Unraveling the hepatic stellate cells mediated mechanisms in aging's influence on liver fibrosis.

Aging enhances numerous processes that compromise homeostasis and pathophysiological processes. Among these, activated HSCs play a pivotal role in advancing liver fibrosis. This research delved into how aging impacts liver fibrosis mechanisms. The study involved 32 albino rats categorized into four groups: Group I (young controls), Group II (young with liver fibrosis), Group III (old controls), and Group IV (old with liver fibrosis). Various parameters including serum ALT, adiponectin, leptin, and cholesterol levels were evaluated. Histopathological analysis was performed, alongside assessments of TGF-ß, FOXP3, and CD133 gene expressions. Markers of fibrosis and apoptosis were the highest in group IV. Adiponectin levels significantly decreased in Group IV compared to all other groups except Group II, while cholesterol levels were significantly higher in liver fibrosis groups than their respective control groups. Group III displayed high hepatic expression of desmin, α-SMA, GFAP and TGF- ß and in contrast to Group I. Increased TGF-ß and FOXP3 gene expressions were observed in Group IV relative to Group II, while CD133 gene expression decreased in Group IV compared to Group II. In conclusion, aging modulates immune responses, impairs regenerative capacities via HSC activation, and influences adipokine and cholesterol levels, elevating the susceptibility to liver fibrosis.

YdbH and YnbE form an intermembrane bridge to maintain lipid homeostasis in the outer membrane of Escherichia coli.

The outer membrane (OM) of didermic gram-negative bacteria is essential for growth, maintenance of cellular integrity, and innate resistance to many antimicrobials. Its asymmetric lipid distribution, with phospholipids in the inner leaflet and lipopolysaccharides (LPS) in the outer leaflet, is required for these functions. Lpt proteins form a transenvelope bridge that transports newly synthesized LPS from the inner membrane (IM) to OM, but how the bulk of phospholipids are transported between these membranes is poorly understood. Recently, three members of the AsmA-like protein family, TamB, YhdP, and YdbH, were shown to be functionally redundant and were proposed to transport phospholipids between IM and OM in Escherichia coli. These proteins belong to the repeating ß-groove superfamily, which includes eukaryotic lipid-transfer proteins that mediate phospholipid transport between organelles at contact sites. Here, we show that the IM-anchored YdbH protein interacts with the OM lipoprotein YnbE to form a functional protein bridge between the IM and OM in E. coli. Based on AlphaFold-Multimer predictions, genetic data, and in vivo site-directed cross-linking, we propose that YnbE interacts with YdbH through ß-strand augmentation to extend the continuous hydrophobic ß-groove of YdbH that is thought to shield acyl chains of phospholipids as they travel through the aqueous intermembrane periplasmic compartment. Our data also suggest that the periplasmic protein YdbL prevents extensive amyloid-like multimerization of YnbE in cells. We, therefore, propose that YdbL has a chaperone-like function that prevents uncontrolled runaway multimerization of YnbE to ensure the proper formation of the YdbH-YnbE intermembrane bridge.

Carbon footprint of pressurized gas metered dose inhalers (pMDI) in Brazil and Porto Alegre: impacts and alternatives / La huella de carbono de los dispositivos inhaladores dosificados de gas presurizado (pMDI) en Brasil y en Porto Alegre: impactos y alternativas / Pegada de carbono dos dispositivos inalatórios dosimetrados de gás pressurizado (pMDI) no Brasil e em Porto Alegre: impactos e alternativas

Objective: To calculate the carbon footprint of pressurized gas-type metered-dose inhalers for asthma and chronic obstructive pulmonary disease control (COPD) dispensed by the brazilian national health service (SUS) in Brazil and in Porto Alegre (RS) in 2019. Method: Collection and analysis of data on the dispensation of salbutamol and beclomethasone by the SUS network and Farmácia Popular do Brasil in 2019, obtained by request to the Ministry of Health. Dispensations were multiplied by the proportional carbon footprint of each device using data already published in the literature. Results: In 2019, the prescription of pMDIs (pressurized metered-dose inhalers) within the Brazilian Unified Health System (SUS) resulted in the emission of approximately 24,889,141 to 60,878,728 metric tons of CO2 equivalent into the atmosphere across Brazil, which is equivalent to traveling by a typical gasoline-powered car from the northernmost to the southernmost point of the country between 23 to 57 million times. Furthermore, in the specific context of Porto Alegre, the emissions ranged from approximately 459,830 to 1,151,008 metric tons of CO2 equivalent, corresponding to traveling by a typical gasoline-powered car from the northernmost to the southernmost point of Brazil between 433,000 to 1 million times. Conclusion: The national health service in Brazil is responsible for emitting a massive amount of GHGs each year due to pMDI-type inhalation devices.  Switching to DPIs or SMIs in the indicated cases would avoid a great environmental damage, and at the same time would be of clinical benefit to patients, since they are the first choice currently recommended by the clinical guidelines for the treatment of asthma and COPD, promoting public health and, at the same time, planetary health.

