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.

Effect of constant light and immobilization stress on rat submandibular saliva secretory response induced by cholinergic and peptidergic agonists

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.

The KAAACI Standardization Committee Report on the procedure and application of the bronchial provocation tests

Bronchial provocation tests are of value in the evaluation of airway hyperresponsiveness. Nonspecific bronchial challenge (methacholine, mannitol, exercise, etc.) is used when the symptoms, physical examination, and measurements of pulmonary function are unremarkable in the diagnosis of asthma, when a patient is suspected of having occupational asthma or exercise-induced bronchoconstriction (EIB), and when a screening test for asthma or EIB is required for some occupational groups in whom bronchospasm would pose an unacceptable hazard. Methacholine inhalation challenge is most widely used pharmacologic challenge and highly sensitive. For appropriate interpretation of the results of methacholine provocation, it is important to perform the test with the standardized protocol and to recognize that inhalation methods significantly influence the sensitivity of the procedure. Indirect challenges (e.g., mannitol and exercise) correlate with airway inflammation and are more specific but less sensitive for asthma. Indirect provocation tests are used to confirm asthma, to differentiate asthma from other airway diseases, and to evaluate EIB.

Methacholine bronchial provocation test in patients with asthma: serial measurements and clinical significance

BACKGROUND/AIMS: The methacholine bronchial provocation test (MBPT) is used to detect and quantify airway hyper-responsiveness (AHR). Since improvements in the severity of asthma are associated with improvements in AHR, clinical studies of asthma therapies routinely use the change of airway responsiveness as an objective outcome. The aim of this study was to assess the relationship between serial MBPT and clinical profiles in patients with asthma. METHODS: A total of 323 asthma patients were included in this study. The MBPT was performed on all patients beginning at their initial diagnosis until asthma was considered controlled based on the Global Initiative for Asthma guidelines. A responder was defined by a decrease in AHR while all other patients were considered non-responders. RESULTS: A total of 213 patients (66%) were responders, while 110 patients (34%) were non-responders. The responder group had a lower initial PC20 (provocative concentration of methacholine required to decrease the forced expiratory volume in 1 second by 20%) and longer duration compared to the non-responder group. Members of the responder group also had superior qualities of life, compared to members of the non-responder group. Whole blood cell counts were not related to differences in PC20; however, eosinophil concentration was. No differences in sex, age, body mass index, smoking history, serum immunoglobulin E, or frequency of acute exacerbation were observed between responders and non-responders. CONCLUSIONS: The initial PC20, the duration of asthma, eosinophil concentrations, and quality-of-life may be useful variables to identify improvements in AHR in asthma patients.

Dyspnea Perception During Induced Bronchoconstriction Is Complicated by the Inhaled Methacholine in Children With Clinical Asthma

PURPOSE: Dyspnea is not widely utilized as an indicator of asthma provocation despite its universal presentation. We hypothesized that dyspnea severity was proportionate with the lung function decline, methacholine dose-step, and the degree of bronchial hyperresponsiveness (BHR). METHODS: We retrospectively analyzed 73 children's bronchial provocation test data with an assessment of dyspnea at every dose-step. Dyspnea severity was scored using a modified Borg (mBorg) scale. A linear mixed effect analysis was performed to evaluate the relationship between the mBorg scale, the percentage fall in the forced expiratory volume in 1 second (FEV1) (ΔFEV1%), the methacholine dose-step, and the degree of BHR (BHR grade). RESULTS: Subjects were divided into 5 BHR groups based on their last methacholine dose-steps. The mBorg scores did not differ significantly among BHR groups (P=0.596, Kruskal-Wallis test). The linear mixed effect analysis showed that ΔFEV1% was affected by the methacholine dose-step (P < 0.001) and BHR grade (P < 0.001). The mBorg score was affected by the dose-step (P < 0.001) and BHR grade (P=0.019). We developed a model to predict the mBorg score and found that it was affected by the methacholine dose-step and ΔFEV1%, elevating it by a score of 0.039 (χ² [1]=21.06, P < 0.001) and 0.327 (χ² [1]=47.45, P < 0.001), respectively. A significant interaction was observed between the methacholine dose-step and ΔFEV1% (χ² [1]=16.20, P < 0.001). CONCLUSIONS: In asthmatic children, inhaled methacholine, as well as the degree of BHR and lung function decline, may affect dyspnea perception during the bronchial provocation test. If we wish to draw meaningful information from dyspnea perception, we have to consider various complicating factors underlying it.

