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.

Prueba de estimulación por frío en el control tensional de pacientes hipertensos en la atención preoperatoria

Fundamento: la hipertensión arterial constituye un problema de salud mundial. Su hiperreactividad se evidencia en pacientes sometidos a estrés quirúrgico. Objetivo: evaluar la eficacia de la prueba de estimulación por frío para el control tensional del paciente hipertenso en la atención preoperatoria. Métodos: se realizó un estudio descriptivo, transversal y prospectivo durante el año 2019 en el Hospital General Docente Vladimir Ilich Lenin de Holguín. El universo estuvo constituido por todos los pacientes hipertensos pendientes de cirugía electiva, la muestra por 150 pacientes hipertensos diagnosticados. Se utilizaron las variables: edad, sexo, resultado de la prueba de estimulación por frío, comportamiento tensional perioperatorio y complicaciones tensionales perioperatorias. Se emplearon indicadores estadísticos del tipo descriptivo como valores absolutos y porcientos. Resultados: predominó el sexo masculino con 58 pacientes, los grupos etáreos de 18 a 29 años con 36 pacientes (33,03 %) y el grupo de 70 y más años con 25 pacientes (22,94 %). 80 pacientes (73,39 %) tuvieron una prueba negativa. Hubo una elevada correspondencia entre resultado negativo y normotensión perioperatoria con 78 pacientes (98,73 %). La principal complicación fue la suspensión de la operación por elevación de las cifras tensionales en 20 pacientes (66,67 %). Su sensibilidad fue del 80 % y la especificidad del 93,67 %. La probabilidad de no padecer las complicaciones fue del 92,50 % en pacientes con resultado negativo. Conclusiones: la prueba fue efectiva al establecer una acertada relación entre el resultado positivo y la ocurrencia de complicaciones tensionales en el paciente en la atención preoperatoria. Existió correspondencia entre el control estable preoperatorio y la estabilidad tensional trans y posoperatoria.

Background: arterial hypertension constitutes a global health problem. Its hyperreactivity is evidenced in patients subjected to surgical stress. Objective: to evaluate the effectiveness of the cold stimulation test for blood pressure control of hypertensive patients in preoperative care. Methods: a descriptive, cross-sectional and prospective study was carried out during 2019 at the Vladimir Ilich Lenin General Teaching Hospital in Holguín. The universe consisted of all hypertensive patients pending elective surgery, the sample by 150 diagnosed hypertensive patients. The variables used were: age, sex, result of the cold stimulation test, perioperative stress behavior and perioperative stress complications. Descriptive statistical indicators such as absolute values ​​and percentages were used. Results: the male sex predominated with 58 patients, the age groups from 18 to 29 years with 36 patients (33.03 %) and the group of 70 years and over with 25 patients (22.94 %). 80 patients (73.39 %) had a negative test. There was a high correspondence between the negative result and perioperative normotension with 78 patients (98.73 %). The main complication was the suspension of the operation due to elevated blood pressure figures with 20 patients (66.67 %). Its sensitivity was 80 % and specificity 93.67 %. The probability of not suffering complications was 92.50 % in patients with a negative result. Conclusions: the test was effective by establishing a correct relationship between the positive result and the occurrence of blood pressure complications in the patient in the preoperative care. There was correspondence between preoperative stable control and trans and postoperative tension stability.

Perivascular Innervation in the Nasal Mucosa and Clinical Findings in Patients with Allergic Rhinitis and Idiopathic Rhinitis

Abstract Introduction The nonspecific hyperreactivity of rhinitis has been attributed to neurotrophins activating sensory nerves and inflammatory cells. The relationship between these markers and the intensity of the symptoms is not well established and few studies have evaluated individuals with idiopathic rhinitis. Objective The present study aims to evaluate whether perivascular innervation and nerve growth factor (NGF) are related to the intensity of the clinical conditions in allergic rhinitis (AR) and idiopathic rhinitis (IR). Methods A total of 15 patients with AR and 15 patients with IR with the indication for inferior turbinectomy (associated or not with septoplasty) were selected. The patients received a score according to their signs and symptoms. After the surgery, we quantified eosinophils, mast cells, NGF, and nerve fibers in the nasal turbinate. Results The score of the signs and symptoms was higher in the AR group. Nerve growth factor was found in the cytoplasm of inflammatory cells in the submucosa in greater quantity in the AR group. The nerve fibers were distributed throughout the tissue, mainly in the subepithelial, glandular, and vascular regions, and there was no difference between the groups. Greater perivascular innervation was associated with a higher signs and symptoms score. Conclusions We concluded that these findings suggest that the NGF produced by submucosal inflammatory cells stimulates increased perivascular innervation in rhinitis, thus directly reflecting in more intense clinical conditions, especially in AR.

