Giulia Cangiano

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.

Incidence and predisposing factors for severe disease in previously healthy term infants experiencing their first episode of bronchiolitis.

Aim:  To determine the incidence and predisposing factors for severe bronchiolitis in previously healthy term infants <12 months of age experiencing their first episode of bronchiolitis.

Detection of respiratory viruses in the 2009 winter season in Rome: 2009 Influenza A (H1N1) complications in children and concomitant type 1 diabetes onset

We investigated clinical characteristics and complications, particularly type 1 diabetes onset, in children hospitalized for 2009 pandemic influenza A (H1N1) virus and compared number of consultations, rate of hospitalization and virus identification in children hospitalized for acute respiratory symptoms (ARS) during the winter season 2009–2010 and 2004–2005. Patients were tested for 2009 H1N1 virus and 14 respiratory viruses on pharyngeal brush/nasal aspirates, using a RT-PCR or nested PCR assays. Consultations and hospitalizations were extracted from operative system GIPSE. The total number of consultations increased by 12%, consultation rate for ARS by 13% and number of hospitalizations by 56% from 2004–2005 to 2009–2010. In 2004–2005, Influenza A virus was identified in only 7% of hospitalized children, while in 2009–2010 the 2009 H1N1 virus was identified in 21%. Three children attending the hospital for ARS and 2009 H1N1 infection had ketoacidosis as the onset manifestation of type 1 diabetes. By comparing the number of new diabetes diagnoses among the two winter seasons, we found a higher number of new diagnoses in October 2009 January 2010 than in the same period in 2004–2005 (19 vs 10). Six children (13%), all presenting with pre-existing diseases, were admitted to the pediatric intensive care unit. No children died. The outbreak of this novel virus has increased pediatric consultation rates and hospitalizations compared with previous winters without causing deaths. The children at highest risk for severe infection are those with comorbidities. The 2009 H1N1 virus seems in some way involved in the pathogenesis of type 1 diabetes.

Virological and clinical characterization of respiratory infections in children attending an emergency department during the first autumn–winter circulation of pandemic A (H1N1) 2009 influenza virus

Abstract To characterize respiratory virus infections during the first autumn-winter season of pandemic A (HINI) 2009 influenza virus (A/HINI/2009) circulation, a prospective study in children attending a paediatric emergency department at the Sapienza University hospital, Rome, was conducted from November 2009 to March 2010. By means of both nasal washings and pharyngeal swabs, enrolled children were checked for 14 respiratory viruses. The majority of acute respiratory infections resulted from viral pathogens (135/231, 58%). Overall, the most common was respiratory syncytial virus (RSV), in 64% of positive samples; A/HINI/2009 was the only influenza virus found in 16% and rhinovirus (RV) in 15%. Virus-positive children did not differ significantly from virus-negative children in signs and symptoms at presentation; of the virus groups, RSV-infected children were younger and more frequently admitted to intensive-care units than those infected with A/HINI/2009 and RV. Of the hospitalized children, stratified by age, both infants and children aged >1 year with RSV were most severely affected, whereas A/HINI/2009 infections were the mildest overall, although with related pulmonary involvement in older children. Children with RV infections, detected in two flares partially overlapping with the A/HINI/2009 and RSV peaks, presented with bronchiolitis, wheezing and pneumonia. Leukocytosis occurred more frequently in RV-infected and A/HINI/2009-infected children, and numbers of blood eosinophils were significantly elevated in RV-infected infants. Given the fact that clinical and epidemiological criteria are not sufficient to identify viral respiratory infections, a timely virological diagnosis could allow different infections to be managed separately.

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.

Old and new uses of surfactant

Exogenous surfactant has been the primary life-saving therapy for respiratory distress syndrome (RDS) of preterm infants for many years. More recently, early surfactant treatment administered less invasively by transient endotracheal intubation and combined to nasal ventilation has been shown to further improve neonatal outcome by reducing the need of mechanical ventilation. In addition to RDS, other neonatal and pediatric respiratory disorders characterized by surfactant inactivation or dysfunction, such as pulmonary hemorrhage, aspiration pneumonia, and viral lower respiratory tract infection, might also be amenable to surfactant replacement therapy. However, the nature of lung injury and the influence of co-morbidities may reduce the efficacy of surfactant in these conditions. Currently under investigation are new syntethic surfactant formulations which may be more effective and resistant to inactivation than natural ones and could be produced at a lower cost. The use of surfactants to deliver drugs directly to the lung also seems to be a promising technique worthy of study.

