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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]

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]