NIHRDataInsights/HRCSData huggingface dataset:
Title: A stratified phenotype-specific medicine approach in the management of COPD exacerbations in primary care
Funder: Department of Health and Social Care

Abstract: Background: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are debilitating and a major NHS burden. Treatment guidelines recommend oral steroids and antibiotics but failure to respond to is common. AE-COPD aetiology and response to treatment is varied. Current one-size-fits-all' approaches are unsatisfactory. Hypothesis: A personalised stratified treatment approach in AE-COPD in primary care using near-patient testing to derive phenotypes of COPD is superior to current strategies Study design: Double-blind randomised placebo control study Expected outcomes: Treatment failure rates are reduced in AE-COPD receiving phenotype-specific near-patient testing directed therapyAnticipated benefits: Health economics benefits and guideline changes in AE-COPD management

Lay abstract: Background: Acute exacerbations of chronic obstructive pulmonary disease (AE-COPD) are debilitating and a major NHS burden. Treatment guidelines recommend oral steroids and antibiotics but failure to respond to is common. AE-COPD aetiology and response to treatment is varied. Current one-size-fits-all' approaches are unsatisfactory. Hypothesis: A personalised stratified treatment approach in AE-COPD in primary care using near-patient testing to derive phenotypes of COPD is superior to current strategies Study design: Double-blind randomised placebo control study Expected outcomes: Treatment failure rates are reduced in AE-COPD receiving phenotype-specific near-patient testing directed therapyAnticipated benefits: Health economics benefits and guideline changes in AE-COPD management

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RESPIRATORY
Title: Non-pharmacological approaches to the management of chronic respiratory disease
Funder: Department of Health and Social Care

Abstract: Approximately 8 million people in the UK have respiratory problems, which are now the second most common cause of death. Although much effort and resources have been invested into developing new drugs, less has been done to develop, validate, or discover the relative benefits of, non-pharmacological approaches. During this Fellowship, patient-focused physical therapies will be investigated for their clinical effectiveness, mechanisms of benefit, and patient acceptability. We will discover the optimal methods of delivering breathing retraining for asthma, develop innovative monitoring systems for chronic respiratory disorders, and assess novel systems of portable oxygen therapy for Chronic Obstructive Pulmonary Disease (COPD).

Lay abstract: Approximately 8 million people in the UK have respiratory problems, which are now the second most common cause of death. Although much effort and resources have been invested into developing new drugs, less has been done to develop, validate, or discover the relative benefits of, non-pharmacological approaches. During this Fellowship, patient-focused physical therapies will be investigated for their clinical effectiveness, mechanisms of benefit, and patient acceptability. We will discover the optimal methods of delivering breathing retraining for asthma, develop innovative monitoring systems for chronic respiratory disorders, and assess novel systems of portable oxygen therapy for Chronic Obstructive Pulmonary Disease (COPD).

