Metabolomic Profiling of Infants With Recurrent Wheezing After Bronchiolitis

Abstract

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 bronchiolitis 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 physician-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.

Metabolic changes during respiratory syncytial virus infection of epithelial cells

“…Metabolic studies may complement transcriptomic an proteomic analysis unraveling new aspects of virus-host interactions and, therefore, new potential intervention strategies. Metabolomic analyses on HRSV infection have been conducted only very recently, mostly in the biological fluids of infected patients [19][20][21][22][23][24]. An alternative to analyzing biofluids from infected individuals is to use cellular models in more controlled experimental settings, such as cultured cells that directly support the entire viral replication cycle.…”

Toward Personalized Medicine in Bronchiolitis

“…Weak antiviral plasmacytoid dendritic cell responses were characteristic of an endotype grouping preterm and infants older than 4 months (15). Recently, using urine for untargeted metabolomic analyses based on mass spectrometry in 52 Italian children with bronchiolitis, major involvement of the citric acid cycle discriminated those prone to subsequently experience recurrent wheezing (16).…”

The Metabolomics of Childhood Atopic Diseases: A Comprehensive Pathway-Specific Review

“…Characteristics of the included studies are presented in the Supplementary Materials (Table S1) . Asthma was examined in 19 studies [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], wheeze in six [ 14 , 19 , 32 , 33 , 34 , 35 ], AD in two [ 36 , 37 ], and allergy (allergic rhinitis or food allergy) in five studies [ 16 , 17 , 18 , 35 , 38 ]. The number of atopic children with either asthma, wheeze, allergy, or AD ranged from 20 [ 14 , 36 ] to 380 [ 27 ].…”