PONE-D-23-06071The effects of pulmonary rehabilitation on inflammatory biomarkers in patients with chronic obstructive pulmonary disease: Protocol for a systematic reviewPLOS ONE

Dear Dr. Newman,

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Academic Editor

PLOS ONE

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Partly

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2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

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4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

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5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Thank you for the paper. It is very enlightening, but I have a few comments for the authors that they could consider.

Data availability statement:

Since this is a protocol, this statement “No datasets were generated or analysed during the current study” is not applicable to the study design. The authors should specifically highlight which platform will be used to share the data used in this study.

Abstract

Introduction

Line 38- 39: The two sentences can be joined to form one. I suggest that you replace cornerstone treatment with “one of the strategies used in the management of individuals with COPD irrespective of severity but its effect on systemic inflammation is poorly understood.”

Still in the abstract: the rationale for conducting the systematic review is not clear. Is it because the effect is poorly understood or because there is no previous systematic review highlighting the effect?

Materials and methods:

Line 45: What do you mean from inception?

Line 49: The inclusion criteria 1 is not clear. “PR with an exercise component of at least 4 weeks “or I would rather suggest that the authors edit it to make it clearer.

Line 56: Conclusion not conclusions

Line 57- 59: I suggest the authors considered rewording the sentence to “The results from this systematic review will summarize the status on evidence highlighting/ showing/ illustrating the effect of PR on systemic inflammation and a manuscript will be drafted and submitted to a peer-reviewed journal or shared at conferences.”

Main text

Introduction

Line 65 to 73: There is no need to define what COPD or Acute Exacerbation of COPD is, it is common knowledge. The authors should highlight the burden then move on to how systemic inflammation comes into the picture.

Line 74 to 85: COPD is a product of localized inflammation in lungs which is supported by the pathological changes highlighted in line 75 and 76. I suggest that the authors highlight how this localized inflammation becomes systemic inflammation. Authors should also know that biomarkers are proxies of the pathological state of the organs case in point the lungs. The authors should consider highlighting biomarkers that are highly specific to COPD or AECOPD and not all inflammatory biomarkers as these might be associated with other diseases.

Line 86- 95: The authors highlighted what PR is. The rationale for conducting the systematic review is not clear.

Methods

Under intervention:

“the included studies will have an exercise component for at least 4 weeks in length.”

Outcome of interest:

“Enzyme-linked immunosorbent assay” this is not a marker rather a test.

Could the authors focus on COPD specific biomarkers? Or provide a justification as to why they are considering all these biomarkers in the introduction that appear nonspecific?

Line 110- 111: Please include a reference for the reporting guidelines.

Line 120: Instead of “of” consider “for.”

Line 157: In the data extraction: The authors should include existing co-morbidities focusing on diseases that induce chronic inflammation or that contribute to high concentrations of inflammatory biomarkers.

Line 206: The authors report that meta-analyses will be conducted where possible. Why bring this up now? Why aren’t they doing a meta-analysis in the first place?

Line 213: The authors could change conclusion to “Significance.”

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Reviewer #1: No

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The effects of pulmonary rehabilitation on inflammatory biomarkers in patients with chronic obstructive pulmonary disease: Protocol for a systematic review and meta-analysis

PONE-D-23-06071R1

Dear Dr. Newman,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Felix Bongomin, MB ChB, MSc, MMed, FECMM

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Does the manuscript provide a valid rationale for the proposed study, with clearly identified and justified research questions?

The research question outlined is expected to address a valid academic problem or topic and contribute to the base of knowledge in the field.

Reviewer #1: Yes

**********

2. Is the protocol technically sound and planned in a manner that will lead to a meaningful outcome and allow testing the stated hypotheses?

The manuscript should describe the methods in sufficient detail to prevent undisclosed flexibility in the experimental procedure or analysis pipeline, including sufficient outcome-neutral conditions (e.g. necessary controls, absence of floor or ceiling effects) to test the proposed hypotheses and a statistical power analysis where applicable. As there may be aspects of the methodology and analysis which can only be refined once the work is undertaken, authors should outline potential assumptions and explicitly describe what aspects of the proposed analyses, if any, are exploratory.

Reviewer #1: Yes

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3. Is the methodology feasible and described in sufficient detail to allow the work to be replicable?

Descriptions of methods and materials in the protocol should be reported in sufficient detail for another researcher to reproduce all experiments and analyses. The protocol should describe the appropriate controls, sample size calculations, and replication needed to ensure that the data are robust and reproducible.

Reviewer #1: Yes

**********

4. Have the authors described where all data underlying the findings will be made available when the study is complete?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception, at the time of publication. The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above and, if applicable, provide comments about issues authors must address before this protocol can be accepted for publication. You may also include additional comments for the author, including concerns about research or publication ethics.

You may also provide optional suggestions and comments to authors that they might find helpful in planning their study.

(Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Abstract

Line 24: I suggest the authors remove “common.”

Line 27: I think this sentence is incomplete “and extrapulmonary manifestations of…….” What is the author trying to say/ write?

Introduction:

Line 57- 59: Is there a difference between that sentence and the sentence in line 51- 52? I think they all mean the same. I suggest that the authors delete one.

I further suggest that the authors re-align the first paragraph. Here is my recommendation:

Line 51 to 52 open then paragraph. This could be followed by sentences from line 60 to 69.

The sentences which start from line 52 “It is associated with primary respiratory impairments including dyspnea, coughing, sputum production, wheezing, and extrapulmonary systemic manifestations, such as muscle loss and cachexia, cardiovascular disease, osteoporosis, and metabolic syndromes (i.e., diabetes) to line 55 can be rephrase and start second the paragraph. This could make it easy to follow and so that we do not have a mix of symptoms and statistics.

Another suggestion to the authors for their consideration. Since there is no specific biomarker to show the effect of PR on systemic inflammation, you could mention that the meta-analysis could provide evidence to build on this assumption.

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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: Yes: Andrew Weil Semulimi

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