Research activity codes: 6.7 PHYSICAL
Health categories: RESPIRATORY
Title: Pulmonary epithelial barrier and immunological junctions at birth and in early life - key determinants of development of asthma?
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Inception of asthma, the commonest chronic childhood disease, is determined by early life events including aeroallergen sensitization, bacterial and viral infections. Reduction in lung function, established by age six, is sustained throughout life. Not all wheezy children develop asthma, and mechanisms underlying progression of preschool wheeze to asthma are unknown. Airway epithelial function as associated immune responses are key drivers of this process in established asthma. Mouse models indicate that the microbiota directs immune development and skews allergic responses. The relationship between epithelial and immune development, and their interactions with the airway microbiota in preschool children is unknown. We will profile airway epithelial cells from babies and young children and compare to severe paediatric asthma, in order to identify gene signatures that stratify controls, wheezers and asthmatics, validating this in established birth cohorts. We will investigate the evolution of epithelial function, immune responses and airway microbiome following allergen, viral and bacterial exposures. We will determine the molecular mechanisms whereby epithelial-immune-microbial-gene interactions are skewed towards asthma rather than resolution. Our vision is to understand what initiates asthma and facilitate development of biomarkers predicting progression of preschool wheeze to asthma. Our over-arching goal is asthma prevention and improvement of lifelong lung health.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: RESPIRATORY
Title: 2014 Doctoral Fellowship: Investigation of Aspirin as a novel therapy for the Acute Respiratory Distress Syndrome
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: The Acute Respiratory Distress Syndrome (ARDS) is a common devastating clinical syndrome characterised by respiratory failure requiring mechanical ventilation and is associated with a high mortality and morbidity. ARDS is caused by inflammatory mediated damage to the alveolar epithelium and endothelium. There is in vitro and in vivo data from animal models of ARDS to indicate aspirin may be a potential therapeutic agent in ARDS. Our observational data have indicated aspirin use is associated with reduced mortality in patients with ARDS. In addition we have data from the human ex vivo lung perfusion (EVLP) model of ARDS that aspirin decreases pulmonary inflammation. The hypothesis to be tested is that aspirin is a safe and effective treatment for ARDS The study is a randomised, double blind, placebo controlled phase 2 study. The primary objective of the study is to investigate if aspirin improves important surrogate clinical outcomes. The secondary objectives will investigate the mechanisms by which aspirin may modulate the course of ARDS. Patients within 72-hours of onset of ARDS will be randomised to aspirin 75mg or identical placebo for up to 14days. The primary outcome is oxygenation index, a validated measure of pulmonary function. This study will provide data to design a phase 3 clinical study to investigate the effect of aspirin in ARDS. The results from this clinical trial will also provide new understanding of the pathogenesis of ARDS and the potential modulation thereof by aspirin. The NI Critical Care Translational Research Group is fully supportive of this project.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY
Title: 2015 Doctoral Fellowship: Evaluation of mechanisms in and methods of inhibiting ventilator induced lung injury
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Acute hypoxaemic respiratory failure and the acute respiratory distress syndrome occur in approximately 15000 patients in Intensive Care each year in the UK. These patients require mechanical ventilation which itself is injurious and contributes to lung damage and resultant morbidity and mortality. Despite clear evidence that low tidal volume ventilation can protect such patients, clinical studies indicate that many patients are not ventilated in a protective manner, frequently because the elevated PaCO2 levels that occur with low tidal volume ventilation increase intracranial pressure, induce pulmonary hypertension and reduce renal blood flow. Other strategies are therefore needed to reduce ventilator-induced injury. In this proposal we will investigate the mechanisms of ventilator induced injury and how it may be prevented. We will use the ex vivo perfused human lung to model ventilator induced injury (this has only been done in animal studies previously), and will study the kinetics of injury and its regulation by inflammatory / other mediators. We will use perfusate from injuriously ventilated lungs to identify if soluble mediators can induce injury in a protectively ventilated lung. We will study the perfusate in cell culture models to identify the class of mediator (lipid vs protein), and identity of mediators which drive injury. This will identify important targets for inhibition in lung injury. Furthermore we will collect BAL, blood and urine from patients recruited to the REST trial, a large trial of extracorporeal CO2 removal which allows ultra-protective ventilation, to identify how patients ventilated this way are protected form injury. Taken together these studies will characterize the time course and regulation of ventilator induced lung injury in human lungs for the first time, and will identify potential targets for therapy to inhibit ventilator-induced injury in those at risk.


Research activity codes: 5.7 PHYSICAL
Health categories: RESPIRATORY
Title: 2018 GPARTS - Dr Jonathan Stewart - Linkage of primary and secondary healthcare records to identify the prevalence, characteristics and clinical outcomes of patients with Severe Asthma in Northern Ireland
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Severe Asthma is confirmed asthma that is uncontrolled despite adherence to maximal optimized therapy and treatment of contributory factors, or that worsens when high dose treatment is reduced. This patient subgroup is difficult to diagnose and associated with significant morbidity. There is evidence of improved clinical outcomes if these patients are identified and offered specialist management including novel monoclonal antibody treatment. There is significant inequity in Asthma care across the United Kingdom, with unacceptable variation in prevalence, frequency of exacerbations, provision of services and health outcomes across geography, age, ethnicity and socio-economic groups. Data linkage presents a unique opportunity to better understand this high-risk subgroup and to shed light on how inequalities in care and outcomes might be mitigated. Asthma patients have healthcare records held in various databases throughout the Health and Social Care system. Primary care records provide the most representative dataset for patients with an asthma diagnosis and have many unique properties which make them essential to gain an accurate picture of SRA clinical burden. We plan to use primary healthcare record data from the Northern Ireland asthma population including quality and outcome framework parameters, prescribing and laboratory data linked to secondary healthcare record datasets including admissions and emergency department attendances to determine the prevalence, characteristics and clinical outcomes of patients with SRA in Northern Ireland. This novel proof of concept study could lead to improved clinical outcomes and pave the way for similar linkage studies for other conditions.


