PONE-D-22-24143CLINICAL AND LIFESTYLE PATTERNS IN ASIAN CHILDREN WITH INFLAMMATORY BOWEL DISEASE IN THE U.S.PLOS ONE

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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: No

Reviewer #2: Partly

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

Reviewer #1: No

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: In this study, Wenjing Zong, et al. described disease phenotype and lifestyle practices including dietary pattern in Asian American children with Inflammatory Bowel Disease.

Strengths of the study:

- Study question is valid

- Adequate literature review was performed.

- The author's major findings were clearly presented. They adequately address the stated research objectives.

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The manuscript can be improved by addressing following concerns.

- Research methodology is not clearly explained. How did authors compare dietary patterns between the study population and control group? It is not clear if the difference between the two groups is statistically significant. It is difficult to conclude that the study population followed a Westernized diet that increased the risk of developing IBD based on the study findings.

- Authors may want to add hospitalizations and Surgical history data for study/control population

- Correct Spelling mistake - About 2/3 of all patients reduced diary intake post-diagnosis (Results section Line 196).

Reviewer #2: The authors of this manuscript seek to define the phenotype of children with IBD who are of Asian ancestry here in the U.S. They describe a moderate size cohort of patients amidst a large quarternary care center. Although the phenotype appears similar to other patients seen at the center, they report a higher rate of perianal involvement in their Asian patients with Crohn's disease and higher rates of proctitis in their Asian patients with UC. They go on to describe dietary habits (pre- and post-diagnosis).

This is an important topic (that is appropriate for the audience of PLoS One) although I do have some concerns about the manuscript as currently written including a number of clarifications that are needed as it takes away from the flow of the paper.

Major Concerns:

1) The duration of IBD diagnosis is not described. The authors allude to the recall bias limitation but that may be magnified if patients were diagnosed many years prior to the survey as compared to a recent diagnosis. This would be especially true for an adult-aged patient who won't be

2) Some of the comparative data was extracted from a worksheet via the ICN pathway suggesting that procedure to collect/confirm phenotypic data on cases whereas the non-Asian IBD cohort was collected in a different process. This discrepancy should at least be addressed in the limitations if not corrected

3) At the end of the Survey Design section in Methods, it is stated that if the survey failed to confirm whether the race of the subject is race, they would be excluded and they also would be excluded if they did not complete the survey. It is not clear if this exclusion is for only the survey section or for the entire study. I would assume that with only 79 surveys analyzed, that this pertains only to the dietary analysis. This should be clarified.

4) The analysis regarding Vitamin D status found that time of year was not associated with level. The description of Vitamin D was not discussed well in the methods section. It is not clear if multiple Vitamin D levels from the same patient was included in the analysis or if random values of Vitamin D across individual patients were compared. Similarly, it's not clear if included levels were after repletement.

5) It's not clear if the determination of whether someone had Vitamin D deficiency or insufficiency were through the entirety of their Crohn's history or only in one particular time course. While the numbers are high, if someone who had sufficient levels in Years 1, 2, and 4 had a low Vitamin D level in Year 3, that would be a different phenotype than someone deficient in Years 1-4. This needs to be clarified. Reference 32 also uses a different definition of Vitamin D deficiency so the 16% cited isn't an adequate comparator.

6) Much of the dietary data is descriptive in nature without clear statistical analysis but statements are made about certain foods being consumed at rare rates. Is there any strict definition of "rare"?

Minor Concerns:

1) It's not fully clear to me what is meant in the patient population section that the charts of cases were reviewed by "a gastroenterologist and a study team member" (i.e. whether 2 people reviewed it or whether it was a study team member that was a gastroenterologist).

2) It's not fully clear to me why international second opinions were excluded but other second opinions remained in (as their phenotype might be less accurate)

3) When the age at diagnosis is discussed for the Asian patients with IC, it is stated that it is lower, although it's not clear what comparative group is being used. I suspect this is "lower than Asian UC cohort and Asian CD cohort" but that should be clarified. Similarly, in that section, there is the statement of a large percentage of patients diagnosed before 6 years of age but not clear if this is the Asian IBD group or Asian IC group (or another group).

4) When zip code data was analyzed and 92% of patients were reported to reside "locally", it's not clear what is meant: within state? within several states? by geographic distance?

5) In the Asian UC cohort, they describe that the "highest proportion of the patients have pancolitis". I suspect this is meant to be the majority of patients have pancolitis rather than this cohort has a higher percentage of pancolitis (since Table 1 suggests that is not the case).

6) The phenotype of the South Asian patients seems to be quite similar. It seems that this section could be shortened and that table be moved in as a Supplementary Table. The wording around the perianal Crohn's involvement gives the impression that this is different than the overall Asian cohort but it appears that it is quite similar.

7) It might be helpful to also state what percentage of patients have EITHER a first or second degree relative with IBD. It's not clear whether the 16 out of 79 patients that had a second degree family member with IBD did NOT have a first degree family member with IBD.

8) There appears to be a word missing in the paragraph in the Discussion section regarding Vitamin D status that starts with "Furthermore"

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Reviewer #1: No

Reviewer #2: No

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CLINICAL AND LIFESTYLE PATTERNS IN ASIAN CHILDREN WITH INFLAMMATORY BOWEL DISEASE IN THE U.S.

PONE-D-22-24143R1

Dear Dr. Albenberg,

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,

Valérie Pittet, PhD

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

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

Reviewer #1: Yes

Reviewer #2: Yes

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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: 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

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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: I have no additional comments and all my concerns were addressed. The manuscript is ready for publication if other reviewers concerns are addressed.

Reviewer #2: The authors have made improvements to the manuscript based on the comments that I had submitted and I have no further concerns.

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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

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