Mechanisms, genetics, and pathophysiology

Specific IgE-mediated and non-IgE-mediated mechanisms (IgG, autoimmune) of occupational asthma (OA) are reviewed in this chapter. Also, nonspecific mechanisms (innate mechanisms, epithelial involvement, airway wall remodeling, oxidative stress, neurogenic inflammation) are discussed. Sensitizer-induced OA is the result of a specific IgE-dependent hypersensitivity to a workplace-sensitizing agent, although there may also be important accessory mechanisms in the case of low-molecular-weight (LMW) induced OA. This type of OA is distinguished from irritant-induced asthma, which is the term used to describe OA caused by exposure at work to substances that cause asthma through an irritant mechanism rather than by immunologic sensitization. Also, there is evidence of interaction between the immune-based inflammatory reaction and disease (OA) on the one hand and occupation-based environmental factors on the other hand, as examined in epigenetic studies, some of the genome-wide association type. Most high-molecular-weight (HMW) allergens, such as flours, enzymes, and animal proteins, can induce IgE-mediated responses that cause work-related symptoms in exposed workers. However, the characteristics of immune responses induced by LMW agents and the nature of the effector mechanisms in chemical respiratory allergy are more controversial. Animal models of OA exposed to LMW and HMW agents are presented and their rationale outlined: selected animal species, methodology of sensitization (skin and airborne, skin-lung interaction), physiological, proteomic, genomic and inflammatory markers, signaling pathways of inflammation, as well as stimulation of cholinergic and sensory nerves. The pathophysiology of OA is also described with regards to various mechanisms of airflow limitation, bronchial hyperresponsiveness, and airway inflammation (eosinophilic and neutrophilic) in sensitized subjects and workers with OA.

ISBN:1032043423

Publication year:2021