Changes in lung function and dyspnea perception in Colombian Covid-19 patients after a 12-week pulmonary rehabilitation program

Carlos D. Páez-Mora; Diana Carolina Zona; Teddy Angarita-Sierra; Matilde E. Rojas-Paredes; Daniela Cano-Trejos

doi:10.1371/journal.pone.0300826

Peer Review History

Original SubmissionMarch 11, 2024
10 Jun 2024 Decision Letter - Hugh Cowley, Editor PONE-D-24-08060Changes in lung function and dyspnea perception in Colombian Covid-19 patients after a 12-week pulmonary rehabilitation program.PLOS ONE Dear Dr. Zona, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Your manuscript has been evaluated by two reviewers, and their comments are appended below. The reviewers have commented on the study design, conclusions, and the statistical analysis, among their other comments. Please ensure you address each of the reviewers' comments when revising your manuscript. Please submit your revised manuscript by Jul 22 2024 11:59PM. 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You also have the option of uploading the data as Supporting Information files, but we would recommend depositing data directly to a data repository if possible. We will update your Data Availability statement on your behalf to reflect the information you provide. [Note: HTML markup is below. Please do not edit.] 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 ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: Yes ****** 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: No ****** 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: Yes ****** 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: This study involved rehabilitation programs that had positive effects on respiratory function after SARS-CoV-2 infection ,Here are my comments 1.The inclusion criteria did not discriminate between degree of COVID-19 infection which could affect the degree of lung injury.If the patients had only mild diseases,the recovery can happen spontaneously without rehabilitation 2. The FEF 25-75% was nit different between both groups.Why the author conclude that this might be associated with changes in the small airway 3.Tle study did not measure previous lung function before COVID-19 infection,therefore how can you conclude that the cases that didnot improve could be explained by underlying lung disorders. 4,It will be better to perform DLCO test in addition Reviewer #2: Your study is sound and practical about ventilation effectiveness and complications, and demistify exclusion criteria based on comorbidities and demographics. Intensivists and pathologists in other countries also reported alveoli damage depending on the parameters. I noticed the issues below that if addressed will improve the quality of your paper: Sample size n=100 with N=231 corresponds to e=7.5% instead of 5%, either adjust CI or run the analysis with n=146; Normalize VMN/VMNI, IV/NIV and IMV/NIMV abbreviations, also variables e.g. mMRC/MRC; Missing decimal point in Height's P in Table 3; Two plots named FEV1 in Figure 1; Figure 3 is difficult to read with color blindness See https://stackoverflow.com/questions/57153428/r-plot-color-combinations-that-are-colorblind-accessible ; Add summary statistics for spirometry variables pre and post intervention (e.g. in Table 2), supporting the lack of obstructive patterns before PR (in Discussion); Literature has retrospective studies of Covid-19 patients 10+ months after discharge, with radiology evaluations and other PR methods. Did you thought of extending your study or adding another cohort (e.g. without the 100% PR compliance inclusion criteria) ? ****** 6. 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Revision 1
18 Jul 2024 Author Response Dear Editor, We wish to respond to the reviewers of our research article entitled “Changes in Lung Function and Dyspnea Perception in Colombian COVID-19 Patients After a 12-Week Pulmonary Rehabilitation Program.” Below, we address each point. It is important to clarify that these changes have been applied to the manuscript. 1. Is the manuscript technically sound, and do the data support the conclusions? • Coherence errors between sections have been corrected. 2. Have the authors made all data underlying the findings in their manuscript fully available? • All files containing the raw data have been uploaded as supplemental material in Excel format. 3. This study involved rehabilitation programs that had positive effects on respiratory function after SARS-CoV-2 infection. Here are my comments: The inclusion criteria did not discriminate between the degree of COVID-19 infection, which could affect the degree of lung injury. If the patients had only mild disease, recovery could occur spontaneously without rehabilitation. • Severity criteria for SARS-CoV-2 infection have been incorporated into the methodology to support the findings of the study pre- and post-pulmonary rehabilitation. 4. The FEF 25-75% was not different between both groups. Why do the authors conclude that this might be associated with changes in the small airways? • This point has been corrected. 