NIHRDataInsights/HRCSData huggingface dataset:
Title: Development of a new treatment for Chronic Obstructive Pulmonary Disease
Funder: Innovate UK

Abstract: This project aims to deliver an advanced candidate drug for the treatment for Chronic Obstructive Pulmonary Disease (sometimes refered to as emphysema or chronic bronchitis) – a highly debilitating condition that affects more than 200 million people worldwide and leads to over 6 million early deaths every year. The consequent social, economic, and health-care burden is huge. Treatment for COPD usually involves relieving the symptoms, for example by using drugs delived through an inhaler, or supplementary oxygen, to make breathing easier. However the novel therapeutic mechanism that will be pioneered by this programme can be more conveniently taken as a tablet, rather than inhaled, and will target the processes that cause the disease, which should significantly slow - or even halt - its progression. These key aspects differentiates this approach from that of existing drugs, and of many other experimental treatments.


Research activity codes: 5.1 PHARMACEUTICALS
Health categories: RESPIRATORY
Title: Asthma and the circadian clock
Funder: Asthma UK

Abstract: Circadian rhythm A circadian rhythm is any biological process that displays an endogenous, entrainable oscillation of about 24 hours. Circadian rhythms are found in most physiological processes. Clock genes Circadian rhythms are generated by a master clo


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY
Title: Local and systemic circadian cues coordinately regulate innate immunity via an epigenetic circuit.
Funder: Biotechnology and Biological Sciences Research Council

Abstract: Circadian clocks are tightly conserved through evolution, and are essential in permitting anticipation of environmental change (light/dark). We have pioneered studies of clock control of immunity, using the lung as a model. We discovered striking clock-regulated inflammatory reactions, and show that this is driven by specialized bronchial epithelial cells (Clara cells). Disruption of the clock in these cells ablated the circadian rhythm in inflammatory responses, but also exacerbated the inflammatory reaction. This appeared to be driven, at least in part, by the chemokine CXCL5. Moreover, we discovered a critical role for glucocorticoids (Gc) in maintaining time of day regulation of the lung inflammatory response. We now seek to define how local oscillators in the lung operate in conjunction with systemic circadian signals (Gc). This will be achieved using local Gc delivery to the lung by nebulisation, and also by deleting the glucocorticoid receptor (GR) in Clara cells. The identification of CXCL5 as a Gc-regulated, circadian controller of pulmonary inflammation prompts us to define how the circadian, and Gc pathways converge. We will address this using chromatin immunoprecipitation (ChIP) analysis in intact lung, subjected to inflammatory, and glucocorticoid challenge, in wild-type, and Clara cell disrupted clock animals. We will then apply ChIP-sequencing, and transcriptome mapping. We will specifically identify the GR cistrome, and how it is regulated by the clock, and by inflammation. We will exploit these discoveries using in-vivo studies to measure the expression, regulation, and cellular distribution of candidate clock "pioneer" transcription factors in the lung. Again, we will address how these are affected by time of day, and by induced inflammation. Taken together, our studies will define how the circadian machinery operating in an intact animal, comprising both local clocks, and systemic clock signals, regulates organ-specific immunity.


Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING
Health categories: RESPIRATORY
Title: Measuring the risk of B-blocker and NSAID precribing in asthma
Funder: Chief Scientist Office (Scotland)

Abstract: Background Asthma is a common chronic respiratory disease which causes significant morbidity and requires considerable primary and secondary care use. National guidelines state that β-blocker drugs are contraindicated in patients with asthma and cautious use of non-steroidal anti-inflammatory drugs (NSAIDs) is recommended because of the risk of bronchospasm. Despite these safety concerns, β-blockers and NSAIDs are not infrequently prescribed to patients with asthma although their true risk is not well quantified and individual β-blockers and NSAIDs may have differing clinical effects in patients with asthma. Furthermore, β-blockers have recently been proposed as a treatment for asthma. Objectives & Design Existing literature on β-blockers and NSAIDs in asthma will be synthesised by systematic review. The risk of β-blocker and NSAID exposure in asthma patients will be determined using the Self-Controlled Case Series method applied to routine primary care data. The main outcome will be exacerbation of asthma and changes in chronic asthma control and analysis will be stratified by different groups of drugs and patient characteristics. Clinical Implications The research aims are to provide the following medical and scientific benefits:  Measure the level of risk associated with oral and topical β-blockers and oral NSAIDs with asthma.  Determine which, if any, may be safely prescribed to patients with asthma.  Investigate the clinical effects of chronic treatment. Determine whether age, gender or deprivation influence risk when these medicines are prescribed.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY
Title: Supported Self Care for Asthma - development and evaluation on an online
Funder: Chief Scientist Office (Scotland)