Objetivo: Calcular la huella de carbono de los inhaladores de dosis medida de gas presurizado utilizados para el control del asma y la enfermedad pulmonar obstructiva crónica (EPOC) dispensados por el Sistema Único de Salud (SUS) en Brasil y en Porto Alegre (RS) en el año 2019. Método: Recopilación y análisis de datos de dispensación de salbutamol y beclometasona por la red SUS y Farmácia Popular do Brasil en 2019, obtenidos a través de una solicitud al Ministerio de Salud en virtud de la Ley de Acceso a la Información. Las dispensaciones se multiplicaron por la huella de carbono proporcional de cada dispositivo utilizando datos previamente publicados en la literatura. Resultados: La prescripción de los inhaladores de dosis medida de gas presurizado en el SUS en 2019 resultó en la emisión de entre 24,889,141 y 60,878,728 toneladas de CO2-eq en todo Brasil, equivalente a viajar en un automóvil de gasolina común desde el extremo norte hasta el extremo sur del país entre 23 y 57 millones de veces. En el caso de la ciudad de Porto Alegre, las emisiones oscilaron entre 459,830 y 1,151,008 toneladas de CO2-eq, lo que equivale a recorrer la distancia de norte a sur de Brasil entre 433,000 y 1 millón de veces en un automóvil de gasolina común. Conclusión: En el SUS, se emite una enorme cantidad de gases de efecto invernadero (GEE) cada año debido a los dispositivos inhaladores del tipo pMDI. El cambio a DPIs o SMIs en los casos indicados evitaría un gran daño ambiental y, al mismo tiempo, proporcionaría beneficios clínicos a los pacientes, ya que es la primera opción actualmente recomendada por las directrices clínicas para el tratamiento del asma y la EPOC, promoviendo la salud pública y al mismo tiempo la salud del planeta.

Objetivo: Calcular a pegada de carbono dos inaladores do tipo gás pressurizado dosimetrado para controle da asma e doença pulmonar obstrutiva crônica (DPOC) dispensados pelo Sistema Único de Saúde (SUS) no Brasil e em Porto Alegre (RS) no ano de 2019. Método: Coleta e análise de dados de dispensação de salbutamol e beclometasona pela rede SUS e Farmácia Popular do Brasil em 2019, obtidas por solicitação ao Ministério da Saúde através da Lei de Acesso à Informação. As dispensações foram multiplicadas pela pegada de carbono proporcional de cada dispositivo utilizando dados já publicados na literatura. Resultados: A prescrição de pMDI no SUS, em 2019, resultou entre 24.889.141 e 60.878.728 toneladas de CO2-eq liberados na atmosfera em todo o Brasil (equivalente a percorrer 23 a 57 milhões de vezes a distância de norte a sul do Brasil com um carro comum a gasolina); e entre 459.830 e 1.151.008 toneladas de CO2-eq na cidade de Porto Alegre (correspondente a percorrer 433mil a 1 milhão de vezes a distância de norte a sul do Brasil com um carro comum a gasolina). Conclusão: No SUS, emite-se enorme quantidade de GEEs a cada ano devido aos dispositivos inalatórios do tipo pMDI. A troca por DPIs ou SMIs nos casos indicados evitaria um grande dano ambiental, e ao mesmo tempo benefício clínico aos pacientes, pois trata-se da primeira escolha atual preconizada pelas diretrizes clínicas para o tratamento de asma e DPOC, promovendo a saúde pública e ao mesmo tempo a saúde planetária.

Sulfato de magnesio y aminofilina en el tratamiento de niños, niñas y adolescentes hospitalizados. Perfil de uso y respuesta terapéutica

Introducción: Sulfato de magnesio (MgSO4) y aminofilina son broncodilatadores intravenosos utilizados en el tratamiento de niños con broncoobstrucción (BO). La evidencia disponible para recomendar su uso es escasa. Objetivo: Caracterizar el perfil de uso y la respuesta terapéutica al MgSO4 y aminofilina en el tratamiento de la BO en niños hospitalizados en un centro de referencia de Uruguay. Materiales y métodos: Estudio descriptivo de corte transversal mediante revisión de historias y entrevistas. Se incluyeron a todos los menores de 15 años que utilizaron estos fármacos. Se evaluó la respuesta terapéutica a la administración de ambos fármacos en forma exclusiva y concomitante y la presencia de efectos adversos. Resultados: Se incluyeron 102 niños, mediana de edad 4 años, ≤5 años 62%. Los principales diagnósticos fueron: crisis asmática 56% y neumonía viral 31%. Recibieron ambos fármacos 48%, únicamente aminofilina 28% y exclusiva de MgSO4 24%. Se observó buena respuesta terapéutica a la administración: exclusiva de MgSO4 67%, consecutiva de MgSO4 y aminofilina 45% y exclusiva de aminofilina en 34%. En 38,2% se registró al menos un efecto adverso, 64% eran menores de 5 años, riesgo aumentado en 1,5 veces. Conclusiones: Se registraron variadas indicaciones, la mayoría en niños asmáticos y en un porcentaje menor indicaciones fuera de prospecto. Menos de la mitad presentaron buena respuesta luego de la administración de MgSO4 y/o aminofilina. En un porcentaje no despreciable se registraron efectos adversos, predominaron en menores de 5 años. Son necesarios nuevos estudios para continuar caracterizando el perfil de uso y seguridad de estos fármacos.

Introduction: Magnesium sulfate (MgSO4) and aminophylline are intravenous bronchodilators used in the treatment of children with bronchoobstruction (BO). The evidence available to recommend their use is scarce. Objective: To characterize the use profile and therapeutic response to MgSO4 and aminophylline in the treatment of BO in children hospitalized in a reference center in Uruguay. Materials and methods: This was a descriptive cross-sectional study through review of clinical histories and interviews. All children under 15 years of age who used these drugs were included. The therapeutic response to the administration of both drugs exclusively and concomitantly and the presence of adverse effects were evaluated. Results: 102 children were included, median age was 4 years, 62% were ≤5 years. The main diagnoses were: asthmatic crisis, 56% and viral pneumonia, 31%. 48% received both drugs, 28% only aminophylline and 24% exclusively MgSO4. Good therapeutic response was observed to the administration: MgSO4 exclusively, 67%, MgSO4 followed by aminophylline, 45% and aminophylline exclusively in 34%. At least one adverse effect was recorded in 38.2%, of these, 64% were under 5 years of age, risk increased by 1.5 times. Conclusions: Various indications were recorded, the majority in asthmatic children and a smaller percentage off-label indications. Less than half had a good response after the administration of MgSO4 and/or aminophylline. Adverse effects were recorded in a non-negligible percentage, predominating in children under 5 years of age. New studies are necessary to continue characterizing the use and safety profile of these drugs.

