Particulate matter 2.5 triggers airway inflammation and bronchial hyperresponsiveness in mice by activating the SIRT2-p65 pathway / 医学前沿

Exposure to particulate matter 2.5 (PM2.5) potentially triggers airway inflammation by activating nuclear factor-κB (NF-κB). Sirtuin 2 (SIRT2) is a key modulator in inflammation. However, the function and specific mechanisms of SIRT2 in PM2.5-induced airway inflammation are largely understudied. Therefore, this work investigated the mechanisms of SIRT2 in regulating the phosphorylation and acetylation of p65 influenced by PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Results revealed that PM2.5 exposure lowered the expression and activity of SIRT2 in bronchial tissues. Subsequently, SIRT2 impairment promoted the phosphorylation and acetylation of p65 and activated the NF-κB signaling pathway. The activation of p65 triggered airway inflammation, increment of mucus secretion by goblet cells, and acceleration of tracheal stenosis. Meanwhile, p65 phosphorylation and acetylation, airway inflammation, and bronchial hyperresponsiveness were deteriorated in SIRT2 knockout mice exposed to PM2.5. Triptolide (a specific p65 inhibitor) reversed p65 activation and ameliorated PM2.5-induced airway inflammation and bronchial hyperresponsiveness. Our findings provide novel insights into the molecular mechanisms underlying the toxicity of PM2.5 exposure. Triptolide inhibition of p65 phosphorylation and acetylation could be an effective therapeutic approach in averting PM2.5-induced airway inflammation and bronchial hyperresponsiveness.

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.

Study on correlation between FeNO, bronchial hyperresponsiveness and asthma control in preschool children / 重庆医学

Objective To find out the association between the indicators(pulse concussion lung function test index) of bronchial hyperresponsiveness (BHR) with fractional concentration of exhaled nitric oxide (FeNO) at different control periods among preschool asthmatic children.Methods Totally 74 asthmatic children in the pediatric department of our hospital from April 2015 to February 2017 were enrolled in this study,and 25 children undergoing the lung function and FeNO examination served as the controls,aged 3-5 years old.The cases were divided into three groups according to the standard in 2016 version of the Prevention and Treament Guide of Children Bronchial Asthma:asthma control group(n =26),asthma non-control;group(n =48) and control group (n=25).All data of FeNO,resistance of the respiratory system at 5 Hz(R5),resistance of the respiratory system at 5 Hz (R20),difference of R5 and R20(R5-20),reactance area (AX),reactance of the respiratory system at 5 Hz (X5) and resonant frequency of reactance (Fres) were collected.The FeNO,pulse concussion lung function test value and their association were analyzed.Results (1) The FeNO value of asthma the non-control group was significantly higher than that of the asthma control group and the control group,which were 34.00 ± 18.17,20.23± 11.07 and 28.00± 17.30 respectively.The AX detection value of the asthma non-control group was significantly higher than that of the control group(37.29 ± 15.27 vs.30.17 ± 9.50,P＜0.05).(2)R20 had weak correlation with FeNO in the control group(P＜0.05),while R20 had no correlation with FeNO in the non-control group and control group (P＞0.05).FeNO had no obvious correlation with R5,R520,AX,X5 and Fres in the asthma non-control group,asthma control group and control group(P＞0.05).Conclusion In preschool children with asthma,FeNO can reflect the airway eosinophilic inflammation control,and does not reflect the airway hyperresponsiveness.Thereforeit ie needed to combined with FeNO and IOS indicators (airway hyperresponsiveness index AX,etc.),which can more precisely judge whether asthma being controlled.

The effect of the asthmatic mice's airway inflammation and bronchial hyperresponsiveness treated with curcumin / 国际儿科学杂志

