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Exercise testing, exercise training, respiratory disease, review
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Bowhay B, Williams CA, Gibbons MA et al. Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2024, 4:51 (https://doi.org/10.3310/nihropenres.13706.1)
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Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol
[version 1; peer review: 1 approved, 1 approved with reservations]
PUBLISHED 17 Sep 2024
OPEN PEER REVIEW
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Abstract
Plain Language Summary
Corresponding author:
Owen W Tomlinson
Competing interests:
No competing interests were disclosed.
Grant information:
This project is funded by the National Institute for Health and Care Research (NIHR) Exeter Biomedical Research Centre (BRC) (Grant reference number NIHR203320). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care. The funder has had no role in the design of this research.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Copyright:
© 2024 Bowhay B et al.
This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
How to cite: Bowhay B, Williams CA, Gibbons MA et al. Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2024, 4:51 (https://doi.org/10.3310/nihropenres.13706.1)
First published: 17 Sep 2024, 4:51 (https://doi.org/10.3310/nihropenres.13706.1)
Latest published: 04 Jul 2025, 4:51 (https://doi.org/10.3310/nihropenres.13706.2)
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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of this article available.
Introduction
Rationale
Interstitial lung disease (ILD) is a heterogeneous group of approximately 200 chronic lung conditions, which are associated with lung parenchymal fibrosis and/or interstitial inflammation1. Consequently, respiratory failure is the primary cause of mortality in people with ILD2. According to 2017 figures, the median age-standardised incidence rates (ASIR) of ILD in United Kingdom (UK) men was 10.92 per 100,000, and 6.7 per 100,000 for UK women3. From the period between 2001 and 2017, the ASIR has risen by 21.27% for UK men and 25.39% for UK women3. In addition, the median age-standardised death rates indicated that ILD related mortality was 2.04 (IQR 1.13–2.71) per 100 000 population for men and 1.02 (0.68–1.37) per 100,000 population for women3. Unfortunately, ILD are chronic conditions that cannot be cured, therefore maintaining lung function, general function, and quality of life (QoL) of people with ILD (pwILD) is a key focus for patients and clinicians alike4.
A joint statement produced by the American Thoracic Society (ATS) and European Respiratory Society (ERS) recommends regular exercise training and pulmonary rehabilitation (PR) to enhance cardiorespiratory health5, whereby exercise is acknowledged as a planned, structured, and repetitive form of physical activity which is performed for the improvement or maintenance of physical fitness6. International guidelines highlight that exercise training is regarded as a cornerstone of PR5. However, individual patient responses to exercise training are highly variable and a ‘one size fits all’ training approach does not benefit every pwILD, thus placing the onus on to effective PR design.
Pulmonary rehabilitation is an intervention which is developed following comprehensive diagnostic evaluation by a multidisciplinary team; the aim is to utilise these assessment outcomes to establish a patient-centred therapeutic program which consists of exercise and patient education to support behaviour change, but also improve physical and mental health for people with chronic respiratory diseases6. Moreover, in support of PR, the British Thoracic Society (BTS) explicitly recommends that PR should be offered to symptomatic individuals with chronic respiratory disease, including pwILD7.
A 2021 Cochrane review of PR in pwILD has found “moderate-certainty” evidence associated with enhanced functional exercise capacity (measured by the six-minute walk test) and “low-certainty” evidence that suggests that PR in pwILD may improve maximum exercise capacity (WRpeak) and dyspnoea8. These benefits are postulated to be sustained in the longer term and there is also no evidence that adverse events were found in the pwILD8. Therefore, PR is not only useful for enhancing QoL in pwILD, but functional capacity as well.
Individual responses to training may be linked to pathophysiological impairments that occur across different ILD subgroups, and the extent and rate of such progression is highly variable8,9. Restrictions in exercise tolerance may be due to ventilation/perfusion (V/Q) mismatch, which occurs when either airflow or blood flow in the lungs is impaired and abnormal ventilatory mechanics can occur at different points for pwILD10. Therefore, pwILD may often require more ventilatory load and capacity to sustain exercise, whilst also attempting to combat muscle fatigue, commonly because of poor blood oxygenation11; this may lower ATP, increase lactate and cause a rise in VCO211. Gas exchange insufficiency, central haemodynamic impairment and muscle deconditioning are unique in pwILD, therefore a personalised approach to PR may provide enhanced outcomes by accounting for these differing mechanisms of exercise intolerance12.
