Toxicology of Industrial Compounds

9
Pulmonary Hyperreactivity to Industrial
Pollutants
JÜRGEN PAULUHN
Bayer AG, Wuppertal
Introduction
Environmental agents, such as ozone, nitrogen dioxide, formaldehyde, and
sulfur dioxide; occupational pollutants, including natural dusts (grain, red
cedar, animal dander), irritant fumes or vapors, and organic acid
anhydrides, reactive dyes, or (di)isocyanates can cause increases in airway
reactivity. Airway hyperreactivity is defined as an exaggerated acute
obstructive response of the airways to one or more nonspecific stimuli. The
incriminated etiologic low-molecular-weight agents all share a common
toxicological characteristic of being irritant in nature. In some cases, the
agents are present as a gas, in others the inciting agent is an aerosol. As yet
it is not clear, for instance, whether induced airway hyperreactivity is a
dose-effect phenomenon and whether a brief high level exposure causes
more prolonged or intense airways response. While the illness clinically
simulates bronchial asthma and is associated with airway hyperreactivity,
it is considered to be different from typical occupational asthma because of
its rapid onset, specific relationship to a single environmental exposure,
and no apparent preexisting period of sensitization to occur with the
apparent lack of an allergic or immunologic etiology. Hence, this illness is
termed reactive airways dysfunction syndrome, or RADS, because the
characteristic finding is hyperreactivity of the airways (Brooks et al.,
1985). Mechanisms to explain the development of RADS focus on the
toxic effects of the irritant exposure on the airways. How this increased
bronchial responsiveness is precisely triggered, amplified, sustained and
how it relates to inflammatory events remains, to a certain extent,
incompletely elucidated (Kay, 1991).
A common pathologie accompaniment or cause of increased airway
hyper-responsiveness is pulmonary inflammation. It is suggested that this
inflammation is responsible for the change in histamine or cholinergic
agonist responsiveness. Because subepithelial irritant receptors are
superficial in location, they could be affected by an extensive bronchial
inflammatory response which might occur after heavy irritant exposure.