Issue 1 • 2022
© 2022 The Royal Australasian College of Physicians
Making a difference through clinical care and research: resetting chronic cough
In 2021, Professor Anne Chang was awarded the Howard Williams Medal for her outstanding contribution to improving the health of children and young people in Australia and/or Aotearoa New Zealand. The following is an edited version of Professor Chang’s oration – Making a difference through clinical care and research: resetting chronic cough – which she delivered at RACP Congress 2021.
Professor Chang commenced her address speaking of the work of the late Howard Williams. She discussed how one of his earliest studies concerned pre-operative fluid replacement to reduce the life-threatening biochemical disturbances associated with pyloric stenosis.
Presenting data from the study she looked at how treatment of this impacted the death rate from 16 per cent to 2 per cent and how significant change in the broader community is possible through the work of clinicians.
She then contrasted the broad focus of the work of Howard Williams with that of Mother Theresa, and her work on improving the life of individual people through a direct one-on-one approach (slide 1).
Following that overview, Professor Chang briefly touched on the paradigm of respiratory health. Acknowledging that she is a respiratory physician and therefore biased, she said she would provide evidence about how improving respiratory health could change the future health trajectory and touch on what individual physicians could do to make a difference.
The two main objectives of her session were to convey: (1) The paradigm of the importance of lung health in children and (2) How you can make a difference.
Lung health is the key to future health
In describing the paradigm, Professor Chang focused on three components: (i) The impact of lung function on future health; (ii) Lung function trajectory; and (iii) Chronic cough and lung health.
She explained that in adults, chronic or productive cough or pneumonia, is associated with future cardiovascular events and disease, while we know that the presence of pneumonia in children also influences adult lung function. ‘When you measure the lung function as an adult, most of it is actually set in childhood. Lung function in young adults is a predictor of all-cause mortality, even in adults as young as 35 years of age.’ As well as this, it is also associated with future cardiovascular disease and all-cause mortality. Professor Chang proceeded to explain how adult lung function is mostly set in childhood, although recent data suggests that catch up lung function can occur.
Professor Chang presented data from the PURE study (published in Lancet Global Health 2019) in which over 126,000 participants aged 35-70 years at enrolment were followed up for a median period of 7.8 years to record cardiovascular and respiratory disease events and deaths.
In the study, researchers grouped lung function according to four different categories: no impairment, mild impairment, moderate impairment and severe impairment – or clinically abnormal lung function. There is a dose effect with future death, and not surprisingly with respiratory issues. This was also seen in cardiovascular deaths – the lower lung function, the higher the risk of was cardiovascular deaths.
That being said, it is important to note that this is a prospective study, and mild and moderate lung function impairment are in a clinically normal range.
The study then looked at population-attributable risk of death and this was adjusted for a range of factors. The impact of mild to moderate FEV1 impairment was 25 per cent. If you compare that to traditional factors, it is larger but not necessarily statistically larger than the things we do know affect our future health. This suggests that lung function set in childhood is important for future health.
This is well known in respiratory medicine. If you are born with low lung function, your lung function trajectory stays low, and if you are born with high lung function, it remains high. Although there is a clear decline with age, in certain groups there is a more rapid decline.
Professor Chang said that this leads to the inevitable question. Can you make a difference to someone born with low lung function? ‘I believe you can,’ she said. Drawing on a study by Andrew Collaro that looked at First Nations children who were optimally treated using the same classification as the PURE study – the lung function significantly improved – and the improvement compared to the baseline was higher if specialist respiratory paediatricians managed their respiratory illness for a longer period.
Working in conjunction with local practitioners can result in substantial improvement. Even when they looked at Bronchiectasis, and the smaller numbers, there was still a significant difference after treatment. Furthermore, when the study compared the paediatric patients treated in the First Nations outreach, to tertiary paediatric patients in Brisbane, the results were similar.
The other key point regarding catch-up lung function comes from a study from Professor Shyamali Dharmage’s group. According to a paper by Dr Bui, they were the first group to demonstrate that you can have a catch-up period but then the decline is at a similar rate to others.
According to Dr Bui’s paper, if you look at early accelerated decline and below average groups, you can see that bronchitis is a significant factor and the commonest symptom of bronchitis is chronic cough; pneumonia is also a significant factor. The other findings showed that asthma and smoking are factors, although this was not a surprise.
Dr Bui drew attention to the fact that after birth, your lungs continue to grow, and that there are things that can be done that can influence lung growth. Therefore, it’s not surprising to know that if you have pneumonia or ongoing inflammation, it may inhibit your lung growth.
In paediatrics, it’s not that easy to test lung function in pre-school aged children, but a Greek study showed that the longer you had been coughing, the more severe your CT scan abnormality score will be – again suggesting that chronic cough can lead to poor lung function if it is not treated.
Doctors often say that parents are overzealous when they come in for a consult for chronic cough. So how do we reset chronic cough and make a difference?
Professor Chang focused on three things: 1. Why a chronic cough is not ‘just a cough’ 2. Evaluation of a child with chronic cough – the principles 3. Example of earlier diagnosis and subsequent effective management of bronchiectasis
She spoke earlier about the relationship between chronic cough and lung function, but went on to highlight two other issues regarding chronic cough: (1) The burden of the disease or burden of the symptom and (2) Missing significant illness. With the burden of the symptom, Professor Chang drew on Julie Marchant’s PhD work, where she asked her patient’s parents how many physicians they saw for their child’s chronic cough before they getting referred. 80 per cent of children had been to the doctor more than five times, while 20 per cent had seen a doctor more than 20 times (slide 2).
