Evidence suggests IgE may play a role in chronic rhinosinusitis (CRS). We sought to determine if treatment with a monoclonal antibody against IgE (omalizumab) is effective in reducing CRS inflammation. We performed a randomized, double blind, placebo controlled clinical trial in subjects with CRS despite treatment (including surgery). Subjects were randomized to receive omalizumab or placebo for 6 months. The primary outcome was quantitative measurement of sinus inflammation on imaging. Secondary outcome measures included quality of life, symptoms, and cellular inflammation, nasal airflow (NPIF) and olfactory testing (UPSIT). Subjects on omalizumab showed reduced inflammation on imaging after treatment, whereas those on placebo showed no change. The net difference, however, was not different between treatments. Treatment with omalizumab was associated with improvement in the Sino-Nasal Outcome Test (SNOT-20) at 3, 5, and 6 months compared to baseline with no significant changes in the control group. Remaining measures showed no significant differences across treatments. We conclude that IgE plays, at most, a small role in the mucosal inflammation of CRS and the symptoms. Placebo controlled, blinded studies with larger enrollment are needed to determine the clinical significance of any potential change.

Psoriasis is a common chronic inflammatory skin disease, affecting 2-4% of world population. MicroRNAs (miRNAs) are short non-coding RNAs that regulate expression of the majority of protein-coding genes. In psoriasis, previous studies have identified deregulation in miRNA expression. Most of these studies utilized full-depth skin biopsies and thus may have missed the cell-specific miRNomic signature. Here, we analyzed the miRNome of CD45 neg sorted epidermal cells from psoriasis patients and healthy skin by next-generation sequencing. We detected, differential expression of 104 miRNAs in the psoriatic epidermal cells, including several known and novel miRNAs. MiR-149 was identified as one of the significantly downregulated miRNAs, and qPCR analysis confirmed its downregulation in psoriatic lesional epidermal cells as compared to non-lesional or normal skin. In primary human keratinocytes and in 3D epidermal equivalents, miR-149 was significantly downregulated by IFN-g. Overexpression of miR-149 suppressed the IFN-induced expression of IL-6 as well as T-cell attracting chemokines, while inhibition of endogenous miR-149 led to increased induction of these mediators. Taken together, we have characterized the cell-specific miRNome of epidermal non-immune cells in psoriasis skin and identified epidermal miRNAs, previously not associated with psoriasis. MiR-149 has been identified as a miRNA regulating the response of keratinocytes to IFN-g. Our results can provide a basis for further functional studies of miRNAs in keratinocytes and lead to the identification of potential targets for topical therapy in psoriasis.

not available. Disclosures: Study sponsored by Novartis. Copyright 2018 SKIN

Purpose of StudyPsoriasis (PSO), a chronic inflammatory skin disease, is associated with increased CV risk and vascular inflammation (VI). However, the effect of therapeutic lifestyle changes (TLC) including exercise on VI over time is unknown. We hypothesized that TLC would lead to an improvement in VI at 1 year accompanied by improvements in aortic wall characteristics.Methods Used65 PSO patients, recruited consecutively, underwent FDG PET/CT, phase contrast MRI scans and clinical visits for evaluation of VI, wall characteristics and exercise frequency, at baseline and 1 year follow-up. VI was measured as Target-to-background ratio (TBR), and aortic distensibility (AD) and wall thickness were assessed by commercial software on phase contrast MRI scans. Clinical parameters were ascertained by both survey and provider.Summary of ResultsVI decreased at 1 year (6.5% decrease in TBR; p<0.0001), and was inversely associated with exercise frequency beyond adjustment for CV risk factors (β=−0.27; p=0.001). Furthermore, this decrease in VI was associated with improvement in AD (40% increase; p<0.001) and aortic wall thickness (8.5% decrease; p<0.001).ConclusionsOur findings suggest that VI improves with TLC. This 6.5% decrease in VI could lead to ∼30% reduction in future adverse events, based on a recent large prospective study. This VI reduction is also associated with improved aortic wall characteristics suggesting that targeting VI as a surrogate marker holds promise to understand the effects of TLC on CV disease.Abstract 23 Figure 1

Purpose of StudyPsoriasis (PSO), a chronic inflammatory disease associated with increased CV risk, provides a clinical human model to study inflammatory atherogenesis. We aimed to assess the major determinants of vascular inflammation (VI) measured by 18FDG PET-MRI in a well-phenotyped PSO cohort.Methods Used124 consecutive patients with PSO underwent 18FDG PET-MRI scans. We used target-to-background ratio to quantify VI 120 minutes post FDG injection. Homeostatic model assessment of insulin resistance (HOMA-IR) was measured, along with cholesterol efflux capacity (CEC) and HDL particle concentration by NMR (Liposcience) fasting.Summary of ResultsOur cohort was middle aged (mean 49±13.3 years) with mild to moderate PSO, and low CV risk (median Framingham Risk Score (FRS) 2, IQR 2–6). PSO was associated with increased VI (β=0.27, p<0.005), compared to healthy controls. VI was associated with HOMA-IR (β=0.26, p<0.001), CEC (β=−0.12, p=0.04) and HDL particle concentration (β=−0.19, p=0.003) beyond traditional CV risk factors (age, gender, FRS and BMI). Among these, HOMA-IR provided maximum incremental value in predicting VI beyond traditional risk factors (χ2=39.36, p<0.001).ConclusionsVI by FDG PET MRI is associated with traditional CV risk factors and cardiometabolic parameters. Insulin resistance and CEC were most strongly associated with VI by 18FDG PET-MRI beyond traditional CV risk factors and BMI in PSO suggesting that cardiometabolic disease increases CV risk in PSO.Abstract 21 Figure 1