Research summary – Gideon Bernstein

Heterogeneity of respiratory disease in children and young adults with sickle cell disease
Alan Lunt, Lucy Mortimer, David Rees, Sue Height, Swee Lay Thein and Anne Greenough
Published in the journal Thorax, November 2017

The purpose of this study was to look at the different types of breathing problems which affect people who have sickle cell disease (SCD). This is important because although it is known that many people with SCD also suffer from lung disease, not every person with SCD is affected in the same way, so it is important to try to categorise the different presentations with the goal of improving future treatment of SCD.
In order to achieve this goal, the study first measured several physical characteristics in each of 114 people with SCD. These included the volume and speed at which they could breathe in and out, the capacity of their lungs, how easy it was for air to travel through their airways, the amount of blood circulating in the lungs, and how well their blood carries oxygen.
The researchers then used a technique called cluster analysis to find three groups of individuals who shared particular characteristics. The first group had more blood in the vessels supplying the lungs, and respiratory disease caused by a combination of narrowed airways and a restricted lung expansion (which makes it harder to breathe). The second group was composed of older patients who had respiratory disease caused by restrictions on how much the lungs can expand, poorer uptake of oxygen in the lungs, and only mild anaemia. The third group were younger patients with lung disease caused by narrowed airways, more evidence of damage to red blood cells., and were most likely to benefit from a reliever asthma inhaler. The people in the third group had been admitted to hospital for their SCD more often.
Further analysis showed that people could be classified into one of the three groups based on results from two simple breathing tests and a blood test, meaning that identifying which group people with SCD fall into could be done relatively easily in future studies or in the clinic.
The results of this study show that respiratory disease experienced by people with SCD can be categorised into three groups, which may help to make future management of this condition easier by delivering more individual treatments.

This summary was produced by Gideon Bernstein, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research summary – Joseph Henley

The influence of dilution on the offline measurement of exhaled nitric oxide
Victoria MacBean, Dharmika Pooranampillai, Catherine Howard, Alan Lunt, and Anne Greenough
Published in the journal Physiological Measurement, February 2018

Asthma is a serious and growing health issue. Asthma UK say that 5.4 million people in the UK receive treatment and that, on average, three people die every day from asthma. People with asthma have inflamed airways and this causes them to breathe out higher-than-normal levels of a gas called nitric oxide (NO). By measuring the amount of NO in a person’s exhaled breath (which scientists call fractional exhaled nitric oxide or “FeNO”) asthma can be diagnosed and other health conditions that affect breathing can be ruled out. FeNO testing also allows the severity of asthma to be tracked so that the patient can know if the treatments they are using are helping or not.
The standard FeNO test requires a long, steady blow into a machine. This makes it unsuitable for young children and so an alternative test is often used, which involves them breathing normally into a bag and then analysing the exhaled air separately afterwards.
The authors of this study wanted to see whether the alternative FeNO test used for young children was accurate and, if not, whether it could be made accurate by adjusting the results using a mathematical equation. The authors devised an equation that took into account the amount of air already in the testing equipment and by how much that air ought to dilute a patient’s FeNO result.
Thirty-five adult participants underwent the standard and alternative FeNO tests using different numbers of exhalations. The alternative FeNO test was also conducted as a laboratory experiment using a precisely measured sample of gas instead of air exhaled by an adult participant.
The study showed that if a participant took multiple breaths during the alternative FeNO test then the FeNO measurements were very different from those provided by the standard test. The results provided by the laboratory experiment showed that the mathematical equation could accurately predict by how much the amount of FeNO detected would be reduced if multiple breaths were used. However, the mathematical formula did not provide accurate predictions when an adult participant undertook the alternative FeNO test. The authors suggested that this might be because the samples of exhaled air were becoming contaminated by air from the participants’ noses (where NO levels are much higher).
The authors of the study concluded that a patient’s true FeNO measurements could not be obtained using the alternative FeNO test if the patient took multiple breaths. This meant that the test is not suitable for young children.