Antecedents of Bronchial Asthma in Children of a Rural Population of Pakistan

Introduction: Bronchial asthma is the most frequent disease in childhood. Its prevalence in Karachi is from 8.2 to 8.5% in urban areas and 7.5% in rural areas. Its etiology is multifactorial. Objectives: To identify the associated risk factors that influence the development of bronchial asthma in children belonging to clinics 5 and 10 of Ruben Batista Rubio de Karachi polyclinic from September / 2016 to October / 2017. Method: An analytical study of cases and controls was carried out. The cases were 31 asthmatics. 1 x 1 matching was performed. Socio-demographic and biomedical variables were studied. The information of the clinical histories was obtained. Chi-square and Odds Ratio tests were used. Results: They presented a family history of atopy and bronchial asthma, 19 cases, 3 controls, X2 = 13.11. In the prenatal stage, 19 cases (61.29%) had exposure to an allergen, X2 = 5.72 OR = 4.55. Respiratory infections with wheezing before 2 years presented 20 cases, (64.52%), X2 = 16.73 OR = 4.44. Early ablation of 19 cases, (61.19%) 3 controls, (9.98%), X2 = 13.11, OR = 14.78. Conclusions: Male patients between 5 and 10 years old were the most frequent. Family history of bronchial asthma and / or atopy, exposure to allergens in the prenatal stage, low birth weight, respiratory infections with wheezing before 2 years, early ablation and malnutrition by excess were identified as factors of associated risks that influenced the development of bronchial asthma.

Metaanálisis. Frecuencia de hiperreactividad plaquetaria en pacientes con DM y HTA sometidos a ICP / Meta-analysis. Frequency of platelet hyperreactivity in patients with DM and HTA undergoing PCI

Resumen Objetivo: Realizar un metaanálisis de la frecuencia de hiperreactividad plaquetaria (HPR) para aspirina y clopidogrel con diferentes agregómetros, en pacientes con diabetes mellitus (DM) e hipertensión (HTA) sometidos a intervención coronaria percutánea (ICP). Método: Revisión sistemática con metaanálisis a partir de 40 búsquedas en tres bases de datos multidisciplinarias (PubMed, ScienceDirect y SciELO), siguiendo las fases de la guía PRISMA entre los años 2005 y 2021. Se garantizaron la reproducibilidad y la calidad metodológica por parte de dos investigadores que usaron la guía STROBE. Los análisis se basaron en frecuencias y metaanálisis de razón de disparidad, para lo cual se empleó el software Epidat con un intervalo de confianza del 95%. Resultados: Se incluyeron 22 estudios. La frecuencia de hiperreactividad plaquetaria para la aspirina fue desde el 18.8% hasta el 81.8% y para el clopidogrel desde el 18.2% hasta el 71.3%, lo que denota una importante heterogeneidad. Se observó que la frecuencia de hiperreactividad plaquetaria en pacientes diabéticos varió del 21% al 78.7%, mientras que en los pacientes hipertensos fue del 17.6% al 76.8%, y finalmente, la hiperreactividad plaquetaria fue 1,38 veces mayor en los pacientes diabéticos que en aquellos que no lo eran y 1,23 veces mayor en los pacientes hipertensos que en aquellos que no lo eran. Conclusiones: La diabetes mellitus y la hipertensión arterial, como enfermedades de base en pacientes sometidos a intervención coronaria percutánea, están asociadas a hiperreactividad plaquetaria, y esta, a su vez, como demostraron estudios previos, al desarrollo de eventos vasculares a largo plazo. De ahí que una valoración posterior al procedimiento con pruebas de agregometría plaquetaria resultaría potencialmente útil en el marco de la terapia personalizada.

Abstract Objective: To perform a metaanalyze of the frequency of platelet hyperreactivity for aspirin and clopidogrel with different aggregometers, in patients with diabetes mellitus and hypertension undergoing percutaneous coronary intervention. Method: Systematic review with metaanalysis using 40 searches in three multidisciplinary databases (PubMed, ScienceDirect and SciELO), following the phases of the PRISMA guide between the years 2005 and 2021. Reproducibility and methodological quality were guaranteed by two researchers using the STROBE guide. The analyzes were based on frequencies and odds ratio metaanalysis, using Epidat software with a 95% confidence interval. Results: 22 studies were included, the frequency of platelet hyperreactivity was from 18.8% to 81.8% in the case of aspirin, and in the case of clopidogrel from 18.2% to 71.3%, which denotes an important heterogeneity. It was observed that the frequency of platelet hyperreactivity in diabetic patients ranged from 21% to 78.7% and in hypertensive patients from 17.6% to 76.8%, and finally it was observed that the platelet hyperreactivity was 1.38 times higher in diabetic patients than in those who were not and 1.23 times higher in hypertensive patients than in those who were not. Conclusions: Diabetes mellitus and hypertension as underlying pathologies in patients undergoing percutaneous coronary intervention are associated with the presence of platelet hyperreactivity, and this in turn -as shown by previous studies-, with the development of long-term vascular events, therefore a subsequent assessment. The procedure with platelet aggregometry tests would be potentially useful in the context of personalized therapy.

