Endotyping asthma related to three different work exposures

2021-07-28

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 IFNγ. 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.

Authors: Hille Suojalehto, Joseph Ndika, Irmeli Lindström, Liisa Airaksinen, Piia Karisola, Harri Alenius
; Full Source: The Journal of allergy and clinical immunology 2021 Jul 28;S0091-6749(21)01139-8. doi: 10.1016/j.jaci.2021.07.019.