Objective To investigate the effect of the asthmatic mice's airway inflammation and bronchial hyperresponsiveness treated with curcumin.Methods The mice were divided into three teams randomly,the normal mice,the asthmatic mice and the curcumin mice.The mice of three teams were detected by lung function,Giemsa dying,HE and PAS dying,and ELISA.Results After the Mch concentration of 6.25 g/L,the value of Penh in asthmatic mice was higher than the control mice,which was sighifiantly different(P ＜ 0.01).However,the value of Penh in curcumin team was lower than asthmatic mice,which was sighifiantly different (P ＜0.01).The number of total white blood cells and eosinophils was higher in asthmatic mice than the contol,which was sighifiantly different(P ＜0.01).However,the number in curcumin team was lowered than asthmatic team(P ＜ 0.01).The IgE content of BALF in asthmatic mice was higher than the control,which was significantly different(P ＜ 0.01).However,the content in curcumin team was lowered than the asthmatic mice,which had a significant difference(P ＜0.01).Pathology of HE staining in asthmatic mice showed the thickening bronchial wall,narrow lumen,peribronchial and perivascular infiltration with a large number of eosinophil-based inflammatory cells,lumen with many inflammatory secretions.However,the curcumin team was alleviated than the asthmatic mice.There were more goblet cells and more mucus secretion in the asthmatic mice by PAS staining.However,the curcumin team was alleviated than the asthmatic mice.Conclusion Curcumin can alleviate the airway inflammation,mucus secretion,airway hyperresponsiveness and the IgE content of bronchoalveolar lavege fluid.

Positive bronchial provocation test and lower small airway function in the cough variant asthma / 临床儿科杂志

ObjectiveTo investigate bronchial provocation test (BPT) and small airway function in children with cough variant asthma (CVA).MethodsA total of 353 children with chronic cough whose mean age was (7.45±2.58) years from three hospitals of Pudong district were enrolled during May 2012 and February 2014. Conventional pulmonary function tests, BPT and questionnaire survey were performed and the difference in pulmonary function was analyzed between children with positive BPT and negative BPT.ResultsIn 353 children with chronic cough, there were 200 children (56.66%) diagnosed as CVA with posi-tive BPT. Compared with BPT negative group, the percentages of nighttime cough and severe dry cough in BPT positive group were signiifcantly higher while the percentages of morning/daytime cough and wet cough were signiifcantly lower (P<0.01). Fur-thermore, the rates of history of atopic dermatitis and rhinitis in BPT positive group were signiifcantly higher than those in BPT negative group (P<0.01). Forced expiratory lfow at 75% relfecting the small airway function was signiifcantly lower in BPT posi-tive group than that in BPT negative group (P=0.032).ConclusionsBronchial hyperresponsiveness and decreased small airway function are the important pathological features of CVA. BPT and spirometry have clinical signiifcances in the CVA diagnosis and the analysis of cause of chronic cough.

The Association of Lung Function, Bronchial Hyperresponsiveness, and Exhaled Nitric Oxide Differs Between Atopic and Non-atopic Asthma in Children

PURPOSE: Although many previous studies have attempted to identify differences between atopic asthma (AA) and non-atopic asthma (NAA), they have mainly focused on the difference of each variable of lung function and airway inflammation. The aim of this study was to evaluate relationships between lung function, bronchial hyperresponsiveness (BHR), and the exhaled nitric oxide (eNO) levels in children with AA and NAA. METHODS: One hundred and thirty six asthmatic children aged 5-15 years and 40 normal controls were recruited. Asthma cases were classified as AA (n=100) or NAA (n=36) from skin prick test results. Lung function, BHR to methacholine and adenosine-5'-monophosphate (AMP), eNO, blood eosinophils, and serum total IgE were measured. RESULTS: The AA and NAA cases shared common features including a reduced small airway function and increased BHR to methacholine. However, children with AA showed higher BHR to AMP and eNO levels than those with NAA. When the relationships among these variables in the AA and NAA cases were evaluated, the AA group showed significant relationships between lung function, BHR to AMP or methacholine and eNO levels. However, the children in the NAA group showed an association between small airway function and BHR to methacholine only. CONCLUSIONS: These findings suggest that the pathogenesis of NAA may differ from that of AA during childhood in terms of the relationship between lung function, airway inflammation and BHR.

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.

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.

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.

