Faculty Bibliography

Gastroesophageal reflux disease (GERD) and Barrett's Esophagus (BE), which are prevalent in the World Trade Center (WTC) exposed and general populations, negatively impact quality of life and cost of healthcare. GERD, a risk factor of BE, is linked to obstructive airways disease (OAD). We aim to identify serum biomarkers of GERD/BE, and assess the respiratory and clinical phenotype of a longitudinal cohort of never-smoking, male, WTC-exposed rescue workers presenting with pulmonary symptoms. Biomarkers collected soon after WTC-exposure were evaluated in optimized predictive models of GERD/BE. In the WTC-exposed cohort, the prevalence of BE is at least 6 times higher than in the general population. GERD/BE cases had similar lung function, D_LCO, bronchodilator response and long-acting beta-agonist use compared to controls. In confounder-adjusted regression models, TNF-alpha ≥ 6 pg/mL predicted both GERD and BE. GERD was also predicted by C-peptide ≥ 360 pg/mL, while BE was predicted by fractalkine ≥ 250 pg/mL and IP-10 ≥ 290 pg/mL. Finally, participants with GERD had significantly increased use of short-acting beta-agonist compared to controls. Overall, biomarkers sampled prior to GERD/BE presentation showed strong predictive abilities of disease development. This study frames future investigations to further our understanding of aerodigestive pathology due to particulate matter exposure.

RATIONALE: Rescue/recovery work at the World Trade Center (WTC) disaster site caused a proximate decline in lung function in Fire Department of the City of New York (FDNY) firefighters. A subset of this cohort experienced an accelerated rate of lung function decline over 15 years of post-9/11 follow-up. OBJECTIVES: To determine if post-exposure inflammatory cell concentrations are biomarkers for subsequent forced expiratory volume (FEV1) decline and incident airflow limitation. METHODS: Individual rates of FEV1 change were calculated for 9,434 firefighters using 88,709 spirometric measurements taken between 9/11/2001 (9/11) and 9/10/2016. We categorized FEV1 change rates into three trajectories: accelerated FEV1 decline (FEV1 loss >64 ml/year), expected FEV1 decline (FEV1 loss between 0-64 ml/year), and improved FEV1 (positive rate of change >0 ml/year). Occurrence of FEV1/FVC<0.70 after 9/11 defined incident airflow limitation. Regression models assessed associations of post-9/11 blood eosinophil and neutrophil concentrations with subsequent FEV1 decline and airflow limitation, adjusted for age, race, smoking, height, WTC exposure level, weight change and baseline lung function. RESULTS: Accelerated FEV1 decline occurred in 12.7% of participants (1,199/9,434), while post-9/11 FEV1 improvement occurred in 8.3% (780/9,434). Eosinophil and neutrophil concentrations were both associated with accelerated vs. expected FEV1 decline after adjustment for covariates (OR: 1.10 per 100 eosinophils/microl, 95% CI: 1.05-1.15 and OR: 1.10 per 1,000 neutrophils/microl, 95% CI: 1.05-1.15). Multivariable-adjusted linear regression models showed that neutrophil concentration was associated with FEV1 decline rate (1.14 ml/year decline per 1000 neutrophils/microl, 95% CI: 0.69-1.60 ml/year, p<0.001), while eosinophil concentration was associated with FEV1 decline rate in ever-smokers (1.46 ml/year decline per 100 eosinophils/microl, 95% CI: 0.65-2.26 ml/year, p<0.001) but not in never-smokers (p for interaction=0.004). Eosinophil concentration was also associated with incident airflow limitation (adjusted HR: 1.10 per 100 eosinophils/microl, 95% CI: 1.04-1.15). Compared with the expected FEV1 decline group, individuals experiencing accelerated FEV1 decline were more likely to have incident airflow limitation (adjusted OR: 4.12, 95% CI: 3.30-5.14). CONCLUSIONS: Elevated post-9/11 blood inflammatory cell concentrations were risk factors for subsequent accelerated FEV1 decline in WTC-exposed firefighters. Accelerated FEV1 decline was associated with incident airflow limitation, suggesting progressive airway injury in this subgroup.

BACKGROUND: Sarcoidosis is thought to represent a genetically-primed, abnormal immune response to an antigen exposure or inflammatory trigger, with both genetic and environmental factors playing a role in disease onset and phenotypic expression. In a population of firefighters with post-WTC-9/11/2001 (9/11) sarcoidosis, we have a unique opportunity to describe the clinical course of incident sarcoidosis during the 15-years post-exposure and, on average, 8-years after diagnosis. METHODS: Among the WTC-exposed cohort, 74 firefighters with post-9/11 sarcoidosis were identified through medical records review. 59 were enrolled in follow-up studies. For each participant, the World Association of Sarcoidosis and Other Granulomatous Diseases organ assessment tool was used to categorize sarcoidosis involvement of each organ system at time of diagnosis and at follow-up. RESULTS: The incidence of sarcoidosis post-9/11 was 25/100,000. Radiographic resolution of intrathoracic involvement occurred in 24 (45%). Lung function for nearly all was within normal limits. Extrathoracic involvement increased, most prominently joints (15%) and cardiac (16%). There was no evidence for calcium dysmetabolism. Few had ocular (5%) or skin (2%) involvement. None had beryllium sensitization. Most (76%) did not receive any treatment. CONCLUSIONS: Extrathoracic disease was more prevalent in WTC-related sarcoidosis than reported for sarcoidosis patients without WTC-exposure or for other exposure-related granulomatous diseases (beryllium disease and hypersensitivity pneumonitis). Cardiac involvement would have been missed if evaluation stopped after electrocardiogram, 48-hour recordings and echocardiogram. Our results also support the need for advanced cardiac screening in asymptomatic patients with strenuous, stressful, public safety occupations, given the potential fatality of a missed diagnosis.

INTRODUCTION: The management of eosinophilic-granulomatosis with polyangiitis (EGPA) with diffuse alveolar hemorrhage (DAH) in patients who have failed first line therapy can be challenging. We present a case of refractory EGPA with DAH and hypoxic respiratory failure that improved with plasma exchange. CASE PRESENTATION: A 75-year-old woman with EGPA with renal and lung involvement presented with hemoptysis. She had multiple EGPA flares in the past and had failed first-line therapy with cyclophosphamide and azathioprine. CT chest was significant for areas of extensive bronchiectasis with areas of fibrosis, as well as new areas of ground glass opacifications (see Fig. 1, A & B). She developed worsening hypoxic respiratory failure requiring intubation. Bronchoscopy with broncheoalveolar lavage was consistent with DAH (see Fig. 1, C). Despite being started on methylprednisolone and antibiotics, she continued to have worsening hypoxia and renal failure. Plasma exchange was initiated with significant improvement in hypoxia. After five sessions of plasma exchange, she had significant clinical improvement in her renal failure and resolution of hypoxic respiratory failure. DISCUSSION: There is a paucity of data available to guide the management of EGPA with DAH and hypoxic respiratory failure in patients who have failed first line therapies. Plasma exchange has been used in glomerulonephritis associated with EGPA with limited results1. Case reports identify a benefit of plasma exchange for treatment of corticosteroid-refractory EGPA with gastrointestinal manifestations2; however, there is no data investigating the role of plasma exchange in the management of pulmonary manifestations of EGPA. From these studies, one can only extrapolate that plasma exchange would treat pulmonary manifestations of EGPA, as was demonstrated in our patient. CONCLUSIONS: The management of hypoxic respiratory failure secondary to EGPA associated DAH is challenging. Treatment options for those that fail conventional therapies are lacking; however, the role of plasma exchange as a new treatment modality is promising

PURPOSE: Our overall goal is to create a sustainable ultrasound(US) intervention in resource-limited settings in Dhaka, Bangladesh. Our baseline needs-assessment of the intensive care unit (ICU) of Dhaka Medical College Hospital (DMCH) found that reliable imaging is not available, including ultrasound. The lack of adequate imaging was found to be a deterrent to the proper care of patients. The growing use of point-of-care ultrasound in the ICU as a tool for rapid diagnosis and management led to the creation of the Bangladesh Ultrasound Initiative. This project is designed to bring a successful point-of-care ultrasound training program to physicians in the ICU and emergency room of DMCH. METHODS: Participants were recruited via posters and emails. Training workshops spanned the course of two days. All sessions included individuals that represented all levels of physician training. The following topics were covered: technical aspects, basic echocardiography, pleural ultrasound, DVT and IVC assessment, US-guided CVL placement, US-guided thoracentesis and FAST exam. Training sessions were divided into three parts: lecture-based learning (2 hours), image interpretation with normal and pathological images shown to participants(1.5 hours), and hands-on practical use with the aid of volunteers(2.5 hours). A pre-test and post-test with the same questions was distributed before and after each workshop respectively. Statistical analysis was completed with the use of a chi-square test and paired t-test. RESULTS: Fifty individuals were included in the final analysis. The pre-test/post-test had a total of 37 questions, 25 of which were knowledge-based. Knowledge-based questions were grouped into the topics covered as listed in the methods section. There was a statistically significant (p<0.05) difference between pre- and post-test scores; the mean pre-test score was 3 (SD=3) and the mean post-test score was 12 (SD=3). A 5-point Likert scale was used to ask questions regarding level of confidence. The mean confidence level on the pre-test was 1 (very unconfident) in every category to 5 (very confident) in the post-test(p<0.05). A subgroup analysis showed no difference in mean pre-test and post-test scores of participants who had attended an ultrasound course at any point prior to our intervention compared to those who had never attended a previous ultrasound course. CONCLUSIONS: The results of this study show that a simple workshop in point-of-care ultrasound, using lectures and hands-on practice, can improve knowledge and confidence with statistical significance. This study also shows that the pre- and post-test scores are similar despite some participants having had training in ultrasound prior to the current intervention

World Trade Center-particulate matter(WTC-PM) exposure and metabolic-risk are associated with WTC-Lung Injury(WTC-LI). The receptor for advanced glycation end-products (RAGE) is most highly expressed in the lung, mediates metabolic risk, and single-nucleotide polymorphisms at the AGER-locus predict forced expiratory volume(FEV). Our objectives were to test the hypotheses that RAGE is a biomarker of WTC-LI in the FDNY-cohort and that loss of RAGE in a murine model would protect against acute PM-induced lung disease. We know from previous work that early intense exposure at the time of the WTC collapse was most predictive of WTC-LI therefore we utilized a murine model of intense acute PM-exposure to determine if loss of RAGE is protective and to identify signaling/cytokine intermediates. This study builds on a continuing effort to identify serum biomarkers that predict the development of WTC-LI. A case-cohort design was used to analyze a focused cohort of male never-smokers with normal pre-9/11 lung function. Odds of developing WTC-LI increased by 1.2, 1.8 and 1.0 in firefighters with soluble RAGE (sRAGE)>/=97pg/mL, CRP>/=2.4mg/L, and MMP-9