Determinants of exhaled nitric oxide levels (FeNO) in childhood atopic asthma: evidence for neonatal respiratory distress as a factor associated with low FeNO levels.

BACKGROUND: In allergic asthmatic children exhaled nitric oxide (FeNO) levels are related to eosinophilic inflammation by correlation analysis. Whether FeNO can be modified by factors potentially influencing the natural history of asthma in early life is not known. OBJECTIVE: To evaluate the frequency of anamnestic factors influencing the natural history of asthma and to identify potential determinants for elevated or low FeNO levels by multivariate analysis. METHODS: One hundred seventy-one children with mild-moderate asthma were stratified according to their FeNO levels into three groups: low (<20 ppb), mid (20-40 ppb), and high (>40 ppb). The frequency of nine anamnestic factors together with indices of allergic sensitization (total and allergen-specific immunoglobulin E [IgE], blood eosinophil counts) and of airflow limitation (forced expiratory volume in one second [FEV(1)]% predicted) were evaluated. Results. Among factors related to the patient history, neonatal respiratory distress was reported only in children with low FeNO levels, whereas this factor was never reported in children with mid-to-high FeNO levels (p = .008). As compared with low FeNO group, mid and high FeNO groups showed higher eosinophil counts and a tendency to have lower FEV(1) values. By multivariate analysis, four factors (eosinophils >300 cells/mm(3), cat-specific IgE, house dust mites [HDM]-specific IgE, FEV(1) ≤ 86% predicted) turned out to be significantly associated with mid-high FeNO levels and two factors (eosinophils >600 cells/mm(3), total IgE >355 kU/L) with high FeNO levels. CONCLUSIONS: Besides confirming the well-known tight association between blood eosinophilia and/or allergic sensitization and FeNO, these data provide new evidence for neonatal respiratory distress as potential factor associated with low FeNO levels in childhood atopic asthma.

Real-time quantification of wild-type contaminants in glyphosate tolerant soybean.

BACKGROUND: Trait purity is a key factor for the successful utilization of biotech varieties and is currently assessed by analysis of individual seeds or plants. Here we propose a novel PCR-based approach to test trait purity that can be applied to bulk samples. To this aim the insertion site of a transgene is characterized and the corresponding sequence of the wild-type (wt) allele is used as diagnostic target for amplification. As a demonstration, we developed a real-time quantitative PCR method to test purity of glyphosate tolerant (Roundup Ready, RR) soybean. RESULTS: The soybean wt sequence at the RR locus was characterized and found to be highly conserved among conventional genotypes, thus allowing the detection of possibly any soybean non-trait contaminant. On the other hand, no amplification product was obtained from RR soybean varieties, indicating that the wt sequence is single copy and represents a suitable marker of conventional soybean presence. In addition, results obtained from the analysis of wt-spiked RR samples demonstrate that it is possible to use the real-time PCR assay to quantify the non-trait contamination with an acceptable degree of accuracy. CONCLUSION: In principle this approach could be successfully applied to any transgenic event, provided that the wild-type sequence is conserved and single copy. The main advantages of the assay here described derive from its applicability to bulk samples, which would allow to increase the number of single seeds or plants forming the analytical sample, thus improving accuracy and throughput while containing costs. For these reasons this application of quantitative PCR could represent a useful tool in agricultural biotechnology.

Activity of budesonide on nasal neutrophilic inflammation and obstruction in children with recurrent upper airway infections. A preliminary investigation.

