Occupational Asthma Reference

Suojalehto H, Ndika J, Lindström I, Airaksinen L, Karisola P, Alenius H, Endotyping asthma related to three different work exposures, J Allergy Clin Immunol, 2021;:,https://doi.org/10.1016/j.jaci.2021.07.019
(Plain text: Suojalehto H, Ndika J, Lindstrom I, Airaksinen L, Karisola P, Alenius H, Endotyping asthma related to three different work exposures, J Allergy Clin Immunol)

Keywords: Finland, welding, isocyanates, mechanisms, genes, flour

Known Authors

Hille Suojalehto, Finnish Institute of Occupational Health Hille Suojalehto

Irmeli Lindstrom, Finnish Institute of Occupational Health Irmeli Lindstrom

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Abstract

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

Objective
We aimed to reveal the molecular mechanisms of work-related asthma associated with flour (FA), isocyanate (IA) or welding fume (WA) exposures 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 underlying disease mechanisms of the blood immune cells and the airway epithelium of 61 men.

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

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

Plain text: Background Work exposures play a significant role in adult-onset asthma, but mechanisms of work-related asthma are not fully elucidated. Objective We aimed to reveal the molecular mechanisms of work-related asthma associated with flour (FA), isocyanate (IA) or welding fume (WA) exposures 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 underlying disease mechanisms of the blood immune cells and the airway epithelium of 61 men. Results Compared to the healthy controls, the WA patients had more differentially expressed genes than the FA and IA patients both in the airway epithelia and in the blood immune cells. In the airway epithelia, active inflammation was detected only in WA patients. In contrast, large number of differentially expressed genes were detected in all asthma groups in blood cells. Disease-related immune functions in blood cells were suppressed in all the asthma groups including leukocyte migration and inflammatory responses and decreased expression of upstream cytokines such as TNF and IFNy. In transcriptome-phenotype correlations, hyperresponsiveness (R~|0.6|) had the highest clinical relevance and associated with a set of exposure-group specific genes. Finally, biomarker subsets of only 5 genes specifically distinguished each of the asthma exposure group. Conclusions This study provides novel data on the molecular mechanisms underlying work-related asthma. We identified set of 5 promising biomarkers in asthma related to flour, isocyanate and welding exposure to be tested and clinically validated in future studies.

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Comments

This is a complicated study investigating molecular mechanisms of work-related asthma due to flour, isocyanates and stainless steel welding. The welders were the only group showing active inflammation from differentially expressed genes in nasal mucosal biopsies, but asymptomatic welders were not included in the controls. All three groups showed activation of genes associated with neutrophil migration and degranulation. The numbers are rather small for generating associations from these three very different agents that can cause indistinguishable clinical disease.
8/18/2021

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