The BTS Clinical Statement on pulmonary rehabilitation states that a validated exercise test should be conducted as a core component of PR programmes to inform individualised prescription7. Personalised exercise via CPET has been earmarked as the future of PR, whereby a comprehensive evaluation of pathophysiological systems serves to indicate a pwILD’s response to exercise, and therefore these values could support effective PR programming13. However no personalised PR guidelines have been developed specifically for pwILD at present11,14, despite them being available for other chronic respiratory diseases such as COPD12.
Recent evidence suggests that personalised, moderate-intensity continuous aerobic exercise (at 60% maximum heart rate; HRmax) and high-intensity interval training (at 80% HRmax) is beneficial in pwILD for improving WRpeak and dysponea15. Moreover, individualised exercise training can enhance antioxidant buffering capacity in people with idiopathic pulmonary fibrosis (IPF), which may corelate with enhanced muscle fatigue resilience16. This clearly demonstrates the functional and physiological value PR can have when using personalised approaches.
Training methods which are tailored to the cardiovascular, pulmonary, and peripheral muscle metabolic limitations of the individual patient are the cornerstone of personalised PR12. For such PR programmes to be effective, the implementation of the fundamental principles of exercise training (e.g. specificity, frequency, intensity, timing, type, overload, progression, adaptation, and reversibility) into clinical practice should be followed5, and it is these principles that can be personalised – however, how this is currently done in pwILD is not clear.
Traditionally, within ILD management, the six-minute walk test (6MWT) has been widely used as a functional outcome17–19, because of ease of use and standardisation. However, the 6MWT cannot highlight the changes in physiological mechanisms which limit exercise tolerance, and safety issues such as ischemia or arrhythmias cannot be easily detected. In addition, the 6MWT outcome lacks the precision required for personalised PR development11.
In contrast to the 6WMT, cardiopulmonary exercise testing (CPET) is now the gold standard for the causal evaluation of exercise intolerance in patients with long term pulmonary conditions20. Several studies have demonstrated that CPET is a safe and valuable method for the comprehensive evaluation of cardiac, pulmonary and muscle function, whilst also recognising physiological factors limiting exercise such as dyspnoea21. Over the last decade, it has been evident that PR programmes are routinely utilising CPET as a more sophisticated, comprehensive, and definitive method to assess pre and post-intervention outcomes16,22,23. Evaluation of CPET outcomes such as VO2peak and heart rate can inform the tailoring of explicit, personalised exercises for the patient, which thresholds to utilise, and how to progress intensity and resistance4,23; adhering to principles of exercise training.
There is therefore a need to develop a valid, reliable, and consistent method for personalising PR based on CPET outcome measures. In clinical practice, several metrics could be used (e.g. VO2peak or heart rate), but it is unclear what metrics are currently used and how they are implemented. This systematic review will seek to address this, with the intention of developing a focus on the most appropriate cardiorespiratory mean variables and intensities for tailoring individualised PR for pwILD.
Objectives
This review aims to identify which cardiorespiratory variables, and intensities, derived from CPET can be used to personalise PR for pwILD. Where possible, these outcomes will be compared against a control. All quantitative study designs will be included. Only full-text, original articles will be included. All outcome measures will compare baseline assessment to that at the end of the exercise training period. In addition to any longer-term follow-up reported by the authors of the included studies.
Methods
Patient and Public Involvement
Pulmonary Rehabilitation was part of the top ten research priorities set out by the James Lind Alliance Priority Setting Partnership24; a steering group of patients, carers, and healthcare professionals. The current SR will work with the Exeter Patients in Collaboration for Pulmonary Fibrosis Research (EPIC PF) group to interpret and disseminate the results.
