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OBJECTIVE: To evaluate the safety of an abbreviated methacholine challenge test (MCT) protocol in children. STUDY DESIGN: This prospective, observational study enrolled children aged 6 through 18 years referred for the MCT. The abbreviated protocol was initiated with a methacholine dose of 0.03 mg/ml and escalated in fourfold increments, unless the forced expiratory volume at 1 second decline exceeded 10%, at which point the next dose was only doubled. The safety of this abbreviated approach was assessed by monitoring adverse events, and specifically, decreases in forced expiratory volume at 1 second over 40%, hypoxemia, or uncontrollable cough. The number of methacholine doses and test duration were recorded and compared with estimated outcomes derived from the full-length MCT protocol. RESULTS: One hundred twelve participants, aged 13.7 years (±3.3), successfully completed the protocol. Fifty-seven (51%) presented a positive MCT response. No significant clinical adverse events were observed. Of all participants, 2.7% exhibited an exaggerated response, in line with previously reported findings for the full-length protocol. The abbreviated approach resulted in an estimated average time-savings of 18:19 minutes per participant, thus reducing test length by 22:47 minutes for a negative MCT and by 14:34 minutes for a positive outcome. CONCLUSIONS: This abbreviated MCT protocol is safe for children and effectively shortens the duration of the MCT.
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BACKGROUND: Spirometry tests with a bronchodilator response (BDR) in FEV1, a methacholine concentration that produces a 20% drop in FEV1 (PC20) ≤ 2 mg/mL, and a positive exercise test have high specificity for the diagnosis of asthma in children. However, the value of forced expiratory flow during the middle half of the FVC maneuver (FEF25-75) in spirometry has been questioned. The objective of this study was to relate the BDR in FEF25-75 of spirometry tests with normal FEV1 and FEV1/FVC to airway hyper-responsiveness (AHR) to methacholine or exercise in children age 5-15 y with clinical suspicion of asthma. METHODS: This was a cross-sectional study of spirometry tests performed between January 2017-December 2019 in children age 5-15 y with diagnostic suspicion of asthma who had a methacholine and/or exercise testing within a period not exceeding 60 d between exams. RESULTS: The mean (± SD) age of the children was 9.04 ± 2.67 y, with a range of 5-15 y, and 56.17% were male. Of the 324 spirometry tests with normal FEV1 and FEV1/FVC, 66 (20.4%) tests showed BDR in FEF25-75. A total of 46.9% and 33.3% of the children with and without BDR in FEF25-75, respectively, had a PC20 value ≤ 2 mg/mL and/or a positive exercise testing (P = .039). CONCLUSIONS: Children with suspected asthma and normal spirometry, other than BDR in FEF25-75, had greater AHR than those without BDR in FEF25-75. BDR in FEF25-75 was not always accompanied by AHR to confirm the diagnosis of asthma, so this study suggests that assessment of FEF25-75 alone is not always reliable for ruling in or ruling out AHR in the setting of otherwise normal spirometry results in children with suspected asthma.
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Asma , Broncodilatadores , Humanos , Masculino , Niño , Preescolar , Adolescente , Femenino , Cloruro de Metacolina , Estudios Transversales , Asma/diagnóstico , Pruebas de Función Respiratoria , Espirometría/métodos , Volumen Espiratorio ForzadoRESUMEN
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.