Seguimiento de niños con diagnóstico de asma grave antes y durante la pandemia por COVID-19 / Follow-up of children diagnosed with severe asthma before and during the COVID-19 pandemic

En la pandemia por COVID-19 se exploraron estrategias de atención para garantizar el seguimiento de niños con asma grave. Estudio prospectivo, observacional, comparativo. Se incluyeron pacientes del programa de asma grave de un hospital pediátrico de tercer nivel (n 74). Se evaluó el grado de control, exacerbaciones y hospitalizaciones durante un período presencial (PP), marzo 2019-2020, y uno virtual (PV), abril 2020-2021. En el PP, se incluyeron 74 pacientes vs. 68 (92 %) del PV. En el PP, el 68 % (46) de los pacientes presentaron exacerbaciones vs. el 46 % (31) de los pacientes en el PV (p 0,003). En el PP, se registraron 135 exacerbaciones totales vs. 79 en el PV (p 0,001); hubo una reducción del 41 %. En el PP, el 47 % (32) de los pacientes tuvieron exacerbaciones graves vs. el 32 % (22) de los pacientes en el PV (p 0,048). Hubo 91 exacerbaciones graves en el PP vs. 49 en el PV (p 0,029), reducción del 46 %. No hubo diferencias en las hospitalizaciones (PP 10, PV 6; p 0,9). La telemedicina fue efectiva para el seguimiento de pacientes con asma grave

During the COVID-19 pandemic, health care strategies were explored to ensure the follow-up of children with severe asthma. This was a prospective, observational, and comparative study. Patients in the severe asthma program of a tertiary care children's hospital were included (n: 74). The extent of control, exacerbations, and hospitalizations during an in-person period (IPP) (March 2019­2020) and an online period (OP) (April 2020­2021) was assessed. A total of 74 patients were enrolled in the IPP compared to 68 (92%) in the OP. During the IPP, 68% (46) of patients had exacerbations versus 46% (31) during the OP (p = 0.003). During the IPP, 135 total exacerbations were recorded compared to 79 during the OP (p = 0.001); this accounted for a 41% reduction. During the IPP, 47% (32) of patients had severe exacerbations versus 32% (22) during the OP (p = 0.048). A total of 91 severe exacerbations were recorded during the IPP compared to 49 during the OP (p = 0.029); the reduction was 46%. No differences were observed in terms of hospitalization (IPP: 10, OP: 6; p = 0,9). Telemedicine was effective for the follow-up of patients with severe asthma.

Paciente varón de tres años con sibilancias y tos crónica / Three-Year-Old Male with Wheezing and Chronic Cough

Se presenta el caso de un niño de 3 años con diagnóstico de asma, rinitis alérgica, características craneofaciales dismórficas e infecciones respiratorias altas y bajas recurrentes, manejado como asma desde un inicio. Como parte del estudio de comorbilidades, se decide realizar una prueba del sudor que sale en rango intermedio y más tarde se encuentra una mutación, donde se obtiene un resultado positivo para una copia que se asocia a fibrosis quística. Se revisará el caso, así como el diagnóstico, clínica y tratamiento del síndrome metabólico relacionado con el regulador de conductancia transmembrana de fibrosis quística (CRMS).

We present the case of a 3-year-old boy with a diagnosis of asthma, allergic rhinitis, dysmorphic craniofacial characteristics and recurrent upper and lower respiratory infections, managed as asthma from the beginning. As part of the study of comorbidi-ties, it was decided to carry out a sweat test that came out in the intermediate range and later one mutation was found, where a positive result was obtained for a copy that is associated with cystic fibrosis. The case will be reviewed, as well as the diagnosis, symptoms and treatment of the metabolic syndrome related to the cystic fibrosis trans-membrane conductance regulator (CRMS).

Impacto pronóstico de la enfermedad pulmonar obstructiva crónica y el asma bronquial en pacientes con insuficiencia cardiaca / Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure

Propósito Analizar el impacto de la enfermedad pulmonar obstructiva crónica (EPOC) y el asma bronquial sobre el manejo terapéutico y el pronóstico de los pacientes con insuficiencia cardiaca (IC). Métodos Análisis de la información contenida en un registro clínico de pacientes remitidos a una unidad especializada de IC entre enero de 2010 y junio de 2022. Se compararon su perfil clínico, el tratamiento y el pronóstico en base a la presencia de EPOC o asma bronquial. El análisis de supervivencia se realizó mediante los métodos de Kaplan-Meier y Cox. La mediana de seguimiento fue de 1.493 días. Resultados Se estudiaron 2.577 pacientes, de los cuales 251 (9,7%) presentaban EPOC y 96 (3,7%), asma bronquial. Observamos diferencias significativas entre los tres grupos con respecto a la prescripción de betabloqueantes (EPOC=89,6%; asma=87,5%; no broncopatía=94,1%; p=0,002) e inhibidores del cotransportador de sodio-glucosa tipo2 (EPOC=35,1%; asma=50%; no broncopatía=38,3%; p=0,036). Además, los pacientes con patología bronquial recibieron con menor frecuencia un desfibrilador (EPOC=20,3%; asma=20,8%; no broncopatía=29%; p=0,004). La presencia de EPOC se asoció de forma independiente con mayor riesgo de muerte por cualquier causa (HR=1,64; IC95%: 1,33-2,02), muerte u hospitalización por IC (HR=1,47; IC95%: 1,22-1,76) y muerte cardiovascular o trasplante cardiaco (HR=1,39; IC95%: 1,08-1,79) en comparación con la ausencia de broncopatía. La presencia de asma bronquial no se asoció a un impacto significativo sobre los desenlaces analizados. Conclusiones La EPOC, pero no el asma bronquial, es un factor pronóstico adverso e independiente en pacientes con IC. (AU)

Purpose To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). Methods Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. Results We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; P=.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; P=.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; P=.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95%CI: 1.33-2.02), all-cause death or HF admission (HR=1.47; 95%CI: 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95%CI: 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. Conclusions COPD, but not asthma, is an adverse independent prognostic factor in patients with HF. (AU)

Asma ocupacional: a propósito de un caso

Se presenta el caso de un trabajador de 31 años que desempeña tareas en un molino de granos desde hace 12 años y que ha desarrollado asma ocupacional. El objetivo del artículo es presentar los fundamentos utilizados para sostener el origen profesional del asma adquirido. Se describen las tareas laborales que desarrolla, materiales y medios de trabajo que utiliza. Se analiza en particular la exposición laboral a polvo orgánico y su vinculación temporal con la sintomatología respiratoria. Esta información permite comprender la importancia de las condiciones en las que realiza el trabajo y la exposición a un factor de riesgo, el polvo orgánico, para el desarrollo de la patología respiratoria laboral. Se realizaron mediciones de volumen máximo espiratorio pulmonar, con técnica de pico flujo, durante la jornada laboral y fuera de ésta. Se observaron variaciones del flujo espiratorio mayores a 20%, tanto durante la jornada laboral como fuera de ella, con similar patrón sintomático, según relata el trabajador. Se concluyó que existe evidencia del nexo causal entre el asma y el trabajo, por lo que se plantea el diagnóstico de asma ocupacional. Se destaca la importancia de evaluar los riesgos laborales en cada actividad para implementar planes de vigilancia de la salud, tanto del operario como del ambiente de trabajo, para prevenir la aparición como la evolución de esta u otras patologías que en muchos casos generan incapacidad para la tarea y deterioro de la calidad de vida de los trabajadores.

We present the case of a 31-year-old worker who has been working in a grain mill for 12 years and has developed work-related asthma. The objective of this article is to present the foundations used to support the occupational origin of the acquired asthma. The study describe the work tasks performed, the materials used, and the working methods. The work-related exposure to organic dust and its temporal relationship with respiratory symptoms is particularly analyzed. This information allows us to understand the importance of working conditions and exposure to organic dust, a risk factor, for the development of this work-related respiratory pathology. Measurements of maximum expiratory lung volume were made using the peak flow technique during and outside of the workday. Expiratory flow variations greater than 20% were observed, both during and outside of the workday, which followed a similar symptomatic pattern as reported by the worker. The study concluded that there is evidence of a causal link between asthma and work, thus suggesting the diagnosis of work-related asthma. The importance of assessing occupational risks in each activity to implement health surveillance plans for both workers and the work environment is highlighted, aiming to prevent the onset and progression of this and other pathologies that often result in work incapacity and deterioration of workers' quality of life.

Apresentamos o caso de um paciente de 31 anos de idade que trabalha em um moinho de grãos há 12 anos e desenvolveu asma ocupacional. O objetivo do artigo é apresentar a justificativa da origem ocupacional da asma adquirida. Descrevemos as tarefas realizadas, os materiais e os meios de trabalho utilizados. Analisamos especialmente a exposição ocupacional à poeira orgânica e sua conexão temporal com a sintomatologia respiratória. Essas informações nos permitem entender a importância das condições em que o trabalho é realizado e a exposição a um fator de risco, a poeira orgânica, para o desenvolvimento da patologia respiratória ocupacional. As medições do volume pulmonar expiratório máximo foram realizadas com a técnica de pico de fluxo durante e fora da jornada de trabalho. Observamos variações no fluxo expiratório superiores a 20%, tanto durante quanto fora do horário de trabalho, com um padrão sintomático semelhante ao relatado pelo trabalhador. Concluímos que há evidências de um nexo causal entre asma e trabalho e, portanto, propomos o diagnóstico de asma ocupacional. Destacamos a importância de avaliar os riscos ocupacionais em cada atividade para implementar planos de vigilância da saúde tanto do trabalhador quanto do ambiente de trabalho, a fim de evitar o surgimento e a evolução dessa ou de outras patologias que, em muitos casos, geram incapacidade para a tarefa e deterioração da qualidade de vida dos trabalhadores.

[Assessment of blood eosinophil count in respiratory disease from primary care]. / Valoración del recuento sanguíneo de eosinófilos en la patología respiratoria desde atención primaria.

Most physicians in general, and family physicians in particular, are familiar with certain parameters when ordering a hematological study, such as hemoglobin (including hematocrit and its features), leukocytes (including lymphocytes) and platelets. Nevertheless, there are two values that we use to overlook which are eosinophils and basophils. Specifically, eosinophils have a tendency to increase with allergic pathology. This article focuses on this type of cells, helping to interpret the values obtained and highlighting their importance in two of the most frequent respiratory pathologies in primary care: asthma and COPD. In addition to observing how the increase or normality of these parameters condition the diagnosis, phenotype and even the treatment.

