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* From the Division of Pulmonary and Critical Care Medicine (Drs. Skloot, Fischler, and Teirstein), Mount Sinai School of Medicine, New York, NY; Department of Medicine (Dr. M. Goldman), UCLA School of Medicine, Los Angeles, CA; Department of Obstetrics/Gynecology and General Internal Medicine (Ms. C. Goldman), West Los Angeles VA Medical Center, Los Angeles, CA; Department of Family Medicine and Community Health (Dr. Schechter), Albert Einstein College of Medicine, New York, NY; and Division of Environmental and Occupational Medicine (Dr. Levin), Mount Sinai School of Medicine, New York, NY.
Correspondence to: Gwen Skloot, MD, FCCP, Assistant Professor of Medicine, Division of Pulmonary and Critical Care Medicine, Mount Sinai Medical Center, One Gustave L. Levy Place, Box 1232, New York, NY 10029; e-mail: Gwen.Skloot{at}msnyuhealth.org
| Abstract |
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Design: Cross-sectional study.
Setting: The Mount Sinai Medical Center, a large tertiary hospital.
Participants: Ninety-six ironworkers engaged in rescue and recovery with exposure onset between September 11, 2001, and September 15, 2001, who responded to an invitation to undergo respiratory evaluation.
Measurements: Medical and exposure history, physical examination, spirometry, forced oscillation (FO), and chest radiographs. The relationships of prevalence of respiratory symptoms and presence of obstructive physiology to smoking, exposure on September 11, duration of exposure, and type of respiratory protection were examined using univariate and linear and logistic regression analyses.
Results: Seventy-four of 96 workers (77%) had one or more respiratory symptoms (similar in smokers [49 of 63 subjects, 78%] and nonsmokers [25 of 33 subjects, 76%]). Cough was the most common symptom (62 of 96 subjects, 65%), and was associated with exposure on September 11. Chest examination and radiograph findings were abnormal in 10 subjects (10%) and 19 subjects (20%), respectively. FO revealed dysfunction in 34 of 64 subjects tested (53%), while spirometry suggested obstruction in only 11 subjects (17%). Lack of a respirator with canister was a risk factor for large airway dysfunction, and cigarette smoking was a risk factor for small airway dysfunction. No other relationships reached statistical significance.
Conclusions: Respiratory symptoms occurred in the majority of ironworkers at the WTC disaster site and were not attributable to smoking. Exposure on September 11 was associated with a greater prevalence of cough. Objective evidence of lung disease was less common. Spirometry underestimated the prevalence of lung function abnormalities in comparison to FO. Continuing evaluation of symptoms, chest radiographs, and airway dysfunction should determine whether long-term clinical sequelae will exist.
Key Words: exposure forced oscillation ironworkers September 11, 2001 spirometry World Trade Center disaster
| Introduction |
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| Materials and Methods |
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Medical and Exposure History
Medical histories were acquired using a prepared questionnaire. Prior upper and lower respiratory conditions (ie, chronic sinusitis and asthma), persistent upper and lower respiratory symptoms (ie, sinus complaints, cough, dyspnea, wheeze, and chest tightness), provocability of these symptoms (eg, in relation to exposure to cold weather or changes in weather, exposure to smoke, diesel exhaust, or chemicals) and smoking history were documented.
Exposure history pertaining to the disaster was obtained by trained industrial hygienists and included assessment of exposure onset (September 11, 2001, or subsequently) and total exposure duration (days). Subjects were also questioned regarding the use of a dust mask and respirator with canister. Prior occupational exposure history was not recorded.
Physical Examination
Physical examination focused on the upper and lower respiratory systems. Swollen turbinates and erythematous nasal mucosa were considered abnormal upper respiratory findings, while wheezing, rhonchi, and prolongation of expiration comprised the lower respiratory abnormalities.
Spirometry
Pulmonary function tests were performed using either a Sensormedics 6200 (SensorMedics; Yorba Linda, CA) or a Jaeger Impulse Oscillation System (IOS) spirometer (Jaeger USA; Yorba Linda, CA) according to standard protocol. The data included FEV1, FVC, and forced expiratory flow during 25% to 75% of the FVC (FEF2575%). Each spirometric maneuver was done in triplicate, and the best FEV1 and FVC values were selected. The predicted values were those of Morris et al.11 Adjustments were made for nonwhite individuals.12 Airways obstruction was defined as FEV1/FVC
0.70 and FEV1 < 80% predicted. Spirograms with FEV1/FVC
0.70 but with FEV1
80% predicted were interpreted as showing borderline obstruction.
FO
FO was performed using a commercial instrument (IOS), calibrated with a standard 3-L syringe, and a known, fixed resistance to verify pressure calibration and frequency fidelity. Measurements (three 30-s trials) were made during tidal breathing using a mouthpiece that stabilizes tongue position to minimize oral resistance while firmly supporting the cheeks. The mouthpiece was connected to the pneumotachometer, and small pressure oscillations "forced" by a loudspeaker attached to the other end of the tube (Fig 1
). The FO instrument applied pressure pulses five times per second. Respiratory resistance and reactance were calculated from oscillatory components of flow and pressure13 at 5 to 35 Hz. Large and small airways mechanics were inferred from responses at high (20 Hz) and low (5 to 15 Hz) frequencies, respectively. Low-frequency oscillations at the mouth are transmitted to the lung periphery, while those at
20 Hz are limited to larger airways.1415 Four parameters were evaluated: (1) respiratory resistance at 5 Hz (R5), a global index influenced by both small and large airways; (2) respiratory resistance at 20 Hz (R20), an index of large airways resistance; (3) respiratory resistance at 5 to 20 Hz (R5-R20), an index of frequency dependence of resistance (f-d R), reflective of small airways function; and (4) an integrated area of low-frequency reactance (AX).1316 This parameter includes all negative values of respiratory reactance between 5 Hz and the frequency at which reactance is zero (resonant frequency). AX is an index of small airways obstruction complementary to f-d R.13161718192021 As a reference standard for R5, we used published FO data of > 400 normal male subjects (45% of whom were smokers), of comparable age to the present cohort, and set the cutoff for the upper limit of normal equal to mean R5 + 1.65 SD.1718 Accordingly, R5 > 3.5 cm H2O/L/s was defined as abnormal. FO tests were performed prior to spirometry to avoid any influence of forced expiratory maneuvers on airways function during resting breathing. Data calculations were reviewed after each test to check that correlations (coherence) among pressure and flow phase and amplitude appeared acceptable (coherence > 0.8).
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15% for respiratory resistance and/or
25% for AX.
Radiologic Testing
Each subject underwent posteroanterior and left lateral chest radiography. The radiographs were reviewed independently by one pulmonologist and a National Institute for Occupational Safety and Health-certified "B" reader, and were scored using the International Labor Office 1980 schema.23
Statistics
Data were analyzed using a standard statistical package (Stata Statistical Software, Version 8.0; Stata Corporation; College Station, TX). Outcome variables included onset of respiratory symptoms after September 11, presence of spirometric obstruction, and FO indices. Risk factors considered were smoking, exposure on September 11, duration of exposure, and type of respiratory protection. Univariate analyses (unpaired t tests and
2) of the outcome variables were carried out. Multivariate analyses of the associations with the risk factors were performed using logistic regression and linear regression for dichotomous and continuous outcome variables, respectively; p < 0.05 was considered significant.
| Results |
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Radiographic evaluation revealed abnormalities in 19 subjects who were referred for further evaluation. Parenchymal changes
1/1 according to the International Labor Office classification were found in five individuals. Seven workers had pleural abnormalities. Subcentimeter lung nodules were detected in seven subjects.
Mean pulmonary function data for spirometry and FO, stratified by smoking behavior, are shown in Table 3 . The 21 subjects who did not undergo FO testing because of time limitations were not statistically different spirometrically from the remaining 75 individuals. Of the subjects who underwent FO testing, 7 subjects had technically unacceptable pulmonary function results and 4 subjects had a history of asthma, so that 64 nonasthmatics were included in the analysis.
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Studies of FO indices showed a higher prevalence of baseline abnormalities. Thirty-four of the 64 nonasthmatics evaluated (53%) manifested R5 above the cutoff value of 3.5 cm H2O/L/s. Mean R5 was 4.4 cm H2O/L/s in these subjects. In comparison, the four subjects with a history of asthma who underwent FO testing manifested a mean R5 of 5.9 cm H2O/L/s. Response to bronchodilator was also more notable from FO data. Improvement in R5 and/or R20 occurred in 25 subjects (60%), while 3 additional subjects (7%) showed improvement in AX alone after nebulized bronchodilator.
The principal study outcomes, namely, the prevalence of respiratory symptoms, spirometric obstruction, and FO indices, were analyzed in relationship to risk factors (ie, smoking, exposure onset and duration, and respiratory protection). There was no significant difference in prevalence of respiratory symptoms between smokers and nonsmokers. Forty-nine of the 63 smokers (78%) and 25 of the 33 nonsmokers (76%) were symptomatic (p = 0.97). We did not find a statistically significant relationship between respiratory symptoms and duration of exposure, but the time of exposure onset significantly influenced prevalence of cough. Thirty-three of 42 ironworkers (78%) at Ground Zero on September 11 complained of cough, as opposed to 29 of 54 subjects (54%) who arrived subsequently (p = 0.02). Respiratory symptoms tended to occur less frequently in workers who wore a respirator with canister (14 of 22 subjects, 64%) than in those without this protection (60 of 74, 81%) during the first week at the site, although this relationship did not reach significance (p = 0.16).
Spirometric obstruction was found in a similar percentage of symptomatic (7 of 46 subjects, 15%) and asymptomatic (4 of 18 subjects, 22%) [p = 0.76] ironworkers, and none of the FO indices distinguished symptomatic from asymptomatic individuals. None of the lung function test results were significantly associated with either exposure onset or duration. Spirometric obstruction was not different in smokers (8 of 45 subjects, 18%) vs nonsmokers (3 of 19 subjects, 16%) [p = 0.87] for any of the indices listed in Table 3, although FEV1/FVC approached significance (p = 0.099). In contrast, significant differences were seen in oscillometric indices reflecting small airways function, since smokers demonstrated a higher AX and R5-R20 than did nonsmokers (mean, 3.9 ± 3.2 vs 1.8 ± 0.98, p = 0.008; and mean, 0.79 ± 0.48 vs 0.46 ± 0.31, p = 0.007, respectively). Additionally, FO results indicated a decreased large airways resistance in individuals who wore a respirator with canister: R20, 2.8 ± 0.48 vs 3.2 ± 0.64 (p = 0.01); R5, 3.4 ± 0.53 vs 3.9 ± 0.92 (p = 0.04).
Because the risk factors studied were not distributed entirely independently of each other, logistic and linear regression analyses of the outcomes were also performed. Analysis of respiratory symptoms revealed that only the association of exposure on September 11 was statistically significant at the conventional 0.05 level, although the association of use of a respirator with canister was close to significant (Table 4 ). When cough, by itself, was considered an outcome, a significant relationship with exposure on September 11 was again found (adjusted odds ratio [OR] = 3.64; 95% confidence interval, 1.35 to 9.83; p = 0.011). As with univariate analysis, the linear regression models of spirometric obstruction did not reveal any statistically significant associations with the risk factors. The model for the FO indexes (Table 5 ) confirmed the relationships noted in the univariate analysis and also demonstrated significant association between R5 and smoking.
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| Discussion |
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The oscillometric data revealed a substantially higher prevalence of lung function abnormalities and bronchodilator response and several significant relationships with risk factors. Smoking was associated with evidence of small airways obstruction (R5, R5-R20, and AX). Use of a respirator with canister was protective in terms of large airways dysfunction. None of the lung function tests discussed in this report distinguished between symptomatic and asymptomatic individuals.
Other investigators have documented the presence of increased respiratory symptoms in rescue workers at the WTC disaster site.5678910 Indeed, "WTC cough" is now well described, particularly in firefighters.8 There have also been reports of symptoms in nearby office workers.25 The importance of early exposure has been concurrently observed by Prezant et al,8 who showed that firefighters at Ground Zero immediately following the collapse had a higher prevalence of respiratory symptoms and bronchial hyperresponsiveness than those who arrived later the same day. In a more recent report, Banauch et al10 showed that bronchial hyperresponsiveness persisted in this group 6 months after the disaster.
In the current study, there was a risk for both reactive airways dysfunction syndrome and irritant-induced asthma. Rescue workers present at the time of the collapse were enveloped in the cloud of debris and were more likely to develop reactive airways dysfunction syndrome.3 Although the ironworkers were not involved early on September 11, a large number were exposed later that day when toxin levels were presumably still quite high. The majority of ironworkers participated in demolition and debris removal over weeks to months and were subject to repetitive, lower-level exposures. A variety of agents containing toxic constituents may have been inhaled, including fire and smoke, dust, and fumes. Most men were not wearing appropriate respiratory protection at the onset of exposure, which may have heightened their risk.26 Although prior occupational exposure may have posed an additional risk for development of respiratory abnormalities after September 11, this report focused on exposures related specifically to the WTC disaster. Even though air sampling beginning on September 18 suggested that levels of toxic dusts and gases were lower than initially suspected,27 earlier measurements1 demonstrated significant concentrations of toxicants (eg, asbestos, glass fibers, lead, and polycyclic aromatic hydrocarbons). Sequelae of such inhalations may take years to become clinically apparent.
The high prevalence of respiratory symptoms in ironworkers was not attributable to smoking, since similar percentages of smokers and nonsmokers were symptomatic. Although Blanc et al2829 have shown that respiratory symptoms following irritant exposure are more common in smokers or individuals with preexisting lung disease, their subjects all encountered brief, high-intensity inhalational exposures. It is possible that the prolonged, repetitive exposures of ironworkers to toxins at the WTC disaster site overwhelmed pulmonary defense mechanisms of both smokers and nonsmokers. The role of smoking as a predisposing factor for respiratory symptoms under the unique circumstances of the WTC catastrophe has not been explored.
Early exposure following the collapse was more provocative of cough than subsequent exposure. The concentration of an inhaled irritant has been identified as a risk factor for the development of respiratory abnormalities.30 Those individuals with earlier exposure presumably inhaled a higher concentration of toxins than those who arrived later. However, longer exposure duration was not associated with a higher prevalence of respiratory symptoms. Although use of a respirator with canister was not significantly associated with reduction in new onset of respiratory symptoms, there was a strong trend favoring protection by respiratory canister (adjusted OR, 0.32; p = 0.052).
The FO data show a substantially higher prevalence of abnormal airflow resistance in ironworkers after exposure at the WTC site than inferred from spirometric abnormalities. Similarly, bronchodilator responsiveness was substantially greater when assessed by FO. The increased sensitivity of FO over spirometry is consistent with earlier reports of subjects with either reactive airways disease or those exposed occupationally to toxic fumes or other inhalants.313233343536373839 Inferences of small or large airways mechanics from FO measures are based on established evidence for f-d R and compliance in patients with chronic airflow obstruction and in asymptomatic cigarette smokers.1831334041 Although unexposed ironworkers were not available to serve as a control group at the time of this evaluation, historical control subjects are available from other studies.18404243 These studies constitute a much smaller normal population than is available for spirometry. While studies over a period of 4 decades using monofrequency sine waves, or multifrequency pseudorandom noise, or impulse oscillation provide similar mean values and variance, it must be appreciated that differences in techniques may allow for some uncertainty regarding an upper limit of normal in clinically healthy, unexposed individuals. With this caveat, we examined more recent IOS studies4243 reporting a mean of R5 in normal subjects of 2.5 to 3 cm H2O/L/s with SD of 0.5 to 0.6 cm H2O/L/s. We accepted the larger of these mean values and 1.65 SD to define an upper limit of normal of 4 cm H2O/L/s. This higher estimated upper limit of normal yields 24 individuals in the present study with abnormal R5, or more than twice the number showing spirometric airflow obstruction. Quite apart from attempts to define "normal" vs "abnormal" in our study population, the present work confirms earlier FO studies demonstrating significant differences in small airway behavior in ever-smokers compared with never-smokers, and reports a new finding of significant differences in large airway behavior independent of smoking history in ironworkers wearing respiratory protection compared with those not using such protection during the first week following September 11, 2001.
FO indexes were influenced by use of a respirator with canister as well as by smoking. While FO evidence of small airways obstruction in smokers is not new and is consistent with previous reports of f-d R in asymptomatic smokers with normal spirometry but not in nonsmokers,183133343542 the demonstration of significantly higher AX in smokers is new. There are no published reports of f-d R and AX in normal adult subjects using an IOS, but unpublished data in 36 normal subjects in the second authors laboratory document a mean R5-R20 of 0.36 cm H2O/L/s (SD, 0.09) and mean AX of 1.5 cm H2O/L (SD, 0.6). Results from the nonsmokers in the present study do not differ significantly from these normal indices of small airways mechanics. Perhaps the more interesting observation was that ironworkers who did not use a respirator with canister had greater large airways resistance than those who did. Increased large airways resistance in these subjects is consistent with high concentrations of large particles in the initial air pollution cloud, and the likelihood of such particles to impact in large airways rather than in the lung periphery. Effective respiratory protection would be expected to favor large airways, and it is notable that there were no significant differences in indices of small airways obstruction (f-d R, AX) related to effective respiratory protection. Because large airways resistance contributes directly to total respiratory resistance, total respiratory resistance was also greater in those who did not use the canister.
In summary, this study documents a high frequency of respiratory symptoms in a cohort of ironworkers present at the WTC disaster site with fewer abnormalities on physical examination, spirometry, and radiographic tests. Routine spirometry underestimated the prevalence of lung function abnormalities in comparison to FO testing. FO confirmed the presence of abnormal small airways function in smokers and identified lack of a respirator with canister as a risk factor for large airways dysfunction. Respiratory symptoms were not attributable to smoking or to exposure duration but were probably influenced by use of appropriate respiratory protection. None of the lung function tests distinguished between symptomatic and asymptomatic individuals. The probability exists that the abnormalities documented in this study are due to exposure at the WTC site. We cannot address this issue with certainty in the absence of baseline data (before September 11, 2001). Follow-up evaluation of symptoms and airways dysfunction should determine whether long-term clinical sequelae exist.
| Footnotes |
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This work was performed at The Mount Sinai School of Medicine and was supported by grants from the Vivian Richenthal Institute of Pulmonary and Critical Care Medicine and The Catherine and Henry J. Gaisman Foundation.
Dr. Michael Goldman is a paid consultant to Jaeger, the company that manufactures the oscillation spirometry equipment.
Received for publication February 5, 2003. Accepted for publication October 17, 2003.
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