The Burden of Comorbidities in Obstructive Sleep Apnea and the Pathophysiologic Mechanisms and Effects of CPAP

Round 1

Reviewer 1 Report

1.) There are several grammatical errors.

2) Please consider the full name of abstracts for the first time such as CPAP,...

3. There are several reviews related to this subject (https://pubmed.ncbi.nlm.nih.gov/34833419/. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694741/, https://onlinelibrary.wiley.com/doi/abs/10.1111/crj.12754, ...). What is a novelty compared to previous reviews?

There are several grammatical errors. "which indicate", "there are not only consequential evidence", "asthma, glucose intolerance", " researches", "after initial ", "Typically, rate", " at the OSAS", ....

Author Response

Thank you very much for all your comments and proposals!

1. There are several grammatical errors.

Thank you for your feedback, our article has been checked by native English speaker.

All these expressions were changed according to the context : "which indicate", "there are not only consequential evidence" there are not only circumstantial evidence , "asthma, glucose intolerance ", " researches", "after initial ", "Typically, rate", " at the OSAS", ....

2. Please consider the full name of abstracts for the first time such as CPAP,...

It is very important observation, we cheeked all used abbreviations again and introduced corresponding corrections

3. There are several reviews related to this subject (https://pubmed.ncbi.nlm.nih.gov/34833419/. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694741/, https://onlinelibrary.wiley.com/doi/abs/10.1111/crj.12754, ...).

We added and discussed proposed references! Thank you very much!

Reviewer 2 Report

In this draft authors review on principal known comorbidities in OSAS and the effect of CPAP therapy on their prognosis.

This reviewer particularly appreciates this work for the quality and the completeness of the information provided.

I have only a concern. The relationship among obesity, inflammation/atherosclerosis, sleep disruption and risk of diabetes development needs to be better discuss together. For this purpose please use these following important papers: 1) doi: 10.1007/s00592-021-01676-z and 2) doi: 10.1016/j.numecd.2020.05.028, includidng them in the references list and comment in discussion

Author Response

Thank you very much for all your comments and proposals!

1. I recommend changing the title of the manuscript. Contrary to the title, there is less about the prevalence of comorbidities in OSA and more about the mechanisms that leads to comorbidities. Therefore, the title “Burden of comorbidities in obstructive sleep apnea, pathophysiologic mechanisms, and therapeutic effects of CPAP” seems more appropriate.

Thank you for your feedback, We accept that suggestion.

2. It looks like you need English proofreading for your manuscript. 

Our article has been checked by native English speaker.

3. Line 66: What is the full spelling of HBP? 

It is very important observation, we cheeked all used abbreviations again and introduced corresponding corrections

4. All the figures are difficult to understand. For examples, what is the meaning of the colored arrows in Figure 1? The hierarchy between oxidative stress and HIF-1, ROS in Figure 2 needs to be reconsidered. In Figure 2, what are the causes atherosclerosis in OSAS?

All these suggestions were accepted and changed according to the contents of the article. The colored figures demonstrate different pathogenic pathways (added in the text of the manuscript)

5. Figures should summarize the description in the manuscript. However, the description of the figure’s construction is often absent from the manuscript.

Very useful remark, figures description was supplemented with the necessary information.

6. The possible mechanism linking OSAS to cancer is not entirely due to hypoxia: the effects of sleep fragmentation should be considered after a careful review of recent papers. The results of intermittent hypoxia on cancer have also been shown in animal or cell culture studies.

We accept that suggestion, and we are already supplemented the content of that paragraph with the information from proposed studies.

7. The organization of paragraphs under subheadings is not the same: Some paragraphs deal primarily with pathophysiologic mechanisms, while others deal with epidemiologic aspects such as associations. The way you organize your paragraphs should be uniform.

We accept that remark and we are added the content of paragraphs with the epidemiologic information, where it was possible.

Reviewer 3 Report

1.     I recommend changing the title of the manuscript. Contrary to the title, there is less about the prevalence of comorbidities in OSA and more about the mechanisms that leads to comorbidities. Therefore, the title “Burden of comorbidities in obstructive sleep apnea, pathophysiologic mechanisms, and therapeutic effects of CPAP” seems more appropriate.

2.     It looks like you need English proofreading for your manuscript.  

3.     Line 66: What is the full spelling of HBP?  

4.     All the figures are difficult to understand. For examples, what is the meaning of the colored arrows in Figure 1? The hierarchy between oxidative stress and HIF-1, ROS in Figure 2 needs to be reconsidered. In Figure 2, what are the causes atherosclerosis in OSAS?

5.     Figures should summarize the description in the manuscript. However, the description of the figure’s construction is often absent from the manuscript.

6.     The possible mechanism linking OSAS to cancer is not entirely due to hypoxia: the effects of sleep fragmentation should be considered after a careful review of recent papers. The results of intermittent hypoxia on cancer have also been shown in animal or cell culture studies.

7.     The organization of paragraphs under subheadings is not the same: Some paragraphs deal primarily with pathophysiologic mechanisms, while others deal with epidemiologic aspects such as associations. The way you organize your paragraphs should be uniform.

Comments for author File: Comments.docx

English proofreading for your manuscript is required. 

Author Response

Thank you for your feedback, we are already supplemented the content our paper paragraphs with the information from proposed studies.

Round 2

Reviewer 1 Report

Dear

There is no problem.

There are some grammatical errors.

Author Response

Thank you very much for your comments! The manuscript was double cheched by native English speaker!

Reviewer 2 Report

No more requests

Author Response

thank you very much!

Reviewer 3 Report

Most of the questions and inquiries were answered appropriately; however, in Figure 2, the arrow indicating that endothelial dysfunction is a cause of atherosclerosis does not seem appropriate. Endothelial dysfunction is considered a marker of atherosclerosis, rather than a cause of atherosclerosis itself. The relationship between endothelial dysfunction and atherosclerosis should be revised. 

Although the author states that the manuscript was edited by a native speaker, it is strongly recommended that the manuscript be re-edited by another native speaker.

Author Response

Thank you for your observation, but in a lot of papers endothelial dysfunction is described not
only as a atherosclerosis marker, but also as a part of complex pathophysiological mechanism .
(https://www.ahajournals.org/doi/full/10.1161/CIRCRESAHA.115.306301
https://link.springer.com/article/10.1007/s11883-017-0678-6
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572357/