Impaired differentiation of small airway basal stem/progenitor cells in people living with HIV.

With highly active anti-retroviral therapy (HAART), higher incidence of airway abnormalities is common in the HIV population consistent with the concept of accelerated lung "aging". Our previous findings demonstrated that HIV induces human airway basal cells (BC) into destructive and inflammatory phenotypes. Since BC function as stem/progenitor cells of the small airway epithelium (SAE), responsible for self-renewal and differentiation of SAE, we hypothesized that BC from people living with HIV (PLWH) may have altered differentiation capacity that contribute to premature aging.

Misalignment between Clinical Mold Antigen Extracts and Airborne Molds Found in Water-damaged Homes.

Epidemiologic studies have demonstrated that exposure to molds and other fungi can play a role in a variety of allergic and pulmonary diseases in susceptible individuals. Species-specific mold antigen extracts are used in the clinical evaluation of suspected mold-related conditions; however, alignment between these extracts and the species of molds identified in the indoor environment of water-damaged homes has not been rigorously evaluated. To identify the predominant genera and species of mold in the air of homes with water damage, mold growth, and/or occupants with respiratory complaints (complaint homes), and to assess their alignment with the mold antigen extracts used in clinical practice.

Up-regulation of ACE2, the SARS-CoV-2 receptor, in asthmatics on maintenance inhaled corticosteroids.

Background: The first step in SARS-CoV-2 infection is binding of the virus to angiotensin converting enzyme 2 (ACE2) on the airway epithelium. Asthma affects over 300 million people world-wide, many of whom may encounter SARS-CoV-2. Epidemiologic data suggests that asthmatics who get infected may be at increased risk of more severe disease.

HIV induces airway basal progenitor cells to adopt an inflammatory phenotype.

Despite the introduction of anti-retroviral therapy, chronic HIV infection is associated with an increased incidence of other comorbidities such as COPD. Based on the knowledge that binding of HIV to human airway basal stem/progenitor cells (BC) induces a destructive phenotype by increased MMP-9 expression through MAPK signaling pathways, we hypothesized that HIV induces the BC to express inflammatory mediators that contribute to the pathogenesis of emphysema. Our data demonstrate that airway BC isolated from HAART-treated HIV nonsmokers spontaneously release inflammatory mediators IL-8, IL-1β, ICAM-1 and GM-CSF.

Current smoking with or without chronic bronchitis is independently associated with goblet cell hyperplasia in healthy smokers and COPD subjects.

COPD, chronic bronchitis (CB) and active smoking have all been associated with goblet cell hyperplasia (GCH) in small studies. Active smoking is strongly associated with CB, but there is a disconnect between CB clinical symptoms and pathology. Chronic cough and sputum production poorly correlate with the presence of GCH or COPD.

Dysregulation of club cell biology in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive, chronic fibrotic lung disease with an irreversible decline of lung function. "Bronchiolization", characterized by ectopic appearance of airway epithelial cells in the alveolar regions, is one of the characteristic features in the IPF lung. Based on the knowledge that club cells are the major epithelial secretory cells in human small airways, and their major secretory product uteroglobin (SCGB1A1) is significantly increased in both serum and epithelial lining fluid of IPF lung, we hypothesize that human airway club cells contribute to the pathogenesis of IPF.

Cell-specific expression of lung disease risk-related genes in the human small airway epithelium.

Background: The human small airway epithelium (SAE) plays a central role in the early events in the pathogenesis of most inherited and acquired lung disorders. Little is known about the molecular phenotypes of the specific cell populations comprising the SAE in humans, and the contribution of SAE specific cell populations to the risk for lung diseases.

Methods: Drop-seq single-cell RNA-sequencing was used to characterize the transcriptome of single cells from human SAE of nonsmokers and smokers by bronchoscopic brushing.

Expression of the SARS-CoV-2 Receptor in the Human Airway Epithelium.

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease (COVID-19), a predominantly respiratory illness. The first step in SARS-CoV-2 infection is binding of the virus to (angiotensin-converting enzyme 2) on the airway epithelium. The objective was to gain insight into the expression of in the human airway epithelium.

Association Between Diaphragmatic Paralysis and Ipsilateral Cervical Spondylosis on MRI.

Purpose: Diaphragmatic paralysis (DP) is an important cause of dyspnea with many underlying etiologies; however, frequently no cause is identified despite extensive investigation. We hypothesized that cervical spondylosis (CS), as manifest by cervical neuroforaminal stenosis on magnetic resonance imaging (MRI), is an underrecognized cause of unilateral DP.

