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Revolutionary technology has potential to help children with asthma

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

BHP members Birmingham Women’s and Children’s Hospitals have initiated a new study which could potentially revolutionise care for young people with asthma using artificial intelligence technology.

Over the next two years, 50 children and families will take part in the Childhood Home Asthma Monitoring  Study (CHAMP), which uses a small table-top electronic device designed by Albus Health, not dissimilar in size to an Amazon ‘Alexa’ virtual assistant, to personally monitor a child’s symptoms and breathing while they sleep.

Using sensors and a microphone, it measures breathing and heart rate by analysing coughs, wheezing and other noises, while also assessing environmental factors, such as humidity and air pollution levels. The data collected over a period of months will help form a unique and personalised set of triggers which is able to warn of a future asthma attack days before it potentially happens, allowing for action to be taken.

Around one in 11 children in the UK has asthma and it’s one of the most common chronic conditions which causes hospitalisations. The potential of this AI technology is potentially huge; positively impacting thousands in the future.

Dr Prasad Nagakumar, Respiratory Consultant, is the Chief Investigator leading this exciting £1.6million CHAMP study, funded by the National Institute for Health Research. He’s looking forward to working alongside partners including Asthma UK, Imperial College London, Oxford Academic Health Science Network and Royal Brompton Hospital, where patients are also being recruited to take part.

Dr Nagakumar said: “I’m delighted that we’ve now started this exciting study, which has such a huge potential. Over the next two years we’ll be working hard to further understand and develop the use of this innovative monitoring and, importantly, prediction technology.

“Our aim is to build algorithms and clinical-supporting tools for the early detection of asthma attacks in children by capturing warning signs before patients or those giving care perceive them.”

Professor Jeremy Kirk, Clinical Director NIHR Clinical Research Network (West Midlands) and Research and Innovation Director at our Children’s Hospital, said: “Asthma is the most common chronic disease in childhood and blights many lives. This project utilises the very newest cutting-edge technologies to give us further understanding of this condition, hopefully enabling better monitoring, optimal care and a reduction in hospital admissions.

“Dr Nagakumar and the team are to be congratulated on being awarded this highly competitive and prestigious grant.”

brain illustration

Genetically-determined levels of inflammation linked to neuropsychiatric illness

Written by Louise Stanley on . Posted in Inflammation and chronic disease, Mental health.

A potential link between inflammation and the structure of specific regions of the brain has been identified by researchers at BHP founder-members the University of Birmingham.

The study, published today in JAMA Psychiatry, may be particularly relevant for neurodevelopmental psychiatric disorders including autism spectrum and schizophrenia.

Researchers say the findings could open up a completely new target for the pharmacological treatment of these disorders, which has not significantly changed since the identification of antipsychotic medications in the mid-late 20th century.

The research was carried out by a team based in the University’s Institute for Mental Health and Institute and Institute of Cancer and Genomic Sciences, with collaborators from the University of Cambridge, Manchester and Bristol. It showed that genes associated with inflammation, particularly interleukin (IL) 6, are linked to a reduction in grey matter volume in certain areas of the brain known to be implicated in neuropsychiatric disorders.

Using records from the UK Biobank, a large-scale biomedical database, the team was able to compare genetic variants which affect levels of IL-6, and other inflammatory genes in more than 20,000 patients with changes in grey matter volume in specific areas of the brain.

They were able to show strong links between IL-6 and brain structure particularly in the temporal and frontal regions. Further analysis using the Allen Human Brain Atlas, showed that genes overexpressed in these areas are associated with conditions such as epilepsy, cognitive dysfunction, and schizophrenia.

Professor Rachel Upthegrove of the University of Birmingham Institute for Mental Health, explained: “This study shows that the IL-6 gene, which we know to be linked to systemic inflammation, also affects brain structure in areas associated with these neuropsychiatric disorders. Understanding these links offers an exciting opportunity to explore new treatments which target IL-6. This could be the first new target for severe mental illnesses including schizophrenia identified in more than 60 years.”

Dr John Williams, of the Institute for Cancer and Genomic Sciences at the University, a first author on the paper, said: “Current treatments for these illnesses act on dopamine, a chemical messenger in the brain associated with mood and attention. These drugs can have side effects, however, and they are not effective in all patients.

