Barlotta A, Pirillo P, Stocchero M, Donato F, Giordano G, Bont L, Zanconato S, Carraro S and Baraldi E.
Background. Bronchiolitis is associated with a greater risk of developing recurrent wheezing, but with currently available tools, it is impossible to know which infants with bronchiolitis will develop this condition. This preliminary prospective study aimed to assess whether urine metabolomic analysis can be used to identify children with bronchiolitis who are at risk of developing recurrent wheezing.
Methods. Fifty-two infants <1 year old treated in the emergency department at University Hospital of Padova for acute bronchi- olitis were enrolled (77% tested positive for respiratory syncytial virus [RSV]). Follow-up visits were conducted for 2 years after the episode of bronchiolitis. Untargeted metabolomic analyses based on mass spectrometry were performed on urine samples collected from infants with acute bronchiolitis. Data modeling was based on univariate and multivariate data analyses.
Results. We distinguished children with and those without postbronchiolitis recurrent wheeze, defined as ≥3 episodes of physi- cian-diagnosed wheezing. Pathway overrepresentation analysis pointed to a major involvement of the citric acid cycle (P < .001) and some amino acids (lysine, cysteine, and methionine; P ≤ .015) in differentiating between these 2 groups of children.
Conclusion. This is the first study showing that metabolomic profiling of urine specimens from infants with bronchiolitis can be used to identify children at increased risk of developing recurrent wheezing.
Keywords. Bronchiolitis; metabolomics; pediatrics; recurrent wheezing; urine; mass spectrometry; citric acid cycle.
Sánchez Luna M, Manzoni P, Paes B, Baraldi E, Cossey V, Kugelman A, Chawla R, Dotta A, Rodríguez Fernández R, Resch B, Carbonell-Estrany X.
Respiratory syncytial virus (RSV) infection is a leading cause of hospitalisation in early childhood and palivizumab is the only licensed intervention for prevention. Palivizumab guidelines should reflect the latest evidence, in addition to costs-effectiveness and healthcare budgetary considerations. RSV experts from Europe, Canada and Israel undertook a systematic review of the evidence over the last 5 years and developed recommendations regarding prophylaxis in industrialised countries. Almost 400 publications were reviewed. This group recommended palivizumab for: preterm infants (<29 and ≤31 weeks gestational age [wGA] and ≤9 and ≤6 months of age, respectively; high-risk 32-35 wGA), former preterm children ≤24 months with chronic lung disease/bronchopulmonary dysplasia, children ≤24 months with significant congenital heart disease; and other high-risk populations, such as children ≤24 months with Down syndrome, pulmonary/neuromuscular disorders, immunocompromised, and cystic fibrosis. Up to 5 monthly doses should be administered over the RSV season. It is our impression that the adoption of these guidelines would help reduce the burden of RSV.
Ascough S, Vlachantoni I, Kalyan M, Haijema BJ, Wallin- Weber S, Dijkstra-Tiekstra M, Ahmed MS, Roosmalen M van, Grimaldi R, Zhang Q, Leenhouts K, Openshaw PJ and Chiu C.
Despite numerous years of research we are still lacking a safe and effective RSV vaccine. This process is hindered by numerous problems: the lack of a correlate of protection being one of them.That this has major consequences for vaccine development, is illustrated by the study performed by Stephanie Ascough, Peter Openshaw and colleagues. In their paper they describe the results of a randomized controlled, phase 1 trial of a novel needle-free RSV vaccine: SynGEM. The vaccine is based on a stable pre-fusion F antigen of the virus, and uses a bacterium-like-particle (BLP) as an immune-enhancing carrier. The study confirms that the vaccine is safe and that it is capable of inducing a mild (about 2 to 3-fold), but prolonged, increase in RSV-specific antibodies. However, the study didn’t reach the endpoint threshold and for now, SynGEM is withheld from proceeding to next phase trials.
This study illustrates, that the lack of a correlate of protection brings an uncertainty to the table, which could lead to the premature termination of a potentially effective RSV vaccine. The use of a human challenge model (HCM) in RSV vaccine development would offer the possibility to circumvent this insecurity. Furthermore it might accelerate RSV-vaccine development.
Written by Sjanna Besteman