<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03818646</url>
  </required_header>
  <id_info>
    <org_study_id>P02470</org_study_id>
    <nct_id>NCT03818646</nct_id>
  </id_info>
  <brief_title>Functional Respiratory Imaging in Bronchiectasis</brief_title>
  <acronym>FRIBE</acronym>
  <official_title>Functional Respiratory Imaging During Pulmonary Exacerbations in Adults With Non-cystic Fibrosis Bronchiectasis</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Papworth Hospital NHS Foundation Trust</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Papworth Hospital NHS Foundation Trust</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Four-week prospective single centre exploratory study in adults with bronchiectasis suffering&#xD;
      a pulmonary exacerbation (defined as a change in one or more of the following: cough; sputum&#xD;
      amount; sputum colour; breathlessness; fevers; and malaise).&#xD;
&#xD;
      The study will recruit ten adult subjects (male and female) who attend the Cambridge Centre&#xD;
      for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United Kingdom. The&#xD;
      study will include individuals with a known diagnosis of bronchiectasis suffering a current&#xD;
      pulmonary exacerbation. Participants seen during their usual clinic review with an&#xD;
      exacerbation will be invited to participate and enrolled to commence the study that same day&#xD;
      (day 0). Participants enrolled will undergo clinical review and a series of standard-of-care&#xD;
      testing including sputum culture, lung function tests and blood analysis. Additional to these&#xD;
      standard investigations, participants will also undertake a series of patient reported&#xD;
      outcomes via validated respiratory questionnaires (Quality of Life - Bronchiectasis - QOL-B;&#xD;
      &amp; Leicester Cough Questionnaire - LCQ) and functional respiratory imaging (FRI). FRI consists&#xD;
      of low dose high-resolution CT at full inspiration and expiration, combined with&#xD;
      computational fluid dynamic testing.&#xD;
&#xD;
      Participants will be treated without delay according to standard of care treatment as per&#xD;
      current international guidelines. Participants may be treated as either an inpatient or&#xD;
      outpatient determined by the treating respiratory physician.&#xD;
&#xD;
      Follow up will occur on day 7, 14 and 28 post enrolment with serial CT imaging on days 0, 14&#xD;
      and 28. No scheduled follow up testing will be required beyond the day 28 visit, however all&#xD;
      participants will receive a follow-up phone call at day 35.&#xD;
&#xD;
      The investigators hypothesize that changes in FRI parameters will be seen pre and post&#xD;
      exacerbation treatment and will correlate with changes in lung function and patient reported&#xD;
      outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic response&#xD;
      in future clinical trials in bronchiectasis.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Four-week prospective single centre exploratory study in adults with bronchiectasis suffering&#xD;
      a pulmonary exacerbation.&#xD;
&#xD;
      The study will endeavour to recruit ten adult subjects (male and female) who attend the&#xD;
      Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United&#xD;
      Kingdom. The study will include individuals with a known diagnosis of bronchiectasis (defined&#xD;
      as symptoms of chronic or recurrent bronchial infection with radiological evidence of&#xD;
      abnormal and permanent dilation of bronchi) not from cystic fibrosis; and a current pulmonary&#xD;
      exacerbation (defined as a 'deterioration in three or more of the following key symptoms for&#xD;
      at least 48h: cough; sputum volume and/or consistency; sputum purulence; breathlessness&#xD;
      and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND that a clinician&#xD;
      determines a change in bronchiectasis treatment is required).&#xD;
&#xD;
      In order to maximise subject recruitment and understanding of the study, all CCLI patients&#xD;
      with bronchiectasis that are known to suffer frequent exacerbations (&gt;2 per year) will be&#xD;
      sent details of the trial including the Patient Information and Consent Form at the time of&#xD;
      study commencement, prior to their individual enrolment. Subjects then seen during their&#xD;
      usual clinic review with a pulmonary exacerbation will be invited to participate and enrolled&#xD;
      to commence the study that same day (day 0). Participants enrolled will undergo clinical&#xD;
      review and a series of standard testing including pulmonary function tests and blood&#xD;
