Dear Dr. Jácome,

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.

==============================

Dear Authors,

We hope this message finds you well.

During the evaluation of your work, we identified the need for some corrections based on the reviewers' observations. In order to proceed with the evaluation process, we kindly request that the necessary modifications be made.

Please ensure that all changes are highlighted in yellow  in the document to facilitate the identification of the revisions made.

We look forward to receiving the revised version to continue the evaluation.

Best regards,

==============================

Please submit your revised manuscript by Apr 28 2025 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.

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We look forward to receiving your revised manuscript.

Kind regards,

Manuela Mendonça Figueirêdo Coelho, Ph.D

Academic Editor

PLOS ONE

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We note that one or more of the authors are employed by a commercial company: AstraZeneca

a. Please provide an amended Funding Statement declaring this commercial affiliation, as well as a statement regarding the Role of Funders in your study. If the funding organization did not play a role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript and only provided financial support in the form of authors' salaries and/or research materials, please review your statements relating to the author contributions, and ensure you have specifically and accurately indicated the role(s) that these authors had in your study. You can update author roles in the Author Contributions section of the online submission form.

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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?

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

**********

3. Have the authors made all data underlying the findings in their manuscript fully available??>

The PLOS Data policy

Reviewer #1: No

Reviewer #2: No

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English??>

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

Reviewer #1: Cunha and colleagues sought to identify the factors associated with the interest in being involved in a Patient and Public Involvement Engagement and Participation (PPIEP) among patients with asthma. It is a secondary analysis of the EPI-ASTHMA nationwide asthma prevalence study where a total of 502 participants with asthma (52 ± 15.9 years, 64.1% females) from 38 primary healthcare centers from mainland Portugal were analyzed. They found that a total of 218 (43.4%) participants with asthma were interested in being involved in the Patient and Public Involvement Engagement and Participation (PPIEP). They concluded that two out of five patients with asthma were interested in participating in PPIEP initiatives. They also indicated that by understanding patient characteristics willing to participate in PPIEP, they could develop strategies to reach a wider audience and make PPIEP more inclusive. The identified associated factors that they observed need to be further investigated.

This is an interesting report based on an effort to analyze willingness of patients to participate in asthma research. I have a few suggestions to improve the presentation along with a few minor comments for corrections to the text:

1. Title – if necessary, you could eliminate the Patient and Public Involvement Engagement and Participation portion.

2. Abstract, p. 2, line 54 – do you have specific strategies in mind that could be included?

3. Introduction – p. 3 – line 72 - was the Patient and Public Involvement Engagement and Participation initiative set up for one study or for many studies? Perhaps a little more background on the development of this program would be helpful. How long has it been going on? Has it been successful? Will it continue?

4. Introduction, p. 4, lines 104 to 105 – what is the goal of this program after having collected this information? In what manner will it continue?

5. Study Design, p.4 – a little more information about the Patient and Public Involvement Engagement and Participation program would be helpful in terms of the scope of the program, target age, entry criteria, exclusion criteria and also the anticipated burden of the study PPIEP is recruiting for and whether that was included in the invitation to particpate. What were potential participants told would be done with their data and the reason for providing their permission?

6. Participants, p.4 – What was the target population surveyed? Were pediatric patients purposely excluded? Was there data collected on their prior participation in asthma or any other studies?

7. Discussion, p. 10, line 216 – what is the description of the disadvantaged population in Portugal? Is it low-income families, homeless, a particular race/ethnicity?

8. Discussion, p. 10, line 242 – What would you consider an important level of diversity and representative population for an asthma study in Portugal? Same is true for p. 11, line 244, what is the underrepresented groups in Portugal? That could be different from other countries, such as the United States.

9. Discussion, p. 11, line 249 – What is secondary care patients?

10. Discussion, p. 11 – it might be of interest to compare your population findings to published studies on the various levels of asthma severity.