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Humanos , Niño , Pruebas de Provocación Bronquial/métodos , Cloruro de Metacolina/administración & dosificación , Hiperreactividad Bronquial/diagnóstico , Hiperreactividad Bronquial/fisiopatologíaRESUMEN
The aim of this work was to analyse the parasympathetic control of submandibular saliva secretory response to cholinergic and peptidergic agonists in rats chronically exposed to constant light or repeated immobilization. Thirty two adult male Wistar rats were used: LL (8 rats exposed to constant light for 20 days), IMO (8 rats submitted to 14:10 h light: dark cycle and immobilized 2 hours daily for 7 days), and control (16 rats not exposed to stress and submitted to 14:10 hours light:dark cycle). Saliva was collected under anesthesia from the salivary ducts of submandibular glands under increasing doses of methacholine and substance P. Secretory responses (µg/saliva/mg dry weight gland) to methacholine were significantly higher in LL and IMO groups compared to control for the following doses (µg/kg body weight): 3 (153±9 versus 46±3, p<0.001 and 76±3 versus 40±3, p<0.001), 10 (379±23 versus 277±8, p<0.001 and 275±19 versus 250±10, p<0.01) and 30 (729±25 versus 695±19, p<0.05 and 1008±39 versus 640±20, p<0.001). Also, responses to substance P were significantly increased in LL and IMO groups compared to control for the following doses: 0.2 (80±3 versus 30±3, p<0.01 and 94±16 versus 31±3, p<0.001), 0.5 (328±20 versus 231±16, p<0.01 and 531±31 versus 219±25,p<0.001), 1 (681±35 versus 547±30, p<0.01 and 1031±63 versus 563±53, p<0.001), and 5 (2222±88 versus 1868±59, p<0.01 and 3230±145 versus 1921±218, p<0.001). In conclusion, supersensitivity of secretory response to both agonists suggests that chronic exposure of rats to stressors capable of activating the sympathetic adrenal system promotes inhibition of the parasympathetic control of salivary secretion.
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Animales , Ratas , Saliva/metabolismo , Glándulas Salivales/fisiología , Salivación/fisiología , Agonistas Colinérgicos/administración & dosificación , Agonistas Adrenérgicos/administración & dosificación , Fototerapia , Ratas Wistar , Anestesia , LuzRESUMEN
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.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Asma/diagnóstico , Espirometría , Asma/epidemiología , Brasil/epidemiología , Pruebas de Provocación Bronquial , Estudios Transversales , Valor Predictivo de las Pruebas , Broncoconstrictores , Cloruro de Metacolina , Sensibilidad y EspecificidadRESUMEN
Background: Benzodiazepines have a direct bronchodilatory effect. Methacholine is a non-selective muscarinic receptor agonist causing bronchoconstriction. Aim: To examine the effects of inhaled benzodiazepines, modulating bronchoconstriction induced by methacholine in patients with asthma. Patients and Methods: Twelve patients with well controlled asthma were studied. On the first day, after determining the initial values of pulmonary function, a dose response curve was carried out with progressive doses of methacholine. After the last dose, when at least a 20% drop of the initial forced expiratory volume in the first second (FEV1) was achieved, vital capacity (VC) and FEV1 were measured at 7, 15 and 30 minutes after provocation. On the second day a diazepam aerosol was inhaled by the patients prior to the same protocol with methacholine. Results: In the first day of testing, methacholine inhalation (6 mg/mL) led to a significant drop in FEV1 from 2.98 to 1.69 L. On the second day of study, in the same patients, previous inhalation with diazepam reduced the changes of FEV1 after inhalation of methacholine. This parameter decreased from 2.48 to 2.21 L. Conclusions: Inhalation of benzodiazepines reduce bronchoconstriction after a methacholine challenge in patients with asthma.
Antecedentes: Las benzodiacepinas tienen un efecto broncodilatador directo. La metacolina es un agonista muscarínico que causa bronco constricción. Objetivo: Evaluar el efecto modulador de la inhalación de diazepam sobre la bronco constricción inducida por metacolina. Pacientes y Métodos: Se estudiaron 12 pacientes con asma bien controlada. En el primer día, se determinó la curva dosis respuesta de parámetros de función pulmonar a una dosis progresiva de metacolina. Después de la última dosis, cuando se consiguió un 20% de reducción en la capacidad vital forzada en el primer segundo (FEV1), se midió FEV1 y la capacidad vital (CV) a los 7, 15 y 30 min después de la provocación. En el segundo día los pacientes se inhalaron con diazepam antes de hacer la prueba con metacolina. Resultados: En el primer día, el FEV1 bajo de 2,98 a 1,69 l con 6 mg/ml de metacolina. En el segundo día, la inhalación de diazepam redujo la respuesta a metacolina con una reducción de FEV1 de 2,48 a 2,21 L. Conclusiones: La benzodiacepinas reducen la respuesta de vasoconstricción a metacolina.