Eligibility criteria
The PRISMA-P has been used to guide this systematic review protocol24. Eligibility for inclusion in this review include the following elements of the PICOS framework (Table 1); conference abstracts will be excluded; articles which are not published in English, unless an English translation is available, will be excluded; there will be no restriction on publication date, or location.
Table 1. Inclusion and exclusion criteria.
Population
People of all ages, sexes and ethnic groups that have been diagnosed with any ILD subtype.
Intervention
Individualised pulmonary rehabilitation or exercise programmes, which have been personalised using CPET derived values. Articles that only describe ‘physical activity’ interventions, and not ‘exercise training’ or ‘pulmonary rehabilitation’, will be excluded. Single or acute bouts of exercise will not classify as exercise training.
Comparison
Outcomes of PR regimens against group baselines, and where possible, against control groups as well will be compared.
Outcomes
Outcomes will be derived from CPET values. It is anticipated this may include, but will not be limited to:
a) Peak volume of oxygen consumption (VO2peak), the gold-standard measure of cardiorespiratory fitness, expressed as mL.kg-1.min-1 or L.min-1;
b) Peak work rate (WRpeak), expressed in watts (W), the maximum achieved work rate during an incremental CPET;
c) Volume of oxygen consumption at anaerobic threshold (VO2-AT) expressed as mL.kg-1.min-1, L.min-1, or %VO2peak;
d) Heart Rate, expressed as the number of times the heart beats per minute (beats·min-1);
e) Rate of perceived exertion (RPE) that can be measured on a 0–10 RPE scale or a Borg 6–20 scale.
Study designs
All quantitative study designs will be included; for instance, RCT’s, single cohort studies and case studies. Only full-text, original articles will be included.
Information sources
Electronic searches will be conducted using Ovid® (Ovid Technologies Inc., New York, NY, USA), incorporating Ovid MEDLINE® (US National Library of Medicine, Bethesda, MD, USA), Ovid EmbaseTM (Elsevier Inc., Philadelphia, PA, USA), EBSCO databases CINAHL Ultimate and SPORTDiscus (EBSCO Information Services, MA, USA) plus CENTRAL and the Cochrane Library (John Wiley and Sons Ltd, Hoboken, NJ, USA) will all be searched up to January 2024.
Search strategy
The search strategy is available at OSFHOME: Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol: Search_Strategy.docx. Available at: https://doi.org/10.17605/OSF.IO/43N29.
Following completion of the Ovid MEDLINE® strategy, specific syntax and subject headings will be created for all Ovid, EBSCO and Cochrane database searches.
Study records
Data management
Independent data extraction will take place using data extraction forms developed for the study. Data to be extracted and included in the table of ‘overview of included studies’ will include author and year, purpose of study, setting, country, sample size, participant demographic and clinical diagnosis, treatment types, study design, primary outcome measures, losses and exclusion of participants. EndNote© 2025 (Clarivate, London, UK) will be utilised for reference storage.
Selection process
A screen of the initial search results will be performed by title and abstract for eligibility and inclusion. The search results will be checked by a single reviewer (BB), then an experienced second reviewer will perform a check of 10%, then a third reviewer (TBC) will check for differences and achieve a consensus through discussion with the reviewers.
Data collection process
Data will be collected by a single reviewer (BB) using a data extraction form. A random double data extraction (10%) check will then be performed by a second reviewer (TBC). Any differences will be highlighted by a third reviewer (TBC), then a discussion with the reviewers will be performed to achieve a consensus. Any missing data will be requested from the study authors, before removal from the review, if no reply is provided.
Data items
The PICOS inclusion and exclusion criteria (Table 1) will be used by (BB and TBC) to as a framework to collate and review all the full text articles which are potentially relevant for the review. If disagreement occurs between the reviewers, then a discussion with the third reviewer (TBC) will be conducted to reach consensus.
