The relationship between adherence to continuous positive airway pressure and nasal resistance measured by rhinomanometry in patients with obstructive sleep apnea syndrome

Nobuhiro Fujito; Yasuyoshi Ohshima; Satoshi Hokari; Atsunori Takahashi; Asuka Nagai; Ryoko Suzuki; Nobumasa Aoki; Satoshi Watanabe; Toshiyuki Koya; Toshiaki Kikuchi

doi:10.1371/journal.pone.0283070

Peer Review History

Original SubmissionOctober 19, 2022
5 Feb 2023 Decision Letter - Hyungchae Yang, Editor PONE-D-22-28859The relationship between adherence to continuous positive airway pressure and nasal resistance measured by rhinomanometry in patients with obstructive sleep apnea syndromePLOS ONE Dear Dr. Ohshima, 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 Mar 22 2023 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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Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: 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: In this study, the authors examined the relationship between nasal resistance measured by rhinomanometry and CPAP adherence. I believe that identifying the key factors related to CPAP adherence is an important task in the treatment of sleep apnea and that nasal resistance is one of the key factors that determines this. This paper also shows that nasal resistance may have an effect on CPAP adherence. However, I have some questions. 1. The participants in the study were divided into groups of good and poor CPAP adherence based on their CPAP usage results. Then, the study analyzed the CPAP results and rhinomanometry results after 1 month, 3 months, and at the time of inclusion in the study. I am curious to know whether all of the participants included in the study are currently using CPAP or if there are also those who have discontinued it. I believe that whether or not patients have discontinued or continued using CPAP, separate from the CPAP parameters, is also an important perspective in evaluating CPAP adherence. And, if possible, it would be good to also show the continuity of CPAP at the time of patient enrollment in the study. 2. I'm curious about the accurate meaning of "213 line's Satisfactory rhinomanometry values." Although the presented table shows that the difference of rhinomanometry values are statistically significant, there doesn't seem to be a big difference in the presented median values. How does the author evaluate rhinomanometry results as satisfactory? What specific value is used as a criterion for predicting CPAP adherence? Additionally, it would be helpful to understand the relationship between rhinomanometry values and CPAP adherence by showing a scatter plot. 3. What is the reason the author thinks that nasal resistance is higher in the Poor adherence group compared to the Good adherence group, but CPAP max pressure is lower in the Poor adherence group? 4. The Poor adherence group shows a higher BMI. How does the author think BMI affects adherence? 5. There is a significant difference in terms of Age, BMI, CT90% between the improvement group and the no improvement group, and Nasal symptom score also consistently high in the no improvement group. Would it be possible that the physiological or anatomical factors of the nose have affected the difference in rhinomanometry results? 6. Can you please provide a more detailed description of what the presented CPAP use rate(%) and CPAP duration of use(min) mean in the paper? Are they measuring adherence by the proportion of usage for at least 4 hours and the number of days used out of total days? Additionally, it would be helpful if additional parameters for evaluating CPAP adherence were also presented. 7. What is the reason for setting the OSA inclusion criteria to AHI 20 or higher? ****** 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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Revision 1
17 Feb 2023 Author Response PONE-D-22-28859 The relationship between adherence to continuous positive airway pressure and nasal resistance measured by rhinomanometry in patients with obstructive sleep apnea syndrome Dear Dr. Hyungchae Yang, We are resubmitting the above-cited manuscript, which has been revised in accordance with the Reviewer’s helpful comments. We attempted to address the issues raised by the Reviewer, and we have carefully corrected any grammatical errors. Our point-by-point responses to the Reviewer’s comments are provided below. Response to Reviewers Reviewer #1: In this study, the authors examined the relationship between nasal resistance measured by rhinomanometry and CPAP adherence. I believe that identifying the key factors related to CPAP adherence is an important task in the treatment of sleep apnea and that nasal resistance is one of the key factors that determines this. This paper also shows that nasal resistance may have an effect on CPAP adherence. However, I have some questions. (Reply) Thank you very much for your comment. We have carefully considered all of your questions, and we provide our responses below. 1. The participants in the study were divided into groups of good and poor CPAP adherence based on their CPAP usage results. Then, the study analyzed the CPAP results and rhinomanometry results after 1 month, 3 months, and at the time of inclusion in the study. I am curious to know whether all of the participants included in the study are currently using CPAP or if there are also those who have discontinued it. I believe that whether or not patients have discontinued or continued using CPAP, separate from the CPAP parameters, is also an important perspective in evaluating CPAP adherence. And, if possible, it would be good to also show the continuity of CPAP at the time of patient enrollment in the study. (Reply) Thank you for bringing this oversight to our attention. We have added the following sentence in the revised manuscript: (Page 9, Lines 149-151) “Fifteen patients changed CPAP treatment (11 with poor CPAP adherence), 24 patients discontinued treatment (17 with poor CPAP adherence), and 6 patients died (5 with poor CPAP adherence).” 2. I'm curious about the accurate meaning of "213 line's Satisfactory rhinomanometry values." Although the presented table shows that the difference of rhinomanometry values are statistically significant, there doesn't seem to be a big difference in the presented median values. How does the author evaluate rhinomanometry results as satisfactory? What specific value is used as a criterion for predicting CPAP adherence? Additionally, it would be helpful to understand the relationship between rhinomanometry values and CPAP adherence by showing a scatter plot. (Reply) We appreciate your insightful question. The scatter plots are indeed very helpful. We have therefore included them in the revised manuscript as Figures 1 and 2. As you suggested, the difference in rhinomanometry values is small, and the statistical cutoff value is 0.165; however, we believe that it is clinically informative. (Figure 1 legend) “Relationship between rhinomanometry values before CPAP introduction and CPAP use rate at enrollment.” (Figure 2 legend) “Relationship between rhinomanometry values before CPAP introduction and CPAP duration of use at enrollment.” 