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.

Role of astograph methacholine provocation test in diagnosis of bronchial asthma / 实用医学杂志

Objective To evaluate the diagnostic value of astograph methacholine provocation test for bronchial asthma.Methods A total of 238 asthma patients and 499 non-asthma patients participated in the detection by astograph methacholine provocation test.Statistical methods were used to analyze the differences of astograph parameters and find the indicators of asthma diagnosis and the critical value.Results Dmin,Cmin and PD15 were much lower in the asthma group (P ＜ 0.01),compared with the the non-asthma group,when SGrs,SGrs/Grs cont were much higher (P ＜ 0.01).SGrs was relevant with Dmin,Cmin,PD15 in the asthma group (P =0.000;r =0.685,r =0.657,r =0.639) as well as the SGrs/Grs cont did (P =0.000,r =0.775;r =0.740,r =0.708).In ROC analysis,Dmin presented an AUC of 0.661,the cutoff value was 2.71 unit,with a sensitivity of 0.739 and specificity of 0.551.PD15 presented an AUC of 0.746,the cutoff value was 4.856 5 unit,with a sensitivity of 0.693 and specificity of 0.684.Conclusion Astograph methacholine provocation test shows good sensitivity and specificity in the diagnosis of asthma,particularly when Dmin ≤ 2.71 Unit or PD15 ≤ 4.8565 Unit as the cutoff value.

Reversion of methacholine induced bronchoconstriction with inhaled diazepam in patients with asthma / Bloqueo de la respuesta bronco constrictora a metacolina con diazepam inhalado en pacientes con asma

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.

Efeito do inibidor de proteinase de origem vegetal EcTI, sobre a inflamação pulmonar alérgica crônica em camundongos Balb/c / Effect of proteinase inhibitor of plant origin EcTI in an experimental model of chronic allergic pulmonary inflammation in Balb/c mice

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,...

Exertional‑induced bronchoconstriction: Comparison between cardiopulmonary exercise test and methacholine challenging test.

Introduction: Exertional‑induced bronchoconstriction is a condition in which the physical activity causes constriction of airways in patients with airway hyper‑ responsiveness. In this study, we tried to study and evaluate any relationship between the findings of cardiopulmonary exercise testing (CPET) and the response to methacholine challenge test (MCT) in patients with dyspnea after activity. Materials and Methods: Thirty patients with complaints of dyspnea following activity referred to “Lung Clinic” of Baqiyatallah Hospital but not suffering from asthma were entered into the study. The subjects were excluded from the study if: Suffering from any other pulmonary diseases, smoking more than 1 cigarette a week in the last year, having a history of smoking more than 10 packets of cigarettes/year, having respiratory infection in the past 4 weeks, having abnormal chest X‑ray or electrocardiogram, and cannot discontinue the use of medicines interfering with bronchial provocation. Baseline spirometry was performed for all the patients, and the values of forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and FEV/FVC were recorded. The MCT and then the CPET were performed on all patients. Results: The mean VO2 (volume oxygen) in patients with positive methacholine test (20.45 mL/kg/min) was significantly lower than patients with negative MCT (28.69 mL/kg/min) (P = 0.000). Respiratory rates per minute (RR) and minute ventilation in the group with positive MCT (38.85 and 1.636 L) were significantly lower than the group with negative methacholine test (46.78 and 2.114 L) (P < 0.05). Also, the O2 pulse rate in the group with negative methacholine test (116.27 mL/beat) was significantly higher than the group with positive methacholine test (84.26 mL/beat) (P < 0.001). Conclusion: Pulmonary response to exercise in patients with positive methacholine test is insufficient. The dead space ventilation in these patients has increased. Also, dynamic hyperinflation in patients with positive methacholine test causes the reduced stroke volume and O2 pulse in these patients.

