Clinimetric Properties of Outcome Measures in Bronchiectasis in the UK

NCT02468271 | Completed

• 1 other identifier: MR/L011263/1
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 7

Brief Summary

There is an increasing demand for researchers and regulatory bodies to use robust outcome measures in clinical trials which have evidence of validity, reliability, and responsiveness. There is currently little agreement on the core clinical endpoints that should be used in bronchiectasis. The importance of improving endpoint outcome measurement is well recognised and groups in other conditions have focused on activities to achieve consensus on a core set of outcomes for clinical trials. The Bronch-UK collaboration has explored the current evidence for clinimetric properties of commonly used outcome measures in bronchiectasis (e.g. forced expiratory volume in one second \[FEV1\], health related quality of life \[HRQoL\], and pulmonary exacerbations). The results of this extensive rigorous literature review of 68 papers clearly demonstrate that whilst there was good evidence for validity for key outcome measures in bronchiectasis there is little information available on their reliability (during periods of clinical stability) or response to treatment (effect sizes). The aim of this study is to explore the clinimetric properties of a range of outcome measures, in order to make recommendations for their use in clinical trials in bronchiectasis.

Conditions

Bronchiectasis

Keywords

Clinimetrics; Lung function; Lung clearance index

Outcome Measures

Primary Outcomes (28)

• Lung clearance index

  Lung clearance index will be measured using the multiple breath inert gas washout (MBW) test. MBW testing measures the functional residual capacity (FRC) and the efficiency with which gas mixes in the lungs. The non-uniformity of ventilation distribution across the lung is often referred to as ventilation inhomogeneity (VI). Measurement of lung clearance index in this study will be performed using the Nitrogen Washout, EXHALYZER D, Ecomedics system. Tests will be performed in triplicate and a minimum of 2 tests with coefficient of variation (CV) \<5% will be required in order to ensure reliable test.

  0 months

• Spirometry

  Spirometry will be performed according to the American Thoracic Society/European Respiratory Society guidelines (Miller et al, 2005). All spirometry manoeuvres will be performed in sitting position whilst wearing nose clips. At least three acceptable manoeuvres will be performed for each time point and the results will meet within-test and between-test criteria for acceptability. A maximum of six manoeuvres will be performed at any time point. The following parameters will be recorded as part of the spirometry assessment: * FEV1 - Forced expiratory volume in one second (L) * FVC - Forced vital capacity (L) * FEV1/FVC (ratio) * FEF25-75 - Forced expiratory flow between 25 and 75% of forced vital capacity (FVC) (L / sec). * Time the participant last administered bronchodilator will be recorded

  0 months

• St Georges Respiratory Questionnaire (SGRQ)

  Is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease and has been validated for use in non-cystic fibrosis bronchiectasis (Wilson et al, 1997). It contains 50 items in two parts. Part 1 the symptoms component is concerned with frequency and severity of symptoms (8 items); Part 2 relates to activities that cause or are limited by breathlessness (16 items) and impact components (26 items) (social functioning, psychological disturbances resulting from airways disease). Part 1 contains several scales and Part 2 has dichotomous (true/false) response except the last question which is a 4-point Likert scale. It takes about 10 minutes to complete the questionnaire. The total score ranges from 0-100, with a higher score indicating a poorer health related quality of life. It assesses the impact of symptoms over the preceding four weeks.

  0 months

• Quality of Life-Bronchiectasis (QOL-B) Questionnaire

  The Quality of Life-Bronchiectasis (QOL-B) questionnaire is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis bronchiectasis. It contains 37 items assessed across eight domains: respiratory symptoms; physical functioning; role; emotional functioning; social functioning; vitality; health perceptions; and, treatment burden. The responses are given in the form of a 4-point Likert scale (except 1 question about sputum colour, which has 6 answer options) with a recall period of 'the last week' (except for the treatment burden and sputum colour questions, which do not specify a recall period). It will take approximately 10-15 minutes to complete this questionnaire. For the outcome, each dimension will be scored separately on a scale of 0 to 100. The questionnaire has demonstrated excellent internal consistency and 2-week test-retest reliability for each scale (Quittner et al, 2014).

