PONE-D-21-01414

A rapid calprotectin test for the diagnosis of pleural effusion

PLOS ONE

Dear Dr. Vázquez-Iglesias,

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.

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In adding to the issues raised by the reviewers, please clarify the main purpose of the paper.

Is a validation of using calprotectin in pleural fluid as a surrogate for leucocytes, in diagnosing malignant or infections effusions? Or is it a comparison between calprotectin POCT and ELISA methods.

Please explain abbreviations at first occurrence if used > 3times, remember the abstract is a separate unity.

The manuscript could benefit from native English editing.

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We look forward to receiving your revised manuscript.

Kind regards,

Pal Bela Szecsi, M.D. D.M.Sci.

Academic Editor

PLOS ONE

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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: Yes

Reviewer #2: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: Yes

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: Yes

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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: The study " A rapid calprotectin test for the diagnosis of pleural effusion" addresses to an important topic in clinical practice: the diagnosis of malignant pleural effusion, especially in cases where the patient has no previous diagnosis of malignant disease,

and/or the cytological examination of the pleural effusion was negative for cancer cells.

The article presents a clear Introduction and objectives and the methodology used is adequate for the study.

Comments:

1) In the pag 4 - Methods - the authors report that only "healthy adults over 18 years were eligible for the study..." If they have pleural effusion, they are not healthy!! I suggest correction.

2) In the page 10 - Results - table 3: The values of Calprotectin presented as 5000 ng/mL in MPE, does it mean that there was no detection with the assay used? If the lower detection value was considered for cases with Calprotectin undetectable by the assay used, this criterion did not prejudice the statistical analysis?

3) The authors should refer to the average cost of the test and the equipment, especially considering its use in developing countries;

4) In the study there is no reference to the positivity of the PE cytology. What was the criterion used in the definition of MPE: cytology or biopsy? It would be interesting to report on the performance of cytology in the case of MPE.

5) Considering the values obtained for specificity, PPV and diagnostic accuracy, would the authors really suggest using this POCT assay for clinical management ??

Reviewer #2: This paper proposes a rapid measurement of calprotectin to diagnose pleural effusion. The diagnostic performance of calprotectin level is verified in clinical practice, and the correlation between the measurement method proposed in this paper and the standard methods is analyzed, which provides effective guidance for clinical diagnosis. However, there are still some problems in this paper:

1. Some abbreviations in this paper are not given full names, so that the paper is less readable.

2. What is the main contribution of this paper? Is the calprotectin level measurement method proposed in this paper for the first time? If so, this paper should focus on the proposed measurement method. Or does the experiment prove that the method can be used in clinical practice? The contribution of this article should be clearly written.

3. The advantages of the Quantum Blue® sCAL measurement method are mentioned in the paper, but the disadvantages of this method are not clearly pointed out, which should be supplemented in this paper.

4. In the assay validation part, is it reasonable to take samples of 5000-24000 to analyze the correlation between the two measurement methods? Need to point out the reason for this analysis, or supplement the correlation analysis of the two measurement methods on 253 samples.

5. The paper does not give the diagnosis result of calprotectin level measured by ELISA method, and the result similar to Table 4 for ELISA method should be given.

6. Does the cut-off value in this paper have guiding significance for the follow-up clinical diagnosis of pleural effusion?

7. there are many relevant predictive models have been proposed for the diagnosis of pleural effusion, the authors should make a deep investigation on this issue in the introduction part, such as the works [1]-[4].

[1] J. M. Seixas, J. Faria, J. B. O. Souza Filho, A. F. M. Vieira, A. Kritski, and A. Trajman, "Artificial neural network models to support the diagnosis of pleural tuberculosis in adult patients," International Journal of Tuberculosis and Lung Disease, vol. 17, pp. 682-686, May 2013.

[2] C.-C. Shu, J.-Y. Wang, C.-L. Hsu, L.-T. Keng, K. Tsui, J.-F. Lin, et al., "Diagnostic role of inflammatory and anti-inflammatory cytokines and effector molecules of cytotoxic T lymphocytes in tuberculous pleural effusion," Respirology, vol. 20, pp. 147-154, Jan 2015.

[3] J. Klimiuk, A. Safianowska, R. Chazan, P. Korczynski, and R. Krenke, "Development and Evaluation of the New Predictive Models in Tuberculous Pleuritis," Adv Exp Med Biol, vol. 873, pp. 53-63, 2015.

[4] Li C, Hou L, Sharma B, Li H, Chen C, Li Y, Zhao X, Huang H, Cai Z, Chen H. Developing a new intelligent system for the diagnosis of tuberculous pleural effusion. Computer Methods & Programs in Biomedicine, 2018, 153: 211-225.

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Reviewer #1: No

Reviewer #2: No

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A rapid calprotectin test for the diagnosis of pleural effusion

PONE-D-21-01414R1

Dear Dr. Vázquez-Iglesias,

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,

Pal Bela Szecsi, M.D. D.M.Sci.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

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: (No Response)

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: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: 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 #2: Yes

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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: Yes

**********

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 adequately answered the questions and included the relevant points of the comments in the new version of the text.

Reviewer #2: The authors have solved all the problems that I have raised, now the paper is ready for publication.

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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: No

Reviewer #2: No