Plasma steroid metabolite profiles are strongly associated with childhood respiratory infection proneness (CRIP)

Abstract

Background: Recurrent respiratory infections are a leading cause of morbidity and mortality in children; endogenous steroids may impact childhood respiratory infection proneness (CRIP).

Aim: To understand the associations between endogenous steroid profiles and CRIP.

Methods: Two pre-birth cohorts were analyzed using a discovery and replication approach: the VDAART discovery population (n=421; NCT00920621) included children with metabolomic profiling at ages 1 and 6 years; and the COPSAC replication population (n=481; NCT00798226) at ages 1.5 and 6 years. Plasma metabolomic profiling was performed by Metabolon (NC, USA) using UPLC-MS/MS. The cumulative number of respiratory infections (e.g., URIs, LRIs) that occurred during the study period was recorded, and Poisson regression was used to evaluate associations between 18 steroid metabolites and the cumulative number of respiratory infections (referred to as CRIP).

Results: Poisson regression analysis demonstrated inverse associations between steroid metabolites and CRIP at a nominal significance threshold in VDAART at age 1 year (P-values: 0.0127-2.33x10-12). Four of these associations replicated in COPSAC at age 18 months (P-values: 0.022-1.55x10-3). In a follow-up inquiry at age 6, reduced steroid levels were associated with increased CRIP in both cohorts. Significant inverse associations were observed for 12 metabolites in VDAART (P-values: 0.035-4.05x10-5) and 14 metabolites in COPSAC at age 6 years (P-values: 0.018-4.28x10-9).

Conclusions: These results suggested that reduced steroid levels in infancy and age 6 are associated with increased occurrence of respiratory infections.