PT - JOURNAL ARTICLE AU - Thilini Samarasinghe AU - Marcel Nold AU - Ina Rudloff AU - Elizabeth. M Skuza AU - Nikeh Shariatian AU - Mandar. S Joshi AU - Philip. J Berger AU - Claudia. A Nold-Petry TI - Late-breaking abstract: Lethal impact of antenatal nicotine and inflammation in newborn mice DP - 2014 Sep 01 TA - European Respiratory Journal PG - P1809 VI - 44 IP - Suppl 58 4099 - http://erj.ersjournals.com/content/44/Suppl_58/P1809.short 4100 - http://erj.ersjournals.com/content/44/Suppl_58/P1809.full SO - Eur Respir J2014 Sep 01; 44 AB - INTRODUCTION: Combined perinatal infection and nicotine exposure is linked with elevated risk of fetal death, growth restriction and abnormal lung development. Alarmingly, 25% of pregnant Australian women continue to smoke and 30% have infection. To date we have no explanation for the danger posed by smoking and infection during pregnancy. We recently noted that nicotine and lipopolysaccharide (LPS) treatment caused high mortality in newborn pups. We hypothesized that the two insults affect survival by producing lung inflammation and impairing perinatal lung liquid reabsorption.METHODS: At E14, C57BL/6 dams were implanted with osmotic mini-pumps to deliver nicotine (NIC, 6mg/kg/day) or water (VEH) for 14 days. At E16, implanted mice were injected with LPS (150µg/kg; ip) or left untreated. At E18, lungs underwent cytokine analysis, histology, abundance of pulmonary IL1-β. Expression of α-ENaC, a component of epithelial channels vital for lung liquid clearance, was detected by immunoblot. In separate pups we compared wet/dry lung ratios at birth in NIC+LPS vs VEH groups.RESULTS: On day 1, mortality was zero in VEH pups, 50% in NIC (p=0.055) and 95% in NIC+LPS (p<0.01). IL1-β, IL-4, IL-5, IL-16, and IL-17 were higher in NIC and NIC+LPS lungs vs VEH. Immunohistochemistry confirmed up-regulation of IL1-β in lungs of NIC and NIC+LPS pups. At E18, lungs from NIC+LPS pups had reduced α-ENaC expression on alveolar luminal surface compared to VEH pups. At birth, NIC+LPS pups had a higher wet/dry lung ratio compared to the VEH pups (6.60±0.2 vs 5.38±0.2 p<0.0003).CONCLUSION: We suggest the lethality of antenatal nicotine and inflammation results from impaired gas exchange across a wet and inflamed pulmonary epithelium.