Effect of physical activity in lymphocytes senescence burden in COPD patients.

Chronic obstructive pulmonary disease (COPD) is regarded as an accelerated-age disease in which chronic inflammation, maladaptive immune responses and senescence cell burden coexist. Accordingly, cellular senescence has emerged as a potential mechanism involved in COPD pathophysiology. In this study, 25 stable COPD patients underwent a daily physical activity promotion program for six months. We reported that increase of physical activity was related to a reduction of the senescent cell burden in COPD patients' circulating lymphocytes. Senescent T-lymphocytes population, characterized by absence of surface expression of CD28, was reduced after physical activity intervention and the reduction was associated to the increase of physical activity level. In addition, the mRNA expression of cyclin-dependent kinases inhibitors, a hallmark of cell senescence, was reduced and, in accordance, the proliferative capacity of lymphocytes was improved post-intervention. Moreover, we observed an increase in functionality in T-cells from patients after intervention, including improved markers of activation, enhanced cytotoxicity and altered cytokines secretions in response to viral challenge. Lastly, physical activity intervention reduced the potential of lymphocytes' secretome to induce senescence in human primary fibroblasts. In conclusion, our study provides, for the first time, evidence of the potential of physical activity intervention in COPD patients to reduce the senescent burden in circulating immune cells.

Endothelial dysfunction and persistent inflammation in severe post-COVID-19 patients: implications for gas exchange.

BACKGROUND: Understanding the enduring respiratory consequences of severe COVID-19 is crucial for comprehensive patient care. This study aims to evaluate the impact of post-COVID conditions on respiratory sequelae of severe acute respiratory distress syndrome (ARDS). METHODS: We examined 88 survivors of COVID-19-associated severe ARDS six months post-intensive care unit (ICU) discharge. Assessments included clinical and functional evaluation as well as plasma biomarkers of endothelial dysfunction, inflammation, and viral response. Additionally, an in vitro model using human umbilical vein endothelial cells (HUVECs) explored the direct impact of post-COVID plasma on endothelial function. RESULTS: Post-COVID patients with impaired gas exchange demonstrated persistent endothelial inflammation marked by elevated ICAM-1, IL-8, CCL-2, and ET-1 plasma levels. Concurrently, systemic inflammation, evidenced by NLRP3 overexpression and elevated levels of IL-6, sCD40-L, and C-reactive protein, was associated with endothelial dysfunction biomarkers and increased in post-COVID patients with impaired gas exchange. T-cell activation, reflected in CD69 expression, and persistently elevated levels of interferon-ß (IFN-ß) further contributed to sustained inflammation. The in vitro model confirmed that patient plasma, with altered levels of sCD40-L and IFN-ß proteins, has the capacity to alter endothelial function. CONCLUSIONS: Six months post-ICU discharge, survivors of COVID-19-associated ARDS exhibited sustained elevation in endothelial dysfunction biomarkers, correlating with the severity of impaired gas exchange. NLRP3 inflammasome activity and persistent T-cell activation indicate on going inflammation contributing to persistent endothelial dysfunction, potentially intensified by sustained viral immune response.

Long-term effect of obstructive sleep apnoea management on blood pressure in patients with resistant hypertension: the SARAH study.

BACKGROUND: There is a close relationship between obstructive sleep apnoea (OSA) and resistant hypertension (RH). However, studies assessing the long-term effect of diagnosing and treating OSA on blood pressure (BP) control in these patients are lacking. METHODS: To address this gap, we recruited 478 RH patients from hypertension units and followed them prospectively after they were screened for OSA through a sleep study. By performing 24-h ambulatory BP monitoring (ABPM) annually, the effect of OSA management was assessed. RESULTS: The patients had a median (interquartile range (IQR)) age of 64.0 (57.2-69.0) years, 67% were males and most were nonsleepy, with a median (IQR) apnoea-hypopnoea index (AHI) of 15.8 (7.9-30.7) events·h-1. The median (IQR) follow-up time was 3.01 (2.93-3.12) years. At baseline, severe OSA was associated with uncontrolled BP, nocturnal hypertension and a nondipper circadian BP pattern. Moreover, these patients had higher BP values during follow-up than did patients in the other groups. However, among patients with moderate and severe OSA, the management of sleep disordered breathing, including the implementation of continuous positive airway pressure treatment, was associated with a reduction in 24-h ABPM parameters, especially night-time BP values, at the 1-year follow-up. These benefits were attenuated over time and only subjects with severe OSA maintained an ABPM night-time reduction at 3 years. Furthermore, clinical variables such as uncontrolled BP, sex and age showed a predictive value for the BP response at 1 year of follow-up. CONCLUSION: A favourable long-term decrease in BP was detected by diagnosing and treating OSA in a cohort of RH patients from hypertension units, but over time this decrease was only partially maintained in severe OSA patients.