      analysis. Additional to these standard investigations, participants will also undertake a&#xD;
      series of patient reported outcomes via validated respiratory questionnaires (Quality of Life&#xD;
      - Bronchiectasis - QOL-B; &amp; Leicester Cough Questionnaire - LCQ) and functional respiratory&#xD;
      imaging (FRI). FRI consists of low dose high-resolution CT at total lung capacity (TLC) and&#xD;
      functional residual capacity (FRC), combined with computational fluid dynamic testing (CFD).&#xD;
&#xD;
      Participants will be treated without delay according to standard usual care as per the&#xD;
      current European Respiratory Society (ERS) and British Thoracic Society (BTS) Bronchiectasis&#xD;
      Guidelines. Participants may be treated as either an inpatient or outpatient determined by&#xD;
      the treating consultant respiratory physician.&#xD;
&#xD;
      Follow up will occur on day 7, 14 and 28 post enrolment. Participants will undergo clinical&#xD;
      review and repeat testing according to the below schedule. No scheduled follow up testing&#xD;
      will be required beyond the day 28 visit, however all participants will receive a follow up&#xD;
      phone call at day 35.&#xD;
&#xD;
      Day 0: Initial consultation - presentation with a pulmonary exacerbation&#xD;
&#xD;
        -  Recruitment, consent and enrolment&#xD;
&#xD;
        -  History and clinical examination&#xD;
&#xD;
        -  Bloods (WCC; neutrophil count; CRP)&#xD;
&#xD;
        -  Pregnancy test (urine dipstick) - if appropriate&#xD;
&#xD;
        -  Lung function testing (FEV1; FVC; TLC)&#xD;
&#xD;
        -  Sputum collection&#xD;
&#xD;
        -  Functional respiratory imaging (HRCT at TLC and FRC; may occur + 48 hours of enrolment)&#xD;
&#xD;
        -  Patient reported outcomes / questionnaires (QOL-B; LCQ)&#xD;
&#xD;
        -  Usual treatment commencement (as per current bronchiectasis guidelines)&#xD;
&#xD;
      Day 7: Mid-treatment follow up (as per usual standard of care)&#xD;
&#xD;
        -  History and clinical review&#xD;
&#xD;
        -  Bloods (WCC, neutrophil count; CRP)&#xD;
&#xD;
      Day 14: End of treatment follow up&#xD;
&#xD;
        -  History and clinical examination&#xD;
&#xD;
        -  Bloods (WCC; neutrophil count; CRP)&#xD;
&#xD;
        -  Pregnancy test (urine dipstick) - if appropriate&#xD;
&#xD;
        -  Lung function testing (FEV1; FVC; TLC)&#xD;
&#xD;
        -  Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 14)&#xD;
&#xD;
        -  Patient reported outcomes / questionnaires (QOL-B; LCQ)&#xD;
&#xD;
      Day 28: Completion of study testing&#xD;
&#xD;
        -  History and clinical examination&#xD;
&#xD;
        -  Bloods (WCC; neutrophil count; CRP)&#xD;
&#xD;
        -  Pregnancy test (urine dipstick) - if appropriate&#xD;
&#xD;
        -  Lung function testing (FEV1; FVC; TLC)&#xD;
&#xD;
        -  Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 28)&#xD;
&#xD;
        -  Patient reported outcomes (QOL-B; LCQ)&#xD;
&#xD;
      Day 35: Phone call by research team member&#xD;
&#xD;
      - No scheduled investigations&#xD;
&#xD;
      No scheduled follow up testing will be required beyond the day 28 visit other then a follow&#xD;
      up phone call at day 35 (see above).&#xD;
&#xD;
      The investigators hypothesize that changes in FRI parameters will be seen pre and post&#xD;
      exacerbation treatment and will correlate well with changes in lung function and patient&#xD;
      reported outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic&#xD;
      response in future clinical trials in bronchiectasis.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">January 2019</start_date>
  <completion_date type="Anticipated">April 2019</completion_date>
  <primary_completion_date type="Anticipated">April 2019</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Airway volume</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Change in image based airway volume from FRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Airway resistance</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Change in image based airway resistance from FRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Lung volume</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Change in image based lung volume from FRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Internal airflow distribution</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Change in image based internal airflow distribution from FRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Airway wall thickness</measure>
    <time_frame>Days 0;14; and 28</time_frame>
