Publications by authors named "Brightling C"
The Epithelial Science Expert Group convened on 18-19 October 2023, in Naples, Italy, to discuss the current understanding of the fundamental role of the airway epithelium in asthma and other respiratory diseases and to explore the future direction of patient care. This review summarises the key concepts and research questions that were raised. As an introduction to the epithelial era of research, the evolution of asthma management throughout the ages was discussed and the role of the epithelium as an immune-functioning organ was elucidated.
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- * These technologies pave the way for decentralized clinical trials, allowing for a more inclusive study population, reduced costs, and faster access to new treatments.
- * The discussion includes the use of digital endpoints, different trial designs, a specific example of a fully decentralized asthma trial, and examines the pros and cons of these methods from various perspectives (clinicians, patients, and regulators).
Background: People hospitalised for coronavirus disease 2019 (COVID-19) have elevated incidence of diabetes. However, it is unclear whether this is due to shared risk factors, confounding or stress hyperglycaemia in response to acute illness.
Methods: We analysed a multicentre prospective cohort study (PHOSP-COVID) of people ≥18 years discharged from NHS hospitals across the United Kingdom following COVID-19.
Article Synopsis
- - The development of the CompOsite iNdexes For Response in asthMa (CONFiRM) aimed to create patient-centered tools that measure responses to biologics for severe asthma in both adults and children, integrating clinical data and quality of life (QoL) indicators.
- - Experts and patients collaborated to identify significant outcome changes and devised CONFiRM scores, which demonstrated high levels of agreement on key factors, with patients emphasizing the importance of quality of life more than healthcare professionals did.
- - The CONFiRM scores effectively measure treatment response, with strong validity metrics indicating their reliability, and they facilitate a comprehensive assessment of biologics’ effectiveness; further studies are required for prospective validation.
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.
Background: In patients with coronavirus disease 2019 (COVID-19) requiring supplemental oxygen, dexamethasone reduces acute severity and improves survival, but longer-term effects are unknown. We hypothesised that systemic corticosteroid administration during acute COVID-19 would be associated with improved health-related quality of life (HRQoL) 1 year after discharge.
Methods: Adults admitted to hospital between February 2020 and March 2021 for COVID-19 and meeting current guideline recommendations for dexamethasone treatment were included using two prospective UK cohort studies (Post-hospitalisation COVID-19 and the International Severe Acute Respiratory and emerging Infection Consortium).
Article Synopsis
- The studies NAVIGATOR and DESTINATION evaluated the effectiveness of tezepelumab in treating severe, uncontrolled asthma.
- Results showed that a higher percentage of patients receiving tezepelumab experienced a complete clinical response and on-treatment clinical remission compared to those on placebo.
- Conclusion suggests that tezepelumab significantly improves patient outcomes, leading to better lung function and fewer asthma exacerbations over time.
Introduction: The interleukin-33/interleukin-1 receptor-like-1 (IL-33/IL1RL1) signalling pathway is implicated in asthma pathogenesis, with IL1RL1 nonsynonymous genetic polymorphisms associated with disease risk. We aimed to determine these variants' effect on IL1RL1 signalling induced by different IL33 isoforms thought to be elevated in the asthmatic airway.
Method: In a project funded by GSK plc, which has developed an IL-33 receptor inhibitor for asthma treatment, human embryonic kidney 293 (HEK293) cells expressing secreted embryonic alkaline phosphatase (SEAP) driven by a nuclear factor kappa-beta (NF-κB) promoter, were transiently transfected with IL1RL1, containing one of four extracellular and Toll/interleukin 1 receptor (TIR) domain haplotypes.
Article Synopsis
- The study aimed to assess the effectiveness of ECG in detecting cardiac issues in post-hospitalized COVID-19 patients through cardiac magnetic resonance (CMR) imaging.
- Results showed that these patients had significantly more ECG abnormalities compared to healthy controls, yet both groups had similar levels of CMR abnormalities.
- Adding additional analyses on repolarization improved ECG's ability to identify patients with CMR abnormalities and reduced the reliance on sex in the diagnostic process.
