Allergen avoidance is associated with a fall in exhaled nitric oxide in asthmatic children.
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Publications and source records attributed to A L Boner.
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Exhaled nitric oxide and eosinophil sputum markers are considered noninvasive ways in which to evaluate airway inflammation in asthma. The aim of this study was to evaluate the relationships between these methods of evaluation in asthmatic children. In a cross-sectional study of 25 mild-moderate asthmatic children (aged 6-13 yrs, 10 patients on inhaled steroids) exhaled NO was measured along with induced sputum by inhalation of hypertonic saline solution. The sputum was processed for eosinophil count and eosinophil cationic protein (ECP) determination. Serum ECP and lung function (forced expiratory volume in one second (FEV1)) were also measured. A significant correlation was observed between exhaled NO and sputum eosinophils (r = 0.438, p = 0.032) as well as between sputum eosinophils and sputum ECP (r = 0.532, p<0.01). No correlation was observed among exhaled NO and serum ECP, sputum ECP, FEV1, respectively. Furthermore no correlation was observed between sputum eosinophil (%) and serum ECP and between sputum eosinophils and FEV1. There was no correlation among the investigated parameters in children treated with inhaled steroids. In conclusion, exhaled NO and sputum eosinophil counts are concordant in evaluating the degree of airway inflammation in patients with mild-to-moderate asthma. However, the association between these two noninvasive markers becomes less in steroid treated patients.
Tumour necrosis factor (TNF) is a proinflammatory cytokine that increases human airway tissue responsiveness and is considered a candidate gene for asthma. Two common polymorphisms (LTalphaNcoI and TNFalpha-308) in the TNF gene complex were studied in 600 subjects from 131 Italian families with atopic asthmatic children. Skin prick test (SPT), total IgE levels, atopy (defined as increased IgE levels or SPT positivity or both), bronchial hyperresponsiveness, and clinical asthma were investigated. The observed distribution of the identical by descent alleles at the LTalphaNcoI locus was different from expected for SPT and atopy (p=0.015). The LTalphaNcoI genotype distribution for increased IgE levels was different between males and females (p=0.0011), and an association of the 2.2 genotype with increased IgE levels was observed in females (p=0.0032). The results indicate that the LTalpha gene, or a closely linked locus, is associated with atopy, and suggest a sex difference in the effect of the gene.
We examined the long arm XY pseudoautosomal region for linkage to asthma, serum IgE, and bronchial hyperresponsiveness. In 57 Caucasian families multipoint nonparametric analyses provide evidence for linkage between DXYS154 and bronchial hyperresponsiveness (P = 0.000057) or asthma (P = 0.00065). This genomic region is approximately 320 kb in size and contains the interleukin-9 receptor gene. These results suggest that a gene controlling asthma and bronchial hyperresponsiveness maybe located in this region and that the interleukin-9 receptor is a potential candidate.
BACKGROUND: Asthma is characterized by bronchial hyperresponsiveness (BHR), bronchial mucosa inflammation and airway epithelial damage. OBJECTIVE: This study was designed to evaluate the effect of mite avoidance on bronchial epithelial shedding in asthmatic children sensitized to Dermatophagoides. METHODS: The percentages of airway epithelial cells and eosinophil have been counted in samples obtained by hypertonic saline-induced sputum before and after a period of antigen avoidance in an Alpine environment (1756 m). The degree of bronchial hyperresponsiveness to methacholine was also evaluated. RESULTS: After avoidance the median (lower, Q1, and upper, Q3, quartile) percentage of epithelial cells in the sputum decreased significantly from 3.50 [0.50;6.98] to 0 [0;0.5] (P=0.012) and eosinophil percentage decreased from 1 [0;5.25] to 0 [0,1.5] (P<0.05). Median (Q1,Q3) PC20 increased significantly from 2.75 [1.53;7.5] to 3.25 [1.65;15.25] mg/ mL (P=0.038). After 3 weeks of re-exposure to mite the epithelial median (Q1,Q3) percentage raised to 3.90 [1.5;6] (P = 0.027), eosinophils to 1.5 [0;3.00] (NS) and PC20 was 5.25 [1.68;14.50] (NS). CONCLUSION: Exposure to house dust mite antigen can induce airway epithelial shedding even in subjects with low eosinophil airway infiltration, thus supporting the idea that epithelial damage in asthmatics sensitized to Dermatophagoides may be due to a proteolytic activity of the mite major antigens.
Exposure to allergens has been shown to lead to sensitization and to the subsequent development of airway hyperresponsiveness in genetically predisposed individuals. Increasing interest is being devoted to mechanisms for the prevention of allergen sensitization and asthma development. Primary prevention (avoiding the sensitization to allergens) requires a large effort as the majority of atopic sensitizations occur in children with no demonstrable risk at the birth. Secondary prevention (deterrence of disease expression despite prior IgE sensitization) requires methods for detecting the population at risk by means of large population screening. Tertiary prevention (minimizing the morbidity for those who already have the disease) may be achieved by allergen avoidance, which has been demonstrated to effectively decrease inflammation in symptomatic patients.
