Corrado Moretti

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.

Foreign body aspiration in children

Abstract Background : The aim was to investigate the role of physical and radiological findings before bronchoscopy in the diagnosis of foreign body aspiration (FBA).

Comparing the effects of nasal synchronized intermittent positive pressure ventilation (nSIPPV) and nasal continuous positive airway pressure (nCPAP) after extubation in very low birth weight infants.

In this study we hypothesized that nasal synchronized intermittent positive pressure ventilation (nSIPPV) would provide more ventilatory support than nasal continuous positive airway pressure (nCPAP) in the immediate post-extubation period in very low birth weight (VLBW) infants. We tested this hypothesis by comparing the effects of these two ventilatory techniques on ventilation, gas exchange, and patient inspiratory effort in 11 preterm infants immediately after extubation. All neonates studied (BW: 1141+/-(SEM) 53 g; GA: 28.1+/-(SEM) 0.5 wks) had received mechanical ventilation because of respiratory distress at birth and were extubated by day 14 of life. Nasal SIPPV and nCPAP were applied in random order to each infant after extubation so that each was his/her own control. Both nCPAP and nSIPPV were delivered at end-expiratory pressures (PEEP) of 3 cm H2O. Inspiratory times (Ti) and peak inspiratory pressures set during nSIPPV were the same as those used at the time of extubation. Recordings lasted 45 min in each mode of ventilation. Tidal volume (Vt), minute volume (Ve), respiratory rate (RR), airway pressure (Paw), transcutaneous PO2 (TcPO2) and PCO2 (TcPCO2) as well as phasic esophageal pressure deflections (Pe), as an estimate of inspiratory effort, were measured. The measurements obtained during both modes of ventilation indicated significant differences between the two techniques. Indeed, application of nSIPPV was associated with a statistically significant increase in Vt and Ve. In addition, Pe decreased by 30% during nSIPPV (P<0.01). TcPCO2 was statistically significantly lower during nSIPPV than nCPAP, and RR as well. These data therefore suggest that nSIPPV may provide more ventilatory support than nCPAP in the post-extubation period with less patient inspiratory effort.

Detection and typing by molecular techniques of respiratory viruses in children hospitalized for acute respiratory infection in Rome, Italy

Detection of a broad number of respiratory viruses is not undertaken currently for the diagnosis of acute respiratory infection due to the large and always increasing list of pathogens involved. A 1‐year study was undertaken on children hospitalized consecutively for acute respiratory infection in a Pediatric Department in Rome to characterize the viruses involved. Two hundred twenty‐seven children were enrolled in the study with a diagnosis of asthma, bronchiolitis, bronchopneumonia, or laringo‐tracheo bronchitis. A molecular approach was adopted using specific reverse transcription (RT)‐PCR assays detecting 13 respiratory viruses including metapneumovirus (hMPV) and the novel coronaviruses NL63 and HKU1; most amplified fragments were sequenced to confirm positive results and differentiate the strain. Viral pathogens were detected in 97 samples (42.7%), with 4.8% of dual infections identified; respiratory syncytial virus (RSV) was detected in 17.2% of children, followed by rhinovirus (9.7%), parainfluenza virus type 3 (PIV3) (7.5%), and influenza type A (4.4%). Interestingly, more than half the patients (9/17) that have rhinovirus as the sole respiratory pathogen had pneumonia. HMPV infected children below 3 years in two peaks in March and June causing bronchiolitis and pneumonia. One case of NL63 infection is described, documenting NL63 circulation in central Italy. In conclusion, the use of a comprehensive number of PCR‐based tests is recommended to define the burden of viral pathogens in patients with respiratory tract infection. J. Med. Virol. 79:463–468, 2007.

Nasal flow-synchronized intermittent positive pressure ventilation to facilitate weaning in very low-birthweight infants: Unmasked randomized controlled trial

Background: Nasal flow‐synchronized intermittent positive pressure ventilation (NFSIPPV) is a new non‐invasive ventilatory mode that delivers synchronized mechanical breaths through the nasal prongs. An unmasked, prospective randomized controlled trial was conducted to compare the efficacy of NFSIPPV and conventional nasal continuous positive airway pressure (NCPAP) in increasing the likelihood for successful extubation in very low‐birthweight infants.

