Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol

Exercise testing, exercise training, respiratory disease, review ALL Metrics - Views Downloads How to cite this article Bowhay B, Williams CA, Gibbons MA et al. Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 4:51 (https://doi.org/10.3310/nihropenres.13706.2) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente Select a format first ▬ ✚ Study Protocol Revised Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations] Previously titled: Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol Ben Bowhay1-3, Craig A Williams2-4, Michael A Gibbons2,3, Chris J Scotton1-3, Owen W Tomlinson https://orcid.org/0000-0003-4063-7682 1-3Ben Bowhay1-3, Craig A Williams2-4, [...] Michael A Gibbons2,3, Chris J Scotton1-3, Owen W Tomlinson https://orcid.org/0000-0003-4063-7682 1-3 PUBLISHED 04 Jul 2025 Author details Author details 1 Clinical & Biomedical Sciences, University of Exeter, Exeter, England, UK 2 Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, England, UK 3 NIHR Biomedical Research Centre, University of Exeter, Exeter, England, UK 4 Public Health & Sport Sciences, University of Exeter, Exeter, England, UK 2 Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, England, UK 3 NIHR Biomedical Research Centre, University of Exeter, Exeter, England, UK 4 Public Health & Sport Sciences, University of Exeter, Exeter, England, UK Ben Bowhay Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Craig A Williams Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Michael A Gibbons Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Chris J Scotton Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Owen W Tomlinson Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing OPEN PEER REVIEW REVIEWER STATUS This review aims to identify which cardiopulmonary exercise test (CPET) derived variables can be used to personalise pulmonary rehabilitation (PR) for people with interstitial lung diseases. A ‘one size fits all’ approach does not benefit every patient due to a multitude of unique characteristics, subsets and phenotypes. No ILD-specific, tailored pulmonary rehabilitation guidelines exist in this area and exercise programme development is lacking. This leads to wide variation in the success within the literature and clinical practice. MEDLINE, Embase, CINAHL, SPORTDiscus and the Cochrane Database of Systematic Reviews will be searched to identify studies that utilise CPET variables for PR development. Quality assessment is to be performed using the Critical Appraisal Skills Program (CASP) checklists for single cohort studies and randomised controlled studies. The primary outcomes found within the included studies for peak volume of oxygen consumption (VO2peak), work rate (WRpeak), oxygen consumption at anaerobic threshold (VO2-AT), heart rate and rate of perceived exertion (RPE) would help determine which variables are optimal for prescription success. Identification of reliable methods to tailor PR for people with interstitial lung disease would enhance what is already known and potentially lead to best practice guideline development. In accordance with the guidelines, this systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO) on 07 May 2024 (registration number CRD42024543174). Interstitial lung diseases (ILD) are a group of around 200 long-term lung conditions, which often lead to lung failure. Pulmonary Rehabilitation (PR) is a mix of exercise, advice and education that is used to support people with ILD (pwILD) to help maintain their lung function, general function, and quality of life. However, a ‘one size fits all’ PR approach may not be best, due to the many challenges found for ILD as a condition. Therefore, using a gold-standard tool like Cardiopulmonary Exercise Testing (CPET) can help to assess these challenges; as we look to understand how the heart, lungs and muscle work during exercise for each pwILD and these outcomes would help support person-centred exercise selection. The systematic review aims to discover which CPET outcomes can be used to tailor PR for people with ILD. A range of databases (MEDLINE, Embase, CINAHL, SPORTDiscus and the Cochrane Database of Systematic Reviews) will be searched to identify studies that meet this aim, and checklists (Critical Appraisal Skills Program, CASP) will then be used to rate the quality of the included studies. No tailored PR guidelines are available for pwILD, which leads to many differences in the success of PR. We will review the current evidence, with the aim to see which CPET outcomes can be used for PR selection. The systematic review results would help to show if technically appropriate methods can be developed for tailored PR in pwILD and support the design of future studies that can guide PR practice. Exercise testing, exercise training, respiratory disease, review Corresponding Author(s) Owen W Tomlinson ([email protected]) 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: © 2025 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 tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 4:51 (https://doi.org/10.3310/nihropenres.13706.2) 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. This protocol has been updated following review. Reviewer #1 has endorsed the manuscript in its current form, yet had valuable commentary which we have incorporated into the updated version. Reviewer #2 provisionally endorsed this version, and we have incorporated further changes in light of their comments. This protocol has been updated following review. Reviewer #1 has endorsed the manuscript in its current form, yet had valuable commentary which we have incorporated into the updated version. Reviewer #2 provisionally endorsed this version, and we have incorporated further changes in light of their comments. To read any peer review reports and author responses for this article, follow the "read" links in the Open Peer Review table. 