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Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration

Stefano Aliberti, Sarah Masefield, Eva Polverino, Anthony De Soyza, Michael R. Loebinger, Rosario Menendez, Felix C. Ringshausen, Montserrat Vendrell, Pippa Powell, James D. Chalmers  on behalf of the EMBARC Study Group
European Respiratory Journal 2016 48: 632-647; DOI: 10.1183/13993003.01888-2015
Stefano Aliberti
1Dept of Pathophysiology and Transplantation, University of Milan, Cardio-thoracic unit and Adult Cystic Fibrosis Center, Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico, Milan, Italy
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  • For correspondence: stefano.aliberti@unimi.it
Sarah Masefield
2European Lung Foundation, Sheffield, UK
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Eva Polverino
3Fundaciò Clìnic, IDIBAPS, CIBERES, Hospital Clinic de Barcelona, Barcelona, Spain
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Anthony De Soyza
4Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK
5Bronchiectasis Service, Freeman Hospital, Newcastle upon Tyne, UK
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Michael R. Loebinger
6Host Defence Unit, Royal Brompton Hospital, London, UK
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Rosario Menendez
7Pneumology Service, Universitary and Polytechnic Hospital La Fe, Valencia, Spain
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Felix C. Ringshausen
8Dept of Respiratory Medicine, Hannover Medical School, Member of the German Center for Lung Research (DZL), Hannover, Germany
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Montserrat Vendrell
9Bronchiectasis Group, Girona Biomedical Research Institute (IDIBGI), Dr. Trueta University Hospital, Girona, Spain
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Pippa Powell
2European Lung Foundation, Sheffield, UK
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James D. Chalmers
10College of Medicine, University of Dundee, Dundee, UK
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    FIGURE 1

    Processes to define both experts' and patients' research priorities in bronchiectasis.

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    FIGURE 2

    a) Aspects of bronchiectasis found either difficult or very difficult by patients. b) Aspects of bronchiectasis found difficult or very difficult by patients in comparison with the percentage of patients who identified the same aspects as “not an issue”.

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  • TABLE 1

    Ranking of experts' research priorities in bronchiectasis

    Research priorityArea of researchScore
     1When and how (molecule, dose, regimen, route (intravenous, oral or inhaled/nebulised) and duration) should Pseudomonas aeruginosa be eradicated in patients with bronchiectasis, and do patients' outcomes improve after that?Acute and long-term suppressive antibiotic therapy4.35/5
     2What are the indications and what 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?Exacerbation4.30/5
     3What are the prevalence and characteristics of microbiological colonisation, and chronic and acute infections (exacerbations and pneumonia) in patients with bronchiectasis across Europe (including bacteria, viruses, fungi, nontuberculous mycobacteria and resistant microorganisms)?Epidemiology4.29/5
     4What are the risk factors and causes of fast progression and poor outcomes (e.g. hospitalisation, lung transplantation and mortality) in patients with bronchiectasis?Outcomes, prognosis and healthcare utilisation4.28/5
     5What is the impact of long-term antibiotic therapy on microbial resistances?Acute and long-term suppressive antibiotic therapy4.21/5
     6When should a long-term suppressive antibiotic therapy (either oral or inhaled/nebulised) be started in patients with bronchiectasis (according to the presence or absence of P. aeruginosa or other pathogens) and what would be end-points for efficacy?Acute and long-term suppressive antibiotic therapy4.20/5
     7What are the key factors leading to P. aeruginosa colonisation?Microbiology and microbial diagnostics4.16/5
     8What are the indications of oral versus inhaled/nebulised long-term suppressive antibiotic treatment?Acute and long-term suppressive antibiotic therapy4.12/5
     9What are the best molecule, 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)?Acute and long-term suppressive antibiotic therapy4.11/5
    10What are the causes of an exacerbation of bronchiectasis?Exacerbation4.09/5
    11When and how (molecule, dose, regimen, route (intravenous, oral or inhaled/nebulised) and duration) should pathogens other than P. aeruginosa be eradicated in patients with bronchiectasis, and do patients' outcomes improve after that?Acute and long-term suppressive antibiotic therapy4.08/5
    12What are the best molecule, dose, regimen and duration for long-term inhaled/nebulised antibiotic therapy in patients with bronchiectasis (according to the presence or absence of P. aeruginosa or other pathogens)?Acute and long-term suppressive antibiotic therapy4.08/5
    13What are the baseline investigations to evaluate aetiologies in patients with bronchiectasis?Aetiology, radiology and pulmonary function tests4.08/5
    14Do different aetiologies of bronchiectasis predetermine microbiological characteristics, and affect severity, patients' quality of life and disease progression in patients with bronchiectasis?Aetiology, radiology and pulmonary function tests4.00/5
    15How should the severity of an exacerbation of bronchiectasis be assessed and what is its impact on long-term outcomes?Exacerbation3.98/5
    16When should airway drainage techniques be started in patients with bronchiectasis, and which one is the most effective and pragmatic?Physiotherapy and pulmonary rehabilitation3.97/5
    17Which is the most useful severity score in clinical practice in patients with bronchiectasis?Outcomes, prognosis and healthcare utilisation3.96/5
    18Does an early referral to a specialist clinic change outcomes in patients with bronchiectasis?Outcomes, prognosis and healthcare utilisation3.96/5
    19What is the average lung function decline in patients with bronchiectasis across Europe and what are the risk or protective factors for that?Aetiology, radiology and pulmonary function tests3.93/5
    20Which factors, including aetiology of bronchiectasis, patients' characteristics or bacteria isolated in sputum, affect macrolide efficacy in patients with bronchiectasis?Acute and long-term suppressive antibiotic therapy3.92/5
    21What are the characteristics of patients' microbiomes, both during the stable state and exacerbation, and what is its impact on severity of the disease and follow-up?Microbiology and microbial diagnostics3.90/5
    22What is the role of viruses, atypicals, fungi and anaerobes (both singly and in co-infection) in patients with bronchiectasis, during both the stable state and exacerbation, and what is their impact of patients' severity and outcomes?Microbiology and microbial diagnostics3.89/5
    23What is the prevalence of different aetiologies of bronchiectasis across Europe?Epidemiology3.87/5
    24Are influenza and/or pneumococcal vaccines and other immunotherapies effective in preventing exacerbations in patients with bronchiectasis?Other3.84/5
    25What are the adverse events of a both oral and inhaled/nebulised suppressive antibiotic therapy in patients with bronchiectasis?Acute and long-term suppressive antibiotic therapy3.83/5
