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The Idealized Lung Clearance Index: tuning in to the silent years of cystic fibrosis

Lead Research Organisation: Imperial College London
Department Name: National Heart and Lung Institute

Abstract

Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.

Publications

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Dobra R (2025) Utility and interpretation of multiple breath washout in children with cystic fibrosis in Archives of disease in childhood - Education & practice edition

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Robinson PD (2022) Impact of cross-sensitivity error correction on representative nitrogen-based multiple breath washout data from clinical trials. in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

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Sandhu D (2023) Computed cardiopulmonography and the idealized lung clearance index, iLCI2.5, in early-stage cystic fibrosis. in Journal of applied physiology (Bethesda, Md. : 1985)

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Short C (2020) Utility of lung clearance index in CF: What we know, what we don't know and musings on how to bridge the gap. in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

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Short C (2022) A Short extension to multiple breath washout provides additional signal of distal airway disease in people with CF: A pilot study. in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society

 
Description Adult CF patients plus healthy controls were initially tested on the iLCI device designed for adults plus the Exhalyzer D device. A paediatric iLCI device is currently being built and will be ready to use during 2022 to investigate how the novel gas analyser can measure the paediatric population.

10 adult CF subjects (5 female) plus 14 healthy controls (7 female), age range 19-54 yrs performed both the novel iLCI test plus the standardised MBW test using the Exhalyzer D device a minimum of 2 times at 2 separate visits.

Device comparison revealed significant differences in FRC measurement likely attributable to device algorithms and design differences. However, there was good inter-repeat FRC reproducibility within guideline recommendations. Additionally, in line with current literature, LCI was a sensitive indicator of disease status.
Exploitation Route Further LGA validation and standardisation work is warranted.
Sectors Healthcare

 
Description feedback on lung function measurement techniques and their acceptability allowed the shaping of a new pre-doctoral fellowship application (MA) from Brompton Hospital, and has helped in recruitment
First Year Of Impact 2023
Sector Healthcare
Impact Types Societal

 
Title Multibreath washout with the Short extension (MBWShX) 
Description a novel adaptation to MBW to enhance sensitivity for lower airway disease by revealing additional signal from gas trapping 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2022 
Provided To Others? Yes  
Impact 1. incorporated into study protocol for the Enhance real-world, observational study 2. built into study protocol for clinimetrics of OE-MRI 3. several other sites have also since adopted the protocol 
 
Title Oxygen Inhanced MRI 
Description non-radiation based technique to assess lower airways disease 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2021 
Provided To Others? No  
Impact 1. manuscripts currently in prep 2. several conference abstracts 
 
Title Standardised lung clearance index 
Description sensitive measure of airways disease; increasingly adopted as an outcome measure in clinical trials. Standardisation, training, certification and quality-controlled over-reading services led by my team as the LCI Core Facility on behalf of the European CF Clinical Trials Network. 
Type Of Material Physiological assessment or outcome measure 
Year Produced 2018 
Provided To Others? Yes  
Impact several novel CF treatments received license extensions into the paediatric age range based on data provided from trials using LCI as the primary outcome 
URL https://www.ecfs.eu/ctn/lci/lci-core-facility-definition
 
Title Update of project The idealised LCI (i-LCI): tuning in on the 'silent years' of paediatric CF 
Description To determine the range and reproducibility of non-invasive indices of ventilation inhomogeneity in people with CF using a novel laser gas analyser (LGA) recently developed that aims to accurately quantify ventilation inhomogeneity to a higher degree than previously possible. The indices measured are to be compared with those measured in normal volunteers. The LGA will be compared to a validated multiple breath washout (MBW) test which also measures ventilation inhomogeneity in the lungs Adult CF patients plus healthy controls were initially tested on the iLCI device designed for adults plus the Exhalyzer D device. A paediatric iLCI device is currently being built and will be ready to use during 2022 to investigate how the novel gas analyser can measure the paediatric population. 10 adult CF subjects (5 female) plus 14 healthy controls (7 female), age range 19-54 yrs performed both the novel iLCI test plus the standardised MBW test using the Exhalyzer D device a minimum of 2 times at 2 separate visits. 
Type Of Material Database/Collection of data 
Year Produced 2021 
Provided To Others? No  
Impact Device comparison revealed significant differences in FRC measurement likely attributable to device algorithms and design differences. However, there was good inter-repeat FRC reproducibility within guideline recommendations. Additionally, in line with current literature, LCI was a sensitive indicator of disease status. Further LGA validation and standardisation work is warranted. 
 
Description Bioxydyn 
Organisation Bioxydn
Country United Kingdom 
Sector Private 
PI Contribution Bespoke analysis of OE-MRI lung scans and aid in interpretation of data
Collaborator Contribution Expertise in novel outcome measure Contributed to presentations and publications
Impact Conference presentations and publications: see listings
Start Year 2021
 
Description European Lung Clearance Index Core Facility 
Organisation European Cystic Fibrosis Society (ECFS)
Country Denmark 
Sector Charity/Non Profit 
PI Contribution Direct the LCI Core Facility Train, certify and standardise operators across European CF clinical trial sites; over-reading and quality assurance service to clinical trial sponsors
Collaborator Contribution Close partnership with counterparts in N. America and Australasia to provide global services
Impact multiple papers listed in publications
Start Year 2021
 
