Faculty Bibliography

INTRODUCTION:Respiratory infections are ubiquitous. The COVID-19 pandemic has refocused our attention on how morbid and potentially fatal they can be, and how host factors have an impact on the clinical course and outcomes. Due to a range of vulnerabilities, patients with sarcoidosis may be at higher risk of poor outcomes from respiratory infections. The objective of the SARCoidosis Outcomes in all respiratory Viral Infectious Diseases (SARCOVID) Study is to determine the short-term and long-term impacts of respiratory viral illnesses (COVID-19 and non-COVID-19) in sarcoidosis. METHODS AND ANALYSIS:Up to 20 clinical sites across the USA are participating in the recruitment of 2000 patients for this observational, prospective study. To ensure that the study cohort is representative of the general population with sarcoidosis, participating sites include those dedicated to reaching under-represented minorities or patients from non-urban areas. Baseline data on demographic features, comorbidities, sarcoidosis characteristics and pre-enrolment lung function will be captured at study entry. During this 3-year study, all acute respiratory infectious events (from SARS-CoV-2 and any other respiratory pathogen) will be assessed and recorded at quarterly intervals. The level of required medical care and survival outcomes determine infection severity, and the impact of infection on quality of life measures will be recorded. Post-infection lung function and imaging results will measure the long-term impact on the trajectory of sarcoidosis. Patients will be analysed according to the clinical phenotypes of cardiac and fibrotic pulmonary sarcoidosis. Control groups include non-infected patients with sarcoidosis and patients with non-sarcoidosis interstitial lung disease. ETHICS AND DISSEMINATION:Each site received local institutional review board approval prior to enrolling patients, with the consent process determined by local institution standards. Data will be published in a timely manner (goal <12 months) at the conclusion of the 3-year follow-up period and will be made available upon request.

BACKGROUND:The novel coronavirus-associated ARDS (COVID-19 ARDS) often requires invasive mechanical ventilation. A spectrum of atypical ARDS with different phenotypes (high vs low static compliance) has been hypothesized in COVID-19. METHODS:test, chi-square test, ANOVA test, and Pearson correlation was used to identify relationship between subject variables and respiratory mechanics. The primary outcome was duration of mechanical ventilation. Secondary outcomes were correlation between fluid status, C- reactive protein, PEEP, and D-dimer with respiratory and ventilatory parameters. RESULTS:= .02). CONCLUSIONS:In our cohort of mechanically ventilated COVID-19 ARDS subjects, high PEEP and D-dimer were associated with increase in physiologic dead space without significant effect on oxygenation, raising the question of potential microvascular dysfunction.

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

Sarcoidosis is a systemic granulomatous disease of unknown etiology. It may develop in response to an exposure or inflammatory trigger in the background of a genetically primed abnormal immune response. Thus, genetic studies are potentially important to our understanding of the pathogenesis of sarcoidosis. We developed a case-control study which explored the genetic variations between firefighters in the Fire Department of the City of New York (FDNY) with World Trade Center (WTC)-related sarcoidosis and those with WTC exposure, but without sarcoidosis. The loci of fifty-one candidate genes related to granuloma formation, inflammation, immune response, and/or sarcoidosis were sequenced at high density in enhancer/promoter, exonic, and 5' untranslated regions. Seventeen allele variants of human leukocyte antigen (HLA) and non-HLA genes were found to be associated with sarcoidosis, and all were within chromosomes 1 and 6. Our results also suggest an association between extrathoracic involvement and allele variants of HLA and non-HLA genes found not only on chromosomes 1 and 6, but also on chromosomes 16 and 17. We found similarities between genetic variants with WTC-related sarcoidosis and those reported previously in sporadic sarcoidosis cases within the general population. In addition, we identified several allele variants never previously reported in association with sarcoidosis. If confirmed in larger studies with known environmental exposures, these novel findings may provide insight into the gene-environment interactions key to the development of sarcoidosis.

Background: Sarcoidosis is a granulomatous disease involving intrathoracic and extrathoracic organs. Genetic and environmental factors, such as exposure to World-Trade Center (WTC) dust after 9/11, may play a role in clinical presentation. Characterization of sarcoidosis in community members with exposure to the WTC dust can provide further insight into the relationship between environmental exposure and sarcoidosis. Methods: Patients with documented sarcoidosis were identified in the WTC Environmental Health Center (EHC), a treatment program for community members. Demographic and clinical data were collected from standardized questionnaires and chart review. Organ involvement was assessed with a standard instrument. Results: Among patients in the WTC EHC, 87 were identified with sarcoidosis after 9/11. Sarcoidosis cases were more likely African-American, local workers, and had more respiratory symptoms, compared with non-sarcoidosis WTC EHC patients. Many (46%) had ≥ Scadding stage 3 on chest imaging, and had reduced lung function measures. Extrathoracic involvement was identified in 33/87 (38%) with a diversity of organs involved. Conclusions: WTC-exposed sarcoidosis in community members is often characterized by severe pulmonary disease and a high rate of diverse extrathoracic involvement. Further analysis is required to characterize the course of disease progression or resolution.

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.