Outcomes and prioritization
Outcomes will be derived from CPET values. Potentially this may include:
Primary outcomes
Peak volume of oxygen consumption (VO2peak), the gold-standard measure of cardiorespiratory fitness, expressed as mL.kg-1.min-1 or L.min-1;
Peak work rate (WRpeak), expressed in watts (W), the maximum achieved work rate during an incremental CPET;
Volume of oxygen consumption at anaerobic threshold (VO2-AT) expressed as mL.kg-1.min-1, L.min-1, or %VO2peak;
Heart Rate, expressed as the number of times the heart beats per minute (b·min-1);
Rate of perceived exertion (RPE) that can be measured on a 0–10 RPE scale or a Borg 6–20 scale.
We anticipate that the main outcomes will be displayed in a summary of findings table using GRADEpro26.
Risk of bias in individual studies
Quality assessment of the included studies will be performed by two reviewers (BB; TBC) using the Critical Appraisal Skills Program (CASP) checklists for single cohort studies27 and randomised controlled studies28, thus accounting for the anticipated variances in study designs for this review. A third reviewer (TBC) would then confirm the results and lead the discussion towards consensus of the included studies. The CASP checklist items are to be marked “Y” (Yes) if well described, “N” (No) if inadequate, and unclear items with a “U” (Unclear).
Data
Synthesis
All analyses will be performed using Review Manager29.
a. Data pertaining to variables used to prescribe, and how, will be narratively discussed and analysed using frequency statistics.
b. Where possible, analyses of between groups to receive personalised PR against controls will be undertaken. If no mean change and standard deviation of change are reported, then a corresponding author data request will be made. If no data or response is gained, then results will be calculated using methods in the Cochrane Handbook30. The summary effect size is estimated by using mean difference (MD) with 95% CI for continuous outcomes.
Standardized mean differences (SMD) will be utilised instead, if different methods or scales are used for the outcome. Heterogeneity will be estimated from the MD and SMD via a χ2 test. In addition, the I2 test will also be utilised to add extra analysis. Signifficant heterogeneity will be reached at P<0.1 in the χ2 test and >50% in the I2 test. A random-effect or fixed-effect model will be selected to merge the outcomes.
Meta-bias(es)
Reporting bias would be explored by examining if the protocol was published prior to study participant recruitment. A Clinical Trial Register at the International Clinical Trials Registry Platform of the World Health Organisation screen would also be conducted. Selective outcome reporting bias would be evaluated by comparing the fixed effect estimate against the random effects model to examine the potential for sample bias. If this occurs, then a random effects estimate would be advantageous, when compared against a fixed effect estimate. Reporting bias could also be examined by funnel plots if ≥10 studies are identified.
Discussion
The current systematic review has been developed to explore how CPET-derived outcomes can help support individualised PR design for pwILD. At present, there are no systematic reviews that provide insights into how CPET values can be utilised for individualised exercise and PR programming in pwILD.
The most relevant databases have been selected specifically for this systematic review, and in addition, all study designs have been included, which although a strength of this systematic review, may add complexity when looking to interpret the results across the board. Thus, due to the potential variability in both the condition subgroups within ILD and how PR interventions may be designed, it is possible that separate analyses may be required.
Commonly used CPET variables will be collated from the included articles, following the comprehensive database searches. This strategy will help to indicate the most appropriate cardiorespiratory values to tailor individualised programmes for pwILD.
Our overall aim following this review is to develop a valid, reliable, and consistent method for personalising PR based on CPET outcome measures to address the current evidence gap. Several metrics may be used (e.g. VO2peak, heart rate), but it is unclear how and why they are utilised in clinical practice to achieve optimal outcomes for pwILD; therefore, this systematic review aims to fill this research gap.
Subject index terms
Interstitial Lung Diseases; Pulmonary Rehabilitation; Exercise; CPET; Treatment Outcomes; Training; Physiotherapy; Systematic Review.
