PONE-D-19-27004

Clinical predictors of radiological pneumonia in the post vaccine era: a cross sectional study from a tertiary hospital in Nepal

PLOS ONE

Dear Dr. Chaudhary,

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.

Please address the following comments before sending out for review:

1. Abstract conclusion, tachypnea is not specific at all (Table 2).
2. The main purpose of the study is to reassess the clinical predictors of radiological pneumonia. In the introduction, please describe the existing known clinical predictors and compare the results in the discussion.
3. Table 2, please give the % of having the symptoms/signs. For example, the % for ‘noisy breathing’ should be 43/97=44.3%. This will help understanding the estimated sensitivity and specificity.
4. Please present the results of the multivariable analysis.
5. Please explain how combinations of signs/symptoms were determined. Why some combinations were considered (or not considered)?

We would appreciate receiving your revised manuscript by Nov 24 2019 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Eric HY Lau, Ph.D.

Academic Editor

PLOS ONE

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Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

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Additional Editor Comments (if provided):

Please address the following comments before sending out for review:

1. Abstract conclusion, tachypnea is not specific at all (Table 2).

2. The main purpose of the study is to reassess the clinical predictors of radiological pneumonia. In the introduction, please describe the existing known clinical predictors and compare the results in the discussion.

3. Table 2, please give the % of having the symptoms/signs. For example, the % for ‘noisy breathing’ should be 43/97=44.3%. This will help understanding the estimated sensitivity and specificity.

4. Please present the results of the multivariable analysis.

5. Please explain how combinations of signs/symptoms were determined. Why some combinations were considered (or not considered)?

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-19-27004R1

Clinical predictors of radiological pneumonia in the post-vaccine era: a cross-sectional study from a tertiary hospital in Nepal

PLOS ONE

Dear Dr. Chaudhary,

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 Authors are expected to address all the criticisms by all Reviewers. In particular, please describe and discuss the findings in Figure 2 and 3 (Reviewer #1 and #3), provide description of the statistical analyses for Tables 2 and 3 (Reviewer #1), and draw conclusion directly from the study results (Reviewer #1), and clarify in the methods whether bacterial or viral CAP were identified. In additional to the above comments, please address:

1. Table 4. The study main findings suggested that Tachypnea had the highest sensitivity, however was not included in the multivariable model. I suggest that the authors may include all variables with p<0.1 from Table 2 in the multivariable model.
2. The authors now added Table 3 to show the results of various combinations of signs/symptoms. However, a description of how the authors come up with these combinations would be helpful.

We would appreciate receiving your revised manuscript by Feb 01 2020 11:59PM. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Eric HY Lau, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (if provided):

The Authors are expected to address all the criticisms by all Reviewers. In particular, please describe and discuss the findings in Figure 2 and 3 (Reviewer #1 and #3), provide description of the statistical analyses for Tables 2 and 3 (Reviewer #1), and draw conclusion directly from the study results (Reviewer #1), and clarify in the methods whether bacterial or viral CAP were identified. In additional to the above comments, please address:

1. Table 4. The study main findings suggested that Tachypnea had the highest sensitivity, however was not included in the multivariable model. I suggest that the authors may include all variables with p<0.1 from Table 2 in the multivariable model.

2. The authors now added Table 3 to show the results of various combinations of signs/symptoms. However, a description of how the authors come up with these combinations would be helpful.

[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: (No Response)

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

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: No

Reviewer #2: Yes

Reviewer #3: Partly

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: No

**********

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

Reviewer #3: 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

Reviewer #3: No

**********

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: 1. In the manuscript, the name of the microorganism should be corrected as Haemophilus influenzae. It is the way it has been used in the bacteriology world since the organism has been defined.

2. In the Methods section, “Ethics Approval” statement should be replaced after “Study Outcomes”.

3. In the Statistical Analysis subsection, it was indicated that statistical analysis was performed using SPSS. The name of the company and country should be indicated as “IBM SPSS Statistics (version 21.0; IBM, Armonk, NY, US)”.

4. In Figure 2 ans 3, symptoms and signs of the patients were presented in an age-based grouping. However, this analysis type has not been indicated in the methods section. Additionally, in the results and discussion sections this analysis has not been commented in any way. These figures give no input into the manuscript. This ag- based analysis and Figure 2 and 3 are unnecessary in the manuscript.

5. In the results section, explanations of Table and Table 3 should be more informative. The frequencies and statistical differences should be explained in a more detailed fashion, since these data are the main ones that the manuscipt is based on

6. The statistical analysis of Tables 2,3, and 4 are not described sufficient detail.

7. In the first paragraph of Discussion section, there is no data discussed from the present manuscript. This paragraph is just explaining what is already known in this era and it is a repeat of introduction section.