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Asma/prevención & control , Broncoconstricción/efectos de los fármacos , Broncoconstrictores/antagonistas & inhibidores , Cloruro de Metacolina/antagonistas & inhibidores , Receptores de GABA/uso terapéutico , Diazepam/farmacología , Valores de Referencia , Asma/fisiopatología , Factores de Tiempo , Benzodiazepinas/uso terapéutico , Administración por Inhalación , Pruebas de Provocación Bronquial/métodos , Capacidad Vital/fisiología , Antropometría , Volumen Espiratorio Forzado/efectos de los fármacos , Volumen Espiratorio Forzado/fisiología , Reproducibilidad de los Resultados , Relación Dosis-Respuesta a DrogaRESUMEN
A prevalência de asma tem crescido e a maioria dos pacientes com asma grave não obtém o controle total dos sintomas com as terapias disponíveis, fazendo-se necessária a busca por novas alternativas terapêuticas. Inibidores de proteinases têm sido estudados como tratamento de processos inflamatórios, dentre eles o Enterolobium contortisiliquum Tripsin Inhibitor (EcTI) OBJETIVO: Avaliar se o inibidor de proteinase EcTI modula a hiperresponsividade brônquica à metacolina, inflamação, remodelamento e estresse oxidativo nas vias aéreas e septos alveolares em um modelo experimental de inflamação pulmonar alérgica crônica. MÉTODOS: Vinte e quatro camundongos Balb/c machos, entre seis e sete semanas de vida, pesando em media 25 g foram divididos em quatro grupos: C (controle), OVA (sensibilizados com ovalbumina, 50 ug intraperironeal (i.p) nos dias 0 e 14 e desafiados nos dias 22, 24, 26, 28); C+EC (controle tratados com EcTI (2 mg/kg/i.p) nos dias 22 a 28); OVA+EC (sensibilizados e desafiados com ovalbumina e também tratados com EcTI (2 mg/kg -i.p) nos dias 22 a 28). No dia 29, foram realizadas realizadas: (i) hiperresponsividade à metacolina e obtidas as respostas máximas de resistência e elastância do sistema respiratório; (ii) análise histopatológica do pulmão para quantificação de eosinófilos, fibras colágenas e elásticas nas vias aéreas (VA) e nos septos alveolares (SA); e (iii) imunohistoquímica para quantificação de células positivas para IFN-y, IL-4, IL-5, IL-13, MMP-9, TIMP-1, TGF-beta, iNOS, NF-kB e fração de volume de isoprostano nas VA e nos SA. Uma semana após o dia 29 foi realizada a técnica de anafilaxia cutanea passiva(PCA) para quantificar IgE e IgG1. A significância foi considerada quando p < 0,05. RESULTADOS: Houve aumento de todos os parâmetros avaliados no grupo OVA em relação ao grupo controle (p < 0,05). Houve atenuação da resposta máxima de Rrs e Ers no grupo OVA+EC comparado as grupo OVA (p < 0,05). O tratamento...
The number of cases of asthma has grown in recent decades. People who have severe asthma are likely to have more attacks and are at greater risk of a fatal attack, which propose to keep up global attention and keep approaching for advances in asthma care. Proteinase inhibitors of vegetable origin have been studied as a modulator of inflammatory responses and diseases. Among these inhibitors is Enterolobium contortisiliquum Trypsin Inhibitor (EcTI). AIMS: To evaluate the effects of EcTI in pulmonary mechanical, eosinophilic recruitment, inflammatory cytokines, remodeling of extracellular matrix and oxidative stressin an experimental model of chronic allergic pulmonary inflammation. METHODS: Twenty-four young adult male pathogen-free mice BALB/c (6-7 weeks old, 25-30g) were divided into 4 groups: C (control), OVA (sensitized with ovalbumin, 50 ug intraperitoneal (i.p), on days 0 and 14 and challenged with ova 1%, on days 22, 24, 26, 28); C+EC (control treated with EcTI- 2 mg/kg/i.p. from days 22 to 28); OVA+EC (sensitized and challenged with ovalbumin and treated with EcTI (2 mg/kg/i.p) from days 22 to 28). At day 29, we performed: (i) Bronchial hyperresponsiveness to methacholine and obtained the maximum response of resistance (Rrs) and elastance (Ers) of the respiratory system; (ii) lung histopathological analysis by morphometry to quantify eosinophils, collagen and elastic fibers volume fraction in airways; and (iii) immunohistochemistry to quantify IFN-y, IL-4, IL-5, IL-13, MMP-9, TIMP-1, TGF-, iNOS, NF-kB positive cells and isoprostane volume fraction in airways. One week after the day 29 we performed PCA technique to quantify IgE and IgG1 antibodies. Significance was considered at p < 0.05. RESULTS: The EcTI treatment in the ovalbumin-sensitized animals attenuated the maximal response of resistance and elastance of respiratory system after methacholine, the number of eosinophils, IL-4, IL-5, IL-13, IFN-y, NF-kB and iNOS-positive cells,...