    <description>Change in image based airway wall thickness from FRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Blood vessel density</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Change in image based blood vessel density from FRI</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Centreline evaluation (airway dimensions over distance into the lung).</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Change in image based centreline evaluation (airway dimensions over distance into the lung) from FRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Lung function</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Correlation of FRI to lung function (FEV1)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>QOL-B</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Correlation of FRI to the QOL-B (Quality of Life Bronchiectasis) questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>LCQ</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Correlation of FRI to the LCQ (Leicester Cough Questionnaire) questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>CRP</measure>
    <time_frame>Days 0; 14; and 28</time_frame>
    <description>Correlation of FRI to CRP (C-reactive protein)</description>
  </secondary_outcome>
  <enrollment type="Anticipated">10</enrollment>
  <condition>Bronchiectasis</condition>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>Functional Respiratory Imaging</intervention_name>
    <description>Functional Respiratory Imaging (FRI) is a novel image based functional diagnostic tool that combines high-resolution CT scans (HRCT) at TLC and FRC with flow simulations (computational fluid dynamics - CFD) providing a 3D visualization and quantification of lung structure and function.</description>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        The study will endeavour to recruit ten adult subjects (male and female) who attend the&#xD;
        Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge,&#xD;
        United Kingdom. The study will include individuals with a known diagnosis of bronchiectasis&#xD;
        (defined as symptoms of chronic or recurrent bronchial infection with radiological evidence&#xD;
        of abnormal and permanent dilation of bronchi) not from cystic fibrosis; and a current&#xD;
        pulmonary exacerbation (defined as a 'deterioration in three or more of the following key&#xD;
        symptoms for at least 48h: cough; sputum volume and/or consistency; sputum purulence;&#xD;
        breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND that a&#xD;
        clinician determines a change in bronchiectasis treatment is required).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Adult male and females ≥18 years and ≤ 80 years&#xD;
&#xD;
          -  Current diagnosis of bronchiectasis (see above definition)&#xD;
&#xD;
          -  Current pulmonary exacerbation (see above definition)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe obstructive airways disease (defined as FEV1 &lt; 30%; FEV1/FVC &lt; 70%)&#xD;
&#xD;
          -  Diagnosis of other active chronic lung disease (asthma; ABPA; COPD; pulmonary&#xD;
             fibrosis)&#xD;
&#xD;
          -  Currently treated non-tuberculous mycobacterial disease&#xD;
&#xD;
          -  Acute congestive cardiac failure&#xD;
&#xD;
          -  Contra-indication or unable to perform HRCT imaging, including pregnancy&#xD;
&#xD;
          -  Contra-indication or unable to perform pulmonary function testing&#xD;
&#xD;
          -  Active lung malignancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
  </eligibility>
  <overall_official>
    <last_name>Ian Smith, MD</last_name>
    <role>Study Director</role>
    <affiliation>Royal Papworth Hospital NHS Foundation Trust</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Timothy Baird, MBBS</last_name>
    <phone>07706229153</phone>
    <email>tmbaird@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Victoria Stoneman, PhD</last_name>
    <phone>0122369865</phone>
    <email>victoria.stoneman@nhs.net</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Royal Papworth Hospital NHS Foundation Trust</name>
      <address>
        <city>Papworth Everard</city>
        <state>Cambridgeshire</state>
        <zip>CB23 3RE</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <contact>
      <last_name>Timothy Baird, MBBS</last_name>
      <phone>07706229153</phone>
      <email>tmbaird@gmail.com</email>
    </contact>
    <contact_backup>
      <last_name>Victoria Stoneman, PhD</last_name>
      <phone>01223639865</phone>
      <email>victoria.stoneman@nhs.net</email>
    </contact_backup>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, Murris M, Canton R, Torres A, Dimakou K, De Soyza A, Hill AT, Haworth CS, Vendrell M, Ringshausen FC, Subotic D, Wilson R, Vilaro J, Stallberg B, Welte T, Rohde G, Blasi F, Elborn S, Almagro M, Timothy A, Ruddy T, Tonia T, Rigau D, Chalmers JD. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017 Sep 9;50(3):1700629. doi: 10.1183/13993003.00629-2017. Print 2017 Sep.</citation>
    <PMID>28889110</PMID>
  </reference>
  <reference>
    <citation>Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119.</citation>
    <PMID>20627931</PMID>
  </reference>
  <reference>
    <citation>Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, Chalmers JD, De Soyza A, Dimakou K, Elborn JS, Feldman C, Flume P, Goeminne PC, Loebinger MR, Menendez R, Morgan L, Murris M, Polverino E, Quittner A, Ringshausen FC, Tino G, Torres A, Vendrell M, Welte T, Wilson R, Wong C, O'Donnell A, Aksamit T; EMBARC/BRR definitions working group. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J. 2017 Jun 8;49(6):1700051. doi: 10.1183/13993003.00051-2017. Print 2017 Jun.</citation>
    <PMID>28596426</PMID>
  </reference>
  <reference>
    <citation>Koser U, Hill A. What's new in the management of adult bronchiectasis? F1000Res. 2017 Apr 20;6:527. doi: 10.12688/f1000research.10613.1. eCollection 2017.</citation>
    <PMID>28491293</PMID>
  </reference>
  <reference>
    <citation>Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, Smeeth L, Brown JS. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J. 2016 Jan;47(1):186-93. doi: 10.1183/13993003.01033-2015. Epub 2015 Nov 5.</citation>
    <PMID>26541539</PMID>
  </reference>
  <reference>
    <citation>Chang AB, Bell SC, Byrnes CA, Grimwood K, Holmes PW, King PT, Kolbe J, Landau LI, Maguire GP, McDonald MI, Reid DW, Thien FC, Torzillo PJ. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand. Med J Aust. 2010 Sep 20;193(6):356-65. doi: 10.5694/j.1326-5377.2010.tb03949.x.</citation>
    <PMID>20854242</PMID>
  </reference>
  <reference>
    <citation>Vendrell M, de Gracia J, Olveira C, Martinez-Garcia MA, Giron R, Maiz L, Canton R, Coll R, Escribano A, Sole A. [Diagnosis and treatment of bronchiectasis. Spanish Society of Pneumology and Thoracic Surgery]. Arch Bronconeumol. 2008 Nov;44(11):629-40. doi: 10.1157/13128330. Spanish.</citation>
    <PMID>19007570</PMID>
  </reference>
  <reference>
    <citation>Vos W, De Backer J, Poli G, De Volder A, Ghys L, Van Holsbeke C, Vinchurkar S, De Backer L, De Backer W. Novel functional imaging of changes in small airways of patients treated with extrafine beclomethasone/formoterol. Respiration. 2013;86(5):393-401. doi: 10.1159/000347120. Epub 2013 Apr 12.</citation>
    <PMID>23595105</PMID>
  </reference>
  <reference>
    <citation>De Backer LA, Vos W, De Backer J, Van Holsbeke C, Vinchurkar S, De Backer W. The acute effect of budesonide/formoterol in COPD: a multi-slice computed tomography and lung function study. Eur Respir J. 2012 Aug;40(2):298-305. doi: 10.1183/09031936.00072511. Epub 2011 Dec 19.</citation>
    <PMID>22183484</PMID>
  </reference>
  <reference>
    <citation>Hajian B, De Backer J, Vos W, Van Holsbeke C, Clukers J, De Backer W. Functional respiratory imaging (FRI) for optimizing therapy development and patient care. Expert Rev Respir Med. 2016 Feb;10(2):193-206. doi: 10.1586/17476348.2016.1136216.</citation>
    <PMID>26731531</PMID>
  </reference>
  <reference>
    <citation>van Geffen WH, Hajian B, Vos W, De Backer J, Cahn A, Usmani OS, Van Holsbeke C, Pistolesi M, Kerstjens HA, De Backer W. Functional respiratory imaging: heterogeneity of acute exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2018 May 30;13:1783-1792. doi: 10.2147/COPD.S152463. eCollection 2018.</citation>
    <PMID>29881268</PMID>
  </reference>
  <reference>
    <citation>Bos AC, van Holsbeke C, de Backer JW, van Westreenen M, Janssens HM, Vos WG, Tiddens HA. Patient-specific modeling of regional antibiotic concentration levels in airways of patients with cystic fibrosis: are we dosing high enough? PLoS One. 2015 Mar 3;10(3):e0118454. doi: 10.1371/journal.pone.0118454. eCollection 2015.</citation>
    <PMID>25734630</PMID>
  </reference>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>November 29, 2018</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>January 25, 2019</last_update_submitted>
  <last_update_submitted_qc>January 25, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 28, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Exacerbation</keyword>
  <keyword>Functional respiratory imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchiectasis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03818646
org study id: P02470
nct id: NCT03818646
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Four-week prospective single centre exploratory study in adults with bronchiectasis suffering
      a pulmonary exacerbation (defined as a change in one or more of the following: cough; sputum
      amount; sputum colour; breathlessness; fevers; and malaise).

