Background

Work exposures play a significant role in adult-onset asthma, but the mechanisms of work-related asthma are not fully elucidated.

Objective

We aimed to reveal the molecular mechanisms of work-related asthma associated with exposure to flour (flour asthma), isocyanate (isocyanate asthma), or welding fumes (welding asthma) and identify potential biomarkers that distinguish these groups from each other.

Methods

We used a combination of clinical tests, transcriptomic analysis, and associated pathway analyses to investigate the underlying disease mechanisms of the blood immune cells and the airway epithelium of 61 men.

Results

Compared with the healthy controls, the welding asthma patients had more differentially expressed genes than the flour asthma and isocyanate asthma patients, both in the airway epithelia and in the blood immune cells. In the airway epithelia, active inflammation was detected only in welding asthma patients. In contrast, many differentially expressed genes were detected in blood cells in all 3 asthma groups. Disease-related immune functions in blood cells, including leukocyte migration and inflammatory responses, and decreased expression of upstream cytokines such as TNF and IFN-γ were suppressed in all the asthma groups. In transcriptome-phenotype correlations, hyperresponsiveness (R ∼ |0.6|) had the highest clinical relevance and was associated with a set of exposure group–specific genes. Finally, biomarker subsets of only 5 genes specifically distinguished each of the asthma exposure groups.

Conclusions

This study provides novel data on the molecular mechanisms underlying work-related asthma. We identified a set of 5 promising biomarkers in asthma related to flour, isocyanate, and welding fume exposure to be tested and clinically validated in future studies.

中文翻译：

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与 3 种不同工作接触相关的内分型哮喘

背景

工作暴露在成人哮喘中起重要作用，但工作相关性哮喘的机制尚未完全阐明。

客观的

我们旨在揭示与暴露于面粉（面粉哮喘）、异氰酸酯（异氰酸酯哮喘）或焊接烟尘（焊接哮喘）相关的工作相关性哮喘的分子机制，并确定将这些群体彼此区分开的潜在生物标志物。

方法

我们结合临床测试、转录组学分析和相关通路分析来研究 61 名男性的血液免疫细胞和气道上皮的潜在疾病机制。

结果

与健康对照组相比，焊接哮喘患者在气道上皮和血液免疫细胞中的差异表达基因均高于面粉哮喘和异氰酸酯哮喘患者。在气道上皮中，仅在焊接哮喘患者中检测到活动性炎症。相比之下，在所有 3 个哮喘组的血细胞中都检测到许多差异表达的基因。在所有哮喘组中，血细胞中与疾病相关的免疫功能，包括白细胞迁移和炎症反应，以及上游细胞因子（如 TNF 和 IFN-γ）的表达降低均受到抑制。在转录组-表型相关性中，高反应性 (R ∼ |0.6|) 具有最高的临床相关性，并且与一组暴露组特异性基因相关。最后，

结论

这项研究提供了有关工作相关性哮喘潜在分子机制的新数据。我们确定了一组 5 种与面粉、异氰酸酯和焊接烟尘暴露相关的有希望的哮喘生物标志物，以在未来的研究中进行测试和临床验证。