Article Synopsis
- Mepolizumab is an anti-IL-5 antibody used to treat severe eosinophilic asthma while oral corticosteroids like prednisolone are commonly used for persistent symptoms despite mepolizumab therapy.
- The MAPLE trial investigated how well prednisolone reduces airway inflammation in patients on mepolizumab, examining sputum and plasma samples for inflammatory proteins.
- Results showed that prednisolone significantly reduced various proteins associated with type 2 inflammation and inflammation pathways, suggesting its important role in managing exacerbations even when patients are treated with mepolizumab.
Background: COVID-19 is known to be associated with increased risks of cognitive and psychiatric outcomes after the acute phase of disease. We aimed to assess whether these symptoms can emerge or persist more than 1 year after hospitalisation for COVID-19, to identify which early aspects of COVID-19 illness predict longer-term symptoms, and to establish how these symptoms relate to occupational functioning.
Methods: The Post-hospitalisation COVID-19 study (PHOSP-COVID) is a prospective, longitudinal cohort study of adults (aged ≥18 years) who were hospitalised with a clinical diagnosis of COVID-19 at participating National Health Service hospitals across the UK.
Article Synopsis
- Pulmonary embolism (PE) is a serious complication of COVID-19 that can lead to chronic thromboembolic pulmonary disease (CTEPD) and chronic thromboembolic pulmonary hypertension (CTEPH), but the true burden and best screening methods for these conditions are still not clear.
- During the study from 2017 to 2022, only a small percentage of CTEPH cases were linked to previous COVID-19 infections, with the CTEPH rates returning to pre-pandemic levels after the second year of the pandemic.
- The findings suggest that while the risk of developing CTEPH after hospitalization for COVID-19 is low, using simple clinical risk scores can help identify patients who may need further evaluation.
Article Synopsis
- The PHOSP-COVID study examined long-term outcomes in COVID-19 hospitalised patients with pre-existing airway diseases compared to those without.* -
- Out of 615 participants with airway diseases, many reported lower recovery rates, higher anxiety and depression levels, and greater mobility issues one year post-discharge.* -
- Overall, individuals with pre-existing airway conditions experienced worse health-related quality of life and more persistent symptoms like breathlessness and fatigue after recovering from COVID-19.*
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.
View Article and Find Full Text PDFThe 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).
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- A study assessed the effects of COVID-19 on multi-organ and metabolic health in patients who were hospitalized with severe cases of the illness, comparing them to healthy controls.
- The findings revealed that patients had a significantly higher insulin response during an oral glucose tolerance test, indicating greater insulin resistance, but no differences in blood glucose levels or fat oxidation were found.
- Patients also reported higher fatigue and had lower physical performance and step counts, suggesting that recovery interventions focused on physical function may be necessary.
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.
Discovery and Validation of a Volatile Signature of Eosinophilic Airway Inflammation in Asthma.
Am J Respir Crit Care Med
November 2024
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).
View Article and Find Full Text PDFBackground: 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.
SARS-CoV-2 infection can result in long COVID, characterized by post-acute symptoms from multiple organs. Current hypotheses on mechanisms underlying long COVID include persistent inflammation and thromboembolism; however, compelling evidence from humans is limited and causal associations remain unclear. Here, we tested the association of thromboembolism-related genetic variants with long COVID in the Long COVID Host Genetics Initiative ( =3,018; =994,582).
View Article and Find Full Text PDFBackground: Long-term tezepelumab treatment in the DESTINATION study (NCT03706079) resulted in reduced asthma exacerbations, reduced biomarker levels, and improved lung function and symptom control in patients with severe, uncontrolled asthma.
Objective: To explore the time course of changes in biomarkers and clinical manifestations after treatment cessation after 2 years of tezepelumab treatment.
Methods: DESTINATION was a 2-year, phase 3, multicenter, randomized, placebo-controlled, double-blind study of tezepelumab treatment in patients (12-80 years old) with severe asthma.