      The study will recruit ten adult subjects (male and female) who attend the Cambridge Centre
      for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United Kingdom. The
      study will include individuals with a known diagnosis of bronchiectasis suffering a current
      pulmonary exacerbation. Participants seen during their usual clinic review with an
      exacerbation will be invited to participate and enrolled to commence the study that same day
      (day 0). Participants enrolled will undergo clinical review and a series of standard-of-care
      testing including sputum culture, lung function tests and blood analysis. Additional to these
      standard investigations, participants will also undertake a series of patient reported
      outcomes via validated respiratory questionnaires (Quality of Life - Bronchiectasis - QOL-B;
      & Leicester Cough Questionnaire - LCQ) and functional respiratory imaging (FRI). FRI consists
      of low dose high-resolution CT at full inspiration and expiration, combined with
      computational fluid dynamic testing.

      Participants will be treated without delay according to standard of care treatment as per
      current international guidelines. Participants may be treated as either an inpatient or
      outpatient determined by the treating respiratory physician.

      Follow up will occur on day 7, 14 and 28 post enrolment with serial CT imaging on days 0, 14
      and 28. No scheduled follow up testing will be required beyond the day 28 visit, however all
      participants will receive a follow-up phone call at day 35.

      The investigators hypothesize that changes in FRI parameters will be seen pre and post
      exacerbation treatment and will correlate with changes in lung function and patient reported
      outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic response
      in future clinical trials in bronchiectasis.
Four-week prospective single centre exploratory study in adults with bronchiectasis suffering
      a pulmonary exacerbation.

      The study will endeavour to recruit ten adult subjects (male and female) who attend the
      Cambridge Centre for Lung Infection (CCLI) at the Royal Papworth Hospital, Cambridge, United
      Kingdom. The study will include individuals with a known diagnosis of bronchiectasis (defined
      as symptoms of chronic or recurrent bronchial infection with radiological evidence of
      abnormal and permanent dilation of bronchi) not from cystic fibrosis; and a current pulmonary
      exacerbation (defined as a 'deterioration in three or more of the following key symptoms for
      at least 48h: cough; sputum volume and/or consistency; sputum purulence; breathlessness
      and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND that a clinician
      determines a change in bronchiectasis treatment is required).

      In order to maximise subject recruitment and understanding of the study, all CCLI patients
      with bronchiectasis that are known to suffer frequent exacerbations (>2 per year) will be
      sent details of the trial including the Patient Information and Consent Form at the time of
      study commencement, prior to their individual enrolment. Subjects then seen during their
      usual clinic review with a pulmonary exacerbation will be invited to participate and enrolled
      to commence the study that same day (day 0). Participants enrolled will undergo clinical
      review and a series of standard testing including pulmonary function tests and blood
      analysis. Additional to these standard investigations, participants will also undertake a
      series of patient reported outcomes via validated respiratory questionnaires (Quality of Life
      - Bronchiectasis - QOL-B; & Leicester Cough Questionnaire - LCQ) and functional respiratory
      imaging (FRI). FRI consists of low dose high-resolution CT at total lung capacity (TLC) and
      functional residual capacity (FRC), combined with computational fluid dynamic testing (CFD).

      Participants will be treated without delay according to standard usual care as per the
      current European Respiratory Society (ERS) and British Thoracic Society (BTS) Bronchiectasis
      Guidelines. Participants may be treated as either an inpatient or outpatient determined by
      the treating consultant respiratory physician.

      Follow up will occur on day 7, 14 and 28 post enrolment. Participants will undergo clinical
      review and repeat testing according to the below schedule. No scheduled follow up testing
      will be required beyond the day 28 visit, however all participants will receive a follow up
      phone call at day 35.

      Day 0: Initial consultation - presentation with a pulmonary exacerbation

        -  Recruitment, consent and enrolment

        -  History and clinical examination

        -  Bloods (WCC; neutrophil count; CRP)

        -  Pregnancy test (urine dipstick) - if appropriate

        -  Lung function testing (FEV1; FVC; TLC)

        -  Sputum collection

        -  Functional respiratory imaging (HRCT at TLC and FRC; may occur + 48 hours of enrolment)

        -  Patient reported outcomes / questionnaires (QOL-B; LCQ)

        -  Usual treatment commencement (as per current bronchiectasis guidelines)

      Day 7: Mid-treatment follow up (as per usual standard of care)