The effect of atopy and allergic diseases on pulmonary function of Korean adolescents

PURPOSE: Pulmonary function test (PFT) plays a key role in the diagnosis and management of asthma in adolescents. But, it is not clear whether adolescents with asthma have significantly reduced lung function when compared with adolescents without asthma. The purpose of this study was to determine the effect of atopy and allergic diseases on pulmonary function and bronchial hyperresponsiveness (BHR) in Korean adolescents. METHODS: A questionnaire survey was conducted on 647 middle school students (male, 264; female, 383) from Seoul city to determine the prevalence of symptoms and diagnosed allergic diseases. We also performed the PFT, methacholine challenge test, skin prick tests and serum total immunoglobulin E. Current atopic dermatitis was diagnosed by doctor's medical examination. RESULTS: Female showed higher values of forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) and higher numbers of BHR (PC20 less than 25 mg/dL) compared to male (P<0.01). BHR was more common in atopy group (P<0.01), but PFT was not significant difference between atopy and nonatopy. Mean values for all spirometric parameters for asthmatic adolescents were in the normal range. Adolescents with asthma symptoms had slightly lower FEV1/FVC and forced expiratory flow 25%-75% than that of adolescents with no history of wheeze ever, asthma diagnosis and current asthma, but there was no statistically significance. CONCLUSION: The majority of adolescents recruited from the general population who reported having asthma symptoms or other allergic diseases had normal lung function. Sex, atopy, and current atopic dermatitis may affect BHR in Korean adolescents.

Association between Recent Acetaminophen Use and Asthma: Modification by Polymorphism at TLR4

The risk of asthma has been increasing in parallel with use of acetaminophen, which is a potential source of oxidative stress. Toll-like receptor 4 (TLR4) plays a critical role not only in innate immunity, but also in mediating reactive oxygen species induced inflammation. Therefore, we investigated associations between acetaminophen usage and TLR4 polymorphism on asthma and bronchial hyperresponsiveness (BHR). The number of 2,428 elementary school children in Seoul and Jeongeup cities was recruited. Subjects who used acetaminophen with a family history of asthma had an increased risk of both asthma diagnosis ever and current asthma. Individuals with CT+TT genotypes at the TLR4 polymorphism, in combination with acetaminophen usage, also demonstrated an increased risk of asthma diagnosis ever (aOR, 2.08; 95% confidence interval [CI], 1.10-3.92). Family history of asthma and acetaminophen usage were risk factors for BHR. Although TLR4 was not an independent risk factor for BHR, individuals with CT+TT genotypes at the TLR4 polymorphism had an increased risk of BHR when combined with acetaminophen usage (aOR, 1.74; 95% CI, 1.03-2.94). In conclusion, acetaminophen usage may be associated with asthma and BHR in genetically susceptible subjects. This effect may be modified by polymorphism at TLR4.

Influence of Chronic Sinusitis and Nasal Polyp on the Lower Airway of Subjects Without Lower Airway Diseases

PURPOSE: Upper and lower respiratory tract pathologies are believed to be interrelated; however, the impact of upper airway inflammation on lung function in subjects without lung disease has not been evaluated. This study investigated the association of CT finding suggesting chronic sinusitis and lung function in healthy subjects without lung disease. METHODS: This was a retrospective study of prospectively collected data from 284 subjects who underwent a pulmonary function test, bronchial provocation test, rhinoscopy, and osteomeatal unit computed tomography offered as a private health check-up option. RESULTS: CT findings showed that the sinusitis group had a significantly lower FEV1/FVC ratio than subjects without sinusitis finding (78.62% vs 84.19%, P=0.019). Among the sinusitis group, subjects classified by CT findings as the extensive disease group had a slightly lower FEV1/FVC than those of the limited disease group (76.6% vs 79.5%, P=0.014) and the associations were independent of the presence of airway hyperresponsiveness. The subjects with nasal polyp had also lower FEV1 and FEV1/FVC than subjects without nasal polyp (FEV1: 100.0% vs 103.6%, P=0.045, FEV1/FVC: 77.4% vs 80.0%, P=0.005). CONCLUSIONS: CT findings suggesting chronic sinusitis and nasal polyp were associated with subclinical lower airway flow limitation even in the absence of underlying lung disease.

