Relationship between atopy and bronchial hyperresponsiveness to indirect stimuli in asthmatic children

PURPOSE: Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. Several BHR studies comparing groups of atopic and nonatopic asthmatics have reported conflicting results. The aim of this study was to compare BHR to indirect stimuli, such as mannitol or exercise, between atopic and nonatopic asthmatics in children. METHODS: We performed a retrospective analysis of data from 110 children with asthma, aged 6–18 years using skin prick tests, and serum total and specific IgE levels. Atopy degree was measured using the sum of graded wheal size or the sum of the allergen-specific IgE. Bronchial provocation tests (BPTs) using methacholine were performed on all subjects. BPTs using indirect simuli, including exercise and mannitol, were also performed. RESULTS: Asthma cases were classified as atopic asthma (n=83) or nonatopic asthma (n=27) from skin prick or allergen-specific IgE test results. There was no significant difference in the prevalence of BHR to mannitol or exercise between atopic and nonatopic asthmatics. Atopic asthma had a significantly lower postexercise maximum decrease in % forced expiratory volume in 1 second (FEV1) (geometric mean [95% confidence interval]: 31.9 [22.9–40.9] vs. 14.0 [9.4–18.6], P=0.015) and a methacholine PC20 (provocative concentration of methacholine inducing a 20% fall in FEV1) than nonatopic asthmatics (geometric mean [95% confidence interval]: 1.24 [0.60–1.87] ng/mL vs. 4.97 [3.47–6.47]) ng/mL, P=0.001), whereas mannitol PD15 (cumulative provocative dose causing a 15% fall in FEV1) was not significantly different between the 2 groups. CONCLUSION: There was no significant difference in the prevalence of BHR to mannitol or exercise between atopic and nonatopic asthmatics in children.

Preliminary Investigation of the Anti-asthmatic Potential of Kalanchoe integra Leaf Extract Using a Model of Allergic Airway Inflammation.

Objective: Kalanchoe integra is known to possess antihistaminic and mast cell stabilizing effect. Inflammatory mediators, such as histamine and eicosanoids have been implicated in the pathophysiology of allergen-induced asthma including bronchospasm, vasodilation, increased vascular permeability, perivascular and peribronchial oedema, acute functional changes in the lungs and diarrhea due to increased intestinal motility. This study is to ascertain the anti-inflammatory effect of Kalanchoe integra aqueous leaf extract (KILE) on bronchial hyper-responsiveness in ovalbumin-sensitized guinea-pigs. Method: Bronchial asthma was induced in guinea pigs using Ovalbumin. In vivo skin tests were carried out on all guinea pigs using ovalbumin and histamine as allergens. The diameters of wheals were recorded and the means determined. OA-sensitized guineapigs were challenged with 2% OA aerosols after 1 hour per os of drugs (KILE or prednisolonefor the treated groups) for two weeks. A piece of excised trachea was suspended in a tissue bath and challenged with histamine in the presence and absence of KILE, as well as Prednisolone (2.5 mg/kg). The results were reported as mean ±S.E.M. Statistical analysis was performed using one-way ANOVA and Bonferroni’s post hoc test. Results: Biological assaying of KILE showed significant dose-dependent reduction in histamine induced vasodilation of cutaneal blood vessels (P<0.05 in all groups at all times of wheal measurements) and contractile responses of isolated trachea to histamine. KILE generally reduced the effect of histamine in all groups. Conclusion: This study has shown that KILE has the potential of alleviating signs of bronchial hyper-responsiveness and skin allergies in ovalbumin-sensitized guinea pigs with the female models been more sensitive than the male counterparts.