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 pwILD7, 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 diseases8. The British Thoracic Society (BTS) explicitly recommends that PR should be offered to symptomatic individuals with chronic respiratory disease, including pwILD8. Therefore, National Health Service in the United Kingdom, alongside the National Respiratory Audit Programme (NRAP) are aiming to drive forward the quality of PR services9. 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, 6MWT) and “low-certainty” evidence that suggests that PR in pwILD may improve maximum exercise capacity (WRpeak) and dyspnoea10. These benefits are postulated to be sustained in the longer term (e.g. 12 months duration) and there is also no evidence that adverse events were found in the pwILD11. Therefore, PR is not only useful for enhancing QoL in pwILD, but functional capacity as well11. However, no PR guidelines have been developed specifically for pwILD at present, despite them being available for other chronic respiratory diseases such as COPD12. Therefore, the James Lind Alliance has made ‘best exercise program for people with Pulmonary Fibrosis’ part of their top ten research priorities13. The main challenge for development of PR guidelines in ILD is related to the breath of pathophysiological impairments that occur across the different ILD subgroups, which may lead to variation in exercise tolerance and capacity14. 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 pwILD14. 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 oxygenation14; this may lower ATP, increase lactate and cause a rise in VCO211. Gas exchange insufficiency, central haemodynamic impairment and muscle deconditioning are prevalent in the ILD population14. Therefore a tailored approach to exercise prescription may provide enhanced physical function outcomes, as tailoring could account for these mechanisms of exercise intolerance in chronic lung diseases15. However, due to the complex characteristics of ILD, a review of the methods used for tailored exercise prescription is required, before comprehensive guidelines in this population can be developed. 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 tailored prescription8. Within ILD management, field tests such as 6-minute walk distance (6MWD)16–18 and the incremental shuttle walk test (ISWT)19 are often used as a functional outcome because they are valid, easy to implement and cost-effective16–19. However, field tests cannot highlight the full spectrum of pathophysiological mechanisms which limit exercise tolerance, and safety issues such as ischemia or arrhythmias cannot be easily detected20. Both aspects are of upmost importance when looking to prescribe exercise in the ILD population, due to the aforementioned physiological impairments14. Therefore, the focus of this systematic review is to explore the potential utility of CPET to provide the precision required for tailored exercise prescription in ILD. Tailored exercise via CPET has been earmarked as the future of PR, whereby a comprehensive evaluation of pathophysiological systems serves to indicate responses to exercise, and therefore these values could support effective PR programming14. Evidence suggests that CPET is now the gold standard for the causal evaluation of exercise intolerance in patients with long term pulmonary conditions21. It has been demonstrated that CPET is a safe and valuable method for the comprehensive evaluation of cardiac, pulmonary and muscle function21, whilst also recognising physiological factors limiting exercise such as dyspnoea22. Exercise prescription methods which are tailored to the cardiovascular, pulmonary, and peripheral muscle metabolic limitations of the individual patient have the potential to be the cornerstone of tailored PR14. Recent evidence suggests that tailored, 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 dysponea23. Moreover, tailored exercise training can enhance antioxidant buffering capacity in people with idiopathic pulmonary fibrosis (IPF), which may corelate with enhanced muscle fatigue resilience24. This clearly demonstrates the functional and physiological value PR can have when using tailored approaches. However, for widespread success of tailored PR programmes in ILD, implementation of exercise prescription principles (e.g. specificity, frequency, intensity, timing, type, overload, progression, adaptation, and reversibility) should be followed and reported accordingly5. At present, it is not clear if this is currently done for pwILD; the current systematic review helps provide an overview of practice regarding the components of exercise prescription in this population. There is also a need to develop a valid, reliable, and consistent method for personalising PR based on CPET outcome measures. 