Newsroom University of 51��

The key to understanding asthma may lie in our body clock

Wed, 20 Oct 2021 10:58:35 +0100

Our body clock allows bodily processes to occur at certain times of the day, like eating, sleeping and body temperature.

But did you know that monitoring a person’s body clock (or circadian rhythm) could help diagnose and treat asthma?

New research supported by Asthma UK, a charity which provides health advice and a helpline to people with asthma as well as funding research into the condition, has revealed that asthma is “highly rhythmic”, meaning it is impacted by a person’s body clock.

It means the symptoms an asthma patient might have such as coughing, wheezing or shortness of breath, could be more intense at different times of day and this insight could revolutionise the way doctors treat the 5.4 million people in the UK who have asthma and help to prevent life-threatening asthma attacks.

The study carried out by Dr Hannah Durrington, a Clinician Scientist at 51�� and a Consultant in Respiratory Medicine at , part of , explored why people with asthma experience worse symptoms at night and in the early hours of the morning.

The results showed that tests used to diagnose asthma should take time of day into account, for example peak flow measurements (a quick test to measure air flow out of the lungs) are lower at 4am than at 4pm, and this is the case for other asthma tests.

Doctors assess the severity of asthma in a patient (particularly eosinophilic asthma, which is associated with high levels of a white blood cell called eosinophils) by measuring the levels of eosinophils in blood or sputum (phlegm).

Dr Durrington, who is also a researcher at the , revealed that these levels naturally change over the course of a day, so if doctors timed appointments around these variations, they would get a much more accurate picture of a person’s asthma.

Her research could help the medical profession determine whether there is an optimum time of day to use inhalers and take other asthma medication, so it has the best chance of keeping symptoms under control.

Dr Durrington said: “Asthma can have a huge impact on people, leaving them coughing, wheezing, gasping for breath and putting them at risk of having a life-threatening asthma attack. It is really exciting to think my research could play a part in making things better for people with asthma, helping doctors assess if patient’s symptoms are at their worst depending on the time of day and identifying exactly when people should take their inhalers to keep them well.”

Dr Erika Kennington, Head of Research at Asthma UK, which funded the study, said: “There is still so much we don’t know about asthma, and studies like these are a vital step in understanding the disease and ultimately leading to us finding a cure for this dreadful illness that causes the deaths of three people every day in the UK. But despite the fact that 5.4 million people in the UK have asthma, only two per cent of all medical research funding in the UK is spent on research into respiratory diseases."

New understanding of asthma medicines could improve future treatment

Mon, 27 Apr 2020 10:00:00 +0100

New research has revealed new insights into common asthma aerosol treatments to aid the drug’s future improvements which could benefit hundreds of millions of global sufferers.

Lung diseases such as asthma are a major global health issue, with an estimated 330 million asthma sufferers worldwide. The most effective treatments are through direct inhalation of medicine to the lungs. However, generating the aerosols for inhalation is a scientific challenge because of our limited knowledge of the microstructure of drug products before they are aerosolised.

In new research announced today University of 51��-based scientists demonstrate how they have used x-ray CT scanning to quantify the tiny microstructures of individual particles from the drug product at the nano-scale.

This is the first time that the 3D microstructure has been revealed and gives scientists and pharmaceutical producers a better understanding of the behaviour of the drug product under aerosolisation.

Lead author of the research, Dr Parmesh Gajjar said: “We have been able to visualise a drug-blend in 3D, and see the interplay between drug and non-drug particles in the medicine. This is important for final quality control of asthma medicines to check the actual amount of drug and to help formulate improved asthma medications.”

Due to the new technological innovation the findings was announced at the conference. The groups work was selected to be a key presentation at the global conference, originally scheduled to take place in Palm Springs but now occurring in a digital format as a result of the global COVID19 pandemic.

The work was made possible through the high-resolution x-ray computed tomography (XCT) instruments in the word leading (HMXIF) at 51�� that provide the capability to analyse a sample at up to 50 nanometres in resolution.

This is particularly important for the inhalation medicines which require aersolisation to generate particles small enough to be adsorb via the lungs. In this project the particles measured less than 5 µm to reach the deepest parts of the lungs.

The work is part of a funded national collaboration “INFORM 2020” between the Universities of Herfordshire, 51��, Leeds and Cambridge, with the support of 3M, Astra Zeneca, Glaxo Smith Kline, Malvern Panalytical and Carl Zeiss Microscopy that is seeking to revolutionise our fundamental understanding of Asthma medications for the design of more effective therapies.

Test could detect patients at risk from lethal fungal spores

Thu, 20 Sep 2018 15:34:00 +0100

Scientists at 51�� have discovered a genetic mutation in humans linked to a 17-fold increase in the amount of dangerous fungal spores in the lungs.

The study, published in Nature Communications could allow doctors to screen patients at risk from Aspergillus, and could easily be developed into a test.

When breathed in, Aspergillus can be life threatening and also make asthma much worse, especially in people with compromised immune systems. It is found in soil, pillows and compost but is capable of living anywhere in a moist environment, so breathing it in is unavoidable .

Aspergillus is normally cleared from the lungs but 4% of people have this newly discovered mutation and in them, Aspergillus thrives in the airways.

“People with asthma, who have had transplant surgery, TB and many other illnesses that lower immunity could feasibly be screened for this genetic mutation. And early detection could save lives,” said who led the study funded by the Fungal infection Trust and supported by the NIHR 51�� Biomedical Research Centre.

discovered the increased risk by comparing normal human cells to cells which had been gene edited to contain the mutation. The gene - known as ZNF77 - is mainly responsible for the extracellular matrix of the lungs’ epithelial tissue- the membrane that protects them. These mutated cells had a weak response to Aspergillus showing how key epithelial cells are to normal defences against this airborne fungus.

Dr Bowyer said: “Until now we never really understood why some people have a much higher Aspergillus load than others. Now that we do, it’s quite a significant advance in understanding this disease. We don’t yet know how or why the mutation occurs but nevertheless this discovery provides the basis for a simple and inexpensive DNA test in those who people who are more at risk from Aspergillus.”

Dr Gago is a Research Fellow funded by the National Centre for the Replacement, Reduction and Refinement of animals in research. She added: “ZNF77 doesn’t actually occur in mice, so the only viable animal models besides humans are primates. Having developed a way to adapt human cell lines so that they can carry mutations associated with disease, we have avoided using primates or any animals entirely.”

The paper ‘Colonization of lungs by Aspergillus fumigatus is controlled by ZNF77’ is published in DOI: 10.1038/s41467-018-06148-7

High blood sugar during pregnancy ups risk of mother’s type 2 diabetes and child’s obesity

Tue, 11 Sep 2018 16:00:00 +0100

Research conducted in part at 51�� has found that mothers with elevated blood glucose during pregnancy – even if not high enough to meet the traditional definition of gestational – were significantly more likely to have developed type 2 diabetes a decade after pregnancy than their counterparts without high blood glucose.

For children born to mothers with elevated or normal glucose, researchers found no statistically significant difference between the two groups of children in terms of their combined overweight and obesity, the study’s primary outcome. However, when obesity was measured alone, children of mothers with elevated blood glucose were significantly more likely to be obese.

The results are part of a published Sept. 11 in the Journal of the American Medical Association. Funded primarily by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), part of the National Institute of Health, and conducted at ten study sites, including 51�� the or HAPO-FUS, followed mothers and their children 10-14 years after birth.

Professor Peter Clayton, who led the 51�� research team, said: “Here in 51��, we recruited more than 500 mother-child pairs from the original HAPO study, conducted when the children were born. Many of the mothers and their children had also helped us with studies through childhood, as part of the 51�� Heart and Growth study.

“The work was carried out by our research team, which included Avni Vyas, Aysha Khan, Fiona Pritchard, Jane Howell and Andy Whatmore (from Developmental Biology & Medicine in the School of Medical Sciences), supported by the NIHR 51�� Clinical Research Facility and the Greater 51�� Clinical Research Network”.

The original HAPO study found that even modestly elevated blood glucose levels increased the risks of complications for the baby both before and shortly after birth. Based on these results many, but not all, organizations adopted a new definition of , a type of diabetes that occurs during pregnancy.

HAPO-FUS compared the long-term effects of blood glucose levels in mothers who would have met the new definition of gestational diabetes with those who did not. Researchers aimed to learn if modest increases in blood glucose increased the mother’s risk of developing type 2 diabetes or prediabetes and the risk of obesity in the mother’s offspring at least a decade after giving birth.

The study found the harms of even modestly elevated blood glucose for both mother and child extend more than a decade. Among women with elevated blood glucose during pregnancy, nearly 11 percent had at the follow-up study visit 10-14 years after childbirth and about 42 percent had . Of their counterparts who did not have elevated blood glucose during pregnancy, about 2 percent had type 2 diabetes and about 18 percent had prediabetes. The study examined 4,697 mothers for type 2 diabetes, prediabetes and other disorders of glucose metabolism.

Researchers analyzed 4,832 children for overweight and obesity, collecting data using body mass index (BMI), body fat percentage, skin fold thickness and waist circumference. They found that these measures all showed that children born to mothers with elevated glucose levels were more likely to be obese. For example, using BMI, 19 percent of children born to mothers with elevated blood glucose were obese, compared with 10 percent for children of mothers with normal glucose.

Adjusting for the mother’s BMI reduced – but did not eliminate – the differences between the groups.

“The differences in mothers and their children due to the mother’s higher blood glucose are very concerning. Even accounting for the mother’s weight, glucose had an independent effect,” said Dr. Barbara Linder, a study author and senior advisor for childhood diabetes research at the NIDDK. “Our findings add to the motivation to find ways to help women at high risk for gestational diabetes who are or plan to get pregnant to take steps to reduce their risk.”

The looked at 23,316 mother-child pairs and found that a mother’s blood sugar levels, even short of diabetes, were associated with her newborn’s birth weight and body fat. HAPO results led an international panel of experts to recommend new diagnostic criteria for gestational diabetes in 2010. However, not all professional groups adopted these proposed criteria.

“HAPO helped redefine gestational diabetes, and now its follow up continues to raise important alarms about the long-term danger of high blood glucose levels during pregnancy,” said study chair Dr. Boyd Metzger, emeritus Tom D. Spies Professor of Nutrition and Metabolism at the Northwestern University Feinberg School of Medicine, Chicago. “This study shows that both mothers with elevated blood glucose levels and their offspring are at higher risk for adverse health effects later in life. More research is needed to find interventions to help both these women and their children.” None of the women in HAPO-FUS were diagnosed with or treated for gestational diabetes during their pregnancy. HAPO recruited an international, racially and ethnically diverse group. Limitations of the data in HAPO include that body mass index was obtained during pregnancy, not before. As well, HAPO-FUS did not collect data on the women or children’s lifestyles to evaluate other factors that could contribute to obesity or type 2 diabetes.

The results build on findings from other studies showing that type 2 diabetes in mothers during pregnancy is associated with obesity in that mother’s offspring and that elevated blood glucose increases risk of type 2 diabetes in the woman after pregnancy.

“HAPO and its follow-up study have shown the detrimental long-term effects of elevated blood glucose on both mother and child and the importance of early intervention for women at risk for gestational diabetes,” said NIDDK Director Dr. Griffin P. Rodgers. “We hope these results will be used to improve the health of generations to come.”

HAPO-FUS was conducted at 10 clinical centers around the world

Body clock could be key to better Asthma treatment

Mon, 10 Sep 2018 15:13:00 +0100

The human body clock could have a significant impact on the way doctors are able to diagnose and treat asthma, according to new research.

Study leader Dr Hannah Durrington from 51�� says the work has important implications on clinical practice in asthma and other inflammatory conditions.

The study of over 300 severe asthmatics found their sputum samples were more than twice as likely to have more inflammatory cells - or eosinophils - in morning clinics than in the afternoon.

Levels of eosinophils - a biomarker in sputum - are used to guide treatment in severe asthma patients.

The study was funded by Asthma UK, the JP Moulton Charitable Trust, the North West Lung Charity and also the NIHR 51�� Biomedical Research Centre.

It is published in the American Journal of Respiratory and Critical Care Medicine.

Doctor and patients have long known that asthma symptoms are at their worst in the small hours of the morning.

But previous research has shown that the worsening symptoms are biological in cause, rather than a result of lying down.

Dr Samantha Walker, Director of Research and Policy at said: “This is an exciting preliminary study that reveals how powerful the body clock can be. If doctors and nurses know that the time of day can affect someone’s asthma they will be able to diagnose and treat them more effectively.

“Around 5.4million people in the UK have asthma and it can have a huge impact on their life, leaving them gasping for breath and at risk of a potentially fatal asthma attack. But asthma is a chronic condition with complex causes and triggers that can differ from patient to patient. More research into better ways of diagnosing asthma is urgently needed to develop better tests and to help develop more targeted treatments. For more information on how Asthma UK is supporting research and to get involved visit .”

Dr Durrington said: “These research results are really exciting but at an early stage – our aim was to understand a bit more about how the body clock affects the biochemistry of a person with asthma.

“But we are pleased because our work should help with the accurate diagnosis and treatment of asthma in the future.

“We feel it may also have important implications on other lung conditions, as well as outside respiratory medicine.

“Based on our results, different clinical decisions could be made depending on whether the patient is allocated a morning or afternoon appointment.

“And it also points towards opportunities for more personalised treatment for asthma care in the future.

“In the same way that measuring glucose levels in diabetes allows adjustment of insulin dosing, we may see asthmatics monitoring their biomarker chemicals during the day, to help inform optimum treatment times.”

51�� is home to the largest biological timing . Dr Durrington also provides an asthma clinic at Wythenshawe Hospital, 51�� University NHS Foundation Trust (MFT).

The paper, '' is published in the American Journal of Respiratory and Critical Care Medicine. DOI: 10.1164/rccm.201807-1289LE

Twitter helps us understand side effects of medicines, scientists find

Mon, 12 Feb 2018 11:00:00 +0000

A study of over 20 thousand Twitter posts has revealed that less serious side-effects of steroids worry patients the most.

51�� team led by examined different types of side-effects discussed by people using prednisolone, a commonly used steroid drug. They found the two most tweeted symptoms were insomnia and weight gain.

They used a computer system to automatically identify tweets containing the drug name as well as identifying mentions of what looked like a likely drug side-effect. It then converted lay terms like “Can’t sleep” to medical terms such as “insomnia”.

While insomnia and weight gain are well-known side-effects of prednisolone, research has historically focussed on more serious side effects such as osteoporosis and fractures.

Little attention has been given to less serious side-effects – yet this study suggests they worry steroid users more.

With the help of sophisticated computer software, 51�� team harvested 159,297 tweets mentioning prednisolone over three years.

Around 20,000 of the tweets also mentioned a suspected side-effect. Of the tweets analysed, 1,737 mentioned insomnia, 1,656 mentioned weight gain, 1,576 mentioned non-specific reactions such as ‘I hate Prednisolone’, and 1,515 reported increased appetite.

The research is published in the journal today.

Team member Dr Rikesh Patel, said: “Though Insomnia and weight gain were the two most commonly discussed side-effects, they are not usually highlighted by clinicians when prescribing prednisolone.

“Part of this is down to a lack of research investigating patient experience with their medications.

“We believe social media such as Twitter can be used to broaden knowledge about drugs and potential side-effects that patients themselves find troublesome.

“And this type of automatic extraction is an efficient way of getting this information, because we’re dealing with large volumes of data.

Professor Dixon added: “Our view is that social media sources such as Twitter can be useful because they can illustrate which drug side-effects patients discuss most commonly, even if they are not necessarily the most serious.

“Less serious side-effects are often missed in other research because patients may not mention their symptoms to their doctors, or they are not recorded in medical records. Yet this is despite them being troublesome.

“This form of research is clearly just one piece of the jigsaw, but it nevertheless is an important one.

“In this example, it helps re-focus our research into steroid-related side effects that are clearly important to patients.

“Social media posts may also give us a future view of how side effects impact on patients’ quality of life.”

Mould discovery in lungs paves way for helping hard to treat asthma

Mon, 15 Jan 2018 15:00:00 +0000

A team at 51�� have found that in a minority of patients they studied, the standard treatment for asthma - oral steroids - was associated with increased levels of the treatable mould Aspergillus in the lung.

The findings could be of valuable help to asthmatics who endure severe and difficult to treat symptoms, by giving doctors the information they need to plan their care more effectively.

The team stress there is no danger to asthmatics from steroid therapy and that patients should continue taking their steroid inhalers or tablets as prescribed.

About 40% of people with severe asthma have allergies to Aspergillus in their lungs.

The research showed that severe asthmatics with allergies were ten times more likely to carry higher levels of mould when on corticosteroid treatment.

Individuals in the study receiving antifungal therapy had lower quantities of the mould in the lung; the fungal load was much higher if the therapy had been stopped.

“Aspergillus infection is usually treatable, but might be able to explain why some asthmatic patients are having persistent symptoms on steroids,” said Dr Paul Bowyer, senior author on the study from 51��.

“We stress there is no danger to any individuals taking steroids to alleviate their asthma.

“But nevertheless this data is important because it may help doctors to consider additional treatments to individuals with allergies to this mould associated with steroids, so they may be helped more effectively.”

Dr Bowyer and Dr Livingstone Chisimba, also from 51�� and colleagues from 51�� University NHS Foundation Trust examined the airways of 48 people with mild to severe asthma, and 10 volunteers with no symptoms.

Dr Chisimba said: “With higher Aspergillus loads seen in those on oral steroids, we believe these data combined with genetic or other biological markers of asthma will uncover a fundamental understanding of the role of the fungal infections in asthma.

“This is a telling finding.”

Though different fungi were found with variation between individuals, the most common was Aspergillus.

Multiple different isolated spores of the mould were detected in the same lung, possibly, say the team, because excess mucus - a characteristic feature of asthma - acts as an efficient spore trap.

That, they explain, allows the spores from inhaled air to accumulate . Excess mucus is able to protect Aspergillus from the body’s normal defences, they say.

The research is published in the Journal of Allergy and Clinical Immunology.

The paper Corticosteroid treatment is associated with increased filamentous fungal burden in airways, published in the Journal of Allergy and Clinical Immunology is available

Funding from the NIHR 51�� Biomedical Research Centre to optimise the treatment of common respiratory and fungal diseases will further build on this research.

Time of day affects test results for asthma, researchers find

Fri, 08 Dec 2017 08:00:00 +0000

New research presented today (Friday 8th December) at theshows the human body clock significantly impacts on sample results used to diagnose and treat asthma when taken at different times of the day. This may have implications for how asthma is diagnosed and treated in the future.

Dr Hannah Durrington, Senior Clinical Lecturer at 51��, who has led the research, funded by Asthma UK, will explain that test results from an asthma patient taken in the morning differ from those taken from the same patient in the afternoon.

Dr Durrington’s research team analysed blood, mucus coughed up from the lungs and the breath of ten moderately severe asthmatics and ten healthy volunteers at different times of the day.

The asthmatic volunteers, as researchers had expected, displayed greater narrowing of their airways in the early hours of the morning than in the afternoon and this corresponded with a change in inflammatory cells - or eosinophils, measured in their sputum. Sputum eosinophil levels can be used to guide treatment in severe asthma patients.

The research also showed that sputum eosinophil levels can vary considerably between the morning and afternoon. They were higher in the morning, lower in the afternoon.

51�� is home to the largest biological timing . Dr Durrington also provides an asthma clinic at Wythenshawe Hospital, 51�� University NHS Foundation Trust (MFT).

Dr Durrington explains:

“These research results are really exciting but at an early stage – our aim was to understand a bit more about how the body clock affects the biochemistry of a person with asthma. We are pleased because our work should help with the accurate diagnosis and treatment of asthma in the future.

“It is really important to stress that this is ongoing scientific work – and no asthma patient should make any adjustment to their treatment regime without consulting their doctor. We are now planning a large randomised clinical trial which we hope in the future will point towards an indication about the optimum time of day for asthma treatments to be taken.

“We feel it may also have important implications on other lung conditions, as well as outside respiratory medicine. It also points towards opportunities for more personalised treatment for asthma care in the future. In the same way that measuring glucose levels in diabetes allows adjustment of insulin dosing, we may see asthmatics monitoring their biomarker chemicals during the day, to help inform optimum treatment times.”

Dr Samantha Walker, Director of Research and Policy at Asthma UK, adds:

"People's body clocks are incredibly powerful. This research, which we are proud to help fund, shows that for the 5.4 million people in the UK who have asthma, the results of an asthma test could differ depending on the time of day the test took place. While this research is at a very early stage, it could have a significant impact on when people with asthma are tested at some stage in the future. We look forward to seeing the results of the next stage of the team’s research in this area."

Citizen scientists to track allergies with new smartphone app

Thu, 18 May 2017 09:31:54 +0100

The public are invited to download a free app to track their seasonal allergy symptoms and to help researchers understand more about why the frequency of allergies are increasing.

A new and improved version of the app that allows users to track their seasonal allergies as part of a major research project, has been launched today, both on Android and iOS, allowing even more users to take part.

The 2017 version of the # app will allow people to record and track their allergic responses in real time, with the data collected then shared anonymously with scientists working to understand more about allergies in the UK.

The app has been produced collaboratively by 51��, the and the .

Researchers still do not understand why the number of people suffering from seasonal allergies, such as hay fever and asthma, is on the rise, but they think it may be linked to environmental changes such as pollen counts, the weather or an increase in air pollutants.

The app is part of the first ever nationwide citizen science project looking to build up a picture of how allergic symptoms change over time. Data collected from members of the public will allow researchers to pinpoint allergy hotspots in the UK and times of the year that allergies are at their most severe, and to correlate this with environmental data.

With around one in four people in the UK suffering from seasonal allergies, and with 5.4 million people with asthma in the UK, the app could add a great deal of valuable new data about the environmental conditions that are associated with triggering allergic responses and breathing difficulties including asthma attacks.

Dr Sheena Cruickshank, from 51�� and British Society for Immunology, said:

“We launched #BritainBreathing last year to work with the public to help us to learn more about seasonal allergies, such as hay fever and asthma. Gathering this type of information via an app from a large cross-section of the public hasn’t been done before, so our first move was to establish how valid our data was. We were pleased to find that the #BritainBreathing app provides strong data that we can use to see patterns of allergy and really unpick how they are caused.

“We know that more people than ever are suffering from seasonal allergies, but we don’t understand why this is. It could be pollution, super pollens, increased cleanliness, or a combination of factors. For our second year, with the help of the public, we hope gain a better picture of the driving forces behind why seasonal allergies are on the rise.”

Dr Laura Bellingan FRSB, director of policy and public affairs at the Royal Society of Biology, said of the project: “This project breaks new ground and has tremendous potential to bring people’s daily experience to the attention of researchers in a very useable way.

“The #BritainBreathing app is one of several citizen science projects with which we’ve been involved. The public have shown real enthusiasm for scientific research and can make an invaluable contribution that does not require prior training but draws on innate knowledge and experience, and as such we are very happy to be able to support this project.

“I would encourage anyone with a smartphone to get involved and to help us understand whether the air we breathe is the air we need.”

The #BritainBreathing project is now in its second year, with over 1,500 users downloading the app last year to record their symptoms. Researchers are hoping that with this new dataset they will also able to put together a comparative analysis and see how allergic responses are changing year on year. We’ll provide regular updates to users to keep them informed on how the project is progressing.

The free app is available for Android and iOS phones. Those who already have the 2016 Android version of the app are encouraged to delete it and replace with this updated version as data recorded in older versions will not be sent to the research team.

Research aims to drag asthma management into the 21st Century

Tue, 02 May 2017 09:47:47 +0100

A new study by University of 51�� researchers, published on (2 May), has probed the features that both patients and healthcare professionals want from an asthma management app.

Asthma treatment is currently managed by the use of written plans which help patients work out when to take their medication or seek advice. However, only a quarter of patients receive this and those that do often find it hard to stick to. To compensate, more than 200 smartphone apps have been developed, but these are often not informed by patient or professional needs.

The National Review of Asthma Deaths in 2014, concluded that two-thirds of asthma deaths were preventable.

The new study from 51�� team incorporates focus group responses and written questionnaires from 183 patients and 63 professionals and has evaluated the features that they both find most useful to help inform future designs for apps.

One of the main functions that patients wanted from a mobile healthcare or ‘mHealth’ app was information on environmental conditions – such as pollen or pollution. They also wanted to be able to collect data that they could show their doctors. Professionals wanted apps to alert patients about when to receive medical help and to monitor adherence to their medication.

The latest study, published in the European Respiratory Journal, is part of a long-term, EU funded project called , to develop a useful and accessible mHealth device.

Lead researcher Dr Andrew Simpson, from 51��, said: “While smartphones have great potential for helping people manage their health, there has been such an explosion of different apps and devices that patients and professionals don’t know what works best or if the design is up to the job.

“The idea of myAirCoach is to carefully work with these groups to find the best design and range of functions which help people manage their asthma.”

With more than 300 million world-wide and 5.4 million in the UK affected by it, asthma is ideal for an mHealth approach. If a device or app can be created which is useful for both patients and healthcare professionals it has the potential to save lives, reduce hospital admissions and reduce the use of rescue medication.

The findings support the recommendations of a , ‘51��ed asthma: how technology will transform care’ which the research team contributed to, that called for asthma to be ‘a focus and an exemplar for investment in technology-enabled self-management and clinician-led management in primary care’.

Dr Simpson concluded: “Although patients and health care professionals we asked had differing priorities, there was overwhelming support for the creation of evidence-based mHealth to support asthma management. The challenge is now to find the right design and technology to make this a reality.”

The paper: ‘Perspectives of patients and healthcare professionals on mHealth for asthma self-management’ was published in the journal Asthma.

Mite-proof bedcovers may reduce asthma flare-ups in children

Fri, 10 Mar 2017 14:00:00 +0000

Bedcovers which form a barrier to house dust mites appear to reduce flare-ups in children, according to new research conducted in 51��.

Mite allergy is one of the most common asthma triggers, and in partnership with viral infection can greatly increase hospital admission risk.

In the study, led by Dr Clare Murray, clinical senior lecturer at 51�� and consultant respiratory paediatrician at the Royal 51�� Children's Hospital, Central 51�� University Hospitals NHS Foundation Trust, children were enrolled aged 3-17 years who had tested positive for mite allergy, and suffered an asthma flare-up or exacerbation that required being treated in accident and emergency or as a hospital inpatient.

After encasing their mattresses, duvets and pillows with mite-proof covers or placebo covers, the children were followed for a year. Neither the children, the investigators nor their health care professionals knew which set of covers the children received.

The findings have been published online ahead of print in the American Thoracic Society’s American Journal of Respiratory and Critical Care Medicine. Results demonstrate that children sleeping with the mite-proof covers compared to the placebo arm of the trial:

Were less likely to have a severe asthma exacerbation that resulted in an accident and emergency visit or hospital admission (29.3 percent vs. 41.5 percent).
Had a 45 percent reduced risk of having an asthma exacerbation that resulted in an accident and emergency visit or hospitalisation and the requirement for systemic corticosteroids.
Went a significantly longer time to their first exacerbation that resulted in an accident and emergency visit or hospitalisation and the requirement for systemic corticosteroids.

Patients were recruited from 14 hospitals with acute pediatric secondary care services in the North West. The study was funded by The JP Moulton Charitable Foundation, and infrastructure support was provided by the North West Lung Centre Charity, situated at University Hospital of South 51��, where Dr Murray’s research team is based.

“Asthma exacerbations are among the most common reasons for hospitalizing children living in the developed world,” said Dr Murray. “It’s a frightening experience for children and their parents, and a single exacerbation can increase the annual cost of treating asthma by three-fold.”

Dr. Murray added that viral infections, especially those causing the common cold, are a major risk factor for asthma exacerbations in children sensitised and exposed to allergens. “Other studies have shown that these two risk factors act synergistically to increase the likelihood of hospital admission by nearly 20-fold,” Dr Murray said. “We have no means of protecting people from cold viruses, but our study indicates that allergen avoidance may be a cost-effective intervention.”

The authors estimated the cost of the bedcovers would be about £130 for a single bed. “This simple measure may reduce asthmatic exacerbations that lead to accident and emergency visits or hospitalisation, particularly in younger children who are allergic only to dust mites,” Dr Murray said.

The mite-proof covers did not significantly reduce the number of children whose exacerbation was treated outside the hospital with only an oral corticosteroid. The authors said it was not clear why this was the case. “It may be that the bedcovers did not prevent the exacerbation, but did reduce its severity,” Dr Murray explained.