        -  History and clinical review

        -  Bloods (WCC, neutrophil count; CRP)

      Day 14: End of treatment follow up

        -  History and clinical examination

        -  Bloods (WCC; neutrophil count; CRP)

        -  Pregnancy test (urine dipstick) - if appropriate

        -  Lung function testing (FEV1; FVC; TLC)

        -  Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 14)

        -  Patient reported outcomes / questionnaires (QOL-B; LCQ)

      Day 28: Completion of study testing

        -  History and clinical examination

        -  Bloods (WCC; neutrophil count; CRP)

        -  Pregnancy test (urine dipstick) - if appropriate

        -  Lung function testing (FEV1; FVC; TLC)

        -  Functional respiratory imaging (HRCT at TLC and FRC; may occur +/- 48 hours of day 28)

        -  Patient reported outcomes (QOL-B; LCQ)

      Day 35: Phone call by research team member

      - No scheduled investigations

      No scheduled follow up testing will be required beyond the day 28 visit other then a follow
      up phone call at day 35 (see above).

      The investigators hypothesize that changes in FRI parameters will be seen pre and post
      exacerbation treatment and will correlate well with changes in lung function and patient
      reported outcomes. This will confirm FRI as a surrogate biomarker for assessing therapeutic
      response in future clinical trials in bronchiectasis.
observational model: Cohort
time perspective: Prospective
measure: Airway volume
time frame: Days 0; 14; and 28
description: Change in image based airway volume from FRI
measure: Airway resistance
time frame: Days 0; 14; and 28
description: Change in image based airway resistance from FRI
measure: Lung volume
time frame: Days 0; 14; and 28
description: Change in image based lung volume from FRI
measure: Internal airflow distribution
time frame: Days 0; 14; and 28
description: Change in image based internal airflow distribution from FRI
measure: Airway wall thickness
time frame: Days 0;14; and 28
description: Change in image based airway wall thickness from FRI
measure: Blood vessel density
time frame: Days 0; 14; and 28
description: Change in image based blood vessel density from FRI
measure: Centreline evaluation (airway dimensions over distance into the lung).
time frame: Days 0; 14; and 28
description: Change in image based centreline evaluation (airway dimensions over distance into the lung) from FRI
measure: Lung function
time frame: Days 0; 14; and 28
description: Correlation of FRI to lung function (FEV1)
measure: QOL-B
time frame: Days 0; 14; and 28
description: Correlation of FRI to the QOL-B (Quality of Life Bronchiectasis) questionnaire
measure: LCQ
time frame: Days 0; 14; and 28
description: Correlation of FRI to the LCQ (Leicester Cough Questionnaire) questionnaire
measure: CRP
time frame: Days 0; 14; and 28
description: Correlation of FRI to CRP (C-reactive protein)
intervention type: Diagnostic Test
intervention name: Functional Respiratory Imaging
description: Functional Respiratory Imaging (FRI) is a novel image based functional diagnostic tool that combines high-resolution CT scans (HRCT) at TLC and FRC with flow simulations (computational fluid dynamics - CFD) providing a 3D visualization and quantification of lung structure and function.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
last name: Ian Smith, MD
role: Study Director
affiliation: Royal Papworth Hospital NHS Foundation Trust
last name: Timothy Baird, MBBS
phone: 07706229153
email: tmbaird@gmail.com
last name: Victoria Stoneman, PhD
phone: 0122369865
email: victoria.stoneman@nhs.net
facility: 
contact: 
contact backup: 
country: United Kingdom
