Epigenetic Inhibitors Differentially Impact TGF-β1 Signaling Cascades in COPD Airway Smooth Muscle Cells.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and incurable airflow obstruction and chronic inflammation. Both TGF-β1 and CXCL8 have been well described as fundamental to COPD progression. DNA methylation and histone acetylation, which are well-understood epigenetic mechanisms regulating gene expression, are associated with COPD progression.

The Role of WNT5a and TGF-β1 in Airway Remodelling and Severe Asthma.

Background: Airway remodelling is a feature of severe asthma with airway epithelial damage observed frequently. We evaluated the role of WNT5a and TGF-β in asthmatic airway biopsies and in sputum and bronchial brushings assessed their role in remodelling.

Methods: WNT5a and TGF-β protein expression were assessed in the lamina propria epithelium of people with asthma (GINA 1-3, n-8 and GINA 4-5, n-14) and healthy subjects (n-9), alongside relevant remodelling markers.

Clinical importance of patient-reported outcome measures in severe asthma: results from U-BIOPRED.

Rationale: Knowledge about the clinical importance of patient-reported outcome measures (PROMs) in severe asthma is limited.

Objectives: To assess whether and to what extent asthma exacerbations affect changes in PROMS over time and asthma-specific PROMs can predict exacerbations in adult patients with severe asthma in usual care.

Methods: Data of 421 patients with severe asthma (62% female; mean age 51.

The Bronchodilator and Anti-Inflammatory Effect of Long-Acting Muscarinic Antagonists in Asthma: An EAACI Position Paper.

As cholinergic innervation is a major contributor to increased vagal tone and mucus secretion, inhaled long-acting muscarinic antagonists (LAMA) are a pillar for the treatment of chronic obstructive pulmonary disease and asthma. By blocking the muscarinic receptors expressed in the lung, LAMA improve lung function and reduce exacerbations in asthma patients who remained poorly controlled despite treatment with inhaled corticosteroids and long-acting β2 agonists. Asthma guidelines recommend LAMA as a third controller to be added on before the initiation of biologicals.

Single-cell RNA sequencing reveals transcriptional changes in circulating immune cells from patients with severe asthma induced by biologics.

Patients with severe eosinophilic asthma often require systemic medication, including corticosteroids and anti-type 2 (T2) cytokine biologics, to control the disease. While anti-IL5 and anti-IL4Rα antibodies suppress the effects of IL-4, IL-5 and IL-13, the molecular pathways modified by these biologics that are associated with clinical improvement remain unclear. Therefore, we aimed to describe the effects of T2-targeting biologics on the gene expression of blood immune cells.

Longitudinal multi-trajectory phenotypes of severe eosinophilic asthma on type 2 biologics treatment.

Background: Limited understanding exists regarding the progression trajectory of severe eosinophilic asthma (SEA) patients on type 2 biologics therapies.

Objective: We aim to explore distinct longitudinal phenotypes of these patients based on crucial asthma biomarkers.

Methods: We enrolled 101 adult patients with SEA.

Development of an asthma health-care burden score as a measure of severity and predictor of remission in SARP III and U-BIOPRED: results from two major longitudinal asthma cohorts.

Background: Current asthma guidelines, including those of the European Respiratory Society (ERS) and American Thoracic Society (ATS), suboptimally predict asthma remission, disease severity, and health-care utilisation. We aimed to establish a novel approach to assess asthma severity based on asthma health-care burden data.

Methods: We analysed prospectively collected data from the Severe Asthma Research Program III (SARP III; USA) and the European Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes (U-BIOPRED; 11 European countries) to calculate a composite burden score based on asthma exacerbations and health-care utilisation, which was modified to include the use of short-acting beta agonists (SABAs) to reflect asthma symptom burden.

A randomized control trial evaluating the advice of a physiological-model/digital twin-based decision support system on mechanical ventilation in patients with acute respiratory distress syndrome.

