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.

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.

Comparison on Ameliorating Effect of Arisaematis Rhizoma and Arisaematis Rhizoma Preparatum on Allergic Asthma in Rats / 中国实验方剂学杂志

ObjectiveTo investigate the therapeutic effects and difference in the effects of Arisaematis Rhizoma （AR） before and after processing （i.e.， Arisaematis Rhizoma Preparatum， ARP） with Zingiberis Rhizoma Recens-Alumen on allergic asthma in rats and to provide a basis for the theory of processing improving the efficacy. MethodA rat model of allergic asthma was established in 70 SD rats by intraperitoneal injection of ovalbumin （OVA）-aluminum hydroxide. The rats were administrated with the aqueous extracts of AR （1.2， 0.3 g∙kg-1） and ARP （1.2， 0.3 g∙kg-1） aqueous extracts by gavage， and montelukast sodium （0.001 g∙kg-1） was used as the positive drug. The T helper cell type 1/type 2 （Th1/Th2） ratio in the serum and bronchoalveolar lavage fluid （BALF） and percentages of inflammatory cells in BALF were determined. Polymerase chain reaction （PCR） was employed to determine the mRNA level of mucin 5AC （MUC5AC） in the lung tissue. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining and PAS staining. Immunohistochemical assay was employed to measure the expression of c-Jun amino-terminal kinase （JNK）， extracellular signal regulated protein kinase （ERK）， and p38 mitogen-activated protein kinase （p38 MAPK） in rat lung tissue. Western blot was employed to determine the protein levels of ERK， p-ERK， JNK， p-JNK， p38， p-p38 in the lung tissue. The effects of AR and ARP were compared based on overall desirability. ResultCompared with the blank group， the levels of interleukin-12 （IL-12） and γ interferon （IFN-γ） in serum and BALF of rats in the model group were significantly lower （P<0.05， P<0.01）， and the levels of interleukin-4 （IL-4）， interleukin-5 （IL-5） and interleukin-13 （IL-13） were significantly higher （P<0.05， P<0.01）. Compared with the model group， the serum and BALF contents of IL-12 and IFN-γ in rats in the montelukast sodium group， high-dose AR group and high-dose ARP group were significantly higher （P<0.05， P<0.01）， and the contents of IL-4， IL-5 and IL-13 were significantly lower （P<0.05， P<0.01）， and the serum contents of IFN-γ in rats in the low-dose AR group and low-dose ARP group were in BALF was significantly higher （P<0.05） and IL-4 and IL-13 were significantly lower （P<0.05， P<0.01）， the percentages of macrophages， lymphocytes， neutrophils， and eosinophils were reduced in BALF， and the expression of JNK/ERK/p38 MAPK signaling pathway and MUC5AC protein was inhibited in lung tissues. Overall assessment of the normalized analysis revealed that the ARP group was slightly more potent than the AR group after administration of the same dose. ConclusionAR and ARP can effectively treat allergic asthma by inhibiting JNK/ERK/p38 MAPK signaling pathway， and the effect is better after concoction， which can provide data support for its "concoction efficiency".

Relationship between self-reported occupational noise exposure and expression levels of plasma inflammatory cytokines in adult asthmatic patients / 公共卫生与预防医学

