Sleep problems are a common side effect of many cancer treatments. Now our critical care research team has shown that a six week exercise programme helps rectal cancer patients get a better night's sleep. Cancer chemotherapy can be extremely tough physically, leaving patients feeling tired and worn out, often affecting the quality of their sleep. Promising new results from a recent trial, published in the journal Perioperative Medicine, suggest that exercise could hold the key to giving these patients the rest they need to get their strength back. 'Prehab' exercise programme Dr Sandy Jack from our NIHR Southampton Respiratory Biomedical Research Unit is investigating the impact of exercise on surgical care and recovery, and in this latest study her team looked at whether a six week exercise programme before surgery can boost cancer patients' recovery. It is well established that patients who are fit and active prior to surgery have better survival outcomes, and Dr Jack and team are focussed on 'prehabilitation' therapy - optimising exercise to better prepare patients for chemotherapy and surgery. Their work has shown improvements in physical fitness going into, and immediately after surgery, and has underpinned a pilot clinical service that has reduced hospital stay length. Improving sleep This particular study looked at sleep quality in 33 rectal cancer patients, comparing those who undertook the six week prehab exercise programme against those who received standard care. Participants wore the SenseWear Armband Pro device to monitor their sleep and activity from just before they started their chemotherapy and radiotherapy treatments until six weeks later, when the exercise programme finished. Sleep efficiency, duration and lying down time were better in those who had the prehab programme, suggesting that exercise could help cancer patients sleep better.

Babies whose mothers felt stressed before they fell pregnant had a higher risk of eczema at age 12 months, new research has shown. Led by Professor Keith Godfrey, director of our NIHR Southampton Biomedical Research Centre, the study is the first to link preconception maternal stress to the risk of atopic eczema in children. The researchers believe the findings support the concept that eczema partly originates as a baby develops in the womb and could reveal ways of reducing the risk of the skin condition. Stress before pregnancy The research, published in Clinical and Experimental Allergy, assessed the stress levels of women recruited to the Southampton Women’s Survey before they were pregnant. They were asked to report how stressed they were in their daily lives, with a sub-group asked about their psychological wellbeing. Around 3000 babies born into the survey were then assessed for eczema at ages six and 12 months. Women who reported that stress affected their health ‘quite a lot’ or ‘extremely’ gave birth to children with a 20% higher likelihood of developing atopic eczema at age 12 months. Mother to child The researchers think this may be due to the mother’s hormonal balance under stress, which can affect the baby’s immune system and could lead to an increased risk of eczema. Their findings also showed that stress and low mood experienced closer to the time of conception could have a greater impact on the risk of atopic eczema in the child. The link was clear even when other factors were accounted for, including a history of eczema in the mother, smoking during pregnancy and infant gestational age, sex and breastfeeding duration. “More research is needed to investigate this interesting association,” commented Prof Godfrey, “but the findings are further evidence of the influence preconception maternal health and wellbeing has on infants.”

New research from our NIHR Biomedical Research Centre has shown that babies with eczema are at greater risk of developing tooth decay as a toddler, and are now looking for a shared cause. Eczema is a skin condition that causes areas of skin to become itchy, dry, cracked, sore and red. Atopic eczema, the most common form of eczema, is most common in children and often develops before a child’s first birthday. In young babies it can be associated with allergies to foods, which generally improve as the baby’s immune system matures. A team of researchers, including Professor Keith Godfrey, Director of the NIHR Southampton Biomedical Research Centre, has identified a link between atopic eczema and tooth decay in early childhood. The results, published in the Journal of Allergy and Clinical Immunology, could help to identify children most at risk of these common conditions, so they can be prevented or treated sooner. Discovering the link The study looked at children from Growing Up in Singapore Towards healthy Outcomes (GUSTO), a long-term project on the health of mothers and their children in pregnancy and early childhood. The researchers asked parents if their child had ever had atopic eczema, and if the answer was yes, went on perform skin prick testing to a variety of possible allergens. After comparing this against the children’s dental record at ages two and three, they found children with atopic eczema and a positive skin prick test reaction were more likely to develop tooth decay. Delving deeper into the cause The researchers are now investigating the cause of this link between tooth decay and eczema, and why these children are more susceptible to them. They suspect that the increased susceptibility to both conditions might stem from an underlying structural problem, making the surface of the children’s teeth and skin less able to act as a barrier. To find out if the two conditions could have a shared genetic cause, they will study genes such as Dlx-3, which is involved in both the formation of tooth enamel and the development of the skin.