SARS-CoV-2 S protein activates NLRP3 inflammasome and deregulates coagulation factors in endothelial and immune cells.

BACKGROUND: Hyperinflammation, hypercoagulation and endothelial injury are major findings in acute and post-COVID-19. The SARS-CoV-2 S protein has been detected as an isolated element in human tissues reservoirs and is the main product of mRNA COVID-19 vaccines. We investigated whether the S protein alone triggers pro-inflammatory and pro-coagulant responses in primary cultures of two cell types deeply affected by SARS-CoV-2, such are monocytes and endothelial cells. METHODS: In human umbilical vein endothelial cells (HUVEC) and monocytes, the components of NF-κB and the NLRP3 inflammasome system, as well as coagulation regulators, were assessed by qRT-PCR, Western blot, flow cytometry, or indirect immunofluorescence. RESULTS: S protein activated NF-κB, promoted pro-inflammatory cytokines release, and triggered the priming and activation of the NLRP3 inflammasome system resulting in mature IL-1ß formation in both cell types. This was paralleled by enhanced production of coagulation factors such as von Willebrand factor (vWF), factor VIII or tissue factor, that was mediated, at least in part, by IL-1ß. Additionally, S protein failed to enhance ADAMTS-13 levels to counteract the pro-coagulant activity of vWF multimers. Monocytes and HUVEC barely expressed angiotensin-converting enzyme-2. Pharmacological approaches and gene silencing showed that TLR4 receptors mediated the effects of S protein in monocytes, but not in HUVEC. CONCLUSION: S protein behaves both as a pro-inflammatory and pro-coagulant stimulus in human monocytes and endothelial cells. Interfering with the receptors or signaling pathways evoked by the S protein may help preventing immune and vascular complications driven by such an isolated viral element. Video Abstract.

Motivation and Confidence about Physical Activity in Chronic Obstructive Pulmonary Disease Patients: Health Benefits Matter to Patients.

INTRODUCTION: Physical activity (PA) has shown great benefits in patients with chronic obstructive pulmonary disease (COPD); however, their PA is below average. Motivational factors associated with PA in COPD have not been widely studied and could be a target for improving adherence to PA. The objective of our study was to identify and understand the different motivational and confidence factors related to low levels of PA in a COPD cohort. METHOD: Observational, prospective, multicenter study of COPD patients. Sociodemographic data, respiratory symptoms, comorbidities, spirometry, and exercise capacity were collected. PA was measured using the Dynaport accelerometer and patient motivation and confidence in PA were assessed by a questionnaire previously used in a COPD population in the USA. RESULTS: Eighty six COPD patients were included, 68.6% being male, with a mean (SD) age of 66.6 (8.5) years and a mean forced expiratory volume in the first second (%) of 50.9% (17.3%). The mean walking time was 82.8 (37.8) minutes/day. Questions related to health benefits and enjoying exercise were ranked highest in the motivation questionnaire and statistically significant differences were found in PA measures between patients with low and high motivation. A lack of confidence regarding hot weather and health-related issues significantly influenced PA levels. Advice from third parties, including healthcare providers, was not associated with higher PA levels. CONCLUSIONS: Improving the health of COPD patients is their main motivation to perform PA. Lack of confidence when it is hot or when they fear for their health is related to low levels of PA. Advice from third parties, including healthcare professionals, is not associated with higher PA. These results are relevant for developing strategies to increase the adherence of COPD patients to PA programs.

