Biomarker profile and disease burden associated with intermittent and long-term oral corticosteroid use in patients with severe asthma prior to biologic initiation in real-life (STAR).

Background: Asthma characterization using blood eosinophil count (BEC) (among other biomarkers and clinical indices) is recommended in severe asthma (SA), but the masking effect of oral corticosteroids (OCS), makes this challenging.

Aim: Our aim was to explore the effect of OCS use (both intermittent [iOCS] and long-term [LTOCS]) prior to biologic initiation on SA phenotype and biomarker profile in real-life and to characterize the burden of SA among patients prescribed LTOCS by biomarker profile.

Methods: This was a registry-based cohort study, including data from 23 countries collected between 2003 and 2023 and shared with the Internatonal Severe Asthma Registry (ISAR).

Prevention of Cardiovascular and Other Systemic Adverse Outcomes in Patients with Asthma Treated with Biologics.

Although clinical trials have documented the oral corticosteroid (OCS)-sparing effect of biologics in patients with severe asthma, little is known about whether this translates to a reduction of new-onset OCS-related adverse outcomes. To compare the risk of developing new-onset OCS-related adverse outcomes between biologic initiators and noninitiators. This was a longitudinal cohort study using pooled data from the International Severe Asthma Registry (ISAR; 16 countries) and the Optimum Patient Care Research database (OPCRD; United Kingdom).

Impact of Biologics Initiation on Oral Corticosteroid Use in the International Severe Asthma Registry and the Optimum Patient Care Research Database: A Pooled Analysis of Real-World Data.

Background: For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited.

Objective: To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in patients with SA from real-world specialist and primary care settings.

Methods: From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, United Kingdom), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2).

Nasal irrigation solution is less cytotoxic to nasal epithelial cells than nasal spray.

Background: Recent studies have demonstrated that corticosteroid delivered by nasal irrigation is superior to nasal spray in the treatment of chronic rhinosinusitis patients who have undergone sinus surgery. However, the local cytotoxicity of both delivery methods has not been previously evaluated. In this study we aimed to evaluate the cytotoxicity of corticosteroid prepared nasal irrigation solution and commercially available corticosteroid nasal spray.

Airway Epithelial-Derived Immune Mediators in COVID-19.

The airway epithelium, which lines the conducting airways, is central to the defense of the lungs against inhaled particulate matter and pathogens such as SARS-CoV-2, the virus that causes COVID-19. Recognition of pathogens results in the activation of an innate and intermediate immune response which involves the release of cytokines and chemokines by the airway epithelium. This response can inhibit further viral invasion and influence adaptive immunity.

Comparative effectiveness of anti-IL5 and anti-IgE biologic classes in patients with severe asthma eligible for both.

Background: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life.

Methods: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R.

Hedgehog Signaling as a Therapeutic Target for Airway Remodeling and Inflammation in Allergic Asthma.

Genome-wide association studies (GWAS) have shown that variants of patched homolog 1 () are associated with lung function abnormalities in the general population. It has also been shown that sonic hedgehog (SHH), an important ligand for PTCH1, is upregulated in the airway epithelium of patients with asthma and is suggested to be involved in airway remodeling. The contribution of hedgehog signaling to airway remodeling and inflammation in asthma is poorly described.

FAM13A as potential therapeutic target in modulating TGF-β-induced airway tissue remodeling in COPD.

Genome-wide association studies have shown that a gene variant in the Family with sequence similarity 13, member A (FAM13A) is strongly associated with reduced lung function and the appearance of respiratory symptoms in patients with chronic obstructive pulmonary disease (COPD). A key player in smoking-induced tissue injury and airway remodeling is the transforming growth factor-β1 (TGF-β1). To determine the role of FAM13A in TGF-β1 signaling, airway epithelial cells were generated using CRISPR-Cas9, whereas overexpression of FAM13A was achieved using lipid nanoparticles.

IL-4Rα blockade reduces influenza-associated morbidity in a murine model of allergic asthma.

Background: Asthma was identified as the most common comorbidity in hospitalized patients during the 2009 H1N1 influenza pandemic. We determined using a murine model of allergic asthma whether these mice experienced increased morbidity from pandemic H1N1 (pH1N1) viral infection and whether blockade of interleukin-4 receptor α (IL-4Rα), a critical mediator of T2 signalling, improved their outcomes.

Methods: Male BALB/c mice were intranasally sensitized with house dust mite antigen (Der p 1) for 2 weeks; the mice were then inoculated intranasally with a single dose of pandemic H1N1 (pH1N1).

Olodaterol exerts anti-inflammatory effects on COPD airway epithelial cells.