  0 months

• EuroQol 5 Dimension (EQ-5D)

  EQ-5D is applicable to a wide range of health conditions and treatments. It provides a simple descriptive profile and a single index value for health status. EQ-5D is primarily designed for self-completion by respondents and is ideally suited for use in postal surveys, in clinics and face-to-face interviews. It is cognitively simple, taking only a few minutes to complete. The EQ-5D essentially consists of 2 pages - the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

  0 months

• Sputum analysis

  A spontaneous sputum sample will be collected at each study visit. Where necessary participants will be instructed to perform cycles of two to three forced expiratory techniques (huffs) followed by coughing to enhance expectoration. All sputum expectorated will be collected in a labelled sterile transparent container and immediately frozen at -80°C until shipment to central lab (Queen's University Belfast). The first priority for sputum processing will be to conduct molecular analysis for sputum microbiology. In addition, where volume allows, processing for sputum inflammatory markers will also be conducted. Where possible a proportion of the sample will be stored at -80oC for future analysis.

  0 months

• Blood analysis

  In total approximately 20mls of blood will be collected from each participant by venepuncture at each visit in accordance with local laboratory procedures in order to analyse white cell count and C-Reactive protein with a 10ml aliquot stored as plasma for inflammatory marker analysis (including but not limited to fibrinogen, TNF alpha, interleukin 6).

  0 months

• Lung clearance index

  Lung clearance index will be measured using the multiple breath inert gas washout (MBW) test. MBW testing measures the functional residual capacity (FRC) and the efficiency with which gas mixes in the lungs. The non-uniformity of ventilation distribution across the lung is often referred to as ventilation inhomogeneity (VI). Measurement of lung clearance index in this study will be performed using the Nitrogen Washout, EXHALYZER D, Ecomedics system. Tests will be performed in triplicate and a minimum of 2 tests with coefficient of variation (CV) \<5% will be required in order to ensure reliable test.

  4 months

• Spirometry

  Spirometry will be performed according to the American Thoracic Society/European Respiratory Society guidelines (Miller et al, 2005). All spirometry manoeuvres will be performed in sitting position whilst wearing nose clips. At least three acceptable manoeuvres will be performed for each time point and the results will meet within-test and between-test criteria for acceptability. A maximum of six manoeuvres will be performed at any time point. The following parameters will be recorded as part of the spirometry assessment: * FEV1 - Forced expiratory volume in one second (L) * FVC - Forced vital capacity (L) * FEV1/FVC (ratio) * FEF25-75 - Forced expiratory flow between 25 and 75% of forced vital capacity (FVC) (L / sec). * Time the participant last administered bronchodilator will be recorded

  4 months

• St Georges Respiratory Questionnaire (SGRQ)

  Is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease and has been validated for use in non-cystic fibrosis bronchiectasis (Wilson et al, 1997). It contains 50 items in two parts. Part 1 the symptoms component is concerned with frequency and severity of symptoms (8 items); Part 2 relates to activities that cause or are limited by breathlessness (16 items) and impact components (26 items) (social functioning, psychological disturbances resulting from airways disease). Part 1 contains several scales and Part 2 has dichotomous (true/false) response except the last question which is a 4-point Likert scale. It takes about 10 minutes to complete the questionnaire. The total score ranges from 0-100, with a higher score indicating a poorer health related quality of life. It assesses the impact of symptoms over the preceding four weeks.

  4 months

• Quality of Life-Bronchiectasis (QOL-B) Questionnaire

  The Quality of Life-Bronchiectasis (QOL-B) questionnaire is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis bronchiectasis. It contains 37 items assessed across eight domains: respiratory symptoms; physical functioning; role; emotional functioning; social functioning; vitality; health perceptions; and, treatment burden. The responses are given in the form of a 4-point Likert scale (except 1 question about sputum colour, which has 6 answer options) with a recall period of 'the last week' (except for the treatment burden and sputum colour questions, which do not specify a recall period). It will take approximately 10-15 minutes to complete this questionnaire. For the outcome, each dimension will be scored separately on a scale of 0 to 100. The questionnaire has demonstrated excellent internal consistency and 2-week test-retest reliability for each scale (Quittner et al, 2014).

  4 months

• EuroQol 5 Dimension (EQ-5D)

  EQ-5D is applicable to a wide range of health conditions and treatments. It provides a simple descriptive profile and a single index value for health status. EQ-5D is primarily designed for self-completion by respondents and is ideally suited for use in postal surveys, in clinics and face-to-face interviews. It is cognitively simple, taking only a few minutes to complete. The EQ-5D essentially consists of 2 pages - the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

  4 months

• Sputum analysis

  A spontaneous sputum sample will be collected at each study visit. Where necessary participants will be instructed to perform cycles of two to three forced expiratory techniques (huffs) followed by coughing to enhance expectoration. All sputum expectorated will be collected in a labelled sterile transparent container and immediately frozen at -80°C until shipment to central lab (Queen's University Belfast). The first priority for sputum processing will be to conduct molecular analysis for sputum microbiology. In addition, where volume allows, processing for sputum inflammatory markers will also be conducted. Where possible a proportion of the sample will be stored at -80oC for future analysis.