OBJECTIVE: While it is widely accepted that inhaled glucocorticosteroids represent an effective treatment for allergic rhinitis, little is known on the specific effects of this therapeutic approach in other upper airway disorders of childhood. The aim of the study was to evaluate the improvement of clinical symptoms and changes in local cellular inflammatory reaction induced by budesonide inhalation suspension in children with recurrent nasal infections using budesonide inhalation suspension delivered by Rinowash, a nebulizer designed to treat upper airway structures. METHODS: In a randomized, controlled-open study, 14 children (5.88+/-0.56 years of age) with recurrent upper airway infections and chronic nasal obstruction were enrolled and randomly treated for 7-10 days either with budesonide inhalation suspension (250 microg/bidie) (nine patients) or with saline solution (five patients). Before and after treatment, inflammatory cells in nasal brushing and nasal symptom score were evaluated. RESULTS: Out of the nine patients treated with budesonide, two were excluded from the analysis because of acute respiratory infections requiring systemic antibiotic treatment. A significant decrease in nasal brushing neutrophil percentage was observed after treatment with budesonide (P=0.016) but not after saline solution treatment (P=1.00). No significant changes in nasal brushing mononuclear cell or eosinophil proportions were observed after treatment with budesonide inhalation suspension or saline solution (P=NS, each comparison). Treatment with budesonide, but not with saline solution, was associated with a significant reduction in nasal obstruction (P=0.016). CONCLUSIONS: These preliminary data indicate that short-term treatment with budesonide inhalation suspension, used for an indication out of label, may significantly reduce local neutrophilic inflammation and nasal obstruction in children with recurrent upper airway infections.

Correlations between exhaled nitric oxide levels, blood eosinophilia, and airway obstruction reversibility in childhood asthma are detectable only in atopic individuals.

The aim of this study was to compare in atopic and nonatopic asthmatic children correlations between two inflammation parameters, i.e., blood eosinophilia and exhaled nitric oxide (FE(NO)), and pulmonary function values, at baseline and after beta(2)-adrenergic bronchodilators. Ninety-two steroid-naive asthmatic children were evaluated: 26 were skin prick test- and RAST-negative (nonatopic subjects), whereas 66 were atopic, 15 being sensitized only to house dust mites (monosensitized) and 51 to mites and to at least one other class of allergens (polysensitized). Baseline spirometric values (FEV(1) and FEF(25-75%)) were similar in atopic and nonatopic groups (P > 0.1, each comparison). However, when compared to nonatopic subjects, atopic children showed a significantly higher degree of blood eosinophilia (3.0% and 6.7% white blood cell count, respectively; P = 0.0001) and higher FE(NO) levels (6.8 ppb and 16.0 ppb, respectively; P = 0.0001). While a positive correlation between FE(NO) levels and blood eosinophilia was observed in atopic children (r = 0.25, P = 0.041), no correlations between these two inflammation parameters and baseline pulmonary function values were demonstrated in any of the asthmatic groups. Inhalation of a beta(2)-agonist drug induced in the two asthmatic populations similar improvements in FEV(1) and FEF(25-75%) and no changes in FE(NO) levels or blood eosinophilia. However, only in atopic children positive correlations were found between percent variation in FEV(1) (delta%FEV(1)) and FE(NO) levels (r = 0.35, P = 0.006) or blood eosinophilia (r = 0.26, P = 0.04). Within the atopic group, no differences were found between mono- and polysensitized individuals in all parameters evaluated. Thus only in atopic children did parameters of inflammation correlate with airway obstruction reversibility.

Clinical, physiologic, and roentgenographic changes after pneumonectomy in a boy with Macleod/Swyer-James syndrome and bronchiectasis.

Macleod/Swyer-James syndrome is an uncommon and complex disease characterized by roentgenographic hyperlucency of one lung or lobe due to loss of the pulmonary vascular structure and to alveolar overdistension. This syndrome seems to be an acquired disease that follows viral bronchiolitis and pneumonitis in childhood. It must be differentiated from many other causes of unilateral lung "transradiancy" on the chest roentgenogram, such as those related to congenital bronchial and/or vascular abnormalities. We here describe an 11-year-old patient with Macleod/Swyer-James syndrome and bronchiectasis resulting in severe recurrent bronchopulmonary infections. Despite the severe impairment of pulmonary function, the patient underwent resection of the right lung with progressive improvement of clinical and physiologic parameters.

Changes in inflammatory and clinical parameters and in bronchial hyperreactivity asthmatic children sensitized to house dust mites following sublingual immunotherapy.