Background: Acute respiratory distress syndrome (ARDS) is highly heterogeneous, both in its clinical presentation and in the patient's physiological responses to changes in mechanical ventilator settings, such as PEEP. This study investigates the clinical efficacy of a physiological model-based ventilatory decision support system (DSS) to personalize ventilator therapy in ARDS patients.

Methods: This international, multicenter, randomized, open-label study enrolled patients with ARDS during the COVID-19 pandemic.

Radiomultiomics: quantitative CT clusters of severe asthma associated with multiomics.

Background: Lung quantitative computed tomography (qCT) severe asthma clusters have been reported, but their replication and underlying disease mechanisms are unknown. We identified and replicated qCT clusters of severe asthma in two independent asthma cohorts and determined their association with molecular pathways, using radiomultiomics, integrating qCT, multiomics and machine learning/artificial intelligence.

Methods: We used consensus clustering on qCT measurements of airway and lung CT scans, performed in 105 severe asthmatic adults from the U-BIOPRED cohort.

Effect of biologic therapies on quality of life in severe asthma: Findings from the PRISM study.

Background: Anti-type 2 (T2) biologic therapies (biologics) improve exacerbation rates, lung function, and asthma-related quality of life (QoL) in patients with severe T2 asthma. However, studies comparing different biologics are lacking. We evaluated the QoL in patients with severe asthma comprehensively and compare the efficacy of different T2-directed biologics using QoL questionnaires.

Host-microbial interactions differ with age of asthma onset.

https://bit.ly/3xSa4Fe

Endotypes of severe neutrophilic and eosinophilic asthma from multi-omics integration of U-BIOPRED sputum samples.

Background: Clustering approaches using single omics platforms are increasingly used to characterise molecular phenotypes of eosinophilic and neutrophilic asthma. Effective integration of multi-omics platforms should lead towards greater refinement of asthma endotypes across molecular dimensions and indicate key targets for intervention or biomarker development.

Objectives: To determine whether multi-omics integration of sputum leads to improved granularity of the molecular classification of severe asthma.

Immune checkpoint inhibitors and SARS-CoV2 infection.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) triggers coronavirus disease 2019 (COVID-19), which predominantly targets the respiratory tract. SARS-CoV-2 infection, especially severe COVID-19, is associated with dysregulated immune responses against the virus, including exaggerated inflammatory responses known as the cytokine storm, together with lymphocyte and NK cell dysfunction known as immune cell exhaustion. Overexpression of negative immune checkpoints such as PD-1 and CTLA-4 plays a considerable role in the dysfunction of immune cells upon SARS-CoV-2 infection.

IL-33 induced gene expression in activated Th2 effector cells is dependent on IL-1RL1 haplotype and asthma status.

https://bit.ly/3WhuMbo

Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.

Volatile organic compounds (VOCs) in asthmatic breath may be associated with sputum eosinophilia. We developed a volatile biomarker signature to predict sputum eosinophilia in asthma. VOCs emitted into the space above sputum samples (headspace) from patients with severe asthma ( = 36) were collected onto sorbent tubes and analyzed using thermal desorption gas chromatography-mass spectrometry (GC-MS).

Effects of toll-like receptor agonists and SARS-CoV-2 antigens on interferon (IFN) expression by peripheral blood CD3 T cells from COVID-19 patients.

Background: Signaling by toll-like receptors (TLRs) initiates important immune responses against viral infection. The role of TLRs in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is not well elucidated. Thus, we investigated the interaction of TLRs agonists and SARS-COV-2 antigens with immune cells in vitro.

TRPA1-PI3K/Akt-OPA1-ferroptosis axis in ozone-induced bronchial epithelial cell and lung injury.

Background: Transient receptor potential (TRP) ankyrin 1 (TRPA1) could mediate ozone-induced lung injury. Optic Atrophy 1 (OPA1) is one of the significant mitochondrial fusion proteins. Impaired mitochondrial fusion, resulting in mitochondrial dysfunction and ferroptosis, may drive the onset and progression of lung injury.