Increased bronchial NO output in severe atopic eczema in children and adolescents

Atopic children have an increased risk for asthma, which is preceded by bronchial inflammation. Exhaled nitric oxide (NO) measured at multiple exhalation flow rates can be used to assess alveolar NO concentration and bronchial NO flux, which reflect inflammation in lung periphery and central airways, respectively. Exhaled breath condensate is another non‐invasive method to measure lung inflammation. The purpose of the present study was to find out if the severity of atopic eczema is associated with lung inflammation that can be observed with these non‐invasive tests. We studied 81 patients (7–22 yr old) with atopic eczema and increased wheat‐specific IgE (≥0.4 kUA/l) and no diagnosis of asthma. Exhaled NO was measured at multiple exhalation flow rates, and bronchial NO flux and alveolar NO concentration were calculated. Cysteinyl‐leukotriene concentrations were measured in exhaled breath condensate. The patients were divided into two groups according to the severity of atopic eczema. Patients with severe atopic eczema had enhanced bronchial NO output as compared with patients with mild eczema (2.1 ± 0.5 vs. 0.9 ± 0.1, p = 0.003). No statistically significant differences in alveolar NO concentrations were found between the groups. In the whole group of patients, the bronchial NO output correlated positively with serum eosinophil protein X (r_s = 0.450, p < 0.001), serum eosinophil cationic protein (r_s = 0.393, p < 0.001), serum total IgE (r_s = 0.268, p = 0.016) and with urine eosinophil protein X (r_s = 0.279, p = 0.012), but not with lung function. Alveolar NO concentration correlated positively with serum eosinophil protein X (r_s = 0.444, p < 0.001) and with serum eosinophil cationic protein (r_s = 0.362, p = 0.001). Measurable cysteinyl‐leukotriene concentrations in exhaled breath condensate were found only in one‐third of the patients, and there were no differences between the two groups. The results show that increased bronchial NO output is associated with eosinophilic inflammation and severe atopic eczema in patients without established asthma.     

Exhaled breath condensate pH measurement in children with asthma, allergic rhinitis and atopic dermatitis

Recent studies have shown that the pH of exhaled breath condensate (EBC) could be predictive of asthma exacerbation. Moreover, it has been documented that both allergic rhinitis and atopic dermatitis constitute risk factors for the occurrence of asthma in a progression of disease known as atopic march. The aim of our study was to establish if condensate pH could be used as a valuable mean of monitoring of asthma in atopic children. We studied 34 atopic children with acute asthma, 70 with stable asthma, 35 children with allergic rhinitis, and 17 with atopic dermatitis. Thirty healthy children were used as controls. All children underwent skin prick tests and lung function tests. Exhaled breath condensate samples were collected with a condensing device and de-aerated with argon. The pH of EBC was measured using a pH meter. Children with acute asthma were treated with inhaled steroids and bronchodilators. We found that the pH of condensate in patients with acute asthma was lower than that of patients with stable asthma, rhinitis, and controls (7.25 vs. 7.32, p < 0.05; 7.25 vs. 7.48, p < 0.02; 7.25 vs. 7.78, p < 0.0001, respectively). Patients with stable asthma, rhinitis, and eczema had also lower pH than that of controls (7.32, 7.48, and 7.44 vs. 7.78; p < 0.0001, p < 0.006, p < 0.04, respectively). Patients with acute asthma normalized their pH after treatment (7.82 vs. 7.25; p < 0.0001). Finally, patients with acute asthma showed a positive correlation between pH and lung functional parameters (forced expiratory volume in 1 s; r = 0.39, p = 0.04). Our study shows that EBC pH measurement may be a promising marker for assessing airway inflammation and monitoring response to anti-inflammatory treatment in asthmatic children. Furthermore, we report the first evidence of airways acidification in children with allergic rhinitis and atopic dermatitis. Therefore, EBC pH assessment may be useful in the evaluation of progression of the atopic march toward the development of asthma later in life. Further studies are recommended in order to confirm this indication.     

