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.

Summary of Arietta’s thesis – Ma’ayan Dee, Neta Fibeesh & Abi Mincer

Systematic review and meta-analysis of health status questionnaires in bronchiectasis

A recent study regarding Bronchiectasis questionnaires was used to understand the quality of life of patients with a chronic lung disease called Bronchiectasis. These results were used to understand the connections between HRQOL (Health Related Quality of Life) and clinical measures, which are other tools we use to assess a disease. The aims of the study were to identify all the evidence and select the appropriate studies that can later be assessed in an unbiased and balanced way. The importance of collecting this data in this way is that it provides useful insights about the quality of life of patients from a personal point of view and helps the researchers understand the effectiveness of their clinical tools.

The searching and selection process using electronic databases were used to choose appropriate studies, for instance patients with cystic fibrosis (a genetic condition) were not chosen. The studies which were chosen were analysed to check for certain criteria that made sure their results were reliable. Then, a meta-analysis (a combination of various data assessments) was used to test how strong the connections between HRQOL and the clinical measures actually were. Out of the initial 1,918 studies first identified, 43 studies were used in the reviews and 38 ended up being chosen as suitable for the meta-analysis.

Results showed that there was a strong relationship between the HRQOL and subjective outcome measures such as fatigue (tiredness) in comparison to objective measures such as ability to exercise and how severe the Bronchiectasis was revealed to be on a CT scan.

 

Development and validation of the Bronchiectasis Health Questionnaire (BHQ): a new patient-reported outcome measure

There is an insufficient amount of questionnaires in relation to assessing the health status of someone with bronchiectasis. The questionnaires themselves are easy to understand and they give an idea of the patient’s perspective. A study was conducted to develop and confirm the value of the BHQ (Bronchiectasis Health Questionnaire). The BHQ is a new tool to measure the health status for patients with bronchiectasis. Questionnaires are needed for individual conditions due to the fact that every disease has its own causes and symptoms. This means that in order to help patients with different diseases questionnaires have to be adapted in order that the questions lead to suitable answers which can thus help those asking the questions to find answers that will lead to help for those taking part.

Patients who took part in the study were recruited from two outpatients clinics. The BHQ was developed by the introduction of item generation as well as item reduction. As well as this, the BHQ was developed by repeated testing and validation.

Two hundred and six patients took part in the study and completed a questionnaire with 65 questions. Fifty five of the questions were removed from the initial questionnaire to make the tool easy to use and more valid. The final version of the BHQ consisted of 10 items with a score between 0-100 with 100 being the best health status.

The BHQ generates a total score and general consensus. It can be used in clinical and research settings in order to assess the effect of bronchiectasis from the perspective of the patient who has the disease.

 

The objective assessment of cough frequency in bronchiectasis

Bronchiectasis is the abnormal widening of the bronchi or their branches, which causes a risk of infection. Cough is a common symptom of this condition and recent advances in technology in the monitoring of cough sound have enabled the assessment of cough frequency to be used to better understand various diseases. This study was aimed at quantifying cough frequency and by doing so investigating how the cough frequency affects the health status of individuals.

54 Bronchiectasis patients were assessed along with 35 healthy people (controls). The researchers measured their health status, cough severity, lung function and 24-hour cough. 24-hour cough was measured using a small portable audio recording device.

Data revealed that the cough frequency was high for patients suffering from Bronchiectasis meaning they coughed a significant amount more that healthy people. Additionally, patients with Bronchiectasis had impaired health status. Various factors associated with the objective cough frequency included sputum production (coughing up phlegm), the frequency of antibiotics for respiratory infections and older age. However, there was no good association between cough frequency and a common lung function test (spirometry).

 

Summary

Overall the studies revealed that questionnaires were a successful technique to provide results regarding the quality of life of those suffering from Bronchiectasis. This shows that a patient’s own perspective is very valuable in medical research and not only their physical condition!

This summarises the PhD research undertaken by Arietta Spinou, under the supervision of Surinder S Birring & Rachel Garrod. The summary was produced by Neta Fibeesh, Abi Mincer & Ma’ayan Dee, Year 12 student from JFS School, Harrow, as part of our departmental educational outreach programme.