This summary was produced by Joseph Henley, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research summary – Michal Benjamin

Respiratory viral infections in infancy and school age respiratory outcomes and healthcare costs
Victoria MacBean, Simon B Drysdale, Muska N Yarzi, Janet L Peacock, Gerrard F Rafferty, Anne Greenough
Published in the journal Pediatric Pulmonology, 2018

Prematurely born infants often have lung problems such as chest infections caused by viruses, and therefore this study was set up in order to explore the impact of chest infections in infancy on lung health later in childhood. From prior research, it was thought that children who had viral chest infections during infancy would have worse breathing function when they got to school age and therefore would depend on medical services more than the average child.
A group of children who had participated in a previous study who were born before 36 weeks of pregnancy and had symptomatic chest infections during infancy were called back when aged between 5-7. During their chest infections as babies, these children had had a sample of mucus taken from the back of the nose and mouth which was tested for a variety of viruses.
When measured at 5-7 years old, various aspects of lung function of the children who had experienced viral chest infections were compared to those of the non-affected children. The results of these tests suggested that children who had had respiratory viruses had poorer lung function than healthy children.
These children also had their medical records examined in order to identify any hospital admissions, emergency department visits, hospital outpatient appointments, other contact with medical professionals, GP attendance and all medication prescriptions. Beyond the first year of life the cost of these medical treatments was recorded. The average healthcare costs of the infants who had not had chest infections were compared to those of the infants who had had respiratory viruses. The ‘virus group’ had a significantly higher respiratory health cost (an average of £431 per year) compared to the group of children who did not have chest infections in infancy (an average of £56 per year).
From these results, the researchers suggested that children who experienced chest infections caused by respiratory viruses had higher healthcare costs and poorer lung function. This study did not identify any one virus as being consistently problematic.

This summary was produced by Michal Benjamin, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research summary – Iva Koshova

Non-volitional assessment of tibialis anterior force and architecture during critical illness
Bronwen Connolly, Matthew Maddocks, Victoria MacBean, William Bernal, Nicholas Hart, Philip Hopkins, Gerrard F Rafferty
Published in the journal Muscle and Nerve, December 2017

After being admitted into the intensive care unit (ICU) some patients experience muscle weakness and as a result they struggle to walk properly and perform other daily tasks. This weakness is not always a direct result of the condition for which the patient was admitted. The term intensive care unit-acquired weakness (ICU-AW) is the name given to functionally unfit muscles of patients who have been admitted to ICU for which there is no other reasonable explanation. ICU-AW is a serious problem as it means the quality of life of patients after their ICU stay can be impaired as their muscle weakness can be quite severe and limit what they can do.
This research was used to investigate whether admission to ICU is the cause of muscle weakness many patients experience after their stay. The researchers tested this by assessing the size and strength of a muscle at the front of the shin. This muscle is easy to access without disrupting patients’ treatment. It is also responsible for balance and walking therefore the researchers found it to be an important muscle to focus on as patients who experience weakened shin muscles can have negatively impacted lives. Moreover, researchers decided to use testing techniques that don’t involve conscious effort from the patient as it meant eliminating limitations such as patient cooperation and motivation, making the research more reliable.
The study included thirteen adults who had been admitted to ICU and who required breathing support for at least 48 hours. Patients’ shin muscle size and strength was assessed on two occasions seven days apart in order to see whether any weakness developed during their ICU stay.
If patients’ ICU stay caused their muscles to decline in ability, like the term ICU-AW suggests, then the researchers would have seen a decrease in strength of their shin muscle. What the results showed, however, was that there was weakness present at the start of their ICU admission, with no further decline in muscle strength during admission, though the muscles did decrease somewhat in size. This finding led the researchers to suggest that ‘critical illness-associated weakness’ would be a more reflective term than ICU-acquired weakness. Of course, it is important to note that due to the small number of patients studied used the data isn’t entirely conclusive as the small sample may not be representative of all patients who experience weakness after an ICU stay.
This study suggests that the ICU environment may not be the cause of the weakness patients experience. This highlights the need for further research into ICU-AW so that more about the condition can be learned; this could lead to a possible way to prevent it from developing in the first place.

This summary was produced by Iva Koshova, Year 13 student from Harris Academy, Greenwich, as part of our departmental educational outreach programme.

Research summary – Miri Frankl

Predicting healthcare outcomes in prematurely born infants using cluster analysis
Victoria MacBean , Alan C. Lunt, Simon B. Drysdale, Muska Nadia Yarzi, Gerrard F. Rafferty and Anne Greenough
Published in the journal Pediatric Pulmonology, May 2018

