Total and specific immunoglobulin E in induced sputum in allergic and non-allergic asthma

Astrid Crespo-Lessmann; Elena Curto; Eder Mateus; Lorena Soto; Alba García-Moral; Montserrat Torrejón; Alicia Belda; Jordi Giner; David Ramos-Barbón; Vicente Plaza

doi:10.1371/journal.pone.0228045

Peer Review History

Original SubmissionSeptember 27, 2019
28 Nov 2019 Decision Letter - Aleksandra Barac, Editor PONE-D-19-27179 Total and specific immunoglobulin E in induced sputum in allergic and non-allergic asthma PLOS ONE Dear Dr. Crespo, 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 by Jan 12 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. 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Please follow this link to our website for more details on competing interests: http://journals.plos.org/plosone/s/competing-interests [Note: HTML markup is below. Please do not edit.] 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: Partly Reviewer #2: No ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: No ****** 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 ****** 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 ****** 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: Dear Editor, The article entitled as “Total and specific immunoglobulin E in induced sputum in allergic and non-allergic Asthma” was reviewed for PLOS ONE on 20 November 2019. It is a valuable study in means of using and evaluating induced sputum and it has a control group. However there are the following points that needs to be solved; - The size of the study group seems to be too small, this may be increased, or the power of the study may be calculated and added. - The subject of the study that comparing total IgE between allergic and nonallergic asthma is not new even tough using induced sputum and spesicifc IgE. - Local allergy or entopy was showed in nonallergic rhinitis or asthma in mucosa biopsy or lavage in 2000’s. However, it has lost its popularity because of the difficulty to diagnose these patients, and not changing the treatment. Furthermore, it is not evaluated as an asthma phenotype. The new point may be investigating entopy between allergic, non-allergic eosinophilic, and non-allergic non-eosinophilic phenotypes. - Subgroup analysis as high and low total ıge may be performed. - There are other allergens such as pollens that may be present in nonallergic astmatics sputum. This question effects the results unconfident. - Mold sensitivity has a great impact on total IgE, and should have been explored. Reviewer #2: The detection limit was 0.35 kU/L for specific IgE and yet the authors report levels in sputum markedly below this level, e.g. for Der p-specific IgE 0.055 kU/L median and 0.04 kU/L average for non-allergic asthma. (See line 173-4 and Table 2.) Thus unfortunately, the data appear to be invalid. ****** 6. 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. 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Attachments Attachment Submitted filename: Dear Editor.docx https://doi.org/10.1371/journal.pone.0228045.r001
Revision 1
3 Jan 2020 Author Response 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: Partly Reviewer #2: No Author’s response: According to the recommendations of the reviewer, we have better drafted the manuscript in key points to make it more understandable, especially in the conclusions (see line 41) 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: N/A Reviewer #2: No Author’s response: The statistical analysis was carried out under the support of a statistician who guided us at all times on the most appropriate analyzes for this study. If you suggest doing some analysis of greater interest in our study, using the database that we have attached to the study, we would be delighted to perform it. 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 Author’s response: As required by the internal policy of Plos one, we have attached our data to a public repository. 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 Author’s response: Thanks for your feedback 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: Dear Editor, The article entitled as “Total and specific immunoglobulin E in induced sputum in allergic and non-allergic Asthma” was reviewed for PLOS ONE on 20 November 2019. It is a valuable study in means of using and evaluating induced sputum and it has a control group. However there are the following points that needs to be solved; - The size of the study group seems to be too small, this may be increased, or the power of the study may be calculated and added. Author’s response: Due to the limited literature and great variability in the results that exist of the IgE values in the induced sputum, for the calculation of the sample size, the reference values of the IgE in the induced sputum will be considered as binding variable reports in literature (references 31 and 32). This sample size is calculated with the Granmo V7.10 program, setting the type I error at the usual 5% (α = 0.05), with a bilateral approximation and with a minimum difference required for a power of 80% or higher (ß = 0.2). Also our study had as a secondary objective to establish a preliminary estimate of total IgE and Der p 1-specific IgE in the induced sputum of healthy individuals. To support the results of this work, a larger sample size would be necessary for future studies. A comment has been added in the manuscript (see line 327) - The subject of the study that comparing total IgE between allergic and nonallergic asthma is not new even tough using induced sputum and specific IgE. Author’s response: The levels of total and specific IgE in blood are extensively studied comparatively in asthmatic and healthy patients, and also in different types of asthmatic patients. However, sputum-induced levels of this immunoglobulin have been