Clinical value of fractional exhaled nitric oxide level in predicting bronchial hyperreactivity in asthmatic children / 国际儿科学杂志

Objective To evaluate the clinical value of fractional exhaled nitric oxide (FeNO) level in asthmatic children to predict bronchial hyperresponsiveness by analyzing the correlation between fraction of exhaled nitric oxide and bronchial provocation test.Methods One hundred and fourteen asthma outpatients of Shengjing Hospital were enrolled, FeNO levels, spirometry and bronchial provocation test were measured.Results In the bronchial provocation test,there were 33 positive and 81 negative cases.The positive group had a significantly higher FeNO levels than the negative ones(19.0 × 10-9 vs.16.0 × 10-9 ,p =0.000).By the ROC curve, the best FeNO cut-off value to predict bronchial hyperresponsiveness was 38.5 × 10-9 with high specificity (92.6％) but relatively low sensitivity (36.4％).There was no relationship between methacholine provocative dose causing a 20％ fall in FEV1 (PD20-FEV1) and the level of FeNO.Conclusion FeNO level has important predicting value for bronchial hyperreactivity in children with asthma.The level of FeNO ＞ 38.5 × 10-9 has high predictive value in asthmatic children with bronchial hyperreactivity.

Pituitary Adenylate Cyclase Activating Peptide (1-38) and its analog (Acetyl-[Ala15, Ala20] PACAP 38-polyamide) reverse methacholine airway hyperresponsiveness in rats

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.

Small Airway Impairment and Bronchial Hyperresponsiveness in Asthma Onset

PURPOSE: Our study tried to find a relationship between baseline FEF25-75% and airway hyperresponsiveness (AHR) and whether a greater FEF25-75% impairment may be a marker of a more severe hyperresponsiveness in subjects with normal FEV1 and FEV1/FVC and suggestive asthma symptoms. Besides, we tried to asses a FEF25-75% cut-off value to identify hyper-reactive subjects. METHODS: 4,172 subjects (2,042 M; mean age: 38.3+/-14.9; mean FEV1 % predicted: 100.5+/-12.7 and FEV1/FVC: 85.4+/-6.8) were examined after performing a methacholine (Mch) test. All subjects reported a symptom onset within 3 years before the test. Subjects with PD20400 microg were arbitrarily considered affected by moderate/severe and borderline AHR, respectively. RESULTS: PD20 values were 213 (IQR:86-557), 340 (IQR:157-872) and 433 (IQR:196-1032) microg in subjects with baseline FEF25-7570% respectively (P70%. The hyperreactive subjects percentage, was higher in those with FEF25-7570% (P70%) was a higher AHR risk factor, especially in subjects with moderate/severe AHR (OR: 2.18 [IQR:1.41-3.37]; P50 and 70% levels were similar both in normoreactive and hyperreactive subjects. CONCLUSIONS: At asthma onset, reduced baseline FEF25-75 values with normal FEV1 and FEV1/FVC may predict AHR. Detectable predictive cut-off values do not exist because even normoreactive subjects can show lower FEF25-75 values. Furthermore, a greater FEF25-75 reduction may be associated to a more severe AHR, suggesting a possible FEF25-75 role in the management of asthma when FEV1 and FEV1/FVC are normal.

Risk factors influencing bronchial hyperresponsiveness to methacholine in school age and adolescence of atopic dermatitis

PURPOSE: Many studies have shown the importance for bronchial hyperresponsiveness (BHR) in children with bronchial asthma and allergic rhinitis. However, studies have not been done in BHR in school age and adolescence with atopic dermatitis (AD). METHODS: The patients with history of bronchial asthma were excluded and methacholine challenge test (MCT) was performed in 103 children with atopic dermatitis. The positive of MCT result is defined as provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC20)< or =8 mg/mL. According of the level of PC20, the patients were divided into two groups. RESULTS: The group 1 (BHR+) was observed in 43 of all patients (41.7%). Of two groups, significant differences were observed in age, body mass index. No significant differences were observed in the number of male, SCORing Atopic Dermatitis (SCORAD) index, admission history, smoking exposure history, other allergic disease, parental allergic disease. The group 1 (BHR+) have higher levels of total eosinophil count compared with the group 2 (BHR-) (629.8+/-360.5/microL vs. 470.2+/-253.9/microL, P=0.01). But no significant association was found between severity of BHR and SCORAD score, total immunoglobulin E, total eosin ophil count and eosinophil cationic protein (r=0.008, P=0.961; r=-0.217, P=0.162; r=0.225, P=0.147; r=-0.032, P=0.841). The list of allergen is that the house dust mite, tree, weed, food, animal hair, and fungus. The house dust mite has correlation with bronchial hypersensitivity statistically and the any of allergen groups, either. CONCLUSION: No significant relationship was observed between degree of BHR and allergy laboratory finding, severity of AD.

Relationships between Fraction of Nitric Oxide, Airway Hyperresponsiveness, Blood Eoshinophil Counts and Serum Eosinophil Cationic Protein in Asthmatic Children / 소아알레르기및호흡기학회지

PURPOSE: The measurement of fraction of nitric oxide (FeNO) is a noticeable tool that reflects airway inflammation in asthmatic patients. We wanted to find out the relationship between pulmonary function, bronchial hyperresponsiveness (AHR), blood eosinophilic inflammatory markers and FeNO level before and after methacholine bronchoprovocation test in asthmatic patients. METHODS: Fifty-five children, who visited the Allergy Clinic of Korea University Anam Hospital from March 2011 to February 2012, due to asthmatic symptoms, such as history of episodic wheezing or dyspnea during the previous year and resolved after using bronchodilators, were enrolled. We performed the baseline pulmonary function and methacholine bronchoprovocation test in the enrolled patients. Blood eosinophil counts and blood eosinophil cationic protein (ECP) were measured. FeNO levels were measured before and after the methacholine bronchoprovocation test. RESULTS: The mean FeNO levels (36.3 ppb) fell after methacholine bronchoprovocation test (25.7 ppb). Forced expiratory volume in one second (FEV1) %pred inversely correlated both with FeNO level before (R2=0.07, P=0.029) and after (R2=0.059, P=0.01) methacholine bronchoprovocation test. The provocative concentration, causing a 20% decrease in FEV1 to methacholine (methacholine PC20) inversely correlated both with FeNO levels before (R2=0.086, P=0.001) and after (R2=0.141, P=0.001) the challenge. FeNO level measured at bronchoconstriction state significantly correlated with blood eosinophil counts (R2=0.112, P=0.028). Serum ECP levels correlated FeNO level, neither before nor after bronchoprovocation. CONCLUSION: The baseline FeNO levels were higher in asthmatic children. However, FeNO levels rather decreased after methacholine induced bronchoconstriction. Repeated spirometry maneuver was considered to have an effect on reducing FeNO levels. FeNO correlated with pulmonary function, airway AHR and blood eosinophil counts.

