Electrophilic PPARγ Ligands Attenuate IL-1β and Silica-Induced Inflammatory Mediator Production in Human Lung Fibroblasts via a PPARγ-Independent Mechanism

Acute and chronic lung inflammation is associated with numerous important disease pathologies including asthma, chronic obstructive pulmonary disease and silicosis. Lung fibroblasts are a novel and important target of anti-inflammatory therapy, as they orchestrate, respond to, and amplify inflammatory cascades and are the key cell in the pathogenesis of lung fibrosis. Peroxisome proliferator-activated receptor gamma (PPARγ) ligands are small molecules that induce anti-inflammatory responses in a variety of tissues. Here, we report for the first time that PPARγ ligands have potent anti-inflammatory effects on human lung fibroblasts. 2-cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid (CDDO) and 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) inhibit production of the inflammatory mediators interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), COX-2, and prostaglandin (PG)E2 in primary human lung fibroblasts stimulated with either IL-1β or silica. The anti-inflammatory properties of these molecules are not blocked by the PPARγ antagonist GW9662 and thus are largely PPARγ independent. However, they are dependent on the presence of an electrophilic carbon. CDDO and 15d-PGJ2, but not rosiglitazone, inhibited NF-κB activity. These results demonstrate that CDDO and 15d-PGJ2 are potent attenuators of proinflammatory responses in lung fibroblasts and suggest that these molecules should be explored as the basis for novel, targeted anti-inflammatory therapies in the lung and other organs

Impact of Pulmonary Rehabilitation Stewardship Program on COPD Patients, Quality Improvement Project

Background: Pulmonary rehabilitation (PR) has multiple benefits in COPD patients. There are multiple barriers to utilize PR including lack of knowledge about the benefits of PR by providers. Objective: We are conducting a Quality Improvement project to improve the referral rate of patients hospitalized for acute exacerbation of COPD to PR. Methods: All patients admitted with a primary diagnosis of acute exacerbation of COPD requiring systemic steroids to Rochester General Hospital in the period between 7/1/2019 and 7/31/2019 were reviewed retrospectively. Between 7/15/2020 and 11/15/2020, we started a PR stewardship program, where we daily review patients hospitalized with acute COPD exacerbation, and then a note will be placed in the chart for the primary team to consider referring patients to PR upon discharge, patients\u27 charts were reviewed after discharge. The rate of referral before and after the intervention was compared. Results: During the pre-intervention period, 16 patients (mean age 67.7) with confirmed COPD by spirometry were hospitalized for COPD exacerbation, among them only 2 were referred to PR upon discharge (12.5%). During the post intervention period, 16 patients (mean age 65.0) were admitted with acute COPD exacerbation, among them 10 were referred to PR upon discharge (62.5%) [50% difference (16.5%-71%, 95% CI), P value = 0.004]. Conclusion: In our QI improvement project, we conclude that having a PR stewardship program to review patients hospitalized with COPD exacerbation significantly improves the referral rate to PR, and might help to improve utilization of those programs by patients who need them

Liver Abscesses Due to Fusobacterium nucleatum: A Case Series

Fusobacteriae are anaerobic gram-negative bacilli, classically involved in the development of septic thrombophlebitis of the internal jugular vein in Lemierre syndrome. The goal of this study is to describe the various presentations, treatment course, and outcomes of patients with Fusobacterium liver abscess(es) and review available literature on this topic. We retrospectively reviewed our microbiologic database for positive cultures of Fusobacteriae species in a tertiary care hospital from July 2018 through November 2022 and identified 5 cases of liver abscess that involved Fusobacterium nucleatum species. Patients presented with a syndrome of fever and chills, abdominal pain, and nausea and vomiting. Laboratory investigations revealed leukocytosis and transaminitis, and imaging revealed liver abscess(es). The identification of the F. nucleatum bacteria involved invasive aspiration of the abscess in all but one case, where it was identified on blood cultures. One patient had a florid picture of sepsis and acute respiratory distress syndrome. All patients responded well with intravenous antibiotics and were discharged home to complete a prolonged course until radiographic resolution. In 3 patients, history and imaging were suggestive of possible sources that may have hematogenously spread to the liver, with history of recent appendectomy in 1 patient, possible appendicitis on computed tomography of the abdomen in another patient, and recent dental manipulation in the third patient. In conclusion, Fusobacteriae should be included in the differential diagnosis of liver abscess, especially in the setting of recent appendicitis or dental disease. Effective treatment includes surgical drainage when feasible and prolonged course of antibiotics with goal of radiologic resolution