Forced expiratory flow between 25% and 75% of vital capacity as a predictor for bronchial hyperresponsiveness in children with allergic rhinitis

PURPOSE: Allergic rhinitis (AR) is regarded as a risk factor for asthma and bronchial hyperresponsiveness (BHR) is frequently observed in patients with AR. The purpose of this study is to analyze the characteristics of AR patients with BHR and identify factors that contribute to the incidence of BHR. METHODS: The medical records of a total of 176 children with AR were analyzed retrospectively. All patients were evaluated by performing spirometry and a methacholine challenge test. RESULTS: One hundred and fifty-five patients (88%) were classified as the BHR-negative group and 21 patients (12%) were classified as the BHR-positive group. Forced expiratory flow between 25% and 75% of vital capacity (FEF25-75 %predicted) was reduced, and total eosinphil counts, total immunoglobulin E (IgE) level, and serum specific IgE levels of Dermatophagoides pteronyssinus and Dermatophagoides farinae were higher in the BHR-positive group compared to the BHR-negative group. However, FEF25-75 was the only statistically significant predictor for the presence of BHR on multivariate logistic regression analysis. The cutoff value to distinguish BHR-positive subjects obtained from a receiver operating characteristics curve of FEF25-75 was 88.4%. A higher frequency of BHR was found in the group with a FEF25-75 less than 88.4%, and the sensitivity, specificity, positive predictive value and negative predictive value were 57.1%, 80.6%, 28.6%, and 93.3%, respectively. CONCLUSION: Reduced FEF25-75 values in children with AR can be helpful in predicting BHR. Children with low FEF25-75 in spirometric tests should be followed closely for apparent onset of clinical symptoms of asthma.

Long-term asthma remission during adolescence

Asthma is a heterogeneous disorder with a variable course, characterized by episodes of cough, wheezing and shortness of breath, reversible airflow limitation, and bronchial hyperresponsiveness (BHR). It begins early in life in many subjects, and it is well recognized that over 50% of asthmatic children go into long-term clinical remission, defined as the complete absence of asthmatic symptoms and no asthma medication for at least 24 months, during adolescence. Several studies have shown spirometric abnormalities and BHR during clinical remission. It is unknown whether these functional abnormalities, which are supposed to be indicative of asthma severity with respect to symptomatic asthma, reflect persistent airway inflammation or merely indicate residual airway damage or are related to another mechanism such as a familial predisposition. It is likely that the nature of BHR in asthma remission is not same as that in symptomatic asthma. We have shown that the former condition is associated with lower levels of blood eosinophils and eosinophilic cationic protein, a lower degree of bronchial responsiveness to exercise, and a more common formation of plateau on the dose-response curve to high-dose inhaled methacholine (i.e., limited maximal airway narrowing), compared to the latter condition. It is still controversial whether BHR in adolescents with asthma remission is reduced by inhaled corticosteroids. Better understanding of the mechanisms that lead to asthma remission, especially that seen during adolescence, is likely to lead to significant advances in our understanding of asthma pathogenesis, and should provide insights into how remission might be induced with therapy. We still have minimal understanding of the mechanism underlying BHR in adolescents with asthma remission. Elucidation of this mechanism would be an important step towards new perspectives that see remission as the next therapeutic frontier in asthma.

Relationship Between Atopy and Bronchial Hyperresponsiveness

Both atopy and bronchial hyperresponsiveness (BHR) are characteristic features of asthma. They are also found among non-asthmatic subjects, including allergic rhinitis patients and the general population. Atopy and BHR in asthma are closely related. Atopy induces airway inflammation as an IgE response to a specific allergen, which causes or amplifies BHR. Moreover, significant evidence of the close relationship between atopy and BHR has been found in non-asthmatic subjects. In this article, we discuss the relationship between atopy and BHR in the general population, asthmatic subjects, and those with allergic rhinitis. This should widen our understanding of the pathophysiology of atopy and BHR.

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.

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 Association of Obesity, Airway Hyperresponsiveness and Atopy in Chronic Cough Patients: Results of a Two-Center Study / 결핵및호흡기질환

BACKGROUND: The rising prevalence of asthma worldwide may be associated with the rising prevalence of obesity in developed nations. Although several studies have suggested a relationship between asthma and obesity, controversy still remains. The aim of this study was to examine the relationship between obesity and asthmatic factors such as atopy, eosinophilia, serum total Ig E and bronchial hyperresponsiveness in chronic cough patients. METHODS: This study was a retrospective, observational study in two centers done between January 2007 and June 2008. The subjects included individuals who had a chronic cough. We examined body mass index (BMI) to measure obesity and pulmonary function. We did a metacholine provocation test for airway hyperresponsiveness (AHR), a skin prick test for atopy, and tests for blood eosinophils and serum IgE. RESULTS: A total of 1022 subjects were included. Airway hyperresponsiveness was not related with obesity (p=0.06), and atopy incidence was significant higher in non obese patients (p=0.00). There was no significant difference in serum IgE and blood eosinophil counts between obese and non obese patients. Forced expiratory volue in one second (FEV1)/forced vital capacity (FVC) was significantly reduced in obese patients (p=0.03), but FEV1 and FVC were no significant difference between obese and non obese patients. CONCLUSION: There is no relationship between obesity and bronchial hyperresponsiveness. The nonobese group appears to have more atopy. The relationship between obesity and bronchial hyperresponsiveness and atopy need further investigation.

Avaliação espirométrica e da hiper-responsividade brônquica de crianças e adolescentes com asma atópica persistente moderada submetidos a natação / Effects of swimming on spirometric parameters and bronchial hyperresponsiveness in children and adolescents with moderate persistent atopic asthma

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.

Avaliação do grau de controle clínico, espirométrico e da intensidade do processo inflamatório na asma / Assessing clinical and spirometric control and the intensity of the inflammatory process in asthma

OBJETIVOS: Revisar o papel da avaliação clínica, da qualidade de vida, da espirometria, do teste de broncoprovocação e dos marcadores inflamatórios na avaliação da asma. FONTES DOS DADOS: Pesquisa nas bases MEDLINE e LILACS. SÍNTESE DOS DADOS: A avaliação clínica auxilia na avaliação do controle da asma e é amplamente preconizada. No entanto, os pacientes podem apresentar obstrução e inflamação das vias aéreas a despeito da normalidade clínica. A espirometria quantifica o grau de obstrução das vias aéreas e auxilia no diagnóstico, enquanto a broncoprovocação pode ser indicada na suspeita de asma com espirometria normal. Já os marcadores inflamatórios do condensado do ar exalado, do escarro induzido e do lavado broncoalveolar, além dos fragmentos da biópsia brônquica, encontram-se alterados na asma e são métodos complexos, quase sempre restritos às pesquisas. A fração exalada de óxido nítrico (FeNO) é elevada nos pacientes com asma, reprodutível e não invasiva, reduzindo-se com o tratamento. O uso da FeNO como auxiliar no ajuste de doses do corticoide inalatório tem sido estudado, mas as vantagens ainda não estão claras. CONCLUSÕES: Vários métodos são necessários para avaliar de forma acurada o controle da asma, e todos têm vantagens e limitações. A avaliação clínico-funcional é útil para o diagnóstico de asma, porém limitada para avaliar de forma precisa a intensidade do processo inflamatório nas vias aéreas. É necessário que mais estudos controlados, randomizados, com adequado poder estatístico sobre a utilidade dos marcadores inflamatórios não invasivos, especialmente a FeNO, no manejo da asma, sejam realizados para determinar sua utilidade clínica.

OBJECTIVES: To review the role of clinical assessment, quality of life assessment, spirometry, bronchial responsiveness test and inflammatory markers for asthma assessment. SOURCES: Search run on MEDLINE and LILACS. SUMMARY OF THE FINDINGS: Clinical assessment aids with assessing asthma control and is widely recommended. However, patients may have airway inflammation and obstruction despite normal clinical findings. Spirometry quantifies the degree of airway obstruction and helps with diagnosis, while the bronchial responsiveness test may be indicated for when asthma is suspected but spirometry is normal. The results of assaying the inflammatory markers in exhaled breath condensate, induced sputum, bronchoalveolar lavage and bronchial biopsy specimens are abnormal in asthma patients, but these are complex techniques almost always restricted to research. Fractional exhaled nitric oxide (FeNO) is elevated in patients with asthma, is reproducible and noninvasive and reduces with treatment. Studies have investigated using FeNO to help with adjusting inhaled corticoid dosages, but the benefits are not clear. CONCLUSIONS: A range of different methods are needed to accurately assess disease control, all with their advantages and limitations. Clinical and functional assessment is useful for diagnosing asthma, but is of limited use for precisely evaluating the intensity of the inflammatory process in the airways. More randomized and controlled studies with adequate statistical power should be carried out to investigate the true utility of noninvasive inflammatory markers, especially FeNO, for asthma management.