Although often overlooked as a locus for toxic exposure effects, the nose represents one of the first sites of impact for airborne pollutants. As such, it not only serves to trap and detoxify numerous forms of potential toxicants but performs many sensory functions equally critical to human health and safety. The impact of exposure to volatile chemicals, particulates, and metal fumes on olfaction can take many forms, ranging from total loss (anosmia) to diminished sensitivity (hyposmia) or distortions in quality (dysosmia). The mechanisms underlying the adverse effects after acute or chronic exposure may also differ, depending on the agent or agents involved in the exposure. Some agents are capable of directly damaging tissue in areas that contain high densities of olfactory receptors. Other nonreactive agents can impair olfaction indirectly through stimulation of inflammatory mediators that possibly interfere with normal signal transduction in the olfactory epithelium or that produce anatomical changes altering the conduction of the chemical molecules to the olfactory epithelium (Dalton and Opiekun 2006
). In the case of the WTC workers, however, further analysis of nasal tissue is required to better identify the exact mechanism underlying the loss of function. In addition, identification of the agent(s) responsible for the damage can only be inferred from air samples collected during this period and retrospective self-reports on their work history.
Although we matched the controls to the WTC workers on a case-by-case basis for exact job title, age, sex, and smoking status, the controls were located in the Philadelphia area, whereas most of the WTC workers came from the New York City region. We did not believe this biased the results, however, because air quality data for typical pollutants collected in both regions strongly confirm the similarity of the ambient exposures, with the Philadelphia region having slightly higher levels of volatile organic compounds (Kleinman et al. 2002
Despite observing substantial impairments in olfactory and trigeminal sensitivity among the WTC workers and volunteers relative to the occupationally matched controls, we did not find a significant difference in odor identification ability between the groups. In prior studies evaluating the effects of chemical exposure on olfactory ability, odor identification performance appeared to be inconsistently sensitive to pollutant exposure. For example, Calderon-Garciduenas et al. (2010)
found decrements in odor identification ability among children and young adults living in Mexico City. However, in two studies comparing residents of Mexico City with residents from an unpolluted area, Hudson et al. found significant differences in threshold sensitivity (Guarneros et al. 2009
; Hudson et al. 2006
), but no effects on odor identification (Guarneros et al. 2009
). Schwartz et al. (1989)
found cumulative exposure effects on odor identification among acrylate-exposed workers only when analyzed using a nested case–control design; overall, there were no significant differences among the exposed workers and matched controls. However, we also note that in our study, between 17% and 20% of individuals in each group performed well below normal on the odor identification test. This prevalence is greater than what would be expected in the general population and may reflect exposure-induced damage related to their occupations, as nearly half of our sample were employed in the construction trades. The additional exposure at the WTC site may not have contributed substantially to odor identification deficits beyond that. Still, there were eight individuals in the WTC group whose odor identification ability was severely impaired and who were also classified as anosmic on the odor threshold test, a higher frequency than observed among the matched controls.
Differences in the levels of cytokines/chemokines in the NLF suggest that inflammatory mechanisms may underlie the functional effects we observed. As IL-6 is one of the most important mediators of the acute phase of response to injury, the lower levels found among the WTC workers with chronic inflammatory symptoms would not be considered unusual (Wang et al. 1997
). Increased levels of IL-8, on the other hand, are frequently found in cases of chronic inflammation of the nasal cavity, which is also consistent with the data (Barraza-Villarreal et al. 2008
; Raulf-Heimsoth et al. 2007
The robust association we found between the degree of exposure to the dust cloud on 9/11 and the loss of trigeminal sensitivity is particularly noteworthy, given that individuals were tested > 2 years after this exposure. Individuals who were not directly exposed to the dust cloud (either because of distance from the towers or by not being in lower Manhattan on 9/11) had significantly decreased ability to detect irritation relative to the matched controls. However, the thresholds of those individuals who were directly exposed in the dust cloud showed the most dramatic signs of impairment. The relationship between trigeminal function and pollutant exposure has not been evaluated as often as that for olfactory function, but should be considered in future studies.
The failure to find a predictive relationship between long-term exposure history at the WTC site and performance on chemosensory function tests was surprising. However, we note that 97% of our test population worked/volunteered in lower Manhattan between 12 September and 18 September, which, after 9/11, was the period during which the potential for pollutant exposure was likely at its highest. If the chemosensory alterations we observed were due primarily to dust exposure on 9/11 and to some degree to other exposures during the first week, then the lack of variance in our exposure data during this week would obscure finding a relationship. We have noted that among the matched controls, sensitivity to the odor of PEA and the irritancy of n-butanol was associated with age. No such relationships were observed among the WTC workers, as the relatively small impact of this variable may have been overshadowed by damage incurred from early exposure at the site.
Although the nasal chemosensory system can be remarkably robust to damage from airborne pollutants (Ruitenberg and Vukovic 2008
), its well-documented regenerative powers can be overwhelmed by certain types of acute or chronic exposures. We undertook this study to determine whether the exposures experienced by individuals in lower Manhattan on 9/11 and those who worked and volunteered in the days, weeks, and months afterward produced long-lasting chemosensory deficits from exposure to the volatile gases, fumes, and dusts associated with that site. Although many of the WTC workers and their matched controls were engaged in occupations where some level of chemosensory dysfunction could be expected to occur, the significantly higher prevalence of chemosensory dysfunction in the WTC group leads us to conclude that the profound exposures experienced in lower Manhattan increased the risk of dysfunction beyond that associated with the workers’ regular occupations.
Notably, the near-absent ability to detect nasal irritation for n-butanol for those individuals who were caught in the dust cloud from the collapse of the towers may be the most significant hazard we documented, as it is this sensory system that is in the first line of defense against many toxicants that could otherwise reach and potentially damage the lower airways. However, the decreased sensitivity to the irritancy of n-butanol may not be predictive of deficits for detecting all nasal irritants. Since the cloning of the capsaicin receptor in 1997, researchers have identified a number of transient receptor potential ion channels on sensory neurons, which appear to confer some level of specificity in the neuronal response to airway irritants (Bessac and Jordt 2008
). Nonetheless, the profoundly decreased sensitivity to n-butanol was not due to specific exposure to this compound, so the deficiency likely represents a more widespread decrement in trigeminal sensory response. Future evaluations should include tests using different classes of airway irritants to evaluate whether exposed individuals sustain a general loss of trigeminal sensitivity.
It is unknown to what degree, if any, recovery of olfactory or trigeminal function has occurred in the interim for these individuals. Nor is it known how many of the WTC-exposed individuals who were not tested in this study have suffered similar chemosensory impairment but who may be unaware that they have lost an important sensory tool for detecting airborne hazards. For this reason, broader screening of chemosensory function among WTC-exposed individuals seems warranted, with a special focus on reevaluating individuals who participated in this study. The goal of such efforts should be not only to determine the prevalence or degree of chronic impairment for these individuals, but also to inform us of the potential for recovery, the factors that may be associated with recovery, and the time course necessary for recovery of function. Moreover, the lessons learned from studying this cohort can also provide important clues for monitoring and protecting the upper airways and chemosensory function in other populations having potential for acute exposure to airborne toxicants.