Background: Dysregulation of the arachidonic acid metabolic pathway is the most widely known pathomechanism of AERD. We performed integrative analysis of transcriptomic and epigenomic profiling with network analysis to determine the novel pathogenic features of AERD. Methods: Ten patients with asthma including 5 patients with AERD and another 5 patients with aspirin tolerant asthma (ATA) were enrolled. Nasal epithelial scraping was performed and nasal mucosa was used in omics profiling. Peripheral eosinophil counts, sputum eosinophil counts, FeNO levels, and pulmonary function test results were evaluated. Differentially expressed genes (DEGs), differentially methylated probes (DMPs) and differentially correlated genes (DCGs) between patients with AERD and those with ATA were analyzed. Network analysis using Ingenuity Pathway Analysis (IPA) was performed to determine the gene connection network and signaling pathways. Results: In total, 1,736 DEGs and 1,401 DMPs were identified. Finally, 19 pairs for DCGs were selected. Among DCGs, genes related to vesicle transport (e.g. STX2 and RAB3B) and sphingolipid dysregulation (e.g. SMPD3) were found to be hypo-methylated and up-regulated in patients with AERD. A total number of 78 asthma-related DEGs were identified by the IPA knowledge base. Using the canonical pathway analysis of IPA, signaling pathways of T helper cell differentiation/activation and Fcε receptor I were generated. Up-regulation of RORγt and down-regulation of MHCII, TNFR, and TGF-β as well as up-regulation of FCER1A and JAK and down-regulation of VAV and cPLA2 were noted in patients with AERD. Conclusions: Distinct pathogenic features were identified by using integrative multi-omics data analysis in patients with AERD.

Background: Little is known about the clinical course of chronic urticaria (CU) and predictors of its prognosis. We evaluated CU patient clusters based on medication scores for the initial 3 months of treatment to investigate time to remission and relapse rates and to identify predictors for CU remission. Methods: In total, 4552 patients (57.9% female; mean age of 38.6 years) with CU were included in this retrospective cohort study. The K-medoids algorithm was used for clustering CU patients. Kaplan-Meier survival analysis with Cox regression was applied to identify predictors of CU remission. Results: Four distinct clusters were identified: patients with consistently low disease activity (cluster 1, n = 1786), with medium-to-low disease activity (cluster 2, n = 1031), with consistently medium disease activity (cluster 3, n = 1332), or with consistently high disease activity (cluster 4, n = 403). Mean age, treatment duration, peripheral neutrophil counts, total IgE, and complements levels were significantly higher for cluster 4 than the other three clusters. Median times to remission were also different among the four clusters (2.1 vs 3.3 vs 6.4 vs 9.4 years, respectively, P < .001). Sensitization to house dust mites (≥ class 3) and female sex were identified as significant predictors of CU remission. Around 20% of patients who achieved CU remission experienced relapse. Conclusion: In this study, we identified four CU patient clusters by analyzing medication scores during the first 3 months of treatment and found that sensitization to house dust mites and female sex can affect CU prognosis.

To the Editor, A COVID-19 epidemic started in China and then disseminated to other Asian countries before becoming a pandemic. It appears that the pandemic has so far resulted in proportionately fewer deaths in China and most Eastern Asian countries. Many reasons can explain this picture.1 One of them is the type of diet in the low mortality countries. 2This paper is the sixth of a series attempting to understand the role of diet in the differences of COVID-19 death rates between and within countries with the aim to identify potential preventive measures against COVID-19. The concept paper 2 was followed by two ecological studies comparing death rates in European countries and the consumption of vegetables or fermented foods. 3,4 We then proposed that sulforaphane from cruciferous vegetables1 and lactobacilli from fermented foods (submitted) were possibly involved in the reduction of insulin resistance in COVID-19.It is noteworthy that fermented foods are largely used in Asia.5,6 It is therefore important to check whether some commonly eaten fermented foods in these countries may explain geographic differences in COVID-19. Kimchi will be used as a model of fermented cabbage.