Abstract: Asthma is common, and Scotland has the highest prevalence of asthma symptoms in the world, with patients accepting higher levels of symptoms and lifestyle limitations than they need to, often as a result of not making full use of proven treatment strategies. The promotion of self-care is a strategy known to improve asthma control, and the use of the internet is increasingly being considered as a tool to augment its use. The overarching objective of this proposal is to produce an online self management tool to support adults with asthma to take a more pro-active role in their management, which will be ready to evaluate in a full scale clinical trial. In order to achieve this I will undertake a systematic review of all published qualitative and quantitative reviews of online asthma self care interventions. The review findings, along with current knowledge of the effectiveness of specific behaviour change interventions, will inform development of an online tool (using freely available open source software called LifeGuide) which will be developed in collaboration with end users. The utility of this tool and the feasibility of undertaking a full scale trial of this intervention will be investigated by undertaking a small pilot study with the primary outcomes of establishing recruitment and retention rates, and secondary outcomes of symptom control, respiratory function, health care utilisation, asthma medication utilisation, and usage data from the Intervention itself. Qualitative interviews with users will help increase understanding of the future implementability of the intervention in practice.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: RESPIRATORY
Title: Deficiency in Lipoxin (LXA4) contributes to persistent neutrophilic airways
Funder: Chief Scientist Office (Scotland)

Abstract: I hypothesize that there is failure of resolution in bronchiectasis, which leads to persistent neutrophilic airways inflammation. My pilot work has shown that there is Lipoxin(LX)A4 deficiency in severe bronchiectasis. MAIN OBJECTIVES 1. Characterize lipids in bronchiectasis airways and peripheral blood to establish the correlation of LXA4/Leukotriene(LT)B4 to disease severity. 2. To investigate a potential mechanism for low levels of LXA4 in bronchiectasis, lipoxin biosynthetic genes expression will be measured. To address the impact of anatomic compartment, gene expression will be measured in peripheral blood, bronchial wash, bronchoalveolar lavage cells and endobronchial biopsies, from patients and healthy controls. 3. Studies to address replacement of LXA4 on airway epithelial cells. I propose that LXA4 will reduce the bronchial epithelial cell inflammatory response to bronchiectasis-relevant pro-inflammatory stimuli. 4. Determine the effect of LXA4 on neutrophil and monocyte-derived macrophage (MDM)- response to inflammatory stimuli and role in phagocytosis of key bacteria implicated in bronchiectasis. I propose that lipoxins will attenuate the inflammatory response, enhance phagocytosis of bacteria by neutrophils and enhance phagocytosis of apoptotic neutrophils by MDms 5. Cohort study to establish if LXA4 deficiency correlates with disease severity. I propose that lipoxin deficiency is an effect of severe disease.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY
Title: Measure Clinical Severity in Infants with Bronchiolitis
Funder: Department of Health (England)

Abstract: Bronchiolitis is an acute respiratory condition and a major cause of illness and death in infants and children worldwide. Many children with this condition need admission to hospital for oxygen and fluid therapy. A number of these children come into hospital very sick or deteriorate rapidly once hospitalised and need support on either high dependency or intensive care units. We want to develop a clinical severity scoring instrument that would help health care professionals make decisions such as when to admit or discharge a child from hospital, or when a child needs intensive care or changes in treatment.


Research activity codes: 1.4 METHODOLOGIES AND MEASUREMENTS;7.3 MANAGEMENT AND DECISION MAKING
Health categories: RESPIRATORY
Title: Improving Inhaler Treatment and Small Airways Assessment in Chronic Obstructive Pulmonary Disease
Funder: Department of Health (England)

Abstract: Patients with chronic obstructive pulmonary disease (COPD) experience breathing difficulties because the airways deep in their lungs become narrowed. COPD patients use inhaler drugs to provide relief from breathlessness. However, current inhalers are inefficient as they deliver a ‘coarse-mist’ of drug-droplets that do not reach the deep airways. In our study, we will use an inhaler of ‘fine-mist’ drug-droplets, tagged with a radioactive tracer to track them. We will take images of the lungs to see if the fine-mist droplets reach the deep airways, and assess if this improves the breathing capacity in our patients. Our research may allow the development of new, more efficient inhalers to improve treatment for patients with COPD.