Characteristics of obstructive sleep apnea related to insulin resistance.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with multiple comorbidities, including diabetes. Its development is preceded by alterations in the initial phase of carbohydrate metabolism characterized by insulin resistance. This study aims to evaluate the role of intermittent hypoxia and sleep fragmentation characteristic of OSA on the risk of insulin resistance among apneic patients without diabetes. METHODOLOGY: 92 consecutive patients with OSA without evidence of diabetes were recruited. Overnight video polysomnography was performed and, the following morning, fasting blood glucose, insulin and glycosylated hemoglobin were determined. Insulin resistance was measured using the HOMA-IR index. RESULTS: Insulin resistance was present in 52.2% of OSA patients. In these subjects, insulin resistance was independently associated to the apnea index during REM sleep (adjusted odds ratio [aOR] 1.09; 95% CI, 1.03 to 1.16; p = 0.004), desaturation index (aOR 1.08; 95% CI: 1.04 to 1.13; p = 0.027), and sleep time with oxygen saturation below 90% (aOR 1.04; 95% CI 1.00 to 1.08; p = 0.049). Furthermore, the HOMA-IR level was also directly related to the desaturation index (standardized regression coefficient [B] = 0.514, p < 0.001) and to the apnea index during REM sleep (B = 0.344, p = 0.002). CONCLUSIONS: Intermittent hypoxia and disturbances in REM sleep emerge as main contributors to insulin resistance in OSA patients yet to experience diabetes onset.

Dynamic hyperinflation is a risk factor for mortality and severe exacerbations in COPD patients.

OBJECTIVE: To assess if dynamic hyperinflation is an independent risk factor for mortality and severe exacerbations in COPD patients. METHODS: A cohort of 141 patients with stable COPD and moderate to very severe airflow limitation, treated according to conventional guidelines, was followed for a median of 9 years. Clinical characteristics were recorded and arterial blood gases, pulmonary function tests, 6-min walk and incremental exercise test with measurement of respiratory pattern and operative lung volumes were performed. Endpoints were all-cause mortality and hospitalization for COPD exacerbation. RESULTS: 58 patients died during the follow-up period (1228 patients x year). The mortality rate was higher in patients with dynamic hyperinflation (n = 106) than in those without it (n = 35) (14.6; 95% CI, 14.5-14.8 vs. 7.2; 95% CI, 7.1-7.4 per 1000 patients-year). After adjusting for sex, age, body mass index, pack-years and treatment with inhaled corticosteroids, dynamic hyperinflation was associated with a higher mortality risk (adjusted hazard ratio [aHR], 2.725; 95% CI, 1.010-8.161), and in a multivariate model, comorbidity, peak oxygen uptake and dynamic hyperinflation were retained as independent predictors of mortality. The time until first severe exacerbation was shorter for patients with dynamic hyperinflation (aHR, 3.961; 95% CI, 1.385-11.328), and dynamic hyperinflation, FEV1 and diffusing capacity were retained as independent risk factors for severe exacerbation. Moreover, patients with dynamic hyperinflation had a higher hospitalization risk than those without it (adjusted incidence rate ratio, 1.574; 95% CI, 1.087-2.581). CONCLUSION: In stable COPD patients, dynamic hyperinflation is an independent prognostic factor for mortality and severe exacerbations.

Dysregulation in CD39/CD73 Axis May Trigger the Upsurge of the Immune Suppressive Agent Adenosine in OSA Patients.

INTRODUCTION: Although higher incidence of cancer represents a major burden for obstructive sleep apnea (OSA) patients, the molecular pathways driving this association are not completely understood. Interestingly, adenosinergic signaling has emerged as a powerful immune checkpoint driving tumor development and progression. METHODS: Here, we explored the expression of the adenosinergic ecto-enzymes CD39 and CD73 in T-lymphocytes of OSA patients without any evidence of cancer, as well as their soluble forms in plasma (sCD39 and sCD73), along with adenosine. In addition, we explored the role of intermittent hypoxia (IH) in this context by in vitro models. RESULTS: Our results showed that CD39 is upregulated while CD73 is downregulated in OSA T-cells' membrane. Moreover, our findings suggest that IH, through HIF-1, mediates the upregulation of both CD39 and CD73; and that CD73 downregulation could be mediated by a higher release of sCD73 by OSA T-lymphocytes. Importantly, we found that both sCD39 and sCD73 are upregulated in OSA plasma, suggesting T-lymphocytes as a potential source for plasmatic sCD73. Finally, our data propose the alterations in CD39/CD73 axis could underlie the upsurge of adenosine levels in the plasma of OSA patients. CONCLUSION: Our study reveals a hypoxia-mediated alteration of the CD39/CD73 axis in OSA patients, which could trigger ADO upregulation, thus potentially contributing to the immune suppressive environment and ultimately facilitating tumor development and progression. Therefore, our data highlights the need for new longitudinal studies evaluating CD39 and/or CD73 as potential cancer-risk prognostic biomarkers in OSA patients.

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.

Sleep apnoea increases biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk patients and those with established lung cancer.