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 highlighting the CPET-derived exercise prescription variables that have been used to tailor PR for pwILD. The PRISMA-P has been used to guide this systematic review protocol25. 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. Population People of all ages, sexes and ethnic groups that have been diagnosed with any ILD subtype. Intervention Tailored PR or exercise programmes, which have used 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) Rate of perceived exertion (RPE) that can be measured on a 0–10 RPE scale or a Borg 6–20 scale. 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. 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 2025. 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. 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© 2026 (Clarivate, London, UK) will be utilised for reference storage. 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 (TBC) 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 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. 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 will be derived from CPET values. We anticipate that the main outcomes will be displayed in a summary of findings table using GRADEpro27. 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 studies28 and randomised controlled studies29, 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). Reporting quality The Consensus on Exercise Reporting Template (CERT) assessment form will be used to check the reporting of exercise programme domains30. This would support researchers to develop effective exercise interventions, that are well constructed and reproduceable. Using the CERT would also help policymakers with making exercise recommendations and guide peer reviewers in manuscripts evaluation30. All analyses will be performed using Review Manager31. 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 tailored 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 Handbook32. 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 P50% 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. The current systematic review has been developed to explore how CPET-derived outcomes can help support tailored PR design for pwILD. At present, there are no systematic reviews that provide insights into how CPET values can be utilised for tailored 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. A potential limitation of this study would be the focus on CPET, without direct comparison against field tests. The potential strength of this review is that exploring CPET, as a tool for tailoring exercise, may help to indicate beneficial methods for PR prescription in the ILD population. The overall aim following this review is to develop a valid, reliable, and consistent method for tailoring 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 for pwILD; therefore, this systematic review aims to fill this research gap. Interstitial Lung Diseases; Pulmonary Rehabilitation; Exercise; CPET; Treatment Outcomes; Training; Physiotherapy; Systematic Review. CPET: Cardiopulmonary Exercise Testing 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 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 In the event of protocol amendments, the date of each amendment will be accompanied by a description of the change and the rationale. Not applicable Not applicable Reporting guidelines are 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: PRISMA-P.doc.x. Available at: https://doi.org/10.17605/OSF.IO/43N2925. Data is available under Creative Commons Zero (CC0): 1.0 Universal. OSFHOME: Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol Available at: https://doi.org/10.17605/OSF.IO/43N2925 This project contains: Inclusion and exclusion criteria - Protocol.docx Search_Strategy.docx Data is available under Creative Commons Zero (CC0): 1.0 Universal. Conceptualisation: CW, MG, CS, OT; Design: BB, OT; Drafting Manuscript: BB; Critical Review of Manuscript: BB, CW, MG, CS, OT; Agreement ot be Accountable: BB, CW, MG, CS, OT. 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is closed on this version, please comment on the latest version above. - 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 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.

- Slade SC, Dionne CE, Underwood M, Buchbinder R. Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement. Br J Sports Med 2016;50(23):1428-1437. (In eng). DOI: 10.1136/bjsports-2016-096651. - Cox NS, Holland AE. Pulmonary rehabilitation: one size does not fit all. Thorax 2025 (In eng). DOI: 10.1136/thorax-2024-222680. - Tomlinson O, Duckworth A, Markham L, et al. Feasibility of cardiopulmonary exercise testing in interstitial lung disease: The PETFIB study. BMJ Open Respiratory Research 2021;8(1) (Article) (In English). DOI: https://dx.doi.org/10.1136/bmjresp-2020-000793. Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocolCompeting Interests: No competing interests. Close 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.

