PONE-D-24-10830BOAS in the Boston Terrier: a healthier screw-tailed breed?PLOS ONE

Dear Dr. Ladlow,

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Ioannis Savvas, DVM, Ph.D.

Academic Editor

PLOS ONE

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2. 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 If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references.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 If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice.

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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: I Don't Know

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 authors effectively provide background information on the significance of brachycephalic obstructive airway syndrome (BOAS) in certain dog breeds, emphasizing related welfare concerns. They introduce their research question, aiming to investigate the prevalence and risk factors for BOAS in Boston Terriers, a breed known for its brachycephalic features. The study, involving 104 Boston Terriers, comprehensively assesses respiratory function and conformational characteristics. By comparing Boston Terriers to other brachycephalic breeds and delving into genetic and health similarities, the authors contextualize their research within the broader field of brachycephaly-related health issues. Overall, this study provides valuable insights into the prevalence and risk factors associated with BOAS in Boston Terriers.

Although not explicitely stated, the authors suggest some key findings, like how their study might help breeders and owners choose Boston Terriers less likely to have BOAS.

The authors also mention other research on BOAS in popular brachycephalic breeds and efforts to address welfare concerns. While they don't go into detail about how their study connects to this research, they imply that their work will help fill gaps in our knowledge about BOAS in Boston Terriers compared to other breeds, which could be valuable for future research.

While the methodology, including whole-body barometric plethysmography and clinical examination, is sound. However, limitations related to sampling bias due to volunteer-based recruitment are acknowledged. Authors might want to consider discussing how this bias could affect how well the findings apply to other groups and suggest ways to fix it, like getting participants from more places (multi-center recruitment).

There are also sample size limitations in analyzing differences between BOAS severity grades. Please address the limitations imposed by the sample size, particularly in analyzing differences between BOAS severity grades. Addressing these limitations, discussing potential implications for the interpretation of the results and consider ing suggestions for future research to address this limitation would strenghten the study’s conclusions.

Clear presentation of results and interpretation of findings in the context of previous research and breed standards is given in the discussion.

Plethysmography serves as a vital tool for evaluating respiratory function, especially in studies investigating brachycephalic obstructive airway syndrome (BOAS) in dogs. However, the study's efficacy may be affected by its sample size. With only 12 BOAS-affected Boston Terriers undergoing whole-body barometric plethysmography, the sample size is relatively small, potentially limiting the statistical power and confidence in the findings regarding respiratory parameters. Moreover, this limitation may have hindered the observation of quantifiable differences in respiratory parameters across different BOAS severity grades. Therefore, while plethysmography is valuable, the study's small sample size should be considered when interpreting the results. Future research with a larger sample size would enhance the validation and robustness of findings concerning respiratory function in BOAS-affected Boston Terriers.

The findings of this study are likely applicable to Boston Terrier populations in similar settings, although variations may exist across different regions. However, it's important to acknowledge that other researchers may have different experiences. Factors such as geographical location and breeding practices could influence the health status of Boston Terriers. For instance, anecdotal evidence suggests that populations in Southern Europe may exhibit higher rates of severe BOAS cases compared to those in other regions. Collaborative research efforts across different regions and populations of Boston Terriers may provide a more comprehensive understanding of BOAS and its associated risk factors

While the main focus is on BOAS, the study also identifies other health issues related to the brachycephalic and screw-tailed phenotype of Boston Terriers, including congenital vertebral malformations, neurological deficits, and ocular abnormalities. However, further research is needed to fully understand the significance of these findings and their implications for breed predisposition to disease.

Overall, the discussion provides a comprehensive overview of the study findings, highlighting the importance of understanding BOAS and its associated risk factors in Boston Terriers, while also acknowledging the need for further research to address other health issues in this breed.

I recommend acceptance for publication with minor revisions to address the identified limitations and clarify certain points.

Reviewer #2: Comments on specific lines:

Line 250 - I was uncertain why a 1-sided test was chosen for analysing the proportion of Grade 0 dogs? Wouldn't it be equally of interest if % Grade 0s in Boston Terriers was either higher or lower than the sample population?

Line 256 - the time periods for the flow rate analysis are referred to sometimes as percentages of the total time and sometimes as decimal fractions. It would be better to keep this consistent throughout.

Line 257 - I'm wondering why you didn't make use of your mixed model to compare the flow rate changes? It would be more usual, I think, to use your model coefficients and their variance-covariance matrix to calculate the predicted flow rate change differences and their variance, and test that way.

Line 261-2 - Is there a word missing in this sentence somewhere? It didn't quite make sense to me.

Line 272 - Again I'm wondering why the choice to use a 1-sided test for the continuous BOAS risk factors.

Line 273 - Should the list of continuous variables in brackets also include EWR, SI and CFR?

Line 339 - I'm not sure you'd really call the change in flow rate in the grade 0s 'steady' as this implies a pretty constant rate - it looks like there is a rather lower rate of increase for 0.5-0.75 than in 0.25-0.5. 'Steady' is much more applicable to the control dogs, though.

Lines 341-2 - I found this sentence to be a little unclear. I think it would help to clarify that you aren't talking about all the groups here just the control and grade 0 dogs.

Line 365 - Whilst the neck girth ratio is clearly significant, 0.62 vs 0.63 seems like a very small difference. Is this small difference likely to be practically / clinically significant?

General comments:

Overall, I think this is an interesting paper on an important subject, with a wide variety of variables looked at, and contributes useful information to those interested in issues around brachy breeds.

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Reviewer #1: Yes: Vladimira Erjavec

Reviewer #2: No

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PONE-D-24-10830R1BOAS in the Boston Terrier: a healthier screw-tailed breed?PLOS ONE

Dear Dr. Ladlow,

Thank you for submitting your revised manuscript to PLOS ONE. Please amend the manuscript according to a minor comment by one of the reviewers, before it can be accepted for publication.

Please submit your revised manuscript by Nov 14 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,

Ioannis Savvas, DVM, 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 #2: (No Response)

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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: I Don't Know

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

**********

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 manuscript presents a well-organized and thorough study on BOAS in Boston Terriers. The manuscript is well-organized, and the data support the conclusions. The methods used are suitable for the study's goals. The statistical analysis seems appropriate, with clear presentation of results, though I am not an expert in statistics and therefore cannot fully assess the appropriateness of the statistical methods used.

The authors have complied with data availability requirements, making the underlying data easily accessible. The manuscript is clearly written, making it straightforward to follow. The discussion is particularly valuable, especially in addressing the differences between Boston Terriers and other brachycephalic breeds, adding useful insights to the existing knowledge.

Reviewer #2: Thank you for addressing the majority of my previous comments. There is one that is still outstanding though - the sentence on line 261-2 that I found to be unclear was this one - 'In the absence of missing values, P values and multiple comparison tests are given the same as repeated measures ANOVA'. In the revised manuscript, it looks like you altered the sentence before this one, which was already fine! I think that it should probably(?) say something like 'In the absence of missing values, P values and multiple comparison tests given by this method are the same as would be obtained by repeated measures ANOVA'. Apologies for the confusion over which sentence I was talking about in my original comments!

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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.

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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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[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.

BOAS in the Boston Terrier: a healthier screw-tailed breed?

PONE-D-24-10830R2

Dear Dr. Ladlow,

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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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,

Ioannis Savvas, DVM, Ph.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: 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

**********

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

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 #2: 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 #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 #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 #2: No

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