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Summary. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 ± 0.7 years) were receiving inhaled steroids (flunisolide, 0.8–1 mg daily) or beclomethasone (0.2–0.4 mg daily), while the remaining 63 (mean age, 12.0 ± 0.4 yrs) were-steroid naive and treated only with inhaled β2-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8–1 mg daily, or beclomethasone, 0.2–0.4 mg daily). Regardless of the type of data analysis (peak , plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P

Gastroesophageal reflux (GER) may be associated with chronic or recurrent asthma-like symptoms secondary to bronchoconstrictor reflexes and/or inhalation of gastric content. The presence of lipid-laden alveolar macrophages has been proposed as an index to establish the degree of gastric aspiration. We evaluated 20 children with "difficult to treat" respiratory symptoms and a clinical history suggestive of GER. All children underwent 24-hr esophageal pH monitoring (pHm) and fiberoptic bronchoscopy with bronchoalveolar lavage (BAL). The amount of lipid per single macrophage was determined by a semiquantitative method, using fluorescence microscopy to detect Nile-Red-stained BAL cells and calculating a lipid-laden macrophage index (LLMI). Eleven children had positive pHm recordings, suggesting the presence of GER (pH-positive patients), and 9 had negative pHm records (pH-negative patients). The pH-positive patients had higher percentages of neutrophils and higher LLMI than the pH-negative children (P 0.05; each correlation). In contrast, a single correlation was found between % BAL neuytrophils and LLMI, both in the pH-positive and in the pH-negative patients (r = 0.72, P = 0.02 and r = 0.71, P = 0.04, respectively). These data demonstrate that a significant proportion of pH-positive patients with respiratory symptoms have BAL abnormalities that suggest airway inflammation and gastric content aspiration. However, the intensity of GER as indicated by pH monitoring does not correspond with BAL data in all patients.

Sinusitis is a common complication of non-allergic and allergic rhinitis, and can trigger lower respiratory diseases, such as bronchitis and asthma. Standard radiography is unable to give any data about the underlying pathological mechanisms (infectious or allergic) involved and infectious rhinosinusitis is very common in pediatric age, even in allergic patients. We investigated the possibility of obtaining more useful diagnostic information, performing nasal brushing (NB) on 117 children with recurrent respiratory symptoms. The following hypothesis were evaluated: (1) whether NB neutrophil/eosinophil percentages and/or NB culture could predict the radiological evidence of maxillary sinusitis; and (2) whether differences between nonallergic and allergic patients could be detected. In the total patient group and in the nonallergic group, the comparison of NB neutrophil percentages in patients with and without maxillary sinusitis showed a statistically significant difference (median 2 and 18%, respectively; P0.001). In the nonallergic group, a NB neutrophil rateor = 5% was chosen as a cut-off between positive and negative NB diagnosis of rhinosinusitis and NB data were compared with radiological investigations. The results obtained showed that NB was fairly sensitive (91%) and predictive (84%). In allergic patients, neither neutrophil nor eosinophil percentages significantly correlated with the presence of sinusitis. Microbiological studies showed that, even if the presence of bacteria in NB resulted associated with sinusitis, a negative culture was not predictive of the absence of the disease. We therefore suggest that NB describes the present inflammatory status of the upper airways, hence, it is more suitable to describe the inflammation related to ongoing upper respiratory tract infections rather than chronic inflammation due to allergic rhinitis, characterized by relapsing episodes of acute inflammation. In conclusion, we propose to consider NB a reliable tool in the diagnosis of rhinosinusitis, particularly in nonallergic pediatric patients. Compared to standard radiological techniques, NB makes it possible to avoid radiation exposure and gives information about the pathological mechanisms involved in the single patient.

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 beta2-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; p0.01). Interestingly, 14 out of 22 asthmatic children had NO levels8.8 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; p0.01, 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 (p0.1, 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.

Background: In gastro-oesophageal reflux (GER), micro-aspirations of gastric fluid may damage the epithelial surface of the airways, an important source of endogenous nitric oxide (NO). Objectives: The aim of the study was to evaluate the possible influence of GER on fractional exhaled nitric oxide (FENO) release. Methods: FENO levels were compared in two age-matched groups of allergic children: (1) 20 with mild asthma, responding to standard anti-asthma pharmacologic therapy (asthmatic children) and (2) 12 with mild ‘asthma-like symptoms’ and GER. Results: No differences in pulmonary functions parameters (FEV1, FVC and FEF25–75%) were found between the two groups of children (p > 0.1); FENO levels were higher in asthmatic children compared with GER children (p = 0.0001). GER children underwent 24-hour oesophageal pH-metry, and possible correlations between pH-metry data, pulmonary functions and FENO levels were evaluated. No correlations were found between pulmonary functions and pH-metry data (p > 0.05, each correlation). In contrast, correlations were observed between FENO levels and pH-metry data, including (1) percentage of study time with pH < 4 (r = –0.80, p = 0.008), (2) number of episodes with pH < 4 (r = –0.76, p = 0.012), and (3) number of episodes >5 min with pH < 4 (r = –0.69, p = 0.02). Conclusions: Thus, FENO levels are lower in allergic children with ‘asthma-like symptoms’ and GER as compared to asthmatic children. The correlations between FENO levels and pH-metry data suggest that inhalation of acid gastric content may interfere with NO production in the airways.