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Animales , Masculino , Ratones , Remodelación de las Vías Aéreas (Respiratorias) , Asma , Inflamación , Cloruro de Metacolina , Ratones Endogámicos BALB C , Estrés Oxidativo , Inhibidores de Proteasas , Inhibidores de TripsinaRESUMEN
The aim of this study was to investigate both functionally and structurally bronchodilator effects of Pituitary adenylate cyclase activating peptide (PACAP38) and acetyl-[Ala15, Ala20] PACAP38-polyamide, a potent PACAP38 analog, in rats challenged by methacholine (MeCh). Male Wistar rats were divided randomly into five groups. Groups 1 and 2 inhaled respectively aerosols of saline or increasing doses of MeCh (0.5, 1, 2.12, 4.25, 8.5, 17, 34 and 68mg/L). The other groups received terbutaline (Terb) (250 µg/rat) (10-6 M), PACAP38 (50 µg/rat) (0.1 mM) or PACAP38 analog (50 µg/rat) associated to MeCh from the dose of 4.25 mg/L. Total lung resistances (RL) were recorded before and 2 min after MeCh administration by pneumomultitest equipment. MeCh administration induced a significant and a dose-dependent increase (p<0.05) of RL compared to control rats. Terb, PACAP38 and PACAP38 analog reversed significantly the MeCh-induced bronchial constriction, smooth muscle (SM) layer thickness and bronchial lumen mucus abundance. PACAP38 analog prevents effectively bronchial smooth muscle layer thickness, mucus hypersecretion and lumen decrease. Therefore, it may constitute a potent therapeutic bronchodilator.
O objetivo deste estudo foi investigar funcionalmente e estruturalmente efeito broncodilatador do peptídeo ativador da adenilato ciclase pituitária (PACAP1-38) e da acetil-[Ala15, Ala20]PACAP 38-poliamida, potente análogo do PACAP-38, nos ratos desafiados pelo metacolina (MeCh). Ratos Wistar machos foram aleatoriamente divididos em cinco grupos. Grupos 1 e 2, inalando aerossóis de solução salina ou doses crescentes de MeCh (0,5, 1, 2,12, 4,25, 8,5, 17, 34 e 68 mg/L). Os outros grupos recebendo terbutalina (Terb) (250 µg/rato) (10-6M), PACAP-38 (50 µg/rato) (0.1 mM) ou análogo do PACAP-38 (50 µg/rato) associados a MeCh na dose de 4,25 mg/L. A resistência pulmonar total (RL) foi registrada antes e 2 min após a administração de Mech pelo equipamento pneumomultiteste. A administração MeCh induziu aumento significativo e dose dependente (p<0,05) de RL em comparação com ratos do grupo controle. Terb e PACAP1-38 e análogo do PACAP-38 reverteram, significativamente, a constrição brônquica induzida por Mech, a espessura do músculo liso (SM) e abundância de muco do lume brônquico. O análogo PACAP-38 do mesmo modo que a Terb impediu a responsividade brônquica a MeCh e pode se constituir em um importante regulador no desenvolvimento da doença inflamatório pulmonar. Contudo, o uso do peptídeo nativo para aplicações terapêuticas é limitado por sua baixa estabilidade metabólica. Consequentemente, o análogo metabolicamente estável representa ferramenta promissora no tratamento de doenças pulmonares inflamatórias.