Researchers at the NIHR Respiratory Biomedical Research Unit have developed a new 3D system to study human infection in the laboratory. Understanding the bacteria that cause tuberculosis (TB) in people better is the target for researchers using a new method, growing tiny spheres of infected lung tissue in the lab. TB kills 1.8 million people each year. A bacterial infection of the lungs, symptoms include a fever and a persistent cough that lasts for weeks, sometimes causing people to cough up blood. This latest research, funded by the Medical Research Council and published in the journal eLife, provides a new method for researchers to study how TB develops and test potential treatments. Creating the spheres By creating spheres of infected lung tissue, laboratory studies may more closely resemble conditions in the body. In order to tackle the technical challenges a diverse team of infectious disease researchers, engineers and bioinformaticians from Southampton and University College London came together. They used a technique known as electrostatic encapsulation to make tiny spheres of collagen – a connecting tissue in the body – and human lung cells. Using a particular collagen matrix to mimic the environment found in a human lung meant they were able to create conditions for the lung cells that more closely reflected events in patients than similar 2D techniques, using single-layers of cells in laboratory dishes. Using this model and infecting the cells with TB, they could investigate what happens in a human body when TB develops. In the long term, they hope to use it to identify new antibiotic treatments and vaccines. A better model These spheres have many advantages as a model of TB over the standard 2D systems, providing an environment that is more similar to the inside of an infected lung. Using the spheres, the researchers were able to study aspects not possible in other 2D model systems, such as testing whether antibiotics can successfully kill the bacteria and treat the infection. The 3D spheres also enable experiments to be conducted for a much longer period, lasting up to three weeks - more than four times longer than standard 2D model systems. This enables research investigating how the infection develops and the effect of treatments over time. The next phase The next phase of the research will be in collaboration with the African Health Research Institute in Durban, in a project being funded by an MRC Global Challenges Research Fund Foundation Award worth £350,000. Durban has a very high incidence of TB, and ideal laboratory infrastructure to introduce the 3D model to study cells from patients at high risk of developing the disease.

Boosting children’s development by providing better support for families has been proposed by team of researchers, including Professor Mark Hanson from the NIHR Southampton Biomedical Research Centre. A review of current evidence on approaches to promoting children’s development, published in the Lancet, has shown that supporting families helps give children the best possible start in life. Covering all aspects of caring for a child, including good nutrition and hygiene, interacting well with the baby and ensuring they stay safe, the review evaluated 40 different approaches and identified 15 that were successful in promoting the healthy development of babies and toddlers. Starting right Babies born into a stable home, with good nutrition and a caring environment tend toreach their developmental milestones, such as walking and talking, at a younger age. The first few years of a baby’s life are a particularly important time, when key brain regions develop, they forma bond with their mother and learn essential skills. Good nutrition for both the mother and child during this period is essential to give babies the best possible start. During pregnancy, women can be given advice on which supplements to take, foods to avoid, and how to eat a healthy diet. And after birth, breastfeeding and a healthy diet for the child can make a big difference. Better support The researchers discovered 15 different approaches that help to improve children’s early development, and recommend ways that these could be introduced on a large scale. If these approaches could be integrated into the existing care the child receives, they are more likely to be effective. This is why they recommend combining support for families, healthcare providers and schools, to cover the entire period from early pregnancy to when the child is five years old. By looking at all aspects of childhood development, they hope these new services will help to give families the support they need to give their child a great start.

