Reviewer ’s report  
 
Title: Typical symptoms and not positive reflux -cough correlation predict cure of 
gastroesophageal  reflux disease related chronic cough after laparoscopic fundoplication: a 
retrospective  study  
 
Version: 0 Date: 30 Nov 2018  
 
Reviewer: Amit  Patel  
 
Reviewer's report:  
 
The authors of this manuscript, "Typical symptoms and not positive reflux -cough correlation 
predict cure of GERD related chronic cough after laparoscopic fundoplication," should be 
congratulated on their efforts. In this retrospective investigation of 79 p atients with chronic 
cough who underwent antireflux surgery (ARS), the authors found that nearly three -fourths of 
patients had significant improvement or cure in their cough symptoms with ARS at median 
follow -up of almost 3 years. Concomitant typical GERD symptoms and numbers of impedance -
detected reflux events were significantly associated with resolution of cough after ARS, but not 
esophageal acid exposure or cough -reflux association.  
 
 
Suggestions:  
 
-Background: nice concise introduction; consider includi ng the more recent Lyon GERD 
consensus group statements as reference(s) (Roman, Gyawali, Savarino)  
 
-Background: suggest clarifying that GERD symptom response rates for ARS vary based on 1) 
evidence for GERD, as in ambulatory reflux monitoring metrics/GERD phenotypes, and 2) the 
particular symptom (which you acknowledge)  
 
-Background: reasonable to mention prior work suggesting value of symptom -reflux association 
on 24 -hr pH -impedance monitoring in prediction of symptomatic improvement with antireflux 
therapy  (there is data in both directions) in background or discussion  
 
-Methods: was pH -impedance monitoring performed on or off PPI?  
 
-Methods: were major esophageal motor disorders on HRM excluded from the study?  
 
-Methods: mention that reflux events were collect ed from pH -impedance monitoring  
 
-Methods: were Likert scales/any numeric scales used for patient -reported symptomatic 
outcomes beyond the cured/excellent/fair/poor categories described here?  
 
-Figure 1: nice diagram, but end it with the study cohort N=79 in stead of N=97 (unable to be 
contacted via telephone for follow -up, patients passed away)  
-Table 1: this can be folded into the text to allow room for another Table or Figure (as below)  
 
-Results: include breakdown of cohort, by symptom, into cured/excellent /fair/poor outcome 
categories (can perhaps replace Table 2 with this)  
 
-Table 3: was BMI/obesity not included in univariate model?  
 
-Results: why were patients selected for different surgical procedures (HRM findings?)  
 
-Results: it is surprising that AET was  not associated with symptom response after ARS - I 
suggest speculation in the discussion on why this might have been the case in this cohort (did it, 
for example, predict typical GERD symptom outcomes in the cohort, if this information is 
available?). ARS  was performed in some of these patients without pathologic AET (presumably, 
off PPI?) and without positive cough -reflux association - can you provide insight into what 
prompted this approach (in our practice, these types of patients are rarely sent for AR S in this 
setting)?  
 
-Discussion: would start with several sentences summarizing the major findings, before 
exploration of pertinent prior literature  
 
-Discussion: there are multiple newer GERD guidelines/consensus statements since 2007, 
including ACG, refer ence these  
 
-Discussion: good use of other references on the topic, but the page -long paragraph on page 7 
can be difficult to get through - suggest clarifying/streamlining this part of the discussion to make 
it easier for readers to comprehend, can also incl ude work from Vaezi's group on the drawbacks 
of symptom -reflux association parameters  
 
-Discussion: inclusion of multivariate analyses, consistency testing should be discussed in results 
in first  
 
 
Are the methods appropriate 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.  
 
Unable to assess  
 
Are the conclusions drawn 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 before 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 recei ved reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for 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 peer review policy of the journal  
Reviewer ’s report  
 
Title: Typical symptoms and not positive reflux -cough correlation predict cure of 
gastroesophageal  reflux disease related chronic cough after laparoscopic fundoplication: a 
retrospective  study  
 
Version: 0 Date: 30 Nov 2018  
 
Reviewer: Amit  Patel  
 
Reviewer's report:  
 
The authors of this manuscript, "Typical symptoms and not positive reflux -cough correlation 
predict cure of GERD related chronic cough after laparoscopic fundoplication," should be 
congratulated on their efforts. In this retrospective investigation of 79 p atients with chronic 
cough who underwent antireflux surgery (ARS), the authors found that nearly three -fourths of 
patients had significant improvement or cure in their cough symptoms with ARS at median 
follow -up of almost 3 years. Concomitant typical GERD symptoms and numbers of impedance -
detected reflux events were significantly associated with resolution of cough after ARS, but not 
esophageal acid exposure or cough -reflux association.  
 
 
Suggestions:  
 
-Background: nice concise introduction; consider includi ng the more recent Lyon GERD 
consensus group statements as reference(s) (Roman, Gyawali, Savarino)  
 
-Background: suggest clarifying that GERD symptom response rates for ARS vary based on 1) 
evidence for GERD, as in ambulatory reflux monitoring metrics/GERD phenotypes, and 2) the 
particular symptom (which you acknowledge)  
 
-Background: reasonable to mention prior work suggesting value of symptom -reflux association 
on 24 -hr pH -impedance monitoring in prediction of symptomatic improvement with antireflux 
therapy  (there is data in both directions) in background or discussion  
 
-Methods: was pH -impedance monitoring performed on or off PPI?  
 
-Methods: were major esophageal motor disorders on HRM excluded from the study?  
 
-Methods: mention that reflux events were collect ed from pH -impedance monitoring  
 
-Methods: were Likert scales/any numeric scales used for patient -reported symptomatic 
outcomes beyond the cured/excellent/fair/poor categories described here?  
 
-Figure 1: nice diagram, but end it with the study cohort N=79 in stead of N=97 (unable to be 
contacted via telephone for follow -up, patients passed away)  
-Table 1: this can be folded into the text to allow room for another Table or Figure (as below)  
 
-Results: include breakdown of cohort, by symptom, into cured/excellent /fair/poor outcome 
categories (can perhaps replace Table 2 with this)  
 
-Table 3: was BMI/obesity not included in univariate model?  
 
-Results: why were patients selected for different surgical procedures (HRM findings?)  
 
-Results: it is surprising that AET was  not associated with symptom response after ARS