Reactive airways dysfunction syndrome following inhalation of hydrogen chloride vapor

Hydrogen chloride is available commercially as an anhydrous gas or an aqueous solution, hydrochloric acid. Exposure to this gas has been associated with the development of reactive airways dysfunction syndrome. However, there are few published reports. A 37-year-old woman developed progressive bronchospasm and acute respiratory failure after cleaning an enclosed space with an unknown concentration of hydrochloric acid gas from a cleaning substance. She had no prior history of asthma or atopy. Severe bronchospasm developed, leading to hypoxemia and diffuse interstitial infiltrates, necessitating orotracheal intubation and admission to the intensive care unit. Asthma-like symptoms such as cough, wheezing, and dyspnea; requiring bronchodilators, and repeated hospitalizations are persistent a year after the accident. Pulmonary function testing showed mild airflow obstruction.

Risk Factors and Comorbidities Associated With the Allergic Rhinitis Phenotype in Children According to the ARIA Classification

PURPOSE: Data are lacking on the association between the allergic rhinitis (AR) phenotype and sensitization to specific allergens or bronchial hyperresponsiveness (BHR) in children. We here investigated risk factors and comorbidities, including sensitization to specific allergens and BHR, for the AR phenotype by AR and its Impact on Asthma (ARIA) classification in a general population-based birth cohort study. METHODS: We enrolled 606 children aged 7 years from the Panel Study of Korean Children. The AR phenotype was assigned in accordance with the ARIA classification in children. Skin prick tests and Provocholine provocation test were performed. Risk factors and comorbidities for AR phenotypes were then analyzed. RESULTS: The prevalence of mild and moderate to severe AR in our study cohort was 37.2% and 8.8%, respectively. Recent use of analgesics or antipyretics and current cat ownership were associated with the risk of mild persistent AR. Sensitizations to Dermatophagoides Pteronyssinus (Der p), Japanese hop and cat were associated with moderate to severe persistent AR. Children with moderate to severe AR had a higher risk of current asthma and BHR compared to mild AR cases (adjusted odds ratio [aOR], 5.26; 95% confidence interval [CI], 1.77–15.62). Moderate to severe AR with allergic sensitization was associated with the highest risk of BHR (aOR, 11.77; 95% CI, 3.40–40.74). CONCLUSIONS: Moderate to severe-persistent AR is more closely related to respiratory comorbidities and sensitizations than mild AR. Stratifying the AR phenotype by ARIA classification may assist in disease management.

Bronchial Response to High and Low Molecular Weight Occupational Inhalant Allergens

PURPOSE: Occupational asthma may be induced by high- or low-molecular weight allergens (HMWA or LMWA, respectively). The study was conducted to compare the pattern of bronchial response in 200 HMWA-induced asthmatics (n = 130) and LMWA-induced asthmatics (n = 70). METHODS: The study participants underwent a single-blind, placebo-controlled specific inhalation challenge (SIC) with workplace allergens, accompanied by evaluation of non-specific bronchial hyperresponsiveness (NSBHR) with methacholine before and after the SIC. RESULTS: A single early bronchial response more frequently occurred in HMWA-induced asthmatics than in LMWA-induced asthmatics (86.2% vs. 20%). An isolated late bronchial response or atypical patterns were more frequently observed in LMWA-induced asthmatics than in LMWA-induced asthmatics (45.7% vs. 3.8% or 34.3% vs. 10%, respectively). Baseline NSBHR before SIC was more often detected in LMWA-induced asthmatics than in HMWA-induced asthmatics (81.4% vs. 54.6%), and the median value of the provocation concentration of methacholine was relevantly lower in these patients before and after SIC. A significant 3-fold increase in NSBHR after SIC was observed more often in LMWA-induced asthmatics than in HMWA-induced asthmatics (82.8% vs. 66.1%). In addition, compared to LMWA-induced asthmatics, HMWA-induced asthmatics were older, were more frequently active smokers, showed lower level of NSBHR, and more frequently continued their work in harmful occupational exposure. CONCLUSIONS: The results of this study suggest that HMWA-induced asthmatics may have milder clinical courses and that there is a possibility of job continuation despite asthma exacerbation requiring medical surveillance.

Actualización de la prueba de provocación bronquial con ejercicio (PPBE) / Update of the bronchial provocation test with exercise

The bronchial challenge test with exercise aims to demonstrate the presence of exercise-induced bronchial hyperreactivity, characteristic of bronchial asthma. Its realization is well standardized, requiring special environmental conditions, preparation and submaximum effort of the patient. The response is measured by spirometry, and it is considered a positive exercise test a drop in the expired volume at the first second (FEV1) of 10%. This article describes the elements necessary to facilitate this exam, according to national and international standards and guidelines.

La prueba de provocación bronquial con ejercicio tiene como objetivo demostrar la presencia de hiperreactividad bronquial inducida por ejercicio, característica del asma bronquial. Su realización está bien estandarizada, requiriendo de condiciones ambientales especiales, preparación y esfuerzo submáximo del paciente. La respuesta se mide mediante espirometría, y se considera una prueba de provocación con ejercicio positivo, a una caída del volumen espirado al primer segundo (VEF1) del 10%. En este artículo se describen los elementos necesarios para facilitar la realización de este examen, acorde a normas y guías nacionales e internacionales.

