In FDNY-FFs—all highly exposed to WTC dust and combustion/pyrolysis products during the morning of the collapse and nearly all with additional cumulative workday exposures to WTC dust—IS analysis were significantly different from controls, in inflammation (percentages of neutrophils and eosinophils that increased with exposure intensity; increased MMP-9) and particulate matter deposition (a shift in PSD toward larger size particles and chemical/mineral analysis consistent with WTC dust).
Firefighters are exposed to numerous irritants (e.g., combustion and pyrolysis products, particulate matter), and such exposures have the potential to alter lung permeability (Bergstrom et al. 1997
; Burgess et al. 2001
). Inflammatory changes have been documented in BAL from nonsmoking firefighters compared with healthy volunteers (Bergstrom et al. 1997
; Burgess et al. 2001
). In a previous case report (Rom et al. 2002
), we found an eosinophilic inflammatory response (70% of total cell count) and increased levels of interleukin-5 in the BAL of an FDNY-FF with acute pneumonitis several weeks after repeated WTC dust exposures. The present study is the first to use IS to characterize differential cell counts, inflammation, particle size deposition, and composition in subjects with WTC exposures. It is also the first to report these findings in firefighters. IS from FDNY-FFs and TA-FFs, all never smokers, had increased percentages of eosinophils and neutrophils compared with healthy nonfirefighter controls. For FDNY-FFs, a significant dose–response relationship was demonstrated, with the proportions of neutrophils and eosinophils increasing as cumulative WTC exposure intensity increased (measured in number of days working at WTC). Neutrophils and eosinophils are important components of the inflammatory cascade responsible for airway inflammation, injury, and remodeling (Azadniv et al. 2001
; Lemiere et al. 2001
; Woodruff et al. 2001
The matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases with a central role in inflammation and combined ability to degrade components of connective tissue matrices (Murphy and Docherty 1992
). MMPs are synthesized and secreted by connective tissue and some hematopoietic cells, and are known to be important mediators of airway inflammation, remodeling, and pulmonary injury (Cataldo et al. 2002
; Li et al. 2002
). We chose to measure MMP-9 because it a
) plays an important role in neutrophil recruitment to the lung (Li et al. 2002
) is detectable in IS with reliable and reproducible results (Cataldo et al. 2002
; Fireman et al. 2004a
); and c
) is increased in IS from workers exposed to hazardous dust (Fireman et al. 2004b
). We found a trend for higher levels of MMP-9 in IS samples from FDNY-FFs than in those from TA-FFs, and both groups were significantly higher than nonfirefighter controls. Moreover, we found a positive correlation between accumulation of neutrophils and MMP-9 levels. In these non-smoking firefighters, the increase in MMP-9 levels provides biochemical evidence for exposure-related immune activation in the lung, complementing the evidence from IS differential cell counts. Persistent inflammation, 10 months after the WTC collapse, is consistent with the clinical findings of new and persistent cough, airway hyperreactivity, and asthma previously reported in FDNY-FFs (Banauch et al. 2003
; Feldman et al. 2004
; Prezant et al. 2002
) and other rescue workers (Safirstein et al. 2003
; Saltzman et al. 2004
; Skloot et al. 2004
) after exposures to WTC dust.
PSD measurements demonstrated significant differences between FDNY-FF and TA-FF IS samples. We found a high load of relatively large particles (1–50 μm in diameter) with irregularly shaped structures in FDNY-FF IS samples that were completely different from the smaller, regular shaped particles found in TA-FF IS samples. Chemical and mineral analyses also demonstrated differences between FDNY-FF and TA-FF IS samples. TA-FF IS showed findings typical of soil contaminants from the Tel-Aviv area. In contrast, a heterogeneous mixture was found in FDNY-FF IS, consistent with exposures to aerosolized building debris and dust and smoke generated by the collapse and fires (Lioy et al. 2002
). Mineral particles were seen in macrophages and epithelial cells. The presence of these particles in epithelial cells illustrates the high concentration of respirable particulate matter, overwhelming normal nasopharyngeal filtering, mucociliary clearance, and alveolar macrophage defense systems (Churg 1996
). Although asbestos fibers were found in the BAL from the FDNY-FFs with eosinophilic pneumonitis after WTC exposure (Rom et al. 2002
), we did not find asbestos fibers in our FDNY-FF IS samples.
Despite our finding significant correlations between inflammation and cumulative WTC exposure and significant differences in PSD between FDNY-FFs and TA-FFs, we could not detect a significant effect of cumulative WTC exposure on PSD. This may be related to other physical factors at the WTC site, such as differences in work location, minute ventilation (related to subject size, physical fitness, experience, and work tasks), specific work task–related exposures, and the use of respiratory protection (minimal during week one and variable thereafter) (CDC 2002b
). It may also reflect potential limitations of scoring cumulative exposure only in terms of workdays, unweighted for the above differences and other variables such as environmental conditions. Additionally, selection bias (all FDNY-FF subjects volunteered for this study) may have influenced our current ability to detect the effect of cumulative exposure. However, the strengths of this study outweigh these limitations and include the following: a
) all FDNY-FFs had significant WTC dust exposures because they were caught in the dust cloud during the collapse and then continued to work at the WTC site for days thereafter; b
) IS provided an assessment of persistent inflammation and cumulative particle deposition because the enormity of the disaster prevented us from collecting IS until 10 months after the collapse; c
) IS assessments were not biased toward acute, transient inflammation and particle deposition because at least 1 month had elapsed between collecting IS and the last workday at the WTC site; and d
) controls were truly unexposed because they were recruited from outside this region—a necessity because by this time nearly every FDNY-FF and most other rescue workers and many Manhattan residents had reported some level of exposure.
We believe the differences between FDNY-FFs, TA-FFs, and controls demonstrate a unique exposure following the WTC collapse ( and ). This conclusion is supported by similarities between quantitative and qualitative analyses of IS sputum samples and dust samples collected from settled material one block east of the WTC. These dust samples demonstrate a complex mixture of coarse particles and fibers consisting of relatively larger particles (> 90% of dust particle mass was > 10 μm in diameter) (Lioy et al. 2002
). Thus, the fact that IS samples from FDNY-FFs had higher amounts of particles > 2.0 μm in diameter than samples from TA-FFs was due to the nature and composition of the sources that dominated FDNY-FF exposure patterns. In 87% of FDNY-FFs, > 20% of the particles found in IS were > 2.0 μm in diameter compared with only 8% of those from TA-FFs. SEM also showed relatively larger and more irregularly shaped particles in FDNY-FFs compared with TA-FFs. Once inhaled, particles > 2.0 μm in diameter are most commonly deposited in the upper airways, causing significant irritation because of their alkaline, caustic nature (Lioy et al. 2002
); this explains the increased incidence of upper airway symptoms (nasal congestion/drip, throat irritation, cough, and gastroesophageal reflux) described in highly and moderately exposed FDNY-FFs (Banauch et al. 2003
; Feldman et al. 2004
; Prezant et al. 2002
Although helpful, measurements obtained from settled dust samples, which are often enriched with larger particles, are not entirely representative of the particle types or size distribution of aerosolized, potentially respirable dust during the height of exposure. In fact, the majority of particles in FDNY-FF IS samples were < 2.0 μm in diameter: 74% of FDNY-FFs had > 60% of PSD < 2.0 μm in diameter (). Compared with settled WTC dust samples, FDNY-FF IS samples demonstrated a distinct leftward shift of the average curve of all PSD measurements toward smaller particles. Particles 2.0 μm in diameter are commonly deposited in the smaller airways. This may explain why post-WTC FDNY-FFs (Banauch et al. 2003
; Prezant et al. 2002
) have shown an increased incidence of bronchial hyperreactivity, reactive airways dysfunction syndrome, and asthma. Six months after the WTC collapse, methacholine challenge testing demonstrated that highly exposed FDNY rescue workers were 6.8 times more likely to have bronchial hyper-reactivity than moderately exposed and unexposed FDNY controls (Banauch et al. 2003
Our findings support both the practical utility and scientific usefulness of IS as a non-invasive method for screening and follow-up monitoring of populations exposed to high concentrations of aerosolized particulates following a disaster—natural or man-made. IS is superior to BAL because it is noninvasive and collection can occur at nearly any field location. In contrast to traditional blood and urine biomonitoring, IS directly samples the lung, the specific target organ of interest following an inhalation exposure. For example, blood and urine samples were collected 1 month after the collapse in a different group of FDNY-FFs, and only a few of the 110 chemicals measured showed significant, yet small, differences when WTC-exposed FDNY-FFs were compared with nonexposed FDNY-FFs (Edelman et al. 2003
). In contrast, IS directly assesses respired particulate matter and pulmonary inflammation, thereby serving an important complementary role to traditional biomonitoring techniques.
In conclusion, IS from FDNY-FFs caught in the WTC dust cloud during the morning of the collapse showed an influx of inflammatory cells, percentages of neutrophils and eosinophils that increased with exposure intensity, increased MMP-9 levels, a shift in PSD toward larger-size particles, and chemical/mineral analyses consistent with exposure to building debris, smoke, and dust generated by the attack on the WTC. If future population studies demonstrate that IS measures of inflammation or PSD correlate with health outcomes, then IS evaluations would be a valuable addition to medical screening/monitoring programs following inhalation exposures.