 0.11, p=0.02, respectively), but this effect did not persist to survival. PaCO2 improved more in patients with severe dyspnoea (MD −0.30, p=0.02), and HRQoL improved only in participants with fewer than three exacerbations (standardised MD 0.52, p=0.03). The results of the mediation analysis showed that the effect on HRQoL is mediated partially (23%) by a change in PaCO2. Interpretation With greater pressure support and better daily NIV usage, a larger improvement in PaCO2 and HRQoL is achieved. Importantly, we demonstrated that the beneficial effect of home NIV on HRQoL is only partially mediated through a reduction in diurnal PaCO2.

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) >= 150 cells/mu L. 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) 92 mu g/umeclidinium (UMEC) 55 mu g/vilanterol (VI) 22 mu g 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. (c) 2024 The Authors. Published by Elsevier Espana, S.L.U. on behalf of SEPAR. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Heteroatom-tagged proteomics allows the absolute quantification of selenoproteins using the heteroatom as a "tag" into a selective and sensitive atomic detector instead of a molecular one. Using this analytical method, about 90% of total selenium in human serum/plasma can be measured as selenoproteins and total selenometabolites and thus, the status of selenium can be determined. Herein, we determined the absolute concentration of selenoproteins in human serum patients with lung cancer (LC) and chronic obstructive pulmonary disease (COPD), a competing cause of morbidity and mortality in smokers as well as an independent risk factor for LC. We conducted an observational study of 154 human serum samples obtained from LC and COPD patients with varying severity of disease, including COPD patients who developed LC during follow-up and healthy controls (HC). Using heteroatom-tagged proteomics, we determined extracellular glutathione peroxidase (eGPx), selenoprotein P (SELENOP), and selenoalbumin (SeAlb). Associations between selenoproteins were also studied as potential biomarkers of disease. The concentration of eGPx was significantly higher in the all-inclusive COPD cohort compared to HC, COPD patients with LC, or those with mild obstructive lung disease, while SELENOP concentration was significantly decreased in LC patients compared to HC and COPD. We found an inverse correlation between SELENOP and SeAlb in HC, but also in LC patients, and especially in patients with COPD and LC. Moreover, we found that eGPx and selenometabolite concentrations were positively associated with LC human serum. Selenoprotein concentrations were altered in COPD and LC when compared to healthy controls suggesting a potential role of the selenoproteome in the diagnosis and/or treatment of these tobacco -related diseases.

Introduction: Exposure to gases and particulate matter released during volcanic eruptions can prove harmful to population health. This paper reports the preliminary results of the ASHES study, aimed at ascertaining the respiratory health effects of the 2021 volcanic eruption in La Palma Island (Spain) on the adult population without previous respiratory disease.Methods: Ambispective cohort study on the healthy adult population. Three exposure groups were considered: Group 1, high exposure; Group 2, moderate exposure; and Group 3, minor or no exposure. We carried out a descriptive analysis of symptoms during and after the eruption, as well as measure lung function after the eruption (through forced spirometry and diffusing capacity of carbon monoxide).Results: The analysis included 474 subjects: 54 in Group 1, 335 in Group 2, and 85 in Group 3. A significant increase in most symptoms was observed for subjects in the groups exposed during the eruption. After the eruption, this increase remained for some symptoms. There seems to be a dose-response relationship, such that the higher the exposure, the higher the odds ratio. A prebronchodilator FEV1/FVC ratio<70% was observed in 13.0% of subjects in Group 1, 8.6% of subjects in Group 2, and 7.1% of subjects in Group 3.Conclusions: This study is the first to report a dose-response relationship between exposure to volcanic eruptions and the presence of symptoms in adults. Furthermore, there is a tendency towards obstructive impairment in individuals with higher exposure.

Self-reported occupational exposure was previously associated with COPD in the Spanish population. This study aimed to analyse the relationship between occupational exposure to various chemical and biological agents, COPD, emphysema, and the bronchial wall area, which was determined by lung computed tomography (CT) in 226 individuals with COPD and 300 individuals without COPD. Lifetime occupational exposures were assessed using the ALOHA(+) job exposure matrix, and CT and spirometry were also performed. COPD was associated with high exposure to vapours, gases, dust and fumes (VGDF) (OR 2.25 95% CI 1.19–4.22), biological dust (OR 3.01 95% CI 1.22–7.45), gases/fumes (OR 2.49 95% CI 1.20–5.17) and with exposure to various types of solvents. High exposure to gases/fumes, chlorinated solvents and metals (coefficient 8.65 95% CI 1.21–16.09, 11.91 95%CI 0.46- 23.36, 14.45 95% CI 4.42–24.49, respectively) and low exposure to aromatic solvents (coefficient 8.43 95% CI 1.16–15.70) were associated with a low 15th percentile of lung density indicating emphysema. We conclude that occupational exposure to several specific agents is associated with COPD and emphysema in the Spanish population.

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.

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 .

Introduction: Eosinophils seem to play two different roles: a physiological and an inflammatory role. This concept has raised the theory of two differentiated populations; inflammatory eosinophils (iEos) and resident eosinophils (rEos). These differences have been shown previously by some authors. This study describes the effect of mepolizumab, omalizumab and dupilumab vs. asthmatic patients with no biological therapy on different eosinophil populations. Material and methods: Four cohorts were collected; asthmatics without biological treatment and asthmatics treated for at least 3 months with mepolizumab, omalizumab or dupilumab. All subjects who had taken systemic steroids in the last 3 months were excluded. Peripheral blood was studied by flow cytometry for surface protein profiles for eosinophilic differentiation (rEos: Siglec-8+CD62L+IL-3Rlo and iEos: Siglec-8+CD62LloIL-3Rhi). The IL-5 receptor and CD11b were also measured Results: The proportion of eosinophils sub-types were different in asthma patients only with mepolizumab (Table 1). IL3 receptors have decreased in patients with mepolizumab and dupilumab than in asthma patients without monoclonal antibodies. CD11b receptors have decreased only in patients with mepolizumab (Figure 1). Conclusions: The effect of monoclonal antibodies is different in the eosinophils sub-types. The eosinophils that remain in peripheral blood despite the use of mepolizumab seem to correspond to rEos with homeostatic functions. Omalizumab and dupilumab do not change the proportion of eosinophils subtypes but decrease IL3 receptor.

Whether called psychogeriatrics, old-age psychiatry, geriatric psychiatry, geriatric psychology, or mental health of the elderly, the clinical disciplines focusing on the mental health problems of older individuals are increasingly becoming recognized as subspecialties of their parent disciplines. Although the rate at which this is occurring is variable, interest is spreading worldwide and will continue to grow.

Lung cancer (LC) is the leading cause of cancer deaths, and chronic obstructive pulmonary disease (COPD) can increase LC risk. Metallomics may provide insights into both of these tobacco-related diseases and their shared etiology. We conducted an observational study of 191 human serum samples, including those of healthy controls, LC patients, COPD patients, and patients with both COPD and LC. We found 18 elements (V, Al, As, Mn, Co, Cu, Zn, Cd, Se, W, Mo, Sb, Pb, Tl, Cr, Mg, Ni, and U) in these samples. In addition, we evaluated the elemental profiles of COPD cases of varying severity. The ratios and associations between the elements were also studied as possible signatures of the diseases. COPD severity and LC have a significant impact on the elemental composition of human serum. The severity of COPD was found to reduce the serum concentrations of As, Cd, and Tl and increased the serum concentrations of Mn and Sb compared with healthy control samples, while LC was found to increase Al, As, Mn, and Pb concentrations. This study provides new insights into the effects of LC and COPD on the human serum elemental profile that will pave the way for the potential use of elements as biomarkers for diagnosis and prognosis. It also sheds light on the potential link between the two diseases, i.e., the evolution of COPD to LC.