- Slade SC, Dionne CE, Underwood M, Buchbinder R. Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement. Br J Sports Med 2016;50(23):1428-1437. (In eng). DOI: 10.1136/bjsports-2016-096651. - Cox NS, Holland AE. Pulmonary rehabilitation: one size does not fit all. Thorax 2025 (In eng). DOI: 10.1136/thorax-2024-222680. - Tomlinson O, Duckworth A, Markham L, et al. Feasibility of cardiopulmonary exercise testing in interstitial lung disease: The PETFIB study. BMJ Open Respiratory Research 2021;8(1) (Article) (In English). DOI: https://dx.doi.org/10.1136/bmjresp-2020-000793. - Discussion is closed on this version, please comment on the latest version above. Author details Author details 1 Clinical & Biomedical Sciences, University of Exeter, Exeter, England, UK 2 Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, England, UK 3 NIHR Biomedical Research Centre, University of Exeter, Exeter, England, UK 4 Public Health & Sport Sciences, University of Exeter, Exeter, England, UK 2 Academic Department of Respiratory Medicine, Royal Devon University Healthcare NHS Foundation Trust, Exeter, England, UK 3 NIHR Biomedical Research Centre, University of Exeter, Exeter, England, UK 4 Public Health & Sport Sciences, University of Exeter, Exeter, England, UK Ben Bowhay Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Roles: Methodology, Writing – Original Draft Preparation, Writing – Review & Editing Craig A Williams Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Michael A Gibbons Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Chris J Scotton Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Owen W Tomlinson Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing Roles: Conceptualization, Methodology, Supervision, Writing – Review & Editing 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. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Article Versions (2) Copyright © 2025 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. metrics VIEWS $counts.viewCount downloads Citations CITE how to cite this article Bowhay B, Williams CA, Gibbons MA et al. Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 4:51 (https://doi.org/10.3310/nihropenres.13706.2) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. track receive updates on this article Track an article to receive email alerts on any updates to this article. Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE ApprovedThe paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approvedFundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 04 Jul 2025 Revised Views 0 How to cite this report: Katagira W. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 4:51 (https://doi.org/10.3310/nihropenres.15241.r36274) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36274 https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36274 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 03 Sep 2025 Approved with Reservations VIEWS 0 This is a highly relevant systematic review. The burden of ILD is increasing globally and poses a growing clinical challenge. Although PR is recognised as a cornerstone of care for chronic lung diseases, there are no ILD-specific, evidence-based guidelines. ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close The burden of ILD is increasing globally and poses a growing clinical challenge. Although PR is recognised as a cornerstone of care for chronic lung diseases, there are no ILD-specific, evidence-based guidelines. ... Continue reading This is a highly relevant systematic review. The burden of ILD is increasing globally and poses a growing clinical challenge. Although PR is recognised as a cornerstone of care for chronic lung diseases, there are no ILD-specific, evidence-based guidelines. CPET is considered the gold standard for assessing exercise capacity; however, there's a paucity of data on how CPET can be used to guide personalised PR in ILD. This protocol addresses that gap. Overall, the protocol is well-written, with robust methodology and is clinically significant. It has been registered in PROSPERO. Patient and Public Involvement is commendable.

1. A good number of technologically advanced PR centers are in Asia, where English is not a primary language. Excluding non-English articles may introduce language bias, but the lack of translators is a legitimate limitation/challenge. 2. Many PR offering centers have limited CPET access; therefore real-world applicability of CPET may be limited. 3. Limited generalisability to resource-limited settings. CPET is resource-intensive, and most low-resource settings will lack access to CPET. 4. CPET offers precision in identifying mechanisms of exercise tolerance and captures the physiological responses; however, for many ILD patients, the improvements may be more psychological and behavioural. 5. The lack of direct comparisons with field tests like ISWT and 6MWT may limit clinic transferability. Perhaps future studies can aim to address this. The burden of ILD is increasing globally and poses a growing clinical challenge. Although PR is recognised as a cornerstone of care for chronic lung diseases, there are no ILD-specific, evidence-based guidelines. CPET is considered the gold standard for assessing exercise capacity; however, there's a paucity of data on how CPET can be used to guide personalised PR in ILD. This protocol addresses that gap. Overall, the protocol is well-written, with robust methodology and is clinically significant. It has been registered in PROSPERO. Patient and Public Involvement is commendable.