Research summary – Morgan Walker

Airways Obstruction and Pulmonary Capillary Blood Volume in Children With Sickle Cell Disease

Catherine Wedderburn, David Rees, Susan Height, Moira Dick, Gerrard F. Rafferty, Alan Lunt, Anne Greenough

Published in the journal Pediatric Pulmonology, published online July 10th 2013

Children with Sickle Cell Disease (SCD) often face many obstacles due to the changes the condition causes in the body’s red blood cells. SCD results in anaemia, which is when there is less haemoglobin in the blood to help carry oxygen around the body. As a result, the heart has to pump much harder in order to ensure that the tissues of the body receive enough oxygen. This increased work by the heart also raises the amount of blood in the lungs, in order to allow sufficient oxygen is absorbed from the air. Children with SCD also frequently experience ‘airway obstruction’, which is the narrowing of the airways that makes it then harder to breathe. Airway narrowing can be caused by asthma, where muscles in the airways constrict, or by other causes.

This research was used to investigate whether the increased blood volume in lungs is associated with the ‘obstruction’ of the airways. The researchers tested this through testing the difference in the airways before and 30 minutes after using a medication called a bronchodilator (the blue asthma ‘reliever’ inhaler) which relaxes the airway muscles, widening the airways.   The study used measurements called spirometry, which tests the amount and speed of air that can be moved in and out of the lungs, and Impulse Oscillometry (IOS), which uses sound waves in order to assess the resistance of the airways (airway narrowing).

If the bronchodilator had a substantial effect, the researchers would be able to say that the airway obstruction was due to an asthma-type condition, as the inhaler would have relaxed the muscles and allowed air to move more easily through the airways. What the results showed, however, was that there was little change in the measurements of lung function after the inhaler was given. The researchers can therefore use this evidence to support the hypothesis that the airway obstruction in SCD may be due to increased blood volume in the lungs.

Therefore, this study suggests that treatment of non-asthma related airway obstruction in SCD patients could perhaps move away from bronchodilators and towards more effective treatments for the anaemia aspect of SCD such as blood transfusions. A great deal of further work is needed but this is a valuable insight into the a potential process underlying breathing problems in SCD.

This summary was produced by Morgan Walker, Year 13 student from Harris City Academy Crystal Palace, as part of our departmental educational outreach programme.

Research summary – Reef Ronel

Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial

Matthew Maddocks, Claire M. Nolan, William D-C. Man, Michael I. Polkey, Nicholas Hart, Wei Gao, Gerrard F. Rafferty, John Moxham, Irene J. Higginson

Published in the journal Lancet Respiratory Medicine, published online December 14th 2015

Patients with severe COPD often have weak legs as breathlessness can limit their ability to be active. Normally, to combat this and other symptoms of COPD, exercise classes called Pulmonary Rehabilitation (PR) are carried out. However, more severely affected patients may struggle to do PR.

An alternative therapy was introduced, neuromuscular electrical stimulation (NMES), to COPD patients with more severe symptoms. NMES is when electricity is used to create muscle contractions, in this case in the thigh muscles. While NMES has been used to strengthen muscles in previous research, this trial is the first to explore the impact on daily activities and the first to investigate the longer-term impact of the treatment.

52 participants with very severe COPD took part in this trial over two years. Participants received 30 minutes of NMES to both sets of thigh muscles daily for 6 weeks; 27 were placebo (‘sham’ stimulation) and 25 received active NMES. The aim: to assess the effectiveness of NMES, as a therapy to be conducted unsupervised at home, and at aiding daily activities. The main measure of effectiveness in this trial was a test of how far participants could walk in 6 minutes.

The results of the walk tests strongly support the use of NMES for severe COPD patients, with the patients who received the active NMES being able to walk substantially further. During interviews active NMES participants expressed a greater ease in everyday tasks (such as climbing the stairs) and stated that they could carry out physical activities for longer. No participants reported any negative views. Unfortunately, the improvement provided by NMES quickly waned after the treatment had stopped. Therefore, all existing evidence suggests that NMES should not be considered a replacement for PR. NMES can be used as an extension to PR, and could be used when patients are unable to take part in PR programmes. In addition, the short duration of effect suggests that longer programmes need to be investigated. Nonetheless, this trial has shown that NMES is a practical home-based therapy, suited to patients with more severe symptoms and has gives suggestions for future research.

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

Research summary – David Launer

Pulmonary function, CT and echocardiographic abnormalities in sickle cell disease

Alan Lunt, Sujal Desai, Athol Wells, David Hansell, Sitali Mushemi, Narbeh Melikian, Ajay Shah, Swee Lay Thein, Anne Greenough

Published in the journal Thorax, August 2014

Sickle Cell Disease (SCD) is amongst the most prevalent genetic diseases worldwide. Only being inherited if both of one’s parents carry a ‘faulty’ gene in their DNA, SCD affects the Haemoglobin molecules that carry oxygen in the blood, distorting the shape of the red blood cells into so-called crescent shaped ‘sickles’.

It has been shown previously that the majority of adults with SCD have changes in their lungs that can be found on a CT scanner, a high powered X-ray scanner that can create a detailed 3D image of the lungs, including airways and blood vessels.

This study showed that findings like particularly large blood vessels in the lung were linked to reduced lung function. This study aimed to show a link between these changes in the lung and the resulting changes in heart function that one can view on an ‘echocardiogram’ in the same group of patients. An ‘echocardiogram’ is a scanner used to observe the way in which the heart functions, from ultrasound waves ‘bouncing’ off the heart. It can view the structure of the heart and vessels, as well as blood flow. In SCD the heart has to pump more blood through the lungs in order to deliver enough oxygen to the tissues.

Adults with SCD were assessed using CT, echocardiography, and other lung function tests such as lung capacity, between the years 2009-2013. This same group of adults had previously been shown to have lung changes on CT scans between 2003-2005.

Whilst there was a large variety in the lung function of the 28 patients with altered lung features, it was demonstrated that lung structure changes seen on CT scans was related to the patients’ decline in lung function, and changes in the function of the heart displayed on echocardiogram tests. Importantly, the results of the study suggest that some of the changes found in the blood vessels between the heart and lungs may be able to explain the differences in the lungs found on CT scan and the decline in lung function. The results of this study help us to understand the complex relationships between heart, lung and blood vessel function in SCD.

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

Research summary – Ashleigh Francis

Airway and alveolar nitric oxide production, lung function and pulmonary blood flow in sickle cell disease
Alan Lunt, Na’eem Ahmed, Gerrard F. Rafferty, Moira Dick, David Rees, Sue Height, Swee Lay Thein, Anne Greenough
Published in the journal Pediatric Research, March 2016

Patients with Sickle Cell Disease (SCD) are often assumed to have asthma because they have ‘airflow obstruction’, which is when airways become narrowed and air is not able to move out of the lungs as quickly or easily as in healthy lungs.
Inflammation in the airways is one of the main features of asthma. Nitric Oxide (NO) is a substance that is produced by the airways when they are inflamed, so therefore can be used to measure the severity of asthma in a patient and find out how inflamed their airways are.
As well as being produced in the airways, NO is also produced in blood vessels, and helps to widen blood vessels.
People with SCD are anaemic, meaning they have less haemoglobin (a protein in the body that carries oxygen) so their cells cannot carry as much oxygen. In order to compensate for this, the heart beats faster and with more power to make sure enough oxygen is picked up from the lungs and delivered to the body.
This study looked at measurements of NO from the airways (representative of asthma) and the alveoli (representative of blood vessel widening), and compared it to lung function tests (to look at airway narrowing) and measures of pulmonary blood flow (how fast blood was circulating around the lungs).
The results showed that the airway NO was not raised, but that there was still airway narrowing occurring.  There was a relationship between how fast blood was circulating through the lungs and NO from the alveoli. This might suggest that previous findings of high NO and airway narrowing resulted in a false assumption that SCD patients’ airway narrowing was down to asthma. This study suggests that the changes in heart and blood vessel function in SCD may have an effect on the airways.
This study was relevant in terms of contributing to medical research because it shows the airway narrowing in SCD patients may not always be down to asthma, so it therefore allows us to target other root causes of the problem.

This summary was produced by Ashleigh Francis, Year 13 student from Harris City Academy Crystal Palace, as part of our departmental educational outreach programme.