Asthma severity and inflammation markers in children

The relationship of airway inflammation with asthma severity remains unclear. Our aim was to correlate the results of recommended methods of assessment of inflammation with measures of asthma control, in children with a wide range of asthma severity. The study was a cross-sectional investigation of 58 children receiving a wide range of treatment, including 10 treated without regular maintenance therapy and 29 treated with high-dose inhaled corticosteroids (CS). Exhaled nitric oxide (NO), serum eosinophil cationic protein (ECP), and induced sputum (processed for eosinophil count and ECP level) were related to recent symptoms, lung function, and bronchial responsiveness. There was no significant correlation between the results of any method. Neither did any marker of airway inflammation relate to recent symptoms, unlike PC₂₀, which did. There was a significant, inverse correlation between the forced expiratory volume in 1 s ( FEV ₁) and both NO and sputum ECP ( r =−0.46, p=<0.001; r =−0.48, p=0.004, respectively). Sputum eosinophils were inversely related to the dose of methacholine that corresponded to a 20% fall in FEV ₁ (PC₂₀) ( r =−0.57, p=0.02). Serum ECP did not relate to any measure of asthma control. There was no association of any recommended inflammation markers with current symptoms and only a weak relationship between them and physiological measures. The place of these markers remains unclear and their use in clinical practice needs further investigation by long-term longitudinal studies.     

Exhaled nitric oxide in asthmatic children and adolescents after nasal allergen challenge

Epidemiological data suggest a comorbidity link between nasal and bronchial allergic disease. Exhaled nitric oxide (FENO) is a sensitive marker of bronchial inflammation and increases after bronchial allergen provocation. We studied FENO in 19 children and adolescents with allergic asthma and 10 controls before and 2, 6 and 24 h after a single nasal allergen challenge. The correlation between FENO and other markers of allergic inflammation, such as eosinophils in blood and eosinophil cationic protein (ECP) in serum and nasal lavage was also assessed. FENO remained unchanged 24 h post-challenge in both steroid and steroid-naive patients. At 6 h post-challenge, FENO decreased in both asthmatics and controls. The asthmatic subjects showed a positive correlation between FENO and blood eosinophils before (r=0.71, p=0.001) and after the challenge, and between FENO and ECP in nasal lavage (r=0.62, p=0.02) 2 h after the challenge. Mean ECP in nasal lavage increased post-challenge but not significantly. We conclude that a single nasal allergen challenge does not augment bronchial inflammation although FENO, is related to blood eosinophil count and to the nasal inflammatory response. Our data do not support the theory of a direct transmission of the nasal inflammation to the lower airways.     

Inflammation markers and symptom activity in children with bronchial asthma. Influence of atopy and eczema

Background. Eosinophil cationic protein (ECP) has been reported to reflect the eosinophil inflammatory activity in asthma. However, the relative impact of asthma symptoms and atopic eczema upon serum (s)-ECP in asthmatic children has not been established.
Objectives. To examine s-ECP levels and s-myeloperoxidase (MPO) in relation to asthma symptoms and atopic eczema in asthmatic children.
Methods. S-ECP and s-MPO were assessed in relation to symptom activity, lung function, exercise induced bronchoconstriction and bronchial responsiveness in 101 children; median age 9 years, range 1-16 years; with moderate to severe asthma, admitted to Voksentoppen Center.
Result. S-ECP was significantly higher in children with persistent compared to episodic or no asthma symptoms in the past four weeks, S-ECP was also higher in children with atopic compared to non-atopic asthma, as well as in those with active compared to past history of no history of atopic eczema. SMPO was higher in children with persistent asthma symptoms, but did not differ in relation to atopy of eczema state. Persistent asthma symptoms had the greatest impact upon s-ECP levels, followed by atopy and active eczema.
Conclusion. S-ECP may be used in assessing symptom activity in asthmatic children, but with the realisation that active eczema and the presence of atopy may also influence levels.     