List of abbreviations
CPET: Cardiopulmonary Exercise Testing
CPETt: Cardiopulmonary Exercise Testing, performed on a treadmill
ILD: Interstitial Lung disease
UK: United Kingdom
PR: Pulmonary Rehabilitation
VO2peak: Peak volume of oxygen consumption
WRpeak: Peak work rate
VO2-AT: Volume of oxygen consumption at anaerobic threshold
RER: Respiratory exchange ratio
VE: Minute ventilation
VE/VCO2 slope
AT: Anaerobic Threshold
HR: Heart Rate
RPE: Rating of perceived exertion
ATS: American Thoracic Society
ERS: European Respiratory Society
BTS: British Thoracic Society
pwILD: people with interstitial lung disease
CASP: Critical Appraisal Skills Program
GRADE: Grading of Recommendations, Assessment, Development, and Evaluations
HRR: Heart Rate Reserve
COPD: Chronic Obstructive Pulmonary Disease
HFA-PEFF: The Heart Failure Association (HFA)-PEFF score
6MWT: Six-minute walk test
6MWD: Six-minute walk distance
ICT: Incremental cycle test
RCT: Randomised controlled trial
Amendments
In the event of protocol amendments, the date of each amendment will be accompanied by a description of the change and the rationale.
Ethics approval and consent to participate
Not applicable
Consent for publication
Not applicable
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Bowhay B, Williams CA, Gibbons MA et al. Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2024, 4:51 (https://doi.org/10.3310/nihropenres.13706.1)
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Harrison S. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2024, 4:51 (https://doi.org/10.3310/nihropenres.14882.r33312)
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Reviewer Report 16 Dec 2024
Samantha Harrison,
Teesside University,, Middlesbrough, UK
Approved with Reservations
VIEWS 19
The manuscript reports a systematic review protocol to identify which variables derived from undertaking a CPET are best used to personalise exercise prescription in pulmonary rehabilitation.
Overall, this is a well presented manuscript and the proposed review ... Continue reading
Overall, this is a well presented manuscript and the proposed review ... Continue reading
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Harrison S. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2024, 4:51 (https://doi.org/10.3310/nihropenres.14882.r33312)
The direct URL for this report is:
https://openresearch.nihr.ac.uk/articles/4-51/v1#referee-response-33312
https://openresearch.nihr.ac.uk/articles/4-51/v1#referee-response-33312
NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article.
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Daynes E. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2024, 4:51 (https://doi.org/10.3310/nihropenres.14882.r32957)
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https://openresearch.nihr.ac.uk/articles/4-51/v1#referee-response-32957
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Reviewer Report 15 Oct 2024
Approved
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Thomlinson and colleagues report a protocol for a systematic review to explore the potential for individualising Pulmonary Rehabilitation (PR) in those with Interstitial Lung Disease (ILD), or more specifically, individualizing the aerobic exercise component of PR. They make a strong
... Continue reading
CITE
HOW TO CITE THIS REPORT
Daynes E. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 1; peer review: 1 approved, 1 approved with reservations]. NIHR Open Res 2024, 4:51 (https://doi.org/10.3310/nihropenres.14882.r32957)
The direct URL for this report is:
https://openresearch.nihr.ac.uk/articles/4-51/v1#referee-response-32957
https://openresearch.nihr.ac.uk/articles/4-51/v1#referee-response-32957
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Author Response 17 Jul 2025Owen W Tomlinson, Clinical & Biomedical Sciences, University of Exeter, Exeter, UK17 Jul 2025Author ResponseExploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol
Reviewer #1: Acceptance
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Reviewer #1: Acceptance
Response: Thank ... Continue reading Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol
Reviewer #1: Acceptance
Response: Thank you for your very comprehensive reviewer reports. We are glad the review protocol aligns with the current research priorities.
Historically, people with ILD were not always included in PR programmes, but it was recommended in the 2023 BTS clinical statement to include those with ILD in PR, which is now captured in national audits (i.e. National Respiratory Audit Programme), (https://www.nrap.org.uk/).
Response: We agree, pulmonary rehabilitation (PR) for people with ILD is in the formative stages and we appreciate that there are challenges with service development. The recent BTS clinical statement for PR is an excellent step forward to evolve practice, alongside the National Respiratory Audit Programme which will help to drive forward the quality of ILD services. Therefore, to enhance the rationale, we have added references to the BTS PR Statement and the NRAP (lines 119-123).
