Post-viral atopic airway disease: pathogenesis and potential avenues for intervention

Introduction: In early childhood, wheezing due to lower respiratory tract illness is often associated with infection by commonly known respiratory viruses such as respiratory syncytial virus (RSV) and human rhinovirus (RV). How respiratory viral infections lead to wheeze and/or asthma is an area of active research.

Areas covered: This review provides an updated summary of the published information on the development of post-viral induced atopy and asthma and the mechanisms involved. We focus on the contribution of animal models in identifying pathways that may contribute to atopy and asthma following respiratory virus infection, different polymorphisms that have been associated with asthma development, and current options for disease management and potential future interventions.

Expert commentary: Currently there are no prophylactic therapies that prevent infants infected with respiratory viruses from developing asthma or atopy. Neither are there curative therapies for patients with asthma. Therefore, a better understanding of genetic factors and other associated biomarkers in respiratory viral induced pathogenesis is important for developing effective personalized therapies.     

基于血管内皮功能相关多生物标记物的哮喘预后研究

目的 分析哮喘儿童血清中血管内皮功能相关标记物的变化情况及其与疾病预后的关系,为儿童哮喘预后的评估提供依据。方法 收集2016年10月-2017年12月在南通大学附属常州儿童医院就诊的89例5～14岁哮喘患儿在哮喘发作期的血清样本和92例健康儿童的血清样本,运用ELISA和其他商用测试盒检测其中内皮功能相关标志物血管内皮生长因子(VEGF)、精氨酸酶I(Arg I)、骨膜蛋白(POSTN)、脂联素(APN)和瘦素的浓度以及诱导型一氧化氮合酶(iNOS)活性,并用高效液相串联质谱(HPLC-MS/MS)检测L-精氨酸、甲基化精氨酸ADMA和SDMA的浓度。此后对哮喘组患儿进行为期1年的随访,记录在此期间出现喘息发作的次数。运用正交偏最小二乘法-判别分析(OPLS-DA)分析数据,筛选对哮喘疾病预后有关键影响的血管内皮功能相关标记物。结果 哮喘组儿童血清中Arg I、POSTN、VEGF和瘦素的含量显著增加,iNOS活性显著增高,L-精氨酸浓度显著下降(P<0.05)。OPLS-DA模型显示,基于内皮功能多标记物哮喘组可以和对照组显著区分,且Arg I、iNOS活性以及VEGF水平的变量重要性因子(VIP)值分别为2.11、1.23、1.09,是区分哮喘组和对照组的关键内皮标记物。随访后1年,随访成功70例,其中反复喘息组(n=27)与非反复喘息组(n=43)相比,血清ADMA和Arg I的含量显著增加,POSTN和APN含量显著减少(P<0.05)。OPLS-DA模型的S-plot图和VIP值排序都表明区分两组的关键内皮标记物是APN、POSTN和Arg I。结论 哮喘儿童血清中多种内皮功能相关的生物标记物稳态失衡,其中APN、POSTN和Arg I对儿童哮喘的疾病预后有较高的预测价值。     

Proteomic genotyping of fingermark donors with genetically variant peptides

Proteomic genotyping detects single amino acid polymorphisms to infer the genotype of corresponding non-synonymous SNPs. Like any DNA genotype, these inferences can be used to estimate random match probability. Fingermarks are a common source of biological evidence that is sample limited and a highly variable source of identifying DNA. Genetically variant peptides from fingermarks, that contain single amino acid polymorphisms, are an additional source of identifying genetic information. To discover these peptide biomarkers epidermal corneocytes from 9 subjects were isolated, processed, digested with trypsin and applied to mass spectrometry. The resulting proteomic and matching exome datasets were used to discover, characterize and validate 60 genetically variant peptides. An average of 28.8 ± 4.4 genetically variant peptides were detected from each subject resulting in a total of 264 SNP allele inferences with 260 true and 4 false positives, a false discovery rate of 1.5%. Random match probabilities were estimated using the genotype frequencies from the matching major populations in the 1000 Genomes Project. Estimates ranged up to a value of 1 in 1.7 × 10⁸, with a median probability of 1 in 2.4 × 10⁶. Furthermore, the proteomically-inferred genotypes are likely to be compatible with the STR-based random match probability estimates since the closest STR locus was 2.2 Mb from the nearest GVP-inferred SNP. This project represents a novel mode of genetic information that can be obtained from fingermarks and has the potential to complement other methods of human identification including analysis of ridge patterns or touch DNA.     

