Table_1_Incidence disparities of obstructive sleep apnea-associated lung cancer by gender; Korean National Health Insurance data analysis.docx

IntroductionObstructive sleep apnea (OSA) is known to increase the risk of various cancers. By analyzing the Korea National Health Insurance Service (KNHIS) registry, the impact of OSA on the lung cancer incidence was analyzed in a retrospective cohort group.MethodsA retrospective cohort of adult patients newly registered with OSA in the KNHIS data from 2007 to 2017 was included and observed until December 2019 (12 years). The main outcome measure was newly diagnosed lung cancer. The control group was set with age and sex that matched those in the OSA group.ResultsThe hazard ratio (HR) of OSA for lung cancer incidence showed a significantly reduced HR of 0.87 (95% CI, 0.82–0.93). The observed significance of this finding was limited to male OSA patients [HR, 0.84 (95% CI, 0.78–0.90)], while no significant association was found in female OSA patients [HR, 1.05 (95% CI, 0.91–1.21)], irrespective of their age.DiscussionOSA patients have a lower risk of developing lung cancer, but this risk reduction is gender-specific, as female OSA patients do not show a reduction in hazard ratio.</p

Signaling pathway for DEP-induced expression of IL-6 and IL-8 in nasal fibroblasts and organ culture of nasal inferior turbinate.

<p>DEP-induced expression of IL-6 and IL-8 is mediated by the dual signaling pathways of p38 and Akt, which converge on the NF-κB pathway.</p

Cytokine and chemokine array in DEP-induced nasal fibroblasts.

<p>After nasal fibroblasts were untreated or treated with DEP (50 μg/ml) for 72 hours, cytokine and chemokine array was performed. Profiles of mean spot pixel density were measured using Quantity One software (Bio-Rad). The relative levels of IL-6 and IL-8 were much higher in DEP-induced nasal fibroblasts than in untreated cells. The levels of MIF, pentraxin-3, and uPAR were also higher in DEP-induced nasal fibroblasts. The graphic data represents the means ± S.E.M. for four donors. * <i>p</i><0.05; ** <i>p</i><0.01 compared to untreated.</p

Effects of diesel exhaust particulates on viability of nasal fibroblasts.

<p>Cytotoxic effects of diesel exhaust particulates in nasal fibroblasts. Nasal fibroblasts were treated with various concentrations (0–800 μg/mL) of diesel exhaust particulates for 72 hours. Cytotoxicity tests were performed by MTT assay. DEP did not affect cell survival until the concentration reached 400 μg/mL. The graphic data represents the means ± SEM of three independent experiments. * <i>p</i><0.05 compared to control.</p

Effect of DEP on expression of IL-6 and IL-8 in nasal fibroblasts.

<p>(A) After treatment with DEP (0–50 μg/mL) for 12 hours, mRNA expression of IL-6 and IL-8 was increased in a dose-dependent manner. (B) After treatment with DEP for 48 hours, protein expression levels of IL-6 and IL-8 were also increased in a dose-dependent manner. The graphic data represents the means ± SEM of three independent experiments. * p<0.05; ** p<0.01 compared to control.</p

Signaling pathway of DEP-induced IL-6 and IL-8 expression in nasal fibroblasts.

<p>(A) The expression level of phosphorylated p38 (p-p38) and Akt (p-Akt) was determined by western blot in nasal fibroblast treated by DEP (50 μg/mL), in the in the presence or absence of SB203580 (p38 inhibitor, 10 μmol/L) or LY294002 (Akt inhibitor, 10 μmol/L). β-actin was used as an internal control. (B) Expression levels of IL-6 and IL-8 were measured by ELISA after treatment with DEP with or without SB203580 or LY294002. The graphic data represents the means ± SEM of three independent experiments. * p<0.05, ** p<0.01 compared to control; † p<0.05 compared to treatment with DEP alone. </p

DEP-induced IL-6 and IL-8 expression and its suppression by signaling pathway inhibitors in <i>ex vivo</i> organ culture.

<p>Nasal inferior turbinate tissues were cultured ex vivo and treated with DEP (50 μg/mL). Expression of IL-6 and IL-8 was increased after treatment, as determined by ELISA. The increased expression was blocked by pretreatment with SB203580 (10 μmol/L), LY294002 (10 μmol/L), or BAY117082 (1uM). The graphic data represents the means ± SEM of three independent experiments. * p<0.05 compared to control; † p<0.05, †† p<0.01 compared to treatment with DEP alone.</p