Actualización en la prueba de provocación bronquial con metacolina en el niño / Update in the bronchial challenge test with methacholine in children

This document updates the recommendations of the bronchial challenge test with methacholine in children. It is based primarily on the recommendations contained in the guide on the technical standard of the bronchial challenge test for methacholine from the European Society of Respiratory Diseases. The main change is the recommendation to use PD20 (methacholine dose that causes a 20% drop in FEV1) instead of PC20 (methacholine concentration that causes a 20% drop in FEV1), which allows for comparable results when different devices and different protocols are used.

Este documento actualiza las recomendaciones de la prueba de provocación bronquial con metacolina en niños. Se basa fundamentalmente en las recomendaciones contenidas en la guía sobre el estándar técnico de la prueba de provocación bronquial de metacolina de la Sociedad Europea de Enfermedades Respiratorias. El principal cambio es la recomendación de utilizar la PD20 (dosis de metacolina que provoca una caída de 20% del VEF1) en vez de PC20 (concentración de metacolina que provoca una caída del 20% en el VEF1), lo cual permite tener resultados comparables cuando se usan diferentes dispositivos y diferentes protocolos.

Balance autonómico basal y durante el ejercicio isométrico en jóvenes con diferente reactividad cardiovascular / Basal autonomic balance and during the isometric exercise in young people with different cardiovascular reactivity

RESUMEN Introducción: El sistema nervioso autónomo desempeña un papel importante en los reajustes cardiovasculares al ejercicio. En la hiperreactividad cardiovascular existe una mayor sensibilidad del sistema simpático ante diferentes estímulos estresantes. Objetivo: Determinar las características del control autonómico cardíaco en adultos jóvenes con diferentes grados de reactividad cardiovascular en condiciones basales y durante el ejercicio isométrico. Método: La muestra estuvo constituida por 97 individuos de ambos sexos, y se dividió en tres grupos: normorreactivos, hiperreactivos y con respuesta hipertensiva, de acuerdo a la respuesta presora a la prueba del peso sostenido. A todos los individuos se les realizó un estudio de variabilidad de la frecuencia cardíaca en reposo y durante la prueba isométrica. Se estudiaron las variables en el dominio de la frecuencia: baja, alta, relación baja/alta en reposo, y los parámetros del diagrama de Poincaré en reposo y durante el ejercicio (valores de desviación estándar 1 [SD1], 2 [SD2], y la razón entre ambos). Resultados: En estado basal los individuos hiperreactivos y con respuesta hipertensiva presentaron un predominio simpático sobre la función cardíaca y una menor variabilidad de la frecuencia cardíaca. Durante el ejercicio isométrico disminuyeron los valores de los ejes SD1 y SD2 en todos los grupos y la razón SD1/SD2 decreció en individuos normorreactivos y con respuesta hipertensiva; pero apenas se modificó en los hiperreactivos. Conclusiones: En los individuos con hiperreactividad cardiovascular ya está presente un desbalance autonómico en estado basal y existe una reducción de la modulación autonómica vagal durante el ejercicio, que puede favorecer el desarrollo de la hipertensión arterial.

ABSTRACT Introduction: The autonomic nervous system plays an important role in cardiovascular readjustments to exercise. In cardiovascular hyperreactivity there is a greater sensitivity of the sympathetic system to different stressors. Objective: To determine the characteristics of cardiac autonomic control in young adults with different degrees of cardiovascular reactivity under basal conditions and during isometric exercise. Method: The sample consisted of 97 individuals of both sexes, and was divided into three groups: normoreactive, hyperreactive and with hypertensive response, according to the pressor response to weight-bearing tests. The individuals underwent a complete study of heart rate variability at rest and during isometric test. The frequency domain for the variables was: low, high, low/high resting ratio, and the parameters of Poincaré plots at rest and during exercise (values of standard deviation 1 [SD1], 2 [SD2], and the reason between them). Results: Under basal conditions, hyperreactive individuals with a hypertensive response had a sympathetic predominance over cardiac function and lower heart rate variability. During the isometric exercise SD1 and SD2 axes values decreased in all groups and SD1/SD2 ratio decreased in normoreactive individuals with hypertensive response; but it was hardly modified in those hyper-reactive. Conclusions: Individuals with cardiovascular hyperreactivity have a prior autonomic imbalance under basal conditions and a reduction of autonomic vagal modulation during exercise that may favor the development of arterial hypertension.

