Silvia Carraro

University of Padova, Padova, Veneto, Italy

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Publications (67)317.96 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Problematic severe asthma is a heterogeneous disease with multiple phenotypes. It is rare (<5% of children with asthma), but accounts for 30-50% of all pediatric asthma healthcare costs. This review looks into the currently used management strategies and the innovative treatments, considering both conventional medications and innovative biological therapies for targeting airway inflammation. Patients with problematic severe asthma should be seen by pediatric asthma specialists using a stepwise approach. The first step is to exclude alternative diagnoses; the second is to consider and exclude comorbidities, and assess adherence to medication; the third step involves identifying the pattern of inflammation; and response to treatment in the fourth. Innovative biological therapies are emerging and healthcare professionals should know how to handle them. Patient phenotyping is the main step towards a targeted therapeutic strategy. A careful management is important for children with severe asthma, who form a small but challenging group of patients. More research efforts are needed to enable a personalized medicine and a biomarker-driven approach.
    Current opinion in pulmonary medicine. 01/2015; 21(1):16-21.
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    ABSTRACT: S-nitrosoglutathione is an endogenous airway smooth muscle relaxant. Increased airway S-nitrosoglutathione breakdown occurs in some asthma patients. We asked whether patients with increased airway catabolism of this molecule had clinical features that distinguished them from other asthma patients. We measured S-nitrosoglutathione reductase expression and activity in bronchoscopy samples taken from 66 subjects in the Severe Asthma Research Program. We also analysed phenotype and genotype data taken from the program as a whole. Airway S-nitrosoglutathione reductase activity was increased in asthma patients (p = 0.032). However, only a subpopulation was affected and this subpopulation was not defined by a "severe asthma" diagnosis. Subjects with increased activity were younger, had higher IgE and an earlier onset of symptoms. Consistent with a link between S-nitrosoglutathione biochemistry and atopy: 1) interleukin 13 increased S-nitrosoglutathione reductase expression and 2) subjects with an S-nitrosoglutathione reductase single nucleotide polymorphism previously associated with asthma had higher IgE than those without this single nucleotide polymorphism. Expression was higher in airway epithelium than in smooth muscle and was increased in regions of the asthmatic lung with decreased airflow. An early-onset, allergic phenotype characterises the asthma population with increased S-nitrosoglutathione reductase activity.
    The European respiratory journal. 10/2014;
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    ABSTRACT: Chronic obstructive respiratory disorders such as asthma and chronic obstructive pulmonary disease often originate early in life. In addition to a genetic predisposition, prenatal and early-life environmental exposures have a persistent impact on respiratory health. Acting during a critical phase of lung development, these factors may change lung structure and metabolism, and may induce maladaptive responses to harmful agents, which will affect the whole lifespan. Some environmental factors, such as exposure to cigarette smoke, type of childbirth and diet, may be modifiable, but it is more difficult to influence other factors, such as preterm birth and early exposure to viruses or allergens. Here, we bring together recent literature to analyse the critical aspects involved in the early stages of lung development, going back to prenatal and perinatal events, and we discuss the mechanisms by which noxious factors encountered early on may have a lifelong impact on respiratory health. We briefly comment on the need for early disease biomarkers and on the possible role of "-omic" technologies in identifying risk profiles predictive of chronic respiratory conditions. Such profiles could guide the ideation of effective preventive strategies and/or targeted early lifestyle or therapeutic interventions.
    The European respiratory journal. 10/2014;
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    ABSTRACT: To assess a group of adolescents with bronchopulmonary dysplasia (BPD) from a biochemical-metabolic standpoint, applying the metabolomic approach to studying their exhaled breath condensate (EBC).
    The Journal of pediatrics. 10/2014;
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    ABSTRACT: Among the risk factors for osteoporosis and fractures, gynecological history (fertile period, parity and breastfeeding) play an important part. Changes in calcium metabolism to enable an adequate mineral transfer to the milk have a prominent role in bone loss during breastfeeding. Data on the influence of breastfeeding in postmenopausal osteoporosis are inconsistent. The aim of the present study was to identify any association between duration of breastfeeding and vertebral fractures in postmenopausal women.
    Bone 08/2014; · 4.46 Impact Factor
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    ABSTRACT: This paper presents an extensive analysis of the degradation of InGaN-based laser diodes submitted to electrical stress. The analyzed devices, with emission in the violet spectral region, were submitted to constant current stress; the degradation process was monitored by means of electro-optical measurements, which indicated that stress induced an increase in the threshold current of the devices, ascribed to the generation of non-radiative defects. After stress, the (thick) top metallization was removed, and the optical behavior of the samples was characterized by microcathodoluminescence and micro-photoluminescence investigation. Results indicate that (i) stress induced a significant degradation of the efficiency of the devices under the ridge, i.e. in the region which is crossed by high current densities during ageing. (ii) the darkening of the ridge was detected both by micro-cathodoluminescence measurements (in which carriers are generated both in the barriers and in the quantum wells) and by micro-photoluminescence analysis with subbandgap excitation (with respect to the barriers). The experimental evidence collected within this paper demonstrates that the degradation of the laser diodes can be ascribed to an increase in the rate of non-radiative recombination within the active region of the devices, possibly due to a defect diffusion process. Hypothesis on the nature of the defects involved in the degradation process are formulated based on capacitance Deep Level Transient Spectroscopy measurements.
    02/2014;
  • Marco Filippone, Silvia Carraro, Eugenio Baraldi
    European Respiratory Journal 11/2013; 42(5):1430-1. · 6.36 Impact Factor
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    ABSTRACT: High serum levels of insulin-like growth factor-1 (IGF-1) seem to coincide with higher rates of some types of cancer and the risk of all-cause mortality in old people. Eating vegetables seems to reduce IGF-1 levels because they are rich in micronutrients such as vitamins. This study investigates the possible association between vitamin intake and IGF-1 levels in a representative group of healthy elderly women with Mediterranean dietary habits. This cross-sectional study included 124 healthy women with a mean age of 71.3±4.2years and a mean body mass index (BMI) of 27.37±3.48kg/m(2) attending a mild fitness program twice a week at public gyms in Padova. The main parameters considered were IGF-1 (measured by chemiluminescence) and diet, assessed on the basis of a 3-day record and a questionnaire on the frequency with which they usually ate certain foods. The mean IGF-1 level for the sample as a whole was 136.2±38.9μg/l, and was significantly lower in women with a higher folate intake (p=0.04). On simple linear analysis, the vitamins found associated with serum IGF-1 levels were: folates (r: -0.25; p=0.003); vitamin E (r: -0.21; p=0.01); vitamin D (r: -0.17; p=0.03); and riboflavin (r: -0.16; p=0.03). After removing the effect of calorie, protein, carbohydrate and fat intake, and other known potential confounders (age, BMI, alcohol intake), only folate intake correlated with IGF-1 levels (r=-0.17; p=0.04). A folate-rich diet could have the effect of lowering circulating IGF-1 levels in elderly women.
    Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 09/2013; · 2.35 Impact Factor
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    ABSTRACT: Bronchopulmonary dysplasia (BPD) is one of the most important sequelae of premature birth and the most common form of chronic lung disease of infancy. From a clinical standpoint BPD subjects are characterized by recurrent respiratory symptoms, which are very frequent during the first years of life and, although becoming less severe as children grow up, they remain more common than in term-born controls throughout childhood, adolescence and into adulthood. From a functional point of view BPD subjects show a significant airflow limitation that persists during adolescence and adulthood and they may experience an earlier and steeper decline in lung function during adulthood. Interestingly, patients born prematurely but not developing BPD usually fare better, but they too have airflow limitations during childhood and later on, suggesting that also prematurity per se has life-long detrimental effects on pulmonary function. For the time being, little is known about the presence and nature of pathological mechanisms underlying the clinical and functional picture presented by BPD survivors. Nonetheless, recent data suggest the presence of persistent neutrophilic airway inflammation and oxidative stress and it has been suggested that BPD may be sustained in the long term by inflammatory pathogenic mechanisms similar to those underlying COPD. This hypothesis is intriguing but more pathological data are needed. A better understanding of these pathogenetic mechanisms, in fact, may be able to orient the development of novel targeted therapies or prevention strategies to improve the overall respiratory health of BPD patients.
    Early human development 08/2013; · 2.12 Impact Factor
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    ABSTRACT: In order to help assess resident performance during training, the Residency Affair Committee of the Pediatric Residency Program of the University of Padua (Italy) administered a Resident Assessment Questionnaire (ReAQ), which both residents and faculty were asked to complete. The aim of this article is to present the ReAQ and its validation. The ReAQ consists of 20 items that assess the six core competencies identified by the Accreditation Council of Graduate Medical Education (ACGME). A many-facet Rasch measurement analysis was used for validating the ReAQ. Between July 2011 and June 2012, 211 evaluations were collected from residents and faculty. Two items were removed because their functioning changed with the gender of respondents. The step calibrations were ordered. The self evaluations (residents rating themselves) positively correlated with the hetero evaluations (faculty rating residents; Spearman's rho = 0.75, p < 0.001). Unfortunately, the observed agreement among faculty was smaller than expected (Exp = 47.1%; Obs = 41%), which indicates that no enough training to faculty for using the tool was provided. In its final form, the ReAQ provides a valid unidimensional measure of core competences in pediatric residents. It produces reliable measures, distinguishes among groups of residents according to different levels of performance, and provides a resident evaluation that holds an analogous meaning for residents and faculty.
    Italian Journal of Pediatrics 07/2013; 39(1):41. · 1.34 Impact Factor
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    ABSTRACT: Food allergy is an increasingly prevalent problem all over the world and especially in westernized countries, and there is an unmet medical need for an effective form of therapy. During childhood natural tolerance development is frequent, but some children with cow's milk or hen's egg allergy and the majority of children with peanut allergy will remain allergic until adulthood, limiting not only the diet of patients but also their quality of life. Within the last several years, the usefulness of immunotherapy for food allergies has been investigated in food allergic patients. Several food immunotherapies are being developed; these involve oral, sublingual, epicutaneous, or subcutaneous administration of small amounts of native or modified allergens to induce immune tolerance. The approach generally follows the same principles as immunotherapy of other allergic disorders and involves administering small increasing doses of food during an induction phase followed by a maintenance phase with regular intake of a maximum tolerated amount of food. Oral immunotherapy seems to be a promising approach for food allergic patients based on results from small uncontrolled and controlled studies. Diet containing heated milk and egg may represent an alternative approach to oral immunomodulation for cow's milk and egg allergic subjects. However, oral food immunotherapy remains an investigational treatment to be further studied before advancing into clinical practice. Additional bigger, multicentric and hopefully randomized-controlled studies must answer multiple questions including optimal dose, ideal duration of immunotherapy, degree of protection, efficacy for different ages, severity and type of food allergy responsive to treatment.
    Current pharmaceutical design 05/2013; · 4.41 Impact Factor
  • Paediatrics & child health 03/2013; 18(3):137-9. · 1.03 Impact Factor
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    ABSTRACT: ABSTRACT BACKGROUND. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor and uncoupler of nitric oxide synthase. By promoting the formation of peroxynitrite, ADMA is believed to contribute to several aspects of asthma pathogenesis, i.e. airway inflammation, oxidative stress, bronchial hyperresponsiveness and collagen deposition. The aim of the present study was to compare this mediator in asthmatic and healthy children using the completely non-invasive exhaled breath condensate (EBC) technique. METHODS. We recruited 77 asthmatic children (5-16y) and 65 healthy children (5-15y) who underwent EBC collection and spirometry. Serum ADMA levels and FENO levels were measured on the same day in a subgroup of asthmatic children. EBC was collected using the Turbo-Deccs (Medivac, Parma, Italy). ADMA levels were measured using the Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry(UPLC-MS/MS) technique. RESULTS. ADMA could be detected in the EBC of 71 asthmatic and 64 healthy subjects. ADMA levels in the EBC of asthmatic children were significantly higher than in the healthy controls (median 0.12[IQR 0.05-0.3] vs 0.07[0.05-0.12], p=0.017), while no difference emerged between the asthmatic children who were or were not on inhaled steroid treatment. No correlation was found between serum and EBC ADMA levels (p>0.5). CONCLUSIONS. We measured ADMA in EBC by UPLC-MS/MS, a reference analytical technique. Higher ADMA levels were found in asthmatic children, supporting a role for this mediator in asthma pathogenesis. This oxidative stress-related mediator also seems to be scarcely affected by steroid therapy. We speculate that ADMA might be a target for new therapeutic strategies designed to control oxidative stress in asthma.
    Chest 02/2013; · 7.13 Impact Factor
  • Microelectronics Reliability 01/2013; 53(9–11):1534 - 1537. · 1.14 Impact Factor
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    ABSTRACT: We present an investigation of the degradation of InGaN/GaN laser diodes grown on a GaN substrate. The results indicate that: (i) Ageing induces a significant increase in the threshold current (Ith) of the lasers, which is attributed to an increase in non-radiative recombination; (ii) Ith increase is correlated to a decrease in the micro-cathodoluminescence signal measured (after the removal of the top metallization) in the region under the ridge; (iii) micro-photoluminescence measurements indicate that constant current stress increases non-radiative recombination within the quantum wells (and not only within the barriers), and induces an increase in the emission wavelength of the degraded region.
    Applied Physics Letters 01/2013; 103(23):233506-233506-4. · 3.52 Impact Factor
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    ABSTRACT: BACKGROUND: Exhaled breath condensate (EBC) is a biofluid collected non invasively that, enabling the measurement of several biomarkers, has proven useful in the study of airway inflammatory diseases, including asthma, COPD and cystic fibrosis. To the best of our knowledge, there is no previous report of any analytical method to detect ADMA in EBC. OBJECTIVES: Aim of this work was to develop an online sample trapping and enrichment system, coupled with an UPLC-MS/MS method, for simultaneous quantification of seven metabolites related to "Arginine-ADMA cycle", using the isotopic dilution. METHODS: Butylated EBC samples were trapped in an online cartridge, washed before and after each injection with cleanup solution to remove matrix components and switched inline into the high pressure analytical column. Multiple reaction monitoring in positive mode was used for analyte quantification by tandem mass spectrometry. RESULTS: Validation studies were performed in EBC to examine accuracy, precision and robustness of the method. For each compound, the calibration curves showed a coefficient of correlation (r(2)) greater than 0.992. Accuracy (%Bias) was <3% except for NMMA and H-Arg (<20%), intra- and inter-assay precision (expressed as CV%) were within ±20% and recovery ranged from 97.1 to 102.8% for all analytes. Inter-day variability analysis on 20 EBC of adult subjects did not demonstrate any significant variation of quantitative data for each metabolite. ADMA and SDMA mean concentrations (μmolL(-1)), measured in EBC samples of asthmatic adolescents are significantly increased (p<0.0001) than in normal controls (0.0040±0.0021 vs. 0.0012±0.0005 and 0.0020±0.0015 vs. 0.0002±0.0001, respectively), as well the ADMA/Tyr (0.34±0.09 vs. 0.12±0.02, p<0.0001) and the SDMA/Tyr ratio (0.10±0.04 vs. 0.015±0.004, p<0.0001). CONCLUSIONS: The proposed method features simple specimen preparation, maintenance of an excellent peak shape of all metabolites and reduced matrix effects as well mass spectrometer noise. Moreover, the possibility to perform different cycles of enrichment, using large injection volumes, compensated for the low concentration of analytes contained in EBC, leading to a good analytical sensitivity. Preliminary data obtained from asthmatic and healthy adolescents, demonstrated that the analytical method applied to EBC seems suitable not only for research purposes, but also for clinical routinely analysis.
    Analytica chimica acta 11/2012; 754C:67-74. · 4.31 Impact Factor
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    ABSTRACT: 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 (O2PLS-DA) model was found for discriminating both between severe asthma cases and healthy controls (R(2) = 0.93; Q(2) = 0.75) and between severe asthma and nonsevere asthma (R(2) = 0.84; Q(2) = 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.
    Allergy 11/2012; · 5.88 Impact Factor
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    ABSTRACT: Quality of life is negatively affected in children with food allergy. Oral immunotherapy is an approach to food allergy that leads to patient desensitization by administering gradually increasing amounts of a given food allergen. The aim of this pilot study is to evaluate how oral immunotherapy affects quality of life in children allergic to cow milk proteins. Thirty children (aged 3-12 years) with cow milk allergy were recruited. Their parents were provided with a validated disease specific quality of life questionnaire (the food allergy quality of life questionnaire – parent form, FAQLQ-PF) before and again 2 months after completing an oral immunotherapy protocol with cow milk. A significant improvement in all the investigated domains - emotional impact, food anxiety and social and dietary limitations - was found. The separate analysis of the different age groups demonstrated that the emotional impact and the food-related anxiety improved in children older than 4, while the social domains improved in each age group. In this pilot experience, oral immunotherapy significantly improves quality of life in children with cow milk allergy. The improvement seems particularly evident in children over 4 years old, who are most likely to benefit from the oral immunotherapy approach. Further placebo-controlled studies are needed to confirm these preliminary results.
    International journal of immunopathology and pharmacology 07/2012; 25(3):793-8. · 2.99 Impact Factor
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    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.
    Allergy 09/2011; 67(1):10-7. · 5.88 Impact Factor
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    ABSTRACT: Fraction of exhaled nitric oxide (Feno), a marker of airway inflammation, has been proposed to be useful for asthma management, but conclusions are inconsistent. This might be due to the failure of mean statistics to characterize individual variability in Feno values, which is possibly a better indicator of asthma control than single measurements. We characterized fractal fluctuations in daily Feno values over time and the relationship between Feno values and symptom scores. We investigated whether these are associated with asthma severity, control, and exacerbation risk. Daily Feno values and symptom scores over 192 days in 41 atopic asthmatic children from the Childhood Asthma Respiratory Inflammatory Status Monitoring study were analyzed. Two methods of time-series analysis were used: detrended fluctuation analysis to quantify fractal patterns in fluctuations in daily Feno values (α value) and cross-correlation to quantify the strength of the relationship between daily Feno values and symptom scores. The associations of α values and cross-correlation with markers of asthma severity and control were assessed by means of regression analysis. Daily fluctuations in Feno values exhibited fractal-type long-range correlations. Those subjects receiving higher doses of inhaled corticosteroids at study entry had a significantly lower α value, corresponding to more random fluctuations in Feno values in those with greater inhaled corticosteroid need. The cross-correlation between Feno values and symptom scores was significantly higher in those subjects who had exacerbations. Fluctuation in Feno values and their cross-correlation to symptom scores contains information on asthma severity and control. Methods that quantify the complexity of asthma over time might assist in identifying asthmatic subjects with concordance between eosinophilic inflammation and symptoms and thus increased exacerbation risk.
    The Journal of allergy and clinical immunology 04/2011; 128(2):293-300. · 12.05 Impact Factor

Publication Stats

1k Citations
317.96 Total Impact Points

Institutions

  • 2003–2012
    • University of Padova
      • • Department of Women’s and Children’s Health SDB
      • • Department of Pediatrics
      Padova, Veneto, Italy
    • Università degli studi di Parma
      Parma, Emilia-Romagna, Italy
  • 2008
    • Erasmus MC
      • Department of Pediatrics
      Rotterdam, South Holland, Netherlands
  • 2006
    • University of Virginia
      • Department of Pediatrics
      Charlottesville, VA, United States