  4 months

• Blood analysis

  In total approximately 20mls of blood will be collected from each participant by venepuncture at each visit in accordance with local laboratory procedures in order to analyse white cell count and C-Reactive protein with a 10ml aliquot stored as plasma for inflammatory marker analysis (including but not limited to fibrinogen, TNF alpha, interleukin 6).

  4 months

• Lung clearance index

  Lung clearance index will be measured using the multiple breath inert gas washout (MBW) test. MBW testing measures the functional residual capacity (FRC) and the efficiency with which gas mixes in the lungs. The non-uniformity of ventilation distribution across the lung is often referred to as ventilation inhomogeneity (VI). Measurement of lung clearance index in this study will be performed using the Nitrogen Washout, EXHALYZER D, Ecomedics system. Tests will be performed in triplicate and a minimum of 2 tests with coefficient of variation (CV) \<5% will be required in order to ensure reliable test.

  8 months

• Spirometry

  Spirometry will be performed according to the American Thoracic Society/European Respiratory Society guidelines (Miller et al, 2005). All spirometry manoeuvres will be performed in sitting position whilst wearing nose clips. At least three acceptable manoeuvres will be performed for each time point and the results will meet within-test and between-test criteria for acceptability. A maximum of six manoeuvres will be performed at any time point. The following parameters will be recorded as part of the spirometry assessment: * FEV1 - Forced expiratory volume in one second (L) * FVC - Forced vital capacity (L) * FEV1/FVC (ratio) * FEF25-75 - Forced expiratory flow between 25 and 75% of forced vital capacity (FVC) (L / sec). * Time the participant last administered bronchodilator will be recorded

  8 months

• St Georges Respiratory Questionnaire (SGRQ)

  Is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease and has been validated for use in non-cystic fibrosis bronchiectasis (Wilson et al, 1997). It contains 50 items in two parts. Part 1 the symptoms component is concerned with frequency and severity of symptoms (8 items); Part 2 relates to activities that cause or are limited by breathlessness (16 items) and impact components (26 items) (social functioning, psychological disturbances resulting from airways disease). Part 1 contains several scales and Part 2 has dichotomous (true/false) response except the last question which is a 4-point Likert scale. It takes about 10 minutes to complete the questionnaire. The total score ranges from 0-100, with a higher score indicating a poorer health related quality of life. It assesses the impact of symptoms over the preceding four weeks.

  8 months

• Quality of Life-Bronchiectasis (QOL-B) Questionnaire

  The Quality of Life-Bronchiectasis (QOL-B) questionnaire is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis bronchiectasis. It contains 37 items assessed across eight domains: respiratory symptoms; physical functioning; role; emotional functioning; social functioning; vitality; health perceptions; and, treatment burden. The responses are given in the form of a 4-point Likert scale (except 1 question about sputum colour, which has 6 answer options) with a recall period of 'the last week' (except for the treatment burden and sputum colour questions, which do not specify a recall period). It will take approximately 10-15 minutes to complete this questionnaire. For the outcome, each dimension will be scored separately on a scale of 0 to 100. The questionnaire has demonstrated excellent internal consistency and 2-week test-retest reliability for each scale (Quittner et al, 2014).

  8 months

• EuroQol 5 Dimension (EQ-5D)

  EQ-5D is applicable to a wide range of health conditions and treatments. It provides a simple descriptive profile and a single index value for health status. EQ-5D is primarily designed for self-completion by respondents and is ideally suited for use in postal surveys, in clinics and face-to-face interviews. It is cognitively simple, taking only a few minutes to complete. The EQ-5D essentially consists of 2 pages - the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

  8 months

• Sputum analysis

  A spontaneous sputum sample will be collected at each study visit. Where necessary participants will be instructed to perform cycles of two to three forced expiratory techniques (huffs) followed by coughing to enhance expectoration. All sputum expectorated will be collected in a labelled sterile transparent container and immediately frozen at -80°C until shipment to central lab (Queen's University Belfast). The first priority for sputum processing will be to conduct molecular analysis for sputum microbiology. In addition, where volume allows, processing for sputum inflammatory markers will also be conducted. Where possible a proportion of the sample will be stored at -80oC for future analysis.