Limitations of the study, which is believed to be the first to study the effect of mite-proof bedcovers and asthma exacerbations, include the fact that the exacerbations and oral corticosteroid use were reported by parents or guardians, not physicians, and the researchers had no information about viruses or other exacerbation triggers.

Although the study was not large enough to conclusively define the subgroups that benefitted the most from the intervention, the authors wrote that their results suggested that younger children testing positive for only house dust mite allergy and living in non-smoking households were more likely to benefit from the mite impermeable bed covers.

The study was funded by The JP Moulton Charitable Foundation. Infrastructure support was provided by the North West Lung Centre Charity.

UK burden of fungal asthma greatly exceeds prior estimates new study warns

Wed, 16 Nov 2016 00:01:00 +0000

Experts are warning of a significant increase in the number of people in the UK who are living with invasive and serious fungal diseases that affect the lungs, bloodstream and brain and can sometimes lead to death.

While invasive fungal infections were estimated by the Health Protection Agency in 2006 a new report is the first comprehensive attempt to capture how many people in the UK suffer from fungal asthma.

Asthma in adults is common in the UK with over 4 million reported cases, and researchers in 51�� believe as many as 300,000 of them are affected by fungal asthma.

The research from the National Aspergillosis Centre based at 51�� – is published by .

Fungal asthma is such a big problem because the UK has one of the highest rates of asthma internationally. The range of estimate reflects uncertainty as no community study has ever been done, despite the large number affected. Asthmatics allergic to and exposed to higher amounts of fungi that they breathe in usually have poor asthma control and require steroid boosters. Antifungal therapy benefits these people, and may prevent deaths from asthma, doctors believe.

Invasive aspergillosis is the commonest missed infectious diagnosis in intensive care in the UK. It is always fatal without therapy and affects from 3,288 to 4,257 patients each year, most undiagnosed. Treated invasive aspergillosis has a 30-85 per cent mortality depending on the patient group.

Dr Bradford Winters in 2012 analysed deaths in intensive care, and invasive aspergillosis was the commonest missed infectious diagnosis.

Pneumocystis pneumonia has been increasing, especially in the non-HIV group, and probably affects over 500 annually. 15-50 per cent of these patients die, even if treated.

Although 1,700 cases of Candida bloodstream infections are reported annually, the actual estimate of tissue invasive cases in hospitalised and critically ill people is 5,124. This carries a ~45% mortality, if diagnosed and treated.

A Health Protection Agency report from 2006 estimated that ~66 per cent of those who die of fungal infection could have been saved with faster recognition and rapid diagnosis.

Experts believe rarer infections and antifungal resistant infections are probably on the increase, including Candida auris and multi-resistant Aspergillus fumigatus derived from the environment.

51��’s , Director of , explained: “While the UK is rich in data sources, there is a remarkable poverty of contemporary studies of fungal diseases. An accurate estimate of total burden will ultimately rely on improved diagnostic testing and laboratory reporting.

“This report gets us closer to true burden of fungal diseases in the UK – necessary for improved diagnosis and reducing death. The scale of the ‘fungal asthma’ problem is staggering, and potentially remediable with antifungal therapy, as I know from treating hundreds of affected patients,” he added.

The paper, ‘’ M. Pegorie, D.W. Denning, W. Welfare was published in the Journal of Infection. doi: 10.1016/j.jinf.2016.10.005

Rafi-tone app set to help millions of children with asthma

Thu, 25 Aug 2016 10:52:29 +0100

Children with asthma will soon be able to breathe easier thanks to an interactive app created by a University of 51�� spin-out company.

, an eye doctor, invented Rafi-tone after his son Rafi suffered with breathing problems.

The Rafi-tone app, available on i-Phone and Android devices, helps children accept their mask and engage with taking medication by involving them in an onscreen fun animated game.

When a whistle sound is emitted by the mask - signaling that the child is breathing and inhaling medication with a spacer correctly - an onscreen ‘Rafi’ fights off attacking colourful cartoon-style baddies.

Professor Aslam, a Consultant Ophthalmologist at 51�� and Central 51�� Foundation Trust (), said his son Rafi’s breathing struggles caused a lot of anxiety for both himself and his wife.

“His condition caused a lot of worry for us - we hated to see him suffer,” he said. “And to make things worse he hated spacers and would push them away and we were concerned he was not getting the medication. There were tears all round.

“After one particular occasion when Rafi struggled for breath I decided to get straight to work - which involved trying to design and align bits of software, hardware and electronics to his spacer.”

He added: “Soon, Rafi was using his spacer while looking at a phone screen which showed simple images when he breathed correctly into the spacer.

“Despite it being in the early hours of the morning, instead of the usual tears and screams he was distracted and engaged with the screen display and took the medication silently and properly. I was amazed to hear him say ‘that was really good daddy, can we do it again in the morning’, before he turned and fell asleep.”

It was after that, that Rafi-Tone - which also stands for ‘Respiratory Aid For Inhalers’ - was born.

Professor Aslam, determined to learn new programming languages to develop and improve the app, produced algorithms to control cartoon characters that reacted when his son Rafi breathed in using his spacer.

He was supported and advised by Clare Murray, a Consultant respiratory paediatrician who helped to set up the initial trials for testing at Royal 51�� Children’s Hospital and ensure the program would give maximum benefit to patients.

Further testing and guidance was provided by paediatrician Shaila Sukthankar and by Margaret Cuffwright, a specialist health visitor in paediatric asthma.

He was also supported by Mark Sanders, Managing Director of Clement Clarke International - a leading respiratory device manufacturer who helped ensure the final arrangement would work with modern devices.

The system evolved through many versions during clinical testing by children at Royal 51�� Children’s Hospital, until the current optimal Rafi-tone app was created.

The Rafi-tone app is University of 51�� spin-out company ’s first product. It works in conjunction with the ‘Flo-Tone’ mask which attaches to the Able Spacer. These are made by Clement Clarke, a company with a long history of producing respiratory devices

Professor Aslam said: “These are exciting times as we expect the Rafi-tone system to be available in September to all children who are prescribed an Able Spacer with small mask.

“There’s nothing that would make me happier than to hear about patients using devices or technologies that I've developed and it having a positive impact on them.”

Professor Aslam described the crucial support he received from 51��’s technology transfer office, , and especially from IP development and partnering manager, Dr Lizzie Crawford, who helped with the development of the product to something that could be delivered to patients in a sustainable way.

Driven by her own experiences with her son and by the positive reactions of patients and carers she is now focused on delivering the potential of the Rafi-tone technology to other groups of respiratory patients.

Funding was provided by Central 51�� University Hospitals NHS Foundation Trust

(CMFT), Innovate UK, UMIP Pathfinder Funding which has helped develop the technology and determine the commercial plans and route to market.

Major new report identifies child suicide risk factors

Thu, 26 May 2016 09:00:00 +0100

Bereavement, bullying, exams and physical health conditions such as acne and asthma are some of the experiences linked to suicide in children and young people according to a new report by 51��’s National Confidential Inquiry into Suicide and Homicide by People with Mental Illness (NCISH).

Researchers studied the reports from a range of investigations and inquiries on 130 people under the age of 20 in England who died by suicide between January 2014 and April 2015, extracting information about their personal circumstances that the reports highlighted. This is the first time there has been a national study of suicide in children and young people in England on this scale.

The researchers found that 28% of the young people who died had been bereaved, in 13% there had been a suicide by a family member or friend. 36% had a physical health condition such as acne or asthma, and 29% were facing exams or exam results when they died. Four died on the day of an exam, or the day after.

Internet use related to suicide was found in 23% of the deaths. This was either searching for information about suicide methods, being a victim of online bullying or posting suicidal thoughts online. Bullying overall had occurred in 22% of cases, mostly face-to-face rather than online.

Over twice as many males as females died by suicide and there were five deaths in those aged under 14. Hanging was the most common method, accounting for 63% of deaths followed by jumping from a height or in front of a train - methods that show a strong lethal intent.

Excessive alcohol or drug use was more common in older teens, and 54% overall had previously self-harmed. In the week before they died, 10% had self-harmed and 27% had told someone of suicidal ideas. 43% had no contact with any services.

Professor Nav Kapur, NCISH Head of Suicide Research said: “Self-harm is strongly associated with increased future risk of suicide and is one of the main warning signs. It is crucial that there is improved help for self-harm and access to mental health care. However, with the variety of factors we found with this study, it is clear that schools, primary care, social services and youth justice all have a role to play.”

This study is the first phase, comprising people under 20 years of age in England and a linked academic paper is published on Thursday May 26th in The Lancet Psychiatry. A larger study widened to the UK and including those under 25 years of age will be published in 2017 and include recommendations for services.

Citizen science app to track UK’s allergy sufferers

Thu, 24 Mar 2016 11:01:00 +0000

British allergy sufferers are to turn citizen scientists in a bid to decode the poorly understood world of seasonal allergies thanks to a free new app.

The app – called #BritainBreathing – a collaboration between the Royal Society of Biology, the British Society for Immunology, and 51��, aims to help the one in four people in the UK who suffer from seasonal allergies like hay fever and asthma.

Experts say the triggers are often poorly understood and little is known about why the incidence of these allergies is increasing.

#BritainBreathing is the first nationwide project aiming to better understand where and when allergy symptoms are occurring, what exacerbates them and why they’re on the rise. It launches on Android today.

By using the #BritainBreathing app, sufferers will be able to track allergy symptoms they record about their eyes, nose and breathing, over time. This might help people to start thinking about what might be triggering their allergies.

Dr Sheena Cruickshank, from 51�� and British Society for Immunology, said: “Seasonal allergies are increasing in the West but we don’t know what is driving this. It could be pollution, super pollens, increased cleanliness, or a combination of factors. What has been missing to answer this question is wide scale human data about what is really happening. Because detailed information on pollen and pollution is available, we want to map Britain Breathing data onto that and perhaps come closer to understanding what really drives allergies, on both an individual and a national level."

The #BritainBreathing app will allow the public to record their allergy symptoms in a simple and straightforward way and then anonymously share that data with researchers. This large open data set, which will also capture information on timing and location, can then be combined with other publicly available data, such as weather, pollen or pollution statistics, to build a better understanding of allergies and their triggers. From these data, scientists can build a clearer picture of the pattern and frequency of allergy incidence across the UK.

The researchers will also create up-to-date visualisations of the national crowd data, for example maps of where particular allergy symptoms are most frequently reported on any given day, so that users can compare their experience to others in their region and beyond.

Jon Kudlick, director of communications at the Royal Society of Biology said: “This is a ground breaking project as it will give users the chance to record and monitor the frequency of their own allergy symptoms, as well as then adding their experiences to the wider data set. Does air pollution add to the misery of those suffering with hay fever? Are people having more asthmatic symptoms in 51�� than in London, and if so why? These are the kind of questions we hope to help answer.”

“This is the Society’s fourth citizen science project. The Starling Survey, Flying Ant Survey and House Spider Survey have received tens of thousands of records over four years, and shown how effective people power can be in helping researchers to find answers to difficult questions.”

The #BritainBreathing app is available on Android at

Find out more on the #website

Follow the project on Twitter:

New antifungal drugs profiled at 51�� fungal disease conference

Fri, 04 Mar 2016 13:56:46 +0000

Researchers gathered in 51�� for the Advances Against Aspergillosis international conference have had the first glimpse of new antifungal agents. Problems with toxicity and resistance limit treatment options currently for the millions of patients worldwide who need antifungal therapy each year.

Three new antifungals were profiled: CD101 from Cidara Therapeutics in San Diego, F901318 from F2G in 51�� and PC945 from Pulmocide in London, as well as earlier stage peptides and new antifungal targets.

Dr Kasuhiro Ito from Pulmocide, working with researchers at Chiba University, Japan, demonstrated that inhaled PC945 was highly effective in early therapy of life-threatening invasive aspergillosis in mice. The compound is a novel azole with activity about 100-fold more against Aspergillus fumigatus than voriconazole, the leading treatment currently. PC945 also reduced inflammation in the lung. PC945 represents the first of a new generation of inhaled antifungals, primarily for fungal asthma, cystic fibrosis and prevention of invasive aspergillosis. Clinical studies of aerosolized PC945 are likely to commence in early 2017.

Dr Nicola Beckman from F2G presented work on the novel compound F901318 and its activity against resistant fungi. F901318 compound is an orotomide, with a new mechanism of action disclosed at ICAAC in September 2015. It is highly active against pan-azole resistant Aspergillus fumigatus, other Aspergillus species and multi-resistant and currently untreatable Scedosporium spp. With the rise in azole resistance across the world (also profiled at the conference), a new class of antifungal is clinically required. Clinical studies of intravenous and oral F901318 are likely to commence in late 2016.

Dr Miesel presented the efficacy of Cidara Therapeutics’ CD101, a novel long acting echinocandin, against invasive aspergillosis. CD101 was highly effective, similar to amphotericin B, in this survival experiment. CD101 will be an intravenous antifungal, with the potential for higher drug exposures than currently marketed echinocandins and once weekly treatment, enabling inpatient and outpatient use and earlier hospital discharge. Clinical studies of CD101 are scheduled to start in the first half of 2016. CD101 has received QIDP, Fast Track and Orphan Drug Designation from the FDA for the treatment of candidemia and invasive candidiasis.

The last new class of antifungal was launched in 2002 – the echinocandins caspofungin and micafungin. The last time a new class of oral antifungal was launched was the azoles – in 1985 with the launch of the now withdrawn ketoconazole. A new azole antifungal isavuconazole (Basilea Pharmaceutica) was launched in 2015. There are no licensed aerosolised antifungals.

Fight against disease goes global as 51�� professor publishes 15 papers in one day

Thu, 15 Oct 2015 15:30:35 +0100

The number of people affected by serious fungal diseases in a population of 636 million in 15 countries
Each paper provides a ‘tool’ for country advocacy for fungal disease and a baseline for future studies

Working with medical colleagues across the world, Professor David Denning has entered the history books by publishing 15 scientific papers on the same day – providing 15 countries with evidence to combat the burden of fungal disease.

In the journal Mycoses, and 47 co-authors from across the world have estimated the number of people affected by serious fungal diseases in a population of 636 million in 15 countries: Belgium, Czech Republic, Denmark, Hungary, Nepal, Qatar, Tanzania, Trinidad and Tobago, Uganda, Germany, Mexico, Senegal, Tanzania, Ukraine and Vietnam.

