Reviewer ’s report  
 
Title: High -resolution manometry in patients with and without globus pharyngeus and/or 
symptoms of laryngopharyngeal reflux  
 
Version: 0 Date: 23 Jun 2017  
 
Reviewer: Valentina Casini  
 
Reviewer's report:  
 
The aim of the study is to identify risk factors and motility parameters in patient with 
laryngopharyngeal sym ptoms refractory to proton pump inhibitors (PPI), in particular globus, 
which is very poorly defined in literature.  
The study is interesting due to the relative high frequency of this symptom during 
gastroenterological visits which appears not always relat ed to gastroesophageal reflux.  
The methodology of the study is appropriate, with a sufficient number of patient and controls, 
divided into four groups according to presence or absence of laryngopharyngeal symptoms 
refractory to proton pump inhibitors (PPI) : G-NR (globus - non reflux), G -R (globus - reflux), 
NG-NR (non globus - non reflux), NG -R (non globus - reflux).  
A limitation of the study, which is reported in the discussion, is the lack of 24 -pH monitoring 
that could better characterized the population . As a matter of fact, the gold standard for this kind 
of population should be a combination with oropharyngeal pH monitoring (i.e. dx -pH 
monitoring).  
The authors should mention which schedule of PPI therapy was performed and for how logn to 
consider the p atient "refractory".  
Data regarding pathological motility measurements during high resolution manometry (HMR) 
are very clear, figures in particularly, confirming a high pressure of the UES (upper esophageal 
sphincter) in those patients with globus accordin g to the only similar study present in literature 
conducted on patients with globus (Peng L. et al J Clin Gastroenterol 2015).  
Regarding the discussion of analysis of sex and life exposure factors in G -NR patients data are 
clear and complete (figure 3 not available).  
The final discussion is complete (highly appreciated references to pathophysiology of UES). If 
possible, in the final part of the discussion, the authors should clarify what kind of "regulation of 
UES pressure" they think about.  
English is fine but a revision of the paragraph "Questionnaire - RSI version" should be 
suggested.  
 
Are the methods appropri ate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions d rawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is  recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections b efore being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open pee r review policy of the journal  
Reviewer ’s report  
 
Title: High -resolution manometry in patients with and without globus pharyngeus and/or 
symptoms of laryngopharyngeal reflux  
 
Version: 0 Date: 23 Jun 2017  
 
Reviewer: Valentina Casini  
 
Reviewer's report:  
 
The aim of the study is to identify risk factors and motility parameters in patient with 
laryngopharyngeal sym ptoms refractory to proton pump inhibitors (PPI), in particular globus, 
which is very poorly defined in literature.  
The study is interesting due to the relative high frequency of this symptom during 
gastroenterological visits which appears not always relat ed to gastroesophageal reflux.  
The methodology of the study is appropriate, with a sufficient number of patient and controls, 
divided into four groups according to presence or absence of laryngopharyngeal symptoms 
refractory to proton pump inhibitors (PPI) : G-NR (globus - non reflux), G -R (globus - reflux), 
NG-NR (non globus - non reflux), NG -R (non globus - reflux).  
A limitation of the study, which is reported in the discussion, is the lack of 24 -pH monitoring 
that could better characterized the population . As a matter of fact, the gold standard for this kind 
of population should be a combination with oropharyngeal pH monitoring (i.e. dx -pH 
monitoring).  
The authors should mention which schedule of PPI therapy was performed and for how logn to 
consider the p atient "refractory".  
Data regarding pathological motility measurements during high resolution manometry (HMR) 
are very clear, figures in particularly, confirming a high pressure of the UES (upper esophageal 
sphincter) in those patients with globus accordin g to the only similar study present in literature 
conducted on patients with globus (Peng L. et al J Clin Gastroenterol 2015).  
Regarding the discussion of analysis of sex and life exposure factors in G -NR patients data are 
clear and complete (figure 3 not available).  
The final discussion is complete (highly appreciated references to pathophysiology of UES). If 
possible, in the final part of the discussion, the authors should clarify what kind of "regulation of 
UES pressure" they think about.  
English is fine but a revision of the paragraph "Questionnaire - RSI version" should be 
suggested.  
 
Are the methods appropri ate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions d rawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is  recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections b efore being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open pee r review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: High -resolution manometry in patients with and without globus pharyngeus and/or 
symptoms of laryngopharyngeal reflux  
 
Version: 0 Date: 23 Jun 2017  
 
Reviewer: Valentina Casini  
 
Reviewer's report:  
 
The aim of the study is to identify risk factors and motility parameters in patient with 
laryngopharyngeal sym ptoms refractory to proton pump inhibitors (PPI), in particular globus, 
which is very poorly defined in literature.  
The study is interesting due to the relative high frequency of this symptom during 
gastroenterological visits which appears not always relat ed to gastroesophageal reflux.  
The methodology of the study is appropriate, with a sufficient number of patient and controls, 
divided into four groups according to presence or absence of laryngopharyngeal symptoms 
refractory to proton pump inhibitors (PPI) : G-NR (globus - non reflux), G -R (globus - reflux), 
NG-NR (non globus - non reflux), NG -R (non globus - reflux).  
A limitation of the study, which is reported in the discussion, is the lack of 24 -pH monitoring 
that could better characterized the population . As a matter of fact, the gold standard for this kind 
of population should be a combination with oropharyngeal pH monitoring (i.e. dx -pH 
monitoring).  
The authors should mention which schedule of PPI therapy was performed and for how logn to 
consider the p atient "refractory".  
Data regarding pathological motility measurements during high resolution manometry (HMR) 
are very clear, figures in particularly, confirming a high pressure of the UES (upper esophageal 
sphincter) in those patients with globus accordin g to the only similar study present in literature 
conducted on patients with globus (Peng L. et al J Clin Gastroenterol 2015).  
Regarding the discussion of analysis of sex and life exposure factors in G -NR patients data are 
clear and complete (figure 3 not available).  
The final discussion is complete (highly appreciated references to pathophysiology of UES). If 
possible, in the final part of the discussion, the authors should clarify what kind of "regulation of 
UES pressure" they think about.  
English is fine but a revision of the paragraph "Questionnaire - RSI version" should be 
suggested.  
 
Are the methods appropri ate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions d rawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is  recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I am able to assess the statistics  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Needs some language corrections b efore being published  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in the past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisation that may in any way gain or lose  
financially from the publication of this  manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursements, fees, funding, or salary from an organization that 
holds  or has applied f or patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to this paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests.  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the website along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my named report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open pee r review policy of the journal  
assistant