Inverse association between Chlamydia pneumoniae respiratory tract infection and initiation of asthma or allergic rhinitis in children

To evaluate the role of Chlamydia pneumoniae respiratory tract infection on pediatric asthma, allergic rhinitis or atopic eczema initiation, children of three age groups (n=1211) were prospectively studied for a C. pneumoniae infection using throat swabs and polymerase chain reaction (PCR) with enzyme immunoassay (EIA) detection. Infected children (study group, SG) were examined monthly until the agent could not be detected, quantifying persistent infection. They were compared with randomly selected, non-infected children without asthma matched for age, gender and origin (control group, CG) regarding lung function and inflammatory parameters as well as initiation of allergic diseases judged by family doctor diagnosis after, in median, 22 months. At the first follow-up examination, SG children revealed a higher leukotriene B4 (median 36 pg/ml vs. 19, p=0.04) and 8-isoprostane (median 15 pg/ml vs. 12, p=0.04) in breath condensate characterizing neutrophil, agent-related inflammation and oxidative stress in the lower airways. Cysteinyl leukotrienes, important in acute allergic inflammation, were without difference. Local, anti C. pneumoniae secretory immunoglobulin A antibodies were higher in children after C. pneumoniae infection (optical density median 0.7 vs. 0.4, p=0.001) confirming PCR-EIA results. At the final examination, there was no difference in pathological lung function tests, parameters of exhaled breath condensate or eosinophilia of the nasal mucosa. Incidence of asthma (0/55 vs. 5/54, p=0.03) and allergic rhinitis [3/53 vs. 10/52, p=0.04, odds ratio and 95% confidence interval-OR 0.25 (0.06;0.98)] as well as prevalence of asthma [1/56 vs. 9/58, p=0.02, OR 0.1 (0.01;0.81)] and allergic rhinitis [6/56 vs. 16/58, p=0.03, OR 0.32 (0.11;0.88)] were lower in the SG children. There was no association in atopic eczema. Three children with persistent infection revealed a slightly higher incidence in allergic rhinitis without significance than those with single C. pneumoniae detection (1/3 vs. 2/50), however, not to the CG. In conclusion a C. pneumoniae upper respiratory tract infection may be regarded as a protective factor for childhood asthma or allergic rhinitis in a population of kindergarten and school-age children.     

Relations between exhaled nitric oxide and measures of disease activity among children with mild-to-moderate asthma

OBJECTIVE: Exhaled nitric oxide (FE(NO)) was evaluated in children with asthma after 4 to 6 years of treatment with budesonide, nedocromil, or albuterol as needed. STUDY DESIGN: FE(NO), spirometry, total eosinophil count, and serum eosinophil cationic protein levels were obtained from 118 children at the Denver site of the Childhood Asthma Management Program upon completion of treatment and after a 2- to 4-month washout. RESULTS: Budesonide-treated patients had significantly lower median (1st, 3rd quartile) FE(NO) (21.5 [13.2, 84.4] vs 62.5 [26.2, 115.0] ppb, P <.01) and eosinophil cationic protein levels (17.4 [10.1, 24.3] vs 24.0 [15.4, 33.9] mg/dL, P =.05) compared with placebo, whereas no differences were noted between nedocromil and placebo groups. After washout, FE(NO) levels were similar between the three treatments. FE(NO) levels significantly correlated with degree of bronchial hyperresponsiveness, bronchodilator reversibility, allergen skin prick tests, serum IgE, and total eosinophil count. FE(NO) levels were also higher in patients with nocturnal symptoms and in patients requiring beta-agonist use at least once weekly. CONCLUSIONS: Budesonide therapy was more effective than nedocromil in reducing FE(NO). Unfortunately, the effects of long-term budesonide were not sustained after its discontinuation. FE(NO) may be a complementary tool to current practice guidelines in assessing asthma control and medication response.     

Comparative effect of triamcinolone, nedocromil and montelukast on asthma control in children: A randomized pragmatic study

Asthma severity can be judged by measurements of symptoms, lung function, and medication requirements. The objective was to compare the effect of a 4-wk monotherapy with low-dose triamcinolone, montelukast and nedocromil on asthma control, lung function, eosinophil blood count, and bronchial hyper-reactivity in children with mild to moderate asthma allergic to dust mite. Two hundred fifty-six children, aged 6-18 yr, with mild to moderate asthma, participated in an 8-wk study. This was a three-arm, randomized no blinding or placebo pragmatic trial comparing the effect of triamcinolone acetonide (400 microg/day), inhaled nedocromil and montelukast sodium on clinical parameters of asthma [score, forced expiratory volume in 1 s (FEV(1))], PC20H, and eosinophil blood count. Two hundred forty-six children completed the study. After 4 wk of treatment with triamcinolone and montelukast, FEV(1) and PC20H significantly increased, and mean total symptoms score and mean number of eosinophil count in serum significantly decreased. Triamcinolone had a stronger effect on PC20H than montelukast. Nedocromil improved total asthma symptoms score and lung function. There was a reduction in the daytime and night-time symptom scores after treatment with all three drugs. Triamcinolone and montelukast had a stronger effect on asthma symptoms than nedocromil. There were statistically significant differences in reduction of nocturnal asthma symptoms between the triamcinolone and nedocromil groups (p < 0.001) and between montelukast and nedocromil (p = 0.001) groups, but not between the triamcinolone and montelukast groups. There was a reduction in beta-agonists use after treatment with all three drugs, with the strongest effect of triamcinolone. The study showed the strongest effect of low-dose inhaled steroids on clinical symptoms, lung function, bronchial hyper-reactivity and eosinophil blood count when compared to other asthma medications.     

Bronchoalveolar lavage in asthmatic children: Evidence of neutrophil activation in mild-to-moderate persistent asthma

Little information is available on cell profiles and mediator production in the lower airways of children with asthma by comparison with the adult population. To study the bronchoalveolar lavage (BAL) cell profiles and production of eosinophil cationic protein (ECP) and myeloperoxidase (MPO) in childhood bronchial asthma, a retrospective study was performed in 29 children (13 allergic asthmatic children and 16 controls). Six of the asthmatics had mild-to-moderate persistent disease and seven had intermittent asthma. The BAL cell count and ECP and MPO values of asthmatic children were compared with those from 16 controls. The asthmatic patients had higher values than controls for the total cell count (p=0.08), for neutrophils (p=0.02), and for ECP and MPO (p<0.001). MPO levels (p=0.04), neutrophil count (p=0.06), and ECP values (p=0.06) were higher in patients with mild-to-moderate persistent asthma than in those with intermittent asthma. Our results demonstrate that neutrophil-mediated inflammation is greater in patients with more severe asthma.     

Clinical value of monitoring eosinophil activity in asthma.

To evaluate the use of eosinophil cationic protein (ECP) in monitoring disease activity in childhood asthma, serum ECP in 175 asthmatic children was assessed. Forty five patients with cystic fibrosis, 23 with lower respiratory tract infections (LRTI), and 87 healthy children were used as controls. Serum ECP concentrations (34.3 micrograms/l v 9.8 micrograms/l) were significantly higher in children with bronchial asthma than in healthy control subjects. In symptomatic patients with asthma serum ECP concentrations were increased compared with those from asymptomatic patients (40.2 micrograms/l v 14.4 micrograms/l), irrespective of treatment modalities (that is steroids, beta 2 agonists, or sodium cromoglycate). Moreover, atopy and infection appeared to be factors enhancing eosinophil activity in bronchial asthma as measured by serum ECP (58.4 micrograms/l v 36.8 micrograms/l and 68.8 micrograms/l v 42.2 micrograms/l, respectively). In a longitudinal trial, antiasthmatic treatment modalities (that is steroids) reduced serum ECP within four weeks (42.2 micrograms/l v 19.0 micrograms/l). In conclusion, the data indicate that (1) eosinophils also play a central part in childhood asthma; (2) serum concentrations of ECP in children with bronchial asthma are related to the disease severity and may thus be used for monitoring inflammation in childhood asthma; (3) eosinophil activity appears to be enhanced by atopy and infection; and (4) longitudinal measurements of serum ECP concentrations may be useful for optimising anti-inflammatory treatment in children with bronchial asthma.     

呼出气冷凝液检测在儿童哮喘诊治中的应用

呼出气冷凝液(EBC)检测技术是目前诊断、评估肺部疾病新的检测方法。EBC是通过收集呼吸道上皮细胞表面覆盖的液体,这是一种非侵入性、操作简单、重复性较好的方法,适合在婴幼儿及儿童哮喘病情评估中使用。哮喘患儿呼吸道炎症或损伤时,EBC pH值、炎性介质、细胞因子等也会随之发生相应的变化,这些炎性标志物变化可作为诊断、评估儿童哮喘的病情和疗效的良好指标。     