Effects of neonatal Streptococcus pneumoniae pneumonia on airway epithelial injury of mice / 解放军医学杂志

Objective To investigate the effects of neonatal Streptococcus pneumoniae pneumonia (S.pp) on airway epithelial injury of mice. Methods Neonatal C57BL/6 (1-week-old) mice were infected intranasally with 2×105 cfu of Streptococcus pneumoniae (S.p) in a volume of 5 μl sterile phosphate buffered saline (PBS) (S.pp group), while the mock-infected controls received the same volume of sterile PBS (control group). Five weeks after the infection, the airway hyperresponsiveness (AHR) was evaluated by invasive body plethysmography system. The lung tissue was harvested, CDH1 and TJP1 mRNA levels were analyzed by RT-PCR. Immunohistochemical method and Western blotting were used to evaluate the expressions of E-cadherin and tight junction protein (ZO-1). Airway inflammation was detected by HE staining, the subcutaneous collagen deposition beneath the airway epithelium was evaluated by Masson staining, and the number of goblet cells was detected by Alcian Blue Periodic Acid Schiff (AB-PAS) staining. Results When the concentration of aerosolized methacholine inhaled by mice ranged from 6.25 to 50 mg/ml, the AHR was obviously higher in S.pp group than that in control group (P<0.001); the levels of CDH1 and TJP1 mRNA in the lung tissue were markedly lower in S.pp group (0.85±0.29 and 0.43±0.16) than those in control group (0.85±0.29 vs. 1.42±0.40, P=0.033; 0.43±0.16 vs. 0.83±0.26, P=0.010, respectively); the expression levels of E-cadherin and ZO-1 in airway epithelium were lower in S.pp group than those in control group (9.66±4.89 vs. 24.52±7.58, P=0.001; 13.54±3.79 vs. 25.53±5.99, P=0.005, respectively); the protein levels of E-cadherin and ZO-1 in lung tissue were remarkably lower in S.pp group than those in control group (0.23±0.06 vs. 0.38±0.06, P=0.019; 0.68±0.12 vs. 0.96±0.16, P=0.032, respectively); the subcutaneous collagen deposition beneath the airway epithelium increased significantly in S.pp group than that in control group (45.54±5.79 vs. 26.3±5.53, P=0.001). The number of goblet cells and inflammatory cell infiltration showed no statistical significance between the two groups. Conclusion Neonatal S.pp may lead to airway epithelial injury and be involved in the formation of AHR.

Insulina modula o fenótipo de células imunes na inflamação alérgica pulmonar, aumentando a resistência pulmonar de camundongos diabéticos / Insulin modulates immune cell phenotype in pulmonary allergic inflammation, increasing the pulmonary resistance of diabetic and healthy mice

Dados mostram que o aparecimento do diabetes mellitus (DM), em pacientes previamente asmáticos, diminui os sintomas da asma, enquanto a insulina agrava a asma. Devido a dados na literatura e por dados prévios do nosso grupo, o presente estudo teve como objetivo avaliar o efeito modulatório da insulina na inflamação alérgica pulmonar em camundongos diabéticos e saudáveis. Camundongos machos dibéticos BALB/c (aloxana, 50mg/kg, iv, 10 dias) foram sensibilizados com ovalbumina (OVA, 20 µg e Al (OH)3, 2 mg) 10 dias após a injeção de aloxana e uma dose reforço foi dada, após 12 dias da primeira de sensibilização, após 6 dias da dose reforço, os animais foram expostos a nebulização durante 7 dias com solução de OVA (1mg/mL) ou solução salina (SAL). Animais diabéticos foram tratados com doses múltiplas de Protamine Hagedorn Neutro (NPH) 2UI e 1UI, respectivamente, por via subcutânea 12 horas antes do desafio com OVA (às 19h) e 1UI (às 7h) 2h antes de cada desafio com OVA. Os animais não diabéticos receberam 1UI de insulina, pela mesma via 2h antes de cada desafio (às 7h), 24h após o último desafio, realizaram-se as seguintes análises: a) expressão de proteína quinase p38, proteína quinase regulada por sinais extracelulares 1 e 2 (ERK 1/2), proteína quinase ativada por estresse ou c-jun NH2- terminal (JNK) , transdutor de sinal e ativador de transcrição 3 (STAT 3) e transdutor de sinal e ativador de transcrição 6 (pSTAT 6) no homogenato de pulmão; b) perfil de imunoglobulinas presentes no soro; c) concentrações de interleucina (IL) IL-4, IL-5, IL-10, IL-13, fator de necrose tumoral alfa (TNF-α), fator de crescimento endotelial vascular (VEGF), fator de crescimento transformador beta (TGF-ß) e interferon-gamma IFN-γ em homogenato de pulmão; d) migração celular em fluído do lavado broncoalveolar (LBA); e) perfil de células imunes na medula óssea, pulmão, timo e baço; f) mecânica pulmonar por BUXCO e FlexiVent. Em comparação com camundongos não diabéticos desafiados com OVA, os animais diabéticos desafiados com OVA mostraram diminuição em: ERK 1, ERK 2, JNK (fosfo54), JNK / SAPK, STAT3, pSTAT6 estava ausente; concentração da imunoglobulinas IgE, IgG1; perfil de citocinas Th2 como IL-4, IL-5, IL-13, TNF-α, VEGF, TGF-ß; infiltrado inflamatório e) ausência de eosinofilia no LBA; células T, células B e eosinófilos na medula óssea, pulmão, timo e baço, e hiper-reatividade das vias aéreas. O tratamento com insulina restaubeleceu todos os parâmetros estudados. Portanto, sugerem que a insulina modula a inflamação alérgica pulmonar tardia em camundongos diabéticos