These estimates have never been attempted before and population rates from 1.7% to 12.5% were found. Each paper provides a ‘tool’ for country advocacy for fungal disease and a baseline for future studies.

Fungal diseases such as cryptococcal meningitis in AIDS and fungal asthma have been regarded as a low priority problems and expertise is lacking in many countries. Having published several papers on global frequency of single fungal diseases, Professor Denning has turned his attention to individual country estimate for all serious fungal infections, using a similar methodology.

By estimating figures for each country the papers provide evidence for people to campaign for better treatment for a range of potentially fatal illnesses.

As well as the 15 in this round of publication, papers have already been released for Ireland, Spain, Nigeria and Israel. Brazil, Jamaica and Dominican Republic are in the pipeline.

, Head of Global Health for the University said: “Understanding how big a problem is in a given country and who is affected, is a key step forward for healthcare planning. Leadership of this neglected area of fungal disease has been lacking at the all levels in the global health agenda, so it is gratifying to see this void being filled.”

Professor Denning said: “I’m delighted that the years of work with friends and colleagues is now visible to help conquer the unaddressed scourge of fungal disease in so many parts of the world. Fifteen papers published together is a once of a lifetime event but I hope that it’s just the start as we try to build a global picture.”

Read the special edition of the journal Mycoses .

Research power against fungal disease revealed at 51�� Centre launch

Wed, 09 Sep 2015 16:33:32 +0100

Around 300 million individuals affected annually and over 1.5 million deaths
MFIG is a new international centre of excellence for fungal infection biology

51�� leads the world in the fight against deadly fungal infections with the opening of new Centre - a powerful partnership between research, doctors and industry to help 300 million people across the globe.

The latest scientific research against the potentially deadly Aspergillus fungus was displayed today (9 September) as (MFIG) was officially opened by Professor Sir Robert Boyd.

From new antifungal drug opportunities to the genetic basis for aspergillosis, the quality of science in this topic has ‘improved immeasurably over the last decade’, according to Professor Keith Gull FRS from Oxford University who spoke at the meeting.

MFIG is a new international centre of excellence for fungal infection biology and translational antifungal research at 51��. It is integrating its research with that of clinicians and industry.

Fungal disease is much more common than many people realise as of 51�� pointed out, with around 300 million individuals affected annually and over 1.5 million deaths.

Aspergillus is responsible for many of these illnesses, a conservative estimate is 13 million. It is an airborne fungus that everyone breathes in daily. In those who are immunosuppressed such as those undergoing organ transplantation or treatment for leukaemia, it causes a disease called invasive aspergillosis.

In those with damage in their lungs such as tuberculosis or COPD, it can cause chronic pulmonary aspergillosis – a slowly progressive and destructive disease of the lungs. In those with asthma or cystic fibrosis it can cause fungal asthma with wheezing?, mucous plugging of the airways, poor asthma control and life-threatening asthmatic attacks.

MFIG is focused on understanding the reasons for this range of disease and why Aspergillus is so commonly fatal.

Professor Sir Robert Boyd, previously Dean of the Medical School in 51�� said: “The opportunity for major health improvements by high quality research crossing traditional boundaries has never been greater. MFIG exemplifies the range of skills and specialised resources necessary to bring out major breakthroughs in fungal disease. I am delighted to see such a strong multidisciplinary team hosted in 51��.”

At the opening meeting, Professor Jack Edwards from the University of California, Los Angeles spoke on the trials and tribulations of developing a fungal vaccine, in this case for potentially fatal Candida infections.

Professor Gerald Bills of The Brown Foundation Institute of Molecular Medicine and Texas Therapeutics Institute, Houston spoke on the latest new class of antifungals, echinocandins, now selling nearly $1 billion annually.

Professor Keith Gull FRS summarised the state of fungal diseases, contrasted with other infections in the keynote lecture, ’Infectious Diseases in the 21st Century: The current state of our ignorance’.

, Director of MFIG, stated: “Our intent is to transform the understanding of Aspergillus biology and disease. We anticipate identifying options for new antifungal drugs, the genetic basis of aspergillosis and a pathway to vaccine development.”

51�� researchers call for antifungal drugs boost

Fri, 27 Mar 2015 11:02:00 +0000

No new antifungal drug has been licensed since 2006, and the last new class of antifungal emerged in 2002. With an estimated 300 million people worldwide with serious fungal disease and 1.3 to 2 million deaths, new agents are desperately needed.

In a Perspective published in the journal today (27 March), 51�� academics and , highlight the problems for doctors: poor responses, antifungal resistance, drug interactions and toxicity to many of the existing drugs.

Last week the US Food and Drug Administration approved a new azole antifungal, isavuconazole, from Basilea. The academics welcome this , but state that many of the existing problems such as resistance and poor responses to therapy in some patients will not be addressed. Completely new classes of antifungal drugs are required, say Denning and Bromley.

Professor Denning, who is a Professor of Infectious Diseases in Global Health at 51��, said: “In our clinics, we have large numbers of untreatable patients going downhill, and current therapy is ineffective or impossible to take for some patients. Many are really desperate and some die years earlier than they should through lack of treatment.”

Dr Mike Bromley, Lecturer at , also at 51��, is trying to identify new antifungals and define how they work on fungal cells. He declared: “New antifungals are tough to find, partly because the human cell machinery is quite similar in fungi, so killing a fungal cell without damaging a human cell is tricky. We have several promising leads however, which we are working on as fast as resources allow.”

The authors point out the very low numbers of funded positions in this area in the UK and USA (few grants awarded), which greatly impedes research in the area. High resistance rates in Candida and Aspergillus are very concerning.

On the plus side, several new development opportunities have opened up, such as chronic pulmonary aspergillosis ( which affects three million people) and fungal asthma (five to twenty million people), which combined with better diagnostics, will allow new clinical development pathways and very large commercial opportunities.

The full opinion piece can be read (a subscription may be required).

Notes for editors

Keep up with the latest news by following 51�� Media Relations team on

Smartphone game helps children to improve asthma inhaler technique

Thu, 04 Dec 2014 09:00:00 +0000

Researchers at 51�� and Central 51�� University Hospitals NHS Foundation Trust have developed a new interactive smartphone game can help children use a key asthma inhaler (‘a spacer’) far more effectively, allowing them to breathe more easily.

Their research was presented at the Winter Meeting yesterday (3 December).

A spacer device is a large plastic container - sometimes with a mask attached. A dose of asthma medication is sprayed into it, which is then inhaled without needing to co-ordinate breathing and pushing down on the asthma inhaler canister. It is particularly useful for babies and small children who do not have this level of co-ordination.

But due to their size and unfamiliarity when first used, getting young children to breathe into ‘spacers’ is not always easy and can cause distress for both children and adults. , a researcher from 51�� and Consultant at was faced with such a problem for his son, Rafi, who experienced repeated distressing wheezing attacks.

This led Dr Aslam to create a new way of using a spacer by mounting a smartphone onto it programmed to display an interactive game linked to the outflow valve of the mask.

Whenever a child breathes properly into the spacer they see themselves winning on a game played on the screen. Specially designed on-screen characters respond to correct breathing technique as part of an ongoing game. For example – the child can ‘blow away’ unfriendly characters to the hero, or blow the hero’s boat across a river.

After seeing the beneficial effects on his own son, Rafi, Dr Aslam developed the new spacer with crucial help from a colleague, Dr Clare Murray, an expert in children’s breathing disorders.

Together they arranged for the game and module to be tested on 14 children admitted to hospital with acute wheezing along with a survey to assess the child’s reaction - and gained both the parents’ and children’s assessment of the benefits of the device.

100% (13/13) of the children who filled in a survey enjoyed the activity and 91% (10/13) felt the spacer helped them take their medication.

Some of the benefits of the inhaler voiced by parents in the survey included – it was enjoyable, it made their child calmer and helped in their inhalation technique – and that it would be useful at home. The study was funded by a grant from Central 51�� University Hospitals NHS Foundation Trust.

, Senior lecturer and Consultant in Respiratory Paediatrics at 51�� and Central 51�� University Hospitals NHS Foundation Trust - and member of the British Thoracic Society said: “As parents are well aware, children are not always the greatest fans of taking medicine or using new treatment devices. And we know some young children do feel anxious about taking their asthma medication through a spacer.

“The good news is that the appliance of new technology, and the power of ‘fun’ really seemed to reap benefits in our study. The interactive game encouraged many of the children to use the spacer effectively. And it also helped tackle the stress and anxiety in both parents and children.

“In our research the inhalers were used to deliver medication to help children with acute asthma problems in a hospital setting. But we believe they also have the potential to work with more regular asthma medication at home as well.

“So in the future we hope the device might play a key role in supporting young children to breathe easier.”

Asthma is a condition that affects the airways – the small tubes that carry air in and out of the lungs. When a person with asthma comes into contact with something that irritates their airways (an asthma trigger), the muscles around the walls of the airways tighten and become narrower, and the lining of the airways becomes inflamed and starts to swell, causing difficulty in breathing and leading to symptoms of asthma.

The UK has among the highest prevalence rates of asthma symptoms in children worldwide, and there were 25,073 emergency hospital admissions for children in the UK in 2011-2012. That means on average there were 69 per day, or one every 21 minutes.

Notes for editors

For media enquiries:

Jamie Brown
Media Relations Officer
51��
Tel: 0161 2758383
Email: jamie.brown@manchester.ac.uk

Why drying washing indoors can pose a health threat

Thu, 27 Nov 2014 00:01:00 +0000

As winter approaches doctors are warning that wet washing dried indoors can pose a serious health threat for people with weakened immune systems or severe asthma.

Experts have found that clothes put on drying frames or draped over warm radiators raise moisture levels in our homes by up to 30 per cent, creating ideal breeding conditions for mould spores – and one in particular called aspergillus fumigatus, which can cause potentially fatal lung infections.

Father of three, Craig Mather from Bolton knows first-hand the damage it can do. For years he dried washing in his bedroom and thought nothing of it. But when he contracted TB in 1997, the disease left his lungs weak, and aggravated the problems he had been left with after childhood asthma.

Craig, who is 43 and a fast food manager, explains: “I only started to recover when my consultant diagnosed chronic pulmonary aspergillosis and prescribed me special drugs to fight the fungal infection. However, I noticed coughing fits and night sweats – particularly when I had wet washing drying on the warm bedroom radiator.

“He told me that it could be making my problems worse, so for the last 12 months I haven’t dried my clothes indoors and I’ve noticed a huge improvement in my health. I can’t do strenuous physical activity, but I am off the drugs and only have to go back to the clinic for check-ups every four months – and I’m able to ride my bike again.”

and his team at the , in 51��, have issued the wet washing warning after treating a growing number of patients who have developed the condition from inhaling the Aspergillus fungal spores.

Dr Denning, who is Professor of Infectious Disease in Global Health at 51�� explains: “It’s estimated that as many as 87 per cent of us dry our clothes indoors in the winter. One load of wet washing contains almost two litres of water, which is released into the room.

“Most of us are either immune to the fungus which grows in these humid conditions, or have a sufficiently healthy system to fight the infection. But, in asthma sufferers it can produce coughing and wheeziness, and in people with weak or damaged immune systems, such as cancer patients undergoing chemotherapy, Aids patients and people who, like Craig, have an auto-immune disease, the fungus can cause pulmonary aspergillosis – a condition which can cause irreparable, and sometime fatal, damage to the lungs and sinuses.

“My advice would be when in doubt, dry wet washing outside, in a tumble dryer or in a well ventilated indoor space away from bedrooms and living areas.

“Be safe rather than sorry,” he adds.

Notes for editors

For more information please contact Susan Osborne, Director of Communications at The Goodwork Organisation on 07836 229208.

Public health interventions needed to tackle grim reaper of 'lifestyle' diseases

Tue, 25 Nov 2014 10:00:00 +0000

Interventions such as the smoking ban help to break habits instead of relying on individuals to make the right decision for their health

More public health interventions, along the lines of the smoking ban, are needed to tackle Britain's devastating toll of ‘lifestyle’ diseases, including heart disease and cancer, according to academics.

A new paper, by Dr Stanley Blue, lecturer in Social Sciences at 51��, claims that there needs to be a shift in public health policy, with less focus on efforts to change individual behaviour and more attention on breaking social habits and practices that are blindly leading us into bad health.

Theories of practice and public health: understanding (un)healthy practices is published in the journal, Critical Public Health, and written by Dr Stanley Blue, lecturer at the School of Social Sciences, Prof Elizabeth Shove, of Lancaster University, Prof Mike Kelly, Director of the Centre of Public Health at NICE, and Chris Carmona, public health analyst at NICE.

The authors say new ideas are needed to tackle non-communicable - or 'lifestyle' diseases - such as heart disease, cancer, asthma and diabetes. They explain how some social practices reinforce each other, such as getting a takeaway and watching TV on a Friday night, whereas others, such as drinking a bottle of wine at home or going to the gym, compete for time in our busy days.

They cite the smoking ban as an example of a measure that effectively decoupled the relationship between going out for a meal or a drink and having a cigarette. A similar approach, with social practice at the heart of public health policy, could be taken to eating and exercise, rather than traditional methods which rely on persuading people to make the 'right' decision by going to the gym or eating their five a day – and which treat such decisions as matters of personal choice.

Dr Stanley Blue said: “Smoking, exercise and eating are fundamentally social practices, therefore we need to re-shape what is deemed socially acceptable and normal in order to change them.

“Current public health policy is dominated by the presumption that individuals are capable of making ‘better’ choices for themselves on the basis of information given to them by the government or other agencies. This does not account for the fact that practices like those of smoking and eating have histories of their own.

"Trying to get individuals to stop smoking or eat healthily overlooks the fact that these are fundamentally social practices. Public health policy will have to find the courage to break away from its traditional mould if it is to stand a chance of confronting the grim reaper of lifestyle diseases."

Notes for editors

Dr Stanley Blue is available for interview.

Theories of practice and public health: understanding (un)healthy practices is published in Critical Public Health and written by: Dr Stanley Blue, lecturer at the School of Social Sciences, 51��; Prof Elizabeth Shove, Director of the DEMAND research centre and Professor of Sociology at Lancaster University; Chris Carmona, Public Health Analyst at NICE and Prof Mike Kelly, Director of Public Health at NICE.