“There are drugs already on the market which target inflammation as well as the opportunity to screen potential new compounds. Finding a new avenue for exploring the links between inflammation, brain structure and neuropsychiatric disorders is really exciting.”

The work is part of the PIMS (Psychosis Immune Mechanism Stratified Medicine Study) programme, led by the University of Birmingham and set up to investigate the links between inflammation and psychosis. In the next phase of the research, the group will carry out experimental studies to knock out IL-6, as well as replicating the Biobank research in more diverse patient cohorts.

a woman injects insulin into her abdomen

Diabetes: Birmingham launches five new research studies

Written by Louise Stanley on . Posted in Clinical trials, Health inequalities, Inflammation and chronic disease.

BHP founder-member the University of Birmingham has announced the launch of five new major studies aimed at improving the prevention, treatment and management of type 1 diabetes – with a particular focus on children and young adults.

The new studies include:

  • The ELSA Study: Led by Professor Parth Narendran, the ELSA Study (EarLy Surveillance for Autoimmune diabetes) will see researchers interviewing families, doctors, nurses and schools, to determine if, and how, the UK should develop a testing and monitoring programme that will identify children at risk of type 1 diabetes. The ELSA Study is being funded by the National Institute for Health Research (NIHR), and is being carried out in collaboration with Birmingham Health Partners, Birmingham Community Healthcare NHS Foundation Trust and the Department of Health and Social Care, as well as the Universities of Cardiff, Warwick, Oxford and Imperial College London.
  • Diabetes and health inequalities: Through £1.9m funding from NIHR, Professor Tim Barrett’s team will ask children and young people with diabetes and their families from poorer and/ or ethnic minority backgrounds how language issues, feelings, income, living conditions and food availability affect how they manage diabetes. They will identify new ways to make diabetes management easier and more successful, and will test these systems in trials involving NHS hospitals.
  • Immunotherapies for diabetes: The greatest barrier to the development of specific immunotherapies for type 1 diabetes is that we currently do not understand the mechanism of how immunotherapies switch off the immune response to our own proteins. A clinical study led by Professor David Wraith, and funded by $735,000 from The Leona M. and Harry B. Helmsley Charitable Trust, will be carried out in collaboration with Cardiff University. It will test a new peptide developed by the University of Birmingham, work which was also funded by the Helmsley Charitable Trust with a $610,000 grant. The new peptide has the potential to control the T-cell immune response in people who are either at risk of developing type 1 diabetes or are newly diagnosed. In this study, the team will assess the changes in immune cells from the site of injection, the draining lymph nodes and peripheral blood. This will be the first in-depth analysis of the molecular changes responsible for antigen-specific immunotherapy in type 1 diabetes.
  • Sight loss and diabetes: Two separate projects led by Dr Jose Romero Hombrebueno will explore the function of membrane-bound cell organelles, known as mitochondria, which generate most of the chemical energy needed to power the cell’s biochemical reactions. The researchers will examine the role of mitochondrial function in both the development of multiple health conditions as the consequence of type 1 diabetes, and also the role it plays in developing diabetic retinopathy – an eye condition that can cause sight loss and blindness in people who have diabetes. The latter research is being funded by Diabetes UK, while the former is being funded by the European Foundation for the Study of Diabetes.
  • Exercise and type 1 diabetes: Led by Dr Alex Wadley and funded by the Rosetrees Trust, this research will examine how a home-based exercise programme impacts autoimmunity in patients with newly diagnosed type 1 diabetes. The project will evaluate whether exercise slows the progression of type 1 diabetes by altering the number and activity of white blood cells in the circulation that have the potential to attach to, enter and degrade the pancreas. Although evidence supports a role for exercise to promote general health and wellbeing in patients with type 1 diabetes, this project aims to provide novel evidence that exercise can directly slow the progression of the disease upon diagnosis.

Parth Narendran, Professor of Diabetes Medicine at the University of Birmingham’s Institute of Immunology and Immunotherapy, said: “The UK has one of the highest incidences of type 1 diabetes in the developed world, at 25 per 100,000 per year, and type 1 diabetes is the most common form of diabetes in children. It occurs when cells that make insulin don’t work as they should, and people with the condition have to self-inject insulin for their entire lives. Studies have recently shown that some medicines can safely delay people getting type 1 diabetes. Some countries, such as the US and Australia, already have surveillance systems to identify people at risk of developing type 1 diabetes and to offer them participation in prevention trials and also to reduce their chances of developing type 1 diabetes as an unexpected emergency. The UK does not have such a system in place. Until now, nobody in the UK has explored whether parents and children would welcome such a system, and how it would work. Through ELSA we will potentially be able to change NHS healthcare policy which would result in the early detection and prevention of this condition and its associated long-term complications.”

Timothy Barrett, Professor of Paediatrics and Child Health at the University of Birmingham’s Institute of Cancer and Genomic Sciences, said: “Diabetes causes high blood sugar levels, which can lead to eye and kidney damage if the condition is not well managed. We know that better sugar control reduces this risk, however, children with diabetes from poorer and/ or ethnic minority groups, often have worse sugar control, while these complications often develop when they are young adults who are working and starting families. There is little evidence to show any previous interventions have helped in reducing health inequalities for children with diabetes in different groups. We will work with young people, their families, and diabetes clinicians to develop an action plan that families feel comfortable with and that will support them to improve their self-management.”

Professor David Wraith, Director of the University of Birmingham’s Institute of Immunology and Immunotherapy, said: “Studies have shown that immunotherapies could play a vital role in treating type 1 diabetes, and it’s essential that we can develop new drugs that could specifically target cells that cause the body’s immune response to behave the wrong way in a person with type 1 diabetes. Our project will help improve our understanding of how the human body’s immune system responds to therapies, which in turn will help the development of new treatments.”

Dr Jose Romero Hombrebueno, Hale-Rudd Lecturer in Experimental Ophthalmology at the University of Birmingham’s Institute of Inflammation and Ageing, said: “It is estimated that 224 million people will have diabetic retinopathy and 70 million will have sight-threatening diabetic retinopathy by 2040. Nearly 90-95% of patients with type 1 diabetes and 78% with type 2 diabetes are expected to develop minimal retinal damage after having diabetes for more than 15 years. Therefore it’s essential that we carry our research that will help advance our knowledge of the underlying causes and potential ways to treat or prevent vision loss in those with diabetes.”

Dr Alex Wadley, of the University of Birmingham’s School of Sport, Exercise and Rehabilitation Sciences, said: “It’s estimated that around 70% of patients with type 1 diabetes do not meet the current recommended exercise guidelines of 150 minutes per week. We are using a home-based exercise programme, which has proven highly popular and safe for individuals with type 1 diabetes, to evaluate how regular exercise impacts the immune system of newly diagnosed patients. Type 1 diabetes is a disease where the body’s own white blood cells attack the pancreas and stop insulin production, resulting in high blood sugar. Regular participation in exercise is key to supporting health and wellbeing in people with type 1 diabetes, but we don’t know how exercise directly impacts these white blood cells that do the damage. With limited therapies available for patients currently, we hope that our findings can promote the use of exercise as an important lifestyle choice for patients and impact standard treatment approaches for type 1 diabetes nationally.’’

tablets

New drug treatment regimen shows promise for patients with lupus

Written by Louise Stanley on . Posted in Clinical trials, Inflammation and chronic disease.

The results of a randomised controlled trial, published in Annals of Internal Medicine, found that a new drug treatment regimen – using belimumab soon after rituximab – reduced a disease-related autoantibody and severe disease flares in lupus patients.

Systemic lupus erythematosus (SLE or lupus) is a long-term autoimmune condition, causing a variety of problems including joint pain, skin rashes, kidney disease and tiredness. While there is no known cure for this debilitating disease, the BEAT-Lupus clinical trial found that the combination of belimumab and rituximab shows promising results; reducing severe lupus flares by 3-fold for patients who had persistent, severe lupus disease requiring rituximab therapy at the beginning of the study.

Senior author Professor Caroline Gordon, Emeritus Professor of Rheumatology and member of the Institute of Inflammation and Ageing’s Rheumatology Research Group, together with colleagues from University College London conducted a phase 2 randomised trial involving 52 patients with SLE that was refractory to conventional treatment and whose physicians had recommended rituximab therapy. Patients were treated with rituximab and then randomly assigned four to eight weeks later to receive intravenous belimumab or placebo for 52 weeks.

The researchers found that IgG anti-dsDNA antibody levels were lower in belimumab-treated patients at 52 weeks compared with placebo-treated patients (geometric mean, 47 versus 103 IU/mL; 70% greater reduction from baseline). The risk for severe flare was reduced significantly with belimumab versus placebo (hazard ratio, 0.27), with three and 10 severe flares in the belimumab and placebo groups, respectively. There was no increase seen in the incidence of serious adverse events in the belimumab group.

Professor Michael Ehrenstein, Chief Investigator of the BEAT-Lupus trial, said: “Thanks to the dedication of the lupus teams at participating hospitals we are delighted to not only have completed recruitment, but also to provide preliminary evidence for a clinical benefit of the combination of rituximab and belimumab, compared to patients treated with rituximab alone.”

“These findings support further exploration of belimumab after rituximab as the first combination biologic therapy for patients with SLE, at least in those whose disease is refractory to conventional therapy and/or requires high corticosteroid dosages,” the authors write.

Professor Gordon previously pioneered the methodology for assessing lupus disease activity and flares using the BILAG-2004 index. The main secondary clinical outcome of reduction of severe lupus flare in the BEAT-Lupus trial was based on this work, and flare was defined using this index.

She explained: “We were delighted to find that this treatment regimen not only reduced disease causing autoantibodies but also reduced severe flares which cause very distressing symptoms and disruption to patients’ lives. This study offers the hope that this combination of drugs will be useful in the future if the results are confirmed in a larger trial.”

The study was funded primarily by Versus Arthritis; GlaxoSmithKline provided belimumab free of charge, as well as some additional funding.

woman in pain

Contraceptive pill can reduce type 2 diabetes risk in women with polycystic ovary syndrome

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

A study led by BHP founder-member the University of Birmingham has revealed for the first time that the contraceptive pill can reduce the risk of type 2 diabetes by over a quarter in women with polycystic ovary syndrome (PCOS).

The research findings also show that women with PCOS have twice the risk of developing type 2 diabetes or pre-diabetes (dysglycemia) – highlighting the urgent need to find treatments to reduce this risk.

In addition to the risk of type 2 diabetes, PCOS – which affects 10% of women world-wide – is also associated with a number of other conditions in the long-term, such as endometrial cancer, cardiovascular disease, and non-alcohol related fatty liver disease (NAFLD).

Symptoms of PCOS include irregular periods or no periods at all, which can lead to fertility issues, and many suffer from unwanted hair growth (known as ‘hirsutism’) on the face or body, hair loss on the scalp, and oily skin or acne. These symptoms are caused by high levels of hormones called androgens in the blood of women with PCOS.

Women with PCOS also often struggle with weight gain and the cells in their body are often less responsive to insulin – the hormone that allows the body to absorb glucose (blood sugar) into the cells for energy. This reduced response to insulin can lead to elevated blood glucose levels and can cause the body to make more insulin, which in turn causes the body to make more androgens. The androgens further increase insulin levels – driving a vicious circle.

The University of Birmingham-led team of scientists carried out two studies to firstly identify the risk of developing type 2 diabetes and pre-diabetes in women with PCOS, and secondly to investigate the impact of the use of combined oral contraceptives, often referred to as ‘the pill’, on the risk of type 2 diabetes and pre-diabetes in women with PCOS. The pill is often given to women with PCOS to improve the regularity of menstrual bleeds.

Using UK patient GP records of 64,051 women with PCOS and 123,545 matched control women without PCOS, they first carried out a large population-based cohort study to analyse the risk of type 2 diabetes and pre-diabetes. They found that women with PCOS were twice at risk of type 2 diabetes or pre-diabetes, compared to those without PCOS. They also identified hirsutism (excessive hair growth) – a clinical sign of high androgen levels – as a significant risk factor for type 2 diabetes and pre-diabetes among women with PCOS.

To investigate the impact of the pill on type 2 diabetes or pre-diabetes, the researchers, including experts at the RCSI University of Medicine and Health Sciences, then carried out a further nested case control study of 4,814 women with PCOS. The scientists found that use of combined oral contraceptives reduced the odds of developing type 2 diabetes and pre-diabetes in women with PCOS by 26%.

The researchers behind the study, published in Diabetes Care, are now planning to carry out a clinical trial to further evidence their findings in the hope it will lead to changes in global healthcare policy.

Co-senior author Professor Wiebke Arlt, Director of the University of Birmingham’s Institute of Metabolism and Systems Research, said: “We knew from previous, smaller studies, that women with PCOS have an increased risk of type 2 diabetes. However, what is important about our research is that we have been able to provide new evidence from a very large population-based study to show for the very first time that we have a potential treatment option – combined oral contraceptives – to prevent this very serious health risk.”

Joint first author Dr Michael O’Reilly, Health Research Board Emerging Clinician Scientist and Clinical Associate Professor at RCSI University of Medicine and Health Sciences, added: “We hypothesise that the pill reduces the risk of diabetes by dampening the action of androgens. How does this work? The pill contains oestrogens which increase a protein in the blood called sex hormone-binding globin (SHBG). SHBG binds androgens and, thereby, renders them inactive. Thus, if the pill is taken, SHBG increases. This decreases the amount of unbound, active androgens, lowering their impact on insulin and diabetes risk.”

Joint first author Anuradhaa Subramanian, also of the University of Birmingham, added: “With one in 10 women living with PCOS, which is a life-long metabolic disorder, it is incredibly important that we find ways of reducing its associated health risks.”

Co-senior author Krish Nirantharakumar, Professor in Health Data Science and Public Health at the University of Birmingham’s Institute of Applied Health Research, added: “Importantly, our data highlight that normal weight women with PCOS were also at increased risk of type 2 diabetes and pre-diabetes. This parallels our previous finding of increased NAFLD risk in normal weight women with PCOS, further challenging the notion that PCOS-related metabolic complications are only relevant in the context of obesity. These data suggest that, rather than obesity in isolation, PCOS-specific factors, including androgen excess, underpin the increased metabolic risk.”

The study was supported by funding from Health Data Research UK, Wellcome Trust, the Health Research Board, and the National Institute for Health Research Birmingham Biomedical Research Centre which is based at BHP founding members the University of Birmingham and University Hospitals Birmingham NHS Foundation Trust.

The research was also carried out in collaboration with the University of Colombo in Sri Lanka, and McGill University in Canada.

Specific cell population plays key role in effect of arthritis and people’s pain

Written by Louise Stanley on . Posted in Inflammation and chronic disease.

Research led by scientists at BHP founder-member the University of Birmingham has identified a new specific population of cells that plays a key role in the affect arthritis has on the body and the subsequent pain felt by patients.

The research team, led by scientists from the University ’s Institute of Inflammation and Ageing, conducted a clinical trial involving 52 patients with osteoarthritis – the most common type of arthritis in the UK – which causes joints to become painful and stiff.

All of the patients had osteoarthritis in their knee and were aged between 35 and 85. Of these patients, 29 had early stage disease, while 22 had end-stage disease.

The team, including experts from the University of Bath and Birmingham’s Royal Orthopaedic Hospital, measured levels of inflammation of the lining of the knee joint at different anatomical sites using MRI scans.

Patient-reported pain severity and pain location was recorded using a knee map, where patients marked the anatomical location of where they felt most pain and where they felt least pain or no pain. The researchers then collected joint lining tissue biopsies from parts of the knee where patients reported feeling pain, as well as areas where patients felt no pain.

Corresponding author Dr Simon Jones, of the Institute of Inflammation and Ageing, said: “Inflammation of the joint lining membrane is a known characteristic feature of osteoarthritis. However, its association with joint pain has previously not been clear because both the amount and specific location of inflammation and the location and severity of pain varies among patients.

“Our findings showed that in patients with osteoarthritis of the knee, inflammation of the joint lining membrane tissue was associated with both the location and severity of patient reported joint pain.

“Critically, for the first time we were able to demonstrate that joint lining tissue at the site of patient-reported pain contained a different gene signature, with specific populations of cells – called synovial fibroblasts – that promoted joint inflammation and the growth and survival of nerve cells.”

A gene signature contains information about the activity of a specific group of genes in a cell or tissue. Gene signatures can show how likely certain diseases of conditions can develop or spread and can be used to help diagnose disease, make a prognosis and plan treatment.

Dr Jones added: “Current pain relief medications for patients with knee osteoarthritis are limited in their effectiveness and can cause adverse side effects. Our data provides the rationale to develop therapeutic drugs that are designed to control the activity of specific joint lining cells in order to alleviate joint pain in osteoarthritis patients.”

The research, funded by Versus Arthritis, was carried out over a period of almost four years and is published in the journal EBioMedicine.