Inhaled corticosteroids are recommended as first-line therapy in patients with moderate to severe asthma. The use of these agents in the milder form of asthma is controversial because of their potential adverse effects, especially in growing children. We investigated 49 asthmatic children (38 treated with beclomethasone dipropionate (BDP) at a daily dose of 276+/-125 microg/day and 11 treated with cromolyn sodium (CS) at a daily dose of 30+/-10 mg/day) for 7.4 months, with bone-mass measurements at baseline and after the treatment period. Evaluation of changes in cortical and trabecular bone mass (bone mineral density [BMD]; m/cm2) was performed by absorptiometry at the proximal forearm and at the lumbar spine, respectively. Furthermore, to correct for bone size changes due to growth, we calculated volumetric BMD (VOL-BMD; mg/cm3). At the end of the treatment period, the children who had received regular inhaled BDP had grown as well as children treated with CS, from 120+/-1.4 to 123+/-1.3 cm and from 118+/-3.2 to 120.3+/-2.8 cm, respectively. No children showed deviation from their percentile level of growth. Trabecular and cortical BMD increased after 7 months of follow-up in both groups to the same extent. When BMD was adjusted for body size (VOL-BMD; mg/cm3), bone mass was found not to have changed after BDP or CS treatment course within and between the two groups.
A study of two DNA polymorphisms (i2 RsaI, E237G) in the gene for the beta subunit of the IgE high affinity receptor (FcepsilonRIbeta) was performed in 168 Italian families with atopic asthmatic children. The prevalence of the E237G allele in the Italian population was 4%, so this polymorphism was unsuitable for this study. The i2 RsaI polymorphism minor allele frequency was 44%, and it had a PIC value of 0.37. Linkage analysis indicated a significant allele sharing in affected sib pairs for bronchial hyper-responsiveness (BHR, p=0.048), but not for allergic asthma. These data indicate an association of bronchial hyper-responsiveness with the FcepsilonRIbeta gene.
Measurement of levels of exhaled nitric oxide (NO) has been proposed as a noninvasive method for evaluating the degree of airway inflammation in asthmatic patients. Some concern in the interpretation of results of such measurement may arise from possible interference by high environmental concentrations of NO inhaled by these patients. The aim of this study was to verify whether environmental concentrations of NO in the range from 0 to 150 ppb can influence levels of exhaled NO. We tested two groups of subjects. The first group, consisting of 16 subjects, was tested when environmental levels of NO were from 0 to 3 ppb and from 20 to 60 ppb, and exhaled NO mean ppb (+/- SEM) levels were 9.81 +/- 1.43 and 9.78 +/- 1.47 (p = ns) (mean +/- SEM), respectively. The second group, consisting of 30 subjects, was tested at ambient NO concentrations of 0 to 3 ppm, 80 to 100 ppm, and 120 to 150 ppb, and for 18 of these subjects who underwent testing under all three conditions investigated, the mean levels of exhaled NO were 9.23 +/- 1.51, 7.78 +/- 1.19, and 9.33 +/- 1.55 ppb (p = ns), respectively. The results of this study suggest that significantly different ambient levels of NO have no effect on levels of exhaled NO.
This study aimed to measure energy intake (EI) and total energy expenditure (TEE) of asthmatic males and to validate diet history as a method of estimating their energy requirements. EI was assessed by dietary history and TEE by the heart-rate monitoring method in a group of asthmatic and nonasthmatic males. Resting energy expenditure (REE) adjusted for fat-free mass was higher in asthmatic than in nonasthmatic males (5,037 versus 4,839 kJ x day(-1), p<0.05). TEE (93+/-1.8 versus 8.4+/-1.4 MJ x day(-1), respectively; p=NS) and EI (9.2+/-15 versus 8.8+/-15 MJ x day(-1), respectively, p=NS) were not statistically different in asthmatic and nonasthmatic male. EI was not statistically different from TEE in both groups of males. Asthmatic males showed an acceptable agreement between TEE and EI at the individual level (range of agreement: -3.2 to 2.9 MJ x day(-1)), and a good agreement at the group level (95% confidence interval for the bias, - 1.1 to 0.8 MJ x day(-1)). Males with mild-to-moderate asthma have a higher metabolic activity per unit fat-free mass than nonasthmatic males. This increased requirement is apparently well compensated by an adequate energy intake. Diet history is a suitable method for estimating energy requirements in males with mild-to-moderate asthma.
