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

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

A Brain Anti-Senescence Transcriptional Program Triggered by Hypothalamic-Derived Exosomal microRNAs.

In contrast to the hypothesis that aging results from cell-autonomous deterioration processes, the programmed longevity theory proposes that aging arises from a partial inactivation of a "longevity program" aimed at maintaining youthfulness in organisms. Supporting this hypothesis, age-related changes in organisms can be reversed by factors circulating in young blood. Concordantly, the endocrine secretion of exosomal microRNAs (miRNAs) by hypothalamic neural stem cells (htNSCs) regulates the aging rate by enhancing physiological fitness in young animals. However, the specific molecular mechanisms through which hypothalamic-derived miRNAs exert their anti-aging effects remain unexplored. Using experimentally validated miRNA-target gene interactions and single-cell transcriptomic data of brain cells during aging and heterochronic parabiosis, we identify the main pathways controlled by these miRNAs and the cell-type-specific gene networks that are altered due to age-related loss of htNSCs and the subsequent decline in specific miRNA levels in the cerebrospinal fluid (CSF). Our bioinformatics analysis suggests that these miRNAs modulate pathways associated with senescence and cellular stress response, targeting crucial genes such as Cdkn2a, Rps27, and Txnip. The oligodendrocyte lineage appears to be the most responsive to age-dependent loss of exosomal miRNA, leading to significant derepression of several miRNA target genes. Furthermore, heterochronic parabiosis can reverse age-related upregulation of specific miRNA-targeted genes, predominantly in brain endothelial cells, including senescence promoting genes such as Cdkn1a and Btg2. Our findings support the presence of an anti-senescence mechanism triggered by the endocrine secretion of htNSC-derived exosomal miRNAs, which is associated with a youthful transcriptional signature.

Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrome.

The COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), has emerged as a global public health concern and its sequels have barely started to outcrop. A good percentage of patients who suffered from COVID-19 are prone to develop long-COVID or post-COVID condition (PCC), a multisystemic, heterogeneous, chronic disorder. Patients with PCC may experience diverse manifestations, of which cardiovascular and neurological symptoms are among the most frequently reported. Indeed, dysautonomia presented as orthostatic intolerance has gained room following recent reports linking postural orthostatic tachycardia syndrome (POTS) with PCC. Disturbances in heart rate (HR) and blood pressure (BP) during postural changes are the cornerstones of orthostatic intolerance seen in patients suffering from PCC. A subtype of POTS, hyperadrenergic POTS, has been widely studied because of its association with mast cell activation syndrome (MCAS). Although a causative relationship between PCC, hyperadrenergic POTS, and MCAS remains unrevealed, these syndromes can overlap. We want to propose here a correlation produced by a close-loop mechanism with positive feedback established after SARS-CoV-2 infection in a previously healthy young patient.

Enfermedad pulmonar obstructiva crónica y salud respiratoria / Chronic obstructive pulmonary disease and respiratory health

La enfermedad pulmonar obstructiva crónica (EPOC) es una enfermedad que cursa con manifestaciones multisistémicas y agudizaciones, y que conlleva una importante carga de morbilidad, mortalidad y costes sanitarios. Distintas medidas terapéuticas y de prevención juegan un papel importante en mejorar el pronóstico y la salud respiratoria de estos pacientes. Realizar actividad física de forma generalizada, llevar a cabo unos hábitos dietéticos y nutricionales adecuados, abandonar el consumo de tabaco y alcanzar un estado de inmunización óptimo son varias de las acciones de salud recomendadas. Estas también enlentecerán el proceso de envejecimiento. Además, se recomienda realizar políticas de salud pública para reducir la contaminación del aire y el cambio climático. Por último, debemos prestar especial atención a las características del sueño de estos pacientes y llevar a cabo un abordaje terapéutico que incluya una mejor calidad del sueño. (AU)

Chronic obstructive pulmonary disease (COPD) is a disease with multisystemic manifestations and exacerbations that lead to a significant burden of morbidity, mortality, and health care costs. Various therapeutic and preventive measures play an important role in improving the prognosis and respiratory health of the patients. General physical activity, proper dietary and nutritional habits, smoking cessation, and achieving an optimal immunization status are some of the recommended health actions. They also slow down the aging process. In addition, public health policies are recommended to reduce air pollution and climate change. Finally, we should pay special attention to the sleep characteristics of these patients and carry out a therapeutic approach that includes better sleep quality. (AU)

Machine learning for the development of diagnostic models of decompensated heart failure or exacerbation of chronic obstructive pulmonary disease.

Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are two chronic diseases with the greatest adverse impact on the general population, and early detection of their decompensation is an important objective. However, very few diagnostic models have achieved adequate diagnostic performance. The aim of this trial was to develop diagnostic models of decompensated heart failure or COPD exacerbation with machine learning techniques based on physiological parameters. A total of 135 patients hospitalized for decompensated heart failure and/or COPD exacerbation were recruited. Each patient underwent three evaluations: one in the decompensated phase (during hospital admission) and two more consecutively in the compensated phase (at home, 30 days after discharge). In each evaluation, heart rate (HR) and oxygen saturation (Ox) were recorded continuously (with a pulse oximeter) during a period of walking for 6 min, followed by a recovery period of 4 min. To develop the diagnostic models, predictive characteristics related to HR and Ox were initially selected through classification algorithms. Potential predictors included age, sex and baseline disease (heart failure or COPD). Next, diagnostic classification models (compensated vs. decompensated phase) were developed through different machine learning techniques. The diagnostic performance of the developed models was evaluated according to sensitivity (S), specificity (E) and accuracy (A). Data from 22 patients with decompensated heart failure, 25 with COPD exacerbation and 13 with both decompensated pathologies were included in the analyses. Of the 96 characteristics of HR and Ox initially evaluated, 19 were selected. Age, sex and baseline disease did not provide greater discriminative power to the models. The techniques with S and E values above 80% were the logistic regression (S: 80.83%; E: 86.25%; A: 83.61%) and support vector machine (S: 81.67%; E: 85%; A: 82.78%) techniques. The diagnostic models developed achieved good diagnostic performance for decompensated HF or COPD exacerbation. To our knowledge, this study is the first to report diagnostic models of decompensation potentially applicable to both COPD and HF patients. However, these results are preliminary and warrant further investigation to be confirmed.

Programa de salud cardiovascular: atenciones en Santiago de Chile en contexto de pandemia / Cardiovascular health program: service in Santiago de Chile during the pandemic

Introducción: Las enfermedades cardiovasculares son una de las principales causas de morbilidad y mortalidad en las Américas y en Chile. La pandemia por COVID-19 ha impactado la oferta de servicios de salud en la atención primaria, afectando el cuidado de las comunidades con alta prevalencia de enfermedades crónicas. En Chile, el Programa de Salud Cardiovascular brinda atención multiprofesional a personas con estas enfermedades en la atención primaria. Objetivo: Describir la variación de las prestaciones de servicios del Programa de Salud Cardiovascular en las comunas de la provincia de Santiago de Chile, durante el periodo 2014-2020 y su relación con la pobreza multidimensional en el periodo de pandemia. Método: Estudio descriptivo y ecológico. Se analizó la variación porcentual de las atenciones de enfermería, medicina y nutrición para cada comuna de la provincia de Santiago durante 2014-2020, utilizando registros del Ministerio de Salud de Chile. Se indagó en la variación 2019-2020 como descripción de la provisión de servicios del Programa de Salud Cardiovascular durante el primer año de pandemia y se analizó su asociación con la pobreza multidimensional. Resultados: La pandemia por COVID-19 impactó fuertemente en las atenciones del Programa de Salud Cardiovascular en la provincia de Santiago. Los controles disminuyeron en promedio un 60.43 %. Los controles de nutrición fueron los más afectados y los menos afectados los controles por medicina. Este impacto no se asoció con el nivel de pobreza multidimensional de cada comuna. Conclusiones: La magnitud en la disminución de atenciones revela la importancia de realizar vigilancia a la oferta de atenciones y ofrece una oportunidad para adelantarse a las consecuencias que esto implica.

Introduction: Cardiovascular diseases are the main cause of morbidity and mortality in the Americas and in Chile. The COVID-19 pandemic has impacted the supply of health services in primary care, affecting the attention of communities with a high prevalence of chronic diseases. In Chile, the Cardiovascular Health Program provides multi-professional primary care to people with these diseases. Aim: To describe the variation in the care assistance of the Cardiovascular Health Program to the communities of the province of Santiago de Chile, along the period of 2014 to 2020 and its relation to the multidimensional poverty during the pandemic. Method: This is a descriptive and ecological study. The percentage of variation in nursing, medicine, and nutrition care was analyzed for each community, using the records of the Ministry of Health of Chile. The variation from 2019 to 2020 was investigated as a description of the assistance of the Cardiovascular Health Program provided during the first year of the pandemic and its association with multidimensional poverty. Results: The COVID-19 pandemic strongly impacted the quality of assistance of the Cardiovascular Health Program control services in the province of Santiago. The controls decreased by an average of 60.43 %. The nutrition services were the most affected and the least affected were the physician services. This impact was not associated with the multidimensional poverty level in each community. Conclusions: It is important to monitor the impact of the pandemic on the assistance of the most prevailing chronic diseases in the population and to anticipate the consequences that this implies.

Introdução: As doenças cardiovasculares são uma das principais causas de morbidade e mortalidade nas Américas e no Chile. A pandemia da COVID-19 impactou a oferta dos serviços de saúde na atenção primária, afetando o atendimento de comunidades com alta prevalência de doenças crónicas. No Chile, o Programa de Saúde Cardiovascular oferece atendimento multiprofissional às pessoas com essas doenças na atenção primária. Objetivo: Descrever a variação na prestação de serviços do Programa de Saúde Cardiovascular nos municípios da província de Santiago do Chile, durante o período 2014-2020 e sua relação com a pobreza multidimensional no período pandêmico. Método: Estudo descritivo e ecológico. A variação percentual das atenções de enfermagem, medicina e nutrição para cada comuna da província de Santiago durante 2014-2020, usando os registos do Ministério da Saúde do Chile. A variação 2019-2020 foi investigada como descrição da prestação de serviços do Programa de Saúde Cardiovascular durante o primeiro ano da pandemia e analisou-se a sua associação com a pobreza multidimensional. Resultados: A pandemia da COVID-19 teve forte impacto no atendimento do Programa de Saúde Cardiovascular na província de Santiago. Os controles diminuíram em média 60,43%. Os controles por nutricionista foram os mais afetados e os menos foram os controles pelo médico. Este impacto não foi associado ao nível de pobreza multidimensional de cada comunidade. Conclusões: A magnitude da diminuição do atendimento revela a importância do monitoramento da oferta de atenção e oferece uma oportunidade de antecipar as consequências que isso implica.

Unexpected Paratracheal Opacity

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Tosferina en el adulto: el enemigo visible / Whooping Cough: The Visible Enemy

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[Translated article] Whooping Cough: The Visible Enemy / Tosferina en el adulto: el enemigo visible

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Immunosenescence, Immune Fitness and Vaccination Schedule in the Adult Respiratory Patient.

Immunosenescence is the gradual deterioration of the immune system caused by advancing age. It is associated with a reduced ability to respond to infections and develop long-term immune memory. It plays a key role in the development of respiratory diseases that are more common in older people, such as asthma, COPD, diffuse interstitial disease and respiratory infections in the elderly. We call immune fitness the establishment of lifestyle habits that can improve our immune capacity. We now know that good eating habits, good social relationships, not smoking, limiting alcohol consumption, exercising, controlling stress levels and establishing a proper vaccination programme can slow down the process of immunosenescence. Influenza and pneumococcal vaccines (PCV13 and PPSV23 conjugate) are well established in the adult vaccination schedule. The new pneumococcal vaccines PCV15 and PCV20 will help to extend protection against pneumococcal disease in adults. The vaccine against COVID-19 is currently the most useful tool to prevent the disease and reduce its pathogenicity. COPD patients and others with respiratory diseases may benefit from prevention of herpes zoster and Bordetella pertussis through vaccination. Respiratory syncytial virus (RSV) vaccine may be another vaccine to be added to the schedule, pending the results of its studies.