poorly reported. Our particular interest was to assess its potential applicability as a diagnostic test in the detection of local allergic reactions at the bronchial level. - Local allergy or entopy was showed in nonallergic rhinitis or asthma in mucosa biopsy or lavage in 2000’s. However, it has lost its popularity because of the difficulty to diagnose these patients, and not changing the treatment. Furthermore, it is not evaluated as an asthma phenotype. The new point may be investigating entopy between allergic, non-allergic eosinophilic, and non-allergic non-eosinophilic phenotypes. Author’s response: We totally agree with the reviewer's opinion. Local allergy has been a controversial issue in the last decade, and in our view further research is needed to define this entity properly. Its loss of popularity has been due, on the one hand, to diagnostic difficulty, so this study has been, in fact, a first approach to a technique that could allow diagnosing it in a simple way. On the other hand, until now it did not imply differences in treatment, but we believe that with the availability of new monoclonal drugs this may change. We also consider that it could help to better understand a group of patients, who because a priori they do not present signs of atopy or eosinophilia, remain limited to conventional treatments. - Subgroup analysis as high and low total IgE may be performed. Author’s response: The main focus of our work was: 1) To measure the levels of total and Dermatophagoides pteronyssinus (d1) specific IgE in the induced sputum (IS) of asthmatic patients and healthy volunteers 2) To correlate the levels of total local IgE and specific IgE to d1 (sputum and peripheral blood) in patients with allergic and non-allergic asthma Since there are few published papers in the literature that have measured levels of total IgE in sputum and since there are no established values of normal sputum total IgE levels, we cannot make this classification as there is no established cut-off point. - There are other allergens such as pollens that may be present in nonallergic asthmatics sputum. This question effects the results unconfident. Author’s response: Our inclusion criteria were particularly strict and detailed in this study. We only selected patients with allergic asthma in whom D. pteronyssinus was the only clinically relevant allergen, in addition to presenting positive prick test, and/or previous high specific IgE for this allergen. If they presented a positive prick test for other allergens and there was any suspicion that their symptoms were related to other allergens to which they were sensitized, they were excluded from the study. This has been clarified in the manuscript (see line 140) - Mold sensitivity has a great impact on total IgE, and should have been explored. Author’s response: This is an interesting point of view, but in our area, dust mites are the most common perennial allergens, and mold sensitization is not particularly common. In fact, in this group of patients, only one of them had a positive prick test for Aspergillus, and it was not clinically relevant (see line 219) Reviewer #2: The detection limit was 0.35 kU/L for specific IgE and yet the authors report levels in sputum markedly below this level, e.g. for Der p-specific IgE 0.055 kU/L median and 0.04 kU/L average for non-allergic asthma. (See line 173-4 and Table 2.) Thus unfortunately, the data appear to be invalid. Author’s response: According to manufacturer’s recommendation, > 2kU/L for total IgE and > 0.35kU/L for specific IgE, are the values to consider a positive test, but as we previously stated, the levels in induced sputum are not described yet. We understand that the previous phrasing could be confusing, so we have modified the corresponding paragraph to better understand this aspect. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0228045.r002
7 Jan 2020 Decision Letter - Aleksandra Barac, Editor Total and specific immunoglobulin E in induced sputum in allergic and non-allergic asthma PONE-D-19-27179R1 Dear Dr. Crespo-Lessman, We are pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it complies with all outstanding technical requirements. Within one week, you will receive an e-mail containing information on the amendments required prior to publication. When all required modifications have been addressed, you will receive a formal acceptance letter and your manuscript will proceed to our production department and be scheduled for publication. Shortly after the formal acceptance letter is sent, an invoice for payment will follow. To ensure an efficient production and billing process, please log into Editorial Manager at https://www.editorialmanager.com/pone/, click the "Update My Information" link at the top of the page, and update your user information. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, you must inform our press team as soon as possible and 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. With kind regards, Aleksandra Barac Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0228045.r003
Formally Accepted
8 Jan 2020 Acceptance Letter - Aleksandra Barac, Editor PONE-D-19-27179R1 Total and specific immunoglobulin E in induced sputum in allergic and non-allergic asthma Dear Dr. Crespo-Lessman: I am pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximize its impact. If they will be preparing press materials for this manuscript, please inform our press team within the next 48 hours. 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. For any other questions or concerns, please email plosone@plos.org. Thank you for submitting your work to PLOS ONE. With kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Aleksandra Barac Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0228045.r004

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