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.

Research paper summary – Amazing-Grace Lawal

Effect of endurance exercise on respiratory muscle function in patients with cystic fibrosis

Charles C. Reilly, Katie Ward, Caroline J. Jolley, Lucy Anne Frank, Caroline Elston, John Moxham, Gerrard F. Rafferty

Published in the journal Respiratory Physiology & Neurobiology, January 2012

Cystic Fibrosis (CF) is a genetic disorder in which the genes that control the movement of salt and water in and out of cells are affected, this leads to a build up of mucus mostly in the lungs but also in the liver, pancreas and intestine. The aim of the study was to determine whether high intensity exercise tasks lead to fatigue (where the muscles become briefly less able to generate force) in the abdominal muscles or the diaphragm in patients with CF.

Two groups of people were tested, one group with 10 patients with CF and the other group with 10 healthy subjects. On two different occasions the test subjects went to the lab to carry out tests. On the first occasion the subjects performed an exercise test to characterise the subjects in terms of their exercise performance and to also calculate a work rate, which was used in the second test. The second occasion involved a cycling endurance test, lung function and respiratory muscle strength testing taken on all subjects. Before and after the exercise tests, subjects underwent magnetic stimulation of their diaphragm and abdominal muscles to assess how much force the muscles could generate.

Average exercise time was similar in the healthy subjects and those with cystic fibrosis, as was the intensity of exercise they performed during the test. The measurements taken show that there were not any significant changes in the responses to magnetic stimulation after exercise in both the healthy subjects and those with CF. A decrease the response to magnetic stimulation of greater than 15% is thought to be indicative of fatigue in respiratory muscles, however, none of the subjects saw a decrease larger than 15%, thus leading to the conclusion that fatigue did not occur in any of the subjects.

The fact that that fatigue did not occur in the diaphragm or abdominal muscles after exercise in the patients with CF suggests that feelings of breathlessness and weakness in leg muscles may be more important in limiting exercise performance in those with CF. Further studies are needed in order to exactly understand the factors that hinder exercise performance of those with CF such as muscle function in non-respiratory muscles.

This summary was produced by Amazing-Grace Lawal, Year 13 student from Harris Academy South Norwood, London as part of our departmental educational outreach programme.

Research paper summary – Casril Liebert

Observational study of the effect of obesity on lung volumes

Joerg Steier, Alan Lunt, Nicholas Hart, Michael I Polkey, John Moxham

Published in the journal Thorax, April 2014

With a rise in obesity, a bigger effort must be made to understand all the factors and effects of obesity on the human body. It is already known that obesity is associated with an increase in work of breathing and neural respiratory drive (the muscular effort required to breathe), as well as changes in lung capacities. It can also cause hypercapnic respiratory failure which is when there’s too much carbon dioxide in the blood. However, the effects on the mechanics of breathing are unclear. This study attempts to measure the effect of obesity on lung volume and various pressures in the chest and better understand the physiological differences between different weight people.

9 obese people and 9 normal weight people volunteered to be measured whilst seated and whilst lying on their back. During the study, the subjects breathed into the mouthpiece of a machine called a spirometer which monitors the speed and volume of air movement into and out of the lungs. Pressures in the chest and abdomen were also measured, along with the amount of air remaining in the lungs after a breath out (functional residual capacity, or FRC).

After evaluating results, it was noted that high pressures in the chest are have an important role in the mechanisms of the respiratory system. The chest and abdomen pressures were found to be much higher in the obese group, and the FRC lower. The strength of the breathing muscles were measured and the result showed that the obese group had weaker muscles. There was a direct relationship seen between subjects’ waist circumference and the chest and abdominal pressures, as well as with the drop in FRC.

One of the main conclusions is that gastric and oesophageal pressures correlated with waist size, since the obese group had significantly higher pressures. One can deduce from this result that these high pressures are inhibiting efficient function of the lungs, and contributing to the reduced volume of air in the lungs. To bring this research into practical everyday healthcare, more could be done to attempt to reduce abdominal pressures in obese patients. By doing so with appropriate treatment in the future, obese people may be able to reach normal lung function, thereby reducing the number of patients suffering from breathlessness and sleeping disorders from respiratory problems.

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

Research paper summary – Djenné Oseitwum-Parris

Measurement of neural respiratory drive via parasternal intercostal electromyography in healthy adult subjects

Victoria MacBean, Cara Hughes, Gavin Nicol, Charles C. Reilly, Gerrard F. Rafferty

Published in the journal Physiological Measurement, October 2016

Parasternal intercostal electromyography (EMGpara) is a method used to measure breathing function by monitoring signals sent from the brain, to the parasternal intercostal muscles (muscles between the ribs). These muscles, together with the diaphragm (a thin muscle under the lungs) and some others, move together to control your breathing. EMGpara can be used to measure a person’s neural respiratory drive (NRD), which is an indication of the strength of the respiratory (breathing) muscles under a certain amount of strain (how hard the muscles may have to work when they are coping with different diseases or environments). This method is an alternative to other more traditional practices that, for example, may involve the use of needles. Therefore, EMGpara is less invasive and ideal for monitoring the breathing muscles in many groups of people.

In the case of this study EMGpara was measured in healthy adults in order to discover what factors determine normal EMGpara readings. The participants were over the age of 18, and were of different body types and sexes.

In preparation for the EMGpara tests, each participant’s body size, shape and composition was measured – this included taking note of their height, weight, hip and waist size, body fat percentage and body mass index – as well as tests to confirm that each person had normally functioning lungs.

Electrode stickers were placed on the chest to measure the EMGpara signals as the subjects breathed normally and effortfully. The tests were repeated at a later date to make sure the results could be reproduced, thereby checking that the EMGpara technique is consistent.

The study suggests that sex is the most important factor in determining EMGpara; a higher value for EMGpara was observed in the women who took part. This may be because in general, woman have smaller lungs and narrower airways compared to men and their respiratory muscles are usually not as strong.

Age did not seem to have a significant effect on the readings; however this could have been because the average age of those involved was only 31, and those who were older were quite athletic, meaning their respiratory health was very good.

The results of this study can be used as a reference for what a normal EMGpara reading is, and therefore they can be used when assessing patients in the future. The study included many people from different backgrounds, so it is quite representative of the population. The study was also important in working out which methods and techniques are best for measuring EMGpara, as well as for highlighting possible areas of further research for future studies.

This summary was produced by Djenné Oseitwum-Parris, Year 12 student from Burntwood School, Wandsworth, as part of our departmental educational outreach programme.