PONE-D-24-04889Moderate-intensity physical activity reduces the role of serum PFAS on COPD: A cross-sectional analysis with NHANES dataPLOS ONE

Dear Dr. Guo,

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Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

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2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

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3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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

Reviewer #2: Yes

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4. 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

Reviewer #2: No

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: GENERAL COMMENTS

This is a study exploring potential associations between perfluoroalkyl substances (PFAS) exposure and the development of chronic obstructive pulmonary disease (COPD). Additionally, authors aimed to evaluate whether physical activity (PA) may protect individuals from developing COPD-related exposure to PFAS. They have used the 2013-2018 National Health and Nutrition Examination Survey (NHANES) data to perform analyses. The rationale for conducting the research has merits even if data and analysis are not robust for concluding on any cause-effect relationship. I miss, however, goodness of fit measures of the models they present.

SPECIFIC COMMENTS

Abstract

Line 28: This part of the sentence sound strange “…that have been studied to demonstrate their possible association with reduced lung function.”. Please improve. Also, begin the next sentence with a capital P (Physical activity).

Line 40: I find your conclusion overly cautious. I suggest something like: “PFAS exposure may increase the risk of developing COPD, but regular moderate-intensity physical activity can protect individuals from evolving to the disease. However, longitudinal studies are needed to support these preliminary findings.”

Introduction

Line 64: I suggest you use a more modern definition of PA, such as that by Piggin, J. (2020). What is physical activity? A holistic definition for teachers, researchers and policy makers. Frontiers in Sports and Active Living, 2, 72. https://www.frontiersin. org/articles/10.3389/fspor.2020.00072

Line 69: The rationale in the previous paragraphs direct the reader that PFAS and physical activity exposures can individually affect COPD in opposing directions, not just different directions.

Materials and Methods

Line 92: Please, add the specific link so that readers can access it easily.

Line 100: I suggest you delete “of sport”.

Line 106: I’m not aware that this article (reference #26) discusses the conversion of MET-min/week to 150min/week of moderate intensity activity. Can you tell in which page, please?

Lines 112–115: Can you provide the rationale and the supporting literature?

Line 121: “Therefore, ln-transformation was performed in the regression analysis to improve the normality”. It doesn’t matter the normality of the independent variable for regression analysis. What matters is the normality of the residuals or errors but in linear regression. More importantly, have you tested the assumptions for trusting the results of the logistic regression: linearity, independence of errors and multicollinearity? Please, report.

Line 126: Is “multinomial” missing before “logistic regression”? Or PA was an independent variable?

Results

Lines 133–134: I believe PA=0, PA=1 and PA=2 are probably the codes used as dependent variables in multinomial logistic regression models. I think they should be deleted. I think however that you should report more clearly in the statistical analysis section the dependent variable categories. You just state “various types of PA” on line 126.

Table 1. Please add the units of measurement in income and body mass index. Also, be consistent with the decimals. Sometimes, you don’t have any, present 1 or 2 decimals.

You have not prepared readers for sections 3.3. and 3.4, and Tables 2, 3 and 4 in the statistical analysis section. Please report there the methods and analyses used.

I’m not following you in section 3.4. Have you conducted separated analysis for each subgroup (just odds ratio) or have you conducted multivariate logistic regression?

Reviewer #2: This article presents interesting assumptions about COPD and physical activity. The work is relevant and with an adequate methodology, but some inaccurate elements need improvement. I have some major and minor comments listed below.

Major comments

#1 Revise English with a mother tongue reviewer.

#2 The hypothesis (lines 62 and 63) is poorly formulated. The relationship between PFAS and COPD was assessed, not the impact.

#3 The definition of physical activity is incomplete; I recommend an umbrella reference such as Caspersen et al. 1985. Additionally, reference 20 refers to a type of exercise and not physical activity. Several studies have proven the effectiveness of physical activity in COPD, that includes any bodily movement requiring energy expenditure.

#4 As an observational study, a guideline for reporting observational studies, such as the STOBE statement https://www.strobe-statement.org/, should be used, and authors should confirm through the checklist that all items are reported.

#5 The discussion is generally written with hasty conclusions and a lot of "certainty" instead of suggesting these relationships between PA, PFAS and COPD, as this study is observational.

Minor comments

#1 Revise acronyms throughout the manuscript. For example, the acronym for physical activity is defined in line 64 but is not used throughout the manuscript.

#2 Authors mention where they obtained the data, but URLs should be available (section 2.1).

#3 Typo in Figure 1: "analyse" instead of "analysis".

#4 In line 98, the "NHANES Physical Activity Questionnaire (PAQ)" is not described (type of question/ answer, scoring...).

#5 Line 112 - confound factors are mentioned, but not how they were obtained, whether through literature or what the reasoning was. Additionally, confirm that all variables are reported coherently in sections 2.4 and 2.5 (models 1 and 2) and the results table, and describe all variables in terms of their meaning (for example, the variable "Cycle" is not clear to what it refers to).

#6 Lines 124 - 125 - need to explain the rationale behind separating the confounding variables in the two models - statistical? Evidence-based?

#7 Table 1 - No indentation on the categories of physical activity.

#8 Lines 203-204 - Reformulate the sentence by removing "cessation".

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Reviewer #1: Yes: Nuno Morais

Reviewer #2: No

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Moderate-intensity physical activity reduces the role of serum PFAS on COPD: A cross-sectional analysis with NHANES data

PONE-D-24-04889R1

Dear Dr. Guo,

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,

Vanessa Carels, PhD

Staff Editor

PLOS ONE

Additional Editor Comments (optional):

Please attend to Reviewer #2's minor comment regarding some missing acronyms throughout the manuscript prior to final submission, thank you!

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: All comments have been addressed

Reviewer #2: All comments have been addressed

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2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

Reviewer #2: (No Response)

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3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: (No Response)

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4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). 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

Reviewer #2: (No Response)

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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

Reviewer #2: (No Response)

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6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: (No Response)

Reviewer #2: The comments have been addressed and the paper has improved significantly, being acceptable for publication. I would just leave a small suggestion to repeat the search for the words "physical activity" throughout the article, as there are still some acronyms missing. Congratulations on your work and dedication!

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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: Nuno Morais

Reviewer #2: No

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