Background

Emerging evidence suggests that disease vulnerability is expressed throughout the airways, the so-called unified airway hypothesis, but the evidence to support this is predominantly indirect.

Objectives

We sought to establish the transcriptomic profiles of the upper and lower airways and determine their level of similarity irrespective of airway symptoms (wheeze) and allergy.

Methods

We performed RNA sequencing on upper and lower airway epithelial cells from 63 children with or without wheeze and accompanying atopy, using differential gene expression and gene coexpression analyses to determine transcriptional similarity.

Results

We observed approximately 91% homology in the expressed genes between the 2 sites. When coexpressed genes were grouped into modules relating to biological functions, all were found to be conserved between the 2 regions, resulting in a consensus network containing 16 modules associated with ribosomal function, metabolism, gene expression, mitochondrial activity, and antiviral responses through IFN activity. Although symptom-associated gene expression changes were more prominent in the lower airway, they were reflected in nasal epithelium and included IL-1 receptor like 1, prostaglandin-endoperoxide synthase 1, CCL26, and periostin. Through network analysis we identified a cluster of coexpressed genes associated with atopic wheeze in the lower airway, which could equally distinguish atopic and nonatopic phenotypes in upper airway samples.

Conclusions

We show that the upper and lower airways are significantly conserved in their transcriptional composition, and that variations associated with disease are present in both nasal and tracheal epithelium. Findings from this study supporting a unified airway imply that clinical insight regarding the lower airway in health and disease can be gained from studying the nasal epithelium.

中文翻译：

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通过气道上皮的转录谱评估儿童的统一气道假说。

背景

越来越多的证据表明，疾病易感性在整个气道中都有表达，即所谓的统一气道假说，但是支持这种说法的证据主要是间接的。

目标

我们试图建立上呼吸道和下呼吸道的转录组谱，并确定它们的相似性水平，而与气道症状（喘鸣）和过敏无关。

方法

我们使用差异基因表达和基因共表达分析确定了转录相似性，对来自63名患有或不患有喘息并伴有特应性过敏的儿童的上，下气道上皮细胞进行了RNA测序。

结果

我们观察到两个站点之间表达的基因中大约91％的同源性。当共表达的基因被分组到与生物学功能有关的模块中时，发现它们在两个区域之间都是保守的，从而形成一个共有网络，其中包含16个与核糖体功能，代谢，基因表达，线粒体活性以及通过IFN活性产生的抗病毒反应相关的模块。尽管症状相关的基因表达变化在下呼吸道更明显，但它们反映在鼻上皮中，并包括IL-1受体（如1，前列腺素-过氧化物合酶1，CCL26）和骨膜素。通过网络分析，我们在下呼吸道中发现了一组与特应性喘息相关的共表达基因，这些基因可以同等地区分上呼吸道样本中的特应性和非特应性表型。

结论

我们显示，上呼吸道和下呼吸道在其转录组成中均显着保守，并且与疾病相关的变异存在于鼻和气管上皮中。这项研究的结果支持统一的气道，这意味着可以通过研究鼻上皮获得有关健康和疾病中下气道的临床见解。