11. Discussion, p.11, line 260 – What is your future vision for the application of this data and meeting your goals for studies? Will PPiEP continue its work and for what purpose?

12. Discussion, Conclusions, p. 11, line 266 – What strategies do you propose?

13. Discussion, Conclusions, p. 11, line 267 – How do you define a diverse perspective for your purposes in conducting asthma studies?

14. References – Check to see that your author format for references is consistent with journal requirements.

Minor corrections:

1. Page 9, line 201- ….did not address…

2. Page 10, line 215 - ….to be cautious regarding…

Reviewer #2: Your study is interesting and beneficial to those interested in patient recruitment. I think it should be published. Your enrollment and demographics are quite similar to what our group found when we investigated participation in survey-based research during the COVID pandemic in the US.

Because the EPI-ASTHMA study is still in press, I am unable to find all of the details related to recruitment (which is why I said details were not available).

For the most part, the research and conclusions are sound. However, one obvious source of bias is that you recruited participants by phone. I think the reason smartphone ownership was so strongly tied to participation was because of the recruitment method. The recruitment method could also introduce bias for other factors such as age, gender, degree of asthma control, etc. However, smartphone usage is the most obvious. This bias definitely needs to be mentioned in your discussion. And in fact, one could argue that smartphone ownership should not be included in your analysis at all.

I noticed that the number of participants in the study was much less than expected. Without access to the EPI-ASTHMA manuscript I do not know why, but this may be worth mentioning. There was also no explanation as to why 16 participants were excluded from your analysis.

There were grammar/syntax errors in lines 134, 201, and 202. THe sentence starting on line 215 does not make sense and needs to be reworked.

Reviewer #3: Dear Authors,

Thank you for your efforts. There are some major points that need improvement:

Title:

The title would benefit from reducing the words. Some words like “factors” are vague and better not to be used in title.

Abstract:

Line 45: “total of 502 participants with asthma (52 ± 15.9 years, 64.1% females)”: Usually these data are described in result not method.

Line 47: A multivariable logistic regression model was built: Please identify what variable the model was built for.

Introduction:

The research aim is clear but brief. Consider adding 1-2 sentences about the significance of identifying these factors and potential implications.

Method:

- The method section is a bit unclear. It is not clearly mentioned if the study is a secondary analysis of data available, or they have actively gathered data. For example, they have stated that they have gotten consent from the participants, meaning active participation. However, in all details they are talking about a third party data gathering refereeing other articles.

- The key variable about PPIEP interest is not well described. Add details about how this was measured.

- Consider adding information about how you handled missing data

- Specify which variables were tested in the simple logistic regressions

- Consider mentioning how you assessed for multicollinearity in your regression models

Result:

- Line 166-171: When reporting the multivariable results, consider adding p-values alongside the odds ratios and confidence intervals.

- The interpretation of OR 1.53 (95%CI 1.00-2.33) for females should be approached with caution as the lower bound of the confidence interval is exactly 1.00, suggesting borderline significance.

- There is a problem in Smartphone ownership data percentage. 198 out of 218 would be 90.8%, not 93.6%. Please check all data again.

Discussion

Try organizing paragraphs more thematically.

Some minor editions:

1. In line 63, “This variation” could be clearer by specifying “This variation in asthma control”.

2. I am not sure whether PCC stands for primary healthcare centres. (Line 110)

3. Line 110: “Data was accessed” should be “Data were accessed”.

4. More clearly define “current asthma” versus “possible asthma” or reference where these definitions can be found.

5. Line 192: “more women than man” shou

**********

what does this mean? ). If published, this will include your full peer review and any attached files.

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Reviewer #1: Yes:  Stanley J. Szefler, MD

Reviewer #2: No

Reviewer #3: Yes:  Noosha Samieefar

**********

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Dear Dr. Jácome,

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.

==============================

Dear Authors,

I would like to sincerely congratulate you on the excellent work carried out in revising the manuscript “Interest in Public Involvement, Engagement and Participation in Research among Patients with Asthma: A Secondary Analysis of the EPI-ASTHMA Study.”

After a careful and detailed review, I confirm that all the reviewers' comments and editorial requirements have been fully addressed. The revisions have made the manuscript much clearer, more consistent, and well-aligned with PLOS ONE’s guidelines.

As an optional suggestion, aiming only to further strengthen the final submission, I would like to propose a few minor improvements :

1. Multicollinearity assessment : Although the absence of multicollinearity evaluation was acknowledged in the response letter, it would be advisable to briefly mention this in the manuscript’s Limitations section. A sentence such as the following could be added:
   “Another limitation is that multicollinearity between predictors was not assessed, which could affect the interpretation of regression results.”
2. Consistency of data collection dates : There is a minor inconsistency regarding the final date of data collection (December 2023 vs. February 2024). I recommend verifying and ensuring consistency throughout the manuscript.
3. Title formatting : Following PLOS ONE formatting style, please consider capitalizing the main words in the title as follows:
   Interest in Public Involvement, Engagement and Participation in Research among Patients with Asthma: A Secondary Analysis of the EPI-ASTHMA Study.

These are only small and non-mandatory recommendations, focused mainly on stylistic refinement and methodological transparency. I emphasize that the manuscript already demonstrates a high technical and scientific standard, and that your careful work throughout the revision process is clearly reflected in the final version.

Congratulations once again to the entire team for the commitment and dedication. I remain available for any further clarifications if needed.

Best regards,

==============================

Please submit your revised manuscript by Jun 11 2025 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.

• 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 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,

Manuela Mendonça Figueirêdo Coelho, 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.

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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

Dear Dr. Jácome,

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.

==============================

Dear authors,

If you have made the corrections requested by the reviewers below, please send a new file with the corrections marked in blue, as well as a response letter regarding each correction.

Thank you

==============================

Please submit your revised manuscript by Jun 26 2025 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.

• 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 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,

Manuela Mendonça Figueirêdo Coelho, 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.

Additional Editor Comments:

Reviewer 01:

Cunha and colleagues sought to identify factors associated with interest in engaging in Patient Engagement and Participation and Public Involvement (PEIEP) among patients with asthma. This is a secondary analysis of the EPI-ASTHMA national asthma prevalence study, which included a total of 502 participants with asthma (52 ± 15.9 years, 64.1% female) from 38 primary health care centers in mainland Portugal. They found that a total of 218 (43.4%) participants with asthma were interested in engaging in PEIEP. They concluded that two out of five patients with asthma were interested in participating in PEIEP initiatives. They also indicated that by understanding the characteristics of patients willing to participate in PEIEP, they could develop strategies to reach a wider audience and make PEIEP more inclusive. The associated factors they identified need to be investigated further. This is an interesting report based on an effort to analyze patient willingness to participate in asthma research. I have a few suggestions for improving the presentation, along with some minor comments for corrections in the text: 1. Title - if necessary, you could eliminate the Patient Engagement and Participation and Public Involvement section. 2. Abstract, p. 2, line 54 - do you have specific strategies in mind that could be included? 3. Introduction - p. 3 - line 72 - was the Patient Engagement and Participation and Public Involvement initiative set up for one study or for many studies? Perhaps a little more background on the development of this program would be helpful. How long has it been going on? Has it been successful? Will it continue? 4. Introduction, p. 4, lines 104-105 - what is the goal of this program once you have collected this information? How will it continue? 5. Study Design, p.4 – a little more information about the Patient and Public Engagement and Participation programme would be helpful in terms of scope of the programme, target age, entry criteria, exclusion criteria and also the anticipated burden of the study for which PPIEP is recruiting and whether this was included in the invitation to participate. What were potential participants told would be done with their data and the reason for providing their permission? 6. Participants, p.4 – Who was the target population studied? Were paediatric patients purposefully excluded? Was there data collected on their previous participation in asthma or any other studies? 7. Discussion, p. 10, line 216 – what is the description of the disadvantaged population in Portugal? Is it low income families, homeless, a particular race/ethnicity? 8. Discussion, p. 10, line 242 – What would you consider an important level of diversity and representative population for an asthma study in Portugal? The same is true for p. 11, line 244, which groups are underrepresented in Portugal? This may be different from other countries, such as the United States. 9. Discussion, p. 11, line 249 - What are secondary care patients? 10. Discussion, p. 11 - It may be interesting to compare your population findings with published studies on the various levels of asthma severity. 11. Discussion, p. 11, line 260 - What is your future vision for applying these data and achieving your study objectives? Will PPiEP continue its work and for what purpose? 12. Discussion, Conclusions, p. 11, line 266 - What strategies do you propose? 13. Discussion, Conclusions, p. 11, line 267 - How do you define a diverse perspective for your purposes in conducting asthma studies? 14. References - Please check that your author's format for references is consistent with the journal's requirements. Minor corrections: 1. Page 9, line 201 - ....did not address... 2. Page 10, line 215 - ....to be cautious about...

Reviewer 02

Your study is interesting and beneficial to those interested in patient recruitment. I think it should be published. Your enrollment and demographics are quite similar to what our group found when we investigated participation in survey-based research during the COVID pandemic in the US. Since the EPI-ASTHMA study is still in the works, I am unable to find all the details related to recruitment (which is why I said the details were not available). For the most part, the research and conclusions are sound. However, one obvious source of bias is that you recruited participants by phone. I think the reason smartphone ownership was so strongly linked to participation was because of the recruitment method. The recruitment method may also introduce bias for other factors such as age, gender, degree of asthma control, etc. However, the use

Revisor 03

Dear Authors,

Thank you for your efforts. There are some major points that need improvement:

Title:

The title would benefit from reducing the words. Some words like “factors” are vague and better not to be used in title.

Abstract:

Line 45: “total of 502 participants with asthma (52 ± 15.9 years, 64.1% females)”: Usually these data are described in result not method.

Line 47: A multivariable logistic regression model was built: Please identify what variable the model was built for.

Introduction:

The research aim is clear but brief. Consider adding 1-2 sentences about the significance of identifying these factors and potential implications.

Method:

- The method section is a bit unclear. It is not clearly mentioned if the study is a secondary analysis of data available, or they have actively gathered data. For example, they have stated that they have gotten consent from the participants, meaning active participation. However, in all details they are talking about a third party data gathering refereeing other articles.

- The key variable about PPIEP interest is not well described. Add details about how this was measured.

- Consider adding information about how you handled missing data

- Specify which variables were tested in the simple logistic regressions

- Consider mentioning how you assessed for multicollinearity in your regression models

Result:

- Line 166-171: When reporting the multivariable results, consider adding p-values alongside the odds ratios and confidence intervals.

- The interpretation of OR 1.53 (95%CI 1.00-2.33) for females should be approached with caution as the lower bound of the confidence interval is exactly 1.00, suggesting borderline significance.

- There is a problem in Smartphone ownership data percentage. 198 out of 218 would be 90.8%, not 93.6%. Please check all data again.

Discussion

Try organizing paragraphs more thematically.

Some minor editions:

1. In line 63, “This variation” could be clearer by specifying “This variation in asthma control”.

2. I am not sure whether PCC stands for primary healthcare centres. (Line 110)

3. Line 110: “Data was accessed” should be “Data were accessed”.

4. More clearly define “current asthma” versus “possible asthma” or reference where these definitions can be found.

5. Line 192: “more women than man” shou

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

[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

Dear Dr. Jácome,

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 by Jul 14 2025 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.

• 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 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,

Manuela Mendonça Figueirêdo Coelho, 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.

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Interest in Public Involvement, Engagement and Participation in Research among Patients with Asthma: A Secondary Analysis of the EPI-ASTHMA Study

PONE-D-25-04695R4

Dear Dr. Jácome,

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