Background: Airway inflammation is a key feature of chronic obstructive pulmonary disease (COPD) and inhaled corticosteroids (ICS) remain the main treatment for airway inflammation. Studies have noted the increased efficacy of ICS and long-acting beta 2 agonist (LABA) combination therapy in controlling exacerbations and improving airway inflammation than either monotherapy. Further studies have suggested that LABAs may have inherent anti-inflammatory potential, but this has not been well-studied.

Various factors affect lipopolysaccharide sensitization in cell cultures.

Commercially available lipopolysaccharide (LPS) is commonly used in research. Although protocols for its use are well established, we experienced a loss of LPS responsiveness in our cell cultures despite no obvious experimental changes. Our cell lines were stimulated with LPS and the media quantified for LPS responsiveness via an IL-8 ELISA.

ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19.

https://bit.ly/3bC29es

Structural and functional variations in human bronchial epithelial cells cultured in air-liquid interface using different growth media.

The human bronchial epithelium is an important barrier tissue that is damaged or pathologically altered in various acute and chronic respiratory conditions. To represent the epithelial component of respiratory disease, it is essential to use a physiologically relevant model of this tissue. The human bronchial epithelium is a highly organized tissue consisting of a number of specialized cell types.

Omalizumab in patients with severe asthma and persistent sputum eosinophilia.

Omalizumab, a recombinant humanized monoclonal antibody targeting the IgE molecule, is the first biologic approved for moderate-to-severe allergic asthmatics, who remain uncontrolled despite high dose inhaled corticosteroid and bronchodilators. Steroid-sparing effect of omalizumab has not been demonstrated in asthmatics with persistent airway eosinophilia in a randomised controlled trial till date. From this double-blind, placebo-controlled, multi-centred, randomized parallel group design, we report that omalizumab is possibly inadequate to control sputum eosinophilia, and therefore may not have a steroid-sparing effect, especially in those maintained on oral corticosteroids daily.

IL-13 signaling through IL-13 receptor α2 mediates airway epithelial wound repair.

Asthma is an airway inflammatory disease characterized by epithelial barrier dysfunction and airway remodeling. Interleukin-13 (IL-13) is a pleiotropic cytokine shown to contribute to features of airway remodeling. We have previously demonstrated that IL-13 is an important mediator of normal airway epithelial repair and health.

A pilot randomized controlled trial on the impact of text messaging check-ins and a web-based asthma action plan versus a written action plan on asthma exacerbations.

Objective: We compared electronic asthma action plans (eAAP) supported by automated text messaging service (SMS) with written asthma action plans (AAP) on assessing acceptability and asthma control improvement. We hypothesized that the patients in eAAP group would have more improvements in their quality of life, asthma control and decreased asthma exacerbations.

Methods: Patients with physician-diagnosed asthma having at least one asthma exacerbation in the previous 12 months were recruited.

Gene expression analysis in asthma using a targeted multiplex array.

Background: Gene expression changes in the structural cells of the airways are thought to play a role in the development of asthma and airway hyperresponsiveness. This includes changes to smooth muscle contractile machinery and epithelial barrier integrity genes. We used a targeted gene expression arrays to identify changes in the expression and co-expression of genes important in asthma pathology.

Urban particulate matter increases human airway epithelial cell IL-1β secretion following scratch wounding and H1N1 influenza A exposure in vitro.

Purpose: The airway epithelium represents the first line of defense against inhaled environmental insults including air pollution, allergens, and viruses. Epidemiological and experimental evidence has suggested a link between air pollution exposure and the symptoms associated with respiratory viral infections. We hypothesized that multiple insults integrated by the airway epithelium NLRP3 inflammasome would result in augmented IL-1β release and downstream cytokine production following respiratory virus exposure.

Expression of surfactant protein D in airways of asthmatics and interleukin-13 modulation of surfactant protein D in human models of airway epithelium.

Background: Surfactant protein D (SP-D), a pattern recognition molecule, has been shown to play roles in host defense such as opsonisation, aggregation of pathogens, and modulation of the inflammatory response. In light of infection-induced exacerbations and damage to the airway epithelium from inflammation, these functions of SP-D make it relevant in the development and pathogenesis of asthma.

Methods: Expression of SP-D was examined in human airway sections and primary airway epithelial cells (AEC) grown in air-liquid interface (ALI) cultures and comparisons were made between those from asthmatic and non-asthmatic donors.

Fluticasone Induces Epithelial Injury and Alters Barrier Function in Normal Subjects.

Objective: The airway epithelium has a number of roles pivotal to the pathogenesis of asthma, including provision of a physical and immune barrier to the inhaled environment. Dysregulated injury and repair responses in asthma result in loss of airway epithelial integrity. Inhaled corticosteroids are a corner stone of asthma treatment.