NYC-WTC_000199644

NYC 9/11 Public Portal Document

j supported by a combination of' animal, studies, pharmacological responses of these CMS disorders, and circumstantial evidence. At the current time these associations are somewhat speculative, but there is suffi­ cient evidence to justify investigations. It is now known that the neuropeptides of neurogenic inflammation reproduce the pathology of asthma (27), and the role of neurogenic inflammation has been docu­ mented in animal models of asthma (2S).

r' © p p. Barnes (29) has tecendy reviewed the cur­ rent evidence for the role of neurogenic inflammation in asthma and has suggested

I p. strategics for reducing neurogenic inflam­ mation in this disease. It is increasingly recognized that respiratory irritants such as VOCs and environmental tobacco smoke can exacerbate asthma and rhinitis (30-32). A number of studies have documented an it increase in the incidence of asthma in industrialized countries, over both the long t- Figure 2. Schematic diagram of neurogenic inflammation triggered by chemical irritants. Chemical irri­ term and during the 1980s (35). In addi­

I tants IC) bind chemical irritant receptors on sensory nerves to release substance P (P) and other media­ tors from nerve endings. Substance P binds receptors on effector cells to trigger inflammation. Neutral endopeptidase |nep), an enzyme located on the membranes of effector cells, degrades substance P and tion, studies during the 1980s established that the American population is exposed to VOCs in the indoor air (54). downregulates neurogenic inflammation. It is proposed that chemical sensitivity syndromes are disor­ The role of neurogenic inflammation ders of the regulation of neurogenic inflammation. and chemical irritants in these respiratory Regulatioa of Neurogenic disorders and the upregulation of neuro­ substances and results from exposure of genic inflammation by inhalant irritants Inflammation trigeminal nerve endings co the irritants. discussed above indicate that there may be The skin and other mucous membranes Neutral endopeptidase degrades substance a relationship between indoor air pollution have similar responses to irritant chemi­ P (i3). NEP is located on the surfaces of with VOCs and the worsening asthma epi­ cals. Recent studies in anosmic subjects cells with substance P receptors, i.e., the demic. Pursuit of this relationship should have separated the common chemical target cells of substance P. Substances that be a research priority. In the past asthma sense from olfaction (15). The common decrease neutral endopeptidase levels was divided into extrinsic asthma, triggered chemical sense and olfaction are depicted increase neurogenic inflammation, while by protein aeroallergens, and intrinsic asth­ in Figure 1. There is evidence that pro­ substances chat increase neutral endopepti­ ma of unknown cause. This distinction tein receptors on cell membranes are the dase suppress neurogenic inflammation. was made before the role of neurogenic activation site for chemical irritants. It is Human recombinant NEP suppresses neu­ inflammation in asthma was appreciated. thought that sensory nerves act as both rogenic inflammation (18-20). Exogenous It may be that asthma would be better clas­ afferent and efferent nerves for neurogenic substances that inhibit NEP include ciga­ sified as immunogenic or neurogenic inflammation triggered by chemical irri­ rette smoke (21), respiratory viruses (Table 1). The distinction between neuro­ tants. In the nose, substance P release has (22-25), and the volatile organic chemical genic and immunologic asthma is limited been verified for exposures to nicotine, toluene diisocyanate (26). to the catalysts because the two types cross capsaicin, ether, formaldehyde, and ciga­ over after the release of mediators, in that rette smoke (16,17). Hence, stimulation Possible Roles of Neurogenic the mediators of neurogenic inflammation of the chemical irritant receptors leads to Inflammation trigger mast cell degranulation, and mast neurogenic inflammation. The relation­ Neurogenic inflammation may play a role cell mediators stimulate peripheral nerves. ship among chemical irritants, sensory in a variety of disorders, from asthma and This “bidirectional regulatory circuit" has nerves, substance P, and NEP is summa­ rhinitis to migraine headache, rheumatoid recendy been reviewed (35). rized in Figure 2. arthritis, and fibromyalgia. Such a role is This crossover phenomenon docs not mean that neurogenic inflammation and immunologic inflammation are clinically / Table 1. Immunogenic versus neurogenic asthma identical in all cases. In the upper airways

f Triggered by Immunogenic Protein aeroallergens Neurogenic Volatile organic chemicals and skin, the initial complaint associated with exposure to chemical irritants is burn­ ing or pain, whereas itching is the initial Interacting with IgE antibody Chemical irritant receptors Located on Mast cells Sensory nerve C-fibers complaint associated with immune-medi­ ated exposures. It may be chat there is Releasing Histamine, leukotrienes, Neuropeptides; substance P. prostoglandins, chemotactic naurokinen A, calcitonin individual variability in the degree co factors gene-related peptide which crossover is clinically manifested. Stimulating Sensory nerve C-fibers Mast cell degranulation The two mechanisms might be differenti­ ated by testing patients with challenging Producing Bronchial inflammation Bronchial inflammation doses of antigens and nonallctgenic chemi­ Manifesting as Asthma Asthma cal irritants, while monitoring clinical

Volume 101, Numbers. August 1993 235

CITY_21MC100_006729509

NYC-WTC_000199645