Exhaled nitric oxide and exercise-induced bronchospasm assessed by FEV1, FEF25-75% in childhood asthma.

The relationship between exhaled nitric oxide (eNO) and bronchial hyperresponsiveness (BHR) should be clarified. The aim of this study was to determine the relationship between eNO and exercise-induced bronchospasm (EIB) by estimation of the each lung parameter in asthmatic children who performed a bicycle ergometer exercise test. Twenty children with asthma were recruited. eNO concentration was examined by the recommended online method. To evaluate BHR, an exercise stress test was performed on a bicycle ergometer. The mean baseline eNO value was significantly correlated with the mean maximum % fall in forced expiratory volume in 1 second (FEV1), forced expiratory flow between 25% and 75% (FEF25-75%) after exercise (r=0.53, r=0.65, respectively). eNO in the EIB-positive group was significantly higher than that in the EIB-negative group by assessing FEV1, FEF25-75% (p<0.005, p=0.005). We demonstrated that the most important lung parameter assessed the occurrence of EIB by a bicycle ergometer exercise test was not only FEV1 but FEF25-75%, which significantly correlated with eNO. This suggests that not only FEV1 but FEF25-75% can be used to evaluate the correlations between BHR (EIB) and airway inflammation (eNO) in asthmatic children. A low eNO is useful for a negative predictor for EIB.     

Exhaled breath condensate nitrite/nitrate and pH in relation to pediatric asthma control and exhaled nitric oxide

BACKGROUND: Combining exhaled breath condensate (EBC) and exhaled nitric oxide (eNO) may be a useful, non-invasive method to assess airway inflammation in pediatric asthma. This cross-sectional study evaluated the relationship of both EBC nitrite/nitrate (NOx) and EBC pH with asthma control and eNO in asthmatic, normal, and atopic children. METHODS: A total of 92 children were recruited, comprising 62 with asthma, 14 with atopy only, and 16 who were normal and non-atopic. All completed a questionnaire for asthma symptoms and control. Variables measured were spirometry, EBC NOx, pH, and eNO. RESULTS: EBC NOx in those with asthma (mean 8.4 microM, CI 7.5-9.4) was significantly elevated when compared with normal (4.8 microM, CI 3.4-6.2, P = 0.0007) and atopic children (6.5 microM, CI 4.0-9.1, P = 0.02). The mean level of eNO was significantly higher in those with asthma (43.7 ppb, CI 34.7-51.1, P < 0.001) and atopy (24 ppb, CI 16.7-31.2, P < 0.05) when compared with normal children (11.5 ppb, CI 6.7-16.2). There was a significantly lower pH in those with asthma and a FEV(1) < 80% predicted (P = 0.03), but no significant overall differences in EBC pH between the three groups of children. There was a significant correlation between eNO and EBC NOx in the group as a whole, but not between eNO and EBC pH. CONCLUSIONS: Mean EBC NOx levels differ between children with asthma, atopy, and those who are normal, but it is not interchangeable with eNO. EBC pH may be an additional marker of asthma control.     

Exhaled nitric oxide predicts exercise-induced bronchoconstriction in asthmatic school children

BACKGROUND: Exercise-induced bronchoconstriction (EIB) is of particular importance in children with asthma. It is an important measure of asthma control and should be monitored by exercise testing. However, exercise testing puts a large demand on health-care resources and is therefore not widely used in routine monitoring of pediatric asthma control. The fractional concentration of exhaled nitric oxide (FeNO) also reflects uncontrolled asthma. We hypothesized that FeNO may be used for prescreening of asthmatic children to exclude those with good asthma control unlikely to have EIB, thereby reducing the need for exercise testing. OBJECTIVE: The aim of this study was to estimate the value of FeNO as a predictor of EIB in asthmatic children. METHODS: Stable outpatient asthmatic school children performed standard exercise challenge tests and measurement of FeNO. RESULTS: FeNO and response to a standardized submaximal exercise test on the treadmill were measured in 111 school children with asthma. EIB could be excluded with a probability of 90% in asthmatic children with FeNO levels < 20 parts per billion (ppb) without current inhaled corticosteroid treatment, and < 12 ppb in children with current inhaled corticosteroid treatment. CONCLUSION: Measurement of FeNO is a simple, and time- and resource-efficient tool that may be used to screen for EIB testing and therefore optimizes the resources for exercise testing in pediatric asthma monitoring.     

