In the 21 years since the attacks on the World Trade Center (WTC) occurred on September 11, 2001, a large body of research has documented long-term health effects among patients who were directly exposed to the disaster. Various studies have shown high prevalence rates of cardiovascular, gastrointestinal, and psychiatric diagnoses among WTC survivors and first responders.1-3 Other research has demonstrated an increased risk of multiple types of cancer in these patients.4,5
Significant research has focused on the respiratory effects of the 9/11 disaster. Findings have demonstrated that “a relatively brief irritant exposure to dust and products of combustion during the WTC collapse could produce non-resolving inflammation in the mucosal surfaces of the aerodigestive system, leading to lung injury, sinus diseases, and gastroesophageal reflux disease,” said Michael D. Weiden, MD, professor of medicine and environmental medicine at New York University Grossman School of Medicine, and medical officer and science advisor to the chief medical officer at the Office of Medical Affairs for the Fire Department of the City of New York (FDNY).2
In 2021, the WTC Health Program, which provides health care services for certain conditions affecting WTC responders and survivors, published a report of updated health trends noted by the program between 2012 and 2020.6 Among the 104,223 patients enrolled in the WTC Health Program as of 2020, the most common noncancerous conditions related to 9/11 exposures are upper respiratory disease (64.0%), gastroesophageal reflux disorder (GERD; 56.4%), obstructive airway disease (49.1%), post-traumatic stress disorder, (23.1%), and depression (11.9%).
WTC Cough Syndrome and WTC Lung Injury
In a review published in December 2021 in Lung, Dr Weiden and colleagues summarized pulmonary complications that have been reported to affect WTC first responders from the FDNY in the 20 years since the attacks.7 They described a range of respiratory conditions that can be linked to the responders’ WTC exposure, including “WTC cough syndrome,” a persistent cough with onset after WTC exposure that has since “been found to be associated with obstructive airways disease, airway hyperreactivity, radiographic evidence of airway inflammation…, GERD, chronic rhinosinusitis, and PTSD,” according to the paper.7 Most of the FDNY responders with WTC cough syndrome were those exposed to the site within the first 48 hours of the disaster.
Additionally, FDNY workers who arrived on site the morning of September 11 were more than 6 times more likely to develop airway hyper-reactivity over the next 6 months compared with FDNY workers with no exposure or later exposure to the site. In follow-up studies, these responders demonstrated persistence of airway hyperreactivity 12 months after exposure as well as 10 to 12 years later.7
Other research has focused on a subset of FDNY rescue workers who had never smoked and developed significant reductions in the mean forced expiratory volume in 1 second (FEV1) in the first year following WTC exposure (reduction of 439 ml; 95% CI, 408-471). The researchers found that these patients showed little to no recovery to pre-9/11 FEV1 levels after a median follow-up period of 6.1 years.8 A newly decreased FEV1 below the lower limit of normal has been dubbed “WTC lung injury” (WTC-LI).7
In a 2018 study examining 15-year health effects of the 9/11 disaster, Dr Weiden and colleagues found that 8.3% of New York City firefighters with initial WTC-related FEV1 decline showed subsequent improvement, whereas 12.7% demonstrated persistent accelerated FEV1 decline.9 After adjusting for covariates, the researchers found that higher blood eosinophil and neutrophil concentrations were associated with subsequent accelerated FEV1 decline (odds ratio [OR], 1.10 per 100 eosinophils/μL; 95% CI, 1.05-1.15; and OR, 1.10 per 1,000 neutrophils/μL; 95% CI, 1.05-1.15, respectively).
Elevated eosinophil levels were linked to incident airflow limitation (adjusted hazard ratio, 1.10 per 100 eosinophils/μL; 95% CI, 1.04-1.15), and patients with accelerated (vs expected) FEV1 decline showed greater odds of incident airflow limitation (adjusted OR, 4.12; 95% CI, 3.30-5.14).9
Higher odds of developing WTC-LI years after exposure have been noted in WTC-exposed patients who showed increased “cardiovascular serum biomarkers, such as apolipoprotein A-I (ApoAI) and ApoAII, C-reactive protein (CRP) levels, soluble Receptor for Advanced Glycation End-Products (sRAGE), and lysophosphatidic acid” in the 6 months after 9/11, according to Weiden and colleagues’ 2021 review.7
Other findings have shown increased incidence of sarcoidosis and obstructive sleep apnea in WTC-exposed patients.7
“The treatment needs of this cohort for WTC cough, FEV1 decline, airway hyperreactivity, sarcoidosis, and WTC-LI underscore the importance of close longitudinal follow-up so that individualized treatment can be initiated after a unique exposure, such as WTC,” the review authors concluded.7
COPD and Asthma-COPD Overlap in WTC-Exposed Survivors
Numerous studies have shown an elevated risk of respiratory illnesses such as asthma and chronic bronchial disease in WTC-exposed populations. Emerging findings have also revealed increasing rates of chronic obstructive pulmonary disease (COPD) among workers and others with early exposure to the WTC site.
In a study presented at the 2021 European Respiratory Society (ERS) International Congress by Rafael E. de la Hoz, MD, MPH, MSc, ATSF, FACP, FCCP, professor of medicine, environmental medicine, and public health at the Icahn School of Medicine at Mount Sinai in New York, he and colleagues examined data from 17,996 patients (85.4% men) who arrived at the WTC site soon after the collapse of the Twin Towers.10
They found spirometrically defined COPD in 3.3% of the sample, with a 30% higher risk among patients who arrived within the first 48 hours compared with those arriving at later timepoints. The greatest risk of COPD was observed in patients with a previous asthma diagnosis, and approximately 40% of patients with COPD demonstrated asthma-COPD overlap (ACO).11
In previous research published in the Journal of Asthma in 2020, de la Hoz et al explored ACO in a sample of 29,911 patients enrolled in the WTC Health Registry. The researchers identified post-9/11 probable ACO (based on self-reported physician-diagnosed asthma plus emphysema, chronic bronchitis, or COPD) in 5.0% of participants.12
After adjustment for demographic variables and smoking status, the odds of having ACO were 38% higher in those exposed to the dust cloud after the attacks and up to 3.39 times higher in those who sustained multiple injuries on 9/11.
Treatment Implications and Future Directions
In a study described in October 2021 in the American Journal of Industrial Medicine, Dr Weiden et al examined the impact of inhaled corticosteroids and long-acting beta agonists (ICS/LABA) on FEV1 trajectories in 1023 WTC-exposed firefighters treated for at least 2 years. Participants with early initiation of ICS/LABA showed a 32.5 mL/y (95% CI, 19.5-45.5) improvement in FEV1 slope.13
Those with later treatment initiation, however, showed a nonsignificant improvement of 7.9 mL/y (95% CI, -0.5 to 17.2), likely because disease onset preceded treatment initiation in these patients. “Careful follow-up with repeated annual spirometry in patients with respiratory symptoms may identify pre-clinical COPD,” Dr Weiden stated. “Loss of more than 64 mL/y of FEV1 may be used to counsel patients about increased risk for COPD and irritant avoidance.”
There is a need for research exploring alternative therapies for patients with accelerated FEV1 decline who do not respond to ICS/LABA. Noting the association between increased IL-4 and accelerated FEV1 decline, Dr Weiden and colleagues plan to investigate whether blocking IL-4 with dupilumab improves FEV1 trajectory in these patients.
We learned more about 9/11-related respiratory issues in a recent interview with Dr de la Hoz.
What are some of the most notable findings regarding respiratory problems in 9/11 survivors and responders, and what has your research added to our understanding of this topic?
One of the most notable findings early on was the heterogeneity of the airway disorders observed. There was, however, the anticipation that more chronic forms of airway disease would eventually emerge. Our study suggests that COPD is one of them and that it had a significant association with early arrival at the disaster site – a gross indicator of higher dust and fumes exposures.10
We also observed that about one-quarter of all COPD patients were lifetime nonsmokers, an observation that has been described for several years that relates to exposures other than tobacco — including environmental and occupational factors — as contributors to COPD causation.
Finally, we have preliminary data suggesting that when these exposed workers with COPD also have asthma, asthma tended to be reported before COPD, suggesting a sequence of events related to the exposures.
What are the broader implications of your findings for clinicians?
There are a number of chronic airway diseases that do not fit easily established clinical definitions, which sometimes mutate into more recognizable diagnoses, but still require treatment and can improve with health-enhancing interventions such as smoking cessation, treatment of comorbid diseases, and attaining a healthier weight.
What are your plans for future research in this area?
The WTC occupational cohorts were noticed to be obese and overweight — and on average, weight gaining — since 2001, and the role played by this factor is the subject of several of our studies.14 We are interested in studies of those subjects whose lung function improved after having experienced deterioration. Weight loss and smoking cessation seemed related to those improvements.
We are also interested in identifying subjects who may develop other types of chronic and disabling lung disease such as interstitial lung diseases.
Finally, we have already identified comorbidity with psychological disorders as a risk factor for respiratory disease development, and we hope to be able to pursue those studies in the future.15
- Sloan NL, Shapiro MZ, Sabra A, et al. Cardiovascular disease in the World Trade Center Health Program General Responder Cohort. Am J Ind Med. 2021;64(2):97-107. doi:10.1002/ajim.23207
- Jordan HT, Osahan S, Li J, et al. Persistent mental and physical health impact of exposure to the September 11, 2001 World Trade Center terrorist attacks. Environ Health. 2019;18(1):12. doi:10.1186/s12940-019-0449-7
- Alper HE, Tuly RA, Seil K, Brite J. Post-9/11 mental health comorbidity predicts self-reported confusion or memory loss in World Trade Center Health Registry enrollees. Int J Environ Res Public Health. 2020;17(19):7330. doi:10.3390/ijerph17197330
- Durmus N, Shao Y, Arslan AA, et al. Characteristics of cancer patients in the World Trade Center Environmental Health Center. Int J Environ Res Public Health. 2020;17(19):7190. doi:10.3390/ijerph17197190
- Smith E, Holmes L, Larkin B. Health trends among 9/11 responders from 2011-2021: a review of World Trade Center Health Program statistics. Prehosp Disaster Med. 2021;36(5):621-626. doi:10.1017/S1049023X21000881
- Azofeifa A, Martin GR, Santiago-Colón A, Reissman DB, Howard J. World Trade Center Health Program – United States, 2012-2020. MMWR Surveill Summ. 2021;70(4):1-21. doi:10.15585/mmwr.ss7004a1
- Cleven KL, Rosenzvit C, Nolan A, et al. Twenty-year reflection on the impact of World Trade Center exposure on pulmonary outcomes in Fire Department of the City of New York (FDNY) rescue and recovery workers. Lung. 2021;199(6):569-578. doi:10.1007/s00408-021-00493-z
- Aldrich TK, Gustave J, Hall CB, et al. Lung function in rescue workers at the World Trade Center after 7 years. N Engl J Med. 2010;362(14):1263-1272. doi:10.1056/NEJMoa0910087
- Zeig-Owens R, Singh A, Aldrich TK, et al. Blood leukocyte concentrations, FEV1 decline, and airflow limitation. A 15-year longitudinal study of World Trade Center-exposed firefighters. Ann Am Thorac Soc. 2018;15(2):173-183. doi:10.1513/AnnalsATS.201703-276OC
- de la Hoz RE, Shapiro M, Nolan A, et al. Association of COPD and asthma COPD overlap (ACO) with World Trade Center (WTC) occupational exposure intensity. ERJ. 2021;58(Suppl. 65):PA3353. doi:10.1183/13993003.congress-2021.PA3353
- European Respiratory Society. Rescue and recovery workers at the World Trade Center site face higher risk of developing COPD. Accessed September 8, 2022.
- Haghighi A, Cone JE, Li J, de la Hoz RE. Asthma-COPD overlap in World Trade Center Health Registry enrollees, 2015-2016. Published online September 15, 2020. J Asthma. doi:10.1080/02770903.2020.1817935
- Goldfarb DG, Putman B, Lahousse L, et al. Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long-acting beta agonists. Am J Ind Med. 2021;64(10):853-860. doi:10.1002/ajim.23272
- de la Hoz RE, Liu X, Celedón JC, et al. Association of obesity with quantitative chest CT measured airway wall thickness in WTC workers with lower airway disease. Lung. 2019;197(4):517-522. doi:10.1007/s00408-019-00246-z
- Brite J, Friedman S, de la Hoz RE, Reibman J, Cone J. Mental health, long-term medication adherence, and the control of asthma symptoms among persons exposed to the WTC 9/11 disaster. J Asthma. 2020;57(11):1253-1262. doi:10.1080/02770903.2019.1672722
This article originally appeared on Pulmonology Advisor