Media enquiries to:

Deborah Linton
Media Relations Officer
Faculty of Humanities
51��
Tel: 0161 275 8257, 07789 948783
Email: deborah.linton@manchester.ac.uk

Boost for lung infection research with new UK-Brazil partnership

Thu, 23 Oct 2014 01:00:00 +0100

51�� has begun a new partnership with a Brazilian university to carry out more research into a fungal lung infection which affects at least three million people worldwide and is 75% fatal.

The researchers from 51�� are joining colleagues from the Escola Paulista de Medicina-Federal University of São Paulo () to examine the prevalence and treatment of chronic pulmonary aspergillosis.

This infection is thought to affect over 17,850 people in Brazil, with 5,600 new cases every year. Follow up of patients with tuberculosis in Brazil in the 1980’s showed 21% to have evidence of Aspergillus infection, similar to the UK.

Yet chronic pulmonary aspergillosis is rarely diagnosed or treated in Brazil, because of a lack of awareness and diagnostic testing. As well as those with tuberculosis, patients with AIDS, asthma and chronic obstructive pulmonary disease are also susceptible to this infection, so actual numbers of sufferers may be twice what is currently recorded.

51��’s is based at University Hospital of South 51�� NHS Foundation Trust (UHSM) and will lead the UK side of the new initiative.

He said: “While we treat nearly 400 UK patients with this condition, across the world, there are estimated to be about 3 million. Currently very few are diagnosed or treated, and after five years about 75% have died. This international program will have an impact throughout Brazil and Latin America.”

Funded by with matching funds from 51��, the programme encourages scientific exchange between universities in São Paulo and 51��, and will involve a study of patients from 17 hospitals in the Brazilian city.

Professor Arnaldo Lopes Colombo of (UNNIFESP) added: “This collaboration is of the utmost importance to Brazil in view of the huge number of undiagnosed fungal infections in the country. We aim to really understand who gets this long term, difficult to treat infection and improve our diagnostic techniques across the country.”

Notes for editors

For media enquiries, please contact Jamie Brown | Media Relations Officer | 51�� | +44(0)161 275 8383 | Jamie.brown@manchester.ac.uk |

Peanut in house dust linked to allergy in children with skin gene mutation

Wed, 22 Oct 2014 01:00:00 +0100

A new study by 51��, working with colleagues at King’s College London and the University of Dundee, has found a strong link between exposure to peanut protein in household dust during infancy and the development of peanut allergy in children genetically predisposed to a skin barrier defect.

Around 2% of school children in the UK are allergic to peanuts. Severe eczema in early infancy has also been linked to food allergies, particularly peanut allergy.

A major break-through in our understanding of eczema has been made with the discovery of the FLG gene which codes for the skin barrier protein, filaggrin.

Mutations in the FLG gene result in an impaired skin barrier which is thought to allow allergens to penetrate the skin and sensitise the body.

The study, published this month in the Journal of Allergy and Clinical Immunology, was carried out in 557 children from the 51�� Asthma and Allergy Study (MAAS) – a flagship study from the University of 51�� and University Hospital of South 51�� led by Professors Adnan Custovic and Angela Simpson – who have been followed from birth (1996/7) to the present day.

The children in MAAS, who are representative of the normal population, have been thoroughly assessed for peanut allergy with skin prick tests, blood tests and in some cases oral food challenge tests and peanut allergy was diagnosed in 3% of them.

They have undergone genetic tests and 9% of them carry mutations in the FLG gene. In addition, dust samples were collected from their home environment in early life, in which it was possible to quantify peanut protein.

Peanut protein is present on hands and in saliva for up to three hours after peanuts or peanut-based food has been eaten, and can persist on table surfaces and sofa or pillow dust even after routine cleaning.

By combining information on genetics and the environment, it was possible to gain insights on risk factors for peanut allergy. For children who did not carry an FLG mutation, the amount of peanut protein in the house dust had no significant effect on whether or not the child developed peanut allergy.

For children with an FLG mutation, higher levels of peanut protein in household dust in infancy increased the likelihood of peanut allergy in childhood. For example, a three-fold increase in house dust peanut exposure during infancy was associated with a three-fold increase in risk of peanut allergy.

Professor Angela Simpson, from 51��’s Institute of Inflammation and Repair, said: “This is yet another example of how both genes and the environment are important in determining whether or not individuals develop allergic diseases. It is only because we were able to follow these children from before birth and take samples from their home environment in early life that it was possible to identify these effects.

“Gaining a better understanding of risk factors for diseases is the first step towards developing methods of prevention that are targeted to individuals at risk, which can be tested in clinical trials.”

Notes for editors

For media enquiries, please call Jamie Brown | Media Relations Officer | 51�� | 0161 275 8383 | Jamie.brown@manchester.ac.uk

‘Peanut allergy: Effect of environmental peanut exposure in children with filaggrin loss-of-function mutations’ by Brough et al is published in the Journal of Allergy and Clinical Immunology and can be accessed at .

The 51�� Asthma and Allergy Study was supported by Medical Research Council grants, JP Moulton Charitable Foundation, North West Lung Centre Charity and National Institute for Health Research Clinical Research Facility at the University of South 51�� NHS Foundation Trust. The Centre for Dermatology and Genetic Medicine at the University of Dundee is supported by the Wellcome Trust.

The study was funded by Action Medical Research and supported by the National Institute for Health Research (NIHR) Clinical Research Facility at Guy’s & St. Thomas’ NHS Foundation Trust and the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and Kings College London.

Drugs used to treat lung disease work with the body clock

Mon, 28 Jul 2014 01:00:00 +0100

Scientists from 51�� have discovered why medication to treat asthma and pneumonia can become ineffective.

The findings, published in Nature Medicine, show that drugs widely used to treat lung diseases work with the body clock.

In the UK pneumonia, which is caused by an infection, affects around 1 in 1000 adults each year and is more serious for babies, young children, the elderly, smokers and those with an underlying health condition.

More than 5 million people in the UK are affected by asthma and the NHS spends around £1 billion a year treating and caring for people with the disease.

The research, led by Professors David Ray and Andrew Loudon from 51��, found out that cells lining the lung airways have their own body clock which is the time-keeper for lung inflammation - both conditions cause swelling (inflammation) in the lungs.

And the team discovered that more severe lung inflammation happens as a result of the loss of the body clock working in these cells.

Professor Loudon said: “We found a key molecule known as CXCL5 that facilitates lung inflammation which is a key regulator of how immune cells get into tissues. The loss of CXCL5 completely prevents the time of day regulation of lung inflammation which opens up new ways to treat lung diseases.”

During the research, the team uncovered how glucocorticoid hormones from the adrenal gland are vital in controlling the level of inflammation in the cells lining the airway.

Professor Ray said: “This hormone works through the glucocorticoid receptor, a major regulator of gene expression. We wanted to find out therefore if glucocorticoid medicines, like prednisolone or dexamethasone would also show a time of day effect, and our research shows they do.”

The team concluded that the rhythm of the clock in the lining of the cells in the lungs is important for lung diseases like asthma, and chronic obstructive pulmonary disease.

Professor Loudon said: “In this work we define a major circadian control on lung inflammation which affects responses to bacterial infection, or pneumonia. We know that many lung diseases indeed show a strong time of day effect, including asthma, and deaths from pneumonia.”

Our bodies anticipate the change from day to night by having an internal, or circadian clock. This explains why it is hard to adjust to shift work. The body clock regulates sleep, but now has been discovered to also regulate our immune system.

“We live in a world that is divided into day and night. As a result our behaviour varies by time of day; we sleep at night, and are active, and eat during the day. Increasingly our lives are disconnected from this ancient rhythm, with artificial light, shift work, and jet lag,” concluded Professor Ray.

Notes for editors

Professor David Ray is available for interview in the UK. Professor Andrew Loudon is available for interview in Asia.

The paper entitled ‘An epithelial circadian clock controls pulmonary inflammation and glucocorticoid action’ by Julie Gibbs, Louise Ince, Laura Matthews, Junjie Mei, Thomas Bell, Nan Yang, Ben Saer, Nicola Begley, Toryn Poolman, Marie Pariollaud, Stuart Farrow, Francesco DeMayo, Tracy Hussel4, G Scott Worthen, David Ray & Andrew Loudon is available upon request.

For further information, please contact:

Alison Barbuti

Media Relations Officer

51��

Tel. +44 (0)161 275 8383 / Mob. 07887 561 318

Email: alison.barbuti@manchester.ac.uk

Fungicides for crops: worrying link to fungal drug resistance warn scientists

Tue, 15 Jul 2014 01:00:00 +0100

Crop spraying on British farms could be aiding a life-threatening fungus suffered by tens of thousand of people in the UK each year.

New research by British and Dutch scientists has found that Aspergillus – a common fungus that attacks the lungs and is found in soil and other organic matter – has become resistant to life - saving drugs in parts of rural Yorkshire.

It’s the first time a link has been made in the UK between drug resistance in Aspergillus and fungicide used on crops. Experts warn their findings, now published, are significant and raise serious implications for transplant patients, those with leukaemia and people who suffer from severe asthma.

In the three-year study, researchers from 51�� and Radboud University, in the Netherlands, compared resistance profiles in 230 fungal samples, collected from rural areas in West Yorkshire which were treated with fungicides, to 290 air and soil samples from inner city sites across Greater 51��.

They found no resistance from the sites in Greater 51�� compared to 1.7% resistance detected in West Yorkshire, implicating fungicide use in agriculture.

Dr Michael Bromley, Lecturer at 51�� and study leader commented: “Given the frequent finding of resistance across northern Europe, it is not a surprise to see resistance in the UK. However, the clear association with triazole fungicide usage is very worrisome, as some unlucky people at risk will breathe in untreatable Aspergillus, with potentially dire consequences.”

Diseases caused by Aspergillus affect millions of people worldwide, causing high morbidity and mortality. The only oral antifungal agents (triazoles) for human use are similar in structure to certain fungicides. The use of certain compounds in agriculture, notably difenoconazole, propiconazole, epoxiconazole, bromuconazole and tebuconazol are particularly likely to lead to resistance, yet are freely used in agriculture. There is a very limited range of antifungal compounds to treat fungal diseases, and some fungi are multi-resistant.

The emerging antifungal resistance in human pathogenic fungi is causing a huge threat to patients, especially to those with weaken immune systems and this study emphasises that there may be even a greater problem in treating such diseases. Previously such resistance has been observed in a few other countries (Netherlands, Denmark, Belgium, Germany, France, India, China, Iran, Tanzania and a few others) raising great concerns among clinicians. No new classes of antifungal agent are currently in clinical development.

These findings come as the Government has announced of a review of the economics of antimicrobial research. However, experts believe current practice across both health and veterinary services is failing to prevent the inappropriate prescription of antibiotics. The Science and Technology Committee has warned that the Government needs to set clear responsibilities at all levels of the NHS and veterinary medicine to achieve better stewardship of the antimicrobial drugs vital in modern medicine.

Notes for editors

For more information pleased contact Susan Osborne, Director of Communications at The Goodwork Organisation, on 07836 229208 or Alison Barbuti Media Relations Officer, Faculty of Medical and Human Sciences 0161 275 8383 alison.barbuti@manchester.ac.uk

* The findings are published by the International Society for Chemotherapy of Infection and Cancer as Bromley MJ, et al. Occurrence of azole-resistant species of Aspergillus in the UK environment in the Journal of Global Antimicrobial Resistance (2014).

Scientists on the research team included Dr Michael J. Bromley, Guss van Muijlwijk, Dr Marcin G. Fraczek, Dr Geoff Robson, Prof Paul E. Verweij, Prof David W. Denning and Dr Paul Bowyer. Guus is a now a final year medical student at Radboud University, and he contributed to the research during an exchange visit in 51��.

51��

51��, a member of the prestigious Russell Group of British universities, is the largest and most popular university in the UK. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance. According to the results of the 2008 Research Assessment Exercise, 51�� is one of the country’s major research institutions, rated third in the UK in terms of ‘research power’, and has had no fewer than 25 Nobel laureates either work or study there. The University had an annual income of £807 million in 2011/12.

The National Aspergillosis Centre (www.nationalaspergillosiscentre.org.uk) is the UK’s referral clinic for patients with chronic pulmonary aspergillosis and related conditions. It was established five years ago and is housed at the University Hospital of South 51�� and funded through the National Health Service Specialised Services. The Aspergillus Website (www.aspergillus.org.uk) was set up in 1998 by the Fungal Infection Trust. It is the most comprehensive source of information about Aspergillus and the diseases it causes available on the Internet. An estimated 75,000 distinct IP addresses log on monthly and over 200,000 other websites link to the Aspergillus Website. Well over 70% of users in any month are new visitors from over 125 countries. Over 1,000 patients are currently registered with the support discussion group on Yahoo! with another 150 on Facebook with 280 LinkedIn members (Aspergillus and Aspergillosis Group).

51�� Asthma and Allergy Study celebrates 18th birthday

Fri, 04 Jul 2014 01:00:00 +0100

Researchers and participants involved in a long-term study into asthma and allergies by 51�� and the University Hospital of South 51�� marked its landmark birthday with a big party at the Wythenshawe-based hospital.

The , a research project run by 51�� and the University Hospital of South 51�� (UHSM) was designed to investigate risk factors for the development of asthma and allergies and has tracked over a thousand babies from their birth to age 18 since it began in the mid-nineties.

Along the way, the researchers have made many important discoveries including: creating a blood test for peanut allergy showing children who were overweight at age three were more likely to have a wheeze and persistent eczema (up to 8 years) showing that showing that children who receive antibiotics before their first birthday are at slightly increased risk of developing asthma, but are not at increased risk of allergies.

MAAS began in 1995 when investigators Professor Adnan Custovic and , from the Institute of Inflammation and Repair, in the University’s Faculty of Medical and Human Sciences (with support from Sr Bridget Simpson and Professor Ashley Woodcock) began screening pregnant women in the antenatal clinics of Wythenshawe (now UHSM) and Stepping Hill Hospitals.

Over 1000 families were recruited for the study from the local population and the team have been following the 1184 babies born throughout 1996 and 1997 ever since.

Over the years, the study participants and their parents have attended for a clinical assessment at UHSM at six key stages of their development, up to age 14.

As the children are now approaching their 18th birthdays, the MAAS study team invited them and their parents to a special open evening at UHSM to meet some of the behind the scenes team and learn more about how they have contributed to the study’s important findings and results.