Reporting of interventions, particularly where there is a degree of personalisation or tailoring is often poor or difficult to interpret, and similarly, the reporting and combining of results may be challenging.
Response: Reporting how interventions are delivered will be top of the agenda for the review. The Consensus on Exercise Reporting Template (CERT) assessment form will be used to check the reporting of exercise programme domains (Slade et al. 2016). This will support researchers to develop effective exercise interventions, that are well constructed and reproduceable. Manuscript changed: added section 3.6 (lines 294-298).
There is a degree of personalisation in PR programmes, typically prescribed by the Incremental Shuttle Walking Test or 6 Minute Walk Test (the latter highlighted by authors), and despite personalisation/tailoring predominantly influencing the duration and absolute intensity of the aerobic exercise component, this would still be considered personalisation.
Response: Tailoring PR and exercise will be on a spectrum, and can be derived from multiple tests, with varying degrees of success. We hope that by using CPET, we can understand the physiological changes that occur as a result of the type, time and intensity of exercise prescribed for people with ILD.
Consider the Incremental Shuttle Walking Test in the introduction and its impact on personalisation, particularly as its use continues to grow within PR services.
Response: 6MWD and ISWT section added to provide a broader spectrum of exercise prescription options. Manuscript changed: line 155-164.
Revise the references, notably to include the James Lind Alliance top 10 priorities for Pulmonary Rehabilitation as the current reference is incorrect.
Response: James Lind Alliance top 10 priorities for Pulmonary Rehabilitation reference now added13, line:131-135.
In some areas Cardiopulmonary Exercise Testing (CPET) is becoming increasingly accessed, however this is not the case for all services, particularly with limited access to equipment and resources.
Response: It is important that we are sensitive to current practice, equipment availability and utilisation of field tests. Our focus is to understand personalisation through CPET in those with ILD, as we would like to identify the physiological changes that pwILD may have in response to tailored exercise. We agree that future research could continue to explore the translation into other, lower resourced areas of care delivery. A sole focus on CPET is a potential limitation, but the manuscript has been updated: line 345-346 to reflect the issues.
Reviewer #2: Approved with reservations.
Response: Thank you for your very comprehensive reviewer reports. We hope the following responses serve to enhance the protocol, especially in relation to the rationale and objectives of the study.
I do wonder about the clinical applicability of findings as CPET testing is seldom used by pulmonary rehabilitation providers.
Response: This point has also been raised by Reviewer#1, and a response has been provided (please see above: final response). There are advantages and disadvantages to each approach in terms of applicability; however, with ILD’s which have a poorer prognosis, such as idiopathic pulmonary fibrosis (IPF), the precision that CPET offers is key to understand the physiological mechanisms of disease, so that we can tailor exercise to meet the individuals’ requirements.
The terms: tailored, individualized and personalized are used inter-changeably.
Response: The term ‘tailored’ has now been selected, and this is applied consistently throughout the manuscript.
The authors state that individual responses to exercise training vary - is this based on research or clinical experience? I think it needs to be acknowledged that this may in part be due to variation in physiological response but psychological and behavioural factors are also likely to be important.
Response: Evidence in research and clinical practice suggests the individual responses of pwILD to exercise training do vary (Cox and Holland, 2025). We appreciate the psychological and behavioural factors associated with PR performance and acceptability. We base our approach on quantitative and qualitative feedback from the study by Tomlinson et al. (2021); where participants revealed many positive experiences of CPET.
The authors state that personalized PR guidelines are available for other chronic respiratory diseases such as COPD yet reference 12 is a review and not guidelines.
Response: Reference 12 updated in manuscript. Line: 133
Please explain how the systematic review proposed builds on this one conducted in 2019 (Armstrong).
Response: The Armstrong (2019) article ‘Personalized exercise training in chronic lung diseases’ does indicate some outline recommendations for people with ILD; this paper covers formative exercise prescription principles, which are only based on two references. However, a deeper insight is warranted for ILD due to the complexity of the diseases, this is why a systematic review is required. This systematic review is needed to provide an overview of how CPET can be utilised for PR, but also serves to detail the current exercise prescription methods applied in ILD. Manuscript updated to reflect our outlook: lines 147-151.
the writing style could be more clear and concise e.g. “thus placing the onus onto effective PR design = emphasizing the importance of individualized PR (this point is repeated).
Response: The writing style, clarity of terminology, referencing and overall objectives have been addressed in the updated manuscript.
These benefits are postulated to be sustained in the longer term = benefits are sustained long-term (add duration ?12m).
Response: We agree this adds more clarity. Manuscript now includes the duration: line: 129.
Please remove detail about methods (searches) from the objective statement.
Response: Line 194-197 in the first manuscript, has been removed in the updated manuscript.
Do the authors mean variables useful to prescribe exercise intensity in this group?
Response: Yes, we are aiming to identify which CPET variables are utilised to prescribe exercise in people with IPF. This has been updated in Table 1.
Did PPIE members feed into the protocol development?
Response: Yes, we worked with the Exeter Patients in Collaboration for Pulmonary Fibrosis (EPIC-PF) group who are a patient and public involvement and engagement group. Our meetings with the attendees helped us to map out and guide the project.
Why will the searches only be up until January 2024. Is the review already underway and if so is it close to publication otherwise searches will be 12m out of date and should be updated.
Response: Due to unforeseen delays, the systematic review searches have been re-run and articles up to January 2025 are now included. Manuscript updated to reflect this change: line: 244.
There is some repetition in the methods section. For example, as written the data management section and data collection process could be merged. The outcomes of interest are stated twice.
Response: Thank you for highlighting this error in the methods section. We have made amendments throughout the protocol methods section, within the manuscript.
REFERENCES
Reviewer #1: Acceptance
Response: Thank you for your very comprehensive reviewer reports. We are glad the review protocol aligns with the current research priorities.
Historically, people with ILD were not always included in PR programmes, but it was recommended in the 2023 BTS clinical statement to include those with ILD in PR, which is now captured in national audits (i.e. National Respiratory Audit Programme), (https://www.nrap.org.uk/).
Response: We agree, pulmonary rehabilitation (PR) for people with ILD is in the formative stages and we appreciate that there are challenges with service development. The recent BTS clinical statement for PR is an excellent step forward to evolve practice, alongside the National Respiratory Audit Programme which will help to drive forward the quality of ILD services. Therefore, to enhance the rationale, we have added references to the BTS PR Statement and the NRAP (lines 119-123).
Reporting of interventions, particularly where there is a degree of personalisation or tailoring is often poor or difficult to interpret, and similarly, the reporting and combining of results may be challenging.
Response: Reporting how interventions are delivered will be top of the agenda for the review. The Consensus on Exercise Reporting Template (CERT) assessment form will be used to check the reporting of exercise programme domains (Slade et al. 2016). This will support researchers to develop effective exercise interventions, that are well constructed and reproduceable. Manuscript changed: added section 3.6 (lines 294-298).
There is a degree of personalisation in PR programmes, typically prescribed by the Incremental Shuttle Walking Test or 6 Minute Walk Test (the latter highlighted by authors), and despite personalisation/tailoring predominantly influencing the duration and absolute intensity of the aerobic exercise component, this would still be considered personalisation.
Response: Tailoring PR and exercise will be on a spectrum, and can be derived from multiple tests, with varying degrees of success. We hope that by using CPET, we can understand the physiological changes that occur as a result of the type, time and intensity of exercise prescribed for people with ILD.
Consider the Incremental Shuttle Walking Test in the introduction and its impact on personalisation, particularly as its use continues to grow within PR services.
Response: 6MWD and ISWT section added to provide a broader spectrum of exercise prescription options. Manuscript changed: line 155-164.
Revise the references, notably to include the James Lind Alliance top 10 priorities for Pulmonary Rehabilitation as the current reference is incorrect.
Response: James Lind Alliance top 10 priorities for Pulmonary Rehabilitation reference now added13, line:131-135.
In some areas Cardiopulmonary Exercise Testing (CPET) is becoming increasingly accessed, however this is not the case for all services, particularly with limited access to equipment and resources.
