Chronic cough is a common problem in children that impairs quality of life, with a burden often unappreciated by health professionals. Protracted Bacterial Bronchitis (PBB) is the most common cause of chronic cough in children. Untreated, it leads to poor future lung health outcomes such as bronchiectasis.

NHMRC-funded researchers at the Queensland University of Technology (QUT) and Menzies School of Health Research in the Northern Territory (Menzies) first described PBB and have made substantial inroads into the understanding of its pathobiology and improving clinical outcomes in children with chronic cough. PBB is now recognised internationally and incorporated into all major international paediatric chronic cough guidelines.

A poster version of this case study is available as a PDF from the Downloads section below.

Origin

Cough is a common reason for presenting to doctors,1 and some patients have chronic cough (>4-weeks duration).

In children, chronic cough impairs the quality of life (QoL) of both children and their parents2 and causes a high healthcare burden.

Single-3,4 and multi-centre2 studies in Australia involving children with chronic cough presenting for the first time to respiratory specialists found that ~80% had seen >5 doctors for their cough, their QoL was as poor as those with cardiac disease and ~12% had a serious underlying illness (e.g. bronchiectasis).

However, the importance of chronic cough as indicating an underlying treatable disease has often been unrecognised by doctors and, until recently, the primary cause of chronic cough was unknown and required investigation by medical researchers.

Image of Bronchi tubes

Credit: iStock, DmitriyDanilchenko

Image: Bronchi are the tubes that carry air into and out of the lungs.

Bronchitis is an infection of the bronchi causing them to become irritated and inflamed. The main symptom of bronchitis is a cough. When a cough brings up mucus, this is a “wet” cough.

Bronchiectasis occurs when the bronchi become enlarged, making them prone to infection and causing breathing difficulties.

Grants and Investment

The need to improve the management of paediatric chronic cough was recognised by a team of researchers led by Anne Chang at QUT/Menzies and a group of collaborating researchers and clinicians located in a range of universities and hospitals in Australia and internationally. Their research – including within the Cough and Airways Group (QUT)/Child Respiratory Group (Menzies) and other related collaboration – has been funded through a range of NHMRC grants and fellowships.

Other funding sources have included: Queensland (Qld) Children’s Hospital Foundation (CHF), Perth CHF, Qld Children’s Medical Research Institute (QCMRI), Qld Health, Western Australian (WA) Health, Royal College of Physicians, Rebecca L Cooper Foundation, Medical Research Future Fund (MRFF), Lung Foundation of Australia, Raine Medical Research and other NGOs.

Photograph of 3 people using a mobile phone

Image: Lesley Versteegh—an Aboriginal research nurse in Chang’s Darwin group—providing education to a mother using a digitalised version of the resources produced by the team. Credit: Menzies School of Health Research

Research and Collaboration

As a consequence of a comprehensive evaluation of children with chronic cough, the team were the first to recognise and describe PBB. They then undertook the first randomised controlled trial (RCT) on using antibiotics for children with chronic wet cough and later synthesised the evidence in a Cochrane Review.

Concurrently, Chang was invited by the American College of Chest Physicians to write the world’s first guidelines on the management of paediatric chronic cough.

Prior to these developments, it was recommended that children with chronic cough be treated like adults, which is now understood to be associated with adverse events.

The team undertook studies focused on improving the management of paediatric chronic cough. These included development of ‘cough pointers’ and RCTs evaluating a chronic cough algorithm involving children presenting to specialists and primary care.

A medical algorithm is a decision-making support tool designed to assist clinicians to provide the most appropriate health-care treatment.

Microbiological studies to understand PBB’s pathobiology during lower airway infection led to the first descriptions of biofilms in PBB and diagnostic criteria for infection.

An RCT involving First Nations children hospitalised for acute respiratory infection led to the discovery of an association between the presence of chronic cough and future bronchiectasis. Along with research on various aspects of bronchiectasis in children—including two international multi-centre RCTs —this provided evidence of the paradigm linking PBB to bronchiectasis, proposed in 2008 and now internationally accepted.

Subsequent research described the enablers and barriers to the timely detection of, and optimal management of children with chronic cough in First Nations communities in the Kimberley, Western Australia.