Objectives To investigate the relationship between self-reported occupational noise exposure and levels of plasma inflammatory cytokines in asthmatic patients. Methods A total of 910 adult asthmatic patients were selected as the study subjects, and their occupational noise exposure history and other related information were collected. The peripheral blood samples were collected from the patients, and the expression levels of plasma soluble CD14 (sCD14), complement factor D (CFD), Eotaxin-11 (CCL11), and IL-9 were determined. The relationship between self-reported occupational noise exposure and the expression levels of the four inflammatory cytokines in patients’ plasma were analyzed using multiple linear regression models. The interactions between confounding factors and self-reported occupational noise exposure were further analyzed by interaction analysis. Results The plasma CCL11, sCD14 and CFD expressions in asthmatic patients with self-reported occupational noise exposure were significantly higher than those in patients without the exposure (P<0.05). After adjusting for confounding factors, compared with patients reporting no occupational noise exposure, the plasma CFD expression was increased by 0.17 (95% CI: 0.02, 0.31) natural logarithm units in patients with self-reported occupational noise exposure. During remission, the levels of plasma CCL11 and sCD14 in asthmatic patients with self-reported occupational noise exposure were increased by 0.27 (95% CI: 0.05, 0.49) and 0.22 (95% CI: 0.02, 0.41) natural logarithm units, respectively, when compared with patients without the exposure. Interaction analysis showed that self-reported occupational noise exposure had significant multiplicative interaction with smoking or pet ownership on plasma CCL11 or CFD expressions in asthmatic patients (all P<0.05). Conclusion Self-reported occupational noise exposure is significantly associated with increased expression levels of plasma CFD, CCL11, and sCD14 in adult asthmatic patients.

Value of biotargeted drugs in airway mucus therapy of asthma / 中国临床药理学与治疗学

Airway mucus plug is a common phenotype in asthma that increases the risk of acute asthma attacks by causing aggravation of airflow obstruction. Given its important role in asthma, treatment targeting airway mucus plugs may be a strategy to control asthma progression and prevent fatal asthma exacerbations. Previous studies have shown that acidosophils and T2 type inflammation are related with the formation of mucus plugs, and biotargeted drugs targeting the above pathways may be effective in the treatment of airway mucus plugs.

Progress in the application of AIT in allergic airway diseases / 中国临床药理学与治疗学

Allergen specific immunotherapy (AIT) is to identify the patient's allergen, give the patient repeated exposure to the allergen extract, and gradually increase the concentration and dose until the target maintenance dose is reached, so that the patient can develop tolerance to the allergen, which is the only treatment that can regulate the pathogenesis of allergic diseases and change its natural course. In recent years, domestic and foreign scholars have made great progress in the clinical practice and research field of AIT. This article reviewed the relevant progress of the mechanism, efficacy and drug administration of AIT.

Immunologic characteristics and management and prospects of targeted biological therapy in adults with severe asthma / 中国临床药理学与治疗学

Severe asthma stands as a formidable contributor to both mortality and morbidity of patients suffering asthma, casting substantial social and economic shadows on communities. As our understanding of asthma's pathophysiology deepens, a beacon of hope emerges in the form of biological targeted therapies, offering a promising avenue for the management of this challenging condition. These therapies, by precisely inhibiting or modulating pivotal molecules in the inflammatory cascade, offer potential benefits in symptom alleviation, lung function enhancement, and risk reduction of acute exacerbations. They signify a paradigm shift in severe asthma treatment. Within the confines of this article, we embark on a systematic exploration of the immunological underpinnings that define severe asthma. By delving into the intricacies of the immune system's role in exacerbating this condition, we aim to offer a comprehensive assessment of both the current landscape and the future prospects of biological therapies. Our objective is to provide a scientifically robust and valuable reference that can guide the individualized treatment of patients grappling with severe asthma.

Progress and prospect of inhaled biological agents in asthma / 中国临床药理学与治疗学

More than 300 million people worldwide suffer from asthma, and the incidence is increasing year by year. As one of the most common chronic diseases, asthma is an immune-mediated inflammatory disease with complex triggering mechanisms and strong heterogeneity. With the in-depth study of physiological and pathological mechanisms, therapeutic small molecule and hormone drugs have been introduced to control and treat most patients, but about 5% - 10% of patients still suffer from various subtypes of difficult to control and treat asthma, that is, severe asthma. In the past decade, with the rapid development of bio-pharmaceutical research, protein and antibody have become the key drugs for the treatment of severe asthma with high efficacy, high specificity and high safety. However, biological drugs are usually administered by injection, they cannot be noninvasive and directly delivered into the lung to quickly absorb and take effect. Therefore, there is an urgent need for the introduction of inhaled biologics with quick effectiveness, convenience, economy and safety in clinical. The review summarizes the existing small molecule, hormone and biological therapy drugs, and summarizes the development of inhalable biological agents of asthma, and analyzes the future prospects of the inhalable biological drugs, which is designed to deepen the perception of the direction of the inhalable biological drugs research, and update the information of the field, in order to provide reference for the development of more inhalable biologics.