Babies with a rash or wheezing when they are less than 18 months old are more likely to develop allergies later in life, according to our latest research with mothers in Singapore. New research by Professor Keith Godfrey from our NIHR Biomedical Research Centre, working with our long-term project with women and babies in Singapore, has identified early indicators that could potentially be used to predict and prevent allergies from developing in young children. Their results, published in the journal Allergy, Asthma and Clinical Immunology, found that babies who had the skin condition eczema or wheezing before they were 18 months old were more likely to go on to develop an allergy as toddlers. Preventing allergy Allergies are a widespread and growing problem in the UK, with 50% of children having some form of allergic condition. They include food allergies, hay fever and the most common form of asthma. Allergies develop due to an excessive immune response, with the body reacting to otherwise harmless substances such as peanuts, pollen or dust mites as if under attack from bacteria, viruses or parasites. Most people with allergies have mild symptoms such as sneezing, a runny or blocked nose, itchy and watery eyes, wheezing, coughing or a rash, but extreme allergic reactions can lead to anaphylaxis, a life threatening shock response that can lead to loss of consciousness. Starting young Because allergies emerge at an early age, predicting which babies are most at risk helps avoid ’sensitisation’ – in which the immune system is exposed to the allergen and starts treating it as a threat. Almost 850 babies took part in the latest study, undergoing allergy tests for dust mites, eggs, peanuts and cow’s milk at18 months and three years old. Mothers’ answers about their lifestyle, whether they had a family history of allergy and the child's general health were also recorded. The data revealed that babies who had eczema or wheezing before they were 18 months old were found to be more likely to go on to develop an allergy by the time they were three. These early indicators could help predict which babies are most likely to develop an allergy, enabling prevention through existing treatments and direct the development of new ones used to catch allergies before they even begin. This approach could have a major impact on the quality of life and health of millions, cutting costs to healthcare and the economy.

On the 18 January 2017 the research leads of Southampton’s new NIHR Biomedical Research Centre came together with colleagues to discuss its work over the next five years. In September 2016 the National Institute for Health Research (NIHR) awarded nearly £15 million to Southampton researchers. Funding a new NIHR Southampton Biomedical Research Centre, this five year award brings together in one centre our strengths in clinical nutrition and respiratory research, data science, microbial science and behavioural science. Researchers and collaborators form across our existing NIHR facilities and beyond came together at the BRC Science Day to discuss the centre's strategy, their ambitions for the centre and to explore new ideas, collaborations and links. Looking ahead The first half of the event focussed on the centre's plans, with an introduction from director-designate Professor Robert Read followed by talks and open-floor discussions covering the nutrition, respiratory and cross-cutting research themes – data science, behavioural science and microbial science. Those cross-cutting themes formed the focus for the three afternoon sessions, exploring ideas and potential collaborations across across scientific and clinical disciplines. A great start This day was the start of the BRC's engagment and events with the local research community, generating plenty of buzz, new ideas and connections by the end of the day. Through this day, and more like it, the BRC leadership team aim to bring the researchers who will form the new centre closer together, to help shape its success from April 2017 onwards.

A Southampton team has been awarded the Team Research Award for research into nutrition in children with primary ciliary dyskinesia (PCD), a rare inherited condition that affects the lungs. Winning the award Southampton has achieved success in competing for the newly established Health Education England (HEE) Wessex Team Research Awards, with the PCD teams awarded prize money to further their research. The Team Research Awards were introduced for the first time in 2016 by HEE Wessex to enable small teams of healthcare professionals to collaborate on an applied clinical research project. In addition to receiving £14,000 in prize money, the PCD team will attend fully funded launch and closing events. Combining our expertise The new collaborative PCD research project will involve staff from both NIHR Southampton Respiratory Biomedical Research Unit and NIHR Southampton Biomedical Research Centre, combining the expertise of Professor Philip Calder’s nutrition team with Professor Jane Lucas’ PCD group. PCD is a rare genetic condition which renders ineffective the tiny hair-like structures lining the airways of our lungs called cilia. Patients with PCD are born unable to clear mucus from their lungs, leaving them with a persistent cough and frequent sinus, ear and chest infections from an early age. Following previous research in patients with cystic fibrosis, where an association between a low body mass index (BMI) and reduced worsening lung function has been demonstrated, the team is keen to investigate the importance of nutrition for children with PCD. Improving children’s lives The team will be led by Dr Woolf Walker, consultant in paediatric respiratory medicine and lead for the National Children’s PCD Management Service in Southampton, and Dr Luise Marino, paediatric lead for dietetics/SLT, along with PCD clinical nurse specialists Amanda Harris and Amanda Friend. “Having the opportunity to answer a clinical question through academic enquiry is so important, as it shapes our clinical practice,” says Luise, “enabling us to improve patient care and the quality of life of the children and the families we see, which at the end of the day is the most important thing.” Children with PCD who take part in the project will undergo a detailed nutritional assessment, the results of which will be use to inform a personalised nutritional intervention for each patient. The aim is then to assess whether this is beneficial in a subsequent study. “The aim of this work is to develop nutrition strategies with the aim of integrating nutrition support into the management of children with PCD, as we feel that it is likely to help improve their outcomes and quality of life,” comments Woolf. “If the data ends up showing that it’s helpful to integrate nutritional support in children with PCD, then we plan to roll this out to all children with PCD in England.” The hope is that, if successful, this study could lead to nutritional schemes for children with other chronic diseases.