    26What are the prevalence and type of long-term suppressive oral (macrolide and nonmacrolide) and nebulised/inhaled antibiotic therapy in patients with bronchiectasis across Europe?Epidemiology3.83/5
    27When should pulmonary rehabilitation be started in patients with bronchiectasis and what is its impact on patients' outcomes?Physiotherapy and pulmonary rehabilitation3.82/5
    28What are incidence, prevalence, patients' demographic characteristics and comorbidities of bronchiectasis across Europe?Epidemiology3.81/5
    29Is airway clearance useful during an acute exacerbation of bronchiectasis?Exacerbation3.80/5
    30Should we establish new breakpoints for predicting bacteria susceptibility when inhaled/nebulised antibiotics are used?Microbiology and microbial diagnostics3.78/5
    31What are the indications/contraindications for lung transplantation in bronchiectasis and what are patients' outcomes after lung transplantation?Other3.73/5
    32Which are the best systemic (e.g. blood) or local (e.g. sputum) inflammatory markers for the diagnosis, management and follow-up of patients with bronchiectasis?Pathogenesis and mechanisms of the disease3.73/5
    33What is the distribution of inhaled/nebulised antibiotics with different formulations and devices in lungs with bronchiectasis?Acute and long-term suppressive antibiotic therapy3.73/5
    34Do specific patient education packages, self-management plans and patients support groups improve outcomes in patients with bronchiectasis?Other3.72/5
    35Where are patients with bronchiectasis managed across Europe, including specialist (bronchiectasis) clinics, CF centres/clinics, respiratory clinics or general practitioners?Epidemiology3.67/5
    36Are other functional tests (such as carbon monoxide diffusing capacity, 6-min walk test, lung clearance index, endurance shuttle walk, incremental exercise tests or accelerometers) markers for severity of the disease, outcomes and end-points for the clinic?Aetiology, radiology and pulmonary function tests3.64/5
    37What is the best approach/score to evaluate radiological severity in patients with bronchiectasis?Aetiology, radiology and pulmonary function tests3.63/5
    38Might cross-infection occur in patients with bronchiectasis and is patients segregation required?Microbiology and microbial diagnostics3.62/5
    39What are the healthcare costs of bronchiectasis management across Europe?Epidemiology3.60/5
    40What is the role of inhaled hyperosmolar therapy (e.g. hyaluronate; mannitol; or NaCl 3%, 6% or 7%)?Nonantibiotic and anti-inflammatory therapies3.53/5
    41What are the radiological changes in bronchiectasis over time?Aetiology, radiology and pulmonary function tests3.52/5
    42What is the impact of haemoptysis on the prognosis of patients with bronchiectasis and how should it be managed?Other3.51/5
    43What 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?Pathogenesis and mech anisms of the disease3.50/5
    44What are the characteristics and outcomes of patients with bronchiectasis undergoing surgery, including segmentectomy, lobectomy or pneumonectomy?Other3.49/5
    45What is the role of systemic steroids during an exacerbation of bronchiectasis?Exacerbation3.47/5
    46Is there an increased rate of innate immune defects (e.g. mannose-binding lectin deficiency, common variable immunodeficiency, IgM or IgA deficiency, or complement deficiency) in specific patients with bronchiectasis?Pathogenesis and mechanisms of the disease3.46/5
    47What is the role of long-term inhaled corticosteroids in patients with bronchiectasis?Nonantibiotic and anti-inflammatory therapies3.38/5
    48What are the frequency of CF heterozygosity, and the role of CFTR and ENaC dysfunction in patients with bronchiectasis?Pathogenesis and mechanisms of the disease3.36/5
    49What is the role of oral mucolytics in patients with bronchiectasis?Nonantibiotic and anti-inflammatory therapies3.35/5
    50What is the role of antiproteinases/elastase inhibitors in patients with bronchiectasis?Nonantibiotic and anti-inflammatory therapies3.19/5
    51What is the role of systemic anti-inflammatory therapies (e.g. steroids or nonsteroidal anti-inflammatory drugs) during the stable state in patients with bronchiectasis?Nonantibiotic and anti-inflammatory therapies3.15/5
    52What is the role of protease–antiprotease imbalance, matrix metalloproteinase and neuron-specific enolase in patients with bronchiectasis?Pathogenesis and mechanisms of the disease3.14/5
    53What is the role of anticholinergic therapy in patients with bronchiectasis?Nonantibiotic and anti-inflammatory therapies3.12/5
    54What is the role of phosphodiesterase type 4 inhibitors in patients with bronchiectasis?Nonantibiotic and anti-inflammatory therapies2.97/5
    55Does daily proton-pump inhibitor use impact clinical outcomes in patients with bronchiectasis?Nonantibiotic and anti-inflammatory therapies2.96/5
    • CF: cystic fibrosis; CFTR: cystic fibrosis transmembrane conductance regulator; ENaC: epithelial sodium channel.