Medicaciones inhaladas y cámaras de inhalación para el asma infantil. Red española de grupos de trabajo sobre asma en pediatría (REGAP) / Inhaled medications and inhalation chambers for childhood asthma. Spanish network of working groups on asthma in pediatrics (REGAP)

El asma, la enfermedad crónica más prevalente en la edad pediátrica, continúa planteando desafíos en su manejo y tratamiento1. Guías nacionales e internacionales destacan la importancia de la educación terapéutica (ET) para lograr el control de esta enfermedad2,3. Esta educación implica la transmisión de conocimientos y habilidades al paciente y su familia, mejorando la adherencia a la medicación, corrigiendo errores en la técnica de inhalación y ajustando el tratamiento según las características individuales de cada paciente4,5. Es esencial que la ET sea progresiva, gradual e individualizada, y que esté presente en todos los niveles asistenciales. La formación en ET de profesionales sanitarios es crucial, especialmente para los pediatras, quienes además deben conocer la extensa variabilidad de medicamentos e inhaladores disponibles y sus indicaciones para cada edad6. Para abordar esta necesidad, el Grupo red española de grupos de trabajo sobre asma en pediatría (REGAP) ha revisado exhaustivamente los inhaladores actualmente disponibles en España para el tratamiento del asma en la edad pediátrica. La revisión incluye una revisión de los distintos sistemas de inhalación y los distintos fármacos inhalados, utilizados para el tratamiento del asma en la edad pediátrica. Esta revisión se actualizará anualmente, incluyendo información sobre fármacos, dispositivos, cámaras de inhalación, indicaciones y financiación. El Grupo REGAP espera que estas tablas sean una valiosa ayuda para los pediatras en su práctica clínica diaria y constituyen una eficaz herramienta de ET.(AU)

Asthma, the most prevalent chronic disease in pediatric age, continues to pose challenges in its management and treatment. National and international guidelines emphasize the importance of therapeutic education (TE) to achieve disease control. TE involves imparting knowledge and skills to the patient and their family, enhancing medication adherence, rectifying errors in inhalation technique, and tailoring treatment based on individual patient characteristics. It is essential for TE to be progressive, gradual, and personalized, spanning all levels of care. Training healthcare professionals in TE is crucial, particularly for pediatricians, who must also be aware of the extensive variability of available meds and inhalers and their respective age-specific indications. Addressing this need, the REGAP Group extensively reviewed inhalers currently available in Spain for pediatric asthma treatment. The review encompassed different inhalation systems and inhaled drugs used for pediatric asthma treatment. This review will be updated annually, providing information on medications, devices, inhalation chambers, indications, and financiation. The REGAP Group hopes that these tables will be a valuable help for pediatricians in their daily clinical practice and serve as an effective TE tool.(AU)

mSphere of Influence: The discovery of a missing link in bacterial cell envelope biogenesis.

Gregory Harrison is a bacteriologist researching essential pathways in bacteria as potential therapeutic targets. In this mSphere of Influence article, he reflects on a series of studies that employ complementary genetic approaches to define the crucial role of AsmA-family proteins in transporting phospholipids between the inner and outer membranes of Gram-negative bacteria. The authors of these three studies identify this family of lipid transporters through the means of bacterial genetics, answering a long-standing question in bacterial physiology, and serving as a reminder that a well-designed genetic strategy can go a long way in uncovering new biology.

Inhaled medications and inhalation chambers for childhood asthma. Spanish network of working groups on asthma in pediatrics (REGAP).

Asthma, the most prevalent chronic disease in pediatric age, continues to pose challenges in its management and treatment. National and international guidelines emphasize the importance of therapeutic education (TE) to achieve disease control. TE involves imparting knowledge and skills to the patient and their family, enhancing medication adherence, rectifying errors in inhalation technique, and tailoring treatment based on individual patient characteristics. It is essential for TE to be progressive, gradual, and personalized, spanning all levels of care. Training healthcare professionals in TE is crucial, particularly for pediatricians, who must also be aware of the extensive variability of available meds and inhalers and their respective age-specific indications. Addressing this need, the REGAP Group extensively reviewed inhalers currently available in Spain for pediatric asthma treatment. The review encompassed different inhalation systems and inhaled drugs used for pediatric asthma treatment. This review will be updated annually, providing information on medications, devices, inhalation chambers, indications, and financiation. The REGAP Group hopes that these tables will be a valuable help for pediatricians in their daily clinical practice and serve as an effective TE tool.

Prognostic impact of chronic obstructive pulmonary disease and bronchial asthma in patients with heart failure.

PURPOSE: To analyze the impact of chronic obstructive pulmonary disease (COPD) and bronchial asthma on therapeutic management and prognosis of patients with heart failure (HF). METHODS: Analysis of the information collected in a clinical registry of patients referred to a specialized HF unit from January-2010 to June-2012. Clinical profile, treatment and prognosis of patients was evaluated, according to the presence of COPD or asthma. Survival analyses were conducted by means of Kaplan-Meier and Cox's methods. Median follow-up was 1493 days. RESULTS: We studied 2577 patients, of which 251 (9.7%) presented COPD and 96 (3.7%) bronchial asthma. Significant differences among study groups were observed regarding to the prescription of beta-blockers (COPD=89.6%; asthma=87.5%; no bronchopathy=94.1%; p=0.002) and SGLT2 inhibitors (COPD=35.1%; asthma=50%; no bronchopathy=38.3%; p=0.036). Also, patients with bronchial disease received less frequently a defibrillator (COPD=20.3%; asthma=20.8%; no broncopathy=29%; p=0.004). COPD was independently associated with increased risk of all-cause mortality (HR=1.64; 95% CI 1.33-2.02), all-cause death or HF admission (HR=1.47; 95% CI 1.22-1.76) and cardiovascular death or heart transplantation (HR=1.39; 95% CI 1.08-1.79) as compared with patients with no bronchopathy. Bronchial asthma was not significantly associated with increased risk of adverse outcomes. CONCLUSIONS: COPD, but not asthma, is an adverse independent prognostic factor in patients with HF.

