Urinary thromboxane and isoprostane levels are elevated in symptom-high T2-biomarker-low severe asthma.

Background: ∼5-10% of patients with asthma have severe disease. A proportion remain symptomatic despite suppression of T2-related inflammation but what drives persistent symptoms remains unclear. Eicosanoids exert a functional role in pulmonary inflammation.

ARTEMISIA: a mechanistic study of a novel Janus kinase 1 inhibitor to advance molecular understanding and precision medicine in asthma.

Background: Patients with uncontrolled asthma despite the use of inhaled corticosteroids (ICS), may have a variety of biological pathways driving their airway inflammation. Londamocitinib (AZD4604), a selective, inhaled, Janus kinase 1 inhibitor, has been designed to target a broad inflammatory cytokine profile including those classically unresponsive to ICS. The ARTEMISIA mechanistic study aims to provide a clear understanding of the pathways impacted by londamocitinib in the lung, determine how this impact is reflected in the nose and periphery, and identify candidate biomarkers of londamocitinib-treatment response in asthma.

Diagnosis and Treatment Options for T2-Low Asthma.

Type 2 (T2)-low asthma is characterized by the absence of T2-mediated eosinophilic airway inflammation. The diagnosis and prevalence of T2-low asthma are complicated by the absence of specific biomarkers, varied cutoffs of existing biomarkers, and biomarker suppression by corticosteroids. The substantial disease burden of T2-low asthma can be attributed to comorbidities, including obesity.

The risk of Long Covid symptoms: a systematic review and meta-analysis of controlled studies.

The global evidence on the risk of symptoms of Long Covid in general populations infected with SARS-CoV-2 compared to uninfected comparator/control populations remains unknown. We conducted a systematic literature search using multiple electronic databases from January 1, 2022, to August 1, 2024. Included studies had ≥100 people with confirmed or self-reported COVID-19 at ≥28 days following infection onset, and an uninfected comparator/control group.

Under the weather: an epidemic thunderstorm asthma event in Leicester, June 2023.

In the context of climate change and increasing global populations, thunderstorm asthma may become a greater threat at both individual and population levels. The unpredictable nature of epidemic thunderstorm asthma events makes them challenging to study; however, they can have devastating consequences. Novel approaches are required to characterise the mechanisms driving these events to allow researchers and other stakeholders to understand who is at risk and when.

Neutrophilic inflammation in sputum or blood does not define a clinically distinct asthma phenotype in ATLANTIS.

Introduction: Neutrophilic asthma has been suggested to be a clinically distinct phenotype characterised by more severe airflow obstruction and higher exacerbation risk. However, this has only been assessed in few and smaller studies, using different cut-offs to define neutrophilia, and with conflicting results. We used data from ATLANTIS, an observational longitudinal study including a large number of patients with asthma and healthy controls.

Improved Annotation of Asthma Gene Variants with Cell Type Deconvolution of Nasal and Lung Expression Quantitative Trait Loci.

Asthma is a genetically complex inflammatory airway disease associated with more than 200 SNPs. However, the functional effects of many asthma-associated SNPs in lung and airway epithelial samples are unknown. Here, we aimed to conduct expression quantitative trait loci (eQTL) analysis using a meta-analysis of nasal and lung samples.

Long term health outcomes in people with diabetes 12 months after hospitalisation with COVID-19 in the UK: a prospective cohort study.

Background: People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and without diabetes.

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.

Nasal epithelial gene expression identifies relevant asthma endotypes in the ATLANTIS study.

Introduction: Asthma is an inflammatory airways disease encompassing multiple phenotypes and endotypes. Several studies suggested gene expression in nasal epithelium to serve as a proxy for bronchial epithelium, being a non-invasive approach to investigate lung diseases. We hypothesised that molecular differences in upper airway epithelium reflect asthma-associated differences in the lower airways and are associated with clinical expression of asthma.

Can we measure whether asthma guidelines lead to improved care?

The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have previously produced separate asthma guidance differing in some key aspects in diagnosis and management leading to confusion, potentially hampering guideline dissemination and uptake. While there are inherent challenges, the upcoming release of new joint BTS/SIGN/NICE asthma guidance presents an opportunity to assess guideline adoption and its impact on clinical practice. The use of prescription data via databases such as OpenPrescribing can be used as a surrogate for guideline adoption and potentially linked to clinical outcomes such as hospital episode statistics (HES).

Sex differences in asthma control, lung function and exacerbations: the ATLANTIS study.

Background: Asthma is a heterogeneous disease with a prevalence and severity that differs between male and female patients.

Question: What are differences between male and female patients with asthma with regard to asthma control, lung function, inflammation and exacerbations?

Methods: We performed a post hoc analysis in the ATLANTIS (Assessment of Small Airways Involvement in Asthma) study, an observational cohort study including patients with asthma from nine countries with a follow-up of 1 year during which patients were characterised with measures of large and small airway function, questionnaires, inflammation and imaging. We compared differences in baseline characteristics and longitudinal outcomes between male and female patients with asthma.

Long COVID and cardiovascular disease: a prospective cohort study.

Background: Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.

Objectives: To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.

Methods: In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months.

An epithelial gene signature of trans-IL-6 signaling defines a subgroup of type 2-low asthma.

Background: Asthma is stratified into type 2-high and type 2-low inflammatory phenotypes. Limited success has been achieved in developing drugs that target type 2-low inflammation. Previous studies have linked IL-6 signaling to severe asthma.

Biologics for severe asthma-Which, when and why?

Asthma is a common chronic inflammatory condition of the airways that affects about 350 million people globally. In 5%-10% of individuals, it is severe, with considerable morbidity and high health care utilization. The goal of asthma management is disease control by reducing symptoms and exacerbations and reducing corticosteroid-related morbidity.

Definitions of non-response and response to biological therapy for severe asthma: a systematic review.

Background: Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma.

Methods: We searched four bibliographic databases from inception to 15 March 2021 Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN).