The goal of the present proposal is to enhance characterization of World Trade Center (WTC)-related lung disease using lung function measurements that can detect lung injury in addition to abnormalities identified in standard spirometry. The proposed studies are based on the concept that spirometry may identify airway injury as a reduction in lung volume or air flow, however, spirometry can often be normal even in symptomatic patients, particularly when injury is located in the distal airways.
To enhance characterization of airway injury in subjects enrolled in the Bellevue Hospital WTC EHC by evaluating spirometry and assessment of distal airway function utilizing oscillometry.
To determine the relationship between development of distal airway dysfunction and simultaneous development of respiratory symptoms during induced bronchoconstriction in subjects enrolled in the Bellevue Hospital WTC EHC
To determine longitudinal lung function as assessed by spirometry and oscillometry in a diverse population exposed to WTC dust while undergoing standardized evaluation and therapy.
The goal of this study is to enhance characterization of World Trade Center (WTC) related lung disease using lung function measurements that can detect lung injury in addition to abnormalities identified in standard spirometry. The research direction is based on the concept that spirometry may identify airway injury as a reduction in lung volume or air flow, however, spirometry can remain normal even in symptomatic patients, particularly when injury is located in the small or distal airways. The studies build upon prior histologic and functional evidence for distal airway abnormalities as a manifestation of obstructive lung diseases. Data have demonstrated:
Thus, characterization of distal airway injury in addition to standard spirometry is crucial for diagnosis, determination of optimal medical therapy and assessment of changes over time. Moreover, identification of distal airway injury may be an early marker of disease that may be progressive but may also be amenable to therapy. These data have broad implications that should be considered during other catastrophes where lung injury is a likely outcome and in airway diseases, such as asthma and COPD, where pathologic involvement of distal airways is common, but where the physiologic phenotype has been elusive.
A "Small Airway Disease Syndrome" provides a mechanism for respiratory disease following WTC dust exposure even in subjects with normal screening spirometry. Addition of forced oscillation to routine assessment of spirometry in the clinical setting uncovered abnormalities in lung function in a persistently symptomatic population with normal spirometry. Studies confirmed a dose response relationship between small airway dysfunction to both magnitude of WTC dust expose, severity of symptoms and reactivity in small airways. Longitudinal data demonstrated improvement of small airway function in subjects with acute response to bronchodilator at baseline. The presence of small airway abnormalities suggests a potential target for treatment, particularly for subjects who remain symptomatic despite usual medical care.
WTC EHC: Joan Reibman, M.D., Professor of Medicine; Roberta M. Goldring, M.D., Professor of Medicine; Yongzhao Shao, Ph.D., Professor of Environmental Medicine; Mengling Liu, Ph.D., Associate Professor of Environmental Medicine; Michael Marmor, Ph.D. Professor of Population Health; Caralee Caplan-Shaw, M.D., Assistant Professor of Medicine; Meredith Turetz, M.D., Assistant Professor of Medicine; Deepak Pradhan, M.D., Instructor of Medicine; Angeliki Kazeros, M.D., Assistant Professor of Medicine; Beno W. Oppenheimer, M.D., Assistant Professor of Medicine; Denise Harrison, M.D., Assistant Professor of Medicine; Ioannis Vlahos, M.D., Assistant Professor of Radiology; Sam Parsia, M.D., Assistant Professor of Medicine; Meng Qian, Research Associate; Quinyi Chen, Research Associate; Samantha Kalish, Research Associate; Maria-Elena Fernandez-Beros, Database Manager
NYC DOHMH: Stephen Friedman, M.D.; Carrie Maslow, Dr.Ph.; Mark Farfel, Sc.D.
Caplan-Shaw CE, Yee H, Rogers L, et al. 2011. Lung pathologic findings in a local residential and working community exposed to World Trade Center dust, gas and fumes. J Occup Environ Med. 53(9):981–91.
Friedman SM, Maslow CB, Reibman J, et aI. 2011. Case-control study of lung function in World Trade Center Health Registry area residents and workers. Am J Respir Crit Care Med. 184(5):582–589.
Liu M, Qian M, Chen Q, et al. 2012. Longitudinal spirometry among patients in a treatment program for community members with World Trade Center-related illness. Journal of Occupational and Environmental Medicine. 54(10):1208–13.
Berger K, Reibman J, Oppenheimer B, et al. 2013. Lessons from the World Trade Center disaster: Airway disease presenting as restrictive dysfunction. Chest. 144(1):249–257.
Kazeros A, Maa M, Patrawalla P, et al. 2013. Elevated peripheral eosinophils are associated with new-onset and persistent wheeze and airflow obstruction in World Trade Center-exposed individuals. Journal of Asthma. 50(1):25–32.
Kazeros A, Zhang E, Cheng X, et al. 2015. Systemic inflammation associated with World Trade Center dust exposures and airway abnormalities in the local community. Journal of Occupational and Environmental Medicine. 57(6):610–616.
Berger K, Turetz M, Liu M, et al. 2015 Dec. Oscillometry complements spirometry in evaluation of subjects following toxic inhalation. European Respiratory Journal Open Research. 1(2) pii:00043-2015.
Berger K, Kalish S, Shao Y, et al. 2016. Isolated small airway reactivity during bronchoprovocation as a mechanism for respiratory symptoms in WTC dust exposed community members. American Journal of Industrial Medicine.59:767–776.