8. The manuscript is presenting a cross-sectional analysis and it does not compare the pre and post-vaccine era data. Both in introduction section and discussion sections, the authors are referring to a change of epidemiology and its reflections on the radiology and clinical signs. However, with the data presented in the manuscript, these evaluations can not be performed. Although authors are hypothizing changes in clinical findings of pneumonia related to vaccine introduction, they did not analyze this in the manuscript.

9. Fourth paragraph of manuscript (line 232), the discussion of the data is weak in explanations.

10. The conclusion section, totally, is not appropriate as a conclusion of this manuscript. It is not supported by the data.

Reviewer #2: About the scientific paper: "Clinical predictors of radiological pneumonia in the post-vaccine era: a cross-sectional study from a tertiary hospital in Nepal"

-A)First, the design , exclusion and inclusion criterial is similar to another old historical cohort of clinical predictors of community acquired pneumonia.

-B)Use of radiological finding as gold standard , not only WHO clinical guide is right.

-C)"The clinical presentation and the radiographic signs of pneumonia may not be the same as found earlier. Considering the change in the epidemiological pattern, the clinical predictors of pediatric pneumonia need

reassessment. Therefore, this hospital-based study was conducted to find the predictors of radiological pneumonia in the post-vaccine era".

This statement is a hypothesis of the authors of this paper and has no bibliographic work to support it.

-D)"Currently, with the introduction of Hemophilus influenzae type b (Hib) and pneumococcal conjugate vaccines (PCV) and global expansion of their coverage,

bacterial agents are on the decline and out-numbered by viral and atypical bacteria".

In this serie you studied include infants with a single dose of conjugate vaccines, which is considered insufficient dose to ensure adequate coverage.

Data that would not emphatically exclude the possible presence of pneumococci or haemophillus as possible etiological agents.

-E)Nasal discharge is inespecific and is associated with flu, the inicial and common manifestation of respiratory symptoms, not only of pneumonia.

-F)The association of wheezing with pulmonary infiltrates in infants is the current basis for the recommendation not to do radiography in bronchiolitis,

given the frequent association of pulmonary pathological findings and possible diagnostic confusion with pneumonia.

Would this have happened in some of the patients included in this series?. The same can be said of the asthmatic crisis.

-G)The central paper hypothesis cannot be demonstrated, given that these clinical predictors are not compared with others taken in the era prevaccine in the same community and population studied.

-H)The prevalence of viruses over bacteria in the etiology of pneumonia alters the clinical presentation of pneumonia ?.

Due to the design in a single hospital and without accompanying etiological studies, it is difficult to answer this question. The works cited do not get into this disquisition.

-I)In conclusion, it is valuable to observe what the high altitude above sea level determines that hypoxemia can be a good predictor of pneumonia.

The design and casuistic are adequate and the sum of signs and symptoms help and much to be able to find and not lose cases of this disease as severe and harmful to children as pneumonia.

By making these changes, these findings could be communicated.

Reviewer #3: The authors conducted an interesting study to analyze a possible association between radiographic findings of pneumonia in children with clinical signs and symptoms. The results are equally interesting, however, some questions need clarifying or undergoing changes to make the article better quality.

a) Were the selected cases all of community-acquired pneumonia? If so, this should be made clear in the text and the expression 'pneumonia' should be replaced throughout 'community acquired pneumonia (CAP)'.

b) The authors do not clarify whether bacterial or viral CAP was identified, this is only briefly described in the discussion (in limitations). This doubt should be clarified in the methods, emphasizing that approximately 30% of the cases of CAP are mixed (viral and bacterial).

c) How was the positive predictive value (PPV) calculated? If it was calculated from the selected sample, the value is certainly overestimated. It is correct to calculate PPV based on population prevalence data using the Bayes equation.

d) An interesting analysis would be to evaluate the association/correlation between radiological findings and leukocyte count, considering that in bacterial PAC, there is a tendency for leukocytosis.

e) The analysis of age subgroups would also be very important.

f) The authors use and cite old references. I suggest the inclusion and citation of some recent references such as: DOI: 10.1016/S1473-3099(15)70017-4; DOI: 10.4046/trd.2015.78.3.196; among others.

g) All text should be revised by a native speaker of the English language and specializes in health issues.

**********

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: Yes: Dr Manuel D. Bilkis

Reviewer #3: No

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-19-27004R2

Clinical predictors of radiological pneumonia: a cross-sectional study from a tertiary hospital in Nepal

PLOS ONE

Dear Dr. Chaudhary,

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.

We would appreciate receiving your revised manuscript. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Frederick Quinn

Academic Editor

PLOS ONE

[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: (No Response)

Reviewer #2: All comments have been addressed

Reviewer #3: (No Response)

**********

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: Partly

Reviewer #2: Yes

Reviewer #3: Partly

**********

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

Reviewer #1: I Don't Know

Reviewer #2: Yes

Reviewer #3: No

**********

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

Reviewer #3: 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: No

Reviewer #2: Yes

Reviewer #3: (No Response)

**********

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: 1) Although most of the reviewer comments were met by the authors in the revision process, I still think that the manuscript does not add any new data into both clinical practice and the literature for further studies.

2) Since the statistical data analysis has already been explained in Results section, the numbers should not be repeated in Discussion section (all the confidence intervals, percentages and so forth).

Reviewer #2: (No Response)

Reviewer #3: The calculation of the positive predictive value (PPV) should be done using the Bayes equation, using the prevalence of real pneumonia in the child population in Nepal and not using data from the 2x2 table (see: Linn S. New patient-oriented diagnosis test characteristics analogous to the likelihood ratios conveyed information on trustworthiness. J Clin Epidemiol. 2005; 58 (5): 450–457. doi: 10.1016 / j.jclinepi.2004.07.009 - see equation 2.11).

If this cannot be done by the authors, I suggest not presenting these values in the manuscript.

**********

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

Reviewer #3: Yes: Altacilio Nunes

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-19-27004R3

Clinical predictors of radiological pneumonia: a cross-sectional study from a tertiary hospital in Nepal

PLOS ONE

Dear Dr. Chaudhary

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.

We would appreciate receiving your revised manuscript. When you are 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.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter.

To enhance the reproducibility of your results, we recommend that if applicable you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

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). This letter should be uploaded as separate file and labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. This file should be uploaded as separate file and labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. This file should be uploaded as separate file and labeled 'Manuscript'.

Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.

We look forward to receiving your revised manuscript.

Kind regards,

Frederick Quinn

Academic Editor

PLOS ONE

[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: (No Response)

Reviewer #2: All comments have been addressed

Reviewer #3: All comments have been addressed

**********

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: Partly

Reviewer #2: Partly

Reviewer #3: Yes

**********

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

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: 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

Reviewer #3: 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: No

Reviewer #2: Yes

Reviewer #3: 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: I still think that the manuscript does not add any new data into the literature and to the clinical practice, either. Diagnosis of pneumonia in children is not an argumentative issue with the defined clinical findings. High respiratory rate, grunting, hypoxemia, decreased breath sounds are already in practice and in literature as signs of pneumonia. Further more, the authors did not study on relation of changes in epidemiology and clinical findings. So, they can not make any comment on that. Epidemiology is the key point in giving decisions on treatment strategies, not in diagnosis of pneumonia, whether it is radiologically approved or not.

Reviewer #2: Knowing exactly the symptoms of pneumonia in children is difficult, but it is essential in developing countries.

At the time of respiratory virus pandemic, knowing the local clinical characteristics of presentation of pneumonia becomes even more important.

Reviewer #3: Decreased breathing (AOR 3.68; CI 0.99-13.76) was not independently associated, as the lower limit of 95%CI is less than 1. Please correct this, moreover, in all confidence intervals the correct form is 95%CI.

**********

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: Yes: manuel david bilkis

Reviewer #3: Yes: Altacilio Nunes

[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 to be viewed.]

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 us at figures@plos.org. Please note that Supporting Information files do not need this step.

PONE-D-19-27004R4

Clinical predictors of radiological pneumonia: a cross-sectional study from a tertiary hospital in Nepal

PLOS ONE

Dear Dr. Dr. Chaudhary,

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.

Please submit your revised manuscript. 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: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Frederick Quinn

Academic Editor

PLOS ONE

[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 #2: All comments have been addressed

Reviewer #3: (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 #2: Yes

Reviewer #3: Yes

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

Reviewer #2: Yes

Reviewer #3: No

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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: (No Response)

Reviewer #3: I repeat, decreased breath sounds (AOR 3.68; 95% CI 0.99-13.76) were not independently associated with radiological pneumonia, please remove it from text! In addition, the result is inaccurate, see the amplitude of the 95%CI.

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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: Yes: Altacilio Nunes

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Clinical predictors of radiological pneumonia: a cross-sectional study from a tertiary hospital in Nepal

PONE-D-19-27004R5

Dear Dr. Chaudhary,

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,

Frederick Quinn

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 #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 #3: Yes

**********

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

Reviewer #3: (No Response)

**********

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 #3: 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 #3: 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 #3: Okay, all the reviewers' suggestions/observations have been incorporated into the text. The quality of the manuscript has improved.

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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 #3: Yes: Altacilio Nunes