Navafenterol, a new drug for the treatment of chronic obstructive airway disease / 中国临床药理学与治疗学

Navafenterol is a new compound with both muscarinic receptor antagonist and β2 receptor agonist effects in a single molecule, who is being developed for the treatment of chronic obstructive airway disease such as chronic obstructive pulmonary disease and asthma. These pilot clinical studies found that it can significantly improve lung function and symptoms, and is safe and well tolerated. Common treatment emergent adverse events include headache, nasopharyngitis, and dizziness. It may become a next-generation bronchodilator for chronic obstructive airway disease. This review introduced the prospective of Navafenterol.

Mechanism of action of formononetin in alleviating allergic asthma through DRP1-NLRP3 signaling pathway / 中国药理学通报

Aim To investigate the mechanism by which formononetin (FN) inhibits mitochondrial dynamic-related protein 1 (DRP1) -NLRP3 axis via intervening the generation of ROS to reduce allergic airway inflammation. Methods In order to establish allergic asthma mouse model, 50 BALB/c mice aged 8 weeks were divided into the control group, model group, FN treatment group and dexamethasone group after ovalbumin (OVA) induction. Airway inflammation and collagen deposition were detected by HampE and Masson staining. Th2 cytokines and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and IgE levels in bronchoalveolar lavage fluid (BALF) were measured by ELISA, ROS in BEAS-2B cells was assessed by DCFH-DA staining, DRP1 expression in lung tissue and BEAS-2B cells was detected by immunohistochemistry and immunofluorescence, and the DRP1-NLRP3 pathway was analyzed by immunoblotting. Results FN treatment could effectively ameliorate the symptoms of asthmatic mouse model, including reducing eosinophil accumulation, airway collagen deposition, decreasing Th2 cytokine and IgE levels, reducing ROS and MDA production, increasing SOD and CAT activities, and regulating DRP1-NLRP3 pathway-related protein expression, thereby relieving inflammation. Conclusion FN ameliorates airway inflammation in asthma by regulating DRP1-NLRP3 pathway.

Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking / 中国药理学通报

Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

Prevalence of Chronic Non-Communicable Respiratory Diseases in Mosul City

@#Introduction: Chronic non-communicable respiratory diseases (CNCRDs) encompass a group of conditions affecting the airways and lung structures, including Chronic Obstructive Pulmonary Disease (COPD), emphysema, allergic rhinitis, asthma, pulmonary arterial hypertension, and cystic fibrosis. CNCRDs pose a significant global health challenge, resulting in approximately four million deaths annually. This study aimed to identify the prevalence and risk factors associated with CNCRDs and measure trends in the prevalence of these risk factors over time. Methods: A cross-sectional epidemiological study was conducted using data collected from primary health centers on both sides of Mosul City. The study period extended from January 1 to July 31, 2022, with information obtained from (40) primary health centers, consisting of (20) centers on the right side and (20) centers on the left side of Mosul. Results: In 2021, the City of Mosul recorded a total of 13,005 registered cases, with 5,598 cases being attributed to asthma (43%), and 7,347 cases being associated with COPD (57%). Bronchial asthma constituted 43% of cases, with 5598 patients, and the highest incidence occurred in the age group between 20-44 years. Conclusion: The prevalence of bronchial asthma and COPD among patients with CNCRDs in Mosul is alarmingly high. It emphasizes the importance of implementing preventive policies and strategies targeting modifiable risk factors for these respiratory conditions.

