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Background Asthma is a heterogeneous disease and its different phenotypes need to be better characterized from a biochemical-inflammatory standpoint. This study aimed to apply the metabolomic approach to exhaled breath condensate (breathomics) to discriminate different asthma phenotypes, with a particular focus on severe asthma in children. Methods In this cross-sectional study, we recruited 42 asthmatic children (age, 8-17 years): 31 with nonsevere asthma (treated with inhaled steroids or not) and 11 with severe asthma. Fifteen healthy children were enrolled as controls. Children performed exhaled nitric oxide measurement, spirometry, exhaled breath condensate ( EBC) collection. Condensate samples were analyzed using a metabolomic approach based on mass spectrometry. Results A robust Bidirectional- Orthogonal Projections to Latent Structures- Discriminant Analysis (O2 PLS- DA) model was found for discriminating both between severe asthma cases and healthy controls ( R2 = 0.93; Q2 = 0.75) and between severe asthma and nonsevere asthma ( R2 = 0.84; Q2 = 0.47). The metabolomic data analysis leads to a robust model also when the 3 groups of children were considered altogether ( K = 0.80), indicating that each group is characterized by a specific metabolomic profile. Compounds related to retinoic acid, adenosine and vitamin D ( Human Metabolome Database) were relevant for the discrimination between groups. Conclusion The metabolomic profiling of EBC could clearly distinguish different biochemical-metabolic profiles in asthmatic children and enabled the severe asthma phenotype to be fully discriminated. The breathomics approach may therefore be suitable for discriminating between different asthma metabolic phenotypes. [ABSTRACT FROM AUTHOR]

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (i CAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on ( ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved. [ABSTRACT FROM AUTHOR]

To cite this article: van der Valk RJP, Baraldi E, Stern G, Frey U, de Jongste JC. Daily exhaled nitric oxide measurements and asthma exacerbations in children. Allergy 2012; 67: 265-271. Abstract Background: Fractional exhaled Nitric Oxide (FeNO) is a biomarker for eosinophilic airway inflammation and can be measured at home on a daily basis. A short-term increase in FeNO may indicate a higher risk of future asthma exacerbations. Objective: To assess changes in FeNO before and after asthma exacerbations compared to a stable control period. Methods: A post hoc analysis was performed on daily FeNO measurements over 30 weeks in children with asthma ( n = 77). Moderate exacerbations were defined by an increase in symptom scores and severe exacerbations by prescription of prednisone. Individual mean and maximum FeNO, the variability of FeNO assessed by the coefficient of variation (CV), and slopes of FeNO in time were all quantified in 3-week blocks. Cross-correlation of FeNO with symptoms and autocorrelation of FeNO were assessed in relation to exacerbations and examined as predictors for exacerbations compared to reference periods using logistic regression. Results: Fractional exhaled nitric oxide could be assessed in relation to 25 moderate and 12 severe exacerbations. The CV, slope, cross-correlation, and autocorrelation of daily FeNO increased before moderate exacerbations. Increases in slope were also randomly seen in 19% of 2-week blocks of children without exacerbations. At least 3-5 FeNO measurements in the 3 weeks before an exacerbation were needed to calculate a slope that could predict moderate exacerbations. No specific pattern of FeNO was seen before severe exacerbations. Conclusion: Fractional exhaled nitric oxide monitoring revealed changes in FeNO prior to moderate exacerbations. Whether this can be used to prevent loss of asthma control should be further explored. [ABSTRACT FROM AUTHOR]

To cite this article: Bozzetto S, Carraro S, Giordano G, Boner A, Baraldi E. Asthma, allergy, and respiratory infections: the vitamin D hypothesis. Allergy 2012; 67: 10-17. Abstract The recent discovery that every tissue in the human body has vitamin D receptors and that vitamin D has pleiotropic effects has prompted an increased interest in this hormone. Vitamin D deficiency is widespread and on the increase. There is no consensus on the serum vitamin D levels to consider appropriate for global health, the cutoffs for its deficiency, or the doses to use for its supplementation. Vitamin D seems to correlate closely with host reactions against various respiratory infections. Epidemiological studies have shown that low serum 25-hydroxyvitamin D levels are associated with a higher risk of upper and lower respiratory infections in children and a shortage of vitamin D may contribute to asthmatic patients' symptoms and morbidity rates. There are studies highlighting associations between childhood asthma, fetal lung and/or immune development, and maternal vitamin D intake. An insufficiency of this vitamin also seems to be implicated in the onset of childhood atopy and food allergies. The hypothesis is that vitamin D could have a central role in these pathological situations and that it may represent a novel preventive and/or therapeutic strategy. This article reviews and discusses published data on the relationship between vitamin D and asthma and allergy, emphasizing the need for controlled, prospective studies on vitamin D supplementation to clarify whether it has a role in the prevention of and treatment for asthma and allergic conditions. [ABSTRACT FROM AUTHOR]

Background: Asthmatic patients have high exhaled nitric oxide (NO) levels. NO-mediated inflammatory actions are mainly due to NO conversion into reactive nitrogen species, which can lead to nitrotyrosine formation. The aim of this study was to assess 3-nitrotyrosine (3-NT) levels in exhaled breath condensate (EBC) of asthmatic and healthy children and to investigate whether there is any relationship with exhaled NO (FENO) and lung function. Methods: The study included 20 asthmatic children (10 steroid-naive with intermittent asthma, 10 steroid-treated with unstable persistent asthma) and 18 healthy controls. They underwent FENO measurement, EBC collection and spirometry. 3-NT was measured by a new liquid chromatography–tandem mass spectrometry (LC-MS/MS) method in isotopic dilution. Results: The median EBC concentration of 3-NT (expressed as nitrotyrosine/tyrosine ratio × 100) in asthmatic children was fivefold higher than in healthy subjects [0.23% (0.12–0.32) vs 0.04% (0.02–0.06), P < 0.001] with no difference between steroid-naive and unstable steroid-treated asthmatic patients. FENO levels were higher in asthmatic [44.6 ppb (36.0–66.0)] than in healthy children [7.5 ppb (6.0–8.8), P < 0.001]. No correlation was found among 3-NT, FENO and lung function parameters. Conclusion: Nitrotyrosine is high in EBC of asthmatic children and could be considered as a noninvasive marker of nitrosative events in the airways. [ABSTRACT FROM AUTHOR]

Montelukast has been shown to be effective in controlling the increase in exhaled NO in asthmatic children re-exposed to house dust mite (HDM). This study compared the effect of low dose inhaled budesonide and oral montelukast in preventing the expected relapse of airway inflammation and reactivity in a group of 24 mild asthmatic children allergic to HDM after a brief period of exposure to relevant allergens.Lung function, bronchial hyperresponsiveness (BHR) to methacholine (PC20), fractional exhaled nitric oxide (FeNO) levels and sputum eosinophilia were evaluated.Pulmonary function remained stable. The BHR was unchanged after exposure in the group treated with budesonide, whereas a significant increase (P = 0.028) was observed in the patients receiving montelukast. No significant difference was observed in FeNO levels after exposure to mite antigen in the two groups. In both the groups of asthmatic children we observed a significant increase in sputum eosinophil % after the exposure to mite antigen.The significant increase in BHR level observed in the group of children receiving montelukast suggests a more comprehensive effect as disease controller by inhaled steroids than by leukotriene antagonist in allergic asthmatic children re-exposed to relevant allergens. [ABSTRACT FROM AUTHOR]

Bodini A, Peroni D, Vicentini L, Loiacono A, Baraldi E, Ghiro L, Corradi M, Alinovi R, Boner AL, Piacentini GL. Exhaled breath condensate eicosanoids and sputum eosinophils in asthmatic children: A pilot study. Pediatr Allergy Immunol 2004: 15: 26–31. © 2004 Blackwell Munksgaard Cysteinyl leukotrienes (cys-LTs), LTB4 and 8-isoprostane are increased in the exhaled breath condensate (EBC) from asthmatic patients. The aim of this study was to investigate whether the measurement of cys-LTs, LTB4 and 8-isoprostane in EBC can reflect the level of airway inflammation assessed by induced sputum in asthmatic children sensitized to house dust mite (HDM) during natural avoidance of HDM allergens. Twelve children were evaluated at the time of admission (T0) and after 3 months of stay (T1) at the Istituto Pio XII (Misurina, Italian Dolomites 1756 m). Sputum eosinophil percentage and measurement of cys-LTs, LTB4 and 8-isoprostanes in the breath condensate at T0 and T1 were evaluated. Eosinophil percentage in induced sputum was 8.5 ± 1.1% at T0 and 3.5 ± 0.4% at T1 (p = 0.011). Neutrophil percentage in sputum was 1.1 ± 0.5% at T0 and 1.5 ± 1.0% at T1 (ns). Cys-LTs mean level was 14.24 ± 4.53 pg/ml at T0 and 4.65 ± 0.68 pg/ml at T1 (p = 0.0125). LTB4 level was 2.36 ± 0.19 pg/ml at T0 and 2.41 ± 0.23 pg/ml at T1 (ns). 8-Isoprostane level reduced from 17.47 ± 3.18 pg/ml at T0 to 7.36 ± 3.26 pg/ml at T1 (p = 0.003). This study show that exhaled cys-LTs and 8-isoprostane, as well as eosinophil percentage in induced sputum, are reduced after allergen avoidance in asthmatic children suggesting a potential application of EBC for the non-invasive evaluation of airway inflammation in asthma in allergic asthmatic children. [ABSTRACT FROM AUTHOR]

Exhaled nitric oxide (FENO) is a surrogate marker of eosinophilic airway inflammation. The measurement of this gas can be easily performed in children and the result is immediately available. Because of these characteristics, measurement of FENO is slowly becoming part of the routine clinical evaluation of an asthmatic patient. FENO measurement may have a role both in the diagnosis of asthma and as a guide in therapy algorithms. For example when FENO levels are persistently normal and the asthmatic child is asymptomatic, the steroid therapy may be decreased or even stopped. In patients with acute or chronic rhinosinusitis the levels of nasal nitric oxide (nNO) are significantly decreased, while they rise up after a course of antibiotics. The measurement of nasal NO has been proposed as a functional test to evaluate sinus ventilation. Nasal NO is significantly reduced also in primary ciliary dyskinesia and can be used as a screening tool to identify patients affected by this condition. [ABSTRACT FROM AUTHOR]

Determines the safety and feasibility of the exhaled breath condensate procedure in a group of asthmatic children with varying levels of severity. Pulmonary function and fractional exhaled nitric oxide measurement; Analysis of pertinent topics and relevant issues; Implications on pediatrics.

In the May 1, 2001 issue of the journal "Thorax," researchers suggest that it is possible to distinguish different patterns of difficult childhood asthma by measuring exhaled nitrogen oxide (NO). The knowledge that severe asthma may have different phenotypes with different types of airway inflammation is not new and has been clearly shown by bronchoalveolar lavage and airway biopsy studies in adult patients. The potential importance of these data lies in the classification of different patterns by using a non-invasive instantaneous measurement such as NO. Exhaled NO levels are known to be increased in atopic asthma, to increase during an exacerbation, to decrease with anti-inflammatory therapy, and to rise as the dose of inhaled steroids is reduced.

The article offers information on study related to poor response of wheezing children with tracheobronchomalacia to asthma therapy. It observed the trend of wheezing children under three years of age, collected from the clinical database and found that several children underwent flexible bronchoscopy. It highlights that main cause of poor response to asthma therapy was tracheobronchomalacia.

The article discusses the case of a three-year-old boy with mild intermittent asthma, who developed life-threatening status asthmaticus refractory to maximal conventional treatment and required extracorporeal membrane oxygenation support for survival. His past medical history was notable for two mild wheezing episodes, with no recurrence in the last 12 months.