Response Of Asthmatic Children Research Articles

Ambient air pollution, lung function, and airway responsiveness in asthmatic children

Ambient air pollution, lung function, and airway responsiveness in asthmatic children

Ambient air pollution, lung function, and airway responsiveness in asthmatic children

Although ambient air pollution has been linked to reduced lung function in healthy children, longitudinal analyses of pollution effects in asthmatic patients are lacking. We sought to investigate pollution effects in a longitudinal asthma study and effect modification by controller medications. We examined associations of lung function and methacholine responsiveness (PC20) with ozone, carbon monoxide (CO), nitrogen dioxide, and sulfur dioxide concentrations in 1003 asthmatic children participating in a 4-year clinical trial. We further investigated whether budesonide and nedocromil modified pollution effects. Daily pollutant concentrations were linked to ZIP/postal code of residence. Linear mixed models tested associations of within-subject pollutant concentrations with FEV1 and forced vital capacity (FVC) percent predicted, FEV1/FVC ratio, and PC20, adjusting for seasonality and confounders. Same-day and 1-week average CO concentrations were negatively associated with postbronchodilator percent predicted FEV1 (change per interquartile range, -0.33 [95% CI, -0.49 to -0.16] and -0.41 [95% CI, -0.62 to -0.21], respectively) and FVC (-0.19 [95% CI, -0.25 to -0.07] and -0.25 [95% CI, -0.43 to -0.07], respectively). Longer-term 4-month CO averages were negatively associated with prebronchodilator percent predicted FEV1 and FVC (-0.36 [95% CI, -0.62 to -0.10] and -0.21 [95% CI, -0.42 to -0.01], respectively). Four-month averaged CO and ozone concentrations were negatively associated with FEV1/FVC ratio (P<.05). Increased 4-month average nitrogen dioxide concentrations were associated with reduced postbronchodilator FEV1 and FVC percent predicted. Long-term exposures to sulfur dioxide were associated with reduced PC20 (percent change per interquartile range, -6% [95% CI, -11% to -1.5%]). Treatment augmented the negative short-term CO effect on PC20. Air pollution adversely influences lung function and PC20 in asthmatic children. Treatment with controller medications might not protect but rather worsens the effects of CO on PC20. This clinical trial design evaluates modification of pollution effects by treatment without confounding by indication.

The bronchodilator response as a predictor of inhaled corticosteroid responsiveness in asthmatic children with normal baseline spirometry

Although inhaled corticosteroids (ICS) are considered first line controller therapy in children with persistent asthma, heterogeneity of the ICS response can be an important clinical problem. The purpose of this study is to determine the value of the bronchodilator response (BDR) in identifying the ICS responder and establish the optimal BDR cut-point that could be particularly useful in the clinic setting when baseline spirometry is normal. Mexican American asthmatic children, 5-18 years, with normal baseline spirometry who required low dose (step 2), or medium dose (step 3) ICS therapy were evaluated by skin prick test for atopy, and pre- and post-bronchodilator spirometry. ICS responders were defined by a ≥7.5% improvement in the FEV1 following 4-6 weeks of therapy. The optimal cut-point was determined by Receiver Operator Characteristic (ROC) curves as the best balance between sensitivity and specificity. There were 34.8% of the 132 study patients who were ICS responders. ROC curves showed the BDR ≥10% to be an optimal cut-point with sensitivity 46%, specificity 76%, positive predictive value (PPV) 50%, and negative predictive value (NPV) 72%. Atopic females with a BDR ≥10% had a PPV of 73%. The composite phenotype of female gender, atopic, and the BDR of ≥10% identified 73% as ICS responders compared to 50% in our overall population with a BDR of ≥10% alone, with minimal false positives. We suggest that the BDR in conjunction with gender and atopic status be considered as potentially useful predictors of the ICS responder, particularly when baseline spirometry is normal.

RUNX transcription factors: association with pediatric asthma and modulated by maternal smoking.