Regulation of Immune Balance by Traditional Chinese Medicine in Treatment of Cough Variant Asthma： A Review / 中国实验方剂学杂志

Cough variant asthma （CVA） is a chronic respiratory disease with cough as its main symptom. The occurrence of CVA is closely related to non-specific airway inflammation， and its pathogenesis involves environmental， genetic， immune， and other factors. In recent years， the advantages of traditional Chinese medicine （TCM） in the treatment of CVA have attracted the attention of experts and scholars in China and abroad， especially its prominent role in regulating immune balance， relieving cough symptoms in CVA patients， and reducing recurrence. T Helper cells 1 （Th1）， T helper cells 2 （Th2）， T helper cells 17 （Th17）， and regulatory T cells （Treg） are derived from CD4+ T cells. Immune imbalance of Th1/Th2 and Th17/Treg is a new hotspot in the pathogenesis of CVA and a potential key target in the treatment of CVA by TCM. Th cell subsets are in dynamic balance under physiological conditions， maintaining respiratory immune homeostasis in which pro-inflammatory cytokines and anti-inflammatory cytokines are balanced. Immature helper T cells （Th0） can be differentiated into Th1， Th2， Th17， Treg， and other cell subsets due to cytokine types in the microenvironment in the stage of CVA maturation. The proliferation of Th2 cells leads to eosinophilic airway inflammation. Excessive differentiation of Th17 cells induces neutrophil airway inflammation. Th1/Th2 and Th17/Treg cells are mutually restricted in number and function， and the immune imbalance of Th1/Th2 and Th17/Treg is easy to aggravate the generation of inflammatory response. Restoring immune balance is particularly important for the airway anti-inflammatory therapy of CVA. In this paper， the imbalance of Th1/Th2 and Th17/Treg and the pathogenesis of CVA were systematically expounded. Meanwhile， the latest research on the regulation of immune imbalance by TCM compound， single TCM， and its effective ingredients in the treatment of CVA was reviewed. It provides ideas and references for revealing the scientific connotation of TCM regulating immune balance therapy of CVA， as well as the development of clinical treatment and basic research of CVA.

Effects of Guben Fangxiao Beverage （固本防哮饮） on Lung Tissue Oxidative Stress and AMPK/Nrf2/HO-1 Pathway in Mice with Bronchial Asthma in Remission / 中医杂志

ObjectiveTo investigate the possible mechanism of Guben Fangxiao Beverage （固本防哮饮） for the prevention and treatment of chronic airway inflammation during asthma remission. MethodsThirty-six female Balb/c mice were randomly divided into normal group， model group， low-， medium-， and high-dose of Guben Fangxiao Beverage group and montelukast sodium group， with 6 mice in each group. Except for the normal group， ovalbumin and respiratory syncytial virus were used in other groups to establish a mouse model of bronchial asthma in remission stage. After molding， the low-， medium-， and high-dose groups of Guben Fangxiao Beverage were respectively given 12， 24， and 36 g/（kg·d）， the montelukast sodium group was given montelukast sodium granule 2.6 mg/（kg·d）， and the mice in the normal group and model group were given 20 ml of double-distilled water， all by gavage， once a day for 28 days. The levels of interleukin 4 （IL-4） and interleukin 5 （IL-5） in the lung tissue of mice were detected； HE staining was used to observe the pathology of the lung tissue and to score the inflammation； DHE staining was used to observe the level of reactive oxygen species （ROS） in the lung tissue， and the activities of mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ in the lung tissue were detected； the levels of serum superoxide dismutase （SOD）， catalase （CAT）， malondialdehyde （MDA） and adenosine triphosphate （ATP） were detected； the protein expression levels of phosphorylated adenosine monophosphate-activated protein kinase （p-AMPK）， nuclear factor erythroid 2-related factor 2 （Nrf2）， haem oxygenase 1 （HO-1） and cAMP responsive element binding protein （CREB） in the lung tissues of the model group were detected by Western blot. ResultsCompared with the normal group， the histopathological results of the lungs of mice in the model group showed an increase in inflammatory cells around the airways and an increase in inflammatory score； DHE staining showed an increase in the level of ROS， and an increase in the levels of IL-4 and IL-5 in the lung tissues； the levels of serum SOD， CAT， and ATP were reduced， and the level of MDA was elevated； the activities of the mitochondrial respiratory chain complexes Ⅰ， Ⅱ， Ⅲ， Ⅳ， and Ⅴ of the lung tissues were reduced， and the activities of p-AMPK， Nrf2， CREB protein expression decreased （P＜0.05）. Compared with the model group， the lung tissue inflammatory cells and inflammation scores of mice in each Guben Fangxiao Beverage dose group and montelukast sodium group were reduced； the levels of ROS， IL-4 and IL-5 in the lung tissue were reduced； the levels of CAT and ATP in the serum increased， and the content of MDA was reduced； and the activities of mitochondrial respiratory chain complexes Ⅰ and Ⅱ， as well as the expression of CREB protein， were elevated in the lung tissue （P＜0.05）. Compared with the high-dose group， the MDA level of the medium-dose Guben Fangxiao Beverage group decreased （P＜0.05）. The activity of mitochondrial respiratory chain complex V in the medium-dose group was higher than that in the montelukast sodium group， and the activity of mitochondrial respiratory chain complex Ⅳ in the medium- and high-dose groups was higher than that in the low-dose group （P＜0.05）. ConclusionGuben Fangxiao Beverage can inhibit oxidative stress and improve mitochondrial function to relieve chronic airway inflammation in bronchial asthma model mice during asthma remission， and its mechanism may be related to the activation of AMPK/Nrf2/HO-1 signaling pathway.