Research activity codes: 5.1 PHARMACEUTICALS;6.1 PHARMACEUTICALS
Health categories: RESPIRATORY
Title: Trajectories in advanced chronic obstructive pulmonary disease (COPD): determining a new paradigm for the care and support of patients and their informal carers at the end of life.
Funder: Department of Health (England)

Abstract: COPD is a chronic progressive condition with high symptom burden accounting for one death every 20 minutes in England and Wales. National strategy states that quality end-of-life care should be available to patients with any condition, yet limited knowledge of the trajectory of need and preferences for care in advanced COPD has created uncertainty in the timing and type of supportive interventions. An innovative mixed-method, multi-perspective (patients, informal carers, clinicians) longitudinal study will inform workshops with national stakeholders to identify scenarios where greatest improvement can be made to care and service delivery, relevant and appropriate to preferences and need.


Research activity codes: 7.2 END OF LIFE CARE
Health categories: RESPIRATORY
Title: Opportunity-Led Research Proposal: VAPrapid Process Evaluation Award
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Aim, objectives and research questions The aim of this study is to complement the NIHR HTA funded 'Protocolised trial of invasive and non-invasive weaning off ventilation' (http://www.hta.ac.uk/project/2911.asp) by conducting a process evaluation alongside the trial. There are three objectives: 1. To explore the delivery of the intervention, i.e. users' experiences of early extubation are NIV as an adjunct to weaning. 2. To answer the following research questions: a) what is the relationship between recruitment rates, trial outcomes and variation in delivery of the intervention? b) what processes mediate the observed relationship between intervention and outcomes? c) do individual Intensive Care Units (ICUs) differ in their responses to the intervention? 3. To inform an approach to undertaking process evaluations of complex health interventions when these are implemented within trials in the critically ill.


Research activity codes: 6.3 MEDICAL DEVICES;7.3 MANAGEMENT AND DECISION MAKING
Health categories: RESPIRATORY
Title: Development of Interventions to Increase Physical Activity Among Inactive
Funder: Chief Scientist Office (Scotland)

Abstract: Studies show that young people with asthma can exercise safely if appropriately treated and can significantly improve their cardiovascular fitness and quality of life by doing so. However, young people with asthma are even less likely to be physically active than their peers and that they attribute this to their asthma. There is a need to develop strategies that address the unique barriers to activity faced by young people with asthma. Our proposal builds on earlier review and qualitative work funded by the CSO. We propose developing one or more co-ordinated multi-Prof.essional interventions to increase activity levels among 12-18 year olds. We seek to develop interventions with two sequential components: • An interactive educational component with motivational and skill developing elements that will create intentions to engage in activity. • A child-specific activity plan that is agreed between parents, health Prof.essionals and school staff, and which will facilitate the translation of intentions into changes in behaviour.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;5.7 PHYSICAL
Health categories: RESPIRATORY
Title: A National Burden of Diseases, Injuries, and Risk Factors Study for Scotland
Funder: Chief Scientist Office (Scotland)

Abstract: In a resource constrained environment there is increasing pressure for strategic planning and priority setting for public health and health services to be informed by robust evidence. Burden of Disease studies provide a comprehensive assessment of health status by estimating population morbidity and mortality using DALYs (disability-adjusted life years) as a summary outcome measure. This project will provide a comprehensive assessment of the current burden of disease, injuries and risk factors for the Scottish population. It will estimate the relative contribution of major disease groupings and risk factors to the overall disease burden for Scotland and investigate whether projections of this disease burden could provide a guide to future demand for NHS services. This work will provide comprehensive data on health needs to inform economic evaluation of population health interventions, support rational resource allocation and identify inequalities in disease burden across sub-populations and socio-economic groups


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RESPIRATORY
Title: Exploring the feasibility of using remote respiratory monitoring to detect and manage exacerbations of chronic obstructive pulmonary disease
Funder: Chief Scientist Office (Scotland)

Abstract: In people with COPD: 1. Does measurement of respiratory rate with less intrusive methods agree with gold standard measures? 2. What is the background variation in respiratory rate and resting respiratory rate? 3. For what period of time does respiratory rate need to be measured to provide a stable indication of resting respiratory rate? 4. How does respiratory rate correlate with perceptions of breathlessness, pulse rate and oxygen saturation? 5. How does respiratory rate vary in people recovering from exacerbations? 6. How acceptable is daily measurement of respiratory rate?