1. A good number of technologically advanced PR centers are in Asia, where English is not a primary language. Excluding non-English articles may introduce language bias, but the lack of translators is a legitimate limitation/challenge. 2. Many PR offering centers have limited CPET access; therefore real-world applicability of CPET may be limited. 3. Limited generalisability to resource-limited settings. CPET is resource-intensive, and most low-resource settings will lack access to CPET. 4. CPET offers precision in identifying mechanisms of exercise tolerance and captures the physiological responses; however, for many ILD patients, the improvements may be more psychological and behavioural. 5. The lack of direct comparisons with field tests like ISWT and 6MWT may limit clinic transferability. Perhaps future studies can aim to address this. - Is the rationale for, and objectives of, the study clearly described? Yes - Is the study design appropriate for the research question? Yes - Are sufficient details of the methods provided to allow replication by others? Yes - Are the datasets clearly presented in a useable and accessible format? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pulmonary Rehabilitation, Post-TB lung disease, Chronic respiratory diseases CITE HOW TO CITE THIS REPORT Katagira W. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 4:51 (https://doi.org/10.3310/nihropenres.15241.r36274) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36274 https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36274 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Views 0 How to cite this report: Harrison S. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 4:51 (https://doi.org/10.3310/nihropenres.15241.r36219) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36219 https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36219 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 20 Aug 2025 Samantha Harrison, Teesside University,, Middlesbrough, UK Approved VIEWS 0 I have no ... Continue reading I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close I have no further comments to make Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pulmonary Rehabilitation; mixed-methods including codesign and PPIE CITE HOW TO CITE THIS REPORT Harrison S. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 4:51 (https://doi.org/10.3310/nihropenres.15241.r36219) The direct URL for this report is: https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36219 https://openresearch.nihr.ac.uk/articles/4-51/v2#referee-response-36219 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Version 1 VERSION 1 PUBLISHED 17 Sep 2024 Views 0 How to cite this report: Harrison S. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 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 this citation. Reviewer Report 16 Dec 2024 Samantha Harrison, Teesside University,, Middlesbrough, UK Approved with Reservations VIEWS 0 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 I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close Overall, this is a well presented manuscript and the proposed review ... Continue reading 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 should yield interesting results. However, I do wonder about the clinical applicability of findings as CPET testing is seldom used by pulmonary rehabilitation providers. The terms: tailored, individualized and personalized are used inter-changeably. I suggest selecting one terms and applying consistently throughout. 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. 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. Furthermore, this published review provides information on personalised exercise prescription for patients with CRD, including ILD. Please explain how the systematic review proposed builds on this one conducted in 2019 (Armstrong). Although the protocol is generally well written, at times 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). These benefits are postulated to be sustained in the longer term” = benefits are sustained long-term (add duration ?12m). Please remove detail about methods (searches) from the objective statement. I think the objective could be clearer – I suggest clarifying what is meant by personalized . Do the authors mean variables useful to prescribe exercise intensity in this group? Did PPIE members feed into the protocol development? 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. 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. Overall, this is a well presented manuscript and the proposed review should yield interesting results. However, I do wonder about the clinical applicability of findings as CPET testing is seldom used by pulmonary rehabilitation providers. The terms: tailored, individualized and personalized are used inter-changeably. I suggest selecting one terms and applying consistently throughout. 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. 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. Furthermore, this published review provides information on personalised exercise prescription for patients with CRD, including ILD. Please explain how the systematic review proposed builds on this one conducted in 2019 (Armstrong). Although the protocol is generally well written, at times 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). These benefits are postulated to be sustained in the longer term” = benefits are sustained long-term (add duration ?12m). Please remove detail about methods (searches) from the objective statement. I think the objective could be clearer – I suggest clarifying what is meant by personalized . Do the authors mean variables useful to prescribe exercise intensity in this group? Did PPIE members feed into the protocol development? 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. 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. - Is the rationale for, and objectives of, the study clearly described? Partly - Is the study design appropriate for the research question? Yes - Are sufficient details of the methods provided to allow replication by others? Yes - Are the datasets clearly presented in a useable and accessible format? Not applicable Competing Interests: No competing interests were disclosed. Reviewer Expertise: Pulmonary Rehabilitation; mixed-methods including codesign and PPIE CITE HOW TO CITE THIS REPORT Harrison S. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 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. Views 0 How to cite this report: Daynes E. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 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 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Reviewer Report 15 Oct 2024 Approved VIEWS 0 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 2. Holland A, Cox N, Houchen-Wolloff L, Rochester C, et al.: Defining Modern Pulmonary Rehabilitation. An Official American Thoracic Society Workshop Report. Annals of the American Thoracic Society. 2021; 18 (5): e12-e29 Publisher Full Text 3. Skivington K, Matthews L, Simpson SA, Craig P, et al.: A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance.BMJ. 2021; 374: n2061 PubMed Abstract | Publisher Full Text I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close 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 case of need for this work, particularly highlighting the lack of guidance specific to those with ILD, which is compounded but the challenges that a large proportion of literature is not focused towards these patients. 