NIHRDataInsights/HRCSData huggingface dataset:
Title: Achieving sustainable improvements in respiratory health through integrated care
Funder: Department of Health and Social Care

Abstract: The overall aim of the theme is to improve the health of patients with chronic lung diseases by establishing new patient centred models of integrated care from early diagnosis through to end of life. The approach will be to study the impact of novel approaches to treatment and service delivery in limited pilot studies. Strategies which improve diagnosis, treatment outcomes and offer health economic benefits will be implemented across the wider AHSN and impacts continually assessed using quantitative techniques established by the theme.


Research activity codes: 7.4 RESOURCES AND INFRASTRUCTURE (DISEASE MANAGEMENT);4.5 RESOURCES AND INFRASTRUCTURE (DETECTION)
Health categories: RESPIRATORY;GENERIC HEALTH RELEVANCE
Title: CADTIME: Clean Air for Delhi Through Interventions, Mitigations and Engagement
Funder: Natural Environment Research Council

Abstract: CADTIME: Clean Air for Delhi Through Interventions, Mitigations and Engagement The Clean Air for Delhi Through Interventions, Mitigations and Engagement (CADTIME) project aims to understand what is required to deliver significant reductions in levels of air pollution, within the confines of factors which are under our control, through affordable, effective interventions that consider and respond to future changes. CADTIME brings together a consortium of institutions and experts from across both India and the United Kingdom with the goal of addressing air quality issues that affect people's health in Delhi. This goal will be achieved through the development of an Integrated Action Plan (IAP), detailing strategies and potential interventions for mitigating air pollution in both the city, and surrounding region. The IAP will be based on development of a sound understanding of the current contributing factors to air pollution across the domestic, transport, industrial and agricultural sectors, for Delhi, as well as forecasting of how those sectors will change across the short, medium and long terms. The plan can only be realised through the contributions of government agencies, local stakeholders and collaboration with population at large. The use of workshops, focus groups and extensive consultation will ensure that proposed strategies are realistic, clearly defined, well targeted and mindful of technological and social constraints. Above all strategies will be economically viable and environmentally sustainable. They will also be far-thinking and cross-cutting, embracing political, technological and behavioural change. The CADTIME project is envisaged to run over a 48-month period. Initial stages of the project will involve the development of modelling tools, such as collating emissions inventories and dispersion models, as well as the collection of information on current policies and best practice for mitigation within the city and region. The international nature of the consortium will allow a golden opportunity for academics and researchers from both nations to learn from each other. Latter stages of the project will see collaboration with stakeholders coming to the fore, as the IAP takes definition and shape. Care will be taken to ensure that, wherever possible, the strategies defined for Delhi will also have relevance to other major urban areas in the sub-continent. In addition to Delhi, the CADTIME consortium includes the Indian Institutes of Technology of Madras and Bombay. Ultimately, the beneficiaries of the CADTIME project will be the Indian People and Government through a reduction in the burden of ill health that is inflicted upon them by air quality.


Research activity codes: 3.2 INTERVENTIONS TO ALTER PHYSICAL AND BIOLOGICAL ENVIRONMENTAL RISKS
Health categories: RESPIRATORY;GENERIC HEALTH RELEVANCE
Title: Exposure to particulate matter on the London Underground in healthy subjects and patients with chronic respiratory disease
Funder: Medical Research Council

Abstract: There is evidence of the health effects of breathing atmospheric particulate matter (PM). In particular that traffic-derived particulates have adverse impacts on ischaemic heart disease and chronic obstructive pulmonary disease (COPD). Inhalation of urban particulate matter induces airway oxidative stress with an acute inflammatory response that may upregulate systemic inflammatory responses. Although the effects of atmospheric PM have been under scrutiny, little is known about the effects of subway PM. A forthcoming report by the Committee on the Medical Effects of Air Pollutants (COMEAP) has highlighted the presence of high concentrations of PM on the London Underground. Many of the PM2.5 measurements made in the London Underground are higher than those measured in other locations worldwide, most probably due to its age, depth, tunnel distance and limited ventilation. PM2.5 mass was found to be approximately 15 times higher in the Underground (mean 302 ugm-3) than roadside environments (mean 26 ugm-3) in central London. Elevated concentrations of PM in the London Underground are caused by additional sources, principally the wear of train consumables (e.g. wheels, brake blocks and electrical contacts), non-rolling stock sources (e.g. rail grinding and wear, people) and station sources (escalators and refurbishment work). The composition of PM therefore has a different composition to that of atmospheric PM, with underground PM2.5 found mainly to contain iron oxides, with the remaining mass made up of elemental carbon and organic carbon. We will undertake a randomised crossover study to investigate the health effects of PM on the London Underground in patients with COPD, and will employ healthy persons as a control group. A study of this disease with a focus on common vascular and inflammatory responses will enhance our understanding of potential mechanisms for cardio-respiratory outcomes.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: RESPIRATORY;GENERIC HEALTH RELEVANCE;INFLAMMATORY AND IMMUNE SYSTEM
Title: Opportunity-Led Research Proposal: The epidemiology, diagnosis and outcomes of Aspergillus infection in ventilator-associated pneumonia: A UK multicentre prospective study
Funder: Health and Social Care Research and Development Division (HSC R&D) of Public Health Agency, Northern Ireland