Exhaled Nitric Oxide and Exercise-Induced Bronchospasm Assessed by FEV1, FEF25 − 75% in Childhood Asthma

The relationship between exhaled nitric oxide (eNO) and bronchial hyperresponsiveness (BHR) should be clarified. The aim of this study was to determine the relationship between eNO and exercise-induced bronchospasm (EIB) by estimation of the each lung parameter in asthmatic children who performed a bicycle ergometer exercise test. Twenty children with asthma were recruited. eNO concentration was examined by the recommended online method. To evaluate BHR, an exercise stress test was performed on a bicycle ergometer. The mean baseline eNO value was significantly correlated with the mean maximum % fall in forced expiratory volume in 1 second (FEV₁), forced expiratory flow between 25% and 75% (FEF25-75%) after exercise (r = 0.53, r = 0.65, respectively). eNO in the EIB-positive group was significantly higher than that in the EIB-negative group by assessing FEV₁, FEF_25?75% (p < 0.005, p = 0.005). We demonstrated that the most important lung parameter assessed the occurrence of EIB by a bicycle ergometer exercise test was not only FEV₁ but FEF_25?75%, which significantly correlated with eNO. This suggests that not only FEV₁ but FEF_25?75% can be used to evaluate the correlations between BHR (EIB) and airway inflammation (eNO) in asthmatic children. A low eNO is useful for a negative predictor for EIB.     

Airway eosinophilia in children with severe asthma: predictive values of noninvasive tests

RATIONALE: Children with severe asthma experience persistent symptoms despite maximal conventional treatment. Fraction of exhaled nitric oxide (Fe(NO)) and sputum eosinophils are used as markers of airway inflammation to guide treatment with steroids, but no data are available on how reliable they are in predicting airway eosinophilia assessed bronchoscopically in these children. OBJECTIVES: To determine how Fe(NO) and sputum eosinophils predict airway eosinophilia measured in both bronchoalveolar lavage (BAL) and endobronchial biopsy. METHODS: Twenty-seven children with moderate to severe persistent asthma attempted measurement of Fe(NO) and sputum eosinophils, followed by bronchoscopy, BAL, and endobronchial biopsy within 24 h. MAIN RESULTS: Significant correlations were found between eosinophils in sputum and both BAL eosinophils (n = 20, r = 0.45, p = 0.045) and Fe(NO) (n = 23, r = 0.42, p = 0.049). The relationship between Fe(NO) and BAL eosinophils was also significant with a stronger correlation (n = 24, r = 0.54, p = 0.006). The positive predictive value (PPV) for increased sputum eosinophil percentage (> 2.5%) to detect elevated eosinophils in BAL (> 1.19%) was 75%; the negative predictive value (NPV) was 63%. All patients with both increased sputum eosinophils and an elevated Fe(NO) value (> 23 ppb) had elevated eosinophils in BAL (PPV, 100%); the NPV of these two markers was 65%. Eight of nine patients without any sputum eosinophils had normal subepithelial eosinophil numbers (< 1.2%; NPV, 89%). However, the PPV of any sputum eosinophils for increased subepithelial eosinophilia was only 36.4%. CONCLUSIONS: There was moderate agreement between both Fe(NO) and sputum eosinophils and BAL eosinophils. There was good NPV, but only poor PPV for these markers for mucosal eosinophilia.     

