Effect of age, COPD severity, and cigarette smoke exposure on bronchial epithelial barrier function.

We investigated the effect of age, cigarette smoke, and chronic obstructive pulmonary disease (COPD) severity on epithelial barrier function. Primary bronchial epithelial cells (PBECs) were obtained from bronchial brushings in eight younger and eight older never-smokers; seven older ex-smokers without COPD, eight patients with COPD Global Initiative for Chronic Obstructive Lung Disease (GOLD) I-III and six patients with COPD GOLD IV, and cultured in the absence/presence of cigarette smoke extract (CSE). Epithelial barrier function was assessed by electric resistance sensing and expression of junctional and antioxidant genes/proteins quantified by qPCR/immunodetection.

IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels.

IL-33 is a proinflammatory cytokine thought to play a role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). A recent clinical trial using an anti-IL-33 antibody showed a reduction in exacerbation and improved lung function in ex-smokers but not current smokers with COPD. This study aimed to understand the effects of smoking status on IL-33.

CRISPR single base-editing: in silico predictions to variant clonal cell lines.

Engineering single base edits using CRISPR technology including specific deaminases and single-guide RNA (sgRNA) is a rapidly evolving field. Different types of base edits can be constructed, with cytidine base editors (CBEs) facilitating transition of C-to-T variants, adenine base editors (ABEs) enabling transition of A-to-G variants, C-to-G transversion base editors (CGBEs) and recently adenine transversion editors (AYBE) that create A-to-C and A-to-T variants. The base-editing machine learning algorithm BE-Hive predicts which sgRNA and base editor combinations have the strongest likelihood of achieving desired base edits.

Early transcriptional responses of bronchial epithelial cells to whole cigarette smoke mirror those of in-vivo exposed human bronchial mucosa.

Background: Despite the well-known detrimental effects of cigarette smoke (CS), little is known about the complex gene expression dynamics in the early stages after exposure. This study aims to investigate early transcriptomic responses following CS exposure of airway epithelial cells in culture and compare these to those found in human CS exposure studies.

Methods: Primary bronchial epithelial cells (PBEC) were differentiated at the air-liquid interface (ALI) and exposed to whole CS.

Increased SARS-CoV-2 Infection, Protease, and Inflammatory Responses in Chronic Obstructive Pulmonary Disease Primary Bronchial Epithelial Cells Defined with Single-Cell RNA Sequencing.

Patients with chronic obstructive pulmonary disease (COPD) develop more severe coronavirus disease (COVID-19); however, it is unclear whether they are more susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and what mechanisms are responsible for severe disease. To determine whether SARS-CoV-2 inoculated primary bronchial epithelial cells (pBECs) from patients with COPD support greater infection and elucidate the effects and mechanisms involved. We performed single-cell RNA sequencing analysis on differentiated pBECs from healthy subjects and patients with COPD 7 days after SARS-CoV-2 inoculation.