Looking at the quality of life of the parents and children who presented with chronic cough, a multi-centre study found no correlation between the respiratory diagnostic groups. It was the cough that is the problem, and the quality of life was the same ball-park as people with diabetes and obesity.
If you don’t take it seriously, you can miss disease in children with chronic cough. So what are the principles of evaluating a child with chronic cough?
Professor Chang focused on three things:
(i) How it came about;
(ii) Systematic evaluation principles and
(iii) Concept and algorithms (slide 3).
Professor Chang discussed the American College of Chest Physicians (ACCP) 1988 guidelines which stated that the approach to managing chronic cough in children is similar to the approach in adults. They suggested that “asthma, upper and lower RTI, and GERD are the most common causes of chronic cough in children”. Now, we all know that this is not true.
While planning to do her PhD on bronchiolitis, Professor Chang said that Professor Peter Phelan encouraged her to focus on cough. So she did a study of the effect of asthma medications on children with non-specific chronic cough. She looked at the change in cough frequency in children treated with salbutamol and inhaled corticosteroids and found that there was no significant difference using those two treatments compared to placebo (Arch Dis Child 1998). That is when we found that asthma is not really a common cause in children with chronic cough.
'Having had the interest in chronic cough in the clinical years, anecdotally we noticed that when we treated children with wet cough with antibiotics, we actually made the cough better.'
Julie Marchant wanted to do her PhD, so we embarked on a cohort study where we evaluated the children through a systematic process. We found that Protracted Bacterial Bronchitis (PBB) was actually the most common aetiology. So what is PBB and how do we diagnose it?
The original description was: 1. History of chronic (>4 weeks duration) moist wet cough 2. Positive BAL bacteria culture and, 3. Response to antibiotic treatment with resolution of the cough within two weeks.
'Over the years we have modified the PBB-clinical to be, BAL criteria to the absence of other causes of wet cough, the PBB-micro to keep the original definition and recurrent PBB as more than three episodes per year (slide 4). This has been accepted in guidelines and recognised all over the world.'
The American Thoracic society has also produced a Patient Education Series. The importance of PBB is that it relates to Chronic Suppurative Lung Disease (CSLD), and bronchiectasis. We proposed this paradigm in 2008 (slide 5) and it is now widely accepted and published in key journals including Lancet and Nature Rev Disease Primer. Coming back to physiology concepts of cough, we know that cough is important for lung hygiene, so we don’t want to supress it. The concept of cough receptors was first proposed by John Widdicombe but the neuropathways of cough has now been elucidated. “Irrespective of the aetiology, it all goes through the same pathway through the vagus nerve.”
When it comes to assessing a child with cough “it’s all led by aetiology” (Slide 6). You need to define the aetiology – there is no space for using empirical treatment unless its aetiology is led by a close history and an examination. Professor Chang suggests that every child has a chest x-ray and a spirometry when age appropriate and that physicians start listening to parents and their children. Then they need to decide if further investigation is required, which requires a watch and wait approach.
Professor Chang suggests three constructs for clinical use when you look at chronic cough: duration, cough quality (things like dry cough, brassy and paroxysmal cough), and the likelihood of an underlying disease.
She listed some of the cough pointers and explored the evidence. 'We looked at the positive and negative likelihood ratio of any of the cough pointers and showed the positive likelihood ratio is good, however the negative likelihood ratio is rather poor. This showed that if it is present it is significant, but if it is absent it doesn’t mean that is necessarily absent.' However, you can see that the negative likelihood ratio overall is very good, therefore taking a thorough history, listening to the parents and ascertaining whether there is a cough pointer present or not will help you determine whether the child needs further investigation.
So, the key thing is to make sure you have to ask the right questions. If you don’t ask the right question, you are not going to get the answer.
Moving on to one-to-one care and whether there is evidence in practice, Professor Chang said: 'When I first went to Alice Springs to do First Nations work, I was appalled to see children with severe bronchiectasis who were not treated.' She shared a letter –regarding a child who was over the age of nine but weighed only 17.3kg – written by a senior clinician. The letter basically said that he couldn’t do anything to help the child.
Professor Chang said 'I knew I had to do something, so I got key leaders from around the country to support me in trying to get these children treated more aggressively and we wrote the first guideline on treating First Nations children with bronchiectasis in 2002. We knew that we had to treat these kids earlier to try and improve their lung function. The kids I used to see in Alice Springs had lung function as low as 30 per cent when they were first diagnosed – it was appalling. Over the years people have asked for the guidelines to be extended, so we have included every child and adult in Australia and Aotearoa New Zealand.”
Professor Chang went on to summarise and said that she hoped she had shown the paradigm of how important respiratory health in childhood is because it links to later outcomes. There is evidence that lung function improves with good clinical care so how you manage a child with chronic cough is really important.
'So, in the footsteps of the wonderful late Howard Williams, we really can make a difference irrespective of our own background and that of our patients. We can make a difference to the individual in the manner of Mother Theresa, and through the clinical research we are privileged to do.'