Relationship between exhaled nitric oxide levels and compliance with inhaled corticosteroids in asthmatic children

Levels of exhaled nitric oxide (eNO) are elevated in subjects with asthma and fall in response to oral or inhaled steroids. This study explored the possibility the measurement of eNO levels could be used to identify subjects who were not adhering to their treatment regimen. Twenty children with asthma attending the respiratory clinic were recruited. Each attended on four occasions 1 month apart when eNO levels were measured. A data logger attached to a pressurised metered dose inhaler was used to objectively monitor use of inhaled corticosteroids (ICSs). The correlation between day and dose compliance with eNO was assessed. The data demonstrated a weak but non-significant correlation between eNO and both day (r = 0.055, P = 0.67) and dose (r = 0.153, P = 0.23). A recorded value of eNO less than 12 was associated with day compliance rates of 3-97%. Of the 19 recorded eNO values greater than 12 ppb almost 80% were from subjects with a day compliance of less than 50% during the preceding month. Of the four values greater than 12 ppb and day compliance > 60% one subject had a poor inhaler technique, one had a mild viral exacerbation and one appeared to be associated with increase pollen exposure. The measurement of eNO may prove to be a useful tool in helping to manage children with asthma but further work is required to define its precise role. Elevated eNO levels in asthmatic children taking ICSs are likely to reflect poor compliance but confounding factors such as disease activity and inhaler technique need to be carefully considered.     

Maternal atopic disease modifies effects of prenatal risk factors on exhaled nitric oxide in infants

In a prospective healthy birth cohort, we determined whether levels of exhaled nitric oxide (eNO) in healthy unselected infants at the age of 1 month were associated with maternal atopic disease and prenatal and early postnatal environmental exposures. Tidal eNO was measured in 98 healthy, unsedated infants (35 from mothers with atopy) (mean age +/- SD, 36.0 +/- 6.2 days) and was compared with histories taken in standardized interviews. eNO was higher in males compared with females (17.7 vs. 14.6 ppb, p = 0.042) and infants exposed to postnatal maternal smoking (+4.4 ppb, p = 0.027), adjusting for weight and tidal breathing parameters. Prenatal tobacco exposure was associated with higher eNO (+12.0 ppb, p = 0.01) in infants of mothers with asthma and lower eNO (-5.7 ppb) in infants of mothers without asthma (p for interaction < 0.0001). Coffee consumption in pregnancy decreased eNO (-6.0 ppb, p = 0.008) only in children of mothers with atopy (p for interaction = 0.015). Paternal atopy had no influence. In the early phase of immunologic development, before the onset of infections and allergic disease, the effect of prenatal or early postnatal environmental factors on eNO was modified by the presence of maternal atopic disease. This underlines the complex interaction of maternal and environmental factors in the development of airway disease.     

Comparison of exhaled nitric oxide,serum eosinophilic cationic protein,and soluble interleukin-2 receptor in exacerbations of pediatric asthma

The hypotheses tested in this study were that during acute asthma exacerbations (1) exhaled nitric oxide concentrations [eNO] are a more sensitive, noninvasive indicator of asthma disease activity than serum markers of inflammation such as eosinophil cationic protein (ECP) or soluble interleukin 2 receptor (sIL2R), and (2) elevated [eNO] are reduced after treatment with glucocorticoids (GC). Peak eNO levels were measured by chemiluminescence during slow expiration. Seven asthmatic subjects (mean age 11 yrs; mean morning FEV1 65% predicted) receiving inhaled GC, and with no radiographic evidence of acute sinusitis, were studied before and after a course of oral GC. Measurements of [eNO], ECP and sIL2R levels, and FEV1% were obtained before and after a course of GC. Six atopic nonasthmatic subjects (mean age 12 years; mean FEV1 94% predicted) and seven normal subjects (mean age 13 years; mean FEV1 100% predicted) were studied. The mean peak [eNO] level (parts per billion: ppb) for the asthma subjects before treatment (52 ± 5 ppb SEM) was greater than the value for both nonasthmatic atopic and normal subjects (16 ± 2 ppb and 14 ± 2 ppb SEM, respectively; P < 0.0001). There was no significant difference in ECP or sIL2R values between asthmatic subjects and either atopic or normal subjects (P > 0.05). Baseline pre-GC treatment ECP levels in the asthmatic subjects were significantly higher (P < 0.002) than post-GC treatment values. The mean peak [eNO] level in the asthmatic subjects declined after oral GC treatment to 14 ± 1 ppb (P < 0.0002) and was less than 2 ppb different from either control group (P > 0.75). We conclude that [eNO] is a more sensitive marker of asthma disease activity than ECP and sIL2R levels. In addition, [eNO] appears to be a more useful indicator of the beneficial response to GC therapy than these other measurements in pediatric asthma. Pediatr. Pulmonol. 1997; 24:305–311. © 1997 Wiley-Liss, Inc.     

呼出气一氧化氮在儿童支气管哮喘诊疗中的应用进展

目的检测典型支气管哮喘（简称哮喘）以及咳嗽变异性哮喘（cVA）患儿中呼出气一氧化氮（eNO）的水平以及和肺功能（PEF）两者的相关性,并探讨eNO检测在儿童哮喘以及CVA中的诊疗价值。方法采用电化学法对6～16岁患有典型哮喘（n=23）、CVA（n=29）的患者进行eNO测定,同时测定呼气峰流速（PEF）。37例无特异性疾病史和家族过敏史,且近两周内无急性呼吸道感染史的儿童作为对照组。结果典型哮喘组,CVA组的eNO水平均明显高于对照组（P〈0．01）,典型哮喘组和CVA的PEF水平均明显低于对照组（P〈0．05）;CVA组的eNO水平高于典型哮喘组（P〈0．05）,PEF水平高于典型哮喘组（P〈0．05）;但是eNO水平与PEF水平无相关性（r=0．061,P〉0．05）;29例CVA患者中,有21例eNO水平〉30ppb（正常水平为5～25ppb）。给予上述29例患者舒利迭或是都保治疗1个月,发现21例eNO水平偏高的患者中,有19例反复咳嗽症状明显减轻,2例症状改善。其余8例,有3例症状减轻,其余5例未见明显疗效。结论典型哮喘患者以及CVA患者的eNO水平均较高,eNO水平和PEF水平无相关性;CVA患者若eNO增高,对激素治疗有效。     

Exhaled nitric oxide and asthma in young children

Exhaled nitric oxide (eNO) has been used to diagnose asthma in adults and children using either the slow vital capacity method (SVCm) or, in younger children, the tidal breathing method (TBm). Adenosine 5'-monophosphate (AMP) challenge also has been found to be a sensitive and specific test for the diagnosis of asthma. In the present study, we used the AMP provocation concentration that caused wheezing (PCW) to confirm the diagnosis of asthma (PCW < or = 200 mg/mL). We studied 36 children (2-7 years) with mild intermittent asthma, 13 children (3-7 years) with moderate persistent asthma treated with inhaled steroids, 20 nonasthmatic children (2-7 years) with chronic cough and recurrent pneumonia, and 15 healthy children (4-6 years). Expired gas was collected in collection bags by the TBm, and eNO was measured. We evaluated the efficacy of eNO values in diagnosing asthma. The mean eNO level of the mild intermittent asthmatic children (5.6 +/- 0.4 ppb) not receiving inhaled corticosteroids was significantly higher (ANOVA P < 0.0001) than that of the moderate persistent asthmatics who were treated with inhaled steroids, the nonasthmatic children with chronic cough, and the group of healthy children (3.7 +/- 0.6 ppb, P < 0.05; 3.2 +/- 0.3 ppb, P < 0.001; 2.2 +/- 0.2 ppb, P < 0.001, respectively). The points of intersection for sensitivity and specificity curves of eNO to differentiate mild intermittent asthmatics from nonasthmatic children with chronic cough and from healthy children were 77% and 88% for eNO values of 3.8 ppb and 2.9 ppb, respectively. We conclude that eNO collected by the TBm can differentiate steroid-naive young children with intermittent asthma from healthy children, from nonasthmatic children with chronic cough, and from asthmatic children treated with inhaled steroids.     

Exhaled Nitric Oxide Levels are not Correlated with Eczema Severity in Chinese Children with Atopic Dermatitis

Asthma is a common atopic disease associated with atopic dermatitis (AD) and allergic rhinitis (AR). Exhaled nitric oxide level (eNO) has been found to be an interesting noninvasive marker of disease severity in children with asthma. However, it is uncertain if eNO may be confounded by any coexisting AD or AR. In this study, eNO in Chinese children with moderate-to-severe AD and no asthma symptoms (n = 53) was measured online by a chemiluminescence analyzer. Severity of AD was assessed using the objective SCORing-Atopic-Dermatitis score and coexisting allergic rhinitis with the Allergic-Rhinitis-Score (ARS). Patients with active symptoms of asthma or inhaled/intranasal corticosteroids were excluded. There was no difference in eNO between genders and no correlation between eNO and AD severity regardless of ARS or bronchial reactivity status. ENO appears to be a noninvasive marker whose level is independent of the two atopic diseases of AD and AR in children old enough to perform exhalation maneuver.     

Exhaled Nitric Oxide Levels are not Correlated with Eczema Severity in Chinese Children with Atopic Dermatitis

Asthma is a common atopic disease associated with atopic dermatitis (AD) and allergic rhinitis (AR). Exhaled nitric oxide level (eNO) has been found to be an interesting noninvasive marker of disease severity in children with asthma. However, it is uncertain if eNO may be confounded by any coexisting AD or AR. In this study, eNO in Chinese children with moderate-to-severe AD and no asthma symptoms (n = 53) was measured online by a chemiluminescence analyzer. Severity of AD was assessed using the objective SCORing-Atopic-Dermatitis score and coexisting allergic rhinitis with the Allergic-Rhinitis-Score (ARS). Patients with active symptoms of asthma or inhaled/intranasal corticosteroids were excluded. There was no difference in eNO between genders and no correlation between eNO and AD severity regardless of ARS or bronchial reactivity status. ENO appears to be a noninvasive marker whose level is independent of the two atopic diseases of AD and AR in children old enough to perform exhalation maneuver.     

Exhaled nitric oxide at school age in prematurely born infants with neonatal chronic lung disease

Prematurely born infants with neonatal chronic lung disease (CLD) have increased respiratory morbidity and bronchial obstruction at school age. To evaluate the possible inflammatory basis of lung function abnormalities, we studied 40 children, 7.5-9.6 years of age, born very prematurely (birth weights, 600-1,575 g) and 14 nonatopic term-born controls, using flow-volume spirometry and exhaled nitric oxide (eNO) measurements. In children born prematurely, eNO was significantly higher in atopics than in nonatopics (respective means, 14.8 vs. 6.3 ppb, P = 0.02). Nonatopic prematurely born infants did not differ significantly from controls (means, 6.3 vs. 6.4 ppb, P = ns). Of the 27 nonatopic children not on regular glucocorticoid inhalations, 9 had a history of CLD. Spirometry indicated bronchial obstruction and values that were significantly lower in prematurely born infants with or without CLD than in controls, and they were lower in the CLD than the non-CLD group. However, no significant differences were observed in eNO levels between CLD, non-CLD, and control groups (means, 6.8, 5.9, and 6.4 ppb, P = ns). In nonatopic schoolchildren born very prematurely and with a history of CLD, we found no evidence of airway inflammation associated with increased eNO concentrations. Neither were eNO levels associated with severity of chronic lung disease, as determined by conventional lung function tests. eNO levels were higher in atopic children born prematurely than in controls.     

Expired nitric oxide and airway obstruction in asthma patients with an acute exacerbation

