PONE-D-25-08475Asthma Status and Suicidal Behavior Risk: A Meta-Analysis of Cohort StudiesPLOS ONE

Dear Dr. He,

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.

The metanalysis fits the criteria for publication in the journal with mostly sound methodology and well presented results. The manuscript will benefit from refinement based on the reviewer's comments including clarifying in the inclusion criteria the definition of Asthma, some subsections clarifications in the methodology with inclusion of the PRISMA checklist and expanding the discussion further on interpretation of the results and implications for practice.

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Toufic Ahmad Chaaban, M.D.

Academic Editor

PLOS ONE

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Additional Editor Comments :

The metanalysis fits the criteria for publication in the journal with mostly sound methodology and well presented results. The manuscript will benefit from refinement based on the reviewer's comments including clarifying in the inclusion criteria the definition of Asthma, some subsections clarifications in the methodology with inclusion of the PRISMA checklist and expanding the discussion further on interpretation of the results and implications for practice.

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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

Reviewer #3: Yes

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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: No

Reviewer #3: 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

Reviewer #3: 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: Thank you for the opportunity to review your manuscript, which is on an interesting and important aspect of asthma care. The manuscript is generally well written and is engaging.

Reading through the manuscript, I had the following queries, which I feel should be addressed:

1) Page 3, Lines 6-8, I would advise removing the reference to asthma's relation to COVID-19 mortality, as it is not relevant to this study

2) It would be useful to have some information on comment on how the authors of the included studies have defined asthma, and particularly whether there was any discussion of severe asthma vs controlled asthma. Anecdotally, we have found severe asthma is particularly associated with negative effects on mental health, and it would be good for authors to comment on whether the papers included looked at asthma severity

3) There is significant heterogeneity in terms of baseline age of patients - did the authors do any work looking at age-adjusted mortality/suicide risk? Often suicidal behaviour will vary in age groups, with (at least in the UK) an increase in middle age, which some studies did not capture

4) Page 12, line 4 - Authors state "For specific suicidal behaviours, the meta-analysis of 4 cohorts showed that...". Could the authors be clearer on what the specific suicidal behaviours are or what they mean by this? It is unclear to my reading

5) Page 14, line 18 - Authors state they propose IL-6 dysregulation as a potential contributor for these findings, but this is actually outlined later in the paper, and could be restructured. The authors state there is post-2019 evidence but do not cite at this point.

Reviewer #2: Overall, this paper is important. I appreciate the work the authors put into compiling the studies in this systematic review.

General Comments:

— Given the similar study by Zhang et al. (2019), titled 'Suicidality among patients with asthma: A systematic review and meta-analysis,' could the authors clarify the added value of this study to the existing literature? Are there any new insights, differences in methodology, or unique findings that distinguish this study from the previous studies?

Specific Line-by-Line Comments

— Page 4, subsection Eligibility criteria, first line of the second paragraph: The statement "Exclusion criteria included: (b) Duplicate publications" may not be accurate. Removing duplicates is a data management step, not an exclusion criterion. It would be clearer to describe this in the study selection process.

— Same subsection (Eligibility criteria): Were language and region considered as criteria? Please clarify whether language or regional restrictions were applied. These factors affect how complete and useful the review is.

— Page 5, Subsection Study Quality: The authors stated that they used three domains from the Newcastle-Ottawa Scale (NOS): selection, comparability, and outcomes. These domains appear to cover the main aspects of study quality. However, given the focus on social behavior and asthma, do you think these three domains are sufficient to assess the quality of the included studies? Additional factors related to social and environmental influences may also be relevant. I would appreciate knowing whether any other factors should be considered alongside these three domains to ensure a comprehensive quality assessment.

— Page 12, Subsection Meta-analysis of current asthma and suicidal behavior risk: The authors suggested the presence of publication bias. Given that publication bias may lead to an incomplete or skewed representation of the evidence, can the quality of the included studies still be considered high? It is important to address how this potential bias might influence the overall quality and conclusions of the review, particularly considering the small sample size of included studies (only 12).

— The PRISMA 2020 for Abstracts checklist is not attached. Why?

— The authors have stated that all data are fully available without restriction. However, I was unable to locate any attached data or a link to access it. Could the authors please clarify where the data can be accessed or provide the appropriate link to ensure transparency and reproducibility?

Reviewer #3: This is a great and interesting meta-analysis exploring the relationship between asthma and suicidal behaviours. The paper was easy to follow and generally well written. I only have 1 main recommendation:

1) I would recommend going into more depth regarding the relationship between asthma and suicidal behaviours as it was a bit unclear in this paper. Specifically, the section in the discussion, 'Interpretation of findings', should be expanded. Rather than listing general reasons for the relationship between asthma and suicidal behaviours, the authors should delve deeper into the specific mechanisms, and how they play a role in suicidal behaviors, and whether their findings support any of these mechanisms. Additionally, the last line of this section mentions "However, residual confounding by unmeasured factors (e.g., childhood trauma, genetic susceptibility) cannot be excluded(48)." - I wonder if the findings from this meta analysis is able to provide more information on what other confounding factors may bias this finding and how.

Perhaps also highlighting why asthma and suicidal behaviours is related in the Introduction would help the reader see that this association could potentially be more than a correlation.

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Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

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Asthma Status and Suicidal Behavior Risk: A Meta-Analysis of Cohort Studies

PONE-D-25-08475R1

Dear Dr. He,

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,

Toufic Ahmad Chaaban, M.D.

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 #2: (No Response)

Reviewer #3: 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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #2: Yes

Reviewer #3: 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 #2: Based on your response, since no language restrictions were applied in your eligibility criteria, did you consider including language as a data item? Reporting this would allow readers to assess how many studies were conducted in different languages and whether language may have influenced the findings or their interpretation.

Reviewer #3: (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 #2: No

Reviewer #3: No

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