Serum interleukin-33 combined with FEF75% z-score and FeNO improves the diagnostic accuracy of asthma in children

Abstract Objective To investigate the diagnostic efficacy of serum IL-33 single indicator and combined indicators for asthma in children. Methods 132 children were initially diagnosed with asthma during acute exacerbation and 100 healthy children were included. Serum IL-33 concentration differences were compared between asthmatic and normal children. Correlations between IL-33 with pulmonary function parameters, FeNO, peripheral blood EOS counts and serum total IgE were analyzed in asthmatic children. ROC curves were used to assess IL-33 diagnostic efficacy and its combined indicators. To prevent overfitting of the predictive model, the hold-out cross-validation method was used. Results (1) Serum IL-33 concentrations were significantly higher in children with asthma than in normal children (p < 0.001). (2) IL-33 concentration was negatively correlated with FVC z-score, FEV1 z-score and FEF75% z-score in asthmatic children (p < 0.05). (3) The area under the ROC curve of IL-33 was 0.821, which was higher than those of FeNO, FVC z-score, and FEV1 z-score. (4) Cross-validation of the combined indicators showed that IL-33 significantly improved asthma diagnostic efficacy. The combination of IL-33, FEF75% z-score, and FeNO showed the highest diagnostic efficacy, with the AUC, sensitivity, and specificity of the combined indicator being 0.954, 90.1%, and 89. 0%, respectively, and good extrapolation of the predictive model. Conclusion Serum IL-33 is higher in children with asthma and increases with the severity of pulmonary ventilation obstruction. A single indicator of serum IL-33 demonstrates moderate diagnostic accuracy, and its combination with FEF75% z-score and FeNO significantly improves the diagnostic accuracy in childhood asthma.