健康管理对高危哮喘儿童家庭单元治疗依从性作用及肺功能指标的影响

目的 分析健康管理对提高以家庭为单位的高危哮喘儿童病情控制及肺功能指标的改善作用,为儿童哮喘防治提供新的思路。方法 选取2014年1月－2016年5月在山东省立医院就诊的93例高危哮喘儿童并随机分为实验组和对照组。实验组给予常规临床治疗加全程健康管理和定期随访;对照组只给予常规临床治疗,未贯穿健康管理,嘱定期随访。结果 实验组患儿的病情控制及各项肺功能指标较之于对照组有明显改善,差异有统计学意义(P<0.05)。结论 加强高危哮喘儿童的家庭单元的防控意识,进行系统、持续的健康管理,定期随访和监测,能明显减少患儿病情发作,提高治疗依从性。     

Tuberculosis and other chronic morbidity profile of sewage workers of Delhi

Background

Sewage management is hazardous due to chronic exposure to chemical gases, bioaerosols and micro-organisms through inhalation; accidental oral intake and penetration through skin or mucous membranes through injuries or breech in personal protective equipment. While there has been some research on isolated infections and multisystem symptom profiling of sewage workers, there is little research on the burden of chronic illnesses like Tuberculosis and Non Communicable Diseases (NCDs).

A novel splice-site variant in CDH23 in a patient with Usher syndrome type 1

ABSTRACT

Background: Gene editing has shown huge potential in correcting aberrant splicing and Cas13 has been identified as being particularly suitable for targeting RNA. It has therefore become increasingly important to highlight new splice site mutations that may be correctable, particularly in genes that are too large to be encoded by AAV vectors. About 20% of Usher Type 1 cases are caused by mutations in CDH23.

Purpose: To report a novel splice site mutation of CDH23 associated with Usher Type 1D.

Materials and Methods: Case report.

Results: A 35-year-old Caucasian female who is congenitally deaf with vestibular dysfunction presented with visual acuity of 6/12 in both eyes. Fundus examination revealed findings typical of retinitis pigmentosa with foveal preservation of photoreceptor layer. Next generation sequencing analysis revealed a novel homozygous variant, c.9319 + 1G>T in CDH23 consistent with the diagnosis of Usher Syndrome Type 1D. The c.9319 + 1G>T variant is predicted to affect splicing at the exon 65/intron 65 boundary, which highly likely leads to complete skipping of exon 65.

Conclusions: We describe a case of a typical Usher Syndrome Type 1D caused by a novel splice site variant in CDH23. Currently there are no treatments for CDH23 related retinal degeneration, partly because the cDNA size of 10kb is too large for AAV vector gene augmentation therapy. Alternative strategies include CRISPR-Cas9 adenine base editors and RNA editing with CRISPR-Cas13. Single-nucleotide editing represents a promising approach for targeting this variant in CDH23 to restore the wildtype splice donor site at this position.     

Oral-lung microbiome interactions in lung diseases

The proximity and continuity of the oral cavity and the lower respiratory tract allows the oropharyngeal microbiome to be a major determinant of the lung microbiome. In addition, host-pathogen interactions related to the oropharyngeal microbiome or its metabolites could propagate systemic inflammation or modulate host defense mechanisms that could affect other organs, including the lung. There is increasing appreciation of the pathophysiologic significance of the lung microbiome, not only in the classical infection-related diseases, pneumonia, bronchiectasis, and cystic fibrosis, but also in chronic noninfectious lung diseases, such as chronic obstructive pulmonary disease, asthma, and pulmonary fibrosis. In this review, we will explore the relationship of the oral microbiome with lung diseases, such as pneumonia, chronic obstructive pulmonary disease, asthma, and cystic fibrosis.