Children born prematurely have higher risks of chest infections caused by viruses. This is associated with poorer respiratory health in infancy and later childhood.
This study is important because it is very difficult to predict respiratory diseases, as the chances of getting the disease, and the degree of severity, will vary substantially between prematurely born children. The large differences in risks to these children means that it’s very important to be able to predict their health. This allows parents and children to have more support, and also means that expensive preventative medicine is only used when necessary.
A group of 168 prematurely born infants were assessed, and had their birth weight, how long the pregnancy was, and how long they were helped to breathe after birth recorded. Throughout the first year after birth the parents reported any symptoms of chest infections (for example, shortness of breath). These same children had follow-up measurement at 5-7 years of age.
A technique called ‘cluster analysis’ analysed the data collected from the children. This is when groups of similar individuals are identified, who share certain characteristics. The outcomes of the different groups can then be assessed. Three distinct groups were detected in the group of 168 infants.
The first and largest group of children, who needed very little help with breathing immediately after birth, had very few chest infections before their first birthday, and didn’t have chest problems later in life.
The second, smaller group of children needed help with breathing for five or more days after birth and were more likely to have mild to moderate chest problems later in life.
The third and smallest group were born weighing less than 882 grams and required a lot of breathing support after birth. These children had the highest risk of developing chest infections and had a lot of health problems later in life (both related to their chest and other health conditions).
This study suggests that prematurely born infants fall into three distinct groups. Knowing which group the baby is in may be useful to clinicians advising parents on their baby’s possible outcomes after preterm births, and researchers with their studies.

This summary was produced by Miri Frankl, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research summary – Sarah Ezzeddine & Neta Fibeesh

Respiratory load perception in overweight and asthmatic children
Victoria MacBean, Lorna Wheatley, Alan C Lunt, Gerrard F. Rafferty
Published in the journal Respiratory Physiology & Neurobiology, February 2017

This study examined differences in children’s awareness of breathing difficulty, specifically the influence of weight and asthma. With obesity on the rise in Western society and asthma being a common long-term medical condition, it is crucial to understand why obese, asthmatic children report more breathlessness than asthmatic children who are not overweight, even when there are no differences in the severity of their asthma. It has previously been suggested that overweight children may have an increased awareness of breathing effort.
This study compared various aspects of breathing across three groups of children: asthmatic children with healthy weight, overweight children with asthma and a control group of healthy weight children. The project involved the children breathing through a device which added resistance to breathing. Children were asked to rate how hard they felt it was to breathe, and the tests also measured the children’s breathing muscle activity to find out how hard the breathing muscles were working as the researchers purposefully increased the children’s effort to breathe.
The anticipated results were that healthy weight asthmatic children and healthy weight children would show similar results, that is that their breathing effort scores would steadily increase as they found it harder to breathe, with the breathing muscles working gradually harder. Meanwhile, the overweight asthmatic children would show a much steeper increase.
From the 27 children who were studied, the results showed that the overweight children gave higher effort scores throughout the tests, but that these increased at the same rate. There were no differences in the way the children’s breathing muscles responded to the tests. The reason for the higher overall effort scores in the overweight asthmatic children was that their muscles are already working harder than the other two groups before the experiment due to the changes that occur in the lung with increased weight. It was then concluded that overweight asthmatic children do not have differences in their awareness of breathing effort, but that their additional body mass means their muscles are already working harder.

This summary was produced by Sarah Ezzeddine, Year 13 student from Harris Academy Peckham and Neta Fibeesh, Year 13 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research summary – Talia Benjamin

Parasternal intercostal muscle activity during methacholine-induced bronchoconstriction
Victoria MacBean, Claire L. Pringle, Alan C. Lunt, Keith D. Sharp, Ashraf Ali, Anne Greenough, John Moxham and Gerrard F. Rafferty
Published in the journal Experimental Physiology, February 2017

Neural respiratory drive (NRD) is commonly used as a measure of respiratory function, as it measures the overall muscular effort required to breathe in the presence of the changes that occur in lung disease. Both bronchoconstriction (airway narrowing) and hyperinflation (over-inflation of the chest, caused by air trapped in deep parts of the lung) occur in lung disease and are known to have detrimental effects on breathing muscle activity. Electromyography (EMG) is a measure of electrical activity being supplied to a muscle and can be used to measure the NRD leaving the brain towards respiratory muscles (in this study the parasternal intercostals – small muscles at the front of the chest). This study aimed to research the individual contributions of bronchoconstriction and hyperinflation on EMG and the overall effectiveness of the EMG as an accurate marker of lung function.

A group of 32 young adults were tested as subjects for this study, all of which had lung function within normal limits at rest, prior to testing. The subjects inhaled increasing concentrations of the chemical methacholine to stimulate the contraction of airway muscles – imitating a mild asthma attack. Subjects’ EMG, spirometry (to measure airway narrowing) and IC (inspiratory capacity) was measured to test for hyperinflation. Detailed statistical testing was used to assess the relationships between all the measures.