Orally exhaled nitric oxide (NO) levels are increased in children with asthma and thought to reflect the local inflammatory events in the airways. NO production in the lower respiratory airway is reflected in the plateau values of the NO curve, recorded while the patient is performing a slow vital capacity manoeuvre. In young patients, however, plateau values may be difficult to obtain, because the slow vital capacity manoeuvre is often terminated prematurely. In the present study, 60 steroid-naive atopic asthmatic children and 17 normal age-matched controls were asked to perform a slow vital capacity manoeuvre, during which fractional exhaled NO (FEno) levels were measured and evaluated as: a) FEno plateau levels of last part of exhalation (NO plateau); b) FEno peak values, c) area under the FEno curve (AUC). Thirteen out of the 60 steroidnaive patients were reevaluated after a short course of inhaled corticosteroid treatment. Independently of the type of data analysis, FEno values of asthmatics were significantly higher than those observed in normal controls (P0.001, each comparison). In addition, possibly because of upper airway NO contamination, FEno peak values were significantly higher than FEno plateau levels in asthmatic patients and in control subjects (P0.001, each comparison). Both in asthmatics and controls, highly positive correlations were observed between: a) FEno plateau and peak values (r0.7, P0.01, each correlation), b) FEno plateau and AUC values (r0.7, P0.01, each correlation) and c) FEno peak and AUC values (r0.9, P0.001, each correlation). In asthmatic patients, the three types of data analysis were equally sensitive in detecting the decrease in FEno levels induced by inhaled steroid therapy (P0.05, each comparison), with a good correlation between the three data analyses (r0.5, P0.05, each correlation). Thus, although quantitatively different, comparable data reflecting airway inflammation can be obtained evaluating FEno plateau, FEno peak, and area under the curve, on account of possible upper airway contamination in FEno peak, FEno plateau should be preferred to measure lower airway NO production.

SUMMARY. Airway nitric oxide (NO) production can be measured by chemiluminescence analyzer in children able to perform a single low exhalation. The aim of the present study was to evaluate whether exhaled NO (e-NO) peaks (first part of the exhalation) were as useful as e-NO plateaus (last part of the exhalation) in evaluating e-NO production in asthmatic children and in detecting responses to inhaled steroid treatment. E-NO peak, plateau, and rate of production values were measured in 100 atopic asthmatic children using a chemiluminescence analyser. Thirty-seven patients (mean age, 11.1 +/- 0.7 years) were receiving inhaled steroids (flunisolide, 0.8-1 mg daily) or beclomethasone (0.2-0.4 mg daily), while the remaining 63 (mean age, 12.0 +/- 0.4 yrs) were-steroid naive and treated only with inhaled beta(2)-agonists on an as-needed basis. Fifteen out of the 63 steroid-naive patients were reevaluated after a short course (3 weeks) of inhaled corticosteroid treatment (flunisolide, 0.8-1 mg daily, or beclomethasone, 0.2-0.4 mg daily). Regardless of the type of data analysis (peak, plateau, or rate of production), the e-NO values of the steroid-naive patients were significantly higher than those of inhaled steroid-treated patients (P0.01, each comparison). Similarly, in the subgroup of steroid-naive patients, the three methods were able to detect a decrease in e-NO levels by inhaled steroid therapy (P0.001, each comparison). Plotting the difference between e-NO peak and e-NO plateau values against their average, the peak e-NO concentrations were higher than e-NO plateau values. This difference was independent of the absolute e-NO concentration. The results of the two types of data analysis seems to agree more closely in steroid-naive patients than in steroid treated patients, or in the subgroup of steroid-naive patients who received a short course treatment with inhaled steroids. In steroid-treated subjects, the differences were up to five times higher for peak than plateau e-NO values. These data suggest that both e-NO plateau and e-NO peak values are useful in detecting airway NO production in atopic asthmatic children, but they cannot be used interchangeably. Because of possible nasal contamination in e-NO peak measurement, we prefer e-NO plateau levels for evaluating lower airway e-NO production.

Introduction: Chez les patients pediatriques, les manifestations habituelles du reflux gastro-oesophagien (RGO), les renvois et les aigreurs, ne sont que la partie emergee de l'iceberg. La plupart des episodes du RGO ne generent pas de regurgitation. L'objectif de cette etude prospective etait d'evaluer l'incidence du RGO chez les patients pediatriques et le role de la chirurgie anti-reflux chez les patients ayant des symptomes respiratoires «rebelles». Methodes: Cinq cent quatre-vingt-quinze enfants presentant des symptomes respiratoires «rebelles» etaient inclus dans une etude prospective a simple insu pour etudier la correlation entre la presentation clinique (avec ou sans asthme), la pHmetrie oesophagienne, le transit oesogastrique, le lavage bronchioalveolaire, le besoin de chirurgie et l'evolution. Resultats: La pHmetrie mettait en evidence une anomalie chez 47 p. 100 des patients asthmatiques (groupe A) et chez 43 p. 100 des patients dont l'asthme n'etait pas le symptome predominant (groupe B). Parmi l'ensemble des 595 patients, une intervention d'anti-reflux etait realisee chez 8 p. 100 devant l'absence de reponse stable au traitement medical. Aucune complication majeure de la chirurgie n'etait constatee. L'amelioration des symptomes respiratoires etait importante (Visick 1) dans 69 p. 100 des cas et moderee (Visick 2) dans 27 p. 100 des cas. Une aggravation des symptomes (Viscik 4) etait observee dans 4 p. 100 des cas. Conclusions: Les resultats de cette etude soulignent l'importance de la symptomatologie, de la reponse clinique aux traitements medicaux et du lavage bronchioalveolaire compares aux mesures du pH oesophagien lors de la prise en charge des patients pediatriques presentant des symptomes respiratoires «rebelles». Actuellement, il n'existe pas d'outil ayant une valeur diagnostique prouvee chez ces patients. La fondoplication est recommandee uniquement en cas de relation fortement suspecte entre les symptomes supra-oesophagiens et le reflux gastro-oesophagien.