Results and Translation

The discovery of PBB has changed international approaches to paediatric chronic cough management and these changes have been incorporated into the European Respiratory Society (ERS) curriculum and all current major chronic cough guidelines.

In June 2022, PBB was recognised as a disease by the World Health Organization (WHO).

Other ongoing work has shown that using an evidenced-based chronic cough algorithm to guide diagnosis and treatment improves parents’ and childrens' QoL and enhances accurate diagnosis. These are now standard practice in point-of-care manuals (e.g. in Up-To-Date, an online resource for physicians).

Utilisation of the concept of wet cough and ‘cough pointers’ is now a standard differentiating feature used in patient education resources internationally. In response to community requests, the team developed First Nations-specific flipcharts and software based around these tools.

Discovery of the association between the presence of chronic cough and future bronchiectasis in First Nations children hospitalised for a respiratory infection led to changes in policy/practice to ensure the children are followed up in the community and are treated for PBB when chronic cough is present. These are now recommendations in First Nations oriented point-of-care manuals and guidelines.

With the Lung Foundation of Australia, podcast and modules for training of health practitioners were produced. The knowledge translation approach in partnership with local champions has led to doctors recognising and treating PBB earlier in First Nations communities in the Kimberley.

Health outcomes and Impact

As a direct consequence of the NHMRC-funded research undertaken by Chang and her colleagues there has been a change in global clinical practice in the treatment of children with chronic cough that has led to improved QoL and clinical outcomes in both urban and First Nations settings.

Improvements include resolution of chronic cough, prevention and reversal of bronchiectasis, improved lung function and reduced use of unnecessary medications. In Australia, these changes are expected to reduce costs by $161 million over the period 2012 to 2041.5

In Australia, there has also been a change in policy and practice involving the follow-up of First Nations children hospitalised with respiratory infections. Prior to the team’s work, chronic cough among First Nations children—and the poor lung health that resulted from it—were often seen as being ‘normal’ among carers.

Better recognition and detection of chronic wet cough (PBB and bronchiectasis), including in remote First Nations communities, has led to improved management and clinical outcomes, such as using the right antibiotics for the right child for the right indication, earlier recognition and detection of bronchiectasis, prevention of severe bronchiectasis, reduced hospitalisations and improvements to patients’ lung function.

The team’s research work has also resulted in capacity building of 11 trainees, including 8 First Nations trainees, in the context of higher degrees by research, undergraduate degrees, vocational education and training and translation activities.

All research and other activities involving First Nations Australians (both in Darwin and Brisbane) are discussed with and informed by the Child Health First Nations Advisory Board at Menzies. Other research activities (since 2019) are informed by a Parent Advisory Group.

Timeline

All grants listed are NHMRC grants unless stated otherwise.

