Airway Chemosensation and Reflex Responses

Peripheral sen ronal fiber typ nation, and stimuli. Chem detected by C ing rapid acce path through sensitive to ca peppers. Cap inducing snee and pain. Resp life-threatenin respiratory ar lenge experim in, an ultra-po potent tussive saicin cough c research to ex background of ed by cough manifests itse increased sen Capsaicin co observed in p pulmonary di (ILD), gastroe airway cough 99). Airway inf saicin cough s Studies in effectively des way response stimuli. For ex saicin prevent sion in mice inflammation rats (60, 67, 93 airway respon and to formal 78, 79, 92). In dioxide-provo observations either directly saicin desens This hypothes tion that ca for categorization of irritant potencies, used as a guideline for the establishment of human exposure limits (68). RD50 parameters have been established for a large number of environmental and industrial irritants, including acids (HCl, sulfur dioxide), bases (ammonia), oxidants (ozone, chlorine, nitrogen dioxide), electrophilic aldehydes (acrolein, formaldehyde, acetaldehyde), alcohols (methanol, ethanol), solvent fumes (acetone, toluene, xylene), and basic industrial chemicals (isocyanates, styrene) (68). Many of these agents are combined with other irritants in complex environmental exposures. For example, photochemical smog contains ozone, nitrogen oxides, and volatile organic compounds (VOCs) such as acrolein, generated through oxidation of chemicals released from vegetation or from human sources such as automobile exhaust. Tobacco smoke, smoke from structural fires, or smoke from burning vegetation contains mixtures of reactive carbonyl compounds (acrolein, methacrolein, croton aldehyde), oxidants, other reactive chemicals, and particulates. Chemical exposure studies in animals showed that reactive irritants can cross-desensitize each other’s ability to initiate respiratory defensive responses. For example, airway challenges by formaldehyde vapors in rats reduced respiratory irritant responses to subsequent exposures to chlorine and acetaldehyde and vice versa (6, 30). These observations suggest that sensory neurons contain a single reactive irritant receptor site. Once this site is saturated through exposure to a reactive irritant, it is rendered unresponsive to subsequent challenges by the same, or other, irritants. Alternatively, several different receptors may exist, cross-desensitizing each other through cellular signaling pathways. In contrast to other sensory systems, little is known about the molecular nature of chemical receptor sites in airway sensory neurons. In the human olfactory system, hundreds of different G-protein-coupled receptors, each restricted in expression to individual neurons, detect components of airborne chemical