5. The study did not measure previous lung function before COVID-19 infection; therefore, how can you conclude that the cases that did not improve could be explained by underlying lung disorders? • Comorbidities were included as variables in the analysis. ANCOVA analysis showed no correlation between age, height, weight, and lung function measures (FVC, FEV1, MRC). Nested ANOVA indicated that the presence or absence of comorbidities did not affect the differences observed in FVC and FEV1 between men and women. The text has been adjusted accordingly. Indeed, we do not have previous data on lung function before COVID-19 infection. 6. It would be better to perform DLCO testing in addition. • DLCO testing was not performed because the research institution lacked this diagnostic capability, due to the technological availability in the Colombian region where the research was conducted. 7. Your study is sound and practical regarding ventilation effectiveness and complications, and it demystifies exclusion criteria based on comorbidities and demographics. Intensivists and pathologists in other countries also reported alveolar damage depending on the parameters. I noticed the issues below that, if addressed, will improve the quality of your paper: Sample size n=100 with N=231 corresponds to e=7.5% instead of 5%; either adjust CI or run the analysis with n=146. • This point has been corrected. 8. Normalize VMN/VMNI, IV/NIV, and IMV/NIMV abbreviations, as well as variables, e.g., mMRC/MRC. • This point has been corrected. 9. Missing decimal point in Height's p-value in Table 3. • This point has been corrected. 10. Two plots are named FEV1 in Figure 1. • This point has been corrected. 11. Figure 3 is difficult to read for individuals with color blindness. • All figures have been reedited. We employed the IBM Color Blind Safe Palette as follows: Ultramarine 40, Indigo 50 (#785EF0), Magenta 50 (#DC267F), Orange 40 (#FE6100), Gold 20 (#FFB000). 12. Add summary statistics for spirometry variables pre- and post-intervention (e.g., in Table 2). • We uploaded a file with the summary statistics for spirometry variables pre- and post-intervention as supplemental material. 13. Supporting the lack of obstructive patterns before PR (in Discussion). • While we acknowledge the importance of expanding the study as suggested, it is not possible to do so due to financial limitations. This is a common challenge in Latin America. However, we consider the study findings to be relevant as they demonstrate the effects of pulmonary function before and after a rehabilitation program in a Latin American region. Finally, we would like to request that the order of the authors presented in the manuscript be maintained. At the time of submitting the manuscript, the page did not allow selecting who is the corresponding author and who is the first author. Attachments Attachment Submitted filename: Response to Reviewers.pdf https://doi.org/10.1371/journal.pone.0300826.r002
24 Sep 2024 Decision Letter - Mehrnaz Kajbafvala, Editor PONE-D-24-08060R1Changes in lung function and dyspnea perception in Colombian Covid-19 patients after a 12-week pulmonary rehabilitation program.PLOS ONE Dear Dr. Zona, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Nov 08 2024 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript: A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Mehrnaz Kajbafvala, Ph.D Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] 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 #3: (No Response) ******** 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 #3: Partly ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #3: Yes ****** 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 #3: 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 Reviewer #3: No ****** 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: the authors have corrected the manuscript as I suggested and should be accpted for publication.however,the corrected part should be highlight to be easier to read Reviewer #3: Please address these questions: Abstract: >For the first time, please use the two abbreviations PR and mMRC in full form. >In the result section you should mention the exact p-value for statistical significance. Line 35: “A large sample of patients is needed to clarify the effects of therapy on respiratory function” is the limitation of the study and there is no need to mention it in the conclusion of the abstract. Introduction: Lines 80-81: “The Ethical Guidelines for Human Research from the Declaration of Helsinki were followed, and written informed consent was obtained for participation.”, You should put this sentence in the method section instead of the introduction section. >Introduction is too long, please omit some unnecessary sentences. Materials and methods: >Please use FEF and PEF in full for the first time and then use them as abbreviations throughout the manuscript. Line 118: ”60 to 80% of the maximum cardiac capacity.”, Please also mention in this section the intensity of the exercises used; mild, moderate, sever. Lines 126-130: Training sessions did not include warm-up? A training session should include both warm-up and cool-down. > The word “we” has been used a lot through the manuscript, please remove some of them and write the sentence in a passive form. Lines 181-186: If there is any reference for classifying the severity of the symptoms, please add. Discussion: Please clarify the limitations of your study at the end of this section. ****** 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: No Reviewer #3: No ******** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. https://doi.org/10.1371/journal.pone.0300826.r003
Revision 2
7 Oct 2024 Author Response Dear Editor’s, Thank you for the opportunity to revise our manuscript titled “Changes in Lung Function and Dyspnea Perception in Colombian COVID-19 Patients After a 12-Week Pulmonary Rehabilitation Program.” We appreciate the valuable feedback from you and the reviewers, which has helped us enhance the quality of our work. Below, we address each point raised by the reviewers. Abstract 1. Use of full forms for PR and mMRC: Thank you for your suggestion. We have revised the manuscript to include the full forms of PR (pulmonary rehabilitation) and mMRC (modified Medical Research Council) the first time they appear. 2. Mentioning exact p-values: We acknowledge that Multidimensional Scaling (MDS) and Linear Discriminant Analysis (LDA) do not provide p-values, as they are classification techniques rather than hypothesis-testing methods. However, we have included exact p-values for all relevant univariate analyses in the results section to enhance clarity. 3. Limitation about sample size in the abstract conclusion: We have removed the statement regarding the need for a larger sample size from the conclusion of the abstract, recognizing it as a limitation more suitable for the discussion section. Introduction 1. Ethical guidelines statement: We have moved the sentence regarding the Ethical Guidelines for Human Research from the Declaration of Helsinki from the introduction to the methods section, as suggested. 2. Omitting unnecessary sentences: We have shortened the introduction by removing the following sentences: o “Which involves evaluating the mechanical properties of the respiratory system through volumes and capacities; it provides relevant information for the classification of both obstructive and restrictive disorders.” o “Which has motivated evaluations of lung function to characterize changes in the lung parenchyma and assess the need for treatment.” Materials and Methods 1. Use of FEF and PEF in full: We have made the requested adjustments and now use FEF (forced expiratory flow) and PEF (peak expiratory flow) in full the first time they appear. 2. Intensity of exercises: The intensity of exercises has been specified in the revised manuscript. 3. Warm-up and cool-down periods: We have rectified the oversight regarding warm-up and cool-down periods, ensuring that training sessions now include both. 4. Reducing use of "we": We have thoroughly revised the manuscript to reduce the frequency of the word "we" and adopted a more passive voice, making the writing more objective. 5. Reference for symptom severity classification: We have added the appropriate reference to support the classification of symptom severity. Discussion 1. Clarifying limitations: We have clarified the limitations of our study at the end of the discussion section, as suggested. Attached, we are sending the unmarked version of the document, as well as the version with track changes to facilitate the review and reading of the changes. We believe these revisions address all the concerns raised by the reviewers. Thank you for your consideration of our manuscript. We look forward to your positive response. Attachments Attachment Submitted filename: Response to Reviewers Sept 2024.pdf https://doi.org/10.1371/journal.pone.0300826.r004
23 Oct 2024 Decision Letter - Mehrnaz Kajbafvala, Editor Changes in lung function and dyspnea perception in Colombian Covid-19 patients after a 12-week pulmonary rehabilitation program. PONE-D-24-08060R2 Dear Dr. Diana Carolina Zona 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. An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager® and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Mehrnaz Kajbafvala, Ph.D Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0300826.r005
Formally Accepted
5 Nov 2024 Acceptance Letter - Mehrnaz Kajbafvala, Editor PONE-D-24-08060R2 PLOS ONE Dear Dr. Zona, I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now being handed over to our production team. At this stage, our production department will prepare your paper for publication. This includes ensuring the following: * All references, tables, and figures are properly cited * All relevant supporting information is included in the manuscript submission, * There are no issues that prevent the paper from being properly typeset If revisions are needed, the production department will contact you directly to resolve them. If no revisions are needed, you will receive an email when the publication date has been set. At this time, we do not offer pre-publication proofs to authors during production of the accepted work. Please keep in mind that we are working through a large volume of accepted articles, so please give us a few weeks to review your paper and let you know the next and final steps. Lastly, if your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. If we can help with anything else, please email us at customercare@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Mehrnaz Kajbafvala Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0300826.r006

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