Exhaled nitric oxide in childhood asthma

Artlich, A.; Hagenah, J.; Jonas, S.; Ahrens, Peter; Gortner, Ludwig

doi:10.1007/s004310050471

Cited by 26 publications

(38 citation statements)

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“…The data presented in this study are similar to those published by other groups [44,46], and confirm the hypothesis that airway inflammation may not be strictly related to the reduction of lung volumes or to the degree of airflow limitation [10].…”

Section: Discussionsupporting

confidence: 91%

Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma

et al. 1999

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Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma. M. Silvestri, D. Spallarossa, V. Frangova Yourukova, E. Battistini, B. Fregonese, G.A. Rossi. #ERS Journals Ltd 1999. ABSTRACT: Increased levels of nitric oxide have been found in expired air of patients with asthma, and these are thought to be related to the airway inflammatory events that characterize this disorder. Since, in adults, bronchial inflammatory changes are present even in mild disease, the present study was designed to evaluate whether a significant proportion of children with mild-intermittent asthma could have increased exhaled air NO concentrations.Twenty-two atopic children (aged 11.1 0.8 yrs) with mild-intermittent asthma, treated only with inhaled b 2 -adrenoreceptor agonists on demand and 22 age-matched controls were studied.NO concentrations in orally exhaled air, measured by chemiluminescence, were significantly higher in asthmatics, as compared to controls (19.4 3.3 parts per billion (ppb) and 4.0 0.5 ppb, respectively; p<0.01). Interestingly, 14 out of 22 asthmatic children had NO levels >8.8 ppb (i.e. >2 standard deviations of the mean in controls). In asthmatic patients, but not in control subjects, statistically significant correlations were found between exhaled NO levels and absolute number or percentage of blood eosinophils (r=0.63 and 0.56, respectively; p<0.01, each comparison). In contrast, exhaled NO levels were not correlated with forced expiratory volume in one second (FEV1) or forced expiratory flows at 25±75% of vital capacity (FEF25±75%) or forced vital capacity (FVC), either in control subjects, or in asthmatic patients (p>0.1, each correlation).These results suggest that a significant proportion of children with mild-intermittent asthma may have airway inflammation, as shown by the presence of elevated levels of nitric oxide in the exhaled air. The clinical relevance of this observation remains to be established. Eur Respir J 1999; 13: 321±326.

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Section: Discussionsupporting

confidence: 91%

Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma

et al. 1999

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“…Therefore, they received a treatment similar to the children treated with low dose inhaled steroids in the present study. Unfortunately in that study the authors did not measure the level of BHR [18]. In contrast, the group of adults studied by JATAKANON et al [23], for which no significant correlation was observed between ENO and FEV1, was more similar to the group of untreated children in our study population, both for treatment and for level of BHR.…”

Section: Resultscontrasting

confidence: 57%

“…Nevertheless, the relationship between ENO and FEV1 is a contrasting issue in the literature with some studies showing a significant correlation [18,25,40], whereas others failed to show such a correlation [23]. In the study by ARTLICH et al [18], the children showing a relationship between ENO and FEV1, were receiving anti-inflammatory treatment, either cromolyn or inhaled steroids. Therefore, they received a treatment similar to the children treated with low dose inhaled steroids in the present study.…”

Section: Resultsmentioning

confidence: 99%

Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children

Piacentini

Bodini

Costella³

et al. 2000

Eur Respir J

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The purpose of the present study was to assess the possible relationships between exhaled nitric oxide (ENO), a circulating marker of eosinophil activation, serum eosinophil cationic protein (SECP), level of airway responsiveness to methacholine and lung function in asthmatic children, as well as to compare these markers between children with and without inhaled steroid therapy.In a cross-sectional study ENO, SECP and bronchial hyperresponsiveness to methacholine were evaluated in a group of 57 asthmatic children (21 without and 36 with regulator inhaled steroid therapy; aged 6±13 yrs).ENO was significantly lower in steroid treated children (p<0.01). No significant differences between steroid treated and untreated children were observed for the provocative concentration of methacholine causing a 20% faill in forced expiratory volume in one second (FEV1; PC20), SECP and FEV1. In the whole study population significant increase correlations were observed between PC20 and SECP (r=-0.329, p=0.013) and between ENO and FEV1% of predicted (r=-0.348, p<0.01). In the group not receiving inhaled steroids the inverse relationship between PC20 and SECP was more evident (r=-0.581, p<0.001). In the steroid-treated group a significant inverse relationship was observed between ENO and FEV1 (r=-0.426, p=0.0011).The level of exhaled nitric oxide and the relationships between lung function, bronchial reactivity and markers of inflammation are different between steroidtreated and untreated asthmatic children. This has implications for the monitoring of asthma in childhood. The relationship between airway inflammation and airway responsiveness has been evaluated by different groups with contrasting results. Some authors [1±6] have found a strong relationship between inflammatory cells in the airway and the level of bronchial responsiveness while others failed to find such a correlation [7±11].Similarly, contrasting results have been found between serum markers of eosinophil activation, in particular serum eosinophil cationic protein (SECP), and the degree of bronchial responsiveness in asthmatic patients [12±15].Recently, the measurement of exhaled nitric oxide (ENO) has been proposed as a noninvasive means for assessing the degree of airway inflammation [16±18]. Some studies have evaluated the effect of treatment with inhaled steroids on the levels of ENO in asthmatic adults [19,20] and one study in children with acute asthma [21]. Furthermore, a few studies have evaluated the relationship of this parameter with the level of airway hyperresponsiveness with contrasting results [22±25].The purpose of the present study was to assess the possible relationship between ENO, a circulating marker of eosinophil activation SECP, level of bronchial hyperresponsiveness (BHR) to methacholine and lung function in asthmatic children, as well as to compare these markers between patients with and without inhaled steroid treatment. Material and methods Subjects and study designFifty-seven children with mild to moderate asthma, clinically st...