Intrauterine smoke exposure (IUS) is a strong risk factor for development of airways responsiveness and asthma in childhood. Runt-related transcription factors (RUNX1-3) have critical roles in immune system development and function. We hypothesized that genetic variations in RUNX1 would be associated with airway responsiveness in asthmatic children and that this association would be modified by IUS. Family-based association testing analysis in the Childhood Asthma Management Program genome-wide genotype data showed that 17 of 100 RUNX1 single-nucleotide polymorphisms (SNPs) were significantly (P < 0.03-0.04) associated with methacholine responsiveness. The association between methacholine responsiveness and one of the SNPs was significantly modified by a history of IUS exposure. Quantitative PCR analysis of immature human lung tissue with and without IUS suggested that IUS increased RUNX1 expression at the pseudoglandular stage of lung development. We examined these associations by subjecting murine neonatal lung tissue with and without IUS to quantitative PCR (N = 4-14 per group). Our murine model showed that IUS decreased RUNX expression at postnatal days (P)3 and P5 (P < 0.05). We conclude that 1) SNPs in RUNX1 are associated with airway responsiveness in asthmatic children and these associations are modified by IUS exposure, 2) IUS tended to increase the expression of RUNX1 in early human development, and 3) a murine IUS model showed that the effects of developmental cigarette smoke exposure persisted for at least 2 wk after birth. We speculate that IUS exposure-altered expression of RUNX transcription factors increases the risk of asthma in children with IUS exposure.

Forced expiratory flow between 25% and 75% of vital capacity and FEV1/forced vital capacity ratio in relation to clinical and physiological parameters in asthmatic children with normal FEV1 values

The assumption that the assessment of forced expiratory flow between 25% and 75% of vital capacity (FEF(25-75)) does not provide additional information in asthmatic children with normal FEV(1) percent predicted has not been adequately tested. We sought to determine whether the measurement of FEF(25-75) percent predicted offers advantages over FEV(1) percent predicted and FEV(1)/forced vital capacity (FVC) percent predicted for the evaluation of childhood asthma. This is a secondary analysis of data from the Pediatric Asthma Controller Trial and the Characterizing the Response to a Leukotriene Receptor Antagonist and Inhaled Corticosteroid trials. Pearson correlation coefficients, Pearson partial correlation coefficients, canonical correlations, and receiver operating characteristic (ROC) curves were constructed. Among 437 children with normal FEV(1) percent predicted, FEF(25-75) percent predicted, and FEV(1)/FVC percent predicted were (1) positively correlated with log(2) methacholine PC(20), (2) positively correlated with morning and evening peak expiratory flow percent predicted, and (3) negatively correlated with log(10) fraction of exhaled nitric oxide and bronchodilator responsiveness. Pearson partial correlations and canonical correlations indicated that FEF(25-75) percent predicted was better correlated with bronchodilator responsiveness and log(2) methacholine PC(20) than were FEV(1) percent predicted or FEV(1)/FVC percent predicted. In the ROC curve analysis, FEF(25-75) at 65% of predicted value had a 90% sensitivity and a 67% specificity for detecting a 20% increase in FEV(1) after albuterol inhalation. FEF(25-75) percent predicted was well correlated with bronchodilator responsiveness in asthmatic children with normal FEV(1). FEF(25-75) percent predicted should be evaluated in clinical studies of asthma in children and might be of use in predicting the presence of clinically relevant reversible airflow obstruction.

Cardiopulmonary responses of asthmatic children to exercise: Analysis of systolic and diastolic cardiac function

The aim of this study was to evaluate aerobic exercise capacity, cardiac features and function in a group of asthmatic children who underwent medical treatment. Dynamic exercise testing was done to evaluate aerobic exercise capacity. Echocardiography was performed to identify the effects that asthma-induced pulmonary changes have on respiratory and cardiac function in these patients. The study involved 20 asthmatic children (aged 7-16 years) who were followed at our hospital and 20 age- and sex-matched, healthy control subjects. Sixteen of the asthma cases were moderate and four were severe. All 40 subjects underwent similar series of assessments: multiple modes of echocardiography, treadmill stress testing, pulmonary function testing. The means for forced expiratory volume in 1 sec, forced expiratory flow 25-75%, maximal voluntary ventilation and inspiratory capacity were all significantly higher in the control group. The patient group had significantly lower mean maximal oxygen uptake and mean endurance time than the controls but there were no significant differences between the groups with respect to respiratory exchange ratio or the ventilatory threshold. The control group means for ejection fraction, fractional shortening, left ventricular mass, and left ventricular mass index were significantly higher than the corresponding patient group results. Children with moderate or severe asthma have lower aerobic capacity than healthy children of the same age. The data suggest that most of these children have normal diastolic cardiac function, but exhibit impaired systolic function and have lower LVM than healthy peers of the same age.