Bronchiolitis: Analysis of 10 consecutive epidemic seasons

Bronchiolitis is the leading cause of hospitalization in infants under 12 months. Our aims were to analyze epidemiological characteristics of infants with bronchiolitis over 10 consecutive seasons and to evaluate whether there are any clinical differences between infants hospitalized for bronchiolitis during epidemic peak months and infants in non‐peak months. We enrolled consecutive enrolled 723 previously healthy term infants hospitalized at the Paediatric Emergency Department, “Sapienza” University of Rome over the period 2004–2014. Fourteen respiratory viruses were detected from nasopharyngeal aspirates by molecular methods. Clinical and demographic data were extracted from clinical charts. Viruses were detected in 351 infants (48.5%): RSV in 234 (32.4%), RV in 44 (6.1%), hBoV in 11 (1.5%), hMPV in 12 (1.6%), co‐infections in 39 (5.4%), and other viruses in 11 (1.5%). Analyzing the 10 epidemic seasons, we found higher incidence for bronchiolitis every 4 years with a peak during the months December–January. Infants hospitalized during peak months had lower family history for asthma (P = 0.003), more smoking mothers during pregnancy (P = 0.036), were slightly higher breastfed (0.056), had lower number of blood eosinophils (P = 0.015) and had a higher clinical severity score (P = 0.017). RSV was detected mostly during peak months, while RV was equally distributed during the seasons. We found some variations in bronchiolitis incidence during epidemics, and discriminative characteristics in infants hospitalized for bronchiolitis during peak months and in non‐peak months, that might reflect two different populations of children. Pediatr Pulmonol. 2016;51:1330–1335.

Risk Factors for Virus-induced Acute Respiratory Tract Infections in Children Younger Than 3 Years and Recurrent Wheezing at 36 Months Follow-up After Discharge

Background: We sought to know more about how 14 common respiratory viruses manifest clinically, and to identify risk factors for specific virus-induced acute respiratory tract infections (ARTIs) in children younger than 3 years old and for wheezing at 36-month follow-up. Methods: We retrospectively studied the clinical records for 273 full-term children (median age, 2.9 months; range, 0.26–39; boys, 61.2%) hospitalized for ARTIs, whose nasopharyngeal specimen tested positive for a respiratory virus and 101 children with no history of respiratory diseases (median age, 8 months; range, 0.5–36.5; boys, 58.4%). At 12, 24 and 36 months after children’s discharge, all parents were interviewed by telephone with a structured questionnaire on wheezing episodes. Results: The most frequently detected viruses were respiratory syncytial virus in bronchiolitis, human rhinovirus in pneumonia and human bocavirus in wheezing. Multivariate analysis identified, as risk factors for virus-induced ARTIs, the presence of siblings [odds ratio (OR): 3.0 (95% confidence interval [CI]: 1.8–5.2)], smoking cohabitants (OR: 2.3 (95% CI: 2–4.2)] and breastfeeding lasting less than 3 months [OR: 0.5 (95% CI: 0.3–0.9)]. The major risk factor for respiratory syncytial virus–induced ARTIs was exposure to tobacco smoke [OR: 1.8 (95% CI: 1.1–3.2)]. Risk factors for human rhinovirus–induced ARTIs were attending day-care [OR: 5.0 (95% CI: 2.3–10.6)] and high eosinophil blood counts [OR: 2.6 (95% CI: 1.2–5.7)]. The leading risk factor for recurrent wheezing was exposure to tobacco smoke [OR: 2.5 (95% CI: 1.1–15.6)]. Conclusions: Each respiratory virus leads to a specific clinical manifestation. Avoiding exposing children to tobacco smoke might restrict viral spread from sick parents and siblings to younger children, prevent severe respiratory diseases, and possibly limit sequelae.

Evaluation of interleukin 28B single nucleotide polymorphisms in infants suffering from bronchiolitis

Abstract The genetic diversity of the host is believed to be the key of the diversity in the clinical presentation of bronchiolitis. The aim of this study was to determine whether the known rs12979860 and rs8099917 single nucleotide polymorphisms (SNPs) in interleukin (IL)28B region, influence clinical features and natural history of bronchiolitis. Both SNPs showed no significant association with the risk of hospitalization for respiratory syncytial virus (RSV), viral load, disease severity, and other clinical features of patients. Interestingly infants carrying IL28B rs12979860 TT genotype had lower age at hospital admission than that of infants carrying CC/CT genotypes. Overall our results indicate that both IL28B SNPs had no impact on the clinical course of bronchiolitis with the only exception of the IL28B rs12979860 SNP which increased the risk of hospitalization for bronchiolitis at early age.