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Respiratory muscle strength, assessed by maximal inspiratory mouth pressure (PImax), and endurance, assessed as the length of time a subject could breathe against inspiratory resistance with a target mouth pressure > or = 70% of PI,max (Tlim), were measured in 20 symptomless asthmatic children, in order to assess the reproducibility of such measurements and their relationship to traditional pulmonary function tests or tests of bronchial hyperresponsiveness. After recording lung volumes and bronchial response to methacholine, PI,max and Tlim were measured twice in the same morning, with a 30-minute interval between each experimental trial. Mean (+/-SD) values of PI,max were 72.2 +/- 20.6 cmH2O in the first and 75.8 +/- 22.9 cmH2O in the second trial. Tlim was 154 +/- 65 and 164 +/- 66 seconds in the first and in the second trial respectively. A lack of agreement between different measurements was seen for both PI,max and Tlim. The coefficient of repeatability was 24.8 for PI,max and 92.3 for Tlim. A significant correlation between age and PI,max as well as between body mass index and PI,max were shown; no similar correlation was found for Tlim. No correlation was found between PI,max and Tlim in either of the two successive runs or between either PI,max or Tlim and lung volumes or bronchial response to methacholine. Our study shows that at this time the reproducibility of PI,max or Tlim in children with asthma in remission seems to be poor, although PI,max has a better reproducibility than Tlim. A standardized procedure to measure PI,max, should be obtainable in the near future. This would improve its clinical usefulness since PI,max is the only noninvasive test to assess respiratory muscle strength that can identify subjects at risk to develop respiratory muscle fatigue during an acute asthmatic attack.
Assessment of asthma severity is important for disease management. Analysis of symptoms past and present, and previous and actual lung function measurements (including variability) is the usual method of evaluation and classification of asthma disease severity and activity. However, symptoms and lung function alterations are the result of pathophysiological processes including inflammation in the bronchial wall which, in chronic phases, precedes the clinical measurements, and are risk factors for disease progression and worsening. Tools for more precise determination of asthma disease processes in the airway wall would be of importance for prophylactic intervention to avoid chronic damage to the airways and acute worsenings to occur.
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Sensitivity of forced expiratory flow between 25% and 75% of the vital capacity (FEF25-75) in detecting airway obstruction was investigated in 14 children with mild-moderate asthma, allergic to house dust mites, while at high altitude (1756 m). Forced vital capacity (FVC), forced expiratory volume in 1 sec (FEV1), FEF25-75, and peak expiratory flow (PEF) were measured every 2 weeks for 12 weeks (total, 84 measurements). The presence or absence of wheezing at the chest auscultation was ascertained before each test. During the study period, a significant improvement of both mean (SD) FEF25-75 [61 (12)% vs. 68 (11)% of the predicted value, p = 0.005] and PEF [95 (16)% vs. 103 (13)%, p = 0.002] was observed. FEV1 changed only marginally [82 (7)% vs. 86 (6)%, p = 0.05]. Wheezing was present on 12/84 occasions. Wheezing was associated with abnormal FEF25-75 values on most occasions but not with abnormal FEV1 or PEF. FEF25-75 was decreased on 51% of days in which wheezing was absent. FEV1 and PEF were, respectively, normal in 69% (p < 0.0001) and 92% (p < 0.0001) of measurements in which FEF25-75 was abnormal. These results suggest that FEF25-75 may be considered a good indicator of airflow obstruction and a sensitive marker of respiratory improvement in asthmatic children during reduced antigen exposure.
The role of nebulized flunisolide solution in controlling recurrent respiratory symptoms was assessed in a double-blind placebo-controlled parallel study on 23 infants and small children (mean age, 14.2 months) with bronchial asthma. Five of the 12 children in the placebo group and 1 of the 11 patients on active treatment had to be withdrawn from the study. Flunisolide significantly improved symptom scores of wheezing and cough. The rescue treatments with salbutamol did not differ between the two groups during the study. Parents considered the active treatment effective in all the patients, while the placebo was considered useful in 4 of 7 children. No side effects were detected with either treatments. This study indicates that nebulized flunisolide may be an effective treatment for infants with recurrent wheezing and cough.
BACKGROUND: Exposure to relevant allergens causes an increase in bronchial hyperresponsiveness, as well as an inflammatory reaction at the site of the bronchial mucosa in patients with asthma. OBJECTIVE: The purpose of this study was to determine whether antigen avoidance can exert an antiinflammatory effect on the eosinophil phase of airway inflammation in children with asthma. METHODS: The level of bronchial hyperreactivity and the percentage of eosinophils in sputum samples obtained by inhalation of hypertonic saline solution, were evaluated in a group of asthmatic children allergic to house dust mite before and after a period of antigen avoidance in an Alpine environment (1756 m). RESULTS: At the end of the avoidance period PC20 increased from a median value (lower and upper quartile: Q1, Q3) of 1.17 (0.74, 4.75) to 3.5 (1.18, 8.87) mg/ml (p = 0.02), and eosinophil percentage in the sputum decreased from a median value (Q1, Q3) of 14.02 (3.34, 28.24) to 2.08 (0, 7.4) (p less than 0.01). CONCLUSION: A 3-month period of antigen avoidance can significantly reduce the eosinophil phase of airway inflammation, along with bronchial hyperresponsiveness, in patients with asthma.