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) [Ref 1] , (https://www.nrap.org.uk/) . Therefore, this is clearly an important area of work and aligns with priorities for research. The methods described are appropriate and robust, following standardised systematic review frameworks and where possible performing meta-analyses. It may be necessary to include sub-group analyses as the authors highlight, and particular considerations in regard to duration of programmes, dose of exercise prescription, disease characteristics (including sub-groups of ILD) and setting of delivery could be valuable. Additionally, the authors intend to include studies from outside of the UK and therefore adjusting for the variability of PR delivery (inpatient vs outpatient, duration of programme, etc) may be necessary in understanding and interpreting the results. There are several strengths to this work. The authors present a robust systematic review plan in an area that is pertinent. They plan to include a variety of studies, and to contact authors for further information/data. They have scheduled bias analysis and are open to appropriate sub-group analysis. Though this work will not be without its challenges. Defining PR will be crucial to the success of this study, which is in part answerable to the requirement of including an exercise intervention, but the definition can vary globally [Ref 2] . 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 {Ref 4] . Finally other considerations that may be useful is determining or defining personalisation. 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. Perhaps personalisation of PR exists on a spectrum from minimal adjustments of the same programme to a completely individualized exercise programme. Somewhere in between lays the authors ambitions of personalising the type, time and intensity of aerobic exercise within PR for those with ILD. This is a well written protocol and clearly articulated the needs of the research. I would recommend minor corrections to firstly consider the Incremental Shuttle Walking Test in the introduction and its impact on personalisation, particularly as its use continues to grow within PR services, and to revise the references, notably to include the James Lind Alliance top 10 priorities for Pulmonary Rehabilitation as the current reference is incorrect. This is an important area of research on a long-neglected group of patients which has the potential to have significant impact to the literature, patients and healthcare providers. As the authors highlight, 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. This is the first step in understanding personalisation through CPET in those with ILD, however further research could continue to explore the translation of this concept into other, lower resourced areas of care delivery. The methods described are appropriate and robust, following standardised systematic review frameworks and where possible performing meta-analyses. It may be necessary to include sub-group analyses as the authors highlight, and particular considerations in regard to duration of programmes, dose of exercise prescription, disease characteristics (including sub-groups of ILD) and setting of delivery could be valuable. Additionally, the authors intend to include studies from outside of the UK and therefore adjusting for the variability of PR delivery (inpatient vs outpatient, duration of programme, etc) may be necessary in understanding and interpreting the results. There are several strengths to this work. The authors present a robust systematic review plan in an area that is pertinent. They plan to include a variety of studies, and to contact authors for further information/data. They have scheduled bias analysis and are open to appropriate sub-group analysis. Though this work will not be without its challenges. Defining PR will be crucial to the success of this study, which is in part answerable to the requirement of including an exercise intervention, but the definition can vary globally [Ref 2] . 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 {Ref 4] . Finally other considerations that may be useful is determining or defining personalisation. 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. Perhaps personalisation of PR exists on a spectrum from minimal adjustments of the same programme to a completely individualized exercise programme. Somewhere in between lays the authors ambitions of personalising the type, time and intensity of aerobic exercise within PR for those with ILD. This is a well written protocol and clearly articulated the needs of the research. I would recommend minor corrections to firstly consider the Incremental Shuttle Walking Test in the introduction and its impact on personalisation, particularly as its use continues to grow within PR services, and to revise the references, notably to include the James Lind Alliance top 10 priorities for Pulmonary Rehabilitation as the current reference is incorrect. This is an important area of research on a long-neglected group of patients which has the potential to have significant impact to the literature, patients and healthcare providers. As the authors highlight, 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. This is the first step in understanding personalisation through CPET in those with ILD, however further research could continue to explore the translation of this concept into other, lower resourced areas of care delivery. - Is the rationale for, and objectives of, the study clearly described? Yes - Is the study design appropriate for the research question? Yes - Are sufficient details of the methods provided to allow replication by others? Yes - Are the datasets clearly presented in a useable and accessible format? Not applicable

1. Man W, Chaplin E, Daynes E, Drummond A, et al.: British Thoracic Society Clinical Statement on pulmonary rehabilitation. Thorax. 2023; 78 (Suppl 5): s2-s15 Publisher Full Text2. Holland A, Cox N, Houchen-Wolloff L, Rochester C, et al.: Defining Modern Pulmonary Rehabilitation. An Official American Thoracic Society Workshop Report. Annals of the American Thoracic Society. 2021; 18 (5): e12-e29 Publisher Full Text 3. Skivington K, Matthews L, Simpson SA, Craig P, et al.: A new framework for developing and evaluating complex interventions: update of Medical Research Council guidance.BMJ. 2021; 374: n2061 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Senior Specialist Physiotherapist in Pulmonary Rehabilitation, expertise in Pulmonary Rehabilitation, Breathlessness Management, Systematic Reviews, Quantitative Methods, Qualitative Methods. CITE HOW TO CITE THIS REPORT Daynes E. Reviewer Report For: Exploring the potential of cardiopulmonary exercise testing (CPET) for tailored pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocol [version 2; peer review: 2 approved, 1 approved with reservations]. NIHR Open Res 2025, 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 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. Version 2 VERSION 2 PUBLISHED 04 Jul 2025 Revised Version 1 VERSION 1 PUBLISHED 17 Sep 2024

is closed on this version, please comment on the latest version above. - 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 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.

