Diagnostic utility of fractional exhaled nitric oxide in prolonged and chronic cough according to atopic status

AbstractBackgroundCough-variant asthma (CVA) and cough-predominant asthma (CPA) are the major causes of persistent cough in Japan. The utility of fractional exhaled nitric oxide (FeNO) measurement in the differential diagnosis of persistent cough has been reported, but the influence of atopic status, which is associated with higher FeNO levels, on the diagnostic utility of FeNO has been unknown.MethodsWe retrospectively analyzed 105 non-smoking patients with prolonged and chronic cough that were not treated with corticosteroids and anti-leukotrienes.ResultsCPA was diagnosed in 37 patients, CVA in 40, and non-asthmatic cough (NAC) in 28. FeNO levels were significantly higher in the CPA [35.8 (7.0–317.9) ppb] and CVA [24.9 (3.1–156.0) ppb] groups than in the NAC group [18.2 (6.9–49.0) ppb] (p < 0.01 by Kruskal–Wallis test). The optimal cut-off for distinguishing asthmatic cough (AC; CPA and CVA) from NAC was 29.2 ppb [area under the curve (AUC) 0.74, p < 0.01]. Ninety-one percent of subjects with FeNO levels ≥29.2 ppb had AC. Meanwhile, 40% of AC patients had FeNO levels <29.2 ppb. Stratified cut-off levels were 31.1 ppb (AUC 0.83) in atopic subjects vs. 19.9 ppb (AUC 0.65) in non-atopic subjects (p = 0.03 for AUC).ConclusionsAlthough high FeNO levels suggested the existence of AC, lower FeNO levels had limited diagnostic significance. Atopic status affects the utility of FeNO levels in the differential diagnosis of prolonged and chronic cough

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

Endovascular treatment for hemothorax via contralateral internal thoracic artery branch after Nuss procedure – A case report

The Nuss procedure is performed widely as a standard surgical treatment for pectus excavatum. Compared to conventional methods, the Nuss procedure excels in cosmetic terms and involves fewer complications. A 14-year-old boy developed right hemothorax with a sudden shock one month after the Nuss procedure. We identified the bleeding from left internal thoracic artery (ITA) branch and achieved hemostasis by endovascular coil embolization. To the best of our knowledge, this is the first to report that the ITA on the contralateral side of the hemothorax was responsible for the bleeding