Update on Postnatal Corticosteroids to Prevent or Treat Bronchopulmonary Dysplasia

AbstractBronchopulmonary dysplasia (BPD) is a major complication of premature birth that significantly affects mortality and long-term morbidity in numerous immature infants. Corticosteroids are particularly suitable for treating BPD, as lung inflammation is central to its pathogenesis. Corticosteroids have considerable, fast beneficial effects on lung function in premature infants with lung disease, but they are also associated with several serious adverse effects, which may have a detrimental impact on long-term outcome. Dexamethasone is the most often used corticosteroid for systemic administration. Despite its value in preventing and treating BPD, its use is associated with several alarming short-term effects and, worst of all, with an increased rate of cerebral palsy in the long term. Dexamethasone nonetheless remains an important therapeutic option for infants with severe lung disease beyond the second to third week of life. Hydrocortisone is an important alternative to dexamethasone, as its use does not appear to be associated with any neurotoxic effects. Its efficacy in the prevention and treatment of BPD has yet to be clearly demonstrated, however. Inhaled corticosteroids might reduce lung inflammation with fewer systemic adverse effects; however, a recent, large randomized trial showed that inhaled budesonide was associated with an excess mortality, despite its beneficial respiratory effects. In another study, instilling budesonide together with surfactant in the trachea of intubated infants with severe respiratory distress appeared safe and achieved a significant reduction in the rate of BPD at 36 postmenstrual weeks. This important finding needs to be confirmed in a larger trial currently underway

Metabolomics applied to urine samples in childhood asthma; differentiation between asthma phenotypes and identification of relevant metabolites

Asthma is a heterogeneous disorder and one of the most common chronic childhood diseases. An improved characterization of asthma phenotypes would be invaluable for the understanding of the pathogenic mechanisms and the correct treatment of this disease. The aim of this pilot study was to explore the potential of metabolomics applied to urine samples in characterizing asthma, and to identify the most representative metabolites. Urine samples of 41 atopic asthmatic children (further subdivided in sub-groups according to the symptoms) and 12 age-matched controls were analyzed. Untargeted metabolic profiles were collected by LC-MS, and studied by multivariate analysis. The group of the asthmatics was differentiated by a model that proved to be uncorrelated with the chronic assumption of controller drugs by part of the patients. The distinct sub-groups were also appropriately modeled. Further investigations revealed a reduced excretion of urocanic acid, methyl-imidazoleacetic acid and of a metabolite resembling the structure of an Ile-Pro fragment in the asthmatics. The meaning of these findings was discussed and mainly correlated with the modulation of immunity in asthma. Metabolic profiles from urines have revealed the potential to characterize asthma and enabled the identification of metabolites which may have a role in the underlying inflammation.JRC.I.6-Systems toxicolog

Metabolomics: moving towards personalized medicine

In many fields of medicine there is a growing interest in characterizing diseases at molecular level with a view to developing an individually tailored therapeutic approach. Metabolomics is a novel area that promises to contribute significantly to the characterization of various disease phenotypes and to the identification of personal metabolic features that can predict response to therapies. Based on analytical platforms such as mass spectrometry or NMR-based spectroscopy, the metabolomic approach enables a comprehensive overview of the metabolites, leading to the characterization of the metabolic fingerprint of a given sample. These metabolic fingerprints can then be used to distinguish between different disease phenotypes and to predict a drug's effectiveness and/or toxicity

Long-term continuous monitoring of the preterm brain with diffuse optical tomography and electroencephalography: A technical note on cap manufacturing

open12noDiffuse optical tomography (DOT) has recently proved useful for detecting whole-brain oxygenation changes in preterm and term newborns' brains. The data recording phase in prior explorations was limited up to a maximum of a couple of hours, a time dictated by the need to minimize skin damage caused by the protracted contact with optode holders and interference with concomitant clinical/nursing procedures. In an attempt to extend the data recording phase, we developed a new custom-made cap for multimodal DOT and electroencephalography acquisitions for the neonatal population. The cap was tested on a preterm neonate (28 weeks gestation) for a 7-day continuous monitoring period. The cap was well tolerated by the neonate, who did not suffer any evident discomfort and/or skin damage. Montage and data acquisition using our cap was operated by an attending nurse with no difficulty. DOT data quality was remarkable, with an average of 92% of reliable channels, characterized by the clear presence of the heartbeat in most of them.openopenAlfonso Galderisi; Sabrina Brigadoi; Simone Cutini; Sara Basso Moro; Elisabetta Lolli; Federica Meconi; Silvia Benavides-Varela; Eugenio Baraldi; Piero Amodio; Claudio Cobelli; Daniele Trevisanuto; Roberto Dell'AcquaGalderisi, Alfonso; Brigadoi, Sabrina; Cutini, Simone; BASSO MORO, Sara; Lolli, Elisabetta; Meconi, Federica; Silvia, Benavides-Varela; Baraldi, Eugenio; Amodio, Piero; Cobelli, Claudio; Trevisanuto, Daniele; Dell'Acqua, Robert

Short term efficacy of nebulized beclomethasone in mild-to-moderate wheezing episodes in pre-school children

<p>Abstract</p> <p>Background</p> <p>Few data are available on the usefulness of short term treatment with low-medium dose of inhaled corticosteroids (ICS) in pre-school children with wheezing exacerbations.</p> <p>Methods</p> <p>To compare the efficacy of one week treatment with 400 μg b.i.d. nebulized beclomethasone dipropionate (BDP), plus nebulized 2500 μg prn salbutamol (BDP group), versus nebulized b.i.d. placebo, plus nebulized prn 2500 μg salbutamol (placebo group), a post-hoc analysis was performed on data obtained in 166 pre-school children with multiple-trigger wheezing, recruited during an acute wheezing episode.</p> <p>Results</p> <p>The percentage of symptom-free days (SFDs) was significantly higher in the BDP group (54.7%) than in the placebo group (40.5%; p = 0.012), with a 35% relative difference. Day-by-day analysis showed that the percentage of SFDs was already higher in the BDP group after 2 days (7.4%), the difference reaching statistical significance at day 6 (12.3%; p = 0.035). Cough score was also reduced in the BDP group (0.11) as compared with the placebo group (0.39; p = 0.048), the difference reaching statistical significance after 5 days of treatment (0.18 and 0.47 respectively; p = 0.047). The mean number of nebulizations per day of prn salbutamol was lower in the BDP group as compared to the placebo group (0.26 and 0.34, respectively), but the difference was not significant (p = 0.366). There were no differences in positive effects of BDP treatment between children with and without risk factors for asthma.</p> <p>Conclusions</p> <p>A 1-week treatment with nebulized BDP and prn salbutamol is effective in increasing SFDs and improving cough in children with wheezing, providing a clinical rationale for the short term use of ICS in episodic wheeze exacerbations in pre-school children.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov (<a href="http://www.clinicaltrials.gov/ct2/show/NCT00497523">NCT00497523</a>)</p

Neonatal Urine Metabolic Profiling and Development of Childhood Asthma

none9Urine metabolomics case-control studies of childhood asthma have demonstrated a discriminative ability. Here, we investigated whether urine metabolic profiles from healthy neonates were associated with the development of asthma in childhood. Untargeted metabolomics by liquid chromatography-mass spectrometry was applied to urine samples collected at age 4 weeks in 171 and 161 healthy neonates born from mothers with asthma from the COPSAC2000 and COPSAC2010 cohorts, respectively, where persistent wheeze/asthma was prospectively diagnosed using a symptom-based algorithm. Univariate and multivariate analyses were applied to investigate differences in metabolic profiles between children who developed asthma and healthy children. Univariate analysis showed 63 and 87 metabolites (q-value 0.60. Database search enabled annotation of three discriminative features: a glucoronidated compound (steroid), 3-hydroxytetradecanedioic acid (fatty acid), and taurochenodeoxycholate-3-sulfate (bile acid). The urine metabolomics profiles from healthy neonates were associated with the development of childhood asthma, but further research is needed to understand underlying metabolic pathways.noneChawes, Bo L; Giordano, Giuseppe; Pirillo, Paola; Rago, Daniela; Rasmussen, Morten A; Stokholm, Jakob; Bønnelykke, Klaus; Bisgaard, Hans; Baraldi, EugenioChawes, Bo L; Giordano, Giuseppe; Pirillo, Paola; Rago, Daniela; Rasmussen, Morten A; Stokholm, Jakob; Bønnelykke, Klaus; Bisgaard, Hans; Baraldi, Eugeni