Methods: A retrospective study was performed assessing cervical spine imaging utilization in the investigation of unilateral DP, and the contribution of CS to its pathogenesis.

Role of KRAS in regulating normal human airway basal cell differentiation.

Background: KRAS is a GTPase that activates pathways involved in cell growth, differentiation and survival. In normal cells, KRAS-activity is tightly controlled, but with specific mutations, the KRAS protein is persistently activated, giving cells a growth advantage resulting in cancer. While a great deal of attention has been focused on the role of mutated KRAS as a common driver mutation for lung adenocarcinoma, little is known about the role of KRAS in regulating normal human airway differentiation.

Exaggerated BMP4 signalling alters human airway basal progenitor cell differentiation to cigarette smoking-related phenotypes.

Airway remodelling in chronic obstructive pulmonary disease (COPD) originates, in part, from smoking-induced changes in airway basal stem/progenitor cells (BCs). Based on the knowledge that bone morphogenetic protein 4 (BMP4) influences epithelial progenitor function in the developing and adult mouse lung, we hypothesised that BMP4 signalling may regulate the biology of adult human airway BCs relevant to COPD.BMP4 signalling components in human airway epithelium were analysed at the mRNA and protein levels, and the differentiation of BCs was assessed using the BC expansion and air-liquid interface models in the absence/presence of BMP4, BMP receptor inhibitor and/or small interfering RNAs against BMP receptors and downstream signalling.

Safety and Tolerability of Comprehensive Research Bronchoscopy in Chronic Obstructive Pulmonary Disease. Results from the SPIROMICS Bronchoscopy Substudy.

Rationale: There is an unmet need to investigate the lower airways in chronic obstructive pulmonary disease (COPD) to define pathogenesis and to identify potential markers to accelerate therapeutic development. Although bronchoscopy is well established to sample airways in various conditions, a comprehensive COPD research protocol has yet to be published.

Objectives: To evaluate the safety and tolerability of a comprehensive research bronchoscopy procedure suitable for multicenter trials and to identify factors associated with adverse events.

Exome sequencing-based identification of novel type 2 diabetes risk allele loci in the Qatari population.

Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and lifestyle factors. To date, the majority of genetic studies of T2D have been in populations of European and Asian descent. The focus of this study is on genetic variations underlying T2D in Qataris, a population with one of the highest incidences of T2D worldwide.

Ambient Pollution-related Reprogramming of the Human Small Airway Epithelial Transcriptome.

Rationale: Epidemiologic studies have demonstrated that exposure to particulate matter ambient pollution has adverse effects on lung health, exacerbated by cigarette smoking. Particulate matter less than or equal to 2.5 μm in aerodynamic diameter (PM) is among the most harmful urban pollutants and is closely linked to respiratory disease.

Ontogeny and Biology of Human Small Airway Epithelial Club Cells.

Rationale: Little is known about human club cells, dome-shaped cells with dense cytoplasmic granules and microvilli that represent the major secretory cells of the human small airways (at least sixth-generation bronchi).

Objectives: To define the ontogeny and biology of the human small airway epithelium club cell.

Methods: The small airway epithelium was sampled from the normal human lung by bronchoscopy and brushing.

Correction: Type 2 Diabetes Risk Allele Loci in the Qatari Population.

[This corrects the article DOI: 10.1371/journal.pone.

Type 2 Diabetes Risk Allele Loci in the Qatari Population.

Background: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians.

Methods: All subjects were ≥3 generation Qataris.

Chronic Cough and Bilateral Pneumothoraces in a Nonsmoker.

An 82-year-old Japanese nonsmoking man presented with persistent dry cough and small left apical pneumothorax. High resolution CT scan of the chest demonstrated bilateral upper lobe pleuroparenchymal thickening and architectural distortion. Serial imaging revealed mild progression and development of small bilateral pneumothoraces, and pneumomediastinum.

CXCL9 Regulates TGF-β1-Induced Epithelial to Mesenchymal Transition in Human Alveolar Epithelial Cells.

Epithelial to mesenchymal cell transition (EMT), whereby fully differentiated epithelial cells transition to a mesenchymal phenotype, has been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). CXCR3 and its ligands are recognized to play a protective role in pulmonary fibrosis. In this study, we investigated the presence and extent of EMT and CXCR3 expression in human IPF surgical lung biopsies and assessed whether CXCR3 and its ligand CXCL9 modulate EMT in alveolar epithelial cells.