UNLABELLED: In allergic patients with rhinoconjunctivitis (RNC), sublingual immunotherapy (SLIT) is effective in reducing both clinical symptoms and immuno-mediated local inflammatory responses. The study evaluates whether SLIT could reduce upper airway inflammation and improve clinical parameters also in children with rhinoconjunctivitis and asthma from house dust mite sensitization. Ten children with mild to intermittent asthma, monosensitized to house dust mites, received SLIT (Der p 1 monthly dose = 48 microg) for 2 years, in addition to "as needed" pharmacologic treatment. Before (T0) and after treatment (T2), changes were evaluated in (1) nasal eosinophilia, (2) intercellular adhesion molecule (ICAM)-1 expression by nasal epithelial cells, (3) RNC, asthma, and drug-intake scores, assessed by diary card, (4) pulmonary function parameters, and (5) bronchial reactivity to methacholine (MCh). RESULTS: All children completed the study without side or adverse effects. After the treatment period, we found no modification in nasal eosinophil values in mean fluorescence channel percentages, but a significant downregulation in ICAM-1 expression by nasal epithelial cells [mean (mfc): T0: 13.5 +/- 3.8 mfc; T2:4.6 +/- 0.5 mfc; p = 0.04]. These changes were associated with a reduction in RNC score [median values: T0: 3.4 (1.4-6.2); T2: 1.1 (0.6-2.4) p = 0.012], asthma score [median values: T0: 0.5 (0.4-1.0); T2: 0.3 (0.1-0.5); p = 0.005] and drug-intake score [median values: T0: 4.2 (3.1-5.3); T2: 1.1 (0-3.0); p = 0.005]. These clinical effects were not associated with changes in pulmonary function parameters (p > 0.05), but with improvement in bronchial reactivity to MCh [mean values: T0: 338.8 (91.5-1255.5); T2: 1698.2 (1,110.5-2,597.1); p = 0.02]. To what extent these observations may be related to the natural improvement of respiratory allergy symptoms with age remains to be determined.

Intermittent gaseous bowel distention: atypical sign of congenital tracheoesophageal fistula.

Three girls, 5-, 9-, and 15-year-old, were evaluated for recurrent airway infections and pneumonia. Chest X-rays, which included the upper portion of the abdomen, showed marked gaseous bowels distention, while computed tomography scans of the chest demonstrated the presence of tracheoesophageal fistula (TEF), confirmed by fiberoptic bronchoscopy. Abdominal gaseous distension, a known possible clinical manifestation of TEF in the neonatal period generated by airflow through the fistula into the oesophagus, has not been reported as a clue to the diagnosis in older children. When detected in patients with recurrent respiratory infection, should raise the suspicion of unrecognized TEF.

Gastroesophageal reflux and its clinical manifestation at gastroenteric and respiratory levels in childhood: physiology, signs and symptoms, diagnosis and treatment.

Gastroesophageal reflux (GER) is a physiological process occurring with different frequency and characteristics in healthy infants, children and adults, most episodes being brief and asymptomatic. By contrast, GER disease (GERD) occurs when this normal event results in the occurrence of symptoms/signs or complications involving the upper portion of the gastroenteral tract and the respiratory system. Transient relaxations of the lower esophageal sphincter represent the major mechanism responsible for reflux episodes, possibly associated with gastroesophageal dysfunctional motility, excessive gastric acid secretion or anatomic abnormalities. The diagnosis of GERD, that is, a causal relationship between reflux and GERD symptoms, may be difficult to determine and make clinically, with support needed from diagnostic evaluations, and final confirmation by response to treatment. Management of GER/GERD should follow a stepwise approach: lifestyle modifications, pharmacologic therapy and surgical procedures; some of these steps may occur simultaneously. In children with mild symptoms and without anatomic abnormalities, the initial choice should be lifestyle modifications and pharmacologic therapy with prokinetic agents, antacids and histamine-2-receptor antagonists. For severe GERD, therapeutic options include proton pump inhibitors and antireflux surgery. In determining the best approach for each individual patient, efficacy, safety, morbidity, compliance and cost must be considered.