Rhinovirus bronchiolitis and recurrent wheezing: 1-year follow-up

The association between bronchiolitis and recurrent wheezing remains controversial. In this prospective study, we assessed risk factors for recurrent wheezing during a 12-month follow-up in 313 infants aged <12 months hospitalised for their first episode of bronchiolitis. Demographic, clinical and laboratory data were obtained with a questionnaire and from medical files. A total of 14 respiratory viruses were concurrently assayed in nasal washings. Parents were interviewed 12 months after hospitalisation to check whether their infants experienced recurrent wheezing. The rate of recurrent wheezing was higher in infants with bronchiolitis than in controls (52.7 versus 10.3%; p<0.001). Multivariate analysis identified rhinovirus (RV) infection (OR 3.3, 95% CI 1.0–11.1) followed by a positive family history for asthma (OR 2.5, 95% CI 1.2–4.9) as major independent risk factors for recurrent wheezing. In conclusion, the virus most likely to be associated with recurrent wheezing at 12 months after initial bronchiolitis is RV, a viral agent that could predict infants prone to the development of recurrent wheezing.

Evaluation of viral load in infants hospitalized with bronchiolitis caused by respiratory syncytial virus

The relationship between viral load, disease severity and antiviral immune activation in infants suffering from respiratory syncytial virus (RSV)-associated bronchiolitis has not been well identified. The main objective of this study was to determine the existence of a correlation between RSV load and disease severity and also between different clinical markers and mRNA levels of the interferon stimulated gene (ISG)56 in infants hospitalized for bronchiolitis. We also evaluated whether viral load tended to be persistent over the course of the RSV infection. The levels of RSV-RNA were quantified in nasopharyngeal washings, collected from 132 infants infected with RSV as a single (90.15%) or as a dual infection with other respiratory viruses (9.85%). Results indicated that viral load was positively related to the clinical severity of bronchiolitis, the length of hospital stay, the levels of glycemia and the relative gene expression of ISG56, whereas an inverse correlation was observed with the levels of hemoglobin. We also found that the RSV load significantly decreased between the first and second nasopharingeal washings sample in most subjects. These results suggest that infants with high RSV load on hospital admission are more likely to have both more severe bronchiolitis and a higher airway activation of antiviral immune response.

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.

Metabolomics in paediatric respiratory diseases and bronchiolitis

The metabolic study of an organism may make it possible to monitor, through the metabolites,the physiology and/or pathology of the organism itself. Metabolomics, in the strictest sense, “the set of metabolites, the final products of the genetic expression”. Most clinical chemistry tests available today rely on old technologies that measure only a single chemical in blood, urine or other biofluids, and these tests are neither sensitive nor specific for any particular disease. Metabolomics offers a holistic approach to systems medicine, with the promise to enhance clinical chemistry diagnostics in several pathologic conditions. The present review covers the application of clinical metabolomics in three different areas of respiratory diseases in pediatrics: asthma, pneumonia and bronchiolitis. Comparison between two 1H-NMR urine spectra by two bronchiolitis patients are also presented.

Outcomes after tongue–lip adhesion or mandibular distraction osteogenesis in infants with Pierre Robin sequence and severe airway obstruction

The objective was to review and compare outcomes after tongue-lip adhesion (TLA) and mandibular distraction osteogenesis (MDO) in infants with severe breathing difficulties related to Pierre Robin sequence (PRS). A single-centre retrospective (2002-2012) study was carried out; 18 infants with severe breathing difficulties related to PRS resistant to conservative treatment, who underwent TLA or MDO to correct airway obstruction, were enrolled. The primary outcome measures were successful weaning from respiratory support and resumption of full oral feeding. Nine underwent TLA and nine MDO. Eight of the nine infants who underwent MDO and all those treated with TLA were successfully weaned from respiratory support. After discharge, residual respiratory distress was diagnosed more commonly after TLA than after MDO (6/9 vs 1/9, P=0.050). Infants resumed oral feeding sooner after MDO than after TLA (mean days after surgery to full oral feeds 44±24 vs 217±134, P<0.003). The length of hospital stay was longer for infants treated with MDO than for those treated with TLA. The rate of complications was similar. Infants with severe airway obstruction related to PRS can benefit safely from either TLA or MDO. Although MDO lengthens the time to discharge, this option stabilizes airway patency of infants with PRS more efficiently and achieves full oral feeding more rapidly than TLA.