Exhaled nitric oxide, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis

Exhaled nitric oxide (eNO) levels are correlated with several markers of atopy and inflammatory activity in the airways, but the relationship between eNO and total serum IgE has not been fully elucidated in the context of allergic sensitization. The aim of this study was to investigate the relationship between eNO, total serum IgE and allergic sensitization in childhood asthma and allergic rhinitis. eNO levels, lung function, skin prick tests and total serum IgE were determined in 109 children (mean age, 10.4 yr) with mild intermittent asthma and in 41 children (mean age, 10.1 yr) with allergic rhinitis; 25 healthy non-atopic children were recruited as controls. eNO levels (median) were significantly higher in patients with asthma (22.7 p.p.b.) and in those with allergic rhinitis (15.3 p.p.b.) than in healthy controls (5.9 p.p.b.). Children with allergic asthma had higher eNO levels than children with allergic rhinitis. A significant positive correlation was found between eNO and total serum IgE (asthma, r = 0.42, p < 0.0001; allergic rhinitis, r = 0.31, p < 0.01), and between eNO and the number of positive skin prick tests (asthma, r = 0.31, p < 0.0001; allergic rhinitis, r = 0.39, p < 0.01). eNO levels were better correlated with total IgE than with the number of positive skin prick tests. This correlation was independent of allergic sensitization. High total serum IgE represents a specific and predictive marker of eNO increase in children with asthma or allergic rhinitis. This finding adds further support to the hypothesis that increased serum IgE could be a marker itself of airway inflammation in patients with allergic disease.     

Vascular endothelial growth factor overexpression in induced sputum of children with bronchial asthma

Vascular endothelial growth factor (VEGF) induces angiogenesis and increases vascular permeability participating in narrowing of the airway lumen that follows lung injury. We sought to investigate the expression of VEGF in induced sputum during and after recovery from acute episodes of bronchial asthma in children. Eighteen asthmatic children with acute attacks of varying severity were subjected to VEGF estimation by an enzymatic immunoassay in induced sputum. They were followed up till complete remission of symptoms and signs and were then retested. VEGF was also estimated in sputum induced from age 34 and sex-matched healthy children enrolled as a control group. The sputum VEGF levels during acute asthma [median = 71 ng/ml; mean (s.d.) = 114.6 (121.8) ng/ml] were significantly higher than the levels estimated during remission [median = 50 ng/ml; mean (s.d.) = 45.7 (24.2) ng/ml] and both were higher than the corresponding levels of the control group [median = 36 ng/ml; mean (s.d.) = 31.3 (17.2) ng/ml]. VEGF levels during asthmatic episodes correlated positively to the recovery levels (r = 0.6, p = 0.009). The patients' VEGF expression did not vary with asthma severity, serum total IgE concentration, peripheral blood eosinophil count, or erythrocyte sedimentation rate of patients. Children on corticosteroids inhalation therapy at enrollment had sputum VEGF levels that were comparable to those on other therapies. The increased expression of sputum VEGF in asthmatic children reinforces the concept that it might have a pathogenetic role in bronchial asthma and may represent a biomarker of airway inflammation.     

Eosinophil cationic protein, myeloperoxidase and tryptase in children with asthma and atopic dermatitis

Serum levels of eosinophil cationic protein (ECP), myeloperoxidase (MPO), tryptase, total IgE and differential blood cell counts were studied in atopic children with: 1) moderate to severe asthma using inhaled steroids and symptom-free for the last 3 weeks (n= 13), 2) mild asthma with sporadic symptoms, using only inhaled β₂-agonists < 3 times/week (n= 15), 3) acute asthmatic attacks admitted to hospital (n= 12), 4) mild to moderate atopic dermatitis (n= 14). Fifteen children without any history of atopy served as controls. ECP, MPO, tryptase and IgE were measured in serum by radioimmunoassays (RIA). The symptom-free children with inhaled steroids had similar median ECP and MPO values as the controls, 8.0 and 360 μg/l, vs. 9.0 and 310 μg/l, while both ECP and MPO were significantly (p < 0.001) increased in the symptom-free children without anti-inflammatory treatment, 32 and 887 μg/l and in those with acute asthma, 28 and 860 μg/l. The children with atopic dermatitis had increased ECP but normal MPO levels, 16.0 and 455 μg/l. Tryptase in serum was not measurable in any patient. All groups except the control group had significantly elevated total IgE levels. The results indicate that in atopic children serum ECP is a good marker of ongoing asthma or atopic dermatitis. The normal levels of ECP and MPO in the children with asthma using inhaled steroids seem to reflect successful anti-inflammatory treatment. The increased levels of ECP and MPO in the children with mild asthma and no anti-inflammatory treatment may indirectly reflect airway inflammation.     