Data show that the onset of diabetes mellitus (DM) in previously asthmatic patients decreases asthma symptoms while insulin worsens asthma. Due to data in the literature and previous data from our group, the present study aimed to evaluate the modulatory effect of insulin on pulmonary allergic inflammation in diabetic and healthy mice. Ovalbumin (OVA, 20 µg and Al (OH)3, 2 mg) were sensitized at 10 days after alloxan injection and a booster dose was given , after 12 days of the first sensitization, after 6 days of booster dose, the animals were exposed to nebulization for 7 days with OVA solution (1mg / mL) or saline solution (SAL). Diabetic animals were treated with multiple doses of Protamine Hagedorn Neutral (NPH) 2UI and 1UI, respectively, subcutaneously 12 hours prior to challenge with OVA (at 7pm) and 1UI (at 7h) 2h before each challenge with OVA. Non-diabetic animals received 1UI of insulin, via the same route 2h before each challenge (at 7h), 24h after the last challenge, the following analyzes were performed: a) expression of protein kinase p38, protein kinase regulated by extracellular signals 1 and 2 (ERK 1/2), stress-activated or c-jun NH2-terminal protein kinase (JNK), signal transducer and transcriptional activator 3 (STAT 3) and signal transducer and transcriptional activator 6 (pSTAT 6) in the lung homogenate; b) profile of immunoglobulins present in serum; c) concentrations of interleukin (IL) IL-4, IL-5, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), transforming TGF-ß) and interferon-gamma IFN-γ in lung homogenate; d) cell migration in bronchoalveolar lavage fluid (BAL); e) profile of immune cells in the bone marrow, lung, thymus and spleen; f) Pulmonary mechanics by BUXCO and FlexiVent. In contrast to non-diabetic mice challenged with OVA, diabetic animals challenged with OVA showed decrease in: ERK 1, ERK 2, JNK (phospho54), JNK / SAPK, STAT3, pSTAT6 was absent; IgE immunoglobulin levels, IgG1; profile of Th2 cytokines such as IL-4, IL-5, IL-13, TNF-α, VEGF, TGF-ß; inflammatory infiltrate e) absence of eosinophilia in BAL; T cells, B cells and eosinophils in the bone marrow, lung, thymus and spleen, and airway hyperreactivity. The insulin treatment restored all parameters studied. Therefore, they suggest that insulin modulates late pulmonary allergic inflammation in diabetic mice

¿Es la patogenia del virus sincitial respiratorio humano un factor de riesgo para el desarrollo de asma infantil? / Is the pathogenesis of the human respiratory syncytial virus a risk factor for the development of childhood asthma?

Resumen El virus sincitial respiratorio humano (VSRh) es considerado como el principal agente causal de infecciones del tracto respiratorio en niños. Su presentación clínica varía en cuanto a la gravedad: desde infecciones no complicadas de la vía aérea superior en adultos y niños sanos, hasta bronquiolitis y bronconeumonía en niños con factores de riesgo y menores de 2 años. Perteneciente a la familia Pneumoviridae y al género Orthopneumovirus, el VSRh es un virus envuelto que contiene un genoma de ácido ribonucleico (RNA) monocatenario de polaridad negativa, que codifica para 7 proteínas estructurales (G, F, SH, M, P, N y L) y 4 no estructurales (NS1, NS2, M1, M2). La presencia del virus se ha considerado como factor de riesgo para el desarrollo de asma infantil, que es una enfermedad inflamatoria de la vía aérea caracterizada por episodios recurrentes de obstrucción de la vía aérea inferior ante estímulos ambientales generalmente inocuos. El riesgo de desarrollar asma aumenta si la primoinfección sucede a edad temprana y si hay factores de riesgo como prematuridad y broncodisplasia pulmonar. En México, debido a la morbilidad y mortalidad asociada al VSRh, y como profilaxis en pacientes de alto riesgo; desde el año 2008, se recomienda el uso del biofármaco Pavilizumab. El objetivo de la presente revisión es describir los factores asociados a la patogénesis VSRh que podrían estar implicados en el desarrollo del asma infantil y, con ello, plantear que población está en riesgo. Para estos fines, se presenta un breve análisis de la biología del virus, la respuesta inmune que se induce durante la infección, así como aquellos fármacos aprobados en México para el tratamiento y profilaxis de infecciones asociadas al VRSh.

