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Cystic fibrosis
Original article
Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis
  1. Benjamin T Kopp1,2,
  2. Rohan Thompson1,
  3. Jeeho Kim2,
  4. Robert Konstan2,
  5. Alejandro Diaz3,
  6. Bennett Smith3,
  7. Chandra Shrestha2,
  8. Lynette K Rogers4,
  9. Don Hayes Jr1,
  10. Dmitry Tumin5,
  11. Frederick W Woodley6,
  12. Octavio Ramilo3,
  13. Don B Sanders7,
  14. Judith A Groner8,
  15. Asuncion Mejias3
  1. 1 Division of Pulmonary Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA
  2. 2 Center for Microbial Pathogenesis, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
  3. 3 Center for Vaccines and Immunity, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
  4. 4 Center for Perinatal Research, The Research Institute at Nationwide Children’s Hospital, Columbus, Ohio, USA
  5. 5 Department of Anesthesiology and Pain Medicine, Nationwide Children’s Hospital, Columbus, Ohio, USA
  6. 6 Division of Gastroenterology, Hepatology and Nutrition, Nationwide Children’s Hospital, Columbus, Ohio, USA
  7. 7 Riley Children’s Hospital, Indianapolis, Indiana, USA
  8. 8 Section of Ambulatory Pediatrics, Nationwide Children’s Hospital, Columbus, Ohio, USA
  1. Correspondence to Dr Benjamin T Kopp, Nationwide Children’s Hospital, Columbus, OH 43205, USA; Benjamin.Kopp{at}nationwidechildrens.org

Abstract

Background Mechanisms 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.

Methods Seventy-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.

Results Hair 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.

Conclusions Infants 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.

  • cystic fibrosis
  • macrophage biology
  • tobacco and the lung
  • paediatric lung disaese

https://doi.org/10.1136/thoraxjnl-2018-211845

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    Footnotes

    • Patient consent for publication Not required.

    • Contributors BTK, RT, JAG and AM designed the study. BTK wrote the manuscript. BK, AD, DT and BS performed statistical analysis. BTK, BS, RT, DBS, DH, FWW, OR, JAG and AM analysed and interpreted data. JK, RK, CS, AD, BS and LR created experimental data. BTK, RT and DBS collected clinical samples. All authors contributed to editing and approved the final manuscript.

    • Funding This work was supported in part by The Ohio State University College of Medicine Roessler research scholarship (JK), a Nationwide Children’s Hospital intramural grant (BTK, RT, AM), an American Academy of Pediatrics Julius B. Richmond Center New Investigator Grant (BTK) and CTSA grant UL1TR001070.

    • Competing interests None declared.

    • Ethics approval This study was approved by the Institutional Review Boards at Nationwide Children’s Hospital (IRB #12–00084) and Riley Children’s Hospital (IRB #1607531974).

    • Provenance and peer review Not commissioned; externally peer reviewed.

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