Peer Review History

Original SubmissionJune 14, 2020
Decision Letter - Linglin Xie, Editor

PONE-D-20-18145

Association between sites and severity of eczema and the onset of cow’s milk and egg allergy in children

PLOS ONE

Dear Dr. Futamura,

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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We look forward to receiving your revised manuscript.

Kind regards,

Linglin Xie

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: Partly

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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: Major comments:

This article is a retrospective study on the association between CMA and EA and the sites and severity of infantile eczema. The study analyzed the data from patients aged 2 – 19 years with atopic disease and was treated in a pediatric allergy clinic. The data analysis has several limitations based on their experimental design, but the authors have clearly stated these limitations in their discussion. The data analyses support their conclusions that IgE-mediated CMA was positively correlated with severe facial eczema during infancy among children with atopic disease.

One major issue with the statistical analyses is that the author conducted multiple tests during their analyses. At the same time, they used a threshold P-value of 0.05 for significance, a typical cut-off when doing a single test. I would suggest that they use an adjusted p-value instead to control the false positive rate for this multiple test case.

Minor comments:

Line 204: It is not very clear why the limitation would allow the authors to observe the relationship they mentioned. Maybe the authors could make the expression clearer for the readers.

Reviewer #2: This manuscript describes a retrospective study about the relationship between eczema and cow milk or egg allergy in children. It demonstrated that the incidence of infantile eczema is higher in subjects with cow milk allergy, especially facial eczema. However, major concerns are also noticed as listed:

1. Language editing is recommended. Such as the usage of “whereas” in the Discussion section

2. Does the paper consider any potential correlation between different sites of infantile eczema? The paper mentioned 289 subjects are involved in the study, while according to Table 2, there seems to be a few subjects with multiple sites of infantile eczema.

3. In the Conclusion section, the paper states that the incidence of IgE-mediated CMA is higher in atopic children during their first year. However, in the “Material and methods” section, it says the collected data were from 2-19 years old patients. Meanwhile, I could not find any data mentioning any significant difference of CMA incidence during their first year.

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6. 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.

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Reviewer #1: No

Reviewer #2: Yes: Yushu Qin

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Revision 1

Reviewer #1: Major comments:

This article is a retrospective study on the association between CMA and EA and the sites and severity of infantile eczema. The study analyzed the data from patients aged 2 – 19 years with atopic disease and was treated in a pediatric allergy clinic. The data analysis has several limitations based on their experimental design, but the authors have clearly stated these limitations in their discussion. The data analyses support their conclusions that IgE-mediated CMA was positively correlated with severe facial eczema during infancy among children with atopic disease.

One major issue with the statistical analyses is that the author conducted multiple tests during their analyses. At the same time, they used a threshold P-value of 0.05 for significance, a typical cut-off when doing a single test. I would suggest that they use an adjusted p-value instead to control the false positive rate for this multiple test case.

RESPONSE: We appreciate your suggestion. We have adjusted the p-values in Table 2 and 3 by Holm-Bonferroni correction and have added the following sentence in the Materials and Methods section; “The multiplicity of tests was adjusted by Holm-Bonferroni correction.” We have also changed the text accordingly.

Minor comments:

Line 204: It is not very clear why the limitation would allow the authors to observe the relationship they mentioned. Maybe the authors could make the expression clearer for the readers.

RESPONSE: We agree that the meaning of that sentence was not clear for readers. We have changed it to “However, we could observe specific relationship of eczema with CMA, but not with EA, in atopic children.”

Reviewer #2: This manuscript describes a retrospective study about the relationship between eczema and cow milk or egg allergy in children. It demonstrated that the incidence of infantile eczema is higher in subjects with cow milk allergy, especially facial eczema. However, major concerns are also noticed as listed:

1. Language editing is recommended. Such as the usage of “whereas” in the Discussion section.

RESPONSE: We appreciate your recommendation. We have asked the language review to the company again and attach the certificate of English editing.

2. Does the paper consider any potential correlation between different sites of infantile eczema? The paper mentioned 289 subjects are involved in the study, while according to Table 2, there seems to be a few subjects with multiple sites of infantile eczema.

RESPONSE: We have analyzed the correlation between different sites of eczema. The results are presented below:

Spearman’s correlation coefficient of each site of infantile eczema (see the attached file)

We have added the following sentences in the Materials and Methods and in the Results; “Spearman’s correlation coefficient was calculated for correlation between different sites of infantile eczema” and “Positive correlations were observed between all eczema site pairs. Strong correlations were found between the upper and lower limbs (correlation coefficient r = 0.83) and moderate correlations were found between the trunk and the upper limb (r = 0.69) and between the trunk and the lower limb (r = 0.65). The other pairs were weakly correlated (all r < 0.40).”

3. In the Conclusion section, the paper states that the incidence of IgE-mediated CMA is higher in atopic children during their first year. However, in the “Material and methods” section, it says the collected data were from 2-19 years old patients. Meanwhile, I could not find any data mentioning any significant difference of CMA incidence during their first year.

RESPONSE: We have mentioned “Caregivers of all patients were asked whether their children presented with eczema in the first year of life” in the Materials and Methods. However, for clearer expression, we have changed the prior sentence to “The study data were collected from electronic medical records and included infantile eczema, previous immediate allergic symptoms…”

Attachments
Attachment
Submitted filename: Response_to_Reviewers.docx
Decision Letter - Linglin Xie, Editor

Association between sites and severity of eczema and the onset of cow’s milk and egg allergy in children

PONE-D-20-18145R1

Dear Dr. Futamura,

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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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,

Linglin Xie

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: 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: Yes

**********

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: 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: (No Response)

Reviewer #2: (No Response)

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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

Formally Accepted
Acceptance Letter - Linglin Xie, Editor

PONE-D-20-18145R1

Association between sites and severity of eczema and the onset of cow’s milk and egg allergy in children

Dear Dr. Futamura:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

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 plosone@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. Linglin Xie

Academic Editor

PLOS ONE

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