The major strength of the MAAS study has been that by following the same children as they grow up, researchers can see how diseases develop longitudinally, and have collected information before symptoms start, which prevents ‘recall bias’.

The investigators can then compare factors in those with, and those without symptoms of asthma or allergic disease, to try to understand what may be important in causing these diseases. They have succeeded in publishing over 60 scientific papers from their findings.

The study is now funded by the Medical Research Council, and has previously been funded by Asthma UK.

Notes for editors

For further information, please contact Alison Barbuti | Media Relations Officer | 51�� | 0161 275 8383 | alison.barbuti@manchester.ac.uk

Nearly half of adults with Cystic Fibrosis are infected by fungi

Fri, 27 Jun 2014 01:00:00 +0100

A medical student from 51�� had made a major discovery which will help doctors diagnose and treat patients with Cystic Fibrosis (CF) while working with a University of 51�� led team at the University Hospital of South 51��.

Jo Armstead spent hundreds of hours accessing data from 30 countries to discover that there are over 75,000 people with the genetic disorder, of whom half are over 18 years with 50 per cent infected by the fungus, Aspergillus.

She spent last summer holidays working with Professor Denning, Director of the NHS National Aspergillosis Centre and Professor of Infectious Diseases in Global Health in the Faculty’s Institute of Inflammation and Repair, and the team at the University Hospital of South 51�� where what started out at a summer project has led to publication in a prestigious journal.

The student, who is in her third year at Newcastle University Medical School, said: “It has been really great to be involved in the first project of its kind ever done, with dramatic results and real opportunities for better health in young CF sufferers.”

Professor Denning, explained: “The life expectancy of people with CF has been increasing, but aspergillosis has a major negative impact on many.

“By painstakingly crunching the numbers, Jo has helped us better understand the scale of the challenge which will lead to better diagnostics and treatment strategies. There will be many patients who over the coming years will be grateful to Jo and her work.”

When she qualifies, Jo is considering a career in acute medicine with expedition medicine to combine her passions for the outdoors and travelling but, for the moment, she is studying hard for exams next month.

Registries for CF have been ongoing for years, but never before has the problem infection aspergillosis been accurately determined. The UK has the second highest number of adult CF sufferers (5,290), second only to the USA (13,657).

Aspergillosis causes the airway infection, bronchitis, and allergy, known as ABPA, which starts in childhood and reaches a peak in late teenage years. Treatment involves antifungal therapy or oral steroids, but is not yet demonstrated to be very effective, with antifungal resistance emerging.

Notes for editors

Contact Susan Osborne, Director of Communications, The Goodwork Organisation on 07836 229208.

Jo Armstead’s report can be found online “Multi-Country Estimate of Different Manifestations of Aspergillosis in Cystic Fibrosis“.

ABPA (non-invasive)

This is a condition where a patient develops an allergy to the spores of the Aspergillus moulds. Predominantly it affects asthma patients, those with cystic fibrosis (CF) and patients with bronchiectasis. 1% to 5% of adult asthmatics might develop this at some time during their lives, whereas 5% to 10% of CF patients may be affected.  Approximately 30% of all asthmatics suffer with severe (20%) or very severe (10%) asthma, and around 40% of both these groups are also sensitised to numerous different fungi – these patients have been grouped into a new category called Severe Asthma with Fungal Sensitisation or SAFS.

Presentation:

ABPA often presents with shortness of breath, coughing and wheezing. There may be pulmonary infiltrates, which do not respond to conventional antibiotics in asthma/CF sufferers. The symptoms are similar to those of asthma: intermittent episodes of feeling unwell, coughing and wheezing. Some patients cough up brown-coloured plugs of mucus. The diagnosis can be made by chest X-ray along with sputum, skin and blood tests. An elevated total serum IgE, together with evidence of Aspergillus sensitisation as seen by either the presence of Aspergillus antibodies, or identification from respiratory fluid, is a positive indication. Lung infiltrates are often seen on X-ray or CT scan.  In the long term ABPA can lead to permanent lung damage (fibrosis) if left untreated.

Treatment:

Oral, long-term, high-dose steroids are the usual method of management and the condition responds well to glucocorticoids. Inhaled steroids are ineffective. Itraconazole (an antifungal drug) has been shown to be of benefit when used in conjunction with steroids and longer term it may reduce the dosage of steroids required for ABPA treatment.

The National Aspergillosis Centre is the UK’s referral clinic for patients with chronic pulmonary aspergillosis and related conditions. It was established 5 years ago and is housed at the University Hospital of South 51�� and funded through the National Health Service Specialised Services.

The Aspergillus Website was set up in 1998 by the Fungal Infection Trust. It is the most comprehensive source of information about Aspergillus and the diseases it causes available on the Internet. An estimated 75,000 distinct IP addresses log on monthly and over 200,000 other websites link to the Aspergillus Website. Well over 70% of users in any month are new visitors from over 125 countries. Over 1,000 patients are currently registered with the support discussion group on Yahoo! with another 150 on Facebook with 280 LinkedIn members (Aspergillus and Aspergillosis Group)

Study may explain link between antibiotic use in infants and asthma

Thu, 15 May 2014 01:00:00 +0100

Children who receive antibiotics before their first birthday might be at a slightly increased risk of developing asthma. However, new research by 51�� suggests that it is impaired viral immunity and genetic variants on a region of chromosome 17 that increase the risk of both antibiotic use in early life and later asthma rather than the antibiotics themselves, as previously thought.

Importantly, the study, which was funded by the Medical Research Council and J P Moulton Charitable Foundation did not find a link between early antibiotic prescription and the development of allergic reactions.

The findings, reported in today (15 May), contradict the prevailing theory that early antibiotic exposure, via changes in gut flora, alters the development of a child’s immune system, increasing susceptibility to allergic asthma later on.

In children, antibiotics are routinely used to treat respiratory infections, ear infections, and bronchitis, and several studies have reported a link between the use of antibiotics during early childhood and the subsequent development of asthma. However, systematic reviews have reported conflicting results and called for additional longitudinal studies to provide definitive answers.

In this study, UK researchers examined data from the 51�� Asthma and Allergy Study (MAAS) which has followed over 1000 children from birth to 11 years.

Information on antibiotic prescription, wheeze and asthma exacerbations were taken from medical records. Skin reaction tests that show whether a child is hypersensitive to allergens were done at ages 3, 5, 8, and 11 years.

At age 11, blood was collected from children who had received at least one course of antibiotics or no antibiotics in the first year of life to compare their immune-system cell response to viruses (rhinovirus; the virus responsible for the common cold, and respiratory syncytial virus; RSV) and bacteria (Haemophilus influenzae and Streptococcus pneumoniae). Genetic testing was also done to look at the links between common genetic variations on chromosome 17, known as 17q21, and antibiotic prescription.

The study’s findings are believed to be the first to show that children with wheezing who were treated with an antibiotic in the first year of life were more than twice as likely as untreated children to experience severe wheeze or asthma exacerbations and be hospitalised for asthma.

Similarly, these children also showed significantly lower induction of cytokines, which are the bodies’ key defence against virus infections such as the common cold. However, no differences were noted in antibacterial responses.

The researchers also identified two genes in the 17q21 region that were associated with an increased risk of early life antibiotic prescription.

Lead author Professor Adnan Custovic, from based at 51��, said: “We speculate that hidden factors which increase the likelihood of both antibiotic prescription in early life and subsequent asthma are an increased susceptibility to viral infections due to impaired antiviral immunity and genetic variants on 17q21.

“However, further studies will be needed to confirm that the impaired immunity was present at the time of the early childhood respiratory symptoms and predated antibiotic prescribing rather than as a consequence of the antibiotics.”

ENDS

Notes for editors

(Image courtesy of Arvind Balaraman / FreeDigitalPhotos.net)

This study was funded by the Medical Research Council and J P Moulton Charitable Foundation. To interview Professor Adnan Custovic or for a copy of the paper, please call Alison Barbuti, Media Relations Officer, +44(0)161 275 8383 or email alison.barbuti@manchester.ac.uk

51��

51��, a member of the Russell Group, is one of the largest and most popular universities in the UK. It has 20 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance. According to the results of the 2008 Research Assessment Exercise, 51�� is one of the country’s major research institutions, rated third in the UK in terms of ‘research power’. The University has an annual income of £807 million and is ranked 40th in the world and fifth in the UK for the quality of its teaching and impact of its research.

Ground-breaking research Centre set to revolutionise asthma care for 5.4m people

Tue, 13 May 2014 01:00:00 +0100

The Asthma UK Centre for Applied Research has launched this month - the UK’s first integrated Centre focused solely on improving the quality of life of people with asthma by finding better treatments and making them available faster than ever before - with input from 51��.

The Centre is co-ordinated through the University of Edinburgh and Queen Mary, University of London and backed by 13 of the UK’s leading academic and NHS organisations – including 51�� and University Hospital of South 51�� NHS Foundation Trust. 51�� has a strong record of research in asthma and allergy, in adults and children and in both primary care and hospital settings, notably the 51�� Asthma and Allergy Study (MAAS), which is a population of 1000 children who were recruited during pregnancy in 1996/7.

More than 5 million people in the UK are affected by asthma yet research into this life-threatening condition is chronically underfunded, taking an average of 17 years currently to develop a new asthma treatment. Asthma UK’s vision for this pioneering, multidisciplinary research initiative is to halve the time it takes to get innovations to people with asthma and to develop the next generation of world class applied asthma researchers. The NHS spends around £1 billion a year treating and caring for people with asthma. In 2008/09 up to 1.1 million working days were lost due to breathing or lung problems.

Ann-Louise Caress, Professor of Nursing in the School of Nursing, Midwifery and Social Work, 51�� and University Hospital of South 51�� NHS Foundation Trust, said: “I'm delighted that 51�� is one of the sites involved in this exciting collaboration. The Centre offers unique opportunities for undertaking research which will be of real benefit to the lives of people with asthma. I'm helping to develop 'patient and public involvement' in the Centre's research. This is a key element of good quality research, to which the Centre has a strong commitment. I'm really proud of the strength of this aspect of the Centre's work.”

Kay Boycott, Asthma UK’s Chief Executive, says: “The introduction into clinical use of the pressurised metered-dose inhaler (pMDI) - the first modern inhaler for asthma management – took over 40 years from initial lab discovery through clinical trials and into practice.

“More than half a century later asthma still kills and there are tens of thousands of people with asthma facing a daily struggle to breathe. This is why it is so vital for Asthma UK to invest significantly in the Asthma UK Centre for Applied Research and to kick start a new era of improved discovery-to-treatment times.”

The Centre is led by is led by Professors Aziz Sheikh and Chris Griffiths, two of the UK’s most talented experts in applied asthma research.

Centre Director Aziz Sheikh says: “The Centre addresses a very real need for collaborative research that can facilitate large-scale trials which have potential to benefit the millions of people affected by asthma. I am delighted that some of the UK’s top asthma researchers are contributing to this unprecedented initiative where they can share expertise and insights to drive forward major improvements in asthma care provision and better outcomes for our patients.”

Centre Co-Director Chris Griffiths says: “The recent National Review of Asthma Deaths (NRAD) reports the urgent need to improve asthma care. The opening of the Asthma UK Centre for Applied Research is perfectly-timed and marks a significant step forward in delivering world-class applied research to improve asthma care and reduce asthma deaths and hospitalisation in the UK.”

Ends

Notes for editors

(Image courtesy of Arvind Balaraman / FreeDigitalPhotos.net)

For interviews with spokespeople, please call the Asthma Centre Media Office on 020 7786 4949 or email mediaoffice@asthma.org.uk. Please call 07951 721393 out of hours.

For 51�� interviews, please contact Alison Barbuti, Media Relations Officer, 0161 275 8383 or email alison.barbuti@manchester.ac.uk.

New research links body clocks to chronic lung diseases

Mon, 17 Mar 2014 00:00:00 +0000

The body clock’s natural rhythm could be utilized to improve current therapies to delay the onset of chronic lung diseases.

Scientists at 51�� have discovered a rhythmic defence pathway in the lung controlled by our body clocks, which is essential to combat daily exposure to toxins and pollutants.

Internal biological timers (circadian clocks) are found in almost all living things driving diverse processes such as sleep/wake cycles in humans to leaf movement in plants. In mammals including humans, circadian clocks are found in most cells and tissues of the body, and orchestrate daily rhythms in our physiology.

The research team’s ground breaking findings, which are being published in Genes & Development, have for the first time found that the circadian clock in the mouse lung rhythmically switches on and off genes controlling the antioxidant defense pathway. This 24 hourly rhythm enables the lungs to anticipate and withstand daily exposure to pollutants.

The research was led by Dr Qing-Jun Meng from 51�� who is also a Medical Research Council (MRC) Research Fellow. He has been studying body clocks for a number of years and has been awarded an MRC Career Development Award to establish the relationship between the disruption of circadian rhythms and the susceptibility to human diseases, especially those associated with old age.

Dr Meng said: “We used a mouse model that mimics human pulmonary fibrosis, and found that an oxidative and fibrotic challenge delivered to the lungs during the night phase (when mice are active) causes more severe lung damages than the same challenge administered during the day which is a mouse’s resting phase.”

This means that the rhythm of this lung clock gives an indication of more suitable times of the day for drugs to be administered to patients suffering from oxidative/fibrotic diseases such as pulmonary fibrosis, asthma, chronic obstructive pulmonary disease.

Dr Meng continued: “Our findings show that timed administration of the antioxidant compound sulforaphane, effectively attenuates the severity of the lung fibrosis in this mouse model.”

In other words the research suggests that taking drug treatments for oxidative and fibrotic diseases according to the lung clock time could increase their effectiveness, which would allow a lower dosage and consequently reduce side effects.

Dr Vanja Pekovic-Vaughan, who was part of the University’s research team, said: “This research is the first to show that a functioning clock in the lung is essential to maintain the protective tissue function against oxidative stress and fibrotic challenges. We envisage a scenario whereby chronic rhythm disruption (e.g., during ageing or shift work) may compromise the temporal coordination of the antioxidant pathway, contributing to human disease.”

This latest study is part of on-going research that is exploring how chronic disruption to body clocks by changes like ageing or shift work contribute to a number of conditions such as osteoarthritis, cardiovascular disease, breast cancer, and mood disorder.

Dr Meng said: “Our next step is to test our theory that similar rhythmic activity of the antioxidant defence pathway also operates in human lungs. This will enable us to translate our findings and identify the proper clock time to treat chronic lung diseases that are known to involve oxidative stress.

“Funded by an MRC Fellowship Partnership Award, we have teamed up with GlaxoSmithKline to explore the potential of utilizing the body clock mechanisms to improve the efficiency of the current antioxidant compounds for diseases. Timing the delivery of drugs - so-called ’chrono-therapy’ or ’chrono-pharmacology’ - has already demonstrated clinical benefits in treatment of cancer and arthritis,” he said.

Professor Stuart Farrow, a Director in the Respiratory therapy area at GSK (who is also the industrial partner for Dr Meng on the MRC Fellowship Partnership Award), commented: “Chronic lung diseases are prevalent and debilitating, and continue to be an important area of unmet medical need. This exciting new research reveals an opportunity to harness the body clock to provide valuable benefit to patients.”

Notes for editors

Kath Paddison

Media Relations Officer

Faculty of Life Sciences

51��

Tel. +44 (0)161 275 2111

Email: kath.paddison@manchester.ac.uk

Please contact us for a copy of the paper ‘The circadian clock regulates rhythmic activation of the NRF2/glutathionemediated antioxidant defense pathway to modulate pulmonary fibrosis’ by Vanja Pekovic-Vaughan, Julie Gibbs, Hikari Yoshitane, Nan Yang, Dharshika Pathiranage, Baoqiang Guo, Aya Sagami, Keiko Taguchi, David Bechtold, Andrew Loudon, Masayuki Yamamoto, Jefferson Chan, Gijsbertus T.J. van der Horst, Yoshitaka Fukada, Qing-Jun Meng

51�� team to lead the world on fungal infection research

Wed, 14 Aug 2013 01:00:00 +0100

51�� has invested in building a world-leading research group to tackle a problem that is largely unrecognised yet affects millions of people each year.

Globally and annually, over 300 million people suffer from serious fungal infections, resulting in 1,350,000 deaths – many of which are unavoidable.

Most serious fungal infections are hidden, occurring as a consequence of other health problems such as asthma, AIDS, cancer or organ transplants. Delays or missed diagnosis often lead to death, serious chronic illness or blindness.

Now, the newly formed multidisciplinary 51�� Fungal Infection Group (MFIG) hopes to make a difference with the recruitment of three leading experts from Edinburgh and London.

Professor Nick Read has moved from Edinburgh University and leads the group, while Dr Elaine Bignell from Imperial College, London, has been appointed as a Reader, and Dr Mike Bromley as a lecturer. 51�� senior lecturers, Dr Paul Bowyer and Peter Warn will also join the MFIG and will work alongside the already thriving research and teaching teams of Professors David Denning and Malcolm Richardson, and Dr Riina Richardson, to form this pioneering Group.

Professor Nick Read is an internationally-renowned fungal cell biologist with over 30 years of research experience and has pioneered the use of advanced live-cell imaging techniques with many fungi, including human pathogens.

Professor Read said: “The opportunity to develop cutting-edge, multidisciplinary science in the relatively neglected but extremely important topic of fungal infection will be internationally unique and I am very excited to be able to join and lead this team of talented scientists in 51��.”

The focus of the MFIG going forward is developing a profound understanding of the biology of the mechanistic basis of * fungal infection, identifying new antifungal drugs and human genetic risk profiling. The team will also work with the a partnership between 51�� and six NHS Trusts which helps health care organisations reap the benefits of research and innovation to drive improvements in care.

Professor Ian Jacobs, University of 51�� Vice President and Dean of the Faculty of Medicine and Human Sciences added: “I am excited by the combination of strong clinical leadership, exemplified by the National Aspergillosis Centre, and internationally competitive science, which these new appointments bring. This fits perfectly with the strategy of our Faculty to develop outstanding science in to health benefit. MFIG can have an impact in the UK and internationally in a neglected area which is responsible for enormous suffering and over a million deaths every year.’’

ENDS

Notes for editors

Nearly 5 million asthmatics could benefit from antifungal therapy

Wed, 08 May 2013 01:00:00 +0100

An estimated 4,837,000 asthmatics with allergic bronchopulmonary aspergillosis (ABPA) could benefit substantially from antifungal treatment, say researchers from 51�� and the University of Toronto.

Their work, published today in the journal Medical Mycology, has also re-estimated the total number of asthmatics worldwide – to reveal a staggering 193 million sufferers. Twenty-four million asthma sufferers live in the United States, 20 million each in India and China, and seven million in the United Kingdom.

Clinical studies have shown that oral antifungal drugs significantly improve symptoms and asthma control in asthmatics with ABPA, treatment endorsed by the Cochrane Collaboration. This is the first time that a global estimate of ABPA numbers has been made.

In national league tables of asthma rates in adults, only Australia and Sweden have a higher prevalence than the UK. In global league tables of ABPA occurrence, New Zealand tops the list with a 3.5% rate in new patients attending chest clinics at hospitals. The rates were 2.6% in Cape Town, 2.3% in Saudi Arabia, 2.5% in China and 0.7% in an older study from Ireland. No population-based studies have been done.

In addition to standard asthma therapy, the antifungal therapy used is itraconazole – now a generic, inexpensive antifungal – with a response rate of 60%. The researchers also found that antifungal therapy also benefits patients with severe asthma sensitized to fungi, called SAFS.

Alternatives include voriconazole and posaconazole, which have 75-80% response rates. In a recent assessment of voriconazole and posaconazole for both ABPA and SAFS, 75% of patients were able to stop taking oral corticosteroids, a major benefit, and 38% of patients had their asthma severity downgraded on antifungal therapy.

Professor David Denning, Professor of Medicine and Medical Mycology at 51�� and Director of the University Hospital of South 51��’s National Aspergillosis Centre, led the study into the total number of asthmatics worldwide. He said the study results implied that asthma admissions and deaths could be avoided with more extensive use of antifungal therapy.

“We were surprised by the number of patients with ABPA, and by the lack of community based studies done,” he said. “Our National Aspergillosis Centre treats hundreds of these patients each year, generally with major improvement, and so a conscious program to seek out ABPA from all asthmatics is required.”

Notes for editors

Image and case studies available.

Image shows an example of severe ABPA with bronchiectasis and lung inflammation.

For further information contact:
Alison Barbuti
Media Relations Officer
Faculty of Medical and Human Sciences
alison.barbuti@manchester.ac.uk
0161 275 8383

To view the paper entitled, Global burden of asthma in adults and ABPA, click .

For further information, also see:

Ground breaking inflammation centre officially opens

Thu, 07 Mar 2013 00:00:00 +0000

Patients suffering from inflammatory diseases are set to benefit from the opening of a ground breaking centre dedicated to investigating this complex area.

The 51�� Collaborative Centre for Inflammation Research (MCCIR) is a unique partnership between 51�� and the two major pharmaceutical companies GlaxoSmithKline and AstraZeneca. It's hoped this new way of working will deliver more effective treatments for a range of conditions such as asthma, arthritis and inflammatory bowel disease. The MCCIR is officially launched on Monday 11 March.

The Director of the MCCIR is Professor Tracy Hussell: “Bringing together academia, industry and clinicians in one centre creates the real possibility of innovation. The ideas that spring from this partnership will fuel the treatments of the future and provide the ideal platform to transfer scientific progress into clinical benefit.”

Inflammatory diseases affect millions of people worldwide, leading to pain, disability and, in some cases premature death. Inflammation is a process by which the body combats infection, diseases such as cancer or trauma and heals itself. However, ongoing inflammation can be very harmful and a feature of patients with a range of conditions.

The centre will be collaborating with clinical and industrial colleagues to identify groups of patients with asthma, arthritis or chronic obstructive pulmonary disease that either spontaneously get better or continue to suffer from severe inflammatory disease. This is with the aim of identifying new avenues for treatment for those with chronic inflammatory diseases.

Professor Hussell was recruited from Imperial College London last year and has been working hard to ensure the centre has world class scientists at its heart: “I am hugely excited by the focus of the centre on maintaining immune health and defining why some people get better spontaneously. Those that get better hold the clues for restoring immune health and, more importantly, ways in which to prevent disease progression".

A good example of some of the work being done at the centre is the research being carried out by Dr James Fildes. His work focuses on understanding the mechanisms involved in repairing injured tissue, primarily in heart and lung transplantation. Up to 80% of lungs that are donated for transplantation are so damaged that they can’t be used. Working with Professor Nizar Yonan’s team at Wythenshawe Hospital, lungs can be successfully repaired to the point where they’re fit for transplantation. Dr Fildes is attempting to understand this process, with the aim of developing new drug targets for the future.

Talking about the MCCIR Dr Fildes says: “Working directly with the pharmaceutical industry will hopefully mean our research can be translated into treatments at a much earlier stage. We believe this will have a real benefit for patients.”

46 year old Sean Bell was born with Cystic Fibrosis. He had a double lung transplant six years ago and has welcomed the launch of the centre: “Being told you need a lung transplant is a frightening experience. The average wait for a donation can be two years or more and up to half of those on the waiting list might die before the operation can take place due to the lack of suitable donor organs available. I was incredibly lucky and the transplant has given me and my family a new lease of life. The work being done at the MCCIR is simply amazing. It’s very likely their research will lead to fewer people dying whilst waiting for donor lungs. We are very lucky to have such a world class facility in 51��.”

It’s this drive for the development of new and better treatments that has seen two of the world’s biggest pharmaceutical companies invest in the MCCIR. Researchers from GSK and AstraZeneca will be working in the centre alongside academic staff.

Talking about the collaboration Dave Allen, Senior Vice-President of Respiratory Research at GlaxoSmithKline says: “The translation of basic research discoveries into new medicines is challenging, but we believe we improve our chances of success through collaborative science. The MCCIR will embody this approach, and I am delighted that GSK has been able to contribute to its development.”

Maarten Kraan, Head of the Respiratory and Inflammation Innovative Medicines Unit at AstraZeneca adds: “The creation of this centre is indicative of a new era of pre-competitive sharing within the pharmaceutical sector and with academic scientists. By working together, we hope to enable a better understanding of inflammatory processes and ultimately achieve faster delivery of new medicines to patients.”

The MCCIR is funded with an initial investment of £5 million from each partner over a three year period. The centre is based at 51�� and will initially house eight principal investigators and their research teams in custom built, state of the art laboratories.

Notes for editors

Interviews: Professor Hussell, Dr James Fildes and Sean Bell are all available for interviews.

Images of the centre, including the laboratories are available from the press office.

Media are welcome to attend all or part of the launch event at The Midland Hotel in 51�� on Monday 11 March between 10:30 and 18:00. This must be arranged through the press office.

Alternatively journalists are welcome to arrange visits to the MCCIR to see the research in action and carry out interviews. This must be organised through the press office.

Professor Hussell is joined by Professors Daniel Davis (from Imperial College London), Andrew MacDonald (from the University of Edinburgh) and Mark Exley (from Harvard), Dr James Fildes, Dr Mark Travis, Dr Amy Saunders and Dr Gloria Lopez-Castejon. All have been recruited for their expertise in areas of innovation with regards to inflammatory disease.

This team will work together to develop concepts and create medicines relevant to a wide variety of inflammatory diseases. GSK is one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines for gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit:

Sean Bell is a trustee of the New Start Charity which provides financial assistance to the heart and lung transplantation programme and future clinical developments in heart and lung surgery at Wythenshawe Hospital. More information can be found at

For interview and image requests please contact:

Morwenna Grills
Media Relations Officer
Faculty of Life Sciences
51��

Tel: 0161 275 2111
Mob: 07920 087466
Email: Morwenna.Grills@manchester.ac.uk

Drug-resistance fears for deadly fungal disease

Thu, 05 May 2011 01:00:00 +0100

Deadly human fungal infections caused by certain strains of Aspergillus fungi appear to be developing resistance to current drug treatments at an alarming rate, say scientists.

University of 51�� researchers, working with colleagues in Newark, USA, have developed a new test that can not only better diagnose Aspergillus infection, but can also spot signs of antifungal resistance to azoles – the class of drugs used to treat patients with aspergillosis.

Using the new test, which uses direct molecular detection rather than culturing the fungus in a Petri dish, the team found that 55% of aspergillosis patients had telltale signs known as ‘markers’ that indicated they had developed resistance to azoles. The findings compare to resistance rates of 28% carried out by the team just two years ago using traditional culturing methods.

Furthermore, the study – published in the prestigious US journal Clinical Infectious Diseases – discovered azole-resistance markers in three-quarters of the small number of aspergillosis patients (eight) whom had never been treated with an azole, suggesting widespread dissemination of resistance.

“Aspergillus significantly worsens asthma symptoms and causes life-threatening infections in those with long-term lung infections or damaged immune systems, such as chemotherapy and transplant patients or people with HIV,” said David Denning, Professor of Medicine and Medical Mycology at 51�� and Director of the National Aspergillosis Centre at the University Hospital of South 51�� NHS Foundation Trust.

“Using an ultrasensitive, real-time test for Aspergillus, similar to the method used to diagnose HIV, MRSA and influenza, we have directly detected azole resistance in people with aspergillosis, without first culturing the fungus in a dish. The presence of Aspergillus was detected in many more samples than using traditional culture methods, and 55% were found to contain azole-resistance markers.

“This is an extraordinarily high rate of resistance, possibly related to fungicide use in agriculture – more than a third of ‘pesticides’ used by UK farmers are azoles – and long treatment courses in patients, so the findings have major implications for the sustainability of azoles for human antifungal therapy.”

The azoles itraconazole (Johnson & Johnson), voriconazole (Pfizer) and posaconazole (Merck) have annual sales of more than $1bn annually. Conventional diagnosis of aspergillosis is limited by poor culture yield, and so the true frequency of azole resistance has been unclear.

In this latest study, the researchers analyzed phlegm from patients with allergic and chronic lung disease caused by Aspergillus and found that almost twice the proportion of individuals tested had resistance markers in their sample compared to a Petri dish (or culture) study carried out by the team in 2008/9.

Professor Denning added: “Not only is molecular testing much more sensitive than conventional culture for diagnosis, but it enables testing for resistance, which until now has been impossible if cultures are negative. Given the rising frequency of resistance in Aspergillus in northern Europe, China and the United States, this study provides key data for doctors to shift antifungal therapy in the face of resistance."