3. What is the reason the author thinks that nasal resistance is higher in the Poor adherence group compared to the Good adherence group, but CPAP max pressure is lower in the Poor adherence group? (Reply) Thank you for your question. This relates to the change of settings to improve adherence in cases of poor adherence, by lowering the maximum pressure when CPAP use was difficult due to high pressure. We have added the following sentence in the limitations section of the revised manuscript: (Page 28, Lines 283-285) “and fourth, manual titration was not performed and the setting pressure was changed depending on the patient's poor adherence status, which may have affected adherence.” 4. The Poor adherence group shows a higher BMI. How does the author think BMI affects adherence? (Reply) Thank you for your question. There are various studies on the relationship between CPAP adherence and BMI, including some that find no association [Chest. 2002;121:430-435., Sleep. 2007;30:320-324.], others that report a U-shaped association [Sleep Medicine. 2018;51:85-91., Respiration. 2014;87:121-128.], and others that find that the higher the BMI the more sleepiness the patient and the more likely they were to experience improvement in sleepiness when treated with CPAP, thus improving adherence. In particular, a meta-analysis shows that BMI ≥30 kg/m2 and ESS score ≥11 can be expected to show stable adherence based on sleepiness improvement [Front Neurol. 2022;27;13:911996.]. Based on an average BMI of 26.6 and an average ESS of 9 in this study, it is difficult to consider the association between BMI and adherence, which we speculate is complicated by the existence of various OSA phenotypes [Chest. 2020;157:403-420.]. Among the various phenotypes, subtypes with severe OSA (AHI, 34-68), high BMI (28-38 kg/m2), low hypoxemia for a given AHI (CT90% 0-12%), and ESS score (9-10) are defined. The pharyngeal collapsibility, low arousal threshold, and/or elevated loop gain may contribute to pathogenesis in this subtype, which has the lowest CPAP use rate. We believe that the poor adherence group may be affected by the inclusion of the second most common PSG phenotype, which is characterized by severe OSA, low hypoxemia, and low CPAP adherence. We have added the following sentence and a relevant reference in the revised manuscript: (Page 27, Lines 272-274) “The poor adherence group might be affected by the inclusion of the phenotype, which was characterized by severe OSA, high BMI (28-38 kg/m2), low hypoxemia, ESS score (9-10), and low CPAP adherence [37]. In addition,” (References) “37. Zinchuk A, Yaggi HK. Phenotypic subtypes of OSA: A challenge and opportunity for precision medicine. Chest. 2020;157: 403–420. doi: 10.1016/j.chest.2019.09.002.” 5. There is a significant difference in terms of Age, BMI, CT90% between the improvement group and the no improvement group, and Nasal symptom score also consistently high in the no improvement group. Would it be possible that the physiological or anatomical factors of the nose have affected the difference in rhinomanometry results? (Reply) Thank you for your question. We do think that the physiological or anatomical factors of the nose may have affected the difference in rhinomanometry results. We have added the following sentence and a relevant reference in the revised manuscript: (Pages 25-26, Lines 246-249) “The BMI and CT90% tended to be different between the improvement and no improvement groups. A relation between obesity and increased nasal resistance and hypoxia has been suggested [30], and physiological and anatomical factors of the nose may have affected the difference in rhinomanometry results.” (References) “30. Tagaya M, Nakata S, Yasuma F, Noda A, Morinaga M, Yagi H, et al. Pathogenetic role of increased nasal resistance in obese patients with obstructive sleep apnea syndrome. Am J Rhinol Allergy. 2010;24: 51–54. doi: 10.2500/ajra.2010.24.3382.” 6. Can you please provide a more detailed description of what the presented CPAP use rate(%) and CPAP duration of use(min) mean in the paper? Are they measuring adherence by the proportion of usage for at least 4 hours and the number of days used out of total days? Additionally, it would be helpful if additional parameters for evaluating CPAP adherence were also presented. (Reply) Thank you for bringing this oversight to our attention. The relevant sentence has been rewritten as follows: (Page 7, Line 112) “estimated by the number of days used out of total days” 7. What is the reason for setting the OSA inclusion criteria to AHI 20 or higher? (Reply) Thank you for your question. This is because of Japanese insurance coverage. We have added the following sentence in the revised manuscript: (Page 6, Lines 85-86) “In Japan, patients with AHI ≥20 are covered by medical insurance for CPAP therapy.” https://doi.org/10.1371/journal.pone.0283070.r002
2 Mar 2023 Decision Letter - Hyungchae Yang, Editor The relationship between adherence to continuous positive airway pressure and nasal resistance measured by rhinomanometry in patients with obstructive sleep apnea syndrome PONE-D-22-28859R1 Dear Dr. Ohshima, 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. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. 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 help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Hyungchae Yang, M.D. & Ph.D Academic Editor PLOS ONE 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 ******** 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 ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: 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 ****** 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 ****** 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: (No Response) ****** 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 ******** https://doi.org/10.1371/journal.pone.0283070.r003
Formally Accepted
6 Mar 2023 Acceptance Letter - Hyungchae Yang, Editor PONE-D-22-28859R1 The relationship between adherence to continuous positive airway pressure and nasal resistance measured by rhinomanometry in patients with obstructive sleep apnea syndrome Dear Dr. Ohshima: I'm 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 let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Dr. Hyungchae Yang Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0283070.r004

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