Intervenciones educativas en asma infantil: Una revisión sistemática / Educational interventions in childhood asthma: A systematic review

Objetivo: Analizar intervenciones educativas en pacientes pediátricos asmáticos para conseguir una técnica adecuada de inhalación y mejorar su automanejo. Diseño: Revisión sistemática basándose en las recomendaciones PRISMA. Fuentes de datos: Se revisaron las bases de datos PubMed, Scopus, Cuiden, Web of Science y Google académico. Selección de estudios: Se incluyeron 16 artículos publicados entre 2014-2021, con acceso a texto completo, idiomas: inglés, francés y español y población pediátrica: 0-18 años. Extracción de datos: Participaron 2.313 niños/as. Las variables analizadas fueron: nivel asistencial, tipo de intervención, realización correcta de la técnica de inhalación, seguimiento de la técnica, entrega de recomendaciones por escrito, categoría profesional-educador, variables relacionadas con la patología respiratoria, absentismo escolar, calidad de vida y costes económicos. Resultados: El nivel de atención sanitaria fue atención primaria, hospitalaria y comunitaria, donde destacaron como educadores: médicos especialistas, enfermeras y farmacéuticos. Las intervenciones educativas más prevalentes son demostración in situ y entrega de recomendaciones o intervenciones multimedia. Varios artículos reportan que no se realiza correctamente la educación en asma, otros enuncian que su técnica mejora tras la intervención, pero la mayoría de ellos resalta la importancia de una revisión periódica de la técnica. Conclusiones: Los autores refieren mejoría de la técnica de inhalación en todas ellas, así como un mayor automanejo de la enfermedad y adherencia al tratamiento. Es necesario intensificar la educación a los pacientes en el correcto manejo de los dispositivos, y el seguimiento y revisión posterior para optimizar el control de la enfermedad.(AU)

Objective: To analyze educational interventions in pediatric asthmatic patients to achieve an adequate inhalation technique and improve their self-management. Design: Systematic review based on the PRISMA recommendations. Data sources: Pubmed, Scopus, Cuiden, Web of Science and Google Scholar databases were reviewed. Study selection: Sixteen articles published between 2014 and 2021 were included, with access to full text, languages: English, French and Spanish and pediatric population: 0–18 years. Data extraction: Two thousand three hundred and thirteen children were participated. The variables analyzed were: level of care, type of intervention, correct performance of the inhalation technique, follow-up of the technique, delivery of written recommendations, professional-educator category, variables related to respiratory pathology, school absenteeism, quality of life and economic costs. Results: The health care level was primary, hospital and community care, where specialist doctors, nurses and pharmacists stood out as educators. The most prevalent educational interventions are on-site demonstration and delivery of recommendations or multimedia interventions. Several articles report that asthma education is not carried out correctly, others state that their technique improves after the intervention, but most of them highlight the importance of periodic review of the technique. Conclusions: The authors report improvement in the inhalation technique in all of them, as well as greater self-management of the disease and adherence to treatment. It is necessary to intensify the education of patients in the correct handling of the devices, and the follow-up and subsequent review to optimize the control of the disease.(AU)

[Educational interventions in childhood asthma: A systematic review]. / Intervenciones educativas en asma infantil: Una revisión sistemática.

OBJECTIVE: To analyze educational interventions in pediatric asthmatic patients to achieve an adequate inhalation technique and improve their self-management. DESIGN: Systematic review based on the PRISMA recommendations. DATA SOURCES: Pubmed, Scopus, Cuiden, Web of Science and Google Scholar databases were reviewed. STUDY SELECTION: Sixteen articles published between 2014 and 2021 were included, with access to full text, languages: English, French and Spanish and pediatric population: 0-18 years. DATA EXTRACTION: Two thousand three hundred and thirteen children were participated. The variables analyzed were: level of care, type of intervention, correct performance of the inhalation technique, follow-up of the technique, delivery of written recommendations, professional-educator category, variables related to respiratory pathology, school absenteeism, quality of life and economic costs. RESULTS: The health care level was primary, hospital and community care, where specialist doctors, nurses and pharmacists stood out as educators. The most prevalent educational interventions are on-site demonstration and delivery of recommendations or multimedia interventions. Several articles report that asthma education is not carried out correctly, others state that their technique improves after the intervention, but most of them highlight the importance of periodic review of the technique. CONCLUSIONS: The authors report improvement in the inhalation technique in all of them, as well as greater self-management of the disease and adherence to treatment. It is necessary to intensify the education of patients in the correct handling of the devices, and the follow-up and subsequent review to optimize the control of the disease.

The Multiple Trajectories of the Allergic March

The allergic march comprises the sequential appearance of a series of allergic comorbidities. However, variability in the onset and progression of allergic diseases generates a heterogeneous scenario that does not follow a linear and single trajectory. Almost half of the pediatric population presents at least 1 allergy symptom. However, only 4%-6% present multimorbidity, with several allergic diseases co-occurring. It has recently been shown that although they share etiological mechanisms and risk factors, allergic diseases arise independently. In most cases, progression is not consecutive, or at least not the same in all patients. TH2-mediated inflammation, epithelial barrier dysfunction, and genetic predisposition play a fundamental role in the etiology of allergic diseases, on which the interaction with the exposome acts decisively. Therefore, studying diseases from an omics point of view is essential when attempting to describe the various trajectories of allergic progression and to propose effective interventions to prevent multimorbidity. In this narrative review, we provide an overview of the current perception of the allergic march, including clinical observations, omics data, risk factors, and measures aimed at modifying its course or even preventing its onset. (AU)