La inmunosenescencia es el deterioro gradual del sistema inmune provocado por el avance de la edad. Se asocia a una menor capacidad para responder a las infecciones y desarrollar memoria inmune a largo plazo. Es parte fundamental en el desarrollo de las enfermedades respiratorias más frecuentes en edades avanzadas, como el asma, la EPOC, la patología intersticial difusa y las infecciones respiratorias del anciano.Llamamos fitness inmunológico al establecimiento de unos hábitos de vida que puedan mejorar nuestra capacidad inmunitaria. Actualmente sabemos que tener buenos hábitos alimentarios, buenas relaciones sociales, no fumar, limitar el consumo de alcohol, hacer ejercicio, controlar los niveles de estrés y establecer un correcto programa de vacunación permiten ralentizar el proceso de inmunosenescencia.Las vacunas de la gripe y las antineumocócicas (la conjugada PCV13 y la PPSV23) están bien establecidas en el calendario vacunal del adulto. Las nuevas vacunas antineumocócicas PCV15 y PCV20 van a servir para ampliar la protección contra la enfermedad neumocócica en el adulto. La vacuna contra la COVID-19 es, en el momento actual, la herramienta más útil para prevenir la enfermedad y disminuir su patogenicidad. Los pacientes con EPOC y otros con enfermedades respiratorias podrían beneficiarse de la prevención del herpes zóster y Bordetella pertussis mediante la vacunación. La vacuna contra el virus respiratorio sincitial (VRS) puede ser otra de las siguientes que formen parte de este calendario, en espera de los resultados de sus estudios.

Decrease in Readmissions after Hospitalisation for COPD Exacerbation through a Home Care Model.

Objective: To decrease readmissions at 30 and 90 days post-discharge from a hospital admission for chronic obstructive pulmonary disease exacerbation (COPDE) through the home care model of the Ambulatory Chronic Respiratory Care Unit (ACRCU), increase patient survival at one year, and validate our readmission risk scale (RRS). Materials and methods: This was an observational study, with a prospective data collection and a retrospective data analysis. A total of 491 patients with a spirometry diagnosis of chronic obstructive pulmonary disease (COPD) requiring hospitalisation for an exacerbation were included in the study. Subjects recruited within the first year (204 cases) received conventional care (CC). In the following year a home care (HC) programme was implemented and of those recruited that year (287) 104 were included in the ACRCU, administered by a specialised nurse. Results: In the group of patients included in the home care model of the Ambulatory Chronic Respiratory Care Unit (ACRCU) a lower number of readmissions was observed at 30 and 90 days after discharge (30.5% vs. 50%, p = 0.012 and 47.7% vs. 65.2%, p = 0.031, respectively) and a greater one-year survival (85.3% vs. 59.1%, p < 0.001). The validation of our RRS revealed that the tool's capacity to predict readmissions at both 30 and 90 days was not high (AUC = 0.69 and AUC = 0.66, respectively). Conclusions: The inclusion of exacerbator or fragile COPD patients in the ACRCU could achieve a decrease in readmissions and an increase in survival. The number of episodes of exacerbation within the 12 months prior to the hospital admission is the variable that best predicts the risk of readmission.

Objetivo: Disminuir los reingresos a los 30 y 90 días tras el alta por un ingreso hospitalario por exacerbación de enfermedad pulmonar obstructiva crónica (EPOC) a través del modelo de atención domiciliaria de la Unidad de Cuidados Crónicos Respiratorios Ambulatorios (UCCRA), aumentar la supervivencia al año y validar nuestra escala de riesgo de reingreso (ERR). Material y métodos: Estudio observacional con recogida prospectiva de datos. Se incluyó en el estudio a un total de 491 pacientes con diagnóstico espirométrico de enfermedad pulmonar obstructiva crónica que requirieron hospitalización por una agudización. Los sujetos reclutados dentro del primer año (204 casos) recibieron atención convencional (AC). Al año siguiente se implementó un programa de atención domiciliaria (AD) y de los pacientes reclutados ese año (287), 104 fueron incluidos en la UCCRA con seguimiento de una enfermera especializada. Resultados: En el grupo de pacientes incluidos en el modelo de atención domiciliaria de la UCCRA se observó un menor número de reingresos a los 30 y 90 días tras el alta (30,5% vs 50%, p = 0,012 y 47,7% vs. 65,2%, p = 0,031, respectivamente) y una mayor supervivencia al año (85,3% vs. 59,1%, p < 0,001). La validación de nuestra ERR reveló que la capacidad de la misma para predecir reingresos tanto a los 30 como a los 90 días no era alta (AUC = 0,69 y AUC = 0,66, respectivamente). Conclusiones: La inclusión de pacientes con EPOC agudizadores o frágiles en la UCCRA podría conseguir una disminución de los reingresos y una aumento de la supervivencia. El número de agudizaciones en los 12 meses previos al ingreso hospitalario es la variable que mejor predice el riesgo de reingreso.