Background: Inflammation is integral to early disease progression in children with CF. The effect of modifiable environmental factors on infection and inflammation in persons with CF is poorly understood. Our prior studies determined that secondhand smoke exposure (SHSe) is highly prevalent in young children with CF. SHSe is associated with increased inflammation, heightened bacterial burden, and worsened clinical outcomes. However, the specific metabolite and signaling pathways that regulate responses to SHSe in CF are relatively unknown. Methods: High-resolution metabolomics was performed on plasma samples from infants (n = 25) and children (n = 40) with CF compared to non-CF controls (n = 15). CF groups were stratified according to infant or child age and SHSe status. Results: Global metabolomic profiles segregated by age and SHSe status. SHSe in CF was associated with changes in pathways related to steroid biosynthesis, fatty acid metabolism, cysteine metabolism, and oxidative stress. CF infants with SHSe demonstrated enrichment for altered metabolite localization to the small intestine, liver, and striatum. CF children with SHSe demonstrated metabolite enrichment for organs/tissues associated with oxidative stress including mitochondria, peroxisomes, and the endoplasmic reticulum. In a confirmatory analysis, SHSe was associated with changes in biomarkers of oxidative stress and cellular adhesion including MMP-9, MPO, and ICAM-1. Conclusions: SHSe in young children and infants with CF is associated with altered global metabolomics profiles and specific biochemical pathways, including enhanced oxidative stress. SHSe remains an important but understudied modifiable variable in early CF disease.
Bibliographical noteFunding Information:
Thank you to all our patients with CF and their families for their participation. This work was supported in part by a Nationwide Children's Hospital intramural grant (BTK, RT, AM), an American Academy of Pediatrics Julius B. Richmond Center New Investigator Grant (BTK), NIEHS CHEAR pilot and feasibility grant (BTK), National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number 1U2CES02653, and the Cure CF Columbus Translational Core (C3TC) and Immune Core (C3IC). C3TC and C3IC are supported by the Division of Pediatric Pulmonary Medicine, the Biopathology Center Core, and the Data Collaboration Team at Nationwide Children's Hospital. C3TC and C3IC grant support provided by The Ohio State University Center for Clinical and Translational Science (National Center for Advancing Translational Sciences, Grant UL1TR002733) and by the Cystic Fibrosis Foundation (Research Development Program, Grant MCCOY19RO). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Thank you to the Minnesota CHEAR Exposure Assessment Hub and the National Exposure Assessment Laboratory at Emory for assistance with sample analysis, and Karin Vevang and Dr. Lisa Patterson for CHEAR project coordination.
- Cystic fibrosis
PubMed: MeSH publication types
- Journal Article