La marcha alérgica ha dado respuesta durante mucho tiempo a un escenario de aparición secuencial de diferentes comorbilidades alérgicas. Sin embargo, la variabilidad en la aparición y progresión de las diferentes enfermedades alérgicas dibuja un escenario heterogéneo que no responde a una trayectoria lineal y única. Aunque en la actualidad casi la mitad de la población infantil presenta al menos un síntoma de alergia, tan solo un 4-6% presenta multimorbilidad, coexistiendo varias entidades alérgicas. Recientemente se ha demostrado que, aunque compartiendo mecanismos etiológicos y factores de riesgo, estas enfermedades alérgicas surgen de manera independiente y que, en la mayoría de los casos, no se observa una progresión consecutiva, o al menos, no la misma en todos los pacientes. La inflamación mediada por células T helper de tipo 2 (Th2), la disfunción de la barrera epitelial y la predisposición genética juegan un papel fundamental en la etiología de estas enfermedades, sobre los que actúan de manera determinante la interacción con el exposoma. Por ello, el estudio de las enfermedades, desde un punto de vista de las ómicas, es fundamental para describir las diferentes trayectorias de la marcha alérgica y proponer intervenciones eficaces para evitar escenarios de multimorbilidad. En esta revisión narrativa se incluye una descripción general de la percepción actual de la marcha alérgica, incluidas observaciones clínicas, datos ómicos, factores de riesgo y medidas preventivas propuestas para modificar su curso o incluso prevenir su aparición. (AU)

Sputum Inflammatory Patterns Are Associated With Distinct Clinical Characteristics in Patients with Occupational Asthma Independently of the Causal Agent

Background: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. Objectives: To further characterize interactions between induced sputum inflammatory patterns, asthma-related outcomes, and the high- or low-molecular-weight category of causal agents in a large cohort of patients with OA. Methods: We conducted a multicenter, retrospective, cross-sectional study of 296 patients with OA confirmed by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. Results: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (OR [95%CI], 1.31 [1.11-1.55] for each 250-µg increment in daily dose), short-acting ß2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild, 2.48 [1.21-5.08]; moderate/severe, 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male sex (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), use of short-acting ß2-agonists once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the previous 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the specific inhalation challenge (4.45 [1.85-11.59]). Conclusion: The findings indicate that sputum inflammatory patterns in patients with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with findings reported in nonoccupational asthma and are not related to the type of causal agent. (AU)

Antecedentes: La heterogeneidad clínica en el asma ocupacional (AO) inducida por agentes sensibilizantes y su relación con los perfiles inflamatorios de las vías respiratorias siguen siendo muy poco conocidas. Objetivos: Profundizar en la caracterización de las interrelaciones entre los patrones inflamatorios en esputo inducido, diversas variables relacionadas con el asma y la categoría de agentes causales de alto o bajo peso molecular, en una gran cohorte de sujetos con AO Métodos: Este estudio multicéntrico, retrospectivo y transversal se llevó a cabo en 296 sujetos con OA confirmada mediante una provocación bronquial específica (SIC) positiva, en los que se obtuvieron muestras de esputo inducido antes y 24 horas después de la SIC. Resultados: El análisis de regresión logística multivariable reveló que la presencia de eosinofilia en esputo ≥3 % se asoció significativamente con una dosis alta de corticosteroides inhalados (odds ratio [intervalo de confianza del 95 %], 1,31 [1,11-1,55] por cada incremento de 250 µg en la dosis diaria), el uso de agonistas ß2 de acción corta menos de una vez al día (3,54 [1,82-7,00]), y un nivel de hiperreactividad bronquial inespecífica inicial (leve: 2,48 [1,21-5,08]); moderado/grave: 3,40 [1,44-8,29]). La neutrofilia en esputo ≥76%, se asoció con la edad (1,06 [1,01-1,11]), el sexo masculino (3,34 [1,29-9,99]), la ausencia de uso de corticosteroides (5,47 [2,09-15,16]), el uso de agonistas ß2 de acción corta una vez o más al día (4,09 [1,71-10,01]), la presencia de ≥ 2 exacerbaciones graves en los últimos 12 meses en el trabajo (4,22 [1,14-14,99]) y reacciones inmediatas aisladas durante la SIC (4,45 [1,85-11,59])... (AU)

Prevalence, T2 Biomarkers, and Cost of Severe Asthma in the Era of Biologics: The BRAVO-1 Study

Background: The last decade has seen new classifications of the pathophysiology of asthma that have changed the treatment options available. Objectives: To update data on the prevalence of T2 asthma, comorbidities, biomarker characterization, and costs of severe asthma in patients aged ≥12 years, taking into account new classifications and treatment options. Methods: Retrospective, observational, nationwide study using a top-down approach. Data were obtained from BIG-PAC®, an electronic medical record database of 1.7 million patients in Spain. The study population comprised patients aged ≥12 years who had received medical care during the period 2016-2017 and been diagnosed with asthma at least 1 year prior to the index date. Patients were followed for 1 year. Results: The prevalence of asthma was 5.5%. Asthma was severe in 3031 of these patients (7.7%), 81.2% of whom presented T2 asthma. Among patients with severe asthma, 64.1% had uncontrolled disease, 31.2% were oral corticosteroid–dependent (37% in the uncontrolled severe asthma group), and only 3.8% were receiving biologics. The most common T2 comorbidities were allergic rhinitis (66.1%), atopic dermatitis (29.1%), and chronic rhinosinusitis with nasal polyps (14.6%). Mortality rates in the total population and uncontrolled severe asthma groups were 4.2% and 5.5%, respectively. The total annual costs per patient with severe asthma were €5890 (uncontrolled) and €2841 (controlled). Conclusions: In the era of biologics, most severe asthma patients present T2 asthma. Despite the availability of new treatments, rates of oral corticosteroid–dependent patients with uncontrolled severe asthma remain high, although biologics continue to be underused. The costs of uncontrolled severe asthma are twice as high as those of controlled severe asthma. (AU)