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Ratas , Adenilil Ciclasas/análisis , Cloruro de Metacolina/análisis , Receptores del Polipéptido Activador de la Adenilato-Ciclasa Hipofisaria/análisis , Broncodilatadores/efectos adversos , Cloruro de Metacolina/farmacocinética , Enfermedades Pulmonares/rehabilitaciónRESUMEN
BACKGROUND: The association between obesity and bronchial hyperreactivity (BHR) in children has not been fully demonstrated in cross-sectional or longitudinal studies, and no study has specifically addressed Latino children. METHODS: A cross-sectional study of 450 children (10-18 years) from public schools was conducted in Mexico city. Among this group, 260 met the study criteria (no chronic respiratory illnesses, including asthma and rhinitis; no acute respiratory infections; and no tobacco-exposure or endocrine or body dysmorphic disorders), and 229 performed reproducible pulmonary function and methacholine challenge tests and were fully analyzed. RESULTS: According to BMI percentiles, 40 were normal weight, 116 were obese, and 73 morbidly obese. Children in the morbidly obese group had significantly higher % FVC than those in the normal-weight group, and obese children had higher % PEF those in the morbidly obese and normal-weight groups. In the BHR methacholine challenge test, baseline FEV1 values among obese children were significantly lower than in the morbidly obese group. Using adjusted percentages for FEV1 , values were significantly lower among obese compared to morbidly obese children at metacholine concentrations of 0.25, 1, and 4 mg/ml. The proportion of positive BHR (PC20 ≤ 16 mg/ml) was higher in these two groups compared to normal-weight children (28.4%, 17.8%, and 12.5%, respectively), although differences were not significant. CONCLUSION: Our findings show that obesity by itself is not a sufficient condition to alter airway responsiveness to methacholine in a group of adolescents.
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Hiperreactividad Bronquial/epidemiología , Pulmón/fisiopatología , Obesidad/epidemiología , Adolescente , Hiperreactividad Bronquial/fisiopatología , Pruebas de Provocación Bronquial , Broncoconstrictores , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Cloruro de Metacolina , México/epidemiología , Obesidad Mórbida/epidemiología , Pruebas de Función RespiratoriaRESUMEN
PURPOSE: Chronic obstructive pulmonary disease (COPD) related to wood smoke exposure is characterized by important inflammation of the central and peripheral airways without significant emphysema. The objective of this study is to describe the bronchial hyperresponsiveness (BHR) level in women with COPD related to wood smoke exposure and to compare it with the BHR in women with COPD related to tobacco smoking. MATERIALS AND METHODS: TWO GROUPS OF WOMEN WITH STABLE COPD WERE STUDIED: (1) wood smoke exposed (WS-COPD); and (2) tobacco smoke exposed (TS-COPD). A methacholine challenge test (MCT) was performed in all patients according to American Thoracic Society criteria. BHR levels were compared using the methacholine concentration, which caused a 20% fall in the FEV1 (PC20). RESULTS: Thirty-one patients, 19 with WS-COPD and 12 with TS-COPD, were included. There were no significant differences between the groups in baseline FVC, FEV1, IC, FEF25-75, and FEF25-75/FVC. All 31 patients had a positive MCT (PC20<16 mg/mL) and the fall in the FEV1 and IC was similar in both groups. The severity of BHR was significantly higher in the WS-COPD patients (PC20: 0.39 mg/mL) than in the TS-COPD patients (PC20: 1.24 mg/mL) (P=0.028). The presence of cough, phlegm, and dyspnea during the test were similar in both groups. CONCLUSION: We found moderate to severe BHR in women with WS-COPD, which was more severe than in the TS-COPD women with similar age and airflow obstruction. This paper suggests that the structural and inflammatory changes induced by the chronic exposure to wood smoke, described in other studies, can explain the differences with TS-COPD patients. Future studies may clarify our understanding of the impact of BHR on COPD physiopathology, phenotypes, and treatment strategies.
