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Respiratory syncytial virus (RSV) is an important respiratory pathogen in infants and children worldwide. Although RSV typically causes mild upper respiratory infections, it frequently causes severe morbidity and mortality, especially in premature infants and children with other chronic diseases. Treatment of RSV is limited by a lack of effective antiviral treatments; however, ribavirin has been used in complicated cases, along with the addition of intravenous immune globulin in specific patients. Vaccination strategies for RSV prevention are heavily studied, but only palivizumab (Synagis®) has been approved for use in the United States in very select patient populations. Research is ongoing in developing additional vaccines, along with alternative therapies that may help prevent or decrease the severity of RSV infections in infants and children. To date, we have not seen a decrement in RSV morbidity and mortality with our current options; therefore, there is a clear need for novel RSV preventative and therapeutic strategies. In this review, we discuss the current and evolving trends in RSV treatment for infants and children.

These findings represent further evidence of the association between factor H dysfunction and HUS.

BackgroundMechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously demonstrated that children with CF and parental-reported secondhand smoke exposure (SHSe) have increased susceptibility to bacterial infections. SHSe hinders arachidonic acid (AA) metabolites that mediate immune function in patients without CF, and may influence CF immune dysfunction. We aimed to define SHSe’s impact on inflammation mediators and infection in children with CF.MethodsSeventy-seven children with CF <10 years of age (35 infants <1 year; 42 children 1–10 years) were enrolled and hair nicotine concentrations measured as an objective surrogate of SHSe. AA signalling by serum and macrophage lipidomics, inflammation using blood transcriptional profiles and in vitro macrophage responses to bacterial infection after SHSe were assessed.ResultsHair nicotine concentrations were elevated in 63% of patients. Of the AA metabolites measured by plasma lipidomics, prostaglandin D2 (PGD2) concentrations were decreased in children with CF exposed to SHSe, and associated with more frequent hospitalisations (p=0.007) and worsened weight z scores (p=0.008). Children with CF exposed to SHSe demonstrated decreased expression of the prostaglandin genes PTGES3 and PTGR2 and overexpression of inflammatory pathways. These findings were confirmed using an in vitro model, where SHSe was associated with a dose-dependent decrease in PGD2 and increased methicillin-resistant Staphylococcus aureus survival in human CF macrophages.ConclusionsInfants and young children with CF and SHSe have altered AA metabolism and dysregulated inflammatory gene expression resulting in impaired bacterial clearance. Our findings identified potential therapeutic targets to halt early disease progression associated with SHSe in the young population with CF.

SHS exposure in CF infants is associated with diminished growth, increased air trapping and bronchodilator responsiveness, and propensity to culture MRSA and facultative anaerobic bacteria, suggesting the need for early, aggressive parental smoking cessation interventions to prevent SHS exposure complications.

Background Mechanisms that facilitate early infection and inflammation in cystic fibrosis (CF) are unclear. We previously showed that young CF children with secondhand smoke exposure (SHSe) have increased susceptibility to respiratory infections. We aimed to define the impact of SHSe and other external factors upon the fecal bacteriome in early CF. Methods Twenty CF infants and children were enrolled, clinical data recorded, and hair nicotine measured as an objective surrogate of SHSe. Fecal samples were collected at clinic visits and bacteriome 16S rRNA gene sequencing performed. Results SHSe was associated with increased alpha diversity and increased relative abundance of Acinetobacter and Akkermansia, along with decreased Bifidobacterium and Lactobacillus. Recent antibiotic exposure predicted bacterial population structure in children less than 2 years of age and was associated with decreased Bacteroides relative abundance. Age was the strongest predictor of overall fecal bacterial composition and positively associated with Blautia and Parabacteroides. Weight for length was negatively associated with Staphylococcus relative abundance. Conclusions SHSe and other external factors such as antibiotics appear to alter fecal bacterial composition in young CF children, but the strongest predictor of overall composition was age. These findings have implications for understanding the intestinal microbiome in young CF children.

OBJECTIVES Dexmedetomidine use for sedation in the pediatric intensive care units (PICUs) has increased since its initial US Food and Drug Administration (FDA) approval in adults. However, there is limited evidence to direct providers regarding current usage, dosing, and monitoring for withdrawal symptoms in pediatric patients. This study sought to determine the utilization of dexmedetomidine and management of dexmedetomidine withdrawal symptoms among PICU physicians. METHODS A questionnaire survey was distributed to all members of the American Academy of Pediatrics Section on Critical Care. It assessed the practice site demographics, indication, dosing, and duration of dexmedetomidine infusion, unit protocol, and strategies for management of dexmedetomidine withdrawal. RESULTS A total of 147 surveys (21.1%) were returned and analyzed. The reported uses for dexmedetomidine were as a primary sedative (59.9%), adjunctive agent for sedation (82.3%), and adjunctive agent to assist weaning sedation (62.6%) or from mechanical ventilation (70.1%). One hundred twenty-nine respondents (87.8%) had concerns over dexmedetomidine withdrawal, with 59 respondents becoming concerned after 120 hours of infusion (45.7%). Most respondents reported managing dexmedetomidine withdrawal symptoms via a regimented wean and initiation of clonidine (81%). Units with &gt;1000 admissions per year were more likely to have a protocol related to dexmedetomidine use (p = 0.021). Units with &gt;1000 admissions per year reported using clonidine for withdrawal at a higher rate, whereas units with ≤1000 admissions per year used a systematic wean of dexmedetomidine (p = 0.014). CONCLUSIONS Dexmedetomidine use in the PICU is varied among pediatric intensive care physicians. Intensivists have withdrawal concerns after dexmedetomidine discontinuation, and the primary management of this withdrawal phenomenon is the initiation of clonidine with a regimented dexmedetomidine wean.

Arthritis may be the first clinical manifestation of primary hypogammaglobulinaemia. In 16 years of 281 patients who had immunodeficiency, 30 had arthritis at presentation. It was more common in Bruton's disease (15 (22%) of 69 patients) than in other forms of immunodeficiency (15 (7%) of 212 patients). Non-septic arthritis was more prevalent than septic arthritis, particularly monoarticular arthritis in Bruton's disease and pauciarticular disease in common variable immunodeficiency. Boys in whom a diagnosis of Bruton's disease was delayed were likely to develop recurrent infections complicated by arthritis.The measurement of serum immunoglobulin concentrations readily differentiates immunodeficiency from conditions such as Stili's disease and dictates subsequent management.