Serum leptin levels correlate with bronchial hyper-responsiveness to mannitol in asthmatic children

PURPOSE: Epidemiological data indicate that obesity is a risk factor in asthma, however effects related to obesity and adipokines on airway inflammation and bronchial hyper-responsiveness (BHR) have not yet been demonstrated in the human airway. The aim of this study was to investigate the relationship between serum adipokine levels and BHR to mannitol in asthmatic children. METHODS: Serum adipokine levels were measured and pulmonary function tests were perfomed: baseline, postbronchodilator inhalation, methacholine inhalation, and mannitol inhalation. The response to mannitol was expressed as the dose causing a 15% decrease in forced expiratory volume in one second (FEV1) (PD15), and as the response-dose ratio (RDR) (% fall in FEV1/cumulative dose). RESULTS: Sixty-nine prepubertal children between the ages of 6 and 10 years were participated in the study. They comprised asthmatic children (n=40) and healthy (n=29). Twenty-two subjects (55.5%) with asthma had a positive mannitol bronchial provocation test (BPT) result. The body mass index (BMI) was higher in those asthmatics with positive mannitol BPTs than in asthmatics with negative mannitol BPTs and in the control group (19.30 kg/m2 vs. 17.60 kg/m2 vs. 17.93 kg/m2, P=0.035, P=0.046). Serum leptin levels were also significantly higher in asthmatics with positive mannitol BPTs than in asthmatics with negative mannitol BPTs and in the control group (10.58 ng/mL vs. 5.49 ng/mL vs. 6.75 ng/mL, P=0.002, P=0.016). Leptin values were significantly associated with a PD15 (r=-0.498, P=0.022) and RDR to mannitol (r=0.346, P=0.033) in asthmatic children after adjustment for BMI. CONCLUSION: Serum leptin levels were significantly associated with BHR to mannitol in asthmatic children.

Fractional Exhaled Nitric Oxide and Impulse Oscillometry in Children With Allergic Rhinitis

PURPOSE: Airway inflammation, bronchial hyper-responsiveness (BHR), and bronchodilator response (BDR) are representative characteristics of asthma. Because allergic rhinitis (AR) is a risk factor for asthma development, we evaluated these 3 characteristics in AR using measurement of fractional exhaled nitric oxide (FeNO), a methacholine challenge test (MCT), and impulse oscillometry (IOS). METHODS: This study included 112 children with asthma (asthma group), 196 children with AR (AR group), and 32 control subjects (control group). We compared pulmonary function parameters and FeNO levels among the 3 groups. The AR group was subdivided into 2 categories: the AR group with BHR and the AR group without, and again pulmonary function and FeNO levels were compared between the 2 subgroups. RESULTS: FeNO levels were more increased in the AR and asthma groups than in the control group; within the AR group, FeNO was higher in the AR group with BHR than in the AR group without. The BDR was more increased in the AR group than in the control group when percent changes in reactance at 5 Hz (Delta X5) and reactance area (Delta AX) were compared. In the AR group, however, there was no difference in Delta X5 and Delta AX between the AR group with BHR and the AR group without. CONCLUSIONS: Reversible airway obstruction on IOS and elevated FeNO levels were observed in children with AR. Because elevated FeNO levels can indicate airway inflammation and because chronic inflammation may lead to BHR, FeNO levels may be associated with BHR in AR. IOS can be a useful tool for detecting lower airway involvement of AR independent of BHR assessed in the MCT.

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.

The effect of Residential Environments on the Bronchial Hyperresponsiveness / 대한산업의학회지

OBJECTIVES: The increased prevalence of asthma over the last 30 years has been reported from many different countries, including Korea. The increased prevalence may be due to increased exposure to indoor air pollutants. METHODS: In this study, the relationship between residential environments and airway hyper-responsiveness has been examined among 280 family members. The bronchial hyper-responsiveness was expressed as the log-transformed slope of FEV decrease over the log-transformed dose of methacholine concentration(BRindex). Simple regression analysis was done for the effect of sex, age, atopic status, and residential environments including active and passive smoking exposures on airway responsiveness. Based on simple regression results, multiple rwegression analysis was performed for total group and also according to sex. RESULTS: The mean of BRindex of residents living in gas boiler heating houses was higher than that of central heating system (p=0.014). Smoking status was a significant determinant of bronchial hyper-responsiveness in both genders; male(p=0.017), female (p%.022). In the male group the mean of BRindex of current smokers was significantly higher than those of ex-smokers and non-smokers, and the mean of BRindex of passive smokers was higher than that of non-smokers, but statistical significance was border-line(p=0.069). In female group, the mean of BRindex of kerosene stove users was higher than that of non-users(p=0.057). CONCLUSIONS: This study suggests that indoor air pollutants including type of heating, passive smoking and kerosene stove use can contribute to the increase in asthma prevalence in Korea.