Abstract The human respiratory syncytial virus (hRSV) is the main pathogen of respiratory tract infections in children. The severity of the infection is depending of its clinical presentation that is moving from uncomplicated upper airway infections, in healthy adults and children, to bronchiolitis and bronchopneumonia that could be developed, in presence of risk factors, in children younger than 2 years. The virus belongs to the Pneumoviridae family and Orthopneumovirus genus, it is an enveloped virus with a single-stranded RNA genome of negative polarity that is codifying 7 structural proteins (G, F, SH, M, P, N and L) and four non-structural proteins (NS1, NS2, M1, M2). The viral infection has been considered as a risk factor for the development of childhood asthma, which is the most common airway inflammatory disease in children and characterized, by recurrent episodes of lower airway obstruction, by harmless environmental stimuli. The risk increases if primary infection occurs at an early age and in risk factors as prematurity and pulmonary broncho-dysplasia. Due to the morbidity and mortality associated with hRSV, since 2008 it has been approved the use of biopharmaceuticals as Palivizumab for prophylaxis in high-risk patients. In the present review, the aim is to present those factors that could be involved in the development of childhood asthma and their possible link to the presence of hRSV. In addition, it is an intention for presenting the possible facts of the risks in the potentially infected population. For a better comprehension of the virus, it is presented a briefly analysis of the viral structure, the induced immune response against the viral infection and those drugs that are approved in Mexico for the treatment and prophylaxis against hRSV.

THE DIAGNOSIS AND DIFFERENTIAL DIAGNOSIS OF ASTHMA IN ADOLESCENTS AND ADULTS

Asthma is the most common chronic respiratory illnessworldwide, and makes up a large part of primary carepractice. Family physicians need to be well-versed inasthma diagnosis, while avoiding overdiagnosis ormisdiagnosis. The tetrad of cough, chest tightness,wheezing and dyspnea are conventionally thought to bethe key presenting symptoms of asthma. However, thesesymptoms can occur in many other conditions, makingaccurate diagnosis of asthma challenging. This article aimsto outline the clinical features and investigations that can help the family physician diagnose asthma and formpossible differential diagnoses in adolescents and adults.Diligent history-taking remains paramount for diagnosis,while no investigation is definitive.

Prevalence, Risk Factors and Cutoff Values for Bronchial Hyperresponsiveness to Provocholine in 7-Year-Old Children

BACKGROUND: A US Food and Drug Administration (FDA)-approved drug methacholine chloride (Provocholine®) was recently introduced to Korea where it is now widely used in clinical practice. We aimed to evaluate the prevalence, risk factors and cutoff value of bronchial hyperresponsiveness (BHR) to Provocholine in 7-year-old children. METHODS: Six hundred and thirty-three children from the Panel Study on Korean Children who visited 16 regional hospitals were evaluated. Skin prick tests, spirometry and bronchial provocation tests for Provocholine as well as a detailed history and physical examinations were performed. The bronchial provocation test was reliably performed on 559 of these children. RESULTS: The prevalence of ever-diagnosed asthma via medical records was 7.7%, and that of current asthma (wheezy episode in the last 12 months + diagnosed asthma by physicians) was 3.2%. The prevalence of BHR to Provocholine was 17.2% and 25.8%, respectively, for a PC20 < 8 and < 16 mg/mL. The risk factors for BHR (PC20 < 16 mg/mL) were atopic dermatitis diagnosis and current dog ownership, whereas those for current asthma were allergy rhinitis diagnosis, a history of bronchiolitis before the age of 3, recent use of analgesics/antipyretics and maternal history of asthma. The BHR prevalence trend showed an increase along with the increased immunoglobulin E (IgE) quartile. The cutoff value of PC20 for the diagnosis of current asthma in children at age 7 was 5.8 mg/mL (sensitivity: 47.1%, specificity: 87.4%). CONCLUSIONS: BHR to Provocholine (PC20 < 8 mg/mL) was observed in 17.2% of 7-year-olds children from the general population and the cutoff value of PC20 for the diagnosis of current asthma was 5.8 mg/mL in this age group. The risk factors for BHR and current asthma showed discrepancies suggesting different underlying mechanisms. Bronchial provocation testing with Provocholine will be a useful clinical tool in the future.

Cat ownership is associated with increased asthma prevalence and dog ownership with decreased spirometry values

The association between pet ownership and the development of allergic and respiratory diseases has been the aim of several studies, however, the effects of exposure in adults remain uncertain. The aims of the present study were to investigate the prevalence of asthma and lung function status among dog and cat owners. This cross-sectional study was performed at two universities with students and workers who were allocated into 3 groups according to pet ownership in the previous year: cat owners, dog owners, and no pets (control group). Subjects underwent spirometry, bronchial challenge test with mannitol, skin prick tests, and questionnaires about animal exposures and respiratory symptoms. Control group comprised 125 subjects; cat owner group, 51 subjects; and dog owner group, 140 subjects. Cat owners had increased asthma prevalence (defined by symptoms and positive bronchial challenge test), but no changes in lung function compared to the control group. The dog owner group had lower spirometry values (forced expiratory volume in one second and lower forced vital capacity), but similar asthma prevalence, compared to the control group. In the cat owner group, excess of asthma may have an immunological basis, since we found an association with atopy. Although we did not have endotoxin data from volunteers' households, we postulated that low values of lung function were associated to exposure to endotoxins present in environments exposed to dogs.