Abstract: While there is a substantial amount of published literature on invasive aspergillosis (IA), almost all of this relates to the neutropenic and stem-cell transplant populations. There are very limited data for the non-neutropenic critically-ill patient group, but estimates of its incidence in this population vary widely. The true incidence of IA in this group is difficult to estimate precisely for several reasons but, importantly, it is underdiagnosed: invasive fungal infections recurrently emerge among the most common missed diagnoses in critically-ill patients. A major barrier to improving the detection rate of IA in the critical care setting is the absence of a validated diagnostic test that is known to perform well. It follows that if the incidence of IA in the UK critical care population was estimated and a test validated, this would lead to an increase in disease detection in this patient group. The proposed study seeks to address this need by validating two novel, rapid, diagnostic tests in a multicentre trial of critically-ill patients with suspected ventilator-associated pneumonia (VAP). Galactomannan and Aspergillus DNA detection by PCR will be evaluated using both blood and bronchoalveolar lavage fluid specimens. Futhermore, we will for the first time establish the incidence of IA in this patient group in the UK critical care setting. We will prospectively recruit 450 patients from six UK intensive care units, fulfilling criteria for clinically suspected VAP, during a 36-month study period beginning December 2011. This recruitment is being carried out as part of a Wellcome Trust-supported c£1M clinical diagnostic trial to evaluate the performance of a novel markerlL-1b for confirming bacterial pneumonia in ventilated patients. As a result, no funding is required for research infrastructure costs, research nurses, recruitment costs, cost of conducting bronchoscopy, nor clinical trials unit research management costs. Furthermore, Gilead Sciences have committed £254k to fund a full-time research fellow for three years as well as meeting the cost of some laboratory tests to be carried out in a national reference laboratory. Therefore, this proposal represents a value-for-money approach to obtaining high quality data by utilising specimens obtained in the course of a high-cost multicentre trial funded from another source. By estimating the burden of illness attributable to IA in this population and also validating the performance of two rapid diagnostic tests, the proposed study will provide data that may increase the number of critically ill patients with IA who receive appropriate diagnosis and treatment.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.4 POPULATION SCREENING
Health categories: RESPIRATORY;INFECTION
Title: Delayed recovery in Community Acquired Pneumonia – causes and opportunities for tailored treatment
Funder: Department of Health (England)

Abstract: Pneumonia is a major cause of illness and death worldwide and is the most common infection related cause of adult admission to hospital in the UK. Community Acquired Pneumonia (CAP) refers to pneumonia in a person who has not recently spent time in hospital. Delayed recovery from CAP affects 30% of adult patients admitted to hospital with pneumonia and can result in protracted illness and major economic cost to the NHS and wider the economy. The reasons why some people recover more slowly than others are not known. It is likely that both the bacteria which cause CAP and the patient’s inflammatory response to CAP are important in determining speed of recovery. The aim of this study is to investigate differences in bacterial populations in the lungs of people with CAP and explore associations with speed of recovery and mechanisms involved in the resolution of inflammation caused by CAP. Over 18 months we will recruit patients admitted to hospital in Liverpool with CAP and study their recovery over 6 months of follow-up. The complete spectrum of bacteria in the lung of each patient will be described using a technique called 16S rRNA sequencing. Patients will be invited to undergo bronchoscopy tests during their recovery to investigate how the lung’s immune system differs in those who recover slowly or quickly. Specifically, we will investigate differences in a mechanism called efferocytosis. We hope the results will lead to treatments to enhance recovery from CAP and to improved antibiotic prescribing guidelines.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY;INFECTION
Title: Information and education provision for patients with bronchiectasis
Funder: Department of Health (England)

Abstract: The chronic lung disease bronchiectasis affects patients' health and quality of life. Better education could help patients self-manage their condition, improving their quality of life and long-term health. Objectives: To identify and understand patients' information needs; developing high-quality, patient-driven information that will improve patients' ability to manage their condition. Design: Qualitative interviews and focus groups will be used to develop the information package. A pilot study will assess acceptability to patients and feasibility of a future trial investigating impact on health and quality of life. Outcomes/benefits: High-quality, patient-driven bronchiectasis information could improve patients' knowledge, self-management, health and quality of life.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: RESPIRATORY;INFECTION
Title: Respiratory Tract Infections In Children With Down’s Syndrome: Towards Better Management Using Health Informatics And Working With Their Carers
Funder: Department of Health (England)

Abstract: One in every 1000 UK babies has Down’s syndrome. Children with Down's syndrome are prone to respiratory infections which may cause them to be admitted to hospital. Since most research on such infections has excluded children with Down’s syndrome, doctors are unsure how best to prevent and treat them. Working with families and doctors involved in the care of children with Down’s syndrome, we will focus on improving management of respiratory infections in these children by linking NHS data on GP visits and hospital admissions to use of vaccines and antibiotics.


Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.1 PHARMACEUTICALS
Health categories: RESPIRATORY;INFECTION
Title: Regulation of interferon production in the lung during respiratory syncytial virus infection
Funder: Medical Research Council

Abstract: Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections in humans. In 2-3% of children the infection leads to severe bronchiolitis such that RSV is by far the most common cause of hospitalisation among infants. Severe bronchiolitis is associated with polymorphisms in several innate immune response genes, in particular many that control the IFN system. Innate IFNs (type I and III) are produced very early and upon direct recognition of the virus. They are important for inducing antiviral responses and to activate cells of the innate and adaptive immune systems The role of these cytokines in regulating host resistance and immunopathology during RSV infection in young and adults is poorly understood. Using a mouse model of RSV disease I will study the molecular and cellular regulation of innate IFN production in response to RSV in vivo. Firstly, I will elucidate which cells are infected by RSV and which cells produce IFNs in response to RSV in vivo. In addition, I will determine which pattern recognition receptors are involved in the induction of innate IFN production. Secondly, I will test the hypothesis that the production of innate IFNs might be limited in the young and that this contributes to the development of immunopathology (bronchiolitis). Neonatal and adult mice lacking individual IFN receptors will be infected with RSV and development of immunopathology will be compared. This will test the prediction that neonates are more dependent on signalling via each of the IFN receptors than adults because of lower overall IFN production. The results from this proposal will increase our understanding of the role of IFNs in immune responses to RSV and in the development of immunopathology during RSV infection. This will assist the development of strategies to find an efficient immune therapy to prevent RSV-associated bronchiolitis and to develop vaccines against RSV.


Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY;INFECTION
Title: The prospective testing of the accuracy of a prognosis prediction score in pleural infection
Funder: Medical Research Council

Abstract: This proposal is to test a potentially powerful, novel, low-cost, and readily translatable prediction model that could be applied at presentation to all patients with pleural infection. If it is successful in prospective clinical testing, this model would allow clinicians to reliably identify subjects with pleural infection at high risk of death and poor outcome to receive targeted extra supportive care, surgery, and newer complex and expensive intrapleural interventions. Successful completion of this study would result in an immediately applicable score, which could be rapidly disseminated into care through specialist care guidelines. The core of the prediction model is a combination score based on the blood urea, albumin, blood pressure, age, and the source of the infection. These factors have been identified using regression analysis from a previous large cohort of patients with pleural infection, and now require prospective testing. This clinical model will be combined with bacterial markers of prognosis recordable at baseline to create a novel multimodality score. If it is successful in prospective clinical testing, it would allow clinicians to reliably identify subjects at high risk of death and poor outcome to receive targeted extra supportive care, surgery, and potentially the complex and expensive intrapleural interventions that have recently shown efficacy in clinical trials conducted by our unit.


Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: RESPIRATORY;INFECTION
Title: Characterising the impact of chronic HIV infection on B cell immunity in the lung of Malawian adults
Funder: Wellcome Trust

Abstract: HIV is a major public health challenge in Sub Saharan Africa and lower respiratory tract infections (LRTIs) remains one of the leading causes of mortality and morbidity in HIV-infected individuals. A lot of studies focusing on peripheral blood have shown HIV-driven perturbations of B cells, however, there is paucity of data on impact of HIV on B cells in the airway. Recently, our group has shown that HIV infection leads to infiltration of B cells into the airway, but whether these B cells are functional is still unclear. My project aims to identify the phenotype, specificity and the functional capacity of the infiltrating B cells, and how this is impacted by antiretroviral therapy. Using flow cytometry, I will determine the phenotype and specificity of the infiltrating B cells, and using an ELISPOT assay I measure their functional potential. I hypothesise that chronic HIV infection alters airway B cell subsets, impairs airway B cell function and leads to recruitment of non HIV-specific B cells into the airway. A better understanding of airway B cell immunity is important for the development of novel therapeutic interventions targeted at reducing the high burden of LRTIs in this susceptible population.