Background: Intermittent hypoxaemia and obstructive sleep apnoea (OSA) have been linked to lung cancer through as yet unidentified pathophysiological mechanisms. This study evaluates the effect of OSA on serum levels of biomarkers of immunosurveillance, lymphangiogenesis and intrinsic tumour cell aggressiveness in high-risk individuals screened for lung cancer and patients with established lung cancer. Methods: Serum samples from individuals participating in a lung cancer screening cohort (SAILS study) or with newly diagnosed lung cancer (SAIL study) were analysed. All patients underwent home sleep apnoea testing. Soluble levels of programmed cell death-1 (PD-1), programmed cell death ligand-1 (PD-L1), cytotoxic T-lymphocyte antigen-4, midkine (MDK), paraspeckle component-1 (PSPC1), transforming growth factor-ß1 (TGF-ß1), SMAD3, matrix metalloproteinase-2 and co-stimulus receptor of the tumour necrosis factor family of receptors (CD137) were determined by ELISA. Results: The presence of moderate-to-severe OSA was associated with increased levels of PSPC1, MDK, PD-L1 and PD-1 in screened individuals, and with higher values of PSPC1, TGF-ß1, PD-L1 and PD-1 in patients with established lung cancer. The findings correlated with nocturnal intermittent hypoxaemia indices. Conclusion: Moderate-to-severe OSA is associated with increased expression of serum biomarkers of immune evasion, lymphangiogenesis and tumour cell aggressiveness in high-risk individuals screened for lung cancer and those with established disease.

Medium-Term Disability and Long-Term Functional Impairment Persistence in Survivors of Severe COVID-19 ARDS: Clinical and Physiological Insights.

BACKGROUND: Although the medium- and long-term sequelae of survivor of acute respiratory distress syndrome (ARDS) of any cause have been documented, little is known about the way in which COVID-19-induced ARDS affects functional disability and exercise components. Our aims were to examine the medium-term disability in severe COVID-19-associated ARDS survivors, delineate pathophysiological changes contributing to their exercise intolerance, and explore its utility in predicting long-term functional impairment persistence. METHODS: We studied 108 consecutive subjects with severe COVID-19 ARDS who remained alive 6 months after intensive care unit (ICU) discharge. Lung morphology was assessed with chest non-contrast CT scans and CT angiography. Functional evaluation included spirometry, plethysmography, muscle strength, and diffusion capacity, with assessment of gas exchange components through diffusing capacity of nitric oxide. Disability was assessed through an incremental exercise test, and measurements were repeated 12 and 24 months later in patients with functional impairments. RESULTS: At 6 months after ICU discharge, a notable dissociation between morphological and clinical-functional sequelae was identified. Moderate-severe disability was present in 47% of patients and these subjects had greater limitation of ventilatory mechanics and gas exchange, as well as greater symptomatic perception during exercise and a probable associated cardiac limitation. Female sex, hypothyroidism, reduced membrane diffusion component, lower functional residual capacity, and high-attenuation lung volume were independently associated with the presence of moderate-severe functional disability, which in turn was related to higher frequency and greater intensity of dyspnea and worse quality of life. Out of the 71 patients with reduced lung volumes or diffusion capacity at 6 months post-ICU discharge, only 19 maintained a restrictive disorder associated with gas exchange impairment at 24 months post-discharge. In these patients, 6-month values for diffusion membrane component, maximal oxygen uptake, ventilatory equivalent for CO2, and dead space to tidal volume ratio were identified as independent risk factors for persistence of long-term functional sequelae. CONCLUSIONS: Less than half of survivors of COVID-19 ARDS have moderate-severe disability in the medium term, identifying several risk factors. In turn, diffusion membrane component and exercise tolerance at 6-month ICU discharge are independently associated with the persistence of long-term functional sequelae.

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. (AU)

Defining the Heterogeneity of Sleep Apnea Syndrome: A Cluster Analysis With Implications for Patient Management / Definiendo la heterogeneidad del Síndrome de Apneas del Sueño: un análisis de clúster con implicaciones en el manejo del paciente

Introduction Obstructive sleep apnea (OSA) is a complex pathology with heterogeneity that has not been fully characterized to date. Our objective is to identify groups of patients with common clinical characteristics through cluster analysis that could predict patient prognosis, the impact of comorbidities and/or the response to a common treatment. Methods Cluster analysis was performed using the hierarchical cluster method in 2025 patients in the apnea-HUGU cohort. The variables used for building the clusters included general data, comorbidity, sleep symptoms, anthropometric data, physical exam and sleep study results. Results Four clusters were identified: (1) young male without comorbidity with moderate apnea and otorhinolaryngological malformations; (2) middle-aged male with very severe OSA with comorbidity without cardiovascular disease; (3) female with mood disorder; and (4) symptomatic male with established cardiovascular disease and severe OSA. Conclusions The characterization of these four clusters in OSA can be decisive when identifying groups of patients who share a special risk or common therapeutic strategies, orienting us toward personalized medicine and facilitating the design of future clinical trials.

