Over the last 10 years, several large clinical trials have been conducted to investigate the safety and efficacy of new medications for the treatment of idiopathic pulmonary fibrosis (IPF). Based on the results of those trials, the 2011 ATS/ERS/JRS/ALAT Clinical Practice Guideline for IPF was updated in 2015 (1). The updates included conditional recommendations to use two FDA-approved antifibrotic medications (pirfenidone and nintedanib). Since the 2015 Guideline, new data from phase 4 studies employing these antifibrotic drugs have become available. Tables 1,2 highlight features of phase 3 and 4 clinical trials respectively for nintedanib and pirfenidone. PirfenidonePirfenidone is an antifibrotic and anti-inflammatory medication that decreases both fibroblast proliferation and the accumulation of collagen (8). In 2010, a randomized

Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity, and diabetes. We examined the association between hypertension, obesity, and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. RESEARCH DESIGN AND METHODS Data were collected from 287 consecutive patients with COVID-19 hospitalized at two hospitals in New Orleans, LA from 30 March to 5 April 2020. MetS was identified per World Health Organization criteria. RESULTS Among 287 patients (mean age 61.5 years; female, 56.8%; non-Hispanic black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR] 3.42 [95% CI 1.52-7.69]), intensive care unit (ICU) (aOR 4.59 [CI 2.53-8.32]), invasive mechanical ventilation (IMV) (aOR 4.71 [CI 2.50-8.87]), and acute respiratory distress syndrome (ARDS) (aOR 4.70 [CI 2.25-9.82]) compared with non-MetS. Multivariable analyses of hypertension, obesity, and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR 2.18 [CI, 1.25-3.81]), ARDS (aOR 2.44 [CI 1.28-4.65]), and IMV (aOR 2.36 [CI 1.33-4.21]). Diabetes was associated with ICU (aOR 2.22 [CI 1.24-3.98]) and IMV (aOR 2.12 [CI 1.16-3.89]). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, CRP, and lactate dehydrogenase (LDH) were associated with mortality (CRP [aOR 3.66] [CI 1.22-10.97] and LDH [aOR 3.49] [CI 1.78-6.83]). CONCLUSIONS In predominantly black patients hospitalized for COVID-19, the clustering of hypertension, obesity, and diabetes as MetS increased the odds of mortality compared with these comorbidities individually. Coronavirus disease 2019 (COVID-19), first described in Wuhan, China in December 2019, is caused by the severe acute respiratory syndrome coronavirus 2 (1). It has spread rapidly worldwide, infecting .7 million people as of 18 June 2020, with the U.S. leading the world both in number of cases (;2 million) and fatalities (.100,000) (2). New Orleans, LA was an early epicenter, with the highest death rate per capita in the U.S. (37.93 per 100,000 people) noted in early April (3). One-third of individuals hospitalized for COVID-19 have severe pneumonia requiring admission to an intensive

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative lung disease with high mortality, and fibroblast‐myofibroblast differentiation (FMD) is thought to be a key event in the pathogenesis of IPF. Histone deacetylase 8 (HDAC8) has been shown to associate with α‐smooth muscle actin (α‐SMA; a marker of FMD) and regulates cell contractility in vascular smooth muscle cells. However, the role of HDAC8 in FMD or pulmonary fibrosis has never been investigated. This study investigated the role of HDAC8 in pulmonary fibrosis, with a focus on FMD. We observed that HDAC8 expression was increased in IPF lung tissue as well as TGF‐β1‐treated normal human lung fibroblasts (NHLFs). Our immunoprecipitation experiments revealed that HDAC8 associated with α‐SMA in TGF‐β1‐treated NHLFs. HDAC8 inhibition with NCC170 (HDAC8‐ selective inhibitor) repressed TGF‐β1‐induced fibroblast contraction and α‐SMA protein expression in NHLFs cultured in collagen gels. HDAC8 inhibition with HDAC8 siRNA also repressed TGF‐β1‐induced expression of CTGF and PAI‐1, and increased PPAR‐γ expression in NHLFs. Chromatin immunoprecipitation quantitative PCR (ChIP‐qPCR) using an antibody against H3K27ac (histone H3 acetylated at lysine 27; a known HDAC8 substrate and a marker for active enhancers) suggested that HDAC8 inhibition with NCC170 ameliorated TGF‐β1‐ induced loss of H3K27ac at the PPAR‐γ gene enhancer. Furthermore, NCC170 treatment significantly decreased fibrosis measured by Ashcroft score as well as type‐1 collagen expression in bleomycin‐treated mouse lungs. In conclusion, these data suggest that HDAC8 contributes to pulmonary fibrosis and that there is a therapeutic potential for HDAC8 inhibitors to treat IPF as well as other fibrotic lung diseases. Support or Funding Information Wetmore Foundation: Shigeki Saito M1: 555007G1; Louisiana Clinical and Translational Science (LA CaTS) Center: Shigeki Saito 1 U54 GM104940 This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