Research activity codes: 2.4 SURVEILLANCE AND DISTRIBUTION
Health categories: RESPIRATORY
Title: Investigating Novel Roles of Integrins in Type 2 Immunity and Asthma
Funder: Medical Research Council

Abstract: Aim 1 - Characterisation of the function of LFA-1 on ILC2 in Asthma We will study ILC2 from the blood of volunteers with and without asthma. Volunteers with asthma will be recruited from the Cambridge severe asthma service. We will use flow cytometry to analyse ILC2 populations and LFA-1 expression on ILC2, comparing patients with severe asthma and obesity (BMI > 30), severe asthma and no obesity (BMI < 30) and matched controls. We will also sort ILC2 to study expression of LFA-1 and other adhesion molecules using PCR. In order to study the function of LFA-1 in asthma, we will pursue a translational approach studying human volunteers while exploring potential mechanisms in murine models. In order to study the murine models, we will generate bone marrow chimeric mice which lack expression of LFA-1 in ILC2. We will compare these mice to wild type mice in murine models of asthma. Aim 2 - Characterisation of CD51 in T-cells in asthma We will employ a similar strategy to explore the function of CD51 in T-cells in asthma. We will isolate T-cells form volunteers with and without asthma and differentiate them into Th2 cells in vitro. We will then compare expression of CD51 on the T-cells differentiated in vitro using flow cytometry and PCR. In order to explore its role in mouse models, we will generate a mouse line which will lack CD51 in CD4+ T-cells (CD4 driven Cre crossed into a floxed CD51 line). Should these studies be successful, we will also seek to study T-cells from the lungs of patients, comparing broncho-alveolar lavage T-cells from patients with asthma and volunteers.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY
Title: BREATHE - The Health Data Research Hub for Respiratory Health
Funder: Medical Research Council

Abstract: "Approximately 12.7 million people report a history of long-standing respiratory illness and respiratory disorders are the third leading cause of death. Lung diseases account for 10% of all inpatient bed-days, cost the NHS £11billion/year and society over £70billion/year. Despite having the richest respiratory datasets in the world, data are fragmented, inconsistently structured and cumbersome to access, severely limiting their utility. Our vision is to transform the UK’s respiratory health through creating Findable, Accessible, Interoperable and Reusable (FAIR) respiratory rich datasets; providing expert support to catalyse their responsible use in respiratory research and innovation. We will position the UK at the forefront of data driven innovation; creating a ‘one-stop’ service for trustworthy, multi-stakeholder utilisation of curated respiratory data for public, private and third sector benefit. Our UK-wide consortium provides the necessary expertise. Our priorities have been co-developed with patients, the public, industry and med-tech partners; together we have identified major opportunities for early, high-profile, case studies. BREATHE will initially focus on asthma and COPD, including respiratory infections, addressing three main themes of crucial importance to the UK life sciences sector: 1) Drug discovery and pharmacogenetics; 2) RWE to improve healthcare systems; 3) Digitally enabled trials New data assets will be made available to the UK Health Data Research (HDR) Alliance and through the HDR Research Innovation Gateway. We will create a UK Respiratory Data Library (with metadata catalogue), curate and link data, and provide open-source algorithms to support secure analyses thereby enhancing the interoperability of datasets. This expandable platform will for example, enable the incorporation of data from wearable sensors into NHS apps to transform respiratory health, supporting rapid evaluation of new drugs and devices in real-world settings, and yielding evidence to underpin policy initiatives. BREATHE will support stakeholders to securely use data to meet their diverse needs. We will work proactively with other Digital Innovation Hubs (DIH) to enhance the UK’s competitiveness. "


Research activity codes: 5.9 RESOURCES AND INFRASTRUCTURE (TREATMENT DEVELOPMENT);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: RESPIRATORY
Title: Phase 1 COVID-19 Data and Connectivity – National Core Study (Phase 1 D&C-NCS)
Funder: Medical Research Council

Abstract: The Data and Connectivity study sits across the other National Core Studies and delivers a national health data research capability to support COVID-19 research questions, ensuring datasets are discoverable and accessible and linkages are established to answer the priority research questions from the other five National Core Studies. Making data available for wider research use will increase the scope of benefits beyond the specific studies above, leading to unexpected benefits and boosting UK research capacity more generally, increasing return on investment for the NCS programme. Data integration and harmonisation of methods and standards will enable rapid research and development of new interventions and technologies across the spectrum of COVID-19, and knowledge and technology transfer to other clinical and public health areas. Collation and linkage between datasets is critical to bringing the core studies together, ensuring that each of them can deliver against their policy priorities e.g. hospital data may not currently be linked with GP data and wider community data (e.g. socioeconomic data or data on housing and the built environment). Access, cleaning, linkage and use of these datasets together is needed to fully understand links between these factors and outcomes. Delivery of the COVID-19 Data and Connectivity Study will involve close interaction with data custodians, the public and patients, and providers of UK-wide national Trusted Research Environments (TREs) to ensure the required data is stored safely and securely, made readily available to approved researchers and is associated with compute, analytical and data services that make it easier to address priority research questions in a transparent and trustworthy way. Phase 1 will: • Continue to respond to emerging COVID-19 research priorities, mapping key datasets required by the National Core Studies, NIHR UPH Studies and SAGE sub-groups to allow research which can inform policy and operational decision making across the UK • Further develop the data infrastructure and services across the UK to allow faster access to high priority health, administrative, molecular, and behavioural data assets for researchers working on the most important COVID-related studies, ensuring priority research questions can be answered efficiently, in a transparent and trustworthy way. • Strengthen and extend the existing national Trusted Research Environments (TRE) and UK Health Data Research Innovation Gateway infrastructure through inclusive four nations approach ensuring the priority datasets for COVID-19 research are findable, accessible, inter-operable and reusable (FAIR) as a single shop window