The Use of Oscillometry as a Measure of Airway Responsiveness in Asthmatic Children After Histamine and Methacholine Bronchoprovocation with Dosimeter-MedicAid and DeVilbiss Nebulizers

To explore the use of oscillometry as a measure of airway responsiveness, 69 asthmatic children underwent histamine and methacholine bronchoprovocation using dosimeter-MedicAid (Jaeger Co.; Germany) and DeVilbiss nebulizers (DeVilbiss, Bornemouth; England). The mean increase in R5 resistance in challenge testing measured after methacholine with the dosimeter-MedicAid nebulizer was 77.14% compared with 65.05% using histamine. Using the dosimeter-DeVilbiss nebulizer, the mean increases in R5 resistance following methacholine and histamine testing were 57.50% and 59.36%, respectively. The resistance R5 over R20 significantly correlated with forced expiratory volume in 1 second (FEV1). The MedicAid produced a more aggressive challenge than the DeVilbliss nebulizer. Oscillometry can be used to monitor the level of airway hyperresponsiveness following bronchoprovocation tests.

Clara cell protein 16 (CC16) gene polymorphism influences the degree of airway responsiveness in asthmatic children

Background: Several studies have indicated linkage of chromosome 11q12-13 to asthma and associated traits. Among other candidate genes, the Clara cell protein 16 (CC16) gene maps to this region. CC16 is expressed in the bronchial epithelium and exhibits potent anti-inflammatory properties. A single-nucleotide polymorphism (SNP) in the CC16 gene (A38G) was previously associated with asthma. Objective: We evaluated the role of the CC16 SNP in pediatric asthma and asthma severity in 2 German study populations. Methods: The German Multicenter Allergy Study (MAS) cohort (n = 872, 94 asthmatic patients) and 112 allergic asthmatic children recruited in Freiburg, Germany, were included in the pres-ent study. Histamine provocations were performed at the age of 7 years in the MAS cohort to determine bronchial hyperreactivity; in the Freiburg study population a standardized exercise-induced decrease in FEV1 was evaluated. For genotyping, melting-curve analysis and restriction enzyme digestion were applied. Results: No association of the CC16*38A allele with asthma could be observed in either study population. However, in asthmatic subjects (MAS cohort) PC20FEV1 values were significantly lower in individuals homozygous or heterozygous for the CC16*38A allele compared with those in subjects with the CC16*38GG genotype (P < .05 and P < .03, respectively). Similarly, allergic asthmatic patients in the Freiburg cohort showed a significantly greater decrease in FEV1 after exercise when homozygous for the CC16*38A allele compared with that seen in asthmatic patients with the *38AG or *38GG genotype (P < .04 and P = .006, respectively). Conclusion: We conclude that the CC16*A38G SNP influences bronchial hyperreactivity and might be a genetic determinant of asthma severity in German children. (J Allergy Clin Immunol 2003;111:515-9.)

Agreement between spirometry and tracheal auscultation in assessing bronchial responsiveness in asthmatic children

We have recently found that changes in lung sounds correspond well with a 20% fall in the forced expiratory volume in 1 s (FEV 1) after methacholine challenge in asthmatic children. Up to now, little was known about the agreement between a 20% fall in FEV 1 and a change in lung sounds after repeated bronchial challenge. In this study we investigated the agreement between the total cumulative histamine dose causing a fall in FEV 1 of 20% or more (PD 20) and the detection of a change in lung sounds (PD lung sounds) after two bronchial challenges on different occasions in asthmatic children. Fifteen asthmatic children (nine boys), mean age 10·8 years (range 9–15), were studied. All performed two histamine challenge tests on 2 days, with a 24 h to 1 week interval. Lung sounds were recorded over the trachea for 1 min and stored on tape. Lung sounds were analysed directly and also scored from the tape-recording by a blinded second investigator. Wheeze, cough, and an increase in respiratory rate were assessed. The relationship between PD 20 and PD lung sounds was calculated by Bland and Altman's measurement of agreement. Eleven children had a positive challenge test (PD 20 ≤ 16·0 mg ml −1) on both test days; four had a positive challenge on one test day. In 24 out of 26 positive challenges, wheeze, cough, prolonged expiration and/or increased respiratory rate were detected one dose-step before, or at the dose-step of histamine that induced a fall in FEV 1 of 20% or more. In two challenges, PD 20 was not detected by a change in lung sounds. In four out of four negative challenges (PD 20 >16·0 mg ml −1) no change in lung sounds could be detected. Good agreement between the logarithm of PD 20 and the logarithm of PD lung sounds was found on both test days. The mean difference was 0·04 and the limits of agreement ( d ± 2 sd of the differences) were 0·04 ± 0·41. A good agreement was found between the total cumulative histamine dose causing a fall in FEV 1 of 20% or more and the detection of a change in lung sounds after two bronchial challenges on different occasions in asthmatic children.

Reevaluation of the Relationship Between Within-Day Bronchial Variability and Bronchial Responsiveness in Asthmatic Children

ABSTRACT: Earlier studies demonstrated a correlation between diurnal bronchial variability and bronchial responsiveness (BR) in asthmatic patients. However, since the most severe bronchial obstruction tends to occur from midnight to early morning, diurnal bronchial variability might underestimate within-day bronchial variability. This study was undertaken to reevaluate the correlation after assessing more precisely the within-day variability of bronchial caliber in 43 children with episodic asthma (23 boys, 20 girls), aged 8–12 years. Seven FEV1 measurements were made every 4 h between 10:00 and 10:00 for 2 consecutive days. The coefficient of variation (CV) of the last six FEV1 was defined as the amplitude. Just after measurement of FEV1 at 10:00 on day 2, measurements of BR to house-dust allergen, histamine, and 7-min free running were made in 14, 14, and 15 patients, respectively. The BR was expressed as the percent change in FEV1 from the baseline value in house-dust inhalation and running challenges, and as the provocative concentration causing a 20% fall in FEV1 (PC20), transformed into a logarithmic scale, in histamine challenge. There were significant correlations between CV [mean (SD), 8.1 (5.3)%] and BR to house-dust [mean (SD),-19.0 (11.8)%] (r =-0.663, p< 0.01), and between CV [mean (SD), 7.4 (5.5)%] and histamine PC20 (geometric mean, 0.38 mg/ml) (r =-0.661, p = 0.01). There was a marginally significant correlation between CV [mean (SD), 6.4 (3.7)%] and BR to running [mean (SD), 28.5 (16.6)%] (r =-0.496, 0.05 < p < 0.1). These re-suits confirmed the reliability of earlier studies that suggested that the bronchial variability may be one of clinical indices of BR to various stimuli in asthmatic patients.

Use of tracheal auscultation for the assessment of bronchial responsiveness in asthmatic children.

It can be difficult to assess bronchial responsiveness in children because of their inability to perform spirometric tests reliably. In bronchial challenges lung sounds could be used to detect the required 20% fall in the forced expiratory volume in one second (FEV1). A study was undertaken to determine whether a change in lung sounds corresponded with a 20% fall in FEV1 after methacholine challenge, and whether the occurrence of wheeze was the most important change. Fifteen children with asthma (eight boys) of mean age 10.8 years (range 8-15) were studied. All had normal chest auscultation before the methacholine challenge test. Lung sounds were recorded over the trachea for one minute and stored on tape. They were analysed directly and also scored blindly from the tape recording by a second investigator. Wheeze, cough, increase in respiratory rate, and prolonged expiration were assessed. The total cumulative methacholine dose causing a fall in FEV1 of 20% or more (PD20) was detected in 12 children by a change in lung sounds - in four by wheeze and in eight by cough, increased respiratory rate, and/or prolonged expiration. In two subjects altered lung sounds were detectable one dose step before PD20 was reached. In three cases in whom no fall in FEV1 occurred, no change in lung sounds could be detected at the highest methacholine dose. Changes in lung sounds correspond well with a 20% fall in FEV1 after methacholine challenge. Wheeze is an insensitive indicator for assessing bronchial responsiveness. Cough, increase in respiratory rate, and prolonged expiration occurs more frequently.

