Restoring Pulmonary and Sleep Services as the COVID-19 Pandemic Lessens. From an Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society-coordinated Task Force.

In March 2020, many elective medical services were canceled in response to the coronavirus disease 2019 (COVID-19) pandemic. The daily case rate is now declining in many states and there is a need for guidance about the resumption of elective clinical services for patients with lung disease or sleep conditions. Volunteers were solicited from the Association of Pulmonary, Critical Care, and Sleep Division Directors and American Thoracic Society.

Role of mTOR As an Essential Kinase in SCLC.

Objectives: SCLC represents 15% of all lung cancer diagnoses in the United States and has a particularly poor prognosis. We hypothesized that kinases regulating SCLC survival pathways represent therapeutically targetable vulnerabilities whose inhibition may improve SCLC outcome.

Methods: A short-hairpin RNA (shRNA) library targeting all human kinases was introduced in seven chemonaive patient-derived xenografts (PDX) and the cells were cultured in vitro and in vivo.

Identifying Smoking-Related Disease on Lung Cancer Screening CT Scans: Increasing the Value.

Background: Lung cancer screening (LCS) via chest computed tomography (CT) scans can save lives by identifying early-stage tumors. However, most smokers die of comorbid smoking-related diseases. LCS scans contain information about smoking-related conditions that is not currently systematically assessed.

Interleukin-6 is required for Neuregulin-1 induced HER2 signaling in lung epithelium.

A clear understanding of the mechanisms that regulate the alveolar epithelium's barrier is critical to develop new therapeutic strategies to mitigate lung injury. The HER2/HER3 receptor tyrosine kinase complex plays a central role in maintaining the alveolar-capillary barrier. This receptor complex is activated by its ligand, neuregulin-1 (NRG-1).

The Kinome of Human Alveolar Type II and Basal Cells, and Its Reprogramming in Lung Cancer.

The discovery of mutant tyrosine kinases as oncogenic drivers of lung adenocarcinomas has changed the basic understanding of lung cancer development and therapy. Yet, expressed kinases (kinome) in lung cancer progenitor cells, as well as whether kinase expression and the overall kinome changes or is reprogrammed upon transformation, is incompletely understood. We hypothesized that the kinome differs between lung cancer progenitor cells, alveolar type II cells (ATII), and basal cells (BC) and that their respective kinomes undergo distinct lineage-specific reprogramming to adenocarcinomas and squamous cell carcinomas upon transformation.

IL-13 induces periostin and eotaxin expression in human primary alveolar epithelial cells: Comparison with paired airway epithelial cells.

Alveolar epithelial cells are critical to the pathogenesis of pulmonary inflammation and fibrosis, which are associated with overexpression of type 2 cytokine IL-13. IL-13 is known to induce the production of profibrotic (e.g.

Do COPD subtypes really exist? COPD heterogeneity and clustering in 10 independent cohorts.

Background: COPD is a heterogeneous disease, but there is little consensus on specific definitions for COPD subtypes. Unsupervised clustering offers the promise of 'unbiased' data-driven assessment of COPD heterogeneity. Multiple groups have identified COPD subtypes using cluster analysis, but there has been no systematic assessment of the reproducibility of these subtypes.

Cigarette Smoke Induces Human Epidermal Receptor 2-Dependent Changes in Epithelial Permeability.

The airway epithelium constitutes a protective barrier against inhaled insults, such as viruses, bacteria, and toxic fumes, including cigarette smoke (CS). Maintenance of bronchial epithelial integrity is central for airway health, and defective epithelial barrier function contributes to the pathogenesis of CS-mediated diseases, such as chronic obstructive pulmonary disease. Although CS has been shown to increase epithelial permeability, current understanding of the mechanisms involved in CS-induced epithelial barrier disruption remains incomplete.

Pulmonary epithelial barrier function: some new players and mechanisms.

The pulmonary epithelium serves as a barrier to prevent access of the inspired luminal contents to the subepithelium. In addition, the epithelium dictates the initial responses of the lung to both infectious and noninfectious stimuli. One mechanism by which the epithelium does this is by coordinating transport of diffusible molecules across the epithelial barrier, both through the cell and between cells.

MUC18 Differentially Regulates Pro-Inflammatory and Anti-Viral Responses in Human Airway Epithelial Cells.

Objective: MUC18 or CD146, a transmembrane glycoprotein, is mainly expressed by endothelial cells and smooth muscle cells where it serves as a cell-cell adhesion molecule. We have found MUC18 up-regulation in airway epithelial cells of patients with asthma and chronic obstructive pulmonary disease (COPD). However, the function of MUC18 in airway epithelial cells remains unclear.

HER2 activation results in β-catenin-dependent changes in pulmonary epithelial permeability.

The receptor tyrosine kinase human epidermal growth factor receptor-2 (HER2) is known to regulate pulmonary epithelial barrier function; however, the mechanisms behind this effect remain unidentified. We hypothesized that HER2 signaling alters the epithelial barrier through an interaction with the adherens junction (AJ) protein β-catenin, leading to dissolution of the AJ. In quiescent pulmonary epithelial cells, HER2 and β-catenin colocalized along the lateral intercellular junction.

Establishing reference intervals for bone turnover markers in healthy postmenopausal women in a nonfasting state.