<b>OBJECTIVE</b> Coronavirus disease 2019 (COVID-19) mortality is high in patients with hypertension, obesity and diabetes mellitus. We examined the association between hypertension, obesity and diabetes, individually and clustered as metabolic syndrome (MetS), and COVID-19 outcomes in patients hospitalized in New Orleans during the peak of the outbreak. <p><b>RESEARCH DESIGN AND METHODS</b> Data were collected from 287 consecutive COVID-19 patients hospitalized at two hospitals in New Orleans, Louisiana from March 30^th to April 5^th, 2020. MetS was identified per WHO criteria.</p> <p><b>RESULTS</b> Among 287 patients (mean age, 61.5 years; female, 56.8%; non-Hispanic Black, 85.4%), MetS was present in 188 (66%). MetS was significantly associated with mortality (adjusted odds ratio [aOR]: 3.42, 95% confidence interval [CI]: 1.52-7.69), ICU (aOR: 4.59, CI: 2.53-8.32), invasive mechanical ventilation (IMV) (aOR: 4.71, CI: 2.50-8.87) and acute respiratory distress syndrome (ARDS) (aOR: 4.70, CI: 2.25-9.82), compared with non-MetS. Multivariable analyses of hypertension, obesity and diabetes individually showed no association with mortality. Obesity was associated with ICU (aOR, 2.18, CI, 1.25-3.81), ARDS (aOR, 2.44, CI, 1.28-4.65), and IMV (aOR, 2.36, CI, 1.33-4.21). Diabetes was associated with ICU (aOR, 2.22, CI, 1.24-3.98) and IMV (aOR, 2.12, CI, 1.16-3.89). Hypertension was not significantly associated with any outcome. Inflammatory biomarkers associated with MetS, C-reactive protein (CRP) and lactate dehydrogenase (LDH) were associated with mortality [CRP (aOR, 3.66, CI, 1.22-10.97), LDH (aOR, 3.49, CI, 1.78-6.83)].</p> <p><b>CONCLUSIONS</b> In predominantly Black patients hospitalized for COVID-19, the clustering of hypertension, obesity and diabetes as MetS increased the odds of mortality compared to these comorbidities individually. </p>

Objective Coronavirus disease 2019 (COVID‐19) has disproportionately impacted the African American community. This study aims to identify the risk factors for severe COVID‐19 disease in African American patients. Methods This was a retrospective cross‐sectional analysis of African American patients with COVID‐19 treated between March 12 and April 9, 2020, at a single tertiary center. The primary outcome of interest was severe disease defined as those requiring intensive care unit (ICU) admission. Results The study included 158 consecutive patients. The mean age was 57 years, and 61% were women. The mean (SD) of BMI was 33.2 (8.6) kg/m2. Overall, patients admitted to the ICU were older (62 vs. 55 years, P = 0.003) and had higher BMI (36.5 kg/m2 vs. 31.9 kg/m2, P = 0.002). In unadjusted and adjusted analysis, the factors most associated with ICU admission in this sample were age (adjusted odds ratio [aOR]: 1.073; 95% CI: 1.033‐1.114), BMI (aOR: 1.115; 95% CI: 1.052‐1.182), and lung disease (aOR: 3.097; 95% CI: 1.137‐8.437). Conclusions This study identified risk factors for severe disease in COVID‐19, specifically in an African American population. Further inclusive research aimed at optimizing clinical care relevant to the African American population is critical to ensure an equitable response to COVID‐19.