RT Journal Article
SR Electronic
T1 Secondhand smoke alters arachidonic acid metabolism and inflammation in infants and children with cystic fibrosis
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 237
OP 246
DO 10.1136/thoraxjnl-2018-211845
VO 74
IS 3
A1 Benjamin T Kopp
A1 Rohan Thompson
A1 Jeeho Kim
A1 Robert Konstan
A1 Alejandro Diaz
A1 Bennett Smith
A1 Chandra Shrestha
A1 Lynette K Rogers
A1 Don Hayes, Jr
A1 Dmitry Tumin
A1 Frederick W Woodley
A1 Octavio Ramilo
A1 Don B Sanders
A1 Judith A Groner
A1 Asuncion Mejias
YR 2019
UL http://thorax.bmj.com/content/74/3/237.abstract
AB 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.