Relationship between body mass index and asthma characteristics in a group of Italian children and adolescents.

The prevalence of asthma and obesity, two often associated conditions, is influenced not only by age and gender but also by lifestyle factors. This study aimed to determine whether, in a Mediterranean northern Italian region, Liguria, an increased prevalence of obesity could be detected in asthmatic children and adolescents and to evaluate the possible relationship between body mass index (BMI) and the characteristics and/or severity of asthma. BMI was determined in 554 asthmatic subjects (2.2-16.1 years) and 625 age-matched controls; BMI was expressed as a continuous variable in standard deviation score (SDS) units, determined as difference between the individual observed value and the reference mean for age and sex, divided by the corresponding standard deviation (BMI-SDS). Overweight/obesity was set at BMI-SDS of 2 or more. BMI-SDS was significantly higher in controls than in asthmatics (p = 0.04); however, the proportion of overweight/obesity subjects (BMI-SDS > or = 2) was similar in controls and in asthmatic patients (p = 0.08). Evaluation of the asthmatic group revealed that BMI-SDS was independent of gender (p = 0.57), atopic sensitization (p = 0.69), and comorbidity with other allergic symptoms (p = 0.60). By contrast, BMI-SDS was lower in preschool-age children than in school-age children and adolescents (p < 0.0001), in subjects with a high rate of acute respiratory tract infections (p = 0.04), and in those not treated with inhaled corticosteroids (IGCs) (p = 0.02). Although an increase in the prevalence of overweight/obesity was not detected in asthmatic children and adolescents, the results reported here suggest a preventive surveillance of calorie intake and a promotion of physical activity in children requiring long-term treatment with inhaled glucocorticosteroids.

Steroid-naive adolescents with mild intermittent allergic asthma have airway hyperresponsiveness and elevated exhaled nitric oxide levels.

Although atopic asthma symptoms often seem to disappear around puberty, subjects in this age group may experience unexpected, often severe, asthma attacks. This may be related to persistence of untreated airway hyperresponsiveness/inflammation in a life period characterized by low perceptiveness of disease-related symptoms. This study was designed to evaluate the prevalence and the severity of bronchial hyperreactivity and the exhaled nitric oxide (FENO) levels in a group of steroid-naive asthmatic adolescents. Fifty-two patients with mild-intermittent asthma were studied, ages 12 to 16, sensitized to house dust mites; 22 age-matched controls, were also studied. Asthma patients showed FEV1, FEF25-75%, and FVC values not significantly different from controls, (p > 0.05, each comparison). By contrast, although none of the control subjects showed bronchial hyperreactivity, increased airway responsiveness to methacholine (MCh) was demonstrated in the majority of the patients and found to be severe in 36.5% (MCh PD20 > or = 400 microg or accumulative dose < or = 1220 microg) and moderate in 32.7% (MCh PD20 400-1400 microg or accumulative dose 1220-4620 microg). In addition, FENO concentrations were significantly higher in asthmatics, as compared with controls (20.4 +/- 5.3 ppb and 4.4 +/- 0.7 ppb, respectively; p < 0.01) and 83% of the patients had FENO levels higher than 8.9 ppb (i.e., > 2 standard deviations of the mean in control subjects). A positive, statistically significant correlation was found between FEF25-75% values and MCh PD20 (r = 0.358; p < 0.01) or MCh accumulative dose (r = 0.355; p < 0.05). No correlations were demonstrated between MCh responsiveness and FVC or FEV1 values or FENO levels and between FENO levels and pulmonary function parameters (p > 0.05). The high incidence of bronchial hyperresponsiveness to MCh and of airway inflammation (as demonstrated by the elevated FENO levels) in adolescents with mild asthma suggests the need for more accurate evaluation and, possibly, for early intervention with antiinflammatory drugs in a significant proportion of patients in this age group.