Introducción La Apnea Obstructiva del Sueño (AOS) es una patología compleja en la que su heterogeneidad no ha sido completamente caracterizada hasta la fecha. Nuestro objetivo es identificar grupos de pacientes con características clínicas comunes, por medio de análisis de clúster, que pudieran se predictivos de un pronóstico, impacto de comorbilidades y/o respuesta a un tratamiento común. Métodos Se realizó un análisis de clúster por el método de conglomerados jerárquico en 2025 pacientes de la cohorte apnea-HUGU. Las variables utilizadas para la construcción de los clúster incluían datos generales, comorbilidad, síntomas de sueño, datos antropométricos, exploración física y resultados del estudio de sueño. Resultados Se identificaron 4 clúster: 1) varón joven sin comorbilidad con apnea moderada y alteraciones de la esfera otorrinolaringológica (ORL) 2) Varón de edad media con AOS muy grave sintomático con comorbilidad sin enfermedad cardiovascular desarrollada. 3) Mujer con alteraciones en el estado de ánimo 4) Varón sintomático con enfermedad cardiovascular establecida y AOS grave. Conclusiones La caracterización de estos cuatro clúster en la AOS puede ser determinante a la hora de identificar grupos de pacientes que comparten un especial riesgo o estrategias terapéuticas comunes orientándonos hacia la medicina personalizada y facilitando el diseño de futuros ensayos clínicos.

Biomarcadores biológicos en las enfermedades respiratorias / Biological Biomarkers in Respiratory Diseases

En los últimos años la llamada «medicina personalizada o de precisión» ha irrumpido con fuerza en el manejo de las enfermedades, entre ellas las respiratorias. La posibilidad de implantar esta forma de trabajar pasa indefectiblemente por el hallazgo y validación de biomarcadores biológicos que se relacionen bien con el diagnóstico, tratamiento o pronóstico de los pacientes respiratorios. En este sentido, la mayoría de enfermedades respiratorias o grupo de las mismas ya cuentan con biomarcadores biológicos de mayor o menor fiabilidad, y se están realizando un gran número de estudios en busca de nuevos de estos indicadores. El objetivo de la presente revisión es poner al día al lector y analizar la literatura científica existente sobre la existencia y validez diagnóstica, terapéutica o pronóstica de los biomarcadores biológicos más importantes en la actualidad en las principales enfermedades respiratorias, así como sobre los retos futuros en este sentido. (AU)

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area. (AU)

[Translated article] Biological Biomarkers in Respiratory Diseases / Biomarcadores biológicos en las enfermedades respiratorias

In recent years, personalized or precision medicine has made effective inroads into the management of diseases, including respiratory diseases. The route to implementing this approach must invariably start with the identification and validation of biological biomarkers that are closely related to the diagnosis, treatment, and prognosis of respiratory patients. In this respect, biological biomarkers of greater or lesser reliability have been identified for most respiratory diseases and disease classes, and a large number of studies are being conducted in the search for new indicators. The aim of this review is to update the reader and to analyze the existing scientific literature on the existence and diagnostic, therapeutic, and prognostic validity of the most important biological biomarkers in the main respiratory diseases, and to identify future challenges in this area. (AU)

En los últimos años la llamada «medicina personalizada o de precisión» ha irrumpido con fuerza en el manejo de las enfermedades, entre ellas las respiratorias. La posibilidad de implantar esta forma de trabajar pasa indefectiblemente por el hallazgo y validación de biomarcadores biológicos que se relacionen bien con el diagnóstico, tratamiento o pronóstico de los pacientes respiratorios. En este sentido, la mayoría de enfermedades respiratorias o grupo de las mismas ya cuentan con biomarcadores biológicos de mayor o menor fiabilidad, y se están realizando un gran número de estudios en busca de nuevos de estos indicadores. El objetivo de la presente revisión es poner al día al lector y analizar la literatura científica existente sobre la existencia y validez diagnóstica, terapéutica o pronóstica de los biomarcadores biológicos más importantes en la actualidad en las principales enfermedades respiratorias, así como sobre los retos futuros en este sentido. (AU)