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“…During spontaneous breathing, the detection of NO derived from the lower airways is hampered by variable admixture of nasal NO into the respiratory gas depending, for example, on the position of the soft palate and the presence of a nose clip [26]. In a previous study comparing healthy and asthmatic children [5], a positive correlation between oral and nasal NO concentrations had indicated incomplete separation of the upper and lower airway NO fractions. In the present study, a modified experimental setup with optimized separation of pulmonary and nasal NO [27] was used and endogenous NO release studied in relation to recent clinical symptoms taking into account regular inhalation of glucocorticosteroids.…”

mentioning

confidence: 99%

NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma

Mattes¹,

Gravesande²,

Reining³

et al. 1999

Eur Respir J

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Bronchial asthma is associated with increased levels of exhaled nitric oxide which are suppressible by glucocorticosteroid inhalation. Children with bronchial asthma were studied to elucidate the relation between endogenous NO release and recent symptoms of bronchial obstruction.Twenty-five children with atopic asthma and 11 healthy control subjects were enrolled and exhaled NO was studied using chemiluminescence analysis. The subjects breathed purified air (<0.5 parts per billion (ppb) NO) exclusively through their mouths. Orally expired NO was measured during continuous nasal aspiration (1.3 L . min -1 ) to remove nasally produced NO. Nasal NO concentration was determined within the aspirated gas.Orally expired NO concentration was 2.50.3 ppb (meanSEM) in healthy control subjects, 3.190.88 ppb (NS) in symptom-free children, and 8.280.81 ppb (p#0.01) in children with bronchial asthma who had had recent symptoms of bronchial obstruction. Similarly, in the subgroup of children treated regularly with inhaled glucocorticosteroids those with recent symptoms had significantly higher orally exhaled NO concentrations than healthy control subjects (9.51.5 ppb, p<0.05). The nasal NO concentration was 152.812.7 ppb in healthy control subjects and not significantly different in asthmatic children.In this group of asthmatic children, recent symptoms of bronchial obstruction were linked to significantly higher concentrations of NO in orally exhaled gas and to increased oral NO excretion rates. If substantiated by further studies, measurement of orally exhaled NO during nasal aspiration may become useful to monitor disease control in asthmatic children. Eur Respir J 1999; 13: 1396±1401. Nitric oxide can be detected in exhaled gas of various mammals including humans [1] and is increased in patients with bronchial asthma [2±8]. In adults, the increase is mainly due to increased production in the lower airways [9,10] although at present it is not clear whether the increased exhaled NO in asthmatics reflects a beneficial response counterbalancing bronchoconstrictor stimuli or contributes to increased tissue damage and perpetuation of immune responses [11,12]. There is sufficient evidence to conclude that NO synthesis is induced by the underlying chronic inflammatory process in bronchial asthma: in vitro studies have shown the inducibility of NO synthesis by inflammatory cytokines relevant to asthma [13,14]. Inducible NO synthase (iNOS) has been detected immunohistochemically in bronchial epithelial cells of asthmatic patients [13] and in alveolar macrophages from areas of chronic inflammation [15]. The inhalation of a pulmonary irritant has been shown to enhance NO production by alveolar macrophages in rats [16]. Furthermore, antigen-induced bronchoconstriction specifically affects exhaled NO levels and is antagonized by endogenous NO in animal studies [17,18]. Treatment with glucocorticosteroids reduces the expression of iNOS in macrophages in vitro [19] and leads to a decrease of exhaled NO levels in adults and childr...

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Exhaled nitric oxide in childhood asthma

Abstract: Children with bronchial asthma have significantly higher levels of orally exhaled nitric oxide than healthy controls.

Cited by 26 publications

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Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma

Orally exhaled nitric oxide levels are related to the degree of blood eosinophilia in atopic children with mild-intermittent asthma

Exhaled nitric oxide, serum ECP and airway responsiveness in mild asthmatic children

NO in exhaled air is correlated with markers of eosinophilic airway inflammation in corticosteroid-dependent childhood asthma

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