Lay abstract: HIV is a major public health challenge in Sub Saharan Africa and lung infections remain one of the leading cause of death in HIV-infected individuals. HIV infection causes adverse effects on the immune system and studies done on blood have shown that one of the key immune cells affected are B cells. However, there is limited knowledge on the effect of HIV infection on B cells found in the lung. Work done in our group has shown that there is increase in the number of B cells in lung during HIV infection, however, whether these B cells are functional is still unclear. My aim is to determine the nature of these B cells found in the airway of HIV-infected individuals and to assess how well these B cells function. Findings from this research will contribute to development of new therapeutic interventions against lung infections.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY;INFECTION
Title: Extracellular polycation signalling in alveolar and systemic inflammation
Funder: Wellcome Trust

Abstract: Critically ill patients with pneumonia often have impaired neutrophil function and disruption of alveolar-capillary barrier integrity. During inflammation, excessive polycation generation activates the calcium-sensing receptor (CaSR), which can potentially compromise neutrophil function and barrier integrity. My over-arching hypothesis is that, during critical illness, CaSR, activated by polycations, mediates impairment of neutrophil, alveolar epithelial and pulmonary endothelial function, leading to reduced bacterial clearance and disruption of alveolar-capillary barrier. To test the hypothesis, I shall use a range of complementary methods to (a) assess the effect of positive and negative allosteric CaSR modulators and polycations on a range of functions in neutrophils and monocytes from critically ill patients at high risk of developing nosocomial infection; (b) isolate human primary alveolar epithelial cells and culture primary human pulmonary microvascular endothelial cells, and assess the effect of CaSR modulators on barrier function, inflammatory signatures, and antimicrobial functions; (c) perform the first temporal assessment of CaSR expression (and effect of CaSR inhibition) in extravasated neutrophils and alveolar macrophages from human healthy volunteers receiving inhaled lipopolysaccharide (LPS) or control; and (d) create neutrophil-specific CaSR knockout mice, assessing the influence of neutrophil CaSR on the natural history of acute pulmonary infection, inflammation, and alveolar-capillary barrier disruption.

Lay abstract: Critically ill patients often develop reduced immune function and inappropriate “leak” of fluid into the airspaces of their lungs, contributing to the high mortality rates. Evidence suggests that activation of a calcium-sensing receptor (CaSR) in their lungs may drive these unwanted processes, but this has not been studied comprehensively. To address this, I shall: - obtain immune cells from critically ill patients and establish if their function can be restored by suppressing CaSR; - grow the key lung cells, and assess whether their anti-leak and anti-infection functions are altered by targeting CaSR; - genetically remove CaSR from the key immune cells (called neutrophils) in mice, to work out how important neutrophil CaSR is in fighting lung infections. The proposal will define the importance of CaSR in critical illness, potentially suggesting new treatment approaches for severe infection, and provide me with knowledge I need to become a leader in this area.

Research activity codes: 2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: RESPIRATORY;INFECTION
Title: Probing the sequence of cellular activation by rhinoviral infection in the airway and identifying how this may be dysregulated in COPD
Funder: Medical Research Council

Abstract: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and disability globally. Human rhinoviruses (RV) are a frequent trigger of acute exacerbations in COPD patients, and contribute considerably to the healthcare and economic burden of this disease. Whilst the receptors responsible for RV detection within human bronchial epithelial cells (HBECs) are known, how endosomal pattern recognition receptors (PRRs) detect RV replication products that are generated within the cytoplasm remains somewhat of an enigma. This study will explore autophagy as the crucial mechanism controlling this process. Our preliminary data reveals that inhibition of autophagy significantly reduces RV-induced cytokine generation in HBECs. Initial work will build on these findings, determining the role of autophagy in modulating the response of HBECs to RV infection, probing its function in viral presentation to PRRs and the resulting effects on viral-induced cytokine generation and prodigy virion production. The autophagic pathway is reportedly augmented in the COPD airway. HBECs from COPD patients and control subjects will therefore be utilised to establish if RV infection is controlled differently in COPD airway epithelial cells due to differences in autophagy. Key autophagy genes and cellular pathways that are dysregulated in COPD will subsequently be identified. This research will therefore comprehensively explore a previously unidentified role for autophagy in regulating the innate immune response of airway epithelial cells to viral infection, both in health and during disease. It is believed that changes to the autophagic pathway in the COPD airway will alter the susceptibility and response to viral infection during acute exacerbations, resulting in increased inflammation with deleterious consequences. Identifying specific genes and pathways that are dysregulated in COPD will thus assist in the future development of novel therapeutics for this complex disease.


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