Expired nitric oxide (eNO) is a marker of airway inflammation that is increased in asthma. The present study was undertaken to examine the clinical utility of eNO as an aid in the assessment of asthma in the emergency department (ED). Fifty-two adult patients with acute asthma, 53 age- and sex-matched controls, and eight patients with stable asthma were enrolled. Subjects performed spirometry, their eosinophil counts and serum total IgE were measured, and a sample of mixed VC expirate was collected for measurement of NO. Mixed expired NO was 8.2 +/- 0.5 ppb in controls, 8.8 +/- 1.5 ppb in patients with stable asthma, and 15.0 +/- 1.0 ppb in patients with acute asthma. A significant difference in eNO was observed in patients with acute asthma and controls (p < 0.001). Twenty-three of the 52 patients with acute asthma versus two of 53 controls had an eNO >/= 15 ppb (p < 0.001). Expired NO concentration correlated with FEV1% (r = -0.42, p < 0.001) and with the peripheral blood eosinophil count (r = 0.34, p < 0.001) in the group of 60 patients with acute and stable asthma. The sensitivity of eNO > 10 ppb and eosinophilia (> 200 cells/microliter) was 90% in predicting airway obstruction (FEV1/FVC < 0. 8). No relationship of eNO was found to serum IgE, self- reported smoking, or glucocorticoid use. Measurement of eNO is a promising clinical tool for assessing acute asthma.     

Does bronchial hyperresponsiveness in childhood predict active asthma in adolescence?

Rationale: Bronchial hyperresponsiveness (BHR) is an important, but not specific, asthma characteristic. Objectives: We aimed to assess the predictive value of BHR tested by methacholine and exercise challenge at age 10 years for active asthma 6 years later. Methods: From a Norwegian birth cohort, 530 children underwent methacholine challenge and exercise-induced bronchoconstriction (EIB) test (n = 478) at 10 years and structured interview and clinical examination at age 16 years. The methacholine dose causing 20% reduction in FEV(1) (PD(20)) and the reduction in FEV(1) (%) after a standardized treadmill test were used for BHR assessment. Active asthma was defined with at least two criteria positive: doctor's diagnosis of asthma, symptoms of asthma, and/or treatment for asthma in the last year. Measurements and Main Results: PD(20) and EIB at 10 years of age increased the risk of asthma (β = 0.94 [95% confidence interval (CI), 0.92-0.96] per μmol methacholine and β = 1.10 [95% CI, 1.06-1.15] per %, respectively). Separately the tests explained 10 and 7%, respectively, and together 14% of the variation in active asthma 6 years later. The predicted probability for active asthma at the age of 16 years increased with decreasing PD(20) and increasing EIB. The area under the curve (receiver operating characteristic curves) was larger for PD(20) (0.69; 95% CI, 0.62-0.75) than for EIB (0.60; 95% CI, 0.53-0.67). Conclusions: BHR at 10 years was a significant but modest predictor of active asthma 6 years later, with methacholine challenge being superior to exercise test.     

The Value of Exhaled Nitric Oxide in Predicting Bronchial Hyperresponsiveness in Children

Reduced attention span and motor skills in children limit the practicability of bronchial provocation tests. To assess exhaled nitric oxide (FeNO) as a surrogate for bronchial hyperresponsiveness (BHR) in children with possible reactive airway disease, FeNO was measured using the single-breath method in 169 successive outpatients 11 ± 5 years of age before lung function testing and subsequent bronchial provocation by exercise (n = 165) and methacholine (n = 134). Baseline forced expiratory volume in 1 second (FEV₁) less than 80% of predicted and/or BHR were seen in 59%. FeNO correlated weakly with PD₂₀ to methacholine (r = ?0.24, p < 0.05), but not with the change in FEV₁ due to exercise-induced bronchoconstriction (EIB) (r = 0.1, p > 0.05). The negative predictive value of FeNO less than 10 ppb for EIB was 94%, but overall accuracy for predicting BHR was low. Measurement of FeNO is not a substitute for bronchial provocation in children.     

Prolonged effect of montelukast in asthmatic children with exercise-induced bronchoconstriction

