PONE-D-21-14468

Out-of-hospital cardiac arrest and ambient air pollution: a dose-effect relationship and a predictive role in OHCA risk.

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: No

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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: Authors have established statistically significant correlations between concentrations of air pollutants and out-of-hospital cardiac arrest. These correlations appear to follow a dose-response curve between concentration and number of events.

The quality of the writing is very good and the conclusions of the authors are sound. The discussion is well thought out. There are some easily modifiable points that can be addressed prior to publication:

1. The figures are of very low quality and should be replaced. Tables are fine.

2. In the regression analyses, presumably the concentrations published are the average over the course of 24 hours (but the y axis of these dose responses is not readable). Was there time-of-day data exposure available? Since cardiovascular events are somewhat rhythmically controlled, it would be interesting to see if these dose-responses were robust enough to correlate with hourly pollutant concentrations. If this is data is not available, perhaps only a brief mention of how the pollutant concentrations were reported.

3. Typo: (first paragraph of Air pollution and incidence of OHCA) ...was still statically significant (Figure 2)... ---> statistically significant

Reviewer #2: Introduction

- "look for a dose-effect curve" sounds very awkward, pls rephrase

Methods

- "A correlation between the mean concentrations of every pollutant among the four provinces was tested via a multivariable regression model.": Pls clarify how does this model work? How did you use a multivariable model to ascertain "correlation" between covariates?

- "We also ran a multivariable logistic model testing the predictive

power of every single pollutant corrected for temperature, daily concentration change and relative humidity": I think the logistic model when implemented in the manner you described, can inform on STRENGTH OF ASSOCIATION, not PREDICTIVE POWER.

- How did you account for seasonality? This is especially important for a 1-year study.

Results

- "R-values": I assume this is pearson's r correlation coefficient? It is confusing to state it as "R-value"

- Fig 2 & 4 are very blurry. I can't make out the words. I will need to examine again when clearer versions are provided.

Discussion

- limitations: the limitation of this simple log regression modelling approach, rather than standards in thie field eg DLNM need to be specified. for example, the inability to account for lag effects will lead to high risk of misclassification of dose-reponse. we know that the lag-specific risk for these pollutants are non-linear and often can be protective at some lag and harmful at some lag. this is a severe limitation of this study.

- Literature review: the discussion will be much improved by the inclusion of below literature

Ho, A. F. W. et al. Health impacts of the Southeast Asian haze problem – A time-stratified case crossover study of the relationship between ambient air pollution and sudden cardiac deaths in Singapore. International Journal of Cardiology 271, 352–358 (2018).

Kojima, S. et al. Association of Fine Particulate Matter Exposure With Bystander-Witnessed Out-of-Hospital Cardiac Arrest of Cardiac Origin in Japan. JAMA Netw Open 3, e203043–e203043 (2020).

Ho, A. F. W. et al. Time‐Stratified Case Crossover Study of the Association of Outdoor Ambient Air Pollution With the Risk of Acute Myocardial Infarction in the Context of Seasonal Exposure to the Southeast Asian Haze Problem. JAHA 8, (2019).

Zhao, B., Johnston, F. H., Salimi, F., Kurabayashi, M. & Negishi, K. Short-term exposure to ambient fine particulate matter and out-of-hospital cardiac arrest: a nationwide case-crossover study in Japan. The Lancet Planetary Health 4, e15–e23 (2020).

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Reviewer #1: No

Reviewer #2: No

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Out-of-hospital cardiac arrest and ambient air pollution: a dose-effect relationship and an association with OHCA incidence.

PONE-D-21-14468R1

Dear Dr. Savastano,

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.

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Kind regards,

Elena Cavarretta, M.D., 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 #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: 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: No

**********

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 have addressed my comments sufficiently and made a good attempt for the other, more rigorous reviewer as well

Reviewer #2: My concerns were satisfactorily addressed. The updated figures, which were of higher resolution, were satisfactory.

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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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Reviewer #1: No

Reviewer #2: No