Vitamin D3 levels and NLRP3 expression in murine models of obese asthma: association with asthma outcomes

Vitamin D (25(OH)D3) is an essential nutrient that plays a role in the immune system. Serum 25(OH)D3 is found to be associated with asthma. However, the role of vitamin D in obese asthma remains unclear. Therefore, we investigated the association between vitamin D levels and asthma outcomes in a murine model of obese asthma. We also evaluated NLRP3 inflammasome activity in the pathogenesis of obese asthma. We divided 20 male Balb/c mice (3-4 weeks old) into 4 groups: normal control, asthma, obese, and obese asthma and developed an obese asthma mouse model. Airway hyperreactivity, cytokine concentrations, 25(OH)D3 levels, NLRP3 mRNA and IL-1β mRNA expressions were measured. Lung histology and bronchoalveolar lavage fluid (BALF) cell count were also determined. Obese asthma mice showed a significant increase in airway hyper-responsiveness, airway inflammation, pro-inflammatory cytokine levels and NLRP3 mRNA, IL-1β mRNA expression. Both asthma and obese groups had lower 25(OH)D3 levels. Vitamin D levels in obese asthma were the lowest among all groups. Vitamin D levels correlated negatively with body weight, lung resistance levels at 25 mg/mL of methacholine, total inflammatory cells, and IL-1β and IL-17 concentrations in BALF. These data demonstrated an association between serum vitamin D levels and outcomes of obese asthma, and indicated that NLRP3 inflammasome may play a role in this disorder.

Accuracy of spirometry for detection of asthma: a cross-sectional study

ABSTRACT BACKGROUND: Asthma is a chronic inflammatory disease with airway hyperresponsiveness. Spirometry is the most commonly used test among asthmatic patients. Another functional test used for diagnosing asthma is the bronchial challenge test. The aim of this study was to analyze the accuracy of spirometry for detecting asthma in the general population. DESIGN AND SETTING: Cross-sectional study with data analysis to evaluate the accuracy of spirometry through calculating sensitivity, specificity and predictive values and through the kappa agreement test. METHODS: Subjects who constituted a birth cohort were enrolled at the age of 23 to 25 years. Spirometric abnormality was defined as reduced forced expiratory volume in one second, i.e. lower than 80% of the predicted value. Measurement of bronchial responsiveness was performed by means of the bronchial challenge test with methacholine. The gold-standard diagnosis of asthma was defined as the presence of bronchial hyperresponsiveness in association with respiratory symptoms. RESULTS: Asthma was detected in 200 subjects (10.4%) out of the sample of 1922 individuals. Spirometric abnormality was detected in 208 subjects (10.9%) of the sample. The specificity of spirometric abnormality for detecting asthma was 90%, sensitivity was 23%, positive predictive value was 22%, and negative predictive value was 91%. The kappa test revealed weak agreement of 0.13 (95% confidence interval, CI: 0.07-0.19) between spirometry and the diagnosis of asthma. CONCLUSION: Spirometry, as a single test, has limitations for detecting asthma in the general population.

The Lung Function Impairment in Non-Atopic Patients With Chronic Rhinosinusitis and Its Correlation Analysis

OBJECTIVES: Chronic rhinosinusitis (CRS) is common disease in otorhinolaryngology and will lead to lower airway abnormality. However, the only lung function in CRS patients and associated factors have not been much studied. METHODS: One hundred patients with CRS with nasal polyps (CRSwNP group), 40 patients with CRS without nasal polyps (CRSsNP group), and 100 patients without CRS were enrolled. The difference in lung function was compared. Meanwhile, CRSwNP and CRSsNP group were required to undergo a bronchial provocation or dilation test. Additionally, subjective and objective outcomes were measured by the visual analogue scale (VAS), 20-item Sino-Nasal Outcome Test (SNOT-20), Lund-Mackay score, Lund-Kennedy endoscopic score. The correlation and regression methods were used to analyze the relationship between their lung function and the above parameters. RESULTS: The forced expiratory volume in 1 second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FEF25-75) of CRSwNP group were significantly lower than other groups (P<0.05). On peak expiratory flow, there was no difference between three groups. In CRSwNP group, FEV1 was negatively correlated with peripheral blood eosinophil count (PBEC) and duration of disease (r=–0.348, P=0.013 and r=–0.344, P=0.014, respectively), FEF25-75 negatively with VAS, SNOT-20 (r=–0.490, P=0.028 and r=–0.478, P=0.033, respectively) in CRSsNP group. The incidence of positive bronchial provocation and dilation test was lower in CRSwNP group (10% and 0%, respectively), with both 0% in CRSsNP group. The multiple linear regression analysis indicated that change ratio of FEV1 before and after bronchial provocation or dilation test were correlated with PBEC in CRSwNP group (β=0.403, P=0.006). CONCLUSION: CRS leading to impaired maximum ventilation and small airway is associated with the existence of nasal polyp. Lung function impairments can be reflected by PBEC, duration, VAS, and SNOT-20. In CRSwNP patients, PBEC is independent predictor of FEV₁ change ratio.