Faculty Bibliography

BACKGROUND:Previously healthy firefighters with World Trade Center (WTC) dust exposure developed airway disease. Risk factors for irritant-associated asthma/COPD overlap are poorly defined. METHODS:/FVC ratio, and BMI included as covariates. RESULTS:BD-PFT diagnosed asthma/COPD overlap in 99 individuals (4.6%), isolated-asthma in 202 (9.5%), and isolated-COPD in 215 (10.1%). Eosinophil concentration≥300 cells/μl was associated with increased risk of asthma/COPD overlap (HR: 1.85, 95% CI: 1.16-2.95), but not with isolated-asthma or isolated-COPD. Serum IL-4 also predicted asthma/COPD overlap (HR: 1.51 per doubling of cytokine concentration, 95% CI: 1.17-1.95). Greater IL-21 concentration was associated with both isolated-asthma and isolated-COPD (HR: 1.73, 95% CI: 1.27-2.35 and HR: 2.06, 95% CI: 1.31-3.23, respectively). CONCLUSIONS:In WTC-exposed firefighters, elevated blood eosinophils and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific Th-2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.

The prevalence of non-cardiac chest pain (NCCP) ranges from 13-33%. A majority of those presenting with a chief complaint of chest pain are found to have a diagnosis of NCCP. Aerodigestive diseases are a cause of NCCP, and billions of dollars are spent annually on the treatment of NCCP. Furthermore, NCCP can cause significant psychological stress. NCCP is commonly diagnosed when patients have chest pain despite a normal cardiac evaluation. The leading cause of NCCP is gastro-oesophageal reflux disease (GORD). GORD should be suspected in patients who report a history of acid regurgitation, cough, dysphagia, and bloating. Another common cause of NCCP is obstructive airway disease (OAD). A thorough history and review of the symptoms should be performed for those with suspected NCCP, especially because of the contributing end organs. It is known that environmental exposures can commonly cause GORD and OAD; however, NCCP has not been fully explored in the context of environmental exposure. Patients with a history of exposure to particulate matter can develop environmental-exposure-associated GORD and coexisting OAD. This narrative review aims to provide a practical overview of NCCP, its causes, their relation to environmental exposure, and associated biomarkers. The authors used a PubMed search that spanned 2003-2018 to accomplish this. Additionally, this review provides a broad overview of biomarkers of GORD-associated NCCP and OAD-associated NCCP due to environmental exposure.

Zika virus (ZIKV) infection has been associated with Guillain-Barré Syndrome (GBS). Roughly 60% of people in countries such as the U.S. live in areas at risk for seasonal spread of ZIKV. ZIKV belongs to a class of diseases that is not typically seen in hospital settings across the U.S. and Europe. We describe the case presentation, management, and treatment of ZIKV infection complicated by GBS. A 64-year-old woman with recent travel to the Dominican Republic presented with rash followed by an acute, ascending polyneuropathy consistent with GBS. She was confirmed to have an acute ZIKV infection by detection of ZIKV nucleic acid by reverse transcription-polymerase chain reaction. She met Brighton Collaboration criteria level 1 evidence for GBS. She received two courses of intravenous immunoglobulin and slowly improved, though still had weakness at discharge. More research is needed to identify the pathophysiology behind ZIKV-associated GBS and its optimal treatment. Prevention is fundamental to limiting infection and spread of ZIKV.

BACKGROUND:In clinical practice, do-not-intubate (DNI) orders are generally accompanied by do-not-resuscitate (DNR) orders. Use of do-not-resuscitate (DNR) orders is associated with older patient age, more comorbid conditions, and the withholding of treatments outside of the cardiac arrest setting. Previous studies have not unpacked the factors independently associated with DNI orders. OBJECTIVE:To compare factors associated with combined DNR/DNI orders versus isolated DNR orders, as a means of elucidating factors associated with the addition of DNI orders. DESIGN/METHODS:Retrospective chart review. SETTING/SUBJECTS/METHODS:Patients who died on a General Medicine or MICU service (n = 197) at an urban public hospital over a 2-year period. MEASUREMENTS/METHODS:Logistic regression was used to identify demographic and medical data associated with code status. RESULTS:Compared with DNR orders alone, DNR/DNI orders were associated with a higher median Charlson Comorbidity Index (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.13-1.43); older age (OR 1.02, 95% CI 1.01-1.04); malignancy (OR 2.27, 95% CI 1.18-4.37); and female sex (OR 1.98, 95% CI 1.02-3.87). In the last 3 days of life, they were associated with morphine administration (OR 2.76, 95% CI 1.43-5.33); and negatively associated with use of vasopressors/inotropes (OR 10.99, 95% CI 4.83-25.00). CONCLUSIONS:Compared with DNR orders alone, combined DNR/DNI orders are more strongly associated with many of the same factors that have been linked to DNR orders. Awareness of the extent to which the two directives may be conflated during code status discussions is needed to promote patient-centered application of these interventions.

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.