In order to interpret bone turnover markers (BTMs), we need to establish healthy reference intervals. It is difficult to establish reference intervals for older women because they commonly suffer from diseases or take medications that affect bone turnover. The aims of this study were: (1) to identify diseases and drugs that have a substantial effect on BTMs; (2) to establish reference intervals for premenopausal and postmenopausal women; and (3) to examine the effects of other factors on BTMs in healthy postmenopausal women.

Bioinformatics-driven discovery of rational combination for overcoming EGFR-mutant lung cancer resistance to EGFR therapy.

Motivation: Non-small-cell lung cancer (NSCLC) is the leading cause of cancer death in the United States. Targeted tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) have been widely and successfully used in treating NSCLC patients with activating EGFR mutations. Unfortunately, the duration of response is short-lived, and all patients eventually relapse by acquiring resistance mechanisms.

Lung fibroblasts accelerate wound closure in human alveolar epithelial cells through hepatocyte growth factor/c-Met signaling.

There are 190,600 cases of acute lung injury/acute respiratory distress syndrome (ALI/ARDS) each year in the United States, and the incidence and mortality of ALI/ARDS increase dramatically with age. Patients with ALI/ARDS have alveolar epithelial injury, which may be worsened by high-pressure mechanical ventilation. Alveolar type II (ATII) cells are the progenitor cells for the alveolar epithelium and are required to reestablish the alveolar epithelium during the recovery process from ALI/ARDS.

Lung cancer screening: past, present and future.

Lung cancer is the leading cause of cancer death for men and women. Most lung cancer cases are diagnosed at an advanced stage, when cure is no longer an option; this heavily influences mortality. Historically, attempts at lung cancer screening using chest x-rays and sputum cytology have failed to influence lung cancer mortality.

Adherence to raloxifene therapy: assessment methods and relationship with efficacy.

Unlabelled: Response to therapy depends on patient compliance but accurate assessment is difficult and adequate levels of adherence are uncertain. Adherence to raloxifene treatment may be assessed more accurately by electronic monitoring than by counting returned tablets. The level of adherence is positively associated with the degree of bone response.

Supine vs decubitus lateral patient positioning in vertebral fracture assessment.

In vertebral fracture assessment (VFA), lateral scans are obtained with the patient positioned supine (C-arm densitometers) or lateral decubitus (fixed-arm densitometers). We aimed to determine the impact of positioning on image quality and fracture definition. We performed supine and decubitus lateral VFA in 50 postmenopausal women and used the algorithm-based qualitative method to identify vertebral fractures.

Human epidermal growth factor receptor signaling in acute lung injury.

Acute lung injury (ALI) is a syndrome marked by increased permeability across the pulmonary epithelium resulting in pulmonary edema. Recent evidence suggests that members of the human epidermal growth factor receptor (HER) family are activated in alveolar epithelial cells during ALI and regulate alveolar epithelial barrier function. These tyrosine kinase receptors, which also participate in the pathophysiology of pulmonary epithelial malignancies, regulate cell growth, differentiation, and migration as well as cell-cell adhesion, all processes that influence epithelial injury and repair.

Endogenous estradiol and the risk of incident fracture in postmenopausal women: the OPUS study.

Some, but not all, studies have found that low endogenous estradiol levels in postmenopausal women are predictive of fractures. The aim of this study was to examine the roles of endogenous estradiol (E(2)), sex hormone binding globulin (SHBG), and dehydroepiandrosterone sulfate (DHEAS) in the prediction of incident vertebral and nonvertebral fractures. The study subjects were 797 postmenopausal women from the population-based OPUS (Osteoporosis and Ultrasound Study) study.

Bronchoalveolar lavage neuregulin-1 is elevated in acute lung injury and correlates with inflammation.

Shedding of neuregulin (NRG)-1 from the pulmonary epithelium leads to activation of the epithelial human epidermal growth factor receptor (HER)2 receptor, increased pulmonary epithelial permeability and acute lung injury (ALI). We sought to determine whether NRG-1 was detectable and elevated in bronchoalveolar lavage (BAL) and plasma from patients with ALI compared with controls and to determine whether a correlation exists between NRG-1 and inflammation and outcome in ALI. Matched BAL and plasma samples were obtained from 23 ALI patients requiring intubation and mechanical ventilation.

Evaluation and treatment of patients with non-small cell lung cancer.

Lung cancer is the most common cause of cancer-related death in the United States; however, recent clinical advances may change this outcome. New data on low-dose computed tomography for lung cancer screening, and technologic advances in surgery and radiation, have improved outcomes for those with early-stage disease. Identification of driver mutations in lung cancer has led to the development of molecular targeted therapy to improve survival of subsets of patients with metastatic disease.

Neuregulin-1-human epidermal receptor-2 signaling is a central regulator of pulmonary epithelial permeability and acute lung injury.

The mechanisms behind the loss of epithelial barrier function leading to alveolar flooding in acute lung injury (ALI) are incompletely understood. We hypothesized that the tyrosine kinase receptor human epidermal growth factor receptor-2 (HER2) would be activated in an inflammatory setting and participate in ALI. Interleukin-1β (IL-1β) exposure resulted in HER2 activation in human epithelial cells and markedly increased conductance across a monolayer of airway epithelial cells.