Faculty Bibliography

Introduction/UNASSIGNED:Biomarkers of metabolic syndrome expressed soon after World Trade Center (WTC) exposure predict development of WTC Lung Injury (WTC-LI). The metabolome remains an untapped resource with potential to comprehensively characterise many aspects of WTC-LI. This case-control study identified a clinically relevant, robust subset of metabolic contributors of WTC-LI through comprehensive high-dimensional metabolic profiling and integration of machine learning techniques. Methods/UNASSIGNED:Never-smoking, male, WTC-exposed firefighters with normal pre-9/11 lung function were segregated by post-9/11 lung function. Cases of WTC-LI (forced expiratory volume in 1s <lower limit of normal, n=15) and controls (n=15) were identified from previous cohorts. The metabolome of serum drawn within 6 months of 9/11 was quantified. Machine learning was used for dimension reduction to identify metabolites associated with WTC-LI. Results/UNASSIGNED:580 metabolites qualified for random forests (RF) analysis to identify a refined metabolite profile that yielded maximal class separation. RF of the refined profile correctly classified subjects with a 93.3% estimated success rate. 5 clusters of metabolites emerged within the refined profile. Prominent subpathways include known mediators of lung disease such as sphingolipids (elevated in cases of WTC-LI), and branched-chain amino acids (reduced in cases of WTC-LI). Principal component analysis of the refined profile explained 68.3% of variance in five components, demonstrating class separation. Conclusion/UNASSIGNED:Analysis of the metabolome of WTC-exposed 9/11 rescue workers has identified biologically plausible pathways associated with loss of lung function. Since metabolites are proximal markers of disease processes, metabolites could capture the complexity of past exposures and better inform treatment. These pathways warrant further mechanistic research.

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.

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.