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

Abstract

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...

Exhaled nitric oxide levels and blood eosinophil counts independently associate with wheeze and asthma events in National Health and Nutrition Examination Survey subjects

“…4 However, in the present study the correlation between FENO and B-Eos values was weak, with an explanatory value of only approximately 4%, which is in line with the previously reported weak-to-moderate correlations between FENO and eosinophil values in blood or sputum 8,23 or between blood and sputum eosinophil values. 24 This, together with the clear-cut additive effect of these 2 markers on the risk for asthma, wheeze, and asthma attacks in our study, indicates that they represent 2 different inflammatory pathways with separate trigger mechanisms.…”

Sputum induction in young cystic fibrosis patients

“…Although the drop in postsalbutamol forced expiratory volume in one second (FEV1) after inhalation was larger in asthmatics than in normals a fall exceeding 20% only occurred in 3/37 patients. Sputum induction using hypertonic saline is also efficacious and safe in adolescent asthmatics [13,14] and isotonic saline sputum induction appears to be safe in children with acute asthma [15]. Although the feasibility of sputum induction has been reported in patients with CF [16], a systematic study of sputum induction in young CF patients is lacking.…”

Use of Exhaled Nitric Oxide Measurement to Identify a Reactive, at-Risk Phenotype among Patients with Asthma

“…As a free radical that reacts with oxidants and antioxidants, nitric oxide (NO) in exhaled breath (FE NO ) reflects the redox state of the airway and has been proposed as a marker of airway inflammation and guide for antiinflammatory therapy in asthma (7). High levels of FE NO are well documented in nonsevere asthma (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and decrease in response to treatment with corticosteroids (22)(23)(24)(25)(26)(27). However, measures of FE NO in 50 patients with severe asthma in the European multicenter study of chronic severe asthma suggest that FE NO levels of patients with severe asthma, who are refractory to conventional treatments, may not be suppressed by corticosteroids (28).…”