The results show that obstruction of the airway was closely related to the increase in EMG, however inspiratory capacity was not related. The data suggests that the overinflation of the chest had less of an effect on the EMG than the airway diameter (bronchoconstriction). This helps advance the understanding of how EMG can be used to assess lung disease.

This summary was produced by Talia Benjamin, Year 13 student from JFS School, Harrow, as part of our departmental educational outreach programme.

A detailed and reflective account of our recent Panel meeting – Iva Koshova

The first meeting of King’s Muscle Lab Student Advisory Panel began with an introduction on what the future panels will consist of as well as some background on the panel. For example, the laboratory was started by Professor John Moxham, to investigate the function of the respiratory and skeletal muscles and how this changes in people with lung disease. I think that it’s an interesting field of research as it enables a group of people from diverse career backgrounds, from physiology to medicine to biomedical engineering, to come together to conduct research. The research team undertakes clinical physiological research in adults and children with and without lung (or other) diseases. After the initial introduction for the panel, the visiting professionals introduced who they were by outlining their career journey from A levels to what they were currently doing. In this meeting the professionals were Miss Claire Pringle, Dr Peter Cho, Miss Hannah Perry and Dr Alexis Cullen. Then we got into groups of around seven people and started the meeting’s discussion topic which was on tobacco and its effects. Each of the visiting professionals took turns to talk to each group.
The discussions within each group were split in four categories, each of which was tailored to the professionals’ specialisation: physical effects of tobacco with Dr Peter Cho; tobacco and the intersection of mental health with Dr Alexis Cullen; public health and tobacco with Miss Claire Pringle; and imaging the effects of tobacco with Miss Hannah Perry. The discussions were initiated by questions from the professionals which people within the groups answered but the discussions were also integrated with expert input from the professionals. In my group the first discussion was with Miss Hannah Perry where we focused on the chemical properties of tobacco. Whilst some people in my group guessed that there were around 200 chemicals within a cigarette, there are approximately 7,000 including over 60 known cancer-causing chemicals. Some of those carcinogenic chemicals are metals or radioactive compounds. It was interesting to discover more of the chemicals inside cigarette smoke other than nicotine and tar. For example, there is also the fatal carbon monoxide and hydrogen cyanide.
The next discussion was with Dr Peter Cho where we discussed some of the physical effects on the body such as breathlessness due to swelling and narrowing of the lung airways and excess mucus in the lung passages. The most intriguing fact we learned in that discussion, in my opinion was the fact that there is permanent damage to the air sacs of the lungs due to scarring from the constant strain from coughing. In the discussion with Dr Alexis Cullen we were stimulated to think about possible relationships between mental health and smoking. For instance, ways in which we could test whether individuals with mental health are more likely to smoke or whether smoking led to and/or worsened mental health. What I found most fascinating was the fact that research needs to be cautious of third factors that could affect the investigation. For example, a third factor could be the socio-economic background of the individuals causing them to either start smoking or affecting their mental health. The final discussion was with Miss Claire Pringle where we discussed ways in which the government could help solve the public issue of smoking. It was interesting because we were made aware of the difficulties of solving such big problems but also discovered that there are some solutions which worked well within certain areas such as banning smoking from certain public areas but didn’t work as well in other areas. Overall, the discussions were great as we weren’t simply told information we were prompted to think and evaluate information regarding the topic. I think that the panel is a fantastic opportunity because we were able to communicate with professionals on subject matters that interested us and gain knowledge from professionals who specialise in that area. Also, there isn’t really any other way to experience this type of learning experience elsewhere. Moreover, it was beneficial as we could learn about possible routes within medicine related jobs as well as discover more roles within the industry.

Iva Koshova, Year 12, Harris Academy Greenwich

A joint post from three Panel students reflecting on our recent tobacco-themed meeting

Selected students from Harris Experience Advanced attended their first King’s Muscle Lab student panel meeting at King’s College London on Monday as part of their academic cultural enhancement. Established by Professor John Moxham, King’s Muscle Lab is a respiratory and physiology research facility, consisting of academics from all fields of health; such as medicine, physiotherapy and nursing and was created with the purpose of investigating the function of respiratory and skeletal muscles and how this changes in people with lung disease. Their work is largely focused on physiology, which is the study of how the systems of the body work and its relation to different conditions and diseases in which people have problems with their breathing. Being a part of the student panel will provide various opportunities and this first meeting was just the start of them.
The students were joined by visiting professionals working in a variety of departments ranging from Psychosis Studies to Health and Social Care in the United Kingdom Government and they gave presentations outlining their carer trajectories and current research areas and roles. Then it was discussion time. The topic brought to the table was ‘Tobacco and its Effects’, and the students were separated into small groups, each with a professional to discuss.
With Dr Alexis Cullen, an expert in psychosis studies, the groups talked about how smoking links to mental health issues, and observed the fact that there are a lot of other contributing factors to consider when looking at the correlation between smoking and mental health issues, for example; stress, home life and family problems. Ms Claire Pringle currently works in the Department of Health and Social Care, United Kingdom Government and the small group discussion with her looked at the social issues surrounding tobacco. The student panel argued whether tobacco could ever be criminalised, and introduced the comparison of Marijuana, discussing whether the use of it could ever be legalised. The role marketing can play in deterring people from smoking was an avenue which was also explored. Packaging of cigarettes is becoming less appealing in government efforts to try to discourage people from smoking, for example the U.K has begun to adopt cigarette packaging with graphic images on them such as people with rotting teeth, and bold letters which read; ‘Smoking Kills’ also appear on the boxes. The physical effects of smoking were explored with Dr Peter Cho. These consist of addiction to nicotine, many types of cancer, and COPD. Whilst the physical effects of smoking are horrific, the most shocking facts however, came from the discussions with Ms Hannah Perry, of the School of Biomedical Engineering and Imaging Sciences. No one expected to hear that there are around 7,000 chemicals inside cigarettes, and 70 of these are carcinogenic.
After the small group talks, the panel reunited to share the things they had learnt with each other. The afternoon was intellectually engaging and students were able to broaden their knowledge, talking about elements of life they come across each day, but do not necessarily give a second thought. They look forward to the next King’s Muscle Lab meeting and what opportunities for the future, panel membership might mean.

By Eliana Oworu, Uzma Niazi and Gisela Simbana-Tipan
(Year 12, HEA, Harris Academy South Norwood)

Reflections on our recent Panel meeting – Gilad Fibeesh

On 26th of February the Student Panel met to hear from academics and discuss tobacco and its effects. The Panel was comprised of students ranging from Year 11 (like myself and fellow JFS School members) to Year 13 with the vast majority sharing a strong interest in biology and many considering pursuing this, medicine or related sciences as a future career option. The attending schools were JFS School, Harris Academy, Burntwood Academy and Graveney School.
Upon arrival, we were briefed by Dr MacBean regarding the agenda for the day and the future opportunities for the panel members including database updating, summarising published researches and many other forms of work experience. The Panel was subsequently introduced to the visiting academics.
Miss Claire Pringle, working in the Department of Health & Social care told us about the various means used to cut down on the number of peoples starting to consume tobacco. It was particularly interesting to find out that the new green packaging of cigarettes has come as a result of market research used to find that the colour is the least appealing as well as, looking into the difficulties that arise when deterring young people from starting smoking through educating them without patronising them.
With Dr Peter Cho, we focussed on the physiological effects of tobacco on the body especially looking at tar and nicotine and considering how they affect people’s body function such as, by raising blood pressure which increases the risk of blood clots that can cause heart attacks. It was intriguing to discover that the harmful effects of tobacco, in terms of causing cancer, were first noticed when researchers compared the list of doctors that smoked and the list of those that developed cancer and spotted a clear correlation.
The topic of medically imaging the effects of tobacco was looked at with Miss Hannah Perry and the mechanisms behind the 3 main imaging methods (CT, PET and MRI) being the main focus of conversation. I found the fact that usually, a radioactive fluorine isotope, is attached to glucose molecules fascinating as a large amount of the glucose goes to the tumour to provide energy for its rapid cell division. The fact that MRI imaging can be used to locate tumours because the fast growth does not allow the tumour to be properly connected to the lymphatic system, which draws away water, was also interesting.
Finally, with Dr Alexis Cullen we looked at understanding the connection between smoking and psychosis and considered the nature of the relationship: does smoking affect the brain by physically cause the development of this mental illness? Or is there some confounding factor which has a link to smoking and a link to psychosis but no direct causational relationship? This along with thinking about some of the ethical concerns involved with research regarding this connection were all ideas discussed.
Overall, the day was filled to the brim with information, questions and answers with some very interesting academics and it is certain that the entire Panel learnt plenty.

Gilad Fibeesh, Year 11, JFS School, Harrow