  • TABLE 2

    Ranking of patients' and carers' research priorities in bronchiectasis

    Research priorityArea of research
     1How does bronchiectasis develop and continue?How bronchiectasis is managed by doctors
     2How can communication between healthcare professionals and each patient be optimised to improve self-management?Self-management by patients
     3What makes some patients get worse?How bronchiectasis is managed by doctors
     4What are causes of bronchiectasis?How bronchiectasis is managed by doctors
     5What are the triggers for an exacerbation?How bronchiectasis is managed by doctors
     6How can self-management programmes and care plans designed with each person be most effective in helping patients have greater control over their condition and recognise/manage an exacerbation?Self-management by patients
     7How can physiotherapy be accessible to all patients, and teach them to use the techniques and how to use the equipment at home effectively?Self-management by patients
     8How can reliable, plain language information on living with bronchiectasis be accessible to patients?Self-management by patients
     9How can patients at increased risk of poor outcomes or needing urgent treatment be identified?How each person's bronchiectasis is monitored
    10How can awareness of bronchiectasis in community care services be improved (e.g. among community-based nurses and physiotherapists)?How bronchiectasis is treated
    11Are there ways to diagnose bronchiectasis earlier?How bronchiectasis is managed by doctors
    12How can awareness of the role of physiotherapy and pulmonary rehabilitation in treating bronchiectasis be improved?How bronchiectasis is treated
    13Can we test new techniques for managing bronchiectasis in real-world environments, such as at home and community settings (not in the laboratory or in hospitals), to improve how bronchiectasis is managed?How bronchiectasis is managed by doctors
    14Is there a link between getting a cold and exacerbation?How bronchiectasis is managed by doctors
    15Can regular lung function testing help notice changes or increased risk of an exacerbation?How each person's bronchiectasis is monitored
    16Is there a relationship between bronchiectasis and other conditions, such as asthma, “acid” reflux and inflammatory bowel diseases?How bronchiectasis is managed by doctors
    17Can new medicines that can be taken in new ways be developed (e.g. inhaled or nebulised)?How bronchiectasis is treated
    18Can regular sputum examinations when a person is stable and during exacerbation help us learn more about how the condition changes?How each person's bronchiectasis is monitored
    19Can we develop better ways of teaching people to use their medicines?How bronchiectasis is treated
    20Can we provide and will providing test results help each patient follow their progress?Self-management by patients
    21How can primary care doctors be educated to prescribe the same dose/length of antibiotic therapy for exacerbations in bronchiectasis as used in CF?How bronchiectasis is treated
    22Can vaccines be developed/used to prevent exacerbations?How bronchiectasis is treated
    23How often/why does bronchiectasis occurs in certain groups of people?How bronchiectasis is managed by doctors
    24How can we ensure that each person has access to a home intravenous antibiotic service to avoid unnecessary hospital admissions?Self-management by patients
    25How can awareness, and use of peer support forums and social media to exchange information be raised?Self-management by patients
    26How can patients have and use equipment at home to monitor their symptoms?How each person's bronchiectasis is monitored
    27How can the monitoring and treatment of coughing up blood be achieved?How each person's bronchiectasis is monitored
    28Can using longer-term antibiotic therapy when a person's condition is stable improve treatment?How bronchiectasis is treated
    29Can having regular computed tomography scans to look for changes and increased risk of an exacerbation improve monitoring?How each person's bronchiectasis is monitored
    • CF: cystic fibrosis.

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    • S. Aliberti
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    Articles discussed:

    • Aliberti S, Masefield S, Polverino E, et al. Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration. Eur Respir J 2016; 48: 632-647. Full Text

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Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration
Stefano Aliberti, Sarah Masefield, Eva Polverino, Anthony De Soyza, Michael R. Loebinger, Rosario Menendez, Felix C. Ringshausen, Montserrat Vendrell, Pippa Powell, James D. Chalmers
European Respiratory Journal Sep 2016, 48 (3) 632-647; DOI: 10.1183/13993003.01888-2015

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Research priorities in bronchiectasis: a consensus statement from the EMBARC Clinical Research Collaboration
Stefano Aliberti, Sarah Masefield, Eva Polverino, Anthony De Soyza, Michael R. Loebinger, Rosario Menendez, Felix C. Ringshausen, Montserrat Vendrell, Pippa Powell, James D. Chalmers
European Respiratory Journal Sep 2016, 48 (3) 632-647; DOI: 10.1183/13993003.01888-2015
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