Immunological and microRNA Features of Allergic Rhinitis in the Context of United Airway Disease

Round 1

Reviewer 1 Report

It is a well written review of the current understanding the relation between AR and BA.

The main message in this article seems to be in line 132-136, but the authours fail to make it clear.

"In the last decades, discovering Th17 cells and regulatory T (Treg) cells has dramatically complicated the established Th1/Th2 paradigm. Moreover, this complicates the understanding of the pathogenesis of AR [29]. Then, the involvement of Th17 cells in neutrophil infiltration and chronic  inflammation. Clinically, the role of Th17 lymphocytes in allergic and autoimmune diseases was confirmed."

Rewording of this paragraph would be necessary.

Author Response

Reviewer 1

It is a well written review of the current understanding the relation between AR and BA.

• Thank you for the overall good evaluation of our paper.

The main message in this article seems to be in line 132-136, but the authours fail to make it clear.

"In the last decades, discovering Th17 cells and regulatory T (Treg) cells has dramatically complicated the established Th1/Th2 paradigm. Moreover, this complicates the understanding of the pathogenesis of AR [29]. Then, the involvement of Th17 cells in neutrophil infiltration and chronic  inflammation. Clinically, the role of Th17 lymphocytes in allergic and autoimmune diseases was confirmed."

Rewording of this paragraph would be necessary.

• Thank you very much for the suggestion. We have rewritten the text accordingly to make the message clear, concise, and comprehensive.

Reviewer 2 Report

Thanks for the opportunity to review this article.

The topic, namely the immunologic profile of allergic rhinitis (AR) and bronchial asthma (BA) with specific reference to miRNAs is of course novel and important. The article is written by a group with experience in this field.

I find the manuscript however to be disjointed and does not address the topic described in the title and abstract in detail. There is an extensive description of the classical immunology of AR (which I would expect to be well known to the reader), blurring between AR and inflammatory sinus disease, only a short section on miRNAs and then a rapid shift into a discussion of monoclonal antibody therapy which is a separate topic.

At times there are claims that I don't necessarily disagree with but think would benefit from being referenced including:

 - Line 39: “nasal and sinus involvement are closely related to bronchial asthma at both pathophysiological and clinical levels”

 - Line 54: affecting the nose and sinuses shares common pathological features with those of the lungs

 - Line 175: “they can serve as noninvasive biomarkers"

There are a number of typos that I have seen, including but not limited to:

Line 44 - 45 “more than one condition(s)”, Line 66: “Among diseases chronic characterized by coughing”, Line 176: “severy”

I am unsure if the comment in line 188 “the standard nonsteroidal anti-inflammatory treatment” is a typo? While corticosteroids are "standard" I am not sure that NSAIDs are considered "standard"?

I also note that miRNAs is not defined in the abstract.

While I consider the topic, namely miRNAs in AR and BA to be worthy of a published review article I do not consider that the manuscript in its current form is ready for publication.

Author Response

Reviewer 2

Thanks for the opportunity to review this article.

The topic, namely the immunologic profile of allergic rhinitis (AR) and bronchial asthma (BA) with specific reference to miRNAs is of course novel and important. The article is written by a group with experience in this field.

• Thank you for the overall good evaluation of our paper.

I find the manuscript however to be disjointed and does not address the topic described in the title and abstract in detail. There is an extensive description of the classical immunology of AR (which I would expect to be well known to the reader), blurring between AR and inflammatory sinus disease, only a short section on miRNAs and then a rapid shift into a discussion of monoclonal antibody therapy which is a separate topic.

• Thank you very much for the comment. Indeed, we put attention also to the description of the classical immune mechanism to emphasize once again their role in the current and novel concept of the united airway pathway/disease. In line with this, we use relatively brief passages for the most common knowledge and increase the sections regarding Th17 cells, respective cytokines, miRNAs, etc.
• However, we agree with the referee that there might be “blurring” and “jumping from topic to topic”, therefore, we add some text to enhance the clarity and logical flow of the paper.

At times there are claims that I don't necessarily disagree with but think would benefit from being referenced including:

 - Line 39: “nasal and sinus involvement are closely related to bronchial asthma at both pathophysiological and clinical levels”

 - Line 54: affecting the nose and sinuses shares common pathological features with those of the lungs

 - Line 175: “they can serve as noninvasive biomarkers"

• Thank you very much for the valuable suggestions. We corrected them all and think that this improved the quality of our paper.

There are a number of typos that I have seen, including but not limited to:

Line 44 - 45 “more than one condition(s)”, Line 66: “Among diseases chronic characterized by coughing”, Line 176: “severy”

• The referee is right to note that there are several typos in our manuscript. We proofread it again, as well as a colleague of ours, bilingual in English and French, for inconsistencies, mistakes, etc.

I am unsure if the comment in line 188 “the standard nonsteroidal anti-inflammatory treatment” is a typo? While corticosteroids are "standard" I am not sure that NSAIDs are considered "standard"?

• We have removed the word “standard”, as it was not the correct adjective.

I also note that miRNAs is not defined in the abstract.

• Thank you for the valuable note. We added the missing information.

While I consider the topic, namely miRNAs in AR and BA to be worthy of a published review article I do not consider that the manuscript in its current form is ready for publication.

• We agree with the referee that miRNAs are a “hot” topic in the area that deserves tremendous interest. However, it was important to us to present the problem with a focus on the united airway disease, including sinusitis, rhinitis, and asthma. Furthermore, we considered as important to have the most common facts as a basis.
• We gave our best to increase the readability and to improve the quality of the paper. miRNAs are just an additional part of the manuscript that aims to cover the other future perspectives with a focus on diagnostics and therapy.

Reviewer 3 Report

Thank you very much for the opportunity to review this article. This review presents a very important and often overlooked problem of united airway disease. It seems to me that it is very necessary to raise this issue.

This overview is well structured and covers many aspects of the issue. However, it seems that the literature could be more current. The most recent citations are from articles from 2018 and 2019, and most are from the first decade of the 20th century. In such a literature review (especially in the rapidly developing field of immunology), more recent reports should be included.

In my opinion, authors should complete this overview of the more recent literature.

Author Response

Reviewer 3

Thank you very much for the opportunity to review this article. This review presents a very important and often overlooked problem of united airway disease. It seems to me that it is very necessary to raise this issue.

• Thank you for the overall good evaluation of our paper.

This overview is well structured and covers many aspects of the issue. However, it seems that the literature could be more current. The most recent citations are from articles from 2018 and 2019, and most are from the first decade of the 20th century. In such a literature review (especially in the rapidly developing field of immunology), more recent reports should be included.

In my opinion, authors should complete this overview of the more recent literature.

• Thank you very much for the valuable recommendations. Indeed, we have missed the most recent papers. After a new search, we have added four papers on the topic from the last 2-5 years.

Round 2

Reviewer 2 Report

Thanks for taking on my comments from the prior review