La notoriedad de la salud respiratoria y de los profesionales sanitarios que la cuidan / Raising awareness of respiratory health and specialists in respiratory diseases

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[Translated article] Raising awareness of respiratory health and specialists in respiratory diseases / La notoriedad de la salud respiratoria y de los profesionales sanitarios que la cuidan

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Documento internacional de consenso sobre apnea obstructiva del sueño / International Consensus Document on Obstructive Sleep Apnea

El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sueño es proporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisiones en la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literatura más actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedades científicas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedades internacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoamericano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una serie de manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los apartados del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejo del paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos de consenso aparte). Palabras clave: Apnea obstructiva del sueño Diagnóstico Tratamiento

The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents). Keywords: Obstructive sleep apnea Diagnosis Treatment

Effect of Dynamic Hyperinflation on Cardiac Response to Exercise of Patients With Chronic Obstructive Pulmonary Disease / Efecto de la hiperinsuflación dinámica en la respuesta cardíaca al ejercicio de pacientes con enfermedad pulmonar obstructiva crónica

Introduction: Although the major limitation to exercise performance in patients with COPD is dynamic hyperinflation (DH), little is known about its relation with cardiac response to exercise. Our objectives were to compare the exercise response of stroke volume (SV) and cardiac output (CO) between COPD patients with or without DH and control subjects, and to assess the main determinants.Methods: Fifty-seven stable COPD patients without cardiac comorbidity and 25 healthy subjects were recruited. Clinical evaluation, baseline function tests, computed tomography and echocardiography were conducted in all subjects. Patients performed consecutive incremental exercise tests with measurement of operating lung volumes and non-invasive measurement of SV, CO and oxygen uptake (VO2) by an inert gas rebreathing method. Biomarkers of systemic inflammation and oxidative stress, tissue damage/repair, cardiac involvement and airway inflammation were measured.Results: COPD patients showed a lower SV/VO2 slope than control subjects, while CO response was compensated by a higher heart rate increase. COPD patients with DH experienced a reduction of SV/VO2 and CO/VO2 compared to those without DH. In COPD patients, the end-expiratory lung volume (EELV) increase was related to SV/VO2 and CO/VO2 slopes, and it was the only independent predictor of cardiac response to exercise. However, in the regression models without EELV, plasma IL-1β and high-sensitivity cardiac troponin T were also retained as independent predictors of SV/VO2 slope.(AU)

Introducción: Aunque la principal limitación para el rendimiento durante el ejercicio en pacientes con EPOC es la hiperinsuflación dinámica (HD), se sabe poco sobre su relación con la respuesta cardíaca al ejercicio. Nuestros objetivos fueron comparar la respuesta al ejercicio del volumen sistólico (VS) y el gasto cardíaco (GC) entre los pacientes con EPOC con o sin HD y sujetos control, y evaluar los principales determinantes.Métodos: Se reclutaron 57 pacientes con EPOC estable sin comorbilidad cardíaca y 25 sujetos sanos. En todos los sujetos se realizó una evaluación clínica, pruebas de función basal, una tomografía computarizada y una ecocardiografía. Los pacientes realizaron pruebas de esfuerzo incrementales consecutivas con medición de los volúmenes pulmonares operativos y medición no invasiva del VS, el GC y el consumo de oxígeno (VO2) mediante un método de reinhalación de gas inerte. Se midieron los biomarcadores de inflamación sistémica y estrés oxidativo, daño/reparación tisular, afectación cardíaca e inflamación de las vías respiratorias.Resultados:Los pacientes con EPOC presentaron una curva más baja de VS/VO2 que los controles, mientras que la respuesta del GC se compensó con un mayor aumento del ritmo cardíaco. Los pacientes con EPOC e HD experimentaron una reducción de VS/VO2 y de GC/VO2 en comparación con aquellos sin HD. En los pacientes con EPOC, el aumento del volumen pulmonar teleespiratorio (EELV, por sus siglas en inglés) se relacionó con las curvas de VS/VO2 y GC/VO2, y fue el único factor predictivo independiente de la respuesta cardíaca al ejercicio. Sin embargo, en los modelos de regresión sin EELV, la IL-1β plasmática y la troponina T cardíaca ultrasensible también se mantuvieron como factores predictivos independientes de la curva de VS/VO2. (AU)