Research activity codes: 5.3 MEDICAL DEVICES
Health categories: RESPIRATORY
Title: 2013 Cochrane Fellowship: Interventions for enhancing adherence to treatment in adults with bronchiectasis
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Over 600 million people worldwide suffer from chronic respiratory disease, presenting an immense challenge to health care systems globally. In Northern Ireland, respiratory disease is the fourth leading cause of death, with chronic respiratory disease consisting 30% of respiratory disease hospital bed days and 13% of deaths in Northern Ireland. Brochiectasis is one of the most neglected chronic respiratory diseases. There is a paucity of evidence for treatments for this condition despite its impact on morbidity, mortality and healthcare costs. Prescribed treatments are often burdensome involving a complex and time-consuming regime of inhaled, nebulised and oral therapies and airway clearance. Consequently, optimising treatment adherence has been highlighted as an important component of disease management. Recent data has shown that only 16% of adults with bronchiectasis studied were adherent to all prescribed treatments and 21% were non-adherent to all prescribed treatments. Furthermore, those who were adherent to inhaled antibiotics had significantly fewer pulmonary exacerbations (2.6 per year) compared to those who were non-adherent (4 per year). These data indicate a need to implement effective strategies to improve adherence in this patient population; however, the most effective types of adherence interventions/components of interventions are unknown. The proposed Cochrane review aims to identify the evidence base for adherence interventions in bronchiectasis and will include any adherence interventions to any treatment prescribed for adults with bronchiecstasis in both primary and secondary care settings e.g general practice and hospital out-patient settings. Sub-group analyses will be conducted by intervention type and settings where appropriate. It is anticipated that interventions may include patient educational and self-management programmes and behavioural interventions such as motivational interviewing. The primary outcome will be adherence to a specified treatment. Secondary outcomes will include health outcomes such as pulmonary exacerations, health-related quality of life, lung function, hospital admissions, mortality and healthcare costs.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RESPIRATORY
Title: Evaluating and improving case finding approaches for undiagnosed COPD in primary care
Funder: Department of Health (England)

Abstract: Aim: 1. Conduct a systematic review of COPD case finding studies. 2. Develop a risk stratification tool for COPD case finding. 3. Audit the management of patients identified through case finding. Methods: 1. A systematic review will first be conducted looking at all relevant trials investigating the effectiveness and cost-effectiveness of COPD case finding. All relevant bibliographic databases including Medline, Embase, and the Cochrane Library will be searched using explicit search criteria. The results of trials will be pooled in a meta-analysis if appropriate. 2. A risk stratification tool for COPD case finding will be developed using data from the case finding trial. This will include ever-smokers aged 40-79 years, with no prior diagnosis of COPD, responding to a simple respiratory questionnaire and undergoing spirometry within the trial. Predictor variables including demographic variables, body mass index, co-morbidities, respiratory symptoms and previous hospital admissions will be examined to develop a risk model for COPD. This model will be used to produce a risk stratification tool which will be validated on a subset of the study population. This will be followed by a cost-effectiveness analysis to estimate the cost per true case identified for differential risk sub-groups. 3. The management of patients identifed with COPD will be audited against the updated NICE guidelines for COPD. Data will be extracted from GP electronic records from all patients identified with COPD through a funded randomised-controlled COPD case finding trial in primary care. An additional set of 100 medical records will be examined manually.


Research activity codes: 7.3 MANAGEMENT AND DECISION MAKING;4.4 POPULATION SCREENING
Health categories: RESPIRATORY
Title: 2010 Doctoral Fellowships: Investigation of Keratincoyte Growth Factor as a novel therapy in acute lung injury
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: Acute Lung Injury (ALI) is a common devastating clinical syndrome characterised by life-threatening respiratory failure requiring mechanical ventilation associated with a high mortality / morbidity. A Cochrane systemic review of 14 different pharmacological treatments concluded that effective pharmacotherapy for ALI was extremely limited. Experimental and clinical studies have demonstrated an improvement in alveolar epithelial function is associated with resolution of pulmonary oedema and an improved outcome in ALI. Keratinocyte Growth Factor (KGF) modulates a range of mechanisms in vitro which are known to be important in the pathogenesis of ALI. In animal models of ALI, KGF treatment reduces alveolar capillary permeability, pulmonary oedema and improved survival. In ex vivo human models of ALI it reduces pulmonary oedema. Clinical studies have indicated that the reparative activity associated with increased KGF in the setting of severe alveolar damage is insufficient and that further augmentation of KGF level may be required for restoration of alveolar function during injury. Hypothesis: KGF may provide beneficial effect to subjects with ALI. Objectives: The primary objective of the study is to investigate if KGF improves important surrogate clinical outcomes. The secondary objectives will investigate the mechanisms by which KGF modulates the course of ALI. Benefits: The benefit of this study will provide data to design a phase 3 clinical study to investigate the effect of KGF therapy on the outcome in ALI.


Research activity codes: 6.1 PHARMACEUTICALS
Health categories: RESPIRATORY