Exposure to the WTC Disaster and Obstructive Airway Disease
Exposure to the WTC Disaster and Obstructive Airway Disease
The study population consisted of 10,671 FDNY firefighters who first arrived at the WTC site to participate in the rescue and recovery effort on or before September 24, 2001. Firefighters who retired after September 11, 2001, were included if they were active FDNY employees on September 11, 2001. We excluded data from the following subjects: 543 subjects with a diagnosis of OAD prior to September 11, 2001; women and nonwhites because of small numbers (n = 657); those who were present at the site but not on active duty for the FDNY on September 11, 2001 (n = 258); those missing information on smoking history (n = 173); and those who did not consent to have their data used for research (n = 110), leaving 8,930 male firefighters in the final analytical cohort. Study participants provided written informed consent. The study was approved by the institutional review board at Montefiore Medical Center (Bronx, New York).
Demographic information came from the FDNY employee database. Beginning in 1996, the FDNY medical program, run by the FDNY Bureau of Health Services, transitioned to electronic medical records with diagnoses coded according to the International Classification of Diseases, Ninth Revision. Physician diagnoses were obtained from these electronic medical records. Since October 2001, the FDNY Bureau of Health Services also has collected data from self-administered health questionnaires completed during routine annual exams, from which we obtained information regarding WTC exposure, smoking status, and current lower respiratory symptoms of cough, shortness of breath, or wheeze.
Because the primary purpose of this study was to determine whether the relative incidence of OAD diagnosis changed significantly during the follow-up period, it was essential that the opportunity to obtain an OAD diagnosis from a FDNY physician remained constant. This means that the likelihood of a physician visit must have been the same across all levels of exposure throughout the follow-up period after controlling for other factors. A programmatic change in January 2007 offered free prescription medications (without copay or deductibles) for all WTC-covered conditions, but it required a diagnosis from a FDNY physician. Because this increased the likelihood that firefighters would seek medical treatment at the FDNY, we limited the study analyses to the first 5 years following September 11, 2001.
FDNY physicians receive detailed instruction in diagnosing and treating respiratory diseases and are trained to use consistent diagnostic criteria. Examining physicians determine diagnoses after integrating information from patient history, physical examination, spirometry, other pulmonary function testing, and chest imaging.
We reviewed the FDNY electronic medical record database from September 11, 2001, through September 10, 2006, for any diagnosis of asthma, chronic bronchitis, or chronic obstructive pulmonary disease (COPD)/emphysema using the following International Classification of Diseases, Ninth Revision, codes for a diagnosis of asthma: 493.0, 493.00, 493.01, 493.02, 493.1, 493.10, 493.11, 493.12, 493.20, 493.21, 493.22, 493.82, 493.9, 493.90, and 493.91. We used the following codes for nonasthma OAD (chronic bronchitis and COPD/emphysema): 491, 491.0, 491.1, 491.2, 491.20, 491.21, 491.22, 491.8, 491.9, 492.8, 494, 494.1, and 496. A person was considered to have new-onset OAD if they had the first diagnosis of asthma, chronic bronchitis, or COPD/emphysema within the study period (September 11, 2001–September 10, 2006). Our primary analyses used any diagnosis of OAD as the outcome; secondary analyses used either asthma or nonasthma OAD as outcomes. To increase the reliability of OAD diagnoses, we required that a diagnosis of asthma or COPD/emphysema be documented 2 or more times after September 11, 2001. When a first diagnosis occurred from September 11, 2001, to September 10, 2006, we allowed the second or confirmatory diagnosis to take place any time through September 10, 2012. Chronic bronchitis required 2 diagnoses within 1 year and at least 1 additional diagnosis in the following 3 years. Multiple visits with the same diagnosis within a 30-day period were counted only once because they were most likely related to a single episode. For all OAD diagnoses, the date of diagnosis used for analyses was the date it was first documented.
Intensity of exposure to the WTC rescue and recovery effort was based on initial arrival time as follows: arrival on the morning of September 11, 2001 (high-exposure group); arrival during the afternoon of September 11, 2001, through September 12, 2001 (moderate-exposure group); or arrival any day between September 13, 2001, and September 24, 2001 (low-exposure group).
Smoking status was characterized by self-reports as of September 10, 2006. Participants were considered "ever smokers" if they reported ever smoking before September 11, 2006. Participants were considered "never smokers" if they consistently reported never smoking on all questionnaires. If smoking status during the study period was missing, but the participant later reported never smoking, he or she was considered a "never" smoker. As previously noted, those whose smoking status was consistently missing (n = 173) were excluded from the final analytical cohort.
Follow-up time started on September 11, 2001, and ended on the earliest date of the following events: first OAD diagnosis, last FDNY physician visit, or September 10, 2006. WTC exposure was modeled by arrival time (3 groups), as described above, and was used in all relative rate analyses. Both moderate- and low-exposure groups were used as the reference population in separate analyses. Smoking was modeled as smoking status as of the end of the study. Age on September 11, 2001, was included in all models. Retirement from active service at the FDNY was modeled as a time-dependent variable.
We estimated relative rates and 95% confidence intervals for OAD incidence as a function of exposure group (high, moderate, low) over the first 5 years after September 11, 2001. These models were run first for an outcome of OAD and then as a sensitivity analysis using an asthma or nonasthma OAD outcome. In analyses by asthma or nonasthma OAD subtype, patients diagnosed with both asthma and nonasthma OAD on the same day (n = 6) were considered to have asthma alone. We used piecewise exponential survival models with 3-month increments as the time interval, allowing for a new baseline incidence rate at each 3-month interval, and the models were fit by maximum likelihood. This method results in estimates of relative rates that are almost always similar to the relative hazards obtained from Cox regression models (and have relative hazard interpretation) but with the advantage of having a full likelihood available to measure goodness-of-fit. Change point analyses were used within the models to estimate the 3-month interval (quarter) for which the relative incidences significantly changed (decreased or increased) from 1 quarter to the next. The goal of the analyses was to identify a change point after which relative incidences did not differ significantly from 1, which would show that the exposure-response relationship between WTC exposure and incident OAD was limited to the period prior to the change point.
Change points were determined using profile likelihood. First, we fit a model without change points that assumed constant incidence rates for each exposure group throughout the follow-up period. We then fit a succession of models with a single change point, allowing each model to change incidence rates at a different follow-up time, at 3-month intervals, with change points varying from 3 months to 57 months after September 11, 2001, resulting in a total of 19 possible models. The maximized likelihood for each model as a function of the change point forms the profile likelihood, and the maximum likelihood across all 19 models determined the best fitting model; the change point associated with that model is the maximum likelihood estimate for the change point that we report. The same process was used for models with 2 or 3 change points, in which each combination of change points was run in separate models and then compared via maximum likelihood. Likelihood ratio tests were used to determine the model with the proper number of change points. To avoid the potential for overfitting with too many change points over the follow-up time, successively more stringent criteria to include more change points were used. In comparing a model with p change points to a model with p − 1 change points, a P value of (0.05) × (0.5) was used as a threshold for selecting the larger model. Thus, to compare a model with 1 change point to a model with 0 change points, a P value threshold of 0.025 was used; to compare a model with 2 change points to a model with 1 change point, a P value threshold of 0.0125 was used, and so on. This sequential testing procedure controls the maximum type I error rate for all tests involving change points at 0.05 regardless of the number of change points considered.
WTC exposure was also modeled as an ordinal predictor (coded 0 for the low-exposure group, 1 for the moderate-exposure group, and 2 for the high-exposure group) to test the hypothesis of a linear trend in exposure-response relationship and to describe how that linear trend varied over the follow-up time using similar change point analyses. Detailed descriptions of the models are included in the Appendix.
Methods
Population
The study population consisted of 10,671 FDNY firefighters who first arrived at the WTC site to participate in the rescue and recovery effort on or before September 24, 2001. Firefighters who retired after September 11, 2001, were included if they were active FDNY employees on September 11, 2001. We excluded data from the following subjects: 543 subjects with a diagnosis of OAD prior to September 11, 2001; women and nonwhites because of small numbers (n = 657); those who were present at the site but not on active duty for the FDNY on September 11, 2001 (n = 258); those missing information on smoking history (n = 173); and those who did not consent to have their data used for research (n = 110), leaving 8,930 male firefighters in the final analytical cohort. Study participants provided written informed consent. The study was approved by the institutional review board at Montefiore Medical Center (Bronx, New York).
Data Sources
Demographic information came from the FDNY employee database. Beginning in 1996, the FDNY medical program, run by the FDNY Bureau of Health Services, transitioned to electronic medical records with diagnoses coded according to the International Classification of Diseases, Ninth Revision. Physician diagnoses were obtained from these electronic medical records. Since October 2001, the FDNY Bureau of Health Services also has collected data from self-administered health questionnaires completed during routine annual exams, from which we obtained information regarding WTC exposure, smoking status, and current lower respiratory symptoms of cough, shortness of breath, or wheeze.
Follow-up Period
Because the primary purpose of this study was to determine whether the relative incidence of OAD diagnosis changed significantly during the follow-up period, it was essential that the opportunity to obtain an OAD diagnosis from a FDNY physician remained constant. This means that the likelihood of a physician visit must have been the same across all levels of exposure throughout the follow-up period after controlling for other factors. A programmatic change in January 2007 offered free prescription medications (without copay or deductibles) for all WTC-covered conditions, but it required a diagnosis from a FDNY physician. Because this increased the likelihood that firefighters would seek medical treatment at the FDNY, we limited the study analyses to the first 5 years following September 11, 2001.
FDNY Physician Diagnoses
FDNY physicians receive detailed instruction in diagnosing and treating respiratory diseases and are trained to use consistent diagnostic criteria. Examining physicians determine diagnoses after integrating information from patient history, physical examination, spirometry, other pulmonary function testing, and chest imaging.
We reviewed the FDNY electronic medical record database from September 11, 2001, through September 10, 2006, for any diagnosis of asthma, chronic bronchitis, or chronic obstructive pulmonary disease (COPD)/emphysema using the following International Classification of Diseases, Ninth Revision, codes for a diagnosis of asthma: 493.0, 493.00, 493.01, 493.02, 493.1, 493.10, 493.11, 493.12, 493.20, 493.21, 493.22, 493.82, 493.9, 493.90, and 493.91. We used the following codes for nonasthma OAD (chronic bronchitis and COPD/emphysema): 491, 491.0, 491.1, 491.2, 491.20, 491.21, 491.22, 491.8, 491.9, 492.8, 494, 494.1, and 496. A person was considered to have new-onset OAD if they had the first diagnosis of asthma, chronic bronchitis, or COPD/emphysema within the study period (September 11, 2001–September 10, 2006). Our primary analyses used any diagnosis of OAD as the outcome; secondary analyses used either asthma or nonasthma OAD as outcomes. To increase the reliability of OAD diagnoses, we required that a diagnosis of asthma or COPD/emphysema be documented 2 or more times after September 11, 2001. When a first diagnosis occurred from September 11, 2001, to September 10, 2006, we allowed the second or confirmatory diagnosis to take place any time through September 10, 2012. Chronic bronchitis required 2 diagnoses within 1 year and at least 1 additional diagnosis in the following 3 years. Multiple visits with the same diagnosis within a 30-day period were counted only once because they were most likely related to a single episode. For all OAD diagnoses, the date of diagnosis used for analyses was the date it was first documented.
WTC Exposure Measurement
Intensity of exposure to the WTC rescue and recovery effort was based on initial arrival time as follows: arrival on the morning of September 11, 2001 (high-exposure group); arrival during the afternoon of September 11, 2001, through September 12, 2001 (moderate-exposure group); or arrival any day between September 13, 2001, and September 24, 2001 (low-exposure group).
Smoking Status
Smoking status was characterized by self-reports as of September 10, 2006. Participants were considered "ever smokers" if they reported ever smoking before September 11, 2006. Participants were considered "never smokers" if they consistently reported never smoking on all questionnaires. If smoking status during the study period was missing, but the participant later reported never smoking, he or she was considered a "never" smoker. As previously noted, those whose smoking status was consistently missing (n = 173) were excluded from the final analytical cohort.
Statistical Analyses
Follow-up time started on September 11, 2001, and ended on the earliest date of the following events: first OAD diagnosis, last FDNY physician visit, or September 10, 2006. WTC exposure was modeled by arrival time (3 groups), as described above, and was used in all relative rate analyses. Both moderate- and low-exposure groups were used as the reference population in separate analyses. Smoking was modeled as smoking status as of the end of the study. Age on September 11, 2001, was included in all models. Retirement from active service at the FDNY was modeled as a time-dependent variable.
We estimated relative rates and 95% confidence intervals for OAD incidence as a function of exposure group (high, moderate, low) over the first 5 years after September 11, 2001. These models were run first for an outcome of OAD and then as a sensitivity analysis using an asthma or nonasthma OAD outcome. In analyses by asthma or nonasthma OAD subtype, patients diagnosed with both asthma and nonasthma OAD on the same day (n = 6) were considered to have asthma alone. We used piecewise exponential survival models with 3-month increments as the time interval, allowing for a new baseline incidence rate at each 3-month interval, and the models were fit by maximum likelihood. This method results in estimates of relative rates that are almost always similar to the relative hazards obtained from Cox regression models (and have relative hazard interpretation) but with the advantage of having a full likelihood available to measure goodness-of-fit. Change point analyses were used within the models to estimate the 3-month interval (quarter) for which the relative incidences significantly changed (decreased or increased) from 1 quarter to the next. The goal of the analyses was to identify a change point after which relative incidences did not differ significantly from 1, which would show that the exposure-response relationship between WTC exposure and incident OAD was limited to the period prior to the change point.
Change points were determined using profile likelihood. First, we fit a model without change points that assumed constant incidence rates for each exposure group throughout the follow-up period. We then fit a succession of models with a single change point, allowing each model to change incidence rates at a different follow-up time, at 3-month intervals, with change points varying from 3 months to 57 months after September 11, 2001, resulting in a total of 19 possible models. The maximized likelihood for each model as a function of the change point forms the profile likelihood, and the maximum likelihood across all 19 models determined the best fitting model; the change point associated with that model is the maximum likelihood estimate for the change point that we report. The same process was used for models with 2 or 3 change points, in which each combination of change points was run in separate models and then compared via maximum likelihood. Likelihood ratio tests were used to determine the model with the proper number of change points. To avoid the potential for overfitting with too many change points over the follow-up time, successively more stringent criteria to include more change points were used. In comparing a model with p change points to a model with p − 1 change points, a P value of (0.05) × (0.5) was used as a threshold for selecting the larger model. Thus, to compare a model with 1 change point to a model with 0 change points, a P value threshold of 0.025 was used; to compare a model with 2 change points to a model with 1 change point, a P value threshold of 0.0125 was used, and so on. This sequential testing procedure controls the maximum type I error rate for all tests involving change points at 0.05 regardless of the number of change points considered.
WTC exposure was also modeled as an ordinal predictor (coded 0 for the low-exposure group, 1 for the moderate-exposure group, and 2 for the high-exposure group) to test the hypothesis of a linear trend in exposure-response relationship and to describe how that linear trend varied over the follow-up time using similar change point analyses. Detailed descriptions of the models are included in the Appendix.
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