  8 months

• Blood analysis

  In total approximately 20mls of blood will be collected from each participant by venepuncture at each visit in accordance with local laboratory procedures in order to analyse white cell count and C-Reactive protein with a 10ml aliquot stored as plasma for inflammatory marker analysis (including but not limited to fibrinogen, TNF alpha, interleukin 6).

  8 months

• Lung clearance index

  Lung clearance index will be measured using the multiple breath inert gas washout (MBW) test. MBW testing measures the functional residual capacity (FRC) and the efficiency with which gas mixes in the lungs. The non-uniformity of ventilation distribution across the lung is often referred to as ventilation inhomogeneity (VI). Measurement of lung clearance index in this study will be performed using the Nitrogen Washout, EXHALYZER D, Ecomedics system. Tests will be performed in triplicate and a minimum of 2 tests with coefficient of variation (CV) \<5% will be required in order to ensure reliable test.

  12 months

• Spirometry

  Spirometry will be performed according to the American Thoracic Society/European Respiratory Society guidelines (Miller et al, 2005). All spirometry manoeuvres will be performed in sitting position whilst wearing nose clips. At least three acceptable manoeuvres will be performed for each time point and the results will meet within-test and between-test criteria for acceptability. A maximum of six manoeuvres will be performed at any time point. The following parameters will be recorded as part of the spirometry assessment: * FEV1 - Forced expiratory volume in one second (L) * FVC - Forced vital capacity (L) * FEV1/FVC (ratio) * FEF25-75 - Forced expiratory flow between 25 and 75% of forced vital capacity (FVC) (L / sec). * Time the participant last administered bronchodilator will be recorded

  12 months

• St Georges Respiratory Questionnaire (SGRQ)

  Is a disease-specific instrument designed to measure impact on overall health, daily life, and perceived well-being in patients with obstructive airways disease and has been validated for use in non-cystic fibrosis bronchiectasis (Wilson et al, 1997). It contains 50 items in two parts. Part 1 the symptoms component is concerned with frequency and severity of symptoms (8 items); Part 2 relates to activities that cause or are limited by breathlessness (16 items) and impact components (26 items) (social functioning, psychological disturbances resulting from airways disease). Part 1 contains several scales and Part 2 has dichotomous (true/false) response except the last question which is a 4-point Likert scale. It takes about 10 minutes to complete the questionnaire. The total score ranges from 0-100, with a higher score indicating a poorer health related quality of life. It assesses the impact of symptoms over the preceding four weeks.

  12 months

• Quality of Life-Bronchiectasis (QOL-B) Questionnaire

  The Quality of Life-Bronchiectasis (QOL-B) questionnaire is a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis bronchiectasis. It contains 37 items assessed across eight domains: respiratory symptoms; physical functioning; role; emotional functioning; social functioning; vitality; health perceptions; and, treatment burden. The responses are given in the form of a 4-point Likert scale (except 1 question about sputum colour, which has 6 answer options) with a recall period of 'the last week' (except for the treatment burden and sputum colour questions, which do not specify a recall period). It will take approximately 10-15 minutes to complete this questionnaire. For the outcome, each dimension will be scored separately on a scale of 0 to 100. The questionnaire has demonstrated excellent internal consistency and 2-week test-retest reliability for each scale (Quittner et al, 2014).

  12 months

• EuroQol 5 Dimension (EQ-5D)

  EQ-5D is applicable to a wide range of health conditions and treatments. It provides a simple descriptive profile and a single index value for health status. EQ-5D is primarily designed for self-completion by respondents and is ideally suited for use in postal surveys, in clinics and face-to-face interviews. It is cognitively simple, taking only a few minutes to complete. The EQ-5D essentially consists of 2 pages - the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises the following 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression.

  12 months

• Sputum analysis

  A spontaneous sputum sample will be collected at each study visit. Where necessary participants will be instructed to perform cycles of two to three forced expiratory techniques (huffs) followed by coughing to enhance expectoration. All sputum expectorated will be collected in a labelled sterile transparent container and immediately frozen at -80°C until shipment to central lab (Queen's University Belfast). The first priority for sputum processing will be to conduct molecular analysis for sputum microbiology. In addition, where volume allows, processing for sputum inflammatory markers will also be conducted. Where possible a proportion of the sample will be stored at -80oC for future analysis.