Description European Lung Clearance Index Core Facility 
Organisation The Hospital for Sick Children (SickKids)
Department MICe Toronto
Country Canada 
Sector Academic/University 
PI Contribution Direct the LCI Core Facility Train, certify and standardise operators across European CF clinical trial sites; over-reading and quality assurance service to clinical trial sponsors
Collaborator Contribution Close partnership with counterparts in N. America and Australasia to provide global services
Impact multiple papers listed in publications
Start Year 2021
 
Description Oxford LGA Group 
Organisation University of Oxford
Department Department of Physiology, Anatomy and Genetics
Country United Kingdom 
Sector Academic/University 
PI Contribution developing more accurate technology to detect distal lung disease in adults and children with a variety of lung conditions
Collaborator Contribution technical expertise and manufacturing of the LGA device
Impact linked publications
Start Year 2020
 
Title The Clinimetric study 
Description Monitoring patients with chronic, inflammatory airways disease particularly in the early stages is hampered by the relative insensitivity of current outcome measures to detect subtle changes. Multiple breath washout is a potential sensitive test that is a useful readout of disease at these early stages but it lacks standardisation and knowledge of variability with reference to standard lung function measures. This is a Cross sectional and longitudinal observation study. The hypothesis is that multiple breath washout-derived indices will provide a robust signal of gas mixing inhomogeneity, correlating with conventional measures of airway disease severity. Multiple breath washout performed on different devices will generate indices which correlate but differ in value. 
Type Diagnostic Tool - Non-Imaging
Current Stage Of Development Late clinical evaluation
Year Development Stage Completed 2022
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Ongoing. 
 
Description A talk at European Cystic Fibrosis Society Conference, Rotterdam, Netherlands, June,2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a talk on 'Impact of corrected Multiple Breath nitrogen Washout (MBW) software on assessment of under/unventilated lung units (UVLU) with the MBWShX'
Year(s) Of Engagement Activity 2022
 
Description Conference talk/poster 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Conference presentation/poster at Physiology conference. Abstract:

Utilising Computational Methods to Determine an Idealised Lung Clearance Index. Sandhu D, Redmond J, Smith NMJ, Short C, Saunders CJ, Couper JH, Fullerton CJ, Richmond G, Talbot NP, Davies JC, Ritchie GAD, Robbins PA
Year(s) Of Engagement Activity 2022
 
Description European Cystic Fibrosis Society Conference, Glasgow, UK, June 2024 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a talk on 'Assessing pulmonary exacerbations (PEx) in the post-modulator era with oxygen enhanced (OE-) MRI and multiple breath washout with short extension (MBWShX).'
Year(s) Of Engagement Activity 2024
 
Description North American Cystic Fibrosis conference, Boston, USA, September 2024 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a talk on 'Silent progression of lung disease in people receiving elexacaftor/tezacaftor/ivacaftor therapy revealed by oxygen-enhanced MRI'
Year(s) Of Engagement Activity 2024
 
Description Presentation at the North American CF Conference 2021 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short presented at the NACF Conference 2021 at workshop 'Multiple Breath Washout: Ready for Prime Time?'

The presentation reached a wide target audience and generated further questions and discussion.
Year(s) Of Engagement Activity 2021
 
Description Symposium honouring Bonnie Ramsey 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Professor Jane Davies gave a symposium of her career research to date in honour of Bonnie Ramsey.
Year(s) Of Engagement Activity 2022
 
Description Talk at CF Clinical Trials Conference 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Professor Jane Davies presented at the Cystic Fibrosis CF Trials Conference in 2022. The title of her talk was Trials in infants and pre-school children.
Year(s) Of Engagement Activity 2022
 
Description Talk at European Cystic Fibrosis Society Conference, Glasgow, UK, June 2024 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a presentation on 'Multiple breath washout- it's not just for kids?'
Year(s) Of Engagement Activity 2024
 
Description Talk at Kings- John Price Conference, paediatric respiratory, London, UK, April 2024 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a talk on 'Imaging Respiratory Physiology'
Year(s) Of Engagement Activity 2024
 
Description Talk at North American Cystic Fibrosis Conference, Philadelphia , USA, November 2022 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a talk on 'Oxygen-enhanced magnetic resonance imaging and multiple-breath washout with or without Short extension as novel functional assessments of cystic fibrosis lung health'
Year(s) Of Engagement Activity 2022
 
Description Talk at North American Cystic Fibrosis Conference, Phoenix, USA, November 2023 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a talk on 'Oxygen-enhanced MRI and multiple-breath washout with short extension are highly sensitive to elexacaftor-tezacaftor-ivacaftor initiation in a group with preserved pulmonary function'
Year(s) Of Engagement Activity 2024
 
Description Talk at Royal Society of Medicine Paediatric Respiratory and ENT Symposium 2022 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Professor Jane Davies presented at the Royal Society of Medicine Paediatric Respiratory and ENT Symposium 2022. The title of her talk was 'Cystic fibrosis: What's new?'
Year(s) Of Engagement Activity 2022
 
Description Talk at the European Cystic Fibrosis Society Conference, Vienna, Austria, June 2023 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Chris Short gave a talk on 'The volume of trapped air (VTA) from multiple breath washout (MBW) substantially underestimates the extent of trapped air (TA) demonstrated with spirometry-controlled computed tomography'
Year(s) Of Engagement Activity 2023
 
Description Talk at the Royal Society of Medicine, November 2024 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Chris Short presented a talk on 'Progress and potential pitfalls: Where are we now with CF lung disease?'
Year(s) Of Engagement Activity 2024