Summary and research needs

Abstract

Environmental exposures to noxious chemicals-both natural and synthetic-at nonlethal levels have been ubiquitous for millennia and range from hydrogen sulfide from volcanoes and hot springs to products of combustion. The harnessing of fire for human uses was a milestone in our acceptance of close proximity to irritant substances. A number of syndromes and conditions have been described that are induced or exacerbated by exposures to irritant chemicals. Irritant asthma and irritant rhinitis are now well-characterized conditions that have a solid scientific underpinning. Respiratory irritants bind to nociceptors on sensory nerve c-fibers in the airway and induce the release of inflammatory mediators, as discussed in Chaps. 1 and 3. For a normal airway, higher doses are needed to induce significant inflammation than in susceptible individuals. The pathophysiology of the increased susceptibility is now established. Inflammation leads to a pathological remodeling of airways. The remodeled airway has a decreased threshold for irritant-induced inflammation. The susceptible airway has a proliferation of nerve fibers, desquamation of epithelial barriers, and lymphocytic infiltrates. Building on this scientific understanding, research is needed to build on our understanding of the mechanisms of other illnesses described in association with irritant exposures. Of particular importance is the need to understand the cerebral manifestations of allergy and irritant sensitivity and the relationship to neuropsychological disabilities. Environmental control units, in which subjects are housed in an environment relatively free of respiratory irritants, followed by controlled challenges with irritant chemicals while monitoring for disease exacerbations and objective parameters of disease, are needed for further research investigations.