Response: It is important that we are sensitive to current practice, equipment availability and utilisation of field tests. Our focus is to understand personalisation through CPET in those with ILD, as we would like to identify the physiological changes that pwILD may have in response to tailored exercise. We agree that future research could continue to explore the translation into other, lower resourced areas of care delivery. A sole focus on CPET is a potential limitation, but the manuscript has been updated: line 345-346 to reflect the issues.
Reviewer #2: Approved with reservations.
Response: Thank you for your very comprehensive reviewer reports. We hope the following responses serve to enhance the protocol, especially in relation to the rationale and objectives of the study.
I do wonder about the clinical applicability of findings as CPET testing is seldom used by pulmonary rehabilitation providers.
Response: This point has also been raised by Reviewer#1, and a response has been provided (please see above: final response). There are advantages and disadvantages to each approach in terms of applicability; however, with ILD’s which have a poorer prognosis, such as idiopathic pulmonary fibrosis (IPF), the precision that CPET offers is key to understand the physiological mechanisms of disease, so that we can tailor exercise to meet the individuals’ requirements.
The terms: tailored, individualized and personalized are used inter-changeably.
Response: The term ‘tailored’ has now been selected, and this is applied consistently throughout the manuscript.
The authors state that individual responses to exercise training vary - is this based on research or clinical experience? I think it needs to be acknowledged that this may in part be due to variation in physiological response but psychological and behavioural factors are also likely to be important.
Response: Evidence in research and clinical practice suggests the individual responses of pwILD to exercise training do vary (Cox and Holland, 2025). We appreciate the psychological and behavioural factors associated with PR performance and acceptability. We base our approach on quantitative and qualitative feedback from the study by Tomlinson et al. (2021); where participants revealed many positive experiences of CPET.
The authors state that personalized PR guidelines are available for other chronic respiratory diseases such as COPD yet reference 12 is a review and not guidelines.
Response: Reference 12 updated in manuscript. Line: 133
Please explain how the systematic review proposed builds on this one conducted in 2019 (Armstrong).
Response: The Armstrong (2019) article ‘Personalized exercise training in chronic lung diseases’ does indicate some outline recommendations for people with ILD; this paper covers formative exercise prescription principles, which are only based on two references. However, a deeper insight is warranted for ILD due to the complexity of the diseases, this is why a systematic review is required. This systematic review is needed to provide an overview of how CPET can be utilised for PR, but also serves to detail the current exercise prescription methods applied in ILD. Manuscript updated to reflect our outlook: lines 147-151.
the writing style could be more clear and concise e.g. “thus placing the onus onto effective PR design = emphasizing the importance of individualized PR (this point is repeated).
Response: The writing style, clarity of terminology, referencing and overall objectives have been addressed in the updated manuscript.
These benefits are postulated to be sustained in the longer term = benefits are sustained long-term (add duration ?12m).
Response: We agree this adds more clarity. Manuscript now includes the duration: line: 129.
Please remove detail about methods (searches) from the objective statement.
Response: Line 194-197 in the first manuscript, has been removed in the updated manuscript.
Do the authors mean variables useful to prescribe exercise intensity in this group?
Response: Yes, we are aiming to identify which CPET variables are utilised to prescribe exercise in people with IPF. This has been updated in Table 1.
Did PPIE members feed into the protocol development?
Response: Yes, we worked with the Exeter Patients in Collaboration for Pulmonary Fibrosis (EPIC-PF) group who are a patient and public involvement and engagement group. Our meetings with the attendees helped us to map out and guide the project.
Why will the searches only be up until January 2024. Is the review already underway and if so is it close to publication otherwise searches will be 12m out of date and should be updated.
Response: Due to unforeseen delays, the systematic review searches have been re-run and articles up to January 2025 are now included. Manuscript updated to reflect this change: line: 244.
There is some repetition in the methods section. For example, as written the data management section and data collection process could be merged. The outcomes of interest are stated twice.
Response: Thank you for highlighting this error in the methods section. We have made amendments throughout the protocol methods section, within the manuscript.
REFERENCES