Introducción: En la última década se han concadenado una serie de clasificaciones de la fisiopatología del asma que han cambiado las opciones de tratamientos disponibles. Objetivos: Actualizar los datos de prevalencia del asma T2, comorbilidades, caracterización de biomarcadores y costes del asma grave en pacientes ≥12 años en esta nueva situación. Métodos: Estudio retrospectivo, observacional y de ámbito nacional con un enfoque descendente. Los datos se obtuvieron de BIG-PAC®, una base de datos de historias clínicas electrónicas de 1,7 millones de pacientes en España. Se incluyeron pacientes ≥12 años que habían recibido atención médica durante el periodo 2016-2017 y que habían sido diagnosticados de asma al menos un año antes de la fecha índice y fueron seguidos durante un año. Resultados: La prevalencia del asma fue del 5,5%. De estos pacientes, 3.031 presentaban asma grave (7,7%), de los cuales el 81,2% presentaba asma T2. Entre los pacientes con asma grave, el 64,1% no estaban controlados, el 31,2% eran dependientes de corticosteroides orales (37% en el grupo de asma grave no controlada) y solo el 3,8% estaban en tratamiento con biológicos. Las comorbilidades T2 más frecuentes fueron la rinitis alérgica (66,1%), la dermatitis atópica (29,1%) y la rinosinusitis crónica con poliposis nasal (14,6%). Las tasas de mortalidad en los grupos de asma grave total y no controlada fueron del 4,2% y del 5,5%, respectivamente. Los costes totales anuales por paciente con asma grave fueron de 5.890 euros (no controlado) y 2.841 euros (controlado). Conclusiones: En la era de los biológicos, la mayoría de los pacientes con asma grave presentan asma T2. A pesar de la disponibilidad de nuevos tratamientos, las tasas de pacientes con asma grave no controlados y dependientes de corticosteroides orales siguen siendo altas, y los biológicos siguen estando infrautilizados. Los costes del asma grave no controlada duplican los del asma grave controlada. (AU)

Airway Reactance Predicts Static Lung Hyperinflation in Severe Asthma

Background: Static lung hyperinflation (SLH) measured using body plethysmography in patients with asthma is associated with poor outcomes. The severity of SLH may be associated with small airway dysfunction (SAD), which can be measured using impulse oscillometry (IOS). Objective: This study aims to determine the correlation between SLH and SAD in patients with severe asthma and assess the improvement in SLH and SAD with treatment. Methods: We analyzed data from patients who were enrolled in the Taiwan Severe Asthma Registry, which comprises a prospective observational cohort. Plethysmography and IOS were performed regularly. The relationship between spirometry and IOS parameters was determined. Changes in the clinical outcomes in response to treatment were analyzed. Results: Of 107 patients with severe asthma, 83 (77.6%) had SLH based on an increased residual volume to total lung capacity ratio (RV/TLC). Most patients were older women with worse pulmonary function and SAD than those without SLH. SAD, defined as increased airway resistance/reactance, was significantly correlated with SLH. Airway reactance at 5 Hz (X5) ≤−0.21 kPa/(L/s) detected SLH with an area under the receiver operating characteristic curve of 0.84 (P<.0001; sensitivity, 85.2%; and specificity, 83.3%). After 12 months, patients who received add-on biologics (vs those who did not) had significantly reduced exacerbations, fractional exhaled nitric oxide level, and blood eosinophil counts, as well as improved forced expiratory volume in the first second, X5, and a trend toward reduced RV/TLC ratio. Conclusion: In severe asthma, airway reactance (X5) could be a novel parameter for assessing SLH. (AU)

Antecedentes: En el asma bronquial, la hiperinsuflación pulmonar estática (SLH) medida mediante pletismografía corporal (Pleth) se asocia a un peor pronóstico. La gravedad de la SLH podría estar asociada con la disfunción de las vías respiratorias pequeñas (SAD), que puede medirse mediante la oscilometría de impulsos (IOS). Objetivo: Este estudio pretende determinar la correlación entre el SLH y la SAD en pacientes con asma grave, y la mejora de ambos parámetros en respuesta al tratamiento. Métodos: Se analizaron los datos de los pacientes que se inscribieron en el Registro de Asma Grave de Taiwán, una cohorte observacional prospectiva. Se realizaron periódicamente mediciones de Pleth e IOS. Se determinó la relación entre los parámetros espirométricos e IOS. Se analizaron los cambios en los parámetros clínicos y funcionales en respuesta al tratamiento. Resultados: De una muestra de 107 pacientes con asma grave, 83 (77,6%) presentaban SLH, definida mediante una relación volumen residual/capacidad pulmonar total (VR/CTP) aumentada. La mayoría de los pacientes eran mujeres de edad avanzada con peor función pulmonar y SAD, en comparación con los que no tenían SLH. El SAD por aumento de la resistencia/reactancia de las vías respiratorias se correlacionó significativamente con el SLH. La reactancia de las vías respiratorias a 5 Hz (X5) ≤-0,21 [kPa/(L/s)] detectó el SLH con un área bajo la curva ROC de 0,84 (p < 0,0001, sensibilidad = 85,2% y especificidad = 83,3%). Después de 12 meses, los pacientes que recibieron tratamiento biológico adicional presentaron una reducción significativa de las exacerbaciones, del nivel de óxido nítrico exhalado, del recuento de eosinófilos en sangre, una mejora del volumen espiratorio forzado en el primer segundo, de la X5, y una tendencia a la reducción del cociente RV/TLC en comparación con los que no recibieron tratamiento biológico... (AU)