Is It Necessary to Re-Evaluate Airway Hyperresponsiveness During Treatment of Mild Asthma? / 대한내과학회지

BACKGROUND/AIMS: Airway hyperresponsiveness (AHR) is one of the typical characteristics of asthma. However, its natural course is unknown. The presence of AHR is often not assessed in asthmatics undergoing medical treatment. We investigated the changes of AHR as compared with clinical parameters in patients with mild asthma. METHODS: We enrolled patients who were diagnosed with asthma, but were asymptomatic for > 3 months while undergoing medical treatment. AHR was measured using a methacholine bronchial provocation test after a 2-week washout period. AHR-negativity was defined as a PC20 > 25 mg/mL. Clinical parameters were retrospectively compared between the AHR-negative and -positive patients. RESULTS: Among 54 patients, 22 (40.7%) were AHR negative. Factors associated with the maintenance of AHR were male sex, presence of dyspnea, and high-dose inhaled corticosteroid plus long-acting beta agonists at initial presentation (respectively, p < 0.05). Age, symptoms other than dyspnea, blood tests, results of spirometry, diagnostic methods at presentation, and time from diagnosis to follow-up testing were not significantly different between AHR-negative and AHR-positive patients. Multivariate analyses failed to show a significant difference between the two groups, except for male sex (p = 0.014). CONCLUSIONS: Approximately 40% of patients with mild asthma show no AHR or clinical remission of the disease. Male sex may be a predictive factor for persistent AHR. However, altered AHR status is not predictable in patients with mild asthma undergoing medical treatment. Therefore, the cessation of regular controller might be advocated, and reassessment of AHR should be mandatory.

Relationship between Bronchial Hyperresponsiveness and Development of Asthma in Preschool Children with Cough Variant Asthma / 소아알레르기및호흡기학회지

PURPOSE: A significant proportion of patients with cough variant asthma (CVA) eventually develops asthma. The aim of this study was to investigate the relationship between bronchial hyperresponsiveness (BHR) and development of asthma in preschool children with CVA. METHODS: We reviewed the medical records of children aged 5 to 7 years who presented with chronic cough and had regular check-up by the school age. All children had methacholine bronchial challenge test (MBCT) at preschool age with a modified auscultation method. The end-point was defined as the appearance of wheezing and/or oxygen desaturation. Positive BHR was defined as end-point concentration (EPC)< or =8 mg/mL. MBCT was performed at the school age with spirometric method. Positive BHR was defined as PC20< or =8 mg/mL. We collected information on the development of wheezing or dyspnoea from the medical records. RESULTS: Thirty-six children with CVA were analyzed. During follow-up (2.1+/-0.9 years), 9/36 children developed wheezing or dyspnoea (group A), and 27/36 children did not (group B). EPC (geometric mean, 95% confidence interval) was significantly lower in group A than group B (1.59 mg/mL, 0.93 to 2.70 mg/mL vs. 3.43 mg/mL, 2.34 to 5.03 mg/mL; P=0.02, respectively). The prevalence of positive BHR at school age was significantly higher in group A than group B (77.8% vs. 22.2%, P<0.01). CONCLUSION: These results suggest that the increase and the persistence of BHR may have an important role in the development of asthma during the course of CVA in preschool children.

Airway Responses to Deep Inspiration in Asthma by Different Bronchial Challenge

OBJECTIVE: Deep inspirations (DI) provide physiologic protection against airway narrowing and DI-induced bronchoprotection and bronchodilation are impaired in asthma. METHODS: To evaluate effect of DI on airway narrowing during methacholine challenge, we compared the 2 minutes tidal breathing method and the breath dosimeter method. Methacholine challenge in 12 asthmatics and 10 healthy controls was cross-overly performed by two methods. On first visit, a questionnaire for symptoms, allergy skin test, spirometry, and methacholine challenge was performed. On second visit, spirometry and methacholine challenge using the 25 mg/mL at 5 minutes intervals during the 2 minutes tidal breathing method and the ten-breath dosimeter method were performed on two separate days at same time each day. RESULTS: The decreases in forced expiratory volume in one second (FEV1) and forced vital capacity during the 2 minutes tidal breathing method and dosimeter method in patients with asthmatics were higher than those in normal controls. The decreases in FEV1 and forced vital capacity during the 2 minutes tidal breathing method were higher than during dosimeter method in both asthmatics and controls. CONCLUSION: These observations indicate that the continuous generation method produce more bronchoconstriction than the dosimeter method during methacholine challenge and asthmatics had more bronchoconstriction than controls, suggesting inhibition of DI enhance methacholine induced airway narrowing in asthmatics.