Southampton researchers have developed a new clinical tool to diagnose the rare disease primary ciliary dyskinesia, enabling more patients to get the specialist care they need. Primary ciliary dyskinesia, or PCD, is a rare genetic condition which renders inneffective the tiny hair-like structures lining the airways of our lungs called cilia. As these cilia are responsible for keeping the lungs clear of the bacteria we breathe in, those with PCD often get sinus, ear and lung infections. Early diagnosis is important to keep the airways as healthy as possible and prevent lung damage. There is currently little guidance for lung, ear, nose and throat specialists for PCD diagnosis and referral for specialist treatment. Now researchers at the NIHR Southampton Respiratory Biomedical Research Unit have published in The European Respiratory Journal a description of their new PCD diagnostic tool PICADAR. Diagnosing it early Patients with PCD are unable to clear mucus from their lungs, leaving them with a persistent cough and frequent sinus, ear and chest infections from a young age, alongside a greater risk of infertility and congenital heart problems. The disease is characterised by malfunctioning cilia, which protrude from specialised cell types and serve a wide variety of functions in the body. Earlier diagnosis for PCD enables the family to receive support and the disease to be managed appropriately from a young age, so improving the long term outlook for the patient. Symptoms such as ear infections, for example, need to be treated differently. Yet the condition often goes undiagnosed or is diagnosed later in life, since current diagnostic methods require expensive equipment and an experienced team, unavailable to doctors referring the patient. Simple and cost effective The study was set up to produce a quick and easy to use scoring tool to predict whether patients showing symptoms have PCD. The researchers recruited patients from Southampton’s PCD diagnostic centre, who had an interview with the doctor at the start of their appointment. During the interview, their doctor asked questions about their symptoms, such as a daily cough, ear infections or heart problems, and used their answers to give a score indicating whether or not they have the condition. This was repeated for a small subset of patients at another clinic to check they received the same diagnosis. This provides a new simple, cost effective guide for doctors to use to determine whether a patient needs to see a PCD specialist. Through improving diagnosis and management of this condition from an early age, it is hoped that this tool will improve the lives of those with PCD.

In a UK-wide clinical trial, our NIHR Respiratory Biomedical Research Unit is testing a promising new drug for a chronic cough, as a key partner in the NIHR Translational Research Partnership. As part of the NIHR Translational Research Partnership (TRP) for inflammatory respiratory disease, we are trialling a new drug as a new treatment for chronic cough. If approved, this could provide the first new cough drug in 50 years and offer hope to the millions of people living with chronic cough for whom few, if any, effective treatments exist. No effective treatment Whilst it is not known exactly how many people suffer from a chronic cough, it is thought to affect around 12-15 percent of the population. A cough is considered to be chronic when a patient has experienced coughing for eight weeks or more, with many patients living with the condition for years and even decades without effective treatment. Some patients experience coughing that is so severe it can lead to them vomiting or losing consciousness. The 12-week trial will involve 200 patients at 47 sites in the UK and US, and will test the drug AF-219, developed by US based biotech company Afferent Pharmaceuticals. The VitaloJAK cough monitor, specially developed by the TRP, will be used to objectively record and count the number of coughs in a 24 hour period. Patient recruitment is now underway and due to complete in the next two months. AF-219 works by selectively blocking the P2X3 receptors, stopping the mechanism by which certain airway nerves become hyper-sensitised. In an initial proof-of-concept study, the drug reduced the number of times people coughed by 75% compared to placebo. Working together The TRP for inflammatory respiratory disease is an NIHR collaboration between nine UK centres, consisting of existing university and NHS hospital partnerships. It is led by internationally recognised investigators in respiratory research, and is one of two NIHR TRPs that provide the life sciences industry with an effective platform for experimental medicine and early development of new drugs and diagnostics. Led by Professor Ratko Djukanovic, NIHR Respiratory Biomedical Research Unit, Southampton’s branch of the TRP works closely with the UK's leading academic and clinical centres for experimental medicine and translational research.

