Faculty Bibliography

Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized.

To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2.

The evolution of lung function, including assessment of small airways, was assessed in individuals enrolled in the World Trade Center Environmental Health Center (WTC-EHC). We hypothesized that a bronchodilator response at initial evaluation shown by spirometry or in small airways, as measured by forced oscillation technique (FOT), would be associated with improvement in large and small airway function over time. Standardized longitudinal assessment included pre and post bronchodilator (BD) spirometry (forced vital capacity, FVC; forced expiratory volume in 1 second, FEV₁) and FOT (resistance at 5 Hz, R₅; resistance at 5 minus 20 Hz, R_5-20). Longitudinal changes were assessed using linear mixed-effects modelling with adjustment for potential confounders (median follow-up 2.86 years; 95% measurements within 4.9 years). Data demonstrated: (1) parallel improvement in airflow and volume measured by spirometry and small airway function (R₅ and R_5-20) measured by FOT; (2) the magnitude of longitudinal improvement was tightly linked to the initial BD response; and (3) longitudinal values for small airway function on FOT were similar to residual abnormality observed post BD at initial visit. These findings suggest presence of reversible and irreversible components of small airway injury that are identifiable at initial presentation. These results have implications for treatment of isolated small airway abnormalities that can be identified by non-invasive effort independent FOT particularly in symptomatic individuals with normal spirometry indices. This study underscores the need to study small airway function to understand physiologic changes over time following environmental and occupational lung injury.

BACKGROUND: Systemic inflammation has emerged as a promising marker and potential mechanism underlying post-traumatic stress disorder (PTSD). The relationship between posttraumatic stress pathology and systemic inflammation has not, however, been consistently replicated and is potentially confounded by comorbid illness or injury, common complications of trauma exposure. METHODS: We analyzed a large naturalistic cohort sharing a discrete physical and mental health trauma from the destruction of the World Trade Center (WTC) towers on September 11, 2001 (n = 641). We evaluated the relationship between multiple physical and mental health related indices collected through routine evaluations at the WTC Environmental Health Center (WTC EHC), a treatment program for community members exposed to the disaster. C-Reactive Protein (CRP), a marker of systemic inflammation, was examined in relation to scores for PTSD, PTSD symptom clusters (re-experiencing, avoidance, negative cognitions/mood, arousal), depression and anxiety, while controlling for WTC exposures, lower respiratory symptoms, age, sex, BMI and smoking as potential risks or confounders. RESULTS: CRP was positively associated with PTSD severity (p < 0.001), trending toward association with depression (p = 0.06), but not with anxiety (p = 0.27). CRP was positively associated with re-experiencing (p < 0.001) and avoidance (p < 0.05) symptom clusters, and trended toward associations with negative cognitions/mood (p = 0.06) and arousal (p = 0.08). CONCLUSIONS: In this large study of the relationship between CRP and posttraumatic stress pathology, we demonstrated an association between systemic inflammation and stress pathology (PTSD; trending with depression), which remained after adjusting for potentially confounding variables. These results contribute to research findings suggesting a salient relationship between inflammation and posttraumatic stress pathology.

OBJECTIVE: Paresthesias can result from metabolic disorders, nerve entrapment following repetitive motions, hyperventilation pursuant to anxiety, or exposure to neurotoxins. We analyzed data from community members exposed to the World Trade Center (WTC) disaster of September 11, 2001, to evaluate whether exposure to the disaster was associated with paresthesias. METHODS: Analysis of data from 3141 patients of the WTC Environmental Health Center. RESULTS: Fifty-six percent of patients reported paresthesias at enrollment 7 to 15 years following the WTC disaster. After controlling for potential confounders, paresthesias were associated with severity of exposure to the WTC dust cloud and working in a job requiring cleaning of WTC dust. CONCLUSIONS: This study suggests that paresthesias were commonly associated with WTC-related exposures or post-WTC cleaning work. Further studies should objectively characterize these paresthesias and seek to identify relevant neurotoxins or paresthesia-inducing activities.This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0.