Accumulating evidence shows that cysteinyl leukotrienes are the most important mediators in exercise-induced bronchoconstriction (EIB). In contrast to several studies in adults, there are few long-term studies of leukotriene receptor antagonists (LTRAs) in children with EIB. The aim of this study was to assess the prolonged clinical and bronchoprotective effects of montelukast in asthmatic children with EIB. We randomly assigned 64 asthmatic children with EIB. Forty subjects received montelukast (5 mg/day), and 24 subjects received placebo once daily for 8 weeks. Exercise challenge was performed before and after 8 weeks of treatment. Of the 40 patients in the montelukast group, 28 patients crossed over after 8 weeks. The response was measured as asthma symptom score, maximum percent fall in forced expiratory volume in 1 sec (FEV(1)) from pre-exercise baseline, and time to recovery of FEV(1) to within 10% of pre-exercise baseline (time to recovery). Following 8 weeks of treatment with montelukast, the montelukast group compared with placebo showed significant improvements in all endpoints, including asthma symptom score, maximum percent fall in FEV(1) after exercise, and time to recovery. In the cross-over group, even 8 weeks after stopping montelukast treatment, all endpoints were significantly and persistently improved. These results indicate that montelukast provides clinical protection from airway hyperresponsiveness in asthmatic children with EIB, and suggest that LTRAs may be useful for the long-term management of asthmatic children with EIB.     

Maximal Airway Narrowing on the Dose-Response Curve to Methacholine Is Increased After Exercise-Induced Bronchoconstriction

The changes in airway responsiveness between before and after exercise in asthma are not well defined. We investigated the effect of exercise on PC20 (bronchial sensitivity) and maximal airway narrowing (MAN) on the dose-response curve to methacholine in 56 mildly asthmatic children. High-dose methacholine inhalation tests were performed before and 7 hr after exercise challenge. Methacholine PC20 was not changed by exercise, irrespective of exercise-induced bronchoconstriction (EIB). However, the subjects with (+)EIB displayed increased MAN after exercise, whereas those with (±)EIB or (—)EIB did not. The results showed that EIB may be followed by increased MAN but not by the change of bronchial sensitivity.     

Applicability of interrupter resistance measurements for evaluation of exercise-induced bronchoconstriction in children

The interrupter technique is a noninvasive method for measuring air-flow resistance during tidal breathing. This method requires minimal cooperation, and is therefore promising for use in uncooperative children. The aim of this study was to evaluate applicability interrupter resistance (Rint) measurements in the assessment of exercise-induced bronchoconstriction (EIB). Fifty children aged 5-12 years with mild to moderate asthma were tested by exercise challenge, consisting of free outdoor running for 6 min at 80-90% of maximal predicted heart rate for age. Rint, forced expiratory volume in 1 sec (FEV1), and peak expiratory flow (PEF) were measured before and 10 min after exercise. EIB was defined as a fall of 10% or more in FEV1 after exercise. The repeatability of Rint was assessed, and its response to exercise challenge was compared with current standardized methods. The mean intermeasurement coefficient of variation was 4.6% (SD, +/- 3.0%), and the repeatability coefficient was 0.056 kPa/l/sec. Eighteen (36%) of the 50 children had EIB after exercise challenge test. The area under the receiver-operating characteristic (ROC) curve was 0.953 (95% confidence interval, 0.853-0.992; P < 0.001), and the optimal Rint cutoff value was 15.2%, producing a sensitivity of 88.9% and a specificity of 96.9%. The positive and negative predictive values were 94.1% and 93.9%, respectively. The kappa value between FEV1 and Rint was 0.83. The repeatability of Rint measurements was good, and the results of exercise challenge tests using Rint measurements have excellent agreement with the current standardized methods to detect EIB. Considering that only minimal comprehension and coordination are needed without forced breathing technique, the Rint measurement can provide a useful alternative for assessment of EIB in children unable to perform reliable spirometry.     

Diagnostic Exercise Challenge Testing

This article reviews the diagnostic challenge methods—both exercise and surrogate—for diagnosis of exercise-induced bronchoconstriction (EIB) and EIB with known asthma. Indirect challenges that release the entire repertoire of mediators representative of EIB and asthma are more specific for diagnosis and are recommended over direct challenges such as methacholine challenge, which are sensitive but nonspecific. Self-reported history and empiric therapeutic trials are not adequate for diagnosis of EIB with or without known asthma. Objective pulmonary function documentation with bronchodilator reversibility or exercise or surrogate challenge are optimal for diagnosis of EIB or EIB with known asthma. Such objective pulmonary function documentation is optimal for the proper management and healthy lifestyle of the exercising athlete or individual.