Acute effect of passive smoking on lung function and airway responsiveness in asthmatic children

The effect of a 1-hour exposure at rest during passive cigarette smoking (20 ppm CO) or Sham was investigated in 11 children with bronchial asthma (age range, 8-13 yr; ten boys, one girl). Nine of the subjects were on regular therapy with inhaled beta 2-agonists and disodium cromoglycate. Both drugs were withheld at least 6 hours prior to each study session. Exposure was performed in an environmental chamber. Before and immediately after exposure, lung function and symptom scores were determined. After exposure, a histamine inhalation challenge was performed to determine the concentrations that caused a 100% increase in SRaw (PC100SRaw) and a 20% fall in FEV1, (PC20FEV1). Mean (SD) SRaw before and after Sham was 8.7 (3.6) and 9.0 (3.2) cmH2O.s, and mean FEV1 (SD) was 1.97 (0.32) and 1.98 (0.40) L, respectively. Before and after cigarette smoking, mean SRaw (SD) was 10.4 (5.3) and 9.4 (3.3) cmH2O.s, and mean FEV1 (SD) was 1.95 (0.37) and 1.94 (0.35 L, respectively. Geometric mean (SD) PC100 SRaw and PC20FEV1 after Sham was 1.39 (3.0) and 0.70 (2.7) mg/mL, and after passive smoking 1.65 (2.5) and 0.96 (2.3) mg/mL, respectively. There were no statistical differences in lung function and PC values between Sham and passive cigarette smoking. The main symptoms during passive smoking were irritation of the eye and the nasopharynx. Our observations suggest that in children with mild bronchial asthma 1 hour of passive cigarette smoking does not cause consistent changes of lung function and bronchial responsiveness.

Diurnal variation in bronchial responsiveness in asthmatic children

To establish the presence of a diurnal variation in bronchial responsiveness in asthmatic children, the increase of peak expiratory flow rate (PEFR) following sympathomimetic inhalation and the response to bronchial provocation with histamine and hyperventilation of cold dry air (HVCDA) were studied. Twenty-nine patients (20 boys, nine girls, aged 9.3 to 17.8 years) measured PEFR before and after sympathomimetic inhalation three times a day for four weeks. A further 15 patients (eight boys, seven girls, aged 6.9 to 18.0 years) underwent bronchial provocation testing every six hours for 24 hours. A diurnal variation in bronchodilator responsiveness was demonstrated in 55% of the first group. Mean amplitude was 60.8% of patients' mean increase in PEFR following bronchodilators. On grouped data, bronchodilation was greater in the morning than in the afternoon (p less than 0.0005) or in the evening (p less than 0.0005). A diurnal variation in the response to bronchial provocation was also found in the second group, but the timing of the rhythm depended on the stimulus used. On grouped data, airways were most sensitive to histamine at 0400 hours and most sensitive to HVCDA at 1600 hours. The diurnal variation demonstrated in bronchial responsiveness could not be attributed to changes in baseline airway caliber and was present, despite the patients' taking sufficient medication to control their asthmatic symptoms.

269 Mite exposure and antibody responses of asthmatic children in Atlanta

269 Mite exposure and antibody responses of asthmatic children in Atlanta

Cardiopulmonary responses of asthmatic children to strenuous exercise. Effect of theophylline.

The purpose of the study were to investigate the cardiopulmonary adaptations of asthmatic children to physical exercise and to evaluate the effects of theophylline. Two groups of children were evaluated. Eight asthmatic children participated in two exercise sessions. Half of the patients received theophylline in predetermined doses during the first session and half prior to the second session. Seventeen normal children matched for age, height, and weight served as controls. Various cardiorespiratory parameters were measured every 2 minutes during exercise and prior to termination of maximal physical effort. The results indicate that children with chronic asthma reach the range of predicted maximal aerobic capacity for their age. Theophylline increases the endurance of asthmatic children to maximal physical efforts without improving the cardiorespiratory parameters that were measured. The use of theophylline in therapeutic doses appears safe under conditions of vigorous exercise.

183. The effect of theophylline anhydrous on cardiorespiratory responses of asthmatic children during maximum exercise

183. The effect of theophylline anhydrous on cardiorespiratory responses of asthmatic children during maximum exercise