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.

Research paper summary – Casril Liebert

Ankle dorsiflexor muscle size, composition and force with ageing and chronic obstructive pulmonary disease

Matthew Maddocks, Matthew Jones, Thomas Snell, Bronwen Connolly, Susanne de Wolf-Linder, John Moxham, Gerrard F. Rafferty

Published in the journal Experimental Physiology, June 2014

Chronic obstructive pulmonary disease (COPD) is the name for a group of lung diseases that cause breathing problems. COPD patients often find it hard to do exercise because their muscles may be slightly weaker compared to a healthy person. The ankle dorsiflexor muscle, at the front of the shin, is used for balance and walking. This research looked at how the ankle dorsiflexor muscles were different between 20 young healthy people, 18 healthy elderly people and 17 people with COPD. This allows us to see how COPD affects the normal ageing process of the muscle.

Firstly, we took scans of the muscle to see what it is made of. We also measured the size of the muscle. The scans showed that the COPD patients had a lot of non-useful tissue in the muscle that doesn’t help the muscle work normally. The strength of the muscle was also measured. This was done by passing electricity into the nerve to the side of the knee that supplies the dorsiflexor muscle. This caused the nerves to react and tense the muscle.

The results showed that patients with severe COPD have ankle weakness. This means that their muscles are not as strong as a healthy person and it is harder to do certain tasks that require strength. The scans also revealed that a greater muscle size was associated with a greater muscle strength, and also that tissue in the muscle without a function is a major cause of muscle weakness. The muscle composition scan discovered that fat and fluid in the muscle was often found in COPD patients. This tissue that isn’t useful creates problems which affect exercise performance and postural control, causing impaired balance and walking abnormalities. The discoveries within this study have allowed us to better understand why muscle strength in COPD patients decreases much more than seen with normal ageing.

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

Research paper summary – David Launer

Longitudinal Assessment of Lung Function in Children With Sickle Cell Disease
Alan Lunt, Emily McGhee, Karl Sylvester, Gerrard F. Rafferty, Moira Dick, David Rees, Sue Height, Swee Lay Thein, Anne Greenough

Published in the journal Pediatric Pulmonology, December 2015

Sickle Cell Disease (SCD) is amongst the most prevalent genetic conditions worldwide. Only being inherited if both one’s parents carry a ‘faulty’ gene in their DNA, SCD affects the Haemoglobin molecules that carry Oxygen in the blood, changing the shape of the red blood cells into so-called crescent shaped ‘sickles’. Despite its commonness, with over 300,000 babies being born with SCD worldwide every year, a clear and consistent picture of how SCD affects the lungs of children with SCD had not yet been researched. This study aimed to research the lung function of children affected by the disorder over time, observing how this changed in early and later childhood, and how this was affected by episodes of ACS (Acute Chest Syndrome) in early childhood, when the sickle-shaped red blood cells can block blood vessels and lead to various different injuries.

Two groups of children were tested. The first, who were slightly younger on average, were
measured twice for their lung function over an average of 2 years, while the second group were measured twice over approximately 10 years. A number of methods were used to test each person’s lung function, including ‘spirometry’ in which the quantity of air one can force out the lungs is measured, among other values like lung capacity. These measurements were then compared to a ‘control’ group of healthy children without SCD at a similar age, to give a normal level of lung function to compare against the SCD patients’.

In both groups of children with SCD, a reduction in lung function over time was seen when compared to the groups of children without SCD. However, the lung function of those in the first, younger, group decreased at a faster rate.

The results suggest that the fastest period of deterioration in lung function takes place in early childhood. Indeed, having an episode of ACS in young childhood was the only factor found that increased the likelihood of worse overall lung function later on. This could explain the faster decline of the younger group, as ACS is more common in younger children. This would seem to conclude that a focus should be placed on preventing ACS in young children as a strategy to improve the general lung function later on of those with SCD.

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