Research activity codes: 2.6 RESOURCES AND INFRASTRUCTURE (AETIOLOGY);3.5 RESOURCES AND INFRASTRUCTURE (PREVENTION);6.9 RESOURCES AND INFRASTRUCTURE (TREATMENT EVALUATION);8.5 RESOURCES AND INFRASTRUCTURE (HEALTH SERVICES)
Health categories: RESPIRATORY
Title: Volatile Biomarker Positioning of Naso-gastric Tubes to Enhance Patient Safety (Acronym: NG-Sure)
Funder: Medical Research Council

Abstract: Naso-gastric tubes (NG-tubes) are used worldwide each year in hospital and community settings (UK-1million; US-1.2 million; EU-10million) to give enteral feeds and medicines to patients unable to swallow/tolerate oral feeds (e.g. from critical illness, deteriorating consciousness level, neurological condition (stroke) or post gastro-intestinal surgery). Accidental misplacement during blind insertion into the respiratory tract or pleura occurs in 1-3% cases, and into the oesophagus in 19%, with later tube migration in up to 50%. If fluids are given down a misplaced tube, serious patient harm or death can result, an NHS Never Event. The recommended first-line NG-tube placement test is to obtain aspirate up the tube and check its acidity with pH paper. A pH of 1 to 5.5 is a 'safe range' to exclude respiratory tract misplacement and to use the tube. Obtaining aspirate is difficult (50-85% chance of success), and pH readings may be unclear. The second-line test is then an X-ray which can be misinterpreted (seen in 57% of never events), is costly, exposes patients to radiation, causes delays in feeding and increases movement/travel of seriously ill hospitalised patients or community patients needing longer-term feeding. A different approach is needed. Our 3-year project aims to produce and test a new portable, sensor-based, NG-tube placement device (NG-Sure). It will measure gases and volatile chemicals at the NG-tube tip, to create 'VOC (volatile organic compound) fingerprints' and a pH reading (without needing aspirate). Fingerpints will differ according to tube location (stomach, lungs or oesophagus). We have proved clinical feasibility of our idea on 33 paired gastric and breath samples, and aim to develop, produce and test a prototype device in patients with a chosen set of sensors. Our experienced team will involve patients, carers, and NHS staff throughout, and examine financial benefits and potential markets.


Research activity codes: 4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY
Title: Does hospitalisation of older patients with severe community acquired pneumonia and sepsis lead to long term immunoparesis?
Funder: Medical Research Council

Abstract: Our overarching aim is to test our hypothesis that an episode of CAP+S in patients over 50 years old causes age-related immunoparesis in both the innate and adaptive immune system that is driven by modification of gene expression in neutrophils, is persistent after hospital discharge, predisposes to secondary infection and maps to adverse longer term outcomes. To achieve this, we will conduct a experimental medicine / translational study in a cohort of CAP+S patients admitted to hospital recruited both in and outside ITU and will address the following research aims: 1. To assess CAP+S related changes in neutrophil and lymphocyte phenotype and function and to define the time course of changes induced by CAP+S. We will serially assess survivors to determine the persistence of these effects and their relationship to clinical outcomes. 2. To understand the mechanisms of any witnessed change. We will use advanced transcriptomic analysis of flow sorted neutrophils to identify variation in gene expression following CAP+S. The results will inform mechanistic and functional studies of relevant intracellular signalling pathways to relate the transcriptome signal to phenotype and function. 3. To determine whether immunoparesis following CAP+S reflects pre-existing immunoparesis in susceptible adults or develops de novo following infective insult, and to link immunoparesis to poor outcomes following secondary infection. We will assess how age related changes in mouse bone marrow neutrophils are influenced following an episode of acute infection and whether the persistence of these effects exaggerates the severity of a secondary bacterial challenge with S. Aureus.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY