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Aston University and Birmingham Children’s Hospital study shows diagnosis and treatment of preschool wheeze needs improvement

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

A study led by Aston University’s Dr Gemma Heath and  Dr Prasad Nagakumar from Birmingham Children’s Hospital – both BHP member organisations – has shown that treatment and diagnosis for preschool wheeze needs more effective evidence-based guidelines.

Preschool wheeze affects approximately 30–40% of children under six. The condition is characterised by episodes of wheezing or breathlessness, with younger children being particularly susceptible due to their narrower airways. Although it can resemble asthma, preschool wheeze is often triggered by viral infections or allergies and does not always mean a child will develop asthma.

The UK has Europe’s second highest prevalence of preschool wheeze in two-year-olds and is a leading cause of emergency hospital visits and hospitalisations in the country. Repeated preschool wheeze attacks are frightening for parents, and result in significant morbidity, healthcare costs and impaired quality of life for both the child and parent.

There is currently no diagnostic pathway or definitive management guidelines for preschool wheeze. The research team interviewed affected parents and carers about their experiences, and found problems with diagnosis and treatment at multiple levels.

The first major issue identified by parents was inconsistent terminologies used by doctors, and confusing and conflicting diagnoses such as asthma, suspected asthma, viral wheeze and allergy. Some reported frustration at the lack of definitive diagnosis, an apparent lack of GP knowledge, sometimes false reassurance that the wheeze was viral rather than asthma, or that the cause was a “mystery”.

A common problem was that investigative tests did not occur until after multiple hospitalisations. Blood tests for particular markers have potential to identify whether asthma or an allergy is likely to have caused the wheeze, and therefore guide treatment. The parents in the study welcomed the idea of timely tests, but stressed that children should not be subjected to repeated testing.

Preschool wheeze is generally managed with steroid and salbutamol inhalers, as for asthma. While parents had concerns about the side-effects and long-term impacts of using the treatments, they deemed the medication “an acceptable cost”.

Parents reported being “terrified” while watching attacks of preschool wheeze, and significant psychological impacts when their child was admitted to hospital. Some had missed work or even given up work to care for their child, with high levels of anxiety, while others said they felt unable to go on holiday overseas due to concerns about healthcare access in the case of a wheeze attack.

Most parents preferred to access care at hospital rather that at doctors’ surgeries due to the perception of a lack of training for GPs and a lack of confidence. However, accessing necessary care can be difficult, including due to childcare difficulties, the cost of hospital parking and a lack of available ambulances.

The research team said that parents’ views highlight the problems and called for clinical trials to determine the efficacy of treatment decisions made according to the results of investigations.

Dr Heath said: “This research demonstrates an urgent need for preschool wheeze management policies and treatment pathways that are evidence-based and co-developed with parents. We have shown that use of investigations such as blood or allergy tests would be acceptable to parents, if they were shown to be helpful in guiding more effective and timely treatments.”

Dr Nagakumar said: “Preschool wheeze has significant impact on young children’s and their parents’ lives. Our research, involving parents with lived experience, will inform future studies to improve the care and reduce the impact of preschool wheeze on the already-stretched emergency health services in the UK.”

Archives of Disease in Childhood doi: 10.1136/archdischild-2024-327781

£3.4m boost for research into paediatric autoimmune brain inflammation

Written by Louise Stanley on . Posted in Birmingham Health Partners, Inflammation and chronic disease.

Dr Sukhvir Wright at Aston University‘s Institute for Health and Neurodevelopment (IHN) and Honorary Consultant Neurologist at Birmingham Children’s Hospital (BCH) – both BHP member organisations – has been awarded a £3.4m Career Development Award from Wellcome to research paediatric autoimmune encephalitis (AE), an inflammatory brain condition.

Every minute, someone in the world is diagnosed with encephalitis, which can be caused by an infection or have an autoimmune cause, where the body’s own immune system starts attacking the brain. The expert neuro-immunology team at BCH cares for children with autoimmune encephalitis all year round.

AE accounts for around a third of cases worldwide, with patients experiencing seizures, cognitive and sleep dysfunction and movement disorders. Although medical professionals are getting better at recognising and treating AE earlier, the long-term outcomes remain frustratingly poor, particularly in children under five.

Some symptoms of the disease, such as seizures, can resolve but others, such as problems with learning and memory, behavioural change and sleep disorders, can become chronic. Why some of these symptoms get better and others persist is not well understood. 

Dr Wright carried out a world-first preliminary study in a group of children with AE at least 18 months after they first developed the condition, using magnetoencephalography (MEG) brain scans. She found distinct long-term brain structure and network changes and believes that these brain changes are responsible for the chronic symptoms of the disease.

During her Career Development Award, Dr Wright will use laboratory models to characterise the mechanisms causing the chronic symptoms, examining the underlying changes from single brain cells to whole brain networks. She will also examine longitudinal brain network changes in children immediately following the acute attack of AE and for up to eight years afterwards using a new optically pumped magnetometer (OPM) MEG scanner.

IHN is an ideal location for the research project, as it houses the UK’s only paediatric clinical and research Wellcome Trust MEG laboratory. The MAG4Health OPM MEG scanner that will be used by Dr Wright was installed in 2024 following a Medical Research Council (MRC) equipment grant for £800,000 led by Aston University’s Dr Caroline Witton in partnership with BCH. The Aston-BCH OPM MEG uses an adjustable cap with sensors which is placed on the patient’s head, which allows some degree of movement and is therefore more acceptable for children.

Combining the data from the laboratory models and human patients will enable Dr Wright and her research team to identify commom pathophysiological targets, mechanisms and predictive biomarkers to reduce the adverse effects of AE and improve long-term outcomes.

Dr Wright is part of the expert neuroimmunology team at BCH, led by Professor Evangeline Wassmer, Paediatric Neurology Consultant. The AE research project will involve Professor Wassmer’s team, the BCH Psychology department led by Jo Horton, Professor Stefano Seri (neurophysiology) and Dr Laavanya Damodaran (liaison psychiatry).

Children and families with lived experience of AE will be directly involved with all aspects of the research to ensure it is answering questions that matter to them, including the family of one of the first AE patients ever treated by the neurology team at BCH. This patient and family involvement will be facilitated by the Epilepsy Research Institute’s Shape Network and Encephalitis International, two charities with which Dr Wright has strong links.

Dr Wright said: “We hope that this project will transform outcomes and optimise brain health in paediatric autoimmune encephalitis and beyond by delivering a significant shift in understanding the acute and long-term effects that autoimmune encephalitis has on children and young people.”

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Fitness app could transform care of rheumatoid arthritis patients

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

Researchers at BHP members Sandwell and West Birmingham NHS Trust and the University of Birmingham aim to transform the care of rheumatoid arthritis (RA) patients by developing an app which links to the Fitbit – a popular activity tracker.

The rheumatology medical team and researchers are leading the groundbreaking clinical trial to create the app which they hope will ease the pain of patients suffering from the crippling disease and provide extra support.

It’s called MISSION-RA which stands for MovIng to Support Sustained Improvement of Outcomes iN Rheumatoid Arthritis.

Sally Fenton, Chief Investigator for the study, said: “The app will be specifically designed for and by people with RA.

“This will be done in two ways. Firstly, a series of interviews, co-design studies and workshops will be carried out to develop the app. Then, artificial intelligence will be used within the app to provide personalised support for people living with RA, based on symptoms such as pain, fatigue and mobility. It is expected the app will be available to download for free so it can be used on a Fitbit in the future.”

RA leads to inflammation of the joints and surrounding tissues which causes flare ups – this is when symptoms become worse. One of the ways to help ease these episodes of pain can be through exercise, physiotherapy and occupational therapy.

Dr Sangeetha Baskar, Clinical Specialty Lead for Rheumatology and Principal Investigator for MISSION-RA explained: “Rheumatoid arthritis is an extremely painful, tiring, psychological and physically debilitating disease. Patients face countless challenges while doing basic daily activities such as dressing, cooking and walking and often become dependent on family members to perform some of their daily tasks. Through this innovative study and the mobile app, we are hoping to help patients increase their physical activity tailored for them and improve their quality of life.”

The first patient from the Trust has already been recruited into the study.

Ana Duarte, Clinical Research Practitioner (CRP) and also Associate Principal Investigator, said: “Overall, the MISSION-RA study has overcome our initial expectations. Patients are very keen and have enjoyed their experience so far. This has also been a great opportunity for the study staff which has led to progression in their careers. Most importantly, this we hope will place SWB’s R&D department and rheumatology team as international leaders in healthcare AI and machine learning.”

MISSION-RA is being delivered in partnership with the National Institute for Health and Care Research (NIHR) and National Rheumatoid Arthritis Society (NRAS).

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Patients with recent onset diabetes fast-tracked more effectively for pancreatic cancer screening

Written by Louise Stanley on . Posted in Cancer outcomes, Early diagnosis and detection, Inflammation and chronic disease.

A recent study, funded by Pancreatic Cancer UK and conducted by researchers at BHP’s University of Birmingham, in collaboration with University of Oxford, University of Nottingham and fellow BHP founder-members University Hospitals Birmingham NHS Foundation Trust, developed a new prediction model as an effective way of identifying individuals suitable for fast-track abdominal imaging.

Weight loss and glycaemic control are known biomarkers that can indicate pancreatic cancer risk and in, accordance with NICE recommendations, people over the age of 60 years with recent onset diabetes and weight loss currently undergo urgent abdominal CT imaging to assess for pancreatic cancer.

Pancreatic cancer is known for its poor prognosis, with less than a quarter of patients surviving past one year after diagnosis. Early detection is important as patients with early-stage disease are more likely to be able to tolerate chemotherapy and therefore have an improved 5-year survival rate, but most patients are not diagnosed until the later stages of the disease. One way of detecting pancreatic cancer patients sooner is through screening patients with diabetes as there is a known association.

By looking at further potential biomarkers to determine which patients would benefit from referral for abdominal imaging, there is a chance of picking more cancers and reducing the cost of imaging those who are not so high-risk.

Dr Shivan Sivakumar, Associate Professor in oncology, specialising in pancreatic, liver and biliary tract cancer, said: “One in ten pancreatic cancer patients have new-onset diabetes and we know that some patients with newly diagnosed diabetes are worth exploring further to improve early detection of pancreatic cancer. We need to more accurately predict which of those patients should be referred for further investigation. We used health data records, from a larger patient population than has previously been studied, to develop a more nuanced method of stratification that could improve referral pathways.”

This study used large-scale, population-representative, linked electronic health data records to develop and evaluate a new prediction model that can be used to predict risk of developing pancreatic cancer within two years of a diabetes diagnosis. The new models used a variety of potential markers and were able to predict pancreatic cancer risk in patients aged between 30 and 85 years, rather than relying on the 60+ rule of thumb.

This study was the largest of its kind and offers improved accuracy compared to previous prediction models as it used a larger data set. The new prediction model could be more effective than current ‘rules-based’ referral guidelines. Further external validation and health economic assessment is recommended.

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New stromal cell treatment trial for chronic inflammatory diseases

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

People with chronic inflammatory diseases are taking part in a new cell therapy clinical trial that one participant said made them feel “miles better”.

The POLARISE trial, being organised by BHP founder-member the University of Birmingham and funded by a grant from Innovate UK is testing a type of cell therapy – stromal cells – to see whether they can resolve symptoms and inflammation in patients with certain autoimmune diseases including rheumatoid arthritis and primary sclerosing cholangitis.

A Phase 2 trial, POLARISE will investigate the safety and activity of ORBCEL – a stromal cell therapy that has been developed by Orbsen Therapeutics Ltd. Stromal cells are rare cells found naturally in the human body where they stimulate resolution of injury and inflammation via a natural healing process called efferocytosis. Stromal cells are also allogeneic – which means they can be purified from one donor and given to multiple patients without causing allergic reactions – so there is no need for donor matching.

These rare stromal cells are ethically sourced and purified from human donor tissue and expanded to therapeutic doses at the University of Birmingham’s Medicines Manufacturing Facility (MMF).

The ORBCEL therapy is administered intravenously across two visits with subsequent hospital appointments to check on the progress of their condition during a two-year trial period.

Philip Newsome, Professor of Hepatology and Honorary Consultant Hepatologist at the University of Birmingham is leading the POLARISE trial, and explained: “Stromal cells are an exciting potential treatment for inflammatory diseases. These diseases are debilitating and very hard to treat as the body has switched a natural defence system for dealing with threats to one that starts attacking itself. It’s therefore critical to find ways to support the body to naturally deal with inflammation rather than turn off the defences which can lead to all sorts of infections. Early results from previous trials using Orbsen’s ORBCEL stromal cell therapy are encouraging and we’re hopeful that the treatment will be beneficial for some patients.”

Stromal cells such as Orbsen’s ORBCEL therapy can be purified from bone marrow or umbilical cord tissues donated by healthy individuals with donor consent under ethical approval by the Anthony Nolan Trust. While each single bone marrow or umbilical cord contains only few thousand stromal cells – these cells can be purified by Orbsen’s technology to undergo controlled expansion in cleanroom bio-reactors to produce a thousand allogenic doses of ORBCEL from each tissue.

Within the Innovate UK-funded Advanced Therapies Treatment Centre (ATTC) Consortium and POLARISE trial – these tissues are transported from the Anthony Nolan centres to the Advanced Therapies Facility (ATF) at the University of Birmingham – where Orbsen and ATF staff collaborated to purify and manufacture doses of Orbsen’s Stromal cell therapy – ORBCEL- using patented technologies and Terumo’s Quantum Cell Expansion Bioreactors.

Orbsen Therapeutics Chief Scientific Officer, Steve Elliman said: “We are delighted to continue our significant and productive clinical collaborations with Prof. Newsome, the University of Birmingham – and the Anthony Nolan Trust – to determine the safety and efficacy of our ORBCEL therapies in patients with chronic inflammatory diseases.

“These First in Human (FIH) trials are difficult to undertake and deliver – even more so during the COVID19 pandemic. These trials are not possible without brave patients – like Hannah Dines – who volunteer to participate in these rigorous safety trials. And so, we take this opportunity to thank the patients, nurses and clinical teams who work so hard to complete these invaluable studies.

“We look forward to completing these important safety trials and look forward to examine how ORBCEL can encourage resolution of symptoms in patients with chronic inflammatory disease.”

The Innovate UK-funded POLARISE trial represent the third major clinical trial collaboration between The University of Birmingham and Orbsen Therapeutics to assess the safety and efficacy of Orbsen’s ORBCEL therapy. Professor Phil Newsome is also leading the EU FP7 funded MERLIN clinical trial that is assessing ORBCEL as a therapy for patients with autoimmune liver diseases. The MERLIN trial is complete and is expected to report in the first half of 2024.

Orbsen is also collaborating with Prof Paul Cockwell at the University of Birmingham and Professor Giuseppe Remuzzi at the Mario Negri to assess the safety of ORBCEL as a therapy for Chronic Kidney Disease caused by Type 2 diabetes, in a Phase 1/2 clinical trial called NEPHSTROM. Professors Cockwell and Remuzzi recently published the first results from NEPHSTROM in the prestigious Journal of the American Society of Nephrology (JASN). In the NEPHSTROM trial publication in JASN, a low dose of ORBCEL was reported to be safe and promote stabilization of kidney function over 18 months in patients suffering with Progressive Chronic Kidney Disease and type 2 diabetes.

Patient story – Hannah Dines, Rio 2016 Paralympian

Self-confessed ‘type A person’, Hannah Dines is one for setting mad goals. Born with cerebral palsy, freelance writer and sportswoman Hannah trained and raced for Great Britain in para-cycling including racing at the Rio 2016 Paralympic games, and now represents GB in adaptive surfing.

However, in 2021 during the buildup to the delayed Tokyo games Hannah was diagnosed with a chronic inflammatory disease called Primary Sclerosing Cholangitis (PSC) in which the bile ducts in the liver get progressively narrower can lead to liver failure and impacts other organs like the spleen, intestines and bowel.

Hannah explains: “I was diagnosed with PSC after struggling with major fatigue and worsening of my spasticity from my cerebral palsy. I would train and feel very ill but do it anyway. I love moving my body and during the training I still felt that joy. Still, I began to fear the symptoms that would come after. I used to call it having an ‘exercise hangover’ though I rarely drank alcohol and was in my twenties. I would ensure I had at least four hours after training to collapse in bed, too tired to even watch TV, feeling too ill to sleep, known as malaise.”

“By the point of diagnosis though I was really ill and sleepy every day, I couldn’t focus but I kept pushing with my training, a part time job and then bed. Finally, a clinical doctor took my blood to put me on an alternative spasticity medication that required a liver function test. That’s when I was sent to a liver clinic and they took a liver biopsy right away and found out my sclerosis was pretty serious.

“It made all my symptoms make sense and because I was young and sporty no-one misdiagnosed me with fatty liver or alcoholism, which was nice, even if it didn’t really lessen the impact of having PSC.”

After receiving her diagnosis, qualified physiologist Hannah knew she wanted to try and take part in a clinical trial although received a series of rejections due to the advanced nature of her PSC.

Hannah continues: “I was recommended for POLARISE and I didn’t hesitate. The day after my first dose I felt incredible and not just because the clinicians administering the drugs were so nice. This effect lasted a couple of days and I truly felt released from PSC.”

“I was still competing at a sport: adaptive surfing and I booked all my contests because I knew I wouldn’t need to cancel. I laughed out loud on an aeroplane because I felt real energy for the first time in years. It was probably the steroids or a placebo effect but my liver function tests also got much better.

“My second dose was a little underwhelming compared to my first, but I still felt miles better. My “malaise” and feeling kind of “dead” had gone away.

“I used to obsess over my blood values and stopped checking them. I started setting goals more than two months in advance, which I had decided not to do after a year of having to cancel everything. We’re now six months and I still big hits of malaise but just to know that respite might be possible like at the start of my trial…that’s really special..

“All I can do is hope the findings are positive and this can become a regular treatment for people with PSC. No matter the result of POLARISE it has given me real hope for the future.”

Not letting PSC stop her, Hannah has taken up adaptive surfing and last year represented GB at the world championships, finishing fourth in her category and supporting Team GB to their most successful championships yet.

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Center of Excellence Award Renewal for Allergy, Asthma and Immunology Center

Written by Louise Stanley on . Posted in Birmingham Health Partners, Inflammation and chronic disease.

The Allergy, Asthma, and Clinical Immunology Center in Birmingham has been successful in renewing its Center of Excellence status for another four-year term – re-affirming the Center’s international recognition for multidisciplinary scientific and clinical innovation – following a successful bid led by Professor Mamidipudi Thirumala Krishna, representing Birmingham Health Partners.

Renowned for its innovative services to accelerate education and research, the Institute of Immunology and Immunotherapy, and the School of Pharmacy at the University of Birmingham in collaboration with the West Midlands Allergy and Immunology service at University Hospitals Birmingham (UHB) NHS Foundation Trust has once again been designated as a World Allergy Organisation (WAO) Center of Excellence.

There are currently 82 Centers worldwide, and only three other similar Centers of Excellence in the UK.

According to the World Allergy Organisation (WAO), their Centers of Excellence accelerate multidisciplinary science and clinical innovation, training, and advocacy worldwide to deliver world-class education, research, and training to stakeholders in asthma, allergy, and clinical immunology.

Professor Mamidipudi Thirumala Krishna said: “This continued recognition of our Center of Excellence signifies our commitment to delivering world-class clinical services, fostering excellence in education and research, and nurturing collaborative relationships both nationally and internationally and contributing to global health.”

Professor Ben Willcox, Director of the Institute of Immunology and Immunotherapy at the University of Birmingham, commented: “We are proud to see our Center of Excellence renewed, guided by the visionary leadership of Professor Krishna. We have over 50 years of experience in world-leading immunology research, and this Center’s status renewal is testament to that.”

Professor Anthony Cox, Head of the School of Pharmacy and Professor in Clinical Pharmacy and Drug Safety, said: “Great news that the World Allergy Organisation Center of Excellence has been extended. The School of Pharmacy is proud to be working with the center on issues related to allergy and medicines – including inappropriately identified drug allergies which have a considerable impact on patient safety and the rational use of medicines.”

Dr Richard Baretto, Clinical Service Lead for the Department of Allergy and Immunology at UHB, added: “This prestigious award from the World Allergy Organisation is testament to the efforts of all the members of the clinical teams, providing excellent care for our patients with allergic disease. It emboldens us all to strive for continued improvement in our service through regular review, research and innovation.”

Professor Adel Mansur, Lead for Birmingham Regional Severe Asthma Service, commented: “On behalf of the Birmingham Regional Severe Asthma Service I am delighted of the news of extending our status as World Allergy Organisation Center of Excellence, recognising the excellent work done in Birmingham. Over the last three years tremendous work and development have been achieved to further strengthen our Center in areas of research, education and training and to lead on clinical excellence in allergy, asthma and clinical immunology.”

“We have adopted various initiatives to improve our patients outcomes, access and equity of service delivery and provide conducive environment for our trainees to learn and develop skills and further their career.  Our national and international contribution to research and education in these fields are also important developments and targets to progress further over the next 4 years which I look forward to with excitement.”

Dr Gareth Walters, NHS consultant in occupational respiratory medicine and interstitial lung diseases in Birmingham, also added: “On behalf of the Birmingham Regional NHS Occupational Lung Disease Service , we are very pleased that our status as a World Allergy Organization Center of Excellence has been renewed for a further 4 years. This is testament to the hard work and dedication of our multi-disciplinary team, who go above and beyond to diagnose and manage a range of occupational lung diseases.”

The Allergy, Asthma and Immunology Center will continue to lead global healthcare innovation and pursue its commitment to excellence in research and education for another term commencing in 2024 to 2028. 

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