Enea Bonci

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).

Increased serum IgE and increased prevalence of eosinophilia in 9-year-old children of smoking parents

We studied the relationship of serum IgE levels and eosinophil counts with passive smoking in 9-year-old, nonselected children from three Italian towns near Rome. Male children of smoking parents had a significantly higher total count and percentage of eosinophils (p = 0.008) and higher IgE levels (p = 0.01) than male children of nonsmoking parents. Prevalence of eosinophilia (defined as greater than or equal to 4% of total white blood cell count) was significantly correlated with the number of cigarettes smoked by parents among boys (p = 0.003) but not among girls (p = 0.20). There was a significant trend (p = 0.008) for prevalence of eosinophilia to increase with increasing levels of serum IgE. For any given level of serum IgE, the frequency of eosinophilia was higher among children of smoking parents than among children of nonsmoking parents. When parental smoking was studied in a multivariable analysis and after controlling for the other variable, it was still significantly associated with eosinophilia in the children of these smoking parents but not with serum IgE levels. We conclude that parental smoking is associated with a significant enhancement of the expression of the most important markers of allergic sensitization in the children of smoking parents. This is particularly evident for boys and may explain, at least in part, the increased frequency of respiratory symptoms in children of smoking parents.

Low 25(OH)D3 levels are associated with total adiposity, metabolic syndrome, and hypertension in Caucasian children and adolescents

OBJECTIVES Evidence of the association between vitamin D and cardiovascular risk factors in the young is limited. We therefore assessed the relationships between circulating 25-hydroxyvitamin D(3) (25(OH)D(3)) and metabolic syndrome (MetS), its components, and early atherosclerotic changes in 452 (304 overweight/obese and 148 healthy, normal weight) Caucasian children. METHODS We determined serum 25(OH)D(3) concentrations in relation to MetS, its components (central obesity, hypertension, low high-density lipoprotein (HDL)-cholesterol, hypertriglyceridemia, glucose impairment, and/or insulin resistance (IR)), and impairment of flow-mediated vasodilatation (FMD) and increased carotid intima-media thickness (cIMT) - two markers of subclinical atherosclerosis. RESULTS Higher 25(OH)D(3) was significantly associated with a reduced presence of MetS. Obesity, central obesity, hypertension, hypertriglyceridemia, low HDL-cholesterol, IR, and MetS were all associated with increased odds of having low 25(OH)D(3) levels, after adjustment for age, sex, and Tanner stage. After additional adjustment for SDS-body mass index, elevated blood pressure (BP) and MetS remained significantly associated with low vitamin D status. The adjusted odds ratio (95% confidence interval) for those in the lowest (<17 ng/ml) compared with the highest tertile (>27 ng/ml) of 25(OH)D(3) for hypertension was 1.72 (1.02-2.92), and for MetS, it was 2.30 (1.20-4.40). A similar pattern of association between 25(OH)D(3), high BP, and MetS was observed when models were adjusted for waist circumference. No correlation was found between 25(OH)D(3) concentrations and either FMD or cIMT. CONCLUSIONS Low 25(OH)D(3) levels in Caucasian children are inversely related to total adiposity, MetS, and hypertension.

C reactive protein and procalcitonin: Reference intervals for preterm and term newborns during the early neonatal period

BACKGROUND There is still no study evaluating the influence of gestational age (GA) per se on C reactive protein (CRP) and procalcitonin (PCT) reference intervals. We therefore investigated how length of gestation, age (hours), and prenatal and perinatal variables might influence the levels of CRP and PCT. We also determined 95% age-specific reference intervals for CRP and PCT in healthy preterm and term babies during the early neonatal period. METHODS One blood sample (one observation per neonate) was taken for CRP and PCT from each newborn between birth and the first 4 (for term), or 5 days (for preterm newborns) of life by using a high-sensitive CRP and PCT assays. RESULTS Independently of gender and sampling time, GA had a significantly positive effect on CRP, and a significantly negative effect on PCT. Compared with healthy term babies, healthy preterm babies had a lower and shorter CRP response, and, conversely, an earlier, higher, and longer PCT response. CRP reference intervals were affected by a number of pro-inflammatory risk factors. CONCLUSIONS Age- and GA-specific reference ranges for both CRP and PCT should be taken into account to optimize their use in the diagnosis of early-onset neonatal sepsis.

Enhanced allergic sensitisation related to parental smoking.

The objective of this study was to assess the role of parental smoking in changes, after a four year interval (1983-7), in the prevalence and severity of the atopic state in 166 pre-adolescent children. Allergy skin prick tests were related to parental smoking habits and their changes during this same interval. The total number of cigarettes smoked by parents decreased in 56 families while it increased in only 16. Boys had significantly more persistently positive skin tests and changed more frequently from negative to positive. The skin test index did not show significant changes in girls. This index did not change in children of persistent non-smokers or those starting to smoke during this period, while it increased among sons of those that quit smoking and of persistent smokers. This was not only due to those boys who became skin test positive during follow up. When analysis was restricted to 14 boys who had been skin test positive in 1983 and whose parents were persistent smokers, the index increased in eight, remained unchanged in four, and decreased in only two. This report supports the hypothesis that parental smoking is a factor that, together with specific allergenic exposure, may enhance allergic sensitisation in children.

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.

Breastfeeding promotion in neonatal intensive care unit: impact of a new program toward a BFHI for high‐risk infants

Aim: The study evaluates a breastfeeding promotion program in an Italian neonatal intensive care unit (NICU) over a period of time.

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.