- Slade SC, Dionne CE, Underwood M, Buchbinder R. Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement. Br J Sports Med 2016;50(23):1428-1437. (In eng). DOI: 10.1136/bjsports-2016-096651. - Cox NS, Holland AE. Pulmonary rehabilitation: one size does not fit all. Thorax 2025 (In eng). DOI: 10.1136/thorax-2024-222680. - Tomlinson O, Duckworth A, Markham L, et al. Feasibility of cardiopulmonary exercise testing in interstitial lung disease: The PETFIB study. BMJ Open Respiratory Research 2021;8(1) (Article) (In English). DOI: https://dx.doi.org/10.1136/bmjresp-2020-000793. Exploring the potential of cardiopulmonary exercise testing (CPET) for individualised pulmonary rehabilitation in people with interstitial lung disease (ILD): A systematic review protocolCompeting Interests: No competing interests. Close 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.

- Slade SC, Dionne CE, Underwood M, Buchbinder R. Consensus on Exercise Reporting Template (CERT): Explanation and Elaboration Statement. Br J Sports Med 2016;50(23):1428-1437. (In eng). DOI: 10.1136/bjsports-2016-096651. - Cox NS, Holland AE. Pulmonary rehabilitation: one size does not fit all. Thorax 2025 (In eng). DOI: 10.1136/thorax-2024-222680. - Tomlinson O, Duckworth A, Markham L, et al. Feasibility of cardiopulmonary exercise testing in interstitial lung disease: The PETFIB study. BMJ Open Respiratory Research 2021;8(1) (Article) (In English). DOI: https://dx.doi.org/10.1136/bmjresp-2020-000793. - Discussion is closed on this version, please comment on the latest version above. Alongside their report, reviewers assign a status to the article: - Approved - Approved with reservations - Not approved | Invited Reviewers | ||| |---|---|---|---| | 1 | 2 | 3 | | | Version 2 (revision) 04 Jul 25 | read | read | | | Version 1 17 Sep 24 | read | read | - Samantha Harrison, Teesside University,, Middlesbrough, UK Sign up for content alerts You are now signed up to receive this alert Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. Consider the following examples, but note that this is not an exhaustive list: Examples of 'Non-Financial Competing Interests' - Within the past 4 years, you have held joint grants, published or collaborated with any of the authors of the selected paper. - You have a close personal relationship (e.g. parent, spouse, sibling, or domestic partner) with any of the authors. - You are a close professional associate of any of the authors (e.g. scientific mentor, recent student). - You work at the same institute as any of the authors. - You hope/expect to benefit (e.g. favour or employment) as a result of your submission. - You are an Editor for the journal in which the article is published. Examples of 'Financial Competing Interests' - You expect to receive, or in the past 4 years have received, any of the following from any commercial organisation that may gain financially from your submission: a salary, fees, funding, reimbursements. - You expect to receive, or in the past 4 years have received, shared grant support or other funding with any of the authors. - You hold, or are currently applying for, any patents or significant stocks/shares relating to the subject matter of the paper you are commenting on. Sign up for content alerts and receive a weekly or monthly email with all newly published articles Register with NIHR Open Research Already registered? Sign in close Error If you are a previous or current NIHR award holder, sign up for information about developments, publishing and publications from NIHR Open Research. We'll keep you updated on any major new updates to NIHR Open Research Sign In If you've forgotten your password, please enter your email address below and we'll send you instructions on how to reset your password. Email us for further assistance. The email address should be the one you originally registered with F1000. Email address not valid, please try again You registered with F1000 via Google, so we cannot reset your password. To sign in, please click here. If you still need help with your Google account password, please click here. You registered with F1000 via Facebook, so we cannot reset your password. To sign in, please click here. If you still need help with your Facebook account password, please click here. Code not correct, please try again Server error, please try again. If your email address is registered with us, we will email you instructions to reset your password. If you think you should have received this email but it has not arrived, please check your spam filters and/or contact for further assistance. Please wait...