Ends

Notes for editors

A copy of the paper, Denning DW, Park S, Lass-Florl C, Fraczek MG, Kirwan M, Gore R, Smith J, Bueid A, Bowyer P, Perlin DS. High frequency triazole resistance found in non-culturable Aspergillus fumigatus from lungs of patients with chronic fungal disease. Clin Infect Dis 2011;52:1123-9, is available on request.

A copy of the 2009 study, Bueid A, Howard SJ, Moore CB, Richardson MD, Harrison E, Bowyer P, Denning DW. Azole antifungal resistance in Aspergillus fumigatus - 2008 and 2009. J Antimicrob Chemother 2010;65:2116-8, is also available.

The primary molecular detection test is Myconostica’s MycAssay Aspergillus, commercialized through Myconostica, a University of 51�� spin-out company, founded by Professor David Denning.

Further information concerning Aspergillus and aspergillosis can be found on

For further information contact:

Aeron Haworth
Media Relations
Faculty of Medical and Human Sciences
51��

Tel: 0161 275 8383
Mob: 07717 881563
Email: aeron.haworth@manchester.ac.uk

51�� nuclear hormone research approach is a UK first

Fri, 14 Jan 2011 00:00:00 +0000

Researchers and doctors from 51�� institutes have joined forces with pharmaceutical company GlaxoSmithKline (GSK) to launch an innovative joined-up approach to tackling chronic inflammatory disease.

The creation of the 51�� Centre for Nuclear Hormone Research in Disease is the first time academics, the NHS and industry have collaborated in a three-way approach to finding new therapies for inflammatory conditions such as asthma, chronic obstructive lung disease (COPD), and rheumatoid arthritis.

The centre will be jointly managed by Professors David Ray and Andrew Loudon from 51�� and the National Institute for Health Research 51�� Biomedical Research Centre (MBRC), and Dr Roberto Solari of GSK. It will focus research efforts on understanding the role of nuclear hormone receptors in inflammatory diseases and seeking to identify compounds that could help lead to new treatments.

Leading the research teams will be Visiting Professor Stuart Farrow, the newly appointed Chair in Experimental Therapeutics at 51�� and the MBRC. Professor Farrow will also continue his current role at GSK, where he has been developing new medicines for lung diseases such as asthma and COPD since 2000.

An external advisory board with industrial and academic representatives will also provide guidance on research strategy.

Initial work will focus on several specific projects which together address the broader aim of understanding the biology of chronic inflammation, what causes it to persist and the best options to develop new therapies.

“This is a tremendously exciting development, bringing together industry expertise in drug discovery with local research and clinical expertise and access to clinical research facilities,” said Stuart Farrow. “Harnessing the capabilities of outstanding researchers, the expertise within the NHS and GSK’s considerable resources creates a very powerful collaboration. Our aim is to speed up the discovery and development of new medicines to treat these major inflammatory diseases.”

David Ray, Deputy Director of the MBRC, added: “Having already worked with Stuart – who is a widely respected researcher in this field - we’re delighted he’s involved in the programme. The free interchange of ideas, facilities and research staff between the various GSK sites world-wide and the 51�� BRC will also maximise training opportunities for young researchers, and the rapid implementation of new ideas. Ultimately we hope this will translate into major benefits for patients affected by these debilitating conditions.”

The new programme will initially run for three years, and the team is also applying for additional industrial and Medical Research Council funding to extend the scope of the collaboration.

Ends

Notes for editors

The NIHR 51�� Biomedical Research Centre was created by the National Institute for Health Research in 2008 to effectively move scientific breakthroughs from the laboratory, through clinical trials and into practice within hospitals to improve patient care. As a partnership between Central 51�� University Hospitals NHS Foundation Trust and 51��, the Biomedical Research Centre is designated as a specialist centre of excellence in genetics and developmental medicine. www.cmft.nhs.uk/brc
51��, a member of the Russell Group, is the largest single-site university in the UK. It has 22 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance. According to the results of the 2008 Research Assessment Exercise, 51�� is now one of the country’s major research universities, rated third in the UK in terms of ‘research power’. The University has an annual income of £684 million and attracted £253 million in external research funding in 2007/08.
GlaxoSmithKline – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit

For further information contact:

Kate Henry
Communications & Public Relations Manager
MBRC

Tel: 0161 276 3281/07825 142219
Email: kate.henry@cmft.nhs.uk

Aeron Haworth
Media Officer
51��

Tel: 0161 275 8383
Email aeron.haworth@manchester.ac.uk

Fresh funding gives hope to new generation of asthma and allergy drugs

Wed, 05 Jan 2011 00:00:00 +0000

Scientists at 51�� and St George’s, University of London, have received an additional Seeding Drug Discovery award of £390,000 from the Wellcome Trust to explore a new class of experimental drugs that block the trigger of allergic reactions before symptoms arise.

The team is developing a series of drugs based on novel chemical compounds known as Allergen Delivery Inhibitors (ADIs). Unlike existing medicines, these compounds target the substances that can trigger allergies and asthma attacks directly. This means that they have the potential to provide relief to people already suffering with allergies, as well as reducing the risk of minor allergies escalating into more serious conditions.

In 2009, the researchers were awarded a £4.3million Seeding Drug Discovery award to investigate ADIs as a potential treatment for asthma and allergy. In the course of that project, they have identified a novel chemical series that shows promise as a preventative treatment. The new funding will be used to explore this further with a view to identifying a lead compound that could be developed into a drug.

Asthma and allergic conditions such as rhinitis, conjunctivitis and dermatitis are escalating problems expected to affect more than 100million people globally by 2011. In the UK, 5.2million adults and 1.1million children currently receive treatment for asthma, creating a significant social and healthcare burden for the NHS.

The first ADI drug being developed by the team – in collaboration with the expert medicinal chemistry partner Domainex – targets house dust mites, globally one of the commonest causes of domestic allergy and a key trigger of asthma attacks.

Dust mites excrete particles, amongst which are powerful enzymes that, when inhaled, can cause an inappropriate immune reaction in people who are prone to allergy, causing damage to the lining of the airways. These allergenic enzymes are abundant in the environment, so they cannot be avoided and susceptible people are constantly at risk.

The team has developed ADIs that bind to the dust mite particles and block their enzymatic activity. Experimentally, these inhibitors reduce the intensity of reactions in established allergy and can even prevent allergy from occurring.

“Millions of people worldwide are allergic to the tiny house dust mites that live in our homes, cars and other building that we frequent,” said Professor David Garrod, in 51��’s Faculty of Life Sciences. “ADIs attack the root cause of the allergy by preventing the inhaled mite enzymes from starting the allergic response. Currently available treatments alleviate symptoms but do not prevent them from occurring. This new grant from the Wellcome Trust will increase our potential to develop ADIs, which will provide a new dimension in the treatment and prevention of allergy.”

Lead researcher Professor Clive Robinson from St George’s, University of London, added: “A compelling feature of the ADI approach is its attack on the pinnacle of the cascade of events that leads to an allergic reaction. Existing medicines target the allergy cascade at a lower, more complex level where success in the discovery of new drugs that modify allergic diseases is notoriously hard to achieve. At present, patients have to rely on therapeutic approaches which have seen no fundamental advances in the past 20 years.

“Used alone or in combination with existing treatments, our investigations indicate that they should improve the quality of life for many patients with allergic disease and may enable some to manage without any other form of treatment. Additionally, ADIs may provide relief for some patients who do not respond well to existing medicines.”

Dr Rick Davis, Business Development Manager at the Wellcome Trust, said: “Allergy is a source of misery for millions worldwide and represents an area of huge unmet medical need. The St George’s-51�� collaboration has made excellent progress in this area and we are pleased to provide continued support for this project.”

Once a lead compound has been identified, the next phase of work will be to refine the drug candidate to take forward into human clinical trials to assess its safety, tolerability and efficacy.

Ends

Notes for editors

51��, a member of the Russell Group, is the largest single-site university in the UK. It has 22 academic schools and hundreds of specialist research groups undertaking pioneering multi-disciplinary teaching and research of worldwide significance.

According to the results of the 2008 Research Assessment Exercise, 51�� is now one of the country’s major research universities, rated third in the UK in terms of ‘research power’. The University had an annual income of £755 million in 2008/09.

St George’s, University of London provides education and training to a wide range of more than 4,000 medical and healthcare students. As well as providing courses in medicine and biomedical sciences, the College also offers courses in midwifery, nursing, paramedic science, physiotherapy, radiography and social work in conjunction with Kingston University. St George’s is dedicated to promoting the prevention, treatment and understanding of disease through excellence in teaching, clinical practice and research. It has a strong reputation for research in areas such as infection and immunity, diseases of the heart and circulation, cell signalling and epidemiology. Other areas of expertise include genetics, health and social care sciences and mental health.

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. It supports the brightest minds in biomedical research and the medical humanities. The Trust’s breadth of support includes public engagement, education and the application of research to improve health. It is independent of both political and commercial interests.

Domainex Ltd. is a UK located Contract Research Organisation committed to excellence in drug discovery. It provides its clients with a range of services, from drug target expression through in-silico hit finding and medicinal chemistry, resulting in eventual candidate drug. It has one of the best track records in the drug discovery CRO industry and has supported a number of Wellcome Trust funded drug discovery programmes. For more information see: www.domainex.co.uk

For further information contact:

Aeron Haworth
Media Relations
51��

Tel: 0161 275 8383
Mob: 07717 881563
Email: aeron.haworth@manchester.ac.uk

New parenting study aims to help kids with asthma

Thu, 07 Oct 2010 01:00:00 +0100

A successful parenting programme that has previously helped children with behavioural problems is being expanded to see if it can also help improve the lives of youngsters with asthma.

The research, by clinical psychologists at 51��, is based on findings that over-protective or overly lenient parenting can make asthma worse.

The study will provide 120 parents of children with asthma with information and guidance on how to manage bad behaviour when it happens and how to prevent problems with asthma.

The research team hope to help parents avoid what they call ‘parenting traps’. Lead researcher Dr Sally Clarke said: “A parenting trap is, for example, letting a child throw a tantrum in a supermarket just because they are unwell.

“This can teach the child to act sick even when they are well and encourage them to use their illness to get out of things they don’t want to do.”

The research team is using a parenting programme recommended by the National Institute for Health and Clinical Excellence (NICE) called ‘Triple P’, which stands for Positive Parenting Programme.

Triple P, which has previously improved the lives of children with behavioural problems and young people with learning disabilities, is being developed specifically for use with children with asthma.

“Triple P is an excellent programme that has already helped improve the lives of many families,” said Dr Clarke. “This new study will test whether the same principles can also improve the quality of life of children with asthma and their families.”

The parents will have access to asthma ‘tip sheets’ and eight weeks’ worth of short video clips, as well as their own self-help booklet. They will be able to participate online or by post.

More information about the study (which has now ended) can be found at

Ends

Notes for editors

This research is being overseen by two of the world’s leading proponents of Triple P, Professor Matthew Sanders, Professor of Clinical Psychology at the University of Queensland, Australia, and Dr Rachel Calam, Reader in Clinical Psychology at 51��.

Dr Sally Clarke is leading the research as part of her Doctorate in Clinical Psychology at 51��.

For further information contact:

Aeron Haworth
Media Relations
Faculty of Medical and Human Sciences
51��

Tel: 0161 275 8383
Mob: 07717 881563
Email: aeron.haworth@manchester.ac.uk

New study to show how our body clock controls disease

Wed, 17 Mar 2010 00:00:00 +0000

New treatments for inflammatory lung diseases and a host of other conditions could be developed following a study into the impact of circadian rhythms – or body clock – at 51��.

In a partnership between the University of 51��, the NIHR 51�� Biomedical Research Centre and GlaxoSmithKline (GSK), a team of scientists will investigate how our biological clock controls inflammation in lung diseases such Chronic Obstructive Pulmonary Disease (COPD). It is hoped that this project, worth more than £500,000, will lead to the development of new drugs which will target how the internal body clock regulates the severity of inflammation. The 51�� team is headed by Professors Andrew Loudon, David Ray and Kath Else, and they will work closely with colleagues in the Discovery Biology group at GSK.

Inflammatory diseases of the lung are a major cause of mortality world-wide. In the case of COPD, the progression of this inflammatory disease is irreversible once commenced. In the UK 27,478 people died as a result of COPD in 2004. Other diseases with an inflammatory aspect include asthma, which is a predisposition to chronic inflammation of the lungs in which the airways are reversibly narrowed. This disease affects 7% of people in the US, 6.5% in the UK and 300 million people worldwide, and causes 4,000 deaths a year in the US.

In order to develop the drugs, the team will first study the mechanisms whereby the circadian clock controls the magnitude of the local inflammatory response; that is, the genes and pathways that connect the clock to the cells responsible for the immune response in the lungs.

Professor Loudon, of the Faculty of Life Sciences, explains: “Many inflammatory diseases are highly rhythmic in presentation and often worse at night.”

“We believe there is also a strong rhythmic control. It has long been speculated that asthma and other inflammatory conditions have an underlying clock mechanism controlling the severity of the disease. These clocks are all over the body, including in cells responsible for the immune response in the lung. In addition the way we metabolise drugs is highly rhythmic.

“Our aim is to gain a sufficient understanding of this process so we can target key parts with specific new drugs.

“We are working with GSK not only to develop new drugs to alleviate symptoms but also reveal optimal timing of therapy, known as chronotherapy. This is a new and exciting area of research. It is being taken very seriously in France, for example, where researchers have for some time been studying the importance of timing of chemotherapy in cancer.”

He adds: “After a decade of research into the area you don’t have to explain to anyone what the circadian clock is these days, which is a very good thing. But in the last three years we have gone further, developing very strong links between the basic science and its clinical application.

“We have detailed insight into how the molecular cogs of the clock work, drive cells and physiology. We have been looking at it organ by organ, cell by cell, unraveling how the clock drives the biology of the organism. Many diseases are rhythmic, so it’s no surprise that when the circadian rhythm is disrupted it is associated with altered physiology.

“This study is just one at the beginning of an exciting new phase in circadian rhythm research.”

Notes for editors

For more information or an interview with Professor Andrew Loudon contact Media Relations Officer Mikaela Sitford on 0161 275 2111, 07768 980942 or Mikaela.Sitford@manchester.ac.uk.

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