Year Event
1995 - 1997 Postgraduate scholarship (Chang)
2002 - 2008 Royal Children’s Hospital (Brisbane) Foundation- Centre for Excellence grant (Chang)
2003 - 2004 Project Grant (Smith-Vaughan)
2003 - 2005 Project Grant (Smith-Vaughan)
2004 - 2008 Early Career Fellowship (Smith-Vaughan)
2004 - 2008 Practitioner Fellowship (Chang)
2005 - 2006 Royal Children’s Hospital (Brisbane) Foundation Major Grant for Established Researchers (Chang)
2006 World’s first description of the diagnostic entity of PBB, World’s first chronic cough guidelines for children — a change in the management paradigm of children with chronic cough (previous recommendations was to treat alike adults with chronic cough)
2008 - 2010 Queensland Government Smart State grant (Chang)
2008 - 2011 Postgraduate Scholarship (Marsh)
2008 - 2011 Project Grant (Chang)
2009 - 2013 Practitioner Fellowship (Chang)
2010 Development of flipcharts and talking posters (in 5 First Nations languages) for health education. These were later modified by the Western Australian group for implementation projects. Following consumer requests, Digital Apps (with 7 First Nations languages and English) developed then launched in 2020-21.
2010 - 2014 Project Grant (Chang) - This grant provided evidence that the presence of chronic cough in First Nations children post hospitalisation (i.e. PBB) is associated with bronchiectasis. This led to changes in policy/practice to ensure First Nations children hospitalised with respiratory infections are followed up in the community and are treated for PBB when chronic cough is present. Recommended in Central Australian Rural Practitioners Association point-of-care manual and Royal Australian College of General Practitioners (RACGP)/ National Aboriginal Community Controlled Health Organisation (NACCHO) guidelines.
2010 - 2015 Children’s Hospital Foundation/Qld Children’s Medical Research Institute—Centre for Excellence program grant (Chang)
2012 Change in policy and practice in the follow-up of First Nations children hospitalised with respiratory infections. This was updated in 2018.
2012 RCT evidence that use of the chronic cough algorithm that incorporates PBB improves QoL and outcomes
2012 - 2013 Channel 7 Children’s Research Foundation grant (Marsh)
2012 - 2014 Project Grant (Smith-Vaughan)
2012 - 2015 Career Development Award (Smith-Vaughan)
2012 - 2016 Project Grant (Chang)
2012 - 2017 Early Career Fellowship (Marsh)
2012 - 2018 Centre of Research Excellence in Lung Health of Aboriginal and Torres Strait Islander Children (Chang)
2013 Incorporation of PBB into the European Respiratory Society Paediatric Curriculum
2013 - 2014 Perpetual Ramaciotti Foundation Establishment Grant (Marsh)
2013 - 2014 Postgraduate Scholarship (McCallum)
2013 - 2015 QCMRI top up scholarship grant (Goyal)
2013 - 2017 Early Career Fellowship (Toombs)
2013 - 2017 Project Grant (Chang)
2014 - 2016 Postgraduate Scholarship (Goyal)
2014 - 2017 Foundation for Children grant (Marsh)
2014 - 2018 Practitioner Fellowship (Chang)
2014 - 2018 Project Grant (Toombs)
2015 - 2019 Project Grant (O’Grady)
2016 - 2019 Early Career Fellowship (McCallum)
2016 - 2018 Project Grant (Hare)
2016 - 2022 Project Grant (Chang)
2017 European Respiratory Society Statement document on PBB
2017 Incorporation of PBB into point of care treatment guideline in Up-To-Date
2017 - 2018 Children’s Foundation Clinical Research grant (Chang)
2017 - 2018 Financial Markets Foundation for Children grant (Hare)
2018 - 2020 WA Health grant (Laird)
2019 - 2020 Postgraduate Scholarship (Laird)
2018 - 2023 Project Grant (Chang)
2019 Implementation of routine follow-up of First Nations children hospitalised at the Royal Darwin Hospital through electronic systems. This promotes earlier detection of PBB and adherence to NACCHO/RACP guidelines.5
2020 - 2024 Partnership Project Grant (Schultz)
2019 - 2021 Translating Research into Practice (TRIP) Fellowship (Schultz)
2019 - 2023 Practitioner Fellowship (Chang)
2019 - 2024 Project Grant (McCallum)
2019 - 2022 Qld CHF grant
2019 - 2020 Perth CHF Investigator Grant (Laird)
2020 - 2025 NHMRC Centre of Research Excellence (CRE) in preventing and managing bronchiectasis, especially in Aboriginal and Torres Strait Islander Children (Chang)
2019 - 2021 Qld CHF fellowship (Marchant)
2021 ERS Clinical Practice Guideline on managing children and adolescents with bronchiectasis. This includes reference to PBB and established an international roadmap on priorities based on needs and priorities of clinicians and parents of children with bronchiectasis.
2021 - 2025 MRFF Investigator Grant (Schultz)
2021 - 2023 Western Australia Child Research Fund grant (Laird)
2021 - 2023 Ideas Grant (Marsh)
2021 - 2024 Ideas Grant (Toombs)
2020 - 2023 Rebecca L Cooper Foundation. Al and Val Rosenstrauss Fellowship (Marsh)
2022 PBB officially recognised as a disease by being assigned a WHO International Classification of Diseases (ICD) code

Researcher profiles

Professor Anne Chang AM

Anne Chang graduated in medicine from The University of Melbourne. She is now a paediatric respiratory physician who is Head of the Child Health Division at Menzies and the Cough and Airways Research Group at QUT. In 2019 she was made a Member of the Order of Australia.