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Hiperreactividad Bronquial/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Humo/efectos adversos , Madera , Anciano , Anciano de 80 o más Años , Hiperreactividad Bronquial/etiología , Colombia , Estudios Transversales , Femenino , Humanos , Persona de Mediana Edad , Enfermedad Pulmonar Obstructiva Crónica/etiología , Pruebas de Función Respiratoria , Índice de Severidad de la Enfermedad , Contaminación por Humo de Tabaco/efectos adversosRESUMEN
OBJETIVO: Investigar os benefícios a médio prazo de um programa de natação em escolares e adolescentes com asma atópica persistente moderada (AAPM). MÉTODOS: Realizou-se um estudo randomizado e prospectivo com crianças e adolescentes (7-18 anos de idade) com AAPM no Hospital de Clínicas da Universidade Estadual de Campinas (UNICAMP), Campinas (SP). Após um período de run in de um mês, 61 pacientes (34 femininos) foram randomizados em dois grupos: grupo natação (GN) (n = 30) e grupo controle (GC) (n = 31) e foram acompanhados durante 3 meses. Os dois grupos receberam fluticasona (pó) inalada (250 mcg, 2 vezes ao dia) diariamente e salbutamol inalado, quando necessário. O programa de natação consistiu em um total de 24 aulas, duas vezes por semana, por 3 meses. O GN e o GC realizaram espirometria, teste de broncoprovocação com metacolina (provocative concentration of methacholine causing a 20 por cento fall in FEV1, PC20 de metacolina), antes e após os 3 meses de estudo. Pressão inspiratória máxima (PImax) e pressão expiratória máxima (PEmax) foram realizadas somente no GN. RESULTADOS: Observou-se que o GN apresentou aumento significativo da PC20 de metacolina (inicial 0,31±0,25 e final 0,63±0,78; p = 0,008), pressão inspiratória máxima (inicial 67,08±17,13 cm H2O e final 79,46±18,66; p < 0,001), pressão expiratória máxima (inicial 71,69±20,01 cm H2O e final 78,92±21,45 cm H2O; p < 0,001). CONCLUSÃO: Crianças e adolescentes com AAPM que se submeteram a um programa de natação apresentaram diminuição estatisticamente significativa da hiper-responsividade brônquica, com aumento dos valores da PC20 de metacolina, quando comparados aos com AAPM que não realizaram natação. O GN também apresentou melhora no componente da força elástica do tórax.
OBJECTIVE: To investigate the medium-term benefits of a swimming program in schoolchildren and adolescents with moderate persistent atopic asthma (MPAA). METHODS: A randomized, prospective study of children and adolescents (age 7-18 years) with MPAA was carried out at the Hospital de Clínicas of Universidade Estadual de Campinas (UNICAMP), Campinas, Brazil. After a 1-month run-in period, 61 patients (34 female) were randomized into two groups, a swimming group (n = 30) and a control group (n = 31), and followed for 3 months. Both patient groups received inhaled fluticasone (dry powder, 250 mcg twice a day) and salbutamol as needed. The swim training program consisted of two weekly classes over a 3-month period for a total of 24 sessions. Both groups underwent spirometric assessment and methacholine challenge test - provocative concentration of methacholine causing a 20 percent fall in FEV1 (PC20) - before and after the study period. Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) were measured only in the swimming group. RESULTS: Significant increases in PC20 (pre-training, 0.31±0.25; post-training, 0.63±0.78; p = 0.008), MIP (pre-training, 67.08±17.13 cm H2O; post-training 79.46±18.66; p < 0.001), and MEP (pre-training, 71.69±20.01 cm H2O; post-training, 78.92±21.45 cm H2O; p < 0.001) were found in the swimming group. CONCLUSION: Children and adolescents with MPAA subjected to a swim training program experienced a significant decrease in bronchial hyperresponsiveness, as determined by increased PC20 values, when compared with asthmatic controls who did not undergo swim training. Participants in the swimming group also showed improvement in elastic recoil of the chest wall.