Análisis bibliométrico de la producción científica cubana sobre asma en Scopus

Introducción: El asma es una entidad con alta prevalencia a nivel mundial y en Cuba, que ha suscitado nuevas investigaciones. Objetivo: Caracterizar la producción científica cubana sobre asma en la base de datos Scopus. Materiales y métodos: Se realizó un estudio observacional, descriptivo y bibliométrico de los artículos publicados sobre asma en Scopus con autores cubanos, desde 1973 hasta 2021. Para la recuperación de los registros se empleó una fórmula de búsqueda. Para el análisis de los datos se usaron los software Bibexcel y VOSviewer. Resultados: Se publicaron 154 investigaciones sobre asma, con predominio de artículos originales (136) y de revisión (12). Las áreas más productivas fueron Medicina (144) e Inmunología y Microbiología (34). Los artículos fueron publicados en 48 revistas; de ellas, 11 fueron cubanas, con la Revista Cubana de Medicina como la más productiva. México aportó el mayor número de colaboraciones (10). El Hospital Clínico Quirúrgico Docente General Calixto García (15) fue el más productivo. Se identificaron tres clústeres de palabras clave, con "human", "asthma" y "Cuban" como términos centrales y de mayor ocurrencia. Conclusiones: Existió una baja producción científica sobre asma, centrada principalmente en artículos originales, en el área de Medicina y en revistas nacionales. Se evidenció colaboración internacional. Los ejes principales de investigación fueron el diagnóstico, tratamiento, investigación básica en modelos animales, nuevas terapéuticas, factores de riesgo y prevención.

Introduction: Asthma is an entity with high prevalence worldwide and in Cuba, which has prompted new research. Objective: To characterize Cuban scientific production on asthma in the Scopus database. Materials and methods: An observational, descriptive and bibliometric study was carried out on articles on asthma published in Scopus by Cuban authors, from 1973 to 2021. A search formula was used to retrieve the records. Bibexcel and VOSviewer were used for data analysis. Results: 154 research papers on asthma were published; with a predominance of original (136) and review articles (12). The most productive areas were Medicine (144) and Immunology and Microbiology (34). Articles were published in 48 journals, of which 11 were Cuban, with the Revista Cubana de Medicina (Cuban Journal of Medicine) being the most productive. Mexico contributed the highest number of collaborations (10). The Teaching Hospital General Calixto García (15) was the most productive. 3 key word clusters were identified, with "human", "asthma" and "Cuban" as central and most occurring terms. Conclusions: There was a low scientific production on asthma, mainly focused on original articles, in the area of Medicine and in national journals. International collaboration was evident. The main areas of research were diagnosis, treatment, basic research in animal models, new therapeutics, risk factors and prevention.

Development of a mobile app for the evaluation of patients with chronic rhinosinusitis

Abstract Objective To develop a mobile application with a standardized routine, to be used by general otolaryngologists for evaluating patients with chronic rhinosinusitis. Methods A systematic review was made to identify outcomes, recommendations and what tests that would be used in the routine evaluation of patients with chronic rhinosinusitis; establish an expert consensus on items to be included in this routine evaluation of patients with chronic rhinosinusitis using the Delphi method; development of an application for use on a mobile device, with the routine evaluation of patients with chronic rhinosinusitis. Results Based on the systematic review, the outcomes used in studies about chronic rhinosinusitis were identified, as well as guidelines recommendations, which showed discrepancies between them. These recommendations and outcomes were presented to specialists in chronic rhinosinusitis, until a consensus was reached. As a result of the Delphi method, the flowchart of the routine evaluation of patients with chronic rhinosinusitis was defined, and then was used for the development of the mobile application. Conclusion The creation of the mobile application for evaluating patients with chronic rhinosinusitis followed an adequate methodology of elaboration made by specialists in the field of chronic rhinosinusitis, standardizing the investigation of these patients. Level of evidence: Level 5.

Aeroallergen sensitization patterns among patients with chronic rhinitis with or without concomitant asthma