Research at the facility is investigating what participants think about genomic testing and their experience of taking part in the NHS’s world-leading project to sequence 100,000 genomes. The 100,000 Genome Project aims to support genomics research across the UK and create a new genomic medicine service within the NHS. It is a national project to identify the underlying genetic causes of rare diseases and cancer. Our NIHR Wellcome Trust Clinical Research Facility has supported a study led by Professor Anneke Lucassen investigating what those involved in the project think about their experience taking part and their views on how the new genomic medicine service should be implemented. Genomics vs genetics Most people have heard of genetics, but the concept of genomics is less familiar. Genetics is the study of genes, usually individual genes and their roles in health and disease. Genomics lookes at the whole genome – a person’s complete set of genetic information. The 100,000 Genome Project is the first national initiative to incorporate genomics into medicine. Since the project has the potential to radically change the healthcare system, and it is important that patients have a say in how the new genomics service will be run. Genomic tests can reveal results for diseases other than the one the patient was tested for, so the service will need to handle this extra information appropriately. They could also have implications for family members, who may be at risk and could be offered the test, or influence a patient’s decision to start their own family. Listening to patients The three year study, led by Dr Sandi Dheensa, involves sending out questionnaires to people involved in the project, including both patients and their close relatives. Interviews will then be conducted with a small subset to delve deeper into the reasons for their answers. Anneke sits on the ethics committee of Genomics England, the company set up by the UK Department of Health to run the 100,000 Genome Project. Her group’s research influences decisions on how to deliver the new NHS genomic medicine service to meet the needs of patients. “It’s really helpful to hear what patients think about this as they go through the process” says Anneke, “previous research focussed on what people thought they would do were genome analysis available. What people do in practice can be quite different to considering a hypothetical situation.” Her research will also look at the referral pathways for patients. “Genomics means that specialists may discover risks of disease they are quite unfamiliar with; cardiologists discovering breast cancer risk, for example.” This will have implications for the health service, and her research results will inform future guidelines for health professionals in this rapidly advancing field of medicine.

Surgeons in Southampton are trialling a new drug based on a chemical antioxidant found in broccoli to improve outcomes for brain haemorrhage patients. Diederik Bulters, consultant neurosurgeon at Southampton General Hospital, and his team are assessing the effect of experimental drug SFX-01 on patients receiving treatment for a bleed on the brain known as a subarachnoid haemorrhage (SAH), a type of stroke. Preventing brain damage SAH is normally caused by a weakness in the wall of a blood vessel that bursts open, leading to a haemorrhage in the brain. More than 6,000 people in England, mainly aged between 45 and 70, are admitted to neurointensive care units with SAH every year. Around half of all cases are fatal, while many of those who survive are left disabled and suffer long-term cognitive and emotional problems. Currently, patients undergo a surgical procedure to repair the bleed. They then receive nimodipine to prevent the common complication cerebral ischaemia, which restricts blood flow to the brain through narrowing of the arteries. Extracting the benefits of broccoli Mr Bulters was already investigating sulforaphane, a chemical antioxidant found in broccoli as a potential treatment for SAH, when Evgen Pharma began developing a synthetic form, SFX-01, as a drug for breast cancer patients to overcome treatment resistance and relapse. After promising early results in the laboratory, Evgen agreed to sponsor a clinical trial of SFX-01 for SAH. Sulforaphane is one of a group of plant chemicals – phytochemicals – that are strong antioxidants and can alter our blood vessels’ functions. By improving blood flow to the brain, SFX-01 could help to prevent complications after SAH. It’s a significant moment for the team, realising the potential benefits of sulforaphane in a form that is stable enough to be administered as a drug. The trial will involve 90 patients over two years, with those receiving SFX-01 given either a 300mg dose capsule or dissolved via nasogastric tube, together with standard treatment nimodipine.