  12 months

• Blood analysis

  In total approximately 20mls of blood will be collected from each participant by venepuncture at each visit in accordance with local laboratory procedures in order to analyse white cell count and C-Reactive protein with a 10ml aliquot stored as plasma for inflammatory marker analysis (including but not limited to fibrinogen, TNF alpha, interleukin 6).

  12 months

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with bronchiectasis

You may qualify if:

• Proven and documented diagnosis of non-cystic fibrosis idiopathic or post-infectious bronchiectasis by high resolution computerised tomography scan including two or more lobes and dilated airways compatible with bronchiectasis at initial diagnosis.
• Able to perform an acceptable spirometry session - defined as three acceptable or usable efforts per American Thoracic Society/European Respiratory Society criteria.
• Able to perform an acceptable LCI session.
• Participants must be able and willing to read and comprehend written instructions, and comprehend and complete the questionnaires required by the protocol
• After full explanation, participants must have signed an informed consent form indicating that they understand the purpose of and the procedures required for the study and are willing to participate in the study.
• Participant 18 years of age or above.

You may not qualify if:

• Women who are pregnant, lactating or in whom pregnancy cannot be excluded.
• Anyone who is participating in or has participated in a clinical trial of an investigational medical product (IMP) within four weeks of first visit.
• Any clinical or genetic features of cystic fibrosis.

Sponsors & Collaborators

• Queen's University, Belfast: lead
• Belfast Health and Social Care Trust: collaborator
• South Eastern Health and Social Care Trust: collaborator
• Royal Brompton & Harefield NHS Foundation Trust: collaborator
• NHS Lothian: collaborator
• Papworth Hospital NHS Foundation Trust: collaborator
• NHS Tayside: collaborator
• University Hospital Southampton NHS Foundation Trust: collaborator
• Cardiff and Vale University Health Board: collaborator
• Medical Research Council: collaborator

Study Sites (7)

Papworth Hospital, NHS Foundation Trust

Cambridge, England, CB23 3RE, United Kingdom

Location

Royal Brompton and Harefield Trust

London, England, SW3 6NP, United Kingdom

Location

University Hospital Southampton, NHS Foundation Trust

Southampton, England, SO16 6YD, United Kingdom

Location

Belfast Health and Social Care Trust

Belfast, Northern Ireland, United Kingdom

Location

NHS Tayside

Dundee, Scotland, DD1 9SY, United Kingdom

Location

NHS Lothian

Edinburgh, Scotland, EH16 4SA, United Kingdom

Location

University Hospitals of Morecambe Bay NHS Foundation Trust

Lancaster, United Kingdom

Location

Related Publications (1)

• O'Neill K, Lakshmipathy GR, Neely C, Cosgrove D, Ferguson K, McLeese R, Hill AT, Loebinger MR, Carroll M, Chalmers JD, Gatheral T, Johnson C, De Soyza A, Hurst JR, Bradbury I, Elborn JS, Bradley JM. Multiple-Breath Washout Outcome Measures in Adults with Bronchiectasis. Ann Am Thorac Soc. 2022 Sep;19(9):1489-1497. doi: 10.1513/AnnalsATS.202006-584OC.

  PMID: 35451922 DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood plasma and sputum specimens

MeSH Terms

Conditions

Bronchiectasis

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases

Study Officials

• Judy M Bradley, PhD

  Belfast Health and Social Care Trust

  PRINCIPAL INVESTIGATOR

• Michael Loebinger, MD

  Royal Brompton and Harefield Trust

  PRINCIPAL INVESTIGATOR

• Stephen Rowan, MD

  South Eastern Health and Social Care Trust

  PRINCIPAL INVESTIGATOR

• Adam Hill, MD

  NHS Lothian

  PRINCIPAL INVESTIGATOR

• Charles Haworth, MD

  Papworth Hospital NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• James Chalmers, MD

  NHS Tayside

  PRINCIPAL INVESTIGATOR

• Mary Carroll, MD

  University Hospital Southampton NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

• James Duckers, MD

  Cardiff and Vale University Health Board

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Respiratory Medicine/Consultant Physician (Respiratory Medicine)

Study Record Dates

• First Submitted: June 3, 2015
• First Posted: June 10, 2015
• Study Start: October 1, 2015
• Primary Completion: May 31, 2018
• Study Completion: July 31, 2019
• Last Updated: July 8, 2021

Record last verified: 2021-07

Locations

GB (7)