α4 Nicotinic Acetylcholine Receptors in Lipopolysaccharide-Related Lung Inflammation.

Sepsis remains an important healthcare challenge. The lungs are often affected in sepsis, resulting in acute lung injury characterized by inflammation. Mechanisms involving lipopolysaccharide (LPS) stimulation of toll-like receptor (TLR) signaling with induction of proinflammatory pathways have been implicated in this process.

Mortality and Health Outcomes Among Patients With Sarcoidosis Treated With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers.

Background: Sarcoidosis is a multisystem inflammatory disease in which management and outcomes can vary widely. The renin-angiotensin-aldosterone system (RAAS) has been implicated in its pathogenesis, yet the impact of RAAS modulators on health outcomes in sarcoidosis remains poorly understood.

Research Question: How do pharmacologic modulators of RAAS affect health outcomes in patients with a diagnosis of sarcoidosis?.

Pulmonary manifestations of alpha 1 antitrypsin deficiency.

Alpha 1 antitrypsin deficiency is a widely under recognized autosomal codominant condition caused by genetic mutations in the SERPINA 1 gene, which encodes for alpha 1 antitrypsin (AAT), a serine protease inhibitor. The SERPINA 1 gene contains 120 variants and mutations in the gene may decrease AAT protein levels or result in dysfunctional proteins. This deficiency leads to unopposed protease activity in tissues, thereby promoting pulmonary and hepatic disease.

Circulating metabolic profile in idiopathic pulmonary fibrosis: data from the IPF-PRO Registry.

Background: The circulating metabolome, reflecting underlying cellular processes and disease biology, has not been fully characterized in patients with idiopathic pulmonary fibrosis (IPF). We evaluated whether circulating levels of metabolites correlate with the presence of IPF, with the severity of IPF, or with the risk of clinically relevant outcomes among patients with IPF.

Methods: We analyzed enrollment plasma samples from 300 patients with IPF in the IPF-PRO Registry and 100 individuals without known lung disease using a set of targeted metabolomics and clinical analyte modules.

Strategies for developing a successful career in academic medicine.

Academic medicine provides physicians an opportunity for long-term career satisfaction and fulfillment. However, despite the potential for great reward, academic careers can be challenging. To better define approaches to successfully navigate academic medicine, the Southern Society for Clinical Investigation sponsored a workshop titled 'Successful Careers in Academic Medicine' during the 2023 Southern Regional Meeting held in New Orleans; the critical elements of which are highlighted in the following summary.

Racial and ethnic disparities in antifibrotic therapy in idiopathic pulmonary fibrosis.

Background And Objective: Racial disparities have been documented in care of many respiratory diseases but little is known about the impact of race on the treatment of interstitial lung diseases. The purpose of this study was to determine how race and ethnicity influence treatment of idiopathic pulmonary fibrosis.

Methods: Adults with idiopathic pulmonary fibrosis (>18 years) were identified using TriNetX database and paired-wised comparisons were performed for antifibrotic treatment among White, Black, Hispanic and Asian patients.

Pulmonary fibrosis and COVID-19.

The COVID-19 pandemic has caused the death of millions and many more have been infected worldwide. The causative virus, SARS-CoV-2, affects the lung where it elicits an aggressive inflammatory response leading to respiratory failure in severe cases. This infection has been linked to pulmonary fibrosis, a process characterized by fibroproliferation and the exaggerated deposition of collagen and other extracellular matrices.

Evaluation of Donor Lungs for Transplantation: The Efficacy of Screening Bronchoscopy for Detecting Donor Aspiration and Its Relationship to the Resulting Allograft Function in Corresponding Recipients.

Background: Potential organ donors often have suffered anoxic and/or traumatic brain injury during which they may have experienced aspiration of gastric material (AGM). Evaluation of such donors typically includes a screening bronchoscopic examination during which determinations of aspiration are made. The efficacy of this visual screening and its relationship to post-transplant allograft function are unknown.

Fibroblasts-Warriors at the Intersection of Wound Healing and Disrepair.