Professor Maree Toombs

Maree Toombs is the Associate Dean Indigenous Engagement in the Faculty of Medicine at The University of Queensland. She is also the past-Chair of Carbal Aboriginal Medical Services and was appointed a Professorial Fellow at Menzies in 2021.

Professor Keith Grimwood

Keith Grimwood is Deputy Head (Research) of the School of Medicine and Dentistry at Griffith University. Grimwood is a paediatric infectious diseases physician with a joint appointment as Professor of Infectious Diseases with Gold Coast Hospital and Health Services.

Associate Professor Julie Marchant

Julie Marchant is an Associate Professor within the School of Public Health and Social Work at QUT. She is a Paediatric Respiratory Physician at the Queensland Children’s Hospital and a senior research fellow in the Cough and Airways Research QUT group, Brisbane.

Associate Professor André Schultz

André Schultz is the Program Head of Respiratory Health and Head of the BREATH Team at Telethon Kids Institute. He is also a paediatric respiratory physician and Director of Cystic Fibrosis at Perth Children’s Hospital, and co-founder and Chair of the multinational chILDRANZ Peer Support Team.

Associate Professor Stephanie Yerkovich

Stephanie Yerkovich is a scientist and biostatistician at Menzies and QUT. She studies both immune development and the association between altered immunity and paediatric and adult respiratory disease, especially in relation to the microbiome and infectious burden.

Associate Professor Heidi Smith-Vaughan

Heidi Smith-Vaughan is a Principal Research Fellow and Associate Director for Research (HDR and ethics) at Menzies. She leads HealthLAB (for health education implementation) and co-leads the Menzies Ramaciotti Regional and Remote Health Science Training Centre.

Dr Robyn Marsh

Robyn Marsh is a Senior Research Fellow at Menzies who leads the Menzies (Darwin) Child Health Division’s Respiratory Microbiome Program and co-leads the Ramaciotti Regional and Remote Health Science Training Centre. She is a 2020 Al & Val Rosenstrauss Fellowship recipient.

Dr Pamela Laird

Pamela Laird is a senior respiratory physiotherapist at Perth Children’s Hospital and the Kimberley/Pilbara specialist respiratory service. Laird is a Raine Fellow and has worked in partnership with Aboriginal communities and other collaborators to develop lung health literacy tools.

Dr Gabrielle McCallum

Gabrielle McCallum is a Senior Research Fellow, Clinical Nurse, and Program Leader of Menzies’ Child Health Respiratory team in Darwin. McCallum’s work includes multi-centre RCTs and other observational studies extending to New Zealand, Alaska and Malaysia.

Dr Vikas Goyal

Vikas Goyal trained as a Paediatric Respiratory and Sleep Medicine Physician, is based at the Queensland Children’s Hospital and works within the Cough and Airways Research QUT group. His PhD focused on bronchiectasis in children and included two international RCTs.

Other researchers

  • A/Prof Kerry-Ann O’Grady, QUT
  • Dr Kim Hare, Menzies
  • Professor Peter Morris, Menzies
  • Dr Katie Baines, University of Newcastle
  • Professor John Upham, The University of Queensland
  • Professor Sandra Hodge, The University of Adelaide

References

This case study was developed with input from Professor Anne Chang and team members and in partnership with Queensland University of Technology and the Menzies School of Health Research.

The information and images from which impact case studies are produced may be obtained from a number of sources including our case study partner, NHMRC’s internal records and publicly available materials.

The following sources were consulted for this case study:

1 Britt H, Miller GC, Bayram C, et al. A decade of Australian general practice activity 2006-07 to 2015-16. Sydney University Press 2016; General practice series no. 41.

2 Chang AB, Robertson CF, van Asperen PP, et al. A multi-centre study on chronic cough in children: burden and etiologies based on a standardized management pathway. Chest 2012; 142: 943-50.

3 Marchant JM, Newcombe PA, Juniper EF, Sheffield JK, Stathis SL, Chang AB. What is the burden of chronic cough for families? Chest 2008; 134: 303-09.

4 Marchant JM, Masters IB, Taylor SM, Cox NC, Seymour GJ, Chang AB. Evaluation and outcome of young children with chronic cough. Chest 2006; 129: 1132-41.

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