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Adolescente , Niño , Femenino , Humanos , Masculino , Asma/fisiopatología , Asma/rehabilitación , Hiperreactividad Bronquial/fisiopatología , Natación/fisiología , Pruebas de Provocación Bronquial , Broncoconstrictores , Terapia por Ejercicio/métodos , Cloruro de Metacolina , Estudios Prospectivos , Espirometría , Estadísticas no ParamétricasRESUMEN
BACKGROUND: It is well known the association between gastroesophageal reflux disease and asthma. The hyperreactivity of the airways is a characteristic of an asthmatic. Many studies associate the increase of the airways reactivity with gastroesophageal reflux disease. AIM: In this study we have evaluated the effect of the intraluminal exposition to gastric juice of trachea on the reactivity to methacholine from rats submitted to a pulmonary allergic inflammation. METHODS: Group of rats were sensitized and challenged with ovalbumin. After 24 hours the animals were sacrificed, and their tracheae were removed to be cultured with gastric juice. The gastric juice was obtained from a donor rat. Subsequently the segments were placed into plastic plates with RPMI-1640 for incubation, under suitable atmosphere and time. After the period of incubation the segments were put into chambers for the analysis of the contractile response to methacholine. RESULTS: We observed reduction in the contractile response of trachea cultured with gastric juice from allergic rats. This result was confirmed by the pharmacological treatments with compound 48/80 and dissodium cromoglicate (mast cells blockade), L-NAME (nitric oxide inhibitor, NO), capsaicin (neuropeptides depletion) and indomethacin (ciclooxigenase inhibitor). CONCLUSIONS: Our results highlight to the existence of a complex interaction between pulmonary allergy and gastric juice in the airways. The involvement of the non-adrenergic non-cholinergic system, NO, prostanoids and mast cells are directly related to this interaction. We suggest that the reduced contractile response observed in vitro may represent a protector mechanism of the airways. Despite its presence in the human body it can not be observed due to the predominant effects of excitatory the non-adrenergic non-cholinergic system.
RACIONAL: É bem estabelecida a relação entre a doença do refluxo gastroesofágico e a asma. A hiperreatividade das vias aéreas é uma das características que o indivíduo asmático desenvolve e diversos estudos associam o aumento da reatividade das vias aéreas com o refluxo gastroesofágico. OBJETIVO: Avaliar a reatividade à metacolina de traquéia exposta intraluminalmente ao suco gástrico de ratos submetidos a inflamação alérgica pulmonar. MÉTODOS: Grupos de ratos foram sensibilizados e broncoprovocados com ovoalbumina. Após 24 horas, os animais foram sacrificados e a traquéia removida para preenchimento de seu lúmen com suco gástrico obtido de um animal doador. A seguir, os segmentos foram colocados em placas plásticas com RPMI-1640 e mantidos em estufa por 3 horas em condições ambientais adequadas. Após o tempo de incubação, os fragmentos foram montados em cubas de vidro para órgão isolado para registro isométrico de contração, através da construção de curvas concentração-efeito à metacolina. RESULTADOS: Observou-se redução da resposta contrátil em traquéia exposta ao suco gástrico proveniente de ratos alérgicos. Os tratamentos farmacológicos com composto 48/80 e cromoglicato de sódio (bloqueio de mastócitos), L-NAME (inibidor de óxido nítrico, NO), capsaicina (depleção de neuropeptídios) e indometacina (inibidor da ciclooxigenase) corroboraram esta observação. CONCLUSÕES: Os resultados apontam para a existência de complexa interação entre a alergia pulmonar e o suco gástrico nas vias aéreas, com o envolvimento do sistema não-adrenérgico não-colinérgico, NO, prostanóides e mastócitos. À luz das evidências in vivo sobre a hiperreatividade das vias aéreas na associação asma e refluxo gastroesofágico, sugere-se que a reduzida resposta contrátil detectada in vitro pode representar um mecanismo protetor das vias aéreas. A despeito de sua presença, esta redução pode não ser observada in vivo devido à proeminência dos efeitos do sistema não-adrenérgico ...
Asunto(s)
Animales , Masculino , Ratas , Asma/complicaciones , Hiperreactividad Bronquial/fisiopatología , Reflujo Gastroesofágico/complicaciones , Asma/inducido químicamente , Asma/fisiopatología , Hiperreactividad Bronquial/inducido químicamente , Broncoconstrictores/farmacología , Reflujo Gastroesofágico/fisiopatología , Cloruro de Metacolina/farmacología , Ovalbúmina/farmacología , Ratas WistarRESUMEN
Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signáis that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signáis involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of reléase from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes.