Daniela De Angelis

Respiratory syncytial virus, human bocavirus and rhinovirus bronchiolitis in infants

Objective: To investigate the prevalence of 14 viruses in infants with bronchiolitis and to study demographic and clinical differences in those with respiratory syncytial virus (RSV), human bocavirus (hBoV) and rhinovirus (RV) infection. Methods: 182 infants aged <12 months hospitalised for bronchiolitis were enrolled. Infants underwent nasal washing for the detection of RSV, influenza virus A and B, human coronavirus OC43, 229E, NL-63, HUK1, adenovirus, RV, parainfluenza 1–3, human metapneumovirus and hBoV. Demographic, clinical and laboratory data were obtained from parents and from patient medical files. Main outcome measurements were age, breastfeeding history, family smoking habits, family history for asthma and atopy, blood eosinophil count, chest radiological findings, clinical severity score and number of days of hospitalisation. Results: A virus was detected in 57.2% of the 182 infants. The most frequently detected viruses were RSV (41.2%), hBoV (12.2%) and RV (8.8%). Infants with dual infections (RSV and hBoV) had a higher clinical severity score and more days of hospitalisation than infants with RSV, RV and hBoV bronchiolitis (mean±SD: 4.7+2.4 vs 4.3±2.4 vs 3.0±2.0 vs 2.9±1.7, p<0.05; and 6.0±3.2 vs 5.3±2.4 vs 4.0±1.6 vs 3.9±1.1 days; p<0.05). Infants with RV infection had higher blood eosinophil counts than infants with bronchiolitis from RSV and hBoV (307±436 vs 138±168 vs 89±19 n/mm3; p<0.05). Conclusions: Although the major pathogen responsible for bronchiolitis remains RSV, the infection can also be caused by RV and hBoV. Demographic characteristics and clinical severity of the disease may depend on the number of viruses or on the specific virus detected.

Analytical and Bootstrap Approximations to Estimator Distributions in L 1 Regression

Abstract Edgeworth and bootstrap approximations to estimator distributions in L1 regression are described. Analytic approximations based on Edgeworth expansions that mix lattice and nonlattice components and allow for an intercept term in the regression are developed under mild conditions, which do not even require a density for the error distribution. Under stronger assumptions on the error distribution, the Edgeworth expansion assumes a simpler form. Bootstrap approximations are described, and the consistency of the bootstrap in the L 1 regression setting is established. We show how the slow rate n −1/4 of convergence in this context of the standard, unsmoothed bootstrap that resamples for the raw residuals may be improved to rate n −2/5 by two methods: a smoothed bootstrap approach based on resampling from an appropriate kernel estimator of the error density and a normal approximation that uses a kernel estimator of the error density at a particular point, its median 0. Both of these methods require ch...

Gene Expression of Nucleic Acid-Sensing Pattern Recognition Receptors in Children Hospitalized for Respiratory Syncytial Virus-Associated Acute Bronchiolitis

ABSTRACT Given the critical role of pattern recognition receptors (PRRs) in acid nucleic recognition in the initiation of innate immunity and the orchestration of adaptive immunity, the aim of this study was to determine whether any heterogeneity of PRR expression in the airway tracts of infants with respiratory syncytial virus (RSV) infection might explain the broad clinical spectrum of RSV-associated bronchiolitis in infants. For this purpose, the levels of melanoma differentiation-associated protein-5 (MDA-5), retinoic acid inducible gene-1 (RIG-1), and Toll-like receptor 3 (TLR-3), TLR-7, TLR-8, and TLR-9 mRNAs were evaluated, using TaqMan quantitative reverse transcription-PCR, in cells from nasopharyngeal washes collected from 157 infants suffering from acute bronchiolitis whether or not they were associated with respiratory viruses. High interindividual variability was observed in both virus-positive and -negative infants; however, the relative gene expression levels of MDA-5, RIG-1, TLR-7, and TLR-8 were significantly higher in the virus-infected group, whereas the expression levels of TLR-3 and TLR-9 were not significantly different. The differences in the gene expression of MDA-5, RIG-1, TLR-7, and TLR-8 were more evident in infants with RSV infection than in those with bocavirus or rhinovirus infection. In RSV-infected infants, PRR-mRNA levels also were analyzed in relation to interferon protein levels, viral load, clinical severity, days of hospitalization, age, and body weight. A significant positive correlation was observed only between RSV viral load and RIG-1 mRNA levels. These findings provide the first direct evidence that, in infants with respiratory virus-associated bronchiolitis, especially RSV, there are substantial changes in PRR gene expression; this likely is an important determinant of the clinical outcome of bronchiolitis.

Non-acid gastro-oesophageal reflux in children with suspected pulmonary aspiration.

BACKGROUND & AIMS In a group of children with suspected pulmonary aspiration, we aimed to describe the type and physical characteristics of gastro-oesophageal reflux (GOR) episodes, and to determine their correlation with the lipid-laden macrophage (LLM) content in bronchoalveolar lavage (BAL). PATIENTS AND METHODS Twenty-one children with a diagnosis of bronchial asthma, recurrent lung consolidations and recurrent laryngotracheitis underwent 24-h multichannel intraluminal impedance and pH (MII-pH) monitoring, fibreoptic bronchoscopy and BAL. The following parameters were evaluated: total number of reflux episodes, number of acid reflux [AR; pH<4] and non-acid reflux [NAR] episodes [pH>4], height of reflux episodes, LLM content and percentage of neutrophils in the BAL. RESULTS The number of NAR episodes and the number of those reaching the proximal oesophagus were significantly higher in patients with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p<0.01 and p<0.01). BAL studies showed a significantly higher LLM content in children with recurrent lung consolidations than in those with bronchial asthma and laryngotracheitis (p<0.01). The LLM content correlated significantly with the total number of reflux episodes (r=0.73; p<0.001) and with those reaching the proximal oesophagus (r=0.67; p<0.001). Finally, the LLM content correlated with the number of NAR episodes (r=0.61; p<0.01), with those reaching the proximal oesophagus (r=0.64; p<0.01) and with the percentage of BAL neutrophils (r=0.7; p<0.01). CONCLUSION NAR episodes reaching the proximal oesophagus correlate with diagnostic marker for pulmonary micro-aspiration. MII-pH monitoring increases the yield in identifying types and proximal extension of reflux episodes, that discriminate between patients with and without pulmonary aspiration.

Seven Percent Hypertonic Saline—0.1% Hyaluronic Acid in Infants With Mild-To-Moderate Bronchiolitis

Our study was aimed to evaluate the efficacy of 7% hypertonic saline and 0.1% hyaluronic acid (7% HS–HA) given by inhalation, in infants hospitalized for mild‐to‐moderate bronchiolitis.

A note on coverage error of bootstrap confidence intervals for quantiles

An interesting recent paper by Falk and Kaufmann[11] notes, with an element of surprise, that the percentile bootstrap applied to construct confidence intervals for quantiles produces two-sided intervals with coverage error of size n −½ , where n denotes sample size. By way of contrast, the error would be O(n −1 ) for two-sided intervals in more classical problems, such as intervals for means or variances. In the present note we point out that the relatively poor performance in the case of quantiles is shared by a variety of related procedures. The coverage accuracy of two-sided bootstrap intervals may be improved to o(n −½ ) by smoothing the bootstrap. We show too that a normal approximation method, not involving the bootstrap but incorporating a density estimator as part of scale estimation, can have coverage error O(n −1+∈ ) , for arbitrarily small ∈ > 0. Smoothed and unsmoothed versions of bootstrap percentile- t are also analysed.

Bootstrapping the correlation coefficient: a comparison of smoothing strategies

Estimation of the sampling standard deviation of the variance stabilised correlation coefficient by the smoothed bootstrap is reconsidered. Four different strategies for empirical choice of the smoothing parameter are discussed and their performances examined through a Monte Carlo experiment.