Blood eosinophils, leukotriene C4 generation, and bronchial hyperreactivity in formerly preterm infants.

Infants born prematurely are known to display longstanding bronchial hyperreactivity. The mechanism responsible for this is still unclear. Eosinophils are thought to play a central part in the development of bronchial hyperreactivity in asthma. It was the aim of this study to assess the relation of bronchial hyperresponsiveness to potential markers of eosinophilic inflammation in peripheral blood. Eosinophil count, the concentration of serum eosinophilic cationic protein, the capacity of purified eosinophils to generate leukotriene C4, and bronchial reactivity was studied in 24 non-atopic children born prematurely, 12 healthy controls, and 12 children with asthma aged 6 to 9 years. There was no difference in serum concentrations on eosinophil cationic protein and eosinophil counts. However, eosinophils from the 15 formerly preterm infants with significant bronchial hyperreactivity generated significantly higher amounts of leukotriene C4 than normal controls and prematurely born children without bronchial hyperreactivity. Levels of leukotriene C4 in this group were comparable with those obtained with eosinophils from patients with asthma. In contrast with cells from the other groups, eosinophils from the children with bronchial hyperreactivity born prematurely show no enhancement of leukotriene C4 generation on prestimulation with platelet activating factor. It is concluded that bronchial hyperreactivity of children born prematurely is accompanied by the prestimulation of eosinophils.     

Blood eosinophils, leukotriene C4 generation, and bronchial hyperreactivity in formerly preterm infants

Infants born prematurely are known to display longstanding bronchial hyperreactivity. The mechanism responsible for this is still unclear. Eosinophils are thought to play a central part in the development of bronchial hyperreactivity in asthma. It was the aim of this study to assess the relation of bronchial hyperresponsiveness to potential markers of eosinophilic inflammation in peripheral blood. Eosinophil count, the concentration of serum eosinophilic cationic protein, the capacity of purified eosinophils to generate leukotriene C4, and bronchial reactivity was studied in 24 non-atopic children born prematurely, 12 healthy controls, and 12 children with asthma aged 6 to 9 years. There was no difference in serum concentrations on eosinophil cationic protein and eosinophil counts. However, eosinophils from the 15 formerly preterm infants with significant bronchial hyperreactivity generated significantly higher amounts of leukotriene C4 than normal controls and prematurely born children without bronchial hyperreactivity. Levels of leukotriene C4 in this group were comparable with those obtained with eosinophils from patients with asthma. In contrast with cells from the other groups, eosinophils from the children with bronchial hyperreactivity born prematurely show no enhancement of leukotriene C4 generation on prestimulation with platelet activating factor. It is concluded that bronchial hyperreactivity of children born prematurely is accompanied by the prestimulation of eosinophils.     

Does the severity of atopic dermatitis correlate with serum IgE levels?

Recent studies suggest an association between atopic phenotypes and serum IgE levels. In contrast to asthma, this association has not been proven for atopic dermatitis. For 345 children (mean age 2.9 years), we investigated a correlation of the severity of eczema (defined by SCORAD score) and serum IgE levels. Additionally, the data was analyzed for differences between children with high and low SCORAD quartile. Parameters such as genetic background, the prevalence of other atopic phenotypes such as bronchial asthma, allergic rhinoconjunctivitis, and allergic sensitization were recorded. Our results indicate a significant correlation between SCORAD and serum IgE levels (R = 0.31, p < 0.001), but the standard deviation was large. Children with atopic dermatitis showed a high prevalence of sensitization to foods independent of the IgE levels; children with high SCORAD levels showed a sensitization to aeroallergens significantly more often (p < 0.02). No differences were found in prevalences of atopic family background, or a number of additional atopic symptoms such as asthma and allergic rhinoconjunctivitis. These results suggest that serum IgE levels seem to correlate with the degree of eczema. Children with severe atopic dermatitis and high IgE levels are at risk for sensitization to food allergens and aeroallergens.     

