Environmental and occupational disease
Endotyping asthma related to 3 different work exposures

https://doi.org/10.1016/j.jaci.2021.07.019Get rights and content
Under a Creative Commons license
open access

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.

Key words

Biomarkers
exposure
transcriptome-phenotype associations
work-related asthma

Abbreviations used

BMI
Body mass index
DEG
Differentially expressed gene
FA
Flour asthma
Feno
Fractional exhaled nitric oxide
IA
Isocyanate asthma
ICS
Inhaled corticosteroid
PCA
Principal component analysis
WA
Welding asthma
WRA
Work-related asthma

Cited by (0)

Supported by the Finnish Work Environment Fund (grant 114350).

Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest.