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Clinical and research priorities for children and young people with bronchiectasis: an international roadmap

Anne B. Chang, Jeanette Boyd, Leanne Bell, Vikas Goyal, I. Brent Masters, Zena Powell, Christine Wilson, Angela Zacharasiewicz, Efthymia Alexopoulou, Andrew Bush, James D. Chalmers, Rebecca Fortescue, Adam T. Hill, Bulent Karadag, Fabio Midulla, Gabrielle B. McCallum, Deborah Snijders, Woo-Jung Song, Thomy Tonia, Keith Grimwood, Ahmad Kantar
ERJ Open Research 2021 7: 00122-2021; DOI: 10.1183/23120541.00122-2021
Anne B. Chang
1Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
2Dept of Respiratory and Sleep Medicine, Queensland Children's Hospital, Brisbane, Queensland, Australia
3Child Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
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  • For correspondence: Anne.chang@menzies.edu.au
Jeanette Boyd
4European Lung Foundation, Sheffield, UK
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Leanne Bell
5European Lung Foundation Bronchiectasis Paediatric Patient Advisory Group, Sheffield, UK
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Vikas Goyal
1Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
2Dept of Respiratory and Sleep Medicine, Queensland Children's Hospital, Brisbane, Queensland, Australia
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I. Brent Masters
1Australian Centre for Health Services Innovation, Queensland University of Technology, Brisbane, Queensland, Australia
2Dept of Respiratory and Sleep Medicine, Queensland Children's Hospital, Brisbane, Queensland, Australia
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Zena Powell
5European Lung Foundation Bronchiectasis Paediatric Patient Advisory Group, Sheffield, UK
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Christine Wilson
6Dept of Physiotherapy, Queensland Children's Hospital, Brisbane, Queensland, Australia
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Angela Zacharasiewicz
7Dept of Pediatrics and Adolescent Medicine, Teaching Hospital of the University of Vienna, Wilhelminen Hospital, Vienna, Austria
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Efthymia Alexopoulou
82nd Radiology Dept, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece
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Andrew Bush
9Dept of Paediatric Respiratory Medicine, Royal Brompton Hospital, and National Heart and Lung Institute, Imperial School of Medicine, London, UK
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James D. Chalmers
10College of Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK
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Rebecca Fortescue
11Population Health Research Institute, St George's University of London, London, UK
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Adam T. Hill
12Dept of Respiratory Medicine, Royal Infirmary and University of Edinburgh, Edinburgh, UK
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Bulent Karadag
13Division of Pediatric Pulmonology, Marmara University Faculty of Medicine, Istanbul, Turkey
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Fabio Midulla
14Dept of Maternal Science, Sapienza University of Rome, Rome, Italy
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Gabrielle B. McCallum
3Child Health Division, Menzies School of Health Research, Darwin, Northern Territory, Australia
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Deborah Snijders
15Dolomiti Local Health and Social Unit, Belluno, Veneto, Italy
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Woo-Jung Song
16Dept of Allergy and Clinical Immunology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, South Korea
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Thomy Tonia
17Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
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Keith Grimwood
18Depts of Infectious Disease and Paediatrics, Gold Coast Health, Southport, Queensland, Australia
19School of Medicine and Menzies Health Institute Queensland, Griffith University, Southport, Queensland, Australia
21These authors contributed equally as senior authors
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Ahmad Kantar
20Pediatric Asthma and Cough Centre, Istituti Ospedalieri Bergamaschi, University and Research Hospitals, Ponte San Pietro, Bergamo, Italy
21These authors contributed equally as senior authors
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    FIGURE 1

    Overview of the project methodology. ELF: European Lung Foundation; ERS: European Respiratory Society.

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    FIGURE 2

    Results from the parent/patient survey relating to aspects of their child's bronchiectasis on their quality of life. a) Mean scores of items rated by parents affecting their child's quality of life. b) Mean scores of items rated by parents affecting their own quality of life. #: e.g. walking far, swimming.

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  • TABLE 1

    Parent/patient survey: clinical needs themes and priorities

    ThemeItems (verbatim from survey questions)Mean score
    Awareness and diagnosisTo find ways to diagnose bronchiectasis earlier, such as by local doctors#3.86
    To improve awareness of bronchiectasis in community care services, e.g. among community-based nurses and physiotherapists3.82
    To identify the cause(s) of bronchiectasis3.80
    Education and support for parents and familiesKnowing more about the role of physiotherapy and pulmonary rehabilitation (a short course of regular exercise sessions and education sessions)3.80
    Having access to reliable, easy to understand information about different aspects of living with bronchiectasis3.78
    Providing each person with copies of their test results so they can keep a useful history of the progress of their own condition3.74
    Develop better ways of teaching people to use their medicines3.71
    Improving access to quality careHaving access to physiotherapy and being taught the techniques and how to use the equipment at home3.94
    Good communication between healthcare professionals and each person with bronchiectasis3.91
    Testing new techniques for managing bronchiectasis in real world environments, such as at home and community3.86
    Better access to tests and experts on bronchiectasis3.80
    Using peer support forums and social media to exchange information with others3.52
    Managing exacerbationsHaving an action management plan for flare-ups/exacerbations3.94
    Having a self-management programme and care plan designed with each person to help them have greater control over their condition and recognise/manage an exacerbation3.92
    Finding triggers of exacerbation3.86
    Educating primary care doctors to prescribe the same dose/length of antibiotic therapy for exacerbations as used in cystic fibrosis¶3.81
    Improving treatmentTo improve how children with bronchiectasis are treated through using longer-term antibiotic therapy when a person's condition is stable+3.71
    Being able to identify people at increased risk of poor outcomes or needing urgent treatment for their bronchiectasis3.85
    Being able to monitor and treat the coughing up of blood3.77
    Improving monitoringHaving regular lung function testing to help notice changes or increased risk of an exacerbation3.76
    Being able to monitor cough3.68
    Regular sputum examinations when a person is stable and during an exacerbation to learn more about how the condition changes3.64
    Having the equipment at home to monitor symptoms3.58
    Ensuring each person has access to a home intravenous antibiotic service to avoid unnecessary hospital admissions3.53
    Having regular computed tomography scans to look for changes or increased risk of an exacerbation§3.45
    • #: refers to parent's/patient's experience of delayed referral from a lack of awareness of the symptoms of bronchiectasis and dismissing children's chronic wet cough; importantly, we do not expect primary care doctors to undertake computed tomography (CT) scans in young children. ¶: refers to parent's/patient's experience that they are often given a shorter antibiotic course (e.g. 3 days as opposed to current guideline recommendations of 14 days [12]) and/or lower doses than what is generally considered optimal; doses for children with CF are generally higher than for those without CF as children with CF have higher volume of distribution and renal clearance mechanisms; thus, we do not suggest prescribing antibiotics using CF-based dosing regimens, as it can be potentially dangerous for some agents. +: refers to identifying when and in whom long-term antibiotics should be used to induce clinical stability. §: the ERS Clinical Practice Guidelines [12] state that “In children/adolescents with bronchiectasis, we suggest the decision to repeat chest CT scans is individualised based on the clinical status and setting. Remarks: Repeat chest CT scans should be considered to answer a question which will change management.”

  • TABLE 2

    Parent/patient survey: research priorities and themes

    Research themeItems (verbatim from survey questions)Mean score
    Understanding mechanisms and biology of bronchiectasisFinding ways to prevent bronchiectasis3.89
    Identifying how bronchiectasis develops and continues3.87
    Identifying the cause(s) of bronchiectasis3.80
    Identifying how often and why bronchiectasis occurs in certain groups of people across the world3.74
    Finding new ways to improve diagnosis and treatmentFinding ways to diagnose bronchiectasis earlier, such as by local doctors#3.86
    Testing new techniques for managing bronchiectasis in real world environments, such as at home and community settings (not in the laboratory or in hospitals)3.86
    Finding new medicines to treat bronchiectasis3.84
    Finding new physiotherapy/airway clearance techniques3.79
    Using longer-term antibiotic therapy when a person's condition is stable¶3.71
    Developing medicines that can be taken in different ways, such as for inhaled or nebulised3.67
    Improving knowledge and treatment of exacerbationsIdentifying triggers for an exacerbation3.86
    Identifying people at increased risk of poor outcomes or needing urgent treatment for their bronchiectasis3.85
    Using vaccines to prevent exacerbations3.78
    Exploring the link between getting a cold (for example rhinovirus) and having an exacerbation3.74
    Improving monitoring and how to identify predictors of disease progressionIdentifying what makes some patients’ bronchiectasis get worse3.92
    Understanding the relationship between bronchiectasis and other medical conditions, e.g. asthma, “acid” reflux3.80
    Being able to monitor and treat the coughing up of blood3.77
    Having regular lung function testing to help notice changes or increased risk of an exacerbation3.76
    Being able to monitor cough3.68
    • #: refers to parent's/patient's experience of delayed referral due to lack of awareness of the symptoms of bronchiectasis and dismissing children's chronic wet cough; we do not expect primary care doctors to undertake computed tomography scans in young children. ¶: refers to identifying when and in whom long-term antibiotics should be used to induce clinical stability.

  • TABLE 3

    Health practitioner survey: research priorities and themes

    ThemeIn children and young people with bronchiectasis (unrelated to cystic fibrosis)Mean score
    Finding new ways to improve treatmentWhen and how (antibiotic, dose, regimen, route (intravenous, oral or inhaled/nebulised) and duration) should pathogens other than Pseudomonas aeruginosa be eradicated, and do patient outcomes improve afterwards?4.27
    What are the optimal and most cost-effective airway clearance techniques?4.26
    When and how (antibiotic, dose, regimen, route (intravenous, oral or inhaled/nebulised) and duration) should P. aeruginosa be eradicated, and do patient outcomes improve afterwards?4.18
    What is the best antibiotic, dose, regimen and duration for long-term oral antibiotic therapy in patients with bronchiectasis (according to the presence or absence of P. aeruginosa or other pathogens)?4.17
    What are the indications of oral versus inhaled/nebulised long-term suppressive antibiotic treatment?4.14
    When should airway clearance techniques be started in patients with bronchiectasis, and how often should it be done during the stable state and for exacerbations?4.09
    What is the impact of long-term antibiotic therapy on anti-microbial resistance?4.03
    What is the role of different mucoactive agents (e.g. inhaled hypertonic or isotonic saline, mannitol, oral erdosteine or N-acetyl cysteine)?4.03
    What are the simple, reliable microbiological tests for determining lower airway infection?3.90
    What are the most efficient clinical trial designs and measurable outcomes?3.83
    What are the key factors leading to P. aeruginosa acquisition and infection?3.78
    Which clinical and microbiological factors affect macrolide efficacy?3.71
    What is the role of surgery (segmentectomy, lobectomy or pneumonectomy) and when should it be undertaken?3.62
    What is the role of long-term inhaled corticosteroids?3.53
    What is the role of non-pharmacological, non-airway clearance technique-based therapeutics, such as singing exercise, wind instruments and yoga during stable states and acute exacerbations?3.45
    What is the best model/approach for transferring an adolescent with bronchiectasis to adult services?3.42
    Finding new ways to improve diagnosisWhat are the baseline investigations to identify underlying aetiologies of bronchiectasis?3.98
    What clinical factors should be present to trigger referring a child for a chest computed tomography scan to diagnose bronchiectasis?3.87
    Improving knowledge and treatment of exacerbationsWhat is the optimal antibiotic therapy (dosage, how many antibiotics, type, oral versus intravenous versus inhaled/nebulised and length of therapy) for an exacerbation of bronchiectasis?4.41
    What are the most important factors to prevent acute exacerbations?4.12
    How to define acute exacerbations that require additional treatment?4.05
    What are the causes of an exacerbation of bronchiectasis?3.84
    Which are the best systemic (e.g. blood) or local (e.g. sputum) inflammatory markers for the diagnosis, management and follow-up for an exacerbation?3.82
    How should the severity of an exacerbation of bronchiectasis be assessed and what is its impact on long-term outcomes?3.78
    What types of biomarker(s) can be used for predicting bronchiectasis exacerbation?3.68
    Improving prevention and monitoringWhat are the risk factors and causes of rapid progression of lung disease and poor outcomes (e.g. hospitalisation, lung transplantation and mortality)?4.17
    How best to prevent development of bronchiectasis?4.16
    Should there be paediatric-focused patient registries?4.06
    What are the best and most pragmatic functional tests (such as carbon monoxide diffusing capacity, 6-min walk test, lung clearance index, endurance shuttle walk, incremental exercise tests or accelerometers) as markers for severity of the disease, outcomes and end-points for the clinic?4.00
    What are the risk or protective factors for lung function decline in patients with bronchiectasis?3.91
    What are the factors that predict radiographic reversibility (on a high-resolution computed tomography scan)?3.84
    What is the best approach/score to evaluate radiographic severity?3.82
    What types of specific patient education packages, self-management plans and patient support groups improve outcomes?3.81
    Should a severity and prognostic score for children that is useful in clinical practice be developed?3.70
    What comorbidities are present and how do they influence bronchiectasis severity?3.59
    Is cross-infection important, what are the best strategies and is strict patient segregation required?3.59
    What types of biomarker(s) can be used to monitor bronchiectasis severity during stable state, so as to define the subgroup who will benefit from more intensive treatment?3.58
    Can endo-phenotyping predict severity and outcomes in children?3.54
    Understanding mechanisms and biology of bronchiectasisDo different aetiologies and/or comorbidities of bronchiectasis predetermine microbiological characteristics and affect severity, patients’ quality of life and disease progression?3.92
    What is the role of viruses, fungi and anaerobes (as single agents and/or polymicrobial infections), during both the stable state and exacerbation, and what is their impact upon patient severity and outcomes?3.85
    Is there an increased rate of primary immune defects (e.g. mannose-binding lectin deficiency, common variable immunodeficiency, IgM or IgA deficiency, or complement deficiency)?3.78
    What is the incidence and prevalence of different aetiologies of bronchiectasis across the world?3.55
    What is the relationship between paediatric and adult bronchiectasis?3.54
    What is the importance of host–pathogen–environment interactions?3.53
    What are the molecular and cellular mechanisms and pathobiological pathways of bronchiectasis development, exacerbations and progression?3.52
    What is the composition and function of the host microbiome, both during the stable state and exacerbations, and does it impact directly disease severity and progression?3.48
    What are the genetic and epigenetic findings in patients with bronchiectasis compared to healthy controls, and what is their role in acquisition of specific pathogens and patients’ outcomes?3.39
    What is the best experimental model system of bronchiectasis?3.24
    OtherWhat are the healthcare costs of bronchiectasis management across the world?3.19
  • TABLE 4

    Derivation of the top 10 research priorities#

    Consensus priorities (parent/patient and health practitioners) and confirmed with two parent advisory groupsParent/patient survey (verbatim from survey questions)Health practitioner survey (verbatim from survey questions)
    Theme: Understanding mechanisms and biology of bronchiectasis
     Identifying risk and protective factors for  bronchiectasisIdentifying what makes some patients’ bronchiectasis get worseHow best to prevent development of bronchiectasis?
    Finding ways to prevent bronchiectasis
     Identifying the underlying aetiologies of  bronchiectasisIdentifying the cause(s) of bronchiectasisWhat are the baseline investigations to identify underlying aetiologies of bronchiectasis?
    Theme: Diagnosis
     Discovering ways to diagnose  bronchiectasis earlier, including ways  to increase health practitioner  awareness and to facilitate earlier  referralsDiscovering ways to diagnose bronchiectasis earlier, such as by local doctors¶
    Theme: Improving knowledge and treatment of exacerbations
     Identifying triggers/prevention factors  and optimal antibiotic treatment for  acute exacerbationsIdentifying triggers for an exacerbationWhat are the most important factors at preventing acute exacerbations?
    Exploring the link between getting a cold (for example rhinovirus) and having an exacerbationWhat is the optimal antibiotic therapy (dosage, how many antibiotics, type, oral versus intravenous versus inhaled/nebulised and length of therapy) for an exacerbation of bronchiectasis?
    Using vaccines to prevent exacerbations
    Theme: Finding new ways to improve treatment
     Finding new and optimal airway  clearance techniquesFinding new physiotherapy/airway clearance techniquesWhat are the optimal and most cost-effective airway clearance techniques?
    When should airway clearance techniques be started in patients with bronchiectasis, and how often should it be done during the stable state and for exacerbations?
     Defining optimal antibiotic therapy for  eradicating specific pathogens (e.g.  Pseudomonas aeruginosa) and for  suppressing bacteria once chronic  infection is establishedUsing longer-term antibiotic therapy when a person's condition is stable+When and how (antibiotic, dose, regimen, route (intravenous, oral or inhaled/nebulised) and duration) should P. aeruginosa be eradicated, and do patient outcomes improve afterwards?
    When and how (antibiotic, dose, regimen, route (intravenous, oral or inhaled/nebulised) and duration) should pathogens other than P. aeruginosa be eradicated, and do patient outcomes improve afterwards?
    What are the indications of oral versus inhaled/nebulised long-term suppressive antibiotic treatment?
    What is the best antibiotic, dose, regimen and duration for long-term oral antibiotic therapy in patients with bronchiectasis (according to the presence or absence of P. aeruginosa or other pathogens)?
     Finding new medications and/or  techniques for managing  bronchiectasisTesting new techniques for managing bronchiectasis in real world environments, such as at home and communityWhat is the role of different mucoactive agents (e.g. inhaled hypertonic or isotonic saline, mannitol, oral erdosteine or N-acetyl cysteine)?
    Finding new medicines to treat bronchiectasis
    Theme: Improving monitoring and how to identify predictors of disease progression
     Identifying lung function tests/indices  that predict outcomesHaving regular lung function testing to help notice changes or increased risk of an exacerbationWhat are the best and most pragmatic functional tests (such as carbon monoxide diffusing capacity, 6-min walk test, lung clearance index, endurance shuttle walk, incremental exercise tests or accelerometers) as markers for severity of the disease, outcomes and end-points for the clinic?
     Understanding the relationship between  causes and comorbidities of  bronchiectasis with clinical outcomesTo know how bronchiectasis affects other body parts/organs in addition to the lungDo different aetiologies and/or comorbidities of bronchiectasis predetermine microbiological characteristics, and affect severity, patients’ quality of life and disease progression?
    To understand the relationship between bronchiectasis and other medical conditions e.g. asthma, “acid” reflux
     Identifying factors associated with worse  bronchiectasis outcomesIdentifying what makes some patients’ bronchiectasis get worseWhat are the risk factors and causes of rapid progression of lung disease and poor outcomes (e.g. hospitalisation, lung transplantation and mortality)?
    Identifying people at increased risk of poor outcomes or needing urgent treatment for their bronchiectasisWhat are the risk or protective factors for lung function decline in patients with bronchiectasis?
    • #: the list is not in order of priority, i.e. all are considered equal. ¶: refers to parent's/patient's experience of delayed referral due to lack of awareness of the symptoms of bronchiectasis and dismissing children's chronic wet cough; we do not expect primary care doctors to undertake computed tomography scans in young children. +: refers to identifying when and in whom long-term antibiotics should be used to induce clinical stability.

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Clinical and research priorities for children and young people with bronchiectasis: an international roadmap
Anne B. Chang, Jeanette Boyd, Leanne Bell, Vikas Goyal, I. Brent Masters, Zena Powell, Christine Wilson, Angela Zacharasiewicz, Efthymia Alexopoulou, Andrew Bush, James D. Chalmers, Rebecca Fortescue, Adam T. Hill, Bulent Karadag, Fabio Midulla, Gabrielle B. McCallum, Deborah Snijders, Woo-Jung Song, Thomy Tonia, Keith Grimwood, Ahmad Kantar
ERJ Open Research Jul 2021, 7 (3) 00122-2021; DOI: 10.1183/23120541.00122-2021

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Clinical and research priorities for children and young people with bronchiectasis: an international roadmap
Anne B. Chang, Jeanette Boyd, Leanne Bell, Vikas Goyal, I. Brent Masters, Zena Powell, Christine Wilson, Angela Zacharasiewicz, Efthymia Alexopoulou, Andrew Bush, James D. Chalmers, Rebecca Fortescue, Adam T. Hill, Bulent Karadag, Fabio Midulla, Gabrielle B. McCallum, Deborah Snijders, Woo-Jung Song, Thomy Tonia, Keith Grimwood, Ahmad Kantar
ERJ Open Research Jul 2021, 7 (3) 00122-2021; DOI: 10.1183/23120541.00122-2021
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