NYC-WTC_000199644

NYC 9/11 Public Portal Document

symptoms and measuring mediators. This fibers in rheumatoid anhritis, and neuro­ Reactive upper-airways dysfunction research would best be carried out by genic inflammation may play a role ig this syndrome (RUDS) also follows a chemical studying upper airway responses, as nasal disorder. Zimmerman has suggested that exposure, and there is persistent chronic washings can be easily obtained for quanti­ neurogenic inflammation may play a role rhinitis. The chief complaint of patients fying mediators. in fibromyalgia (42). with RUDS is chemical sensitivity (47). Another disorder that increased signifi­ Unlike patients with RADS, medical atten­ cantly during the 1980s is migraine head­ Role of Neurogenic Inflammation in tion is not sought on the day of exposure, aches [36). Headache is an early and con­ Chemical Sensitivity Syndromes which probably reflects the fact that sistent consequence of exposure to VOCs. “Sick building syndrome” (SBS) is a term breathing is compromised in RADS but On the basis of pharmaceutical responses used to designate an outbreak of illness not in RUDS. Preliminary study of th; of migraine and animal experiments, associated with indoor air contaminants in nasal mucosa found lymphocytic infii- Nicolodi and Sicuteri proposed that neuro­ new and tightly scaled buildings. Symp­ trares, and elecrron microscopy has shown genic inflammation plays a role in rhe toms include irritation of the eyes, nose, thickening of the basement membrane and pathophysiology of migraine headaches and throat, skin irritation, and neurotoxic desquamation of the respiratory epithelium (37). Silberstein argued that both tension symptoms including mental fatigue and headaches and migraine may be generated difficulty concentrating (43}. The syn­ There are many similarities between by neurogenic inflammation (JS). Buzzi drome is an acquired disorder with onset SBS, MCS, RADS, and RUDS (Fig. 3). In and Moskowitz demonstrated that stimula­ related to moving into a new or renovated each snydrome, a high-dose exposure tion of trigeminal sensory fibers leads to building, and there is wide individual vari­ induces the syndrome, and subsequeni changes consistent with those of migraine ability in onset and symptoms after expo­ exacerbations are associated with low-lc\’c in a rat model, and these changes can be sure. exposures. SBS and MCS include symp­ blocked by the antimigraine drugs suma­ Multiple chemical sensitivity syn­ toms involving more than one organ sys­ triptan and dihydroergotamine (39}. drome (MCS) is a related syndrome with tem, with the respiratory mucosal and cen­ Hardebo has pointed out that the postulate onset related to an environmental expo­ tral nervous system being prominently that neurogenic inflammation mediates sure, most commonly a solvent or pesti­ involved. The major difference between migraine provides a rational explanation cide. After the initial exposure, individu­ SBS and MCS is that SBS refers to a cluster for why serotonin antagonists are effective als become sensitive to low-level chemical of cases associated with a building, while in creating migraine (49). Challenge stud­ exposures with symptoms involving more MCS patients have more generalized com- ies with VOCs on migraine patients, with than one organ system. Though this syn­ pLunts. RADS and RUDS have prominent and without specific pharmacological drome was de-scribed four decades ago airway involvement, with the difference blockage of relevant receptors, is needed to (44.45), it re-mains highly controversial. between the two being that RADS involves elucidate the role of neurogenic inflamma­ Reactive airways dysfunction syn­ the lower airway (asthma), and RUDS tion and chemical irritants in migraine. drome (RADS) is an asthmalike illness involves the upper airway (rhinitis). In one A comparison of neuropeptide staining that develops within minutes to hours small series, 100% of patients with RUDS in the synovium of patients with rheuma­ after an acute exposure to dust, smoke, or had extra-airway manifestations and met toid arthritis, osteoarthritis, and controls solvent. There is persistent bronchial the Cullen case definition (49) for MCS. found weaker staining in the nerve fila­ hyperreactivity with positive methacholine These syndromes may be related at a ments of the rheumatoid arthritis group challenge. The asthma becomes chronic deeper level. All of these illnesses may be (41). The authors suggest that this weaker after the initial exposure and can be diffi­ d.tsorders of the regulation of neurogenic staining is evidence of release from nerve cult to treat (46). infiammation. The inducing exposure may alter the respiratory mucosa in one or more ways. The regulation of neurogenic inflam­ MULTIPLE CHEMICAL SICK E’JiLDJWG mation may be disturbed by die depletion S=?i5SrFiVI7Y SVWDROME (SSS) of NEP or other enzymes, which would SYNDROMS (MCSJ Headache, mucosal irritation, result in a heightened response to subse­ Initiating exposure. difficulty with concentration. quent exposures. The desquamation of the Low level exposures produce Associated with modern respiratory epithelium seen in RUDS may j I buildings. x remove a barrier to chemical irritants, so physical and mental that chemical irritants may reach and trig­ symptoms. CHE?j;iCAL ger the irritant receptors at lower concen­ trations. SEr\!SmVITY Patients with these illnesses complain of symptoms in organ systems in addition to SYNDROr/sES the airways, and some patients have no air­ REACTIVE UPPER EEACTiVE AIRWAYS i AIRWAYS ways symptoms at all. Mechanisms to DYSFUNCTION explain how airway irritants can trigger sys­ DYSFUNCTION temic symptoms must be considered. Fiist, SYNDROME (RADS) SYNDROME (RUDS) it is common for inflammatory illnesses pri­ initiating exposure. Asthma-like Initiating exposure. Upper marily arising in one organ or tissue to pro­ syndrome with bronchial ; airways inflammation. duce systemic manifestations (e.g., th; hyperreactivity. lExtra-airway symptoms. extra-articular manifestations of rheuma­ toid arthritis and the systemic manifesta­ tions of Crohn’s disease). Viral infections Hgure 1 Chemical sensitivity syndromes. The multiple chemical sensitivity syndrome (MCS). sick build­ ing syndrome ISDS). reactive airways dysfunction syndrome (RADS), the reactive upper airways dysfunc­ of the upper airway produce systemic tion syndrome (RUDS) have many features in common. These syndromes may all be disorders of the reg­ symptoms, including myalgias, fever, ulation of neurogenic inflammation. fatigue, and malaise.

236 Environmental Health Perspectives

CITY_21MC100_006729510 NYC-WTC_000199646