WDR46 is a Genetic Risk Factor for Aspirin-Exacerbated Respiratory Disease in a Korean Population

Purpose

The human WD repeat-containing protein 46 (WDR46; also known as C6orf11), located at the disease-relevant centromere side of the class II major histocompatibility complex region, is hypothesized to be associated with risk of aspirin-exacerbated respiratory disease (AERD) as well as a decline in forced expiratory volume in the first second (FEV1), an important diagnostic marker of asthma.

Methods

To investigate the association between WDR46 and AERD, five single-nucleotide polymorphisms (SNPs) were genotyped in 93 AERD cases and 96 aspirin-tolerant asthma controls of Korean ethnicity. Three major haplotypes were inferred from pairwise comparison of the SNPs, and one was included in the association analysis. Differences in the frequency distribution of WDR46 SNPs and haplotype were analyzed using logistic and regression models via various modes of genetic inheritance.

Results

Depending on the genetic model, the logistic and regression analyses revealed significant associations between rs463260, rs446735, rs455567, rs469064, and WDR46_ht2 and the risk of AERD (P=0.007-0.04, P_corr=0.01-0.04) and FEV1 decline after aspirin provocation (P=0.006-0.03, P_corr=0.01-0.03). Furthermore, functional analysis in silico showed that the G>A allele of rs463260 located in the 5'' untranslated region potentially matched a nucleotide sequence within an upstream open reading frame of WDR46.

Conclusions

These findings show for the first time that WDR46 is an important genetic marker of aspirin-induced airway inflammation and may be useful for formulating new disease-management strategies.     

肥大细胞体外脱颗粒的检测方法

目的和方法：模拟体内的脱颗粒反应，分别通过荧光分光光度计和酶活力测定方法定量检测组胺和类胰蛋白酶释放，探讨类胰蛋白酶活力测定法检测肥大细胞脱颗粒的可行性。结果：致敏血清和肥大细胞共孵育后在抗原刺激下，引起组胺和类胰蛋白酶剂量依赖性释放，且二者释放是平行的。结论：与组胺的测定比较，类胰蛋白酶活力测定可以用来标记肥大细胞脱颗粒的程度，该法灵敏可靠，简单可行，为临床上诊断变态反应疾病和筛选变应原提供新的检测方法。     

Emerging Biomarkers Beyond Leukotrienes for the Management of Nonsteroidal Anti-inflammatory Drug (NSAID)-Exacerbated Respiratory Disease

Nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) is a unique condition characterized by aspirin/NSAID hypersensitivity, adult-onset asthma, and/or chronic rhinosinusitis with nasal polyps. Arachidonic acid metabolism dysregulation and intense eosinophilic/type 2 inflammation are central mechanisms in NERD. Studies have been conducted on various biomarkers, and urinary leukotriene E4 is considered the most available biomarker of NERD. However, the pathophysiology of NERD is heterogeneous and complex. Epithelial cells and platelets can interact with immune cells in NERD, and novel biomarkers related to these interactions have recently been investigated. We summarize emerging novel biomarkers of NERD and discuss their roles in the management of NERD.     

近来我国马群中呼吸道疾病流行的病因学研究

通过病因学，血清学和流行病学研究，弄清了近期我国马群中类流感疾病流行的病因为马２亚型流感病毒。采用多克隆和单克隆抗体对分离物进行抗原性分析，结果提示，从我国马群中分离到的流感病毒株是马２（Ｈ３Ｎ８）亚型流感病毒，它绝然不同于过去我们发现的禽的Ｈ３Ｎ８流感病毒。估计它是近期内从国外马群传入我国。     

NPPV治疗慢性阻塞性肺疾病合并 重症呼吸衰竭的临床疗效观察

目的 分析无创正压通气治疗慢性阻塞性肺疾病合并重症呼吸衰竭的临床效果。方法 选择我院2015年3月~2017年4月诊治的慢性阻塞性肺疾病合并重症呼吸衰竭患者86例进行研究,随机分为研究组和对照组,各43例,对照组患者进行常规治疗,研究组在此基础上应用NPPV治疗,对比两组患者的心率、呼吸频率、动脉血气水平、治疗效果和不良反应。结果 研究组患者的心率水平优于对照组[（88.62±1.27）vs（98.37±1.33）]次/min,差异有统计学意义（P＜0.05）;研究组患者呼吸频率低于对照组[（18.24±2.26）vs（27.33±2.71）] 次/min,差异有统计学意义（P＜0.05）;研究组患者PaO2和PaCO2水平均优于对照组,差异有统计学意义（P＜0.05）;研究组治疗总有效率为90.69%,对照组治疗总有效率55.81%,组间比较,差异有统计学意义（P＜0.05）;研究组治疗不良反应率低于对照组,组间比较,差异有统计学意义（P＜0.05）。结论 NPPV在慢性阻塞性肺疾病合并重症呼吸衰竭治疗中发挥了积极的价值,能够改善患者的生理指标,治疗有效率高,不良反应少。     

The Hidden Culprit: A Case of Repeated Anaphylaxis to Cremophor

Drug-induced anaphylaxis is a big pitfall in patients receiving antineoplastic chemotherapy. We report a case of lung cancer patient who experienced two near-fatal anaphylactic reactions that resulted from paclitaxel and multivitamin, seperately. Recurrent severe reactions to different agents led to further investigation to which material the patient was hypersensitive. The skin prick test revealed sensitization to cremophor, which is a commonly used emulsifying agent. This case emphasizes the importance of correctly identifying the culprit drug of anaphylaxis to avoid potentially fatal reaction.     

Electron Microscopy in End Stage Renal Disease: A Case of Fabry's Disease

Fabry's disease is an X-linked error of metabolism with deficiency of the enzyme α-glycosidase A, and glycosphingolipid accumulation in multiple tissues. Patients may be asymptomatic and present with advanced disease. We report a case of a 38 year old white male who presented with end stage renal disease of unknown etiology. He received a living-related donor kidney transplant (mother), but lost the graft after 10 years to multiple episodes of rejection. Review of the native renal biopsy with added ultrastructural studies established the diagnosis of Fabry's disease. Evaluation of renal biopsies showing advanced chronic injury should include electron microscopic studies, which may reveal characteristic diagnostic features, as seen in this case of Fabry's disease. Identification of hereditary disorders involving the kidney is important for appropriate treatment and prevention of disease recurrence. Potential living related donors should be screened for genetic involvement.