Bronchial Hyperresponsiveness to Methacholine and AMP in Children With Atopic Asthma

PURPOSE: Bronchial hyperresponsiveness (BHR) is typically measured by bronchial challenge tests that employ direct stimulation by methacholine or indirect stimulation by adenosine 5'-monophosphate (AMP). Some studies have shown that the AMP challenge test provides a better reflection of airway inflammation, but few studies have examined the relationship between the AMP and methacholine challenge tests in children with asthma. We investigated the relationship between AMP and methacholine testing in children and adolescents with atopic asthma. METHODS: The medical records of 130 children with atopic asthma (mean age, 10.63 years) were reviewed retrospectively. Methacholine and AMP test results, spirometry, skin prick test results, and blood tests for inflammatory markers (total IgE, eosinophils [total count, percent of white blood cells]) were analyzed. RESULTS: The concentration of AMP that induces a 20% decline in forced expiratory volume in 1 second [FEV1] (PC20) of methacholine correlated with the PC20 of AMP (r2=0.189, P<0.001). No significant differences were observed in the levels of inflammatory markers (total eosinophil count, eosinophil percentage, and total IgE) between groups that were positive and negative for BHR to methacholine. However, significant differences in inflammatory markers were observed in groups that were positive and negative for BHR to AMP (log total eosinophil count, P=0.023; log total IgE, P=0.020, eosinophil percentage, P<0.001). In contrast, body mass index (BMI) was significantly different in the methacholine positive and negative groups (P=0.027), but not in the AMP positive and negative groups (P=0.62). The PC20 of methacholine correlated with FEV1, FEV1/forced vital capacity (FVC), and maximum mid-expiratory flow (MMEF) (P=0.001, 0.011, 0.001, respectively), and the PC20 of AMP correlated with FEV1, FEV1/FVC, and MMEF (P=0.008, 0.046, 0.001, respectively). CONCLUSIONS: Our results suggest that the AMP and methacholine challenge test results correlated well with respect to determining BHR. The BHR to AMP more likely implicated airway inflammation in children with atopic asthma. In contrast, the BHR to methacholine was related to BMI.

Assessment of Bronchodilator Responsiveness Following Methacholine-Induced Bronchoconstriction in Children With Asthma

PURPOSE: The aim of this study was to investigate bronchodilator responsiveness (BDR) following methacholine-induced bronchoconstriction and to determine differences in BDR according to clinical parameters in children with asthma. METHODS: The methacholine challenge test was performed in 145 children with mild to moderate asthma, and the provocative concentration causing a 20% decline in FEV1 (PC20) was determined. Immediately after the challenge test, patients were asked to inhale short-acting beta2-agonists (SABAs) to achieve BDR, which was assessed as the change in FEV1% predictedx100/post-methacholine FEV1% predicted. For each subject, the asthma medication, blood eosinophil count, serum total IgE, serum eosinophil cationic protein level, and skin prick test result were assessed. RESULTS: The FEV1 (mean+/-SD) values of the 145 patients were 90.5+/-10.9% predicted, 64.2+/-11.5% predicted, and 86.2+/-11.2% predicted before and after methacholine inhalation, and following the administration of a SABA, respectively. The BDR did not differ significantly according to asthma medication, age, or gender. However, BDR in the atopy group (37.4+/-17.7%) was significantly higher than that in the non-atopy group (30.5+/-10.7%; P=0.037). Patients with blood eosinophilia (38.6+/-18.1%) displayed increased BDR compared with patients without eosinophilia (32.0+/-13.8%; P=0.037). CONCLUSIONS: In children with mild to moderate asthma, the responsiveness to short-acting bronchodilators after methacholine-induced bronchoconstriction was not related to asthma medication, but was higher in children with atopy and/or peripheral blood eosinophilia.