Wound healing is triggered by inflammation elicited after tissue injury. Mesenchymal cells, specifically fibroblasts, accumulate in the injured tissues, where they engage in tissue repair through the expression and assembly of extracellular matrices that provide a scaffold for cell adhesion, the re-epithelialization of tissues, the production of soluble bioactive mediators that promote cellular recruitment and differentiation, and the regulation of immune responses. If appropriately deployed, these processes promote adaptive repair, resulting in the preservation of the tissue structure and function.

Idiopathic Pulmonary Fibrosis Is Associated with Common Genetic Variants and Limited Rare Variants.

Idiopathic pulmonary fibrosis (IPF) is a rare, irreversible, and progressive disease of the lungs. Common genetic variants, in addition to nongenetic factors, have been consistently associated with IPF. Rare variants identified by candidate gene, family-based, and exome studies have also been reported to associate with IPF.

Fibroblast-derived conditioned media promotes lung cancer progression.

Lung cancer is the leading cause of cancer death in men and women in the United States. Recent studies have implicated the tumor microenvironment as a new chemotherapeutic target by demonstrating the importance of tumor cell-stromal interactions in cancer progression. However, the exact mechanisms by which tumor cell-stromal interactions drive lung cancer progression remain undefined, particularly in the lung.

Mice lacking α4 nicotinic acetylcholine receptors are protected against alcohol-associated liver injury.

Background: Chronic heavy alcohol consumption is a major risk factor for the development of liver steatosis, fibrosis, and cirrhosis, but the mechanisms by which alcohol causes liver damage remain incompletely elucidated. This group has reported that α4 nicotinic acetylcholine receptors (α4 nAChRs) act as sensors for alcohol in lung cells. This study tested the hypothesis that α4 nAChRs mediate the effects of alcohol in the liver.

Association of Circulating Proteins with Death or Lung Transplant in Patients with Idiopathic Pulmonary Fibrosis in the IPF-PRO Registry Cohort.

Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease with a variable clinical course. Biomarkers that predict patient outcomes are needed. We leveraged data from 300 patients in the multicenter IPF-PRO Registry to determine associations between circulating proteins and the composite outcome of respiratory death or lung transplant.

The profibrotic and senescence phenotype of old lung fibroblasts is reversed or ameliorated by genetic and pharmacological manipulation of Slc7a11 expression.

Increased senescence and expression of profibrotic genes in old lung fibroblasts contribute to disrepair responses. We reported that primary lung fibroblasts from old mice have lower expression and activity of the cystine transporter Slc7a11/xCT than cells from young mice, resulting in changes in both the intracellular and extracellular redox environments. This study examines the hypothesis that low Slc7a11 expression in old lung fibroblasts promotes senescence and profibrotic gene expression.

Glutamine restores mitochondrial respiration in bleomycin-injured epithelial cells.

Whether from known or unknown causes, loss of epithelial repair plays a central role in the pathogenesis of pulmonary fibrosis. Recently, diminished mitochondrial function has been implicated as a factor contributing to the loss of epithelial repair but the mechanisms mediating these changes have not been defined. Here, we investigated the factors contributing to mitochondrial respiratory dysfunction after bleomycin, a widely accepted agent for modeling pulmonary fibrosis in mice and in vitro systems.

Donor factors and risk of primary graft dysfunction and mortality post lung transplantation: A proposed conceptual framework.

Lung transplantation remains a therapeutic option in end-stage lung disease. However, despite advances in the field, early allograft function can be compromised by the development of primary graft dysfunction (PGD); this being the leading cause of morbidity and mortality immediately following the lung transplant procedure. Several recipient factors have been associated with increased risk of PGD, but less is known about donor factors.

Enhancing Recruitment and Retention of Minority Populations for Clinical Research in Pulmonary, Critical Care, and Sleep Medicine: An Official American Thoracic Society Research Statement.

Well-designed clinical research needs to obtain information that is applicable to the general population. However, most current studies fail to include substantial cohorts of racial/ethnic minority populations. Such underrepresentation may lead to delayed diagnosis or misdiagnosis of disease, wide application of approved interventions without appropriate knowledge of their usefulness in certain populations, and development of recommendations that are not broadly applicable.