Abstract Objectives The aim of this study was to explore the differences in the pattern of allergen sensitization in CR individuals without or with asthma, according to asthma severity. Methods A total of 1066 adults were evaluated. Asthma and chronic⁄allergic rhinits were identified by specialists, questionnaries and skin-prick test. The phenotypic characterization was avaliable from skin-prick test to an aeroallergen extended panel, total IgE and pulmonary function. Using questionnaires and clinical evaluation, participants were classified into the groups: chronic rhinitis alone (CRA) and chronic rhinitis + asthma, the latter subdivided into CR + mild asthma (CRMA) and CR + moderate to severe asthma (CRMSA). Aerollergen sensitization was defined by a positive prick test to one or more allergens associated with nasal symptoms and/or asthma. The association between CR and asthma was evaluated by multivariable logistic regression. The evidence of effect modification of pattern of sensitization in CR on the association with asthma severity and outcomes was examined by introducing interactions terms in the logistic regression models adjusting for confounders. Results Frequency of sensitization to aeroallergens was higher in association with asthma in comparison to CRA (CRMA 70.4%; CRMSA 65.0%; CRA 47.0%; p= 0.000). Similarly, the presence of asthma was associated to aeroallergen multiple sensitization (51.5%) (OR = 2.10, 95% CI 1.27-3.50). Additionally, the sensitization to mites, cockroaches, animal epithelium, grasses, and molds, were higher in asthma (56.8%, 24.3%, 12%, 7.13% and 10.3%, respectively). Sensitization to Alternaria alternata, Cladosporium herbarum and dog epithelium was exclusive in asthma groups. A concomitant asthma diagnosis was directly associated with a positive allergen sensitization at least one allergen (62.7%, OR = 2.45, 95% CI 1.80-3.34) and polissensitization (51.5%, OR = 2.10, 95% CI 1.27-3.50). Conclusion Asthma is associated with multiple allergen sensitization among patients with CR. Some unique profiles of aeroallergen sensitization were observed in patients with CR and asthma. Nevertheless, no difference was found in the sensitization in relation to asthma severity, which suggest atopy is not the main underlying mechanism for asthma severity among patients with CR. Level of evidence: Level 3.

Birth weight and asthma in young adults of a Brazilian birth cohort / Peso ao nascer e asma em adultos jovens de um coorte brasileiro de nascimentos

Abstract This article aims to evaluate the association between birth weight and asthma in adulthood, estimated by employing structural equation modeling. Cohort study with 1,958 participants aged 23-25 years from Ribeirão Preto, São Paulo, Brazil. Standardized questionnaires were applied and pulmonary function evaluated, including bronchial reactivity with methacholine. A theoretical model was proposed to explore the effects of birth weight and asthma in adulthood. Asthma, socioeconomic status at birth (Birth SES), and current socioeconomic status (Adult SES) were obtained by constructs. Maternal age, sex, skin color, body mass index (BMI), smoking, parental asthma history, history of respiratory infection before five years old, history of hospitalization for lung disease before two years old, and atopy were the studied variables. 14.1% of participants were diagnosed with asthma. Birth weight was associated with asthma (Standardized Coefficient - SCtotal=-0.110; p=0.030), and an indirect effect was also observed (SCindirect=-0.220; p=0.037), mediated by hospitalization before two years and respiratory infection before five years. Lower birth weight showed an increased risk of asthma in adulthood and the SES Birth and Adult SES variables underlie this association.

Resumo O objetivo deste artigo é avaliar associação entre peso ao nascer e asma na vida adulta pela análise de equações estruturais. Estudo de coorte com 1.958 participantes de 23-25 anos, residentes em Ribeirão Preto, São Paulo, Brasil. Foram aplicados questionários padronizados e avaliado a função pulmonar, incluindo hiper-reatividade brônquica com metacolina. O modelo teórico foi proposto para explorar os efeitos do peso ao nascer e asma na vida adulta. Asma, status socioeconômico ao nascimento (SES Nascimento) e status socioeconômico adulto (SES adulto) foram obtidos por um construto. Variáveis estudadas: idade materna, idade, sexo, cor da pele, índice de massa corporal (IMC), tabagismo, história de asma dos pais, história de infecção respiratória antes dos cinco anos, história de internação por doença pulmonar antes dos dois anos e atopia. 14,1% dos participantes foram diagnosticados com asma. Peso ao nascer foi associado com asma (Coeficiente Padronizado - CPtotal=-0,110; p=0,030), e foi observado efeito indireto (CPindireto=-0,220; p=0,037), mediado por internação antes dos dois anos e infecção respiratória antes dos 5 anos. Menor peso ao nascer aumentou o risco para asma na vida adulta e as variáveis SES Nascimento e SES adulto foram subjacentes a esta associação.