Exhaled NO and breath condensate

A growing interest has recently directed toward non invasive methods, such as exhaled nitric oxide (FE(NO)) measurement and exhaled breath condensate (EBC) collection, for the assessment of asthmatic inflammation. FE(NO) is a reliable marker of eosinophilic airway inflammation and it can be measured by means of a standardized technique in children starting from the age of 4. FE(NO) may have useful applications both in asthma diagnosis and monitoring. EBC is obtained cooling exhaled air and its composition is believed to mirror the characteristics of airway lining fluid. The compounds detected in EBC are markers of inflammation and oxidative stress occurring in asthmatic lung. While EBC is still only a research tool, FENO measurement is closer to clinical practice and lately it has been included in some treatment algorithms for asthma.     

Increase in the prevalence of rhinitis among Danish children from 1986 to 2001

In recent decades, there has been a worldwide increase in the prevalence of atopic diseases. The aim of this study was to investigate whether there has been a change in the prevalence of rhinitis among children in Denmark from 1986 to 2001. We compared data from two random population-based samples of Danish children, aged 7-17 yr, who were examined in 1986 (n = 527) and 2001 (n = 480) using similar designs. Symptoms of rhinitis, skin test reactivity, and bronchial responsiveness to inhaled histamine were assessed. The prevalence of rhinitis increased from 11.8% in 1986 to 23.3% in 2001 (p < 0.001). The increase was most pronounced among subjects who suffered from non-allergic rhinitis (p < 0.001), and among subjects with severe symptoms (p < 0.001). The prevalence of asymptomatic positive skin prick test (SPT) decreased substantially (p < 0.001). A history of asthma and parental atopic disease were strong predictors of non-allergic rhinitis, whereas a history of asthma, parental atopic disease, bronchial hyperresponsiveness, eczema, and age at examination were statistically significant predictors of allergic rhinitis. The prevalence of non-allergic rhinitis among Danish children has increased substantially from 1986 to 2001. Furthermore, in general more severe symptoms of rhinitis were observed in 2001 compared with 1986. These results underline the importance of using objective measurements such as skin test reactivity when estimating time trends in the prevalence of allergic airways disease, as clinical interviews alone can be misleading.     

Effect of nasal steroid treatment on airway inflammation determined by exhaled nitric oxide in allergic schoolchildren with perennial rhinitis and asthma

Rhinitis is common in asthmatic schoolchildren who are allergic to animal dander and constantly and indirectly exposed to these allergens in their everyday environment. As a patho‐physiological linkage between nasal and bronchial inflammation has been proposed to exist, the primary objective of this study was to determine whether nasal administration of mometasone furoate (MSNF) can reduce bronchial inflammation, as reflected in the level of exhaled nitric oxide (F_ENO) in asthmatic schoolchildren with dander allergy and mild‐to‐moderate rhinitis. Forty such children were assigned randomly to be treated for 4 wk with MSNF or placebo, employing a double‐blind procedure. F_ENO was the primary end‐point measured and secondary end‐points were nasal levels of NO, the concentration of eosinophilic cationic protein (ECP) in nasal lavage, the relative numbers of eosinophils in blood, forced expiratory volume in 1 s (FEV₁), peak expiratory flow (PEF) and scoring of symptoms. There was no significant difference in the F_ENO values of the treated and control groups at any time‐point, whereas the nasal level of ECP was lower in the treated group compared with placebo (p = 0.05) on both days 7 and 28, and compared with baseline for the treated group (p = 0.06 on day 7, p = 0.02 on day 28). Furthermore, the mean blood eosinophil count decreased in the treated group, which also demonstrated lower scores for nasal symptoms compared with placebo, but neither of these differences were statistically significant. FEV₁, PEF and nasal levels of NO remained unchanged in both groups. Four weeks of nasal treatment with MSNF had no effect on bronchial inflammation, as reflected by exhaled NO, whereas signs of nasal and systemic eosinophil activation were reduced. Thus, nasal administration of a steroid as a strategy to reduce asthmatic inflammation remains questionable in mild‐to‐moderately severe cases of perennial rhinitis and asthma.