citation: Polverino E, Goeminne PC, McDonnell MJ, Aliberti S, Marshall SE, Loebinger MR, Murris M, Canton R, Torres A, Dimakou K, De Soyza A, Hill AT, Haworth CS, Vendrell M, Ringshausen FC, Subotic D, Wilson R, Vilaro J, Stallberg B, Welte T, Rohde G, Blasi F, Elborn S, Almagro M, Timothy A, Ruddy T, Tonia T, Rigau D, Chalmers JD. European Respiratory Society guidelines for the management of adult bronchiectasis. Eur Respir J. 2017 Sep 9;50(3):1700629. doi: 10.1183/13993003.00629-2017. Print 2017 Sep.
PMID: 28889110
citation: Pasteur MC, Bilton D, Hill AT; British Thoracic Society Bronchiectasis non-CF Guideline Group. British Thoracic Society guideline for non-CF bronchiectasis. Thorax. 2010 Jul;65 Suppl 1:i1-58. doi: 10.1136/thx.2010.136119.
PMID: 20627931
citation: Hill AT, Haworth CS, Aliberti S, Barker A, Blasi F, Boersma W, Chalmers JD, De Soyza A, Dimakou K, Elborn JS, Feldman C, Flume P, Goeminne PC, Loebinger MR, Menendez R, Morgan L, Murris M, Polverino E, Quittner A, Ringshausen FC, Tino G, Torres A, Vendrell M, Welte T, Wilson R, Wong C, O'Donnell A, Aksamit T; EMBARC/BRR definitions working group. Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research. Eur Respir J. 2017 Jun 8;49(6):1700051. doi: 10.1183/13993003.00051-2017. Print 2017 Jun.
PMID: 28596426
citation: Koser U, Hill A. What's new in the management of adult bronchiectasis? F1000Res. 2017 Apr 20;6:527. doi: 10.12688/f1000research.10613.1. eCollection 2017.
PMID: 28491293
citation: Quint JK, Millett ER, Joshi M, Navaratnam V, Thomas SL, Hurst JR, Smeeth L, Brown JS. Changes in the incidence, prevalence and mortality of bronchiectasis in the UK from 2004 to 2013: a population-based cohort study. Eur Respir J. 2016 Jan;47(1):186-93. doi: 10.1183/13993003.01033-2015. Epub 2015 Nov 5.
PMID: 26541539
citation: Chang AB, Bell SC, Byrnes CA, Grimwood K, Holmes PW, King PT, Kolbe J, Landau LI, Maguire GP, McDonald MI, Reid DW, Thien FC, Torzillo PJ. Chronic suppurative lung disease and bronchiectasis in children and adults in Australia and New Zealand. Med J Aust. 2010 Sep 20;193(6):356-65. doi: 10.5694/j.1326-5377.2010.tb03949.x.
PMID: 20854242
citation: Vendrell M, de Gracia J, Olveira C, Martinez-Garcia MA, Giron R, Maiz L, Canton R, Coll R, Escribano A, Sole A. [Diagnosis and treatment of bronchiectasis. Spanish Society of Pneumology and Thoracic Surgery]. Arch Bronconeumol. 2008 Nov;44(11):629-40. doi: 10.1157/13128330. Spanish.
PMID: 19007570
citation: Vos W, De Backer J, Poli G, De Volder A, Ghys L, Van Holsbeke C, Vinchurkar S, De Backer L, De Backer W. Novel functional imaging of changes in small airways of patients treated with extrafine beclomethasone/formoterol. Respiration. 2013;86(5):393-401. doi: 10.1159/000347120. Epub 2013 Apr 12.
PMID: 23595105
citation: De Backer LA, Vos W, De Backer J, Van Holsbeke C, Vinchurkar S, De Backer W. The acute effect of budesonide/formoterol in COPD: a multi-slice computed tomography and lung function study. Eur Respir J. 2012 Aug;40(2):298-305. doi: 10.1183/09031936.00072511. Epub 2011 Dec 19.
PMID: 22183484
citation: Hajian B, De Backer J, Vos W, Van Holsbeke C, Clukers J, De Backer W. Functional respiratory imaging (FRI) for optimizing therapy development and patient care. Expert Rev Respir Med. 2016 Feb;10(2):193-206. doi: 10.1586/17476348.2016.1136216.
PMID: 26731531
citation: van Geffen WH, Hajian B, Vos W, De Backer J, Cahn A, Usmani OS, Van Holsbeke C, Pistolesi M, Kerstjens HA, De Backer W. Functional respiratory imaging: heterogeneity of acute exacerbations of COPD. Int J Chron Obstruct Pulmon Dis. 2018 May 30;13:1783-1792. doi: 10.2147/COPD.S152463. eCollection 2018.
PMID: 29881268
citation: Bos AC, van Holsbeke C, de Backer JW, van Westreenen M, Janssens HM, Vos WG, Tiddens HA. Patient-specific modeling of regional antibiotic concentration levels in airways of patients with cystic fibrosis: are we dosing high enough? PLoS One. 2015 Mar 3;10(3):e0118454. doi: 10.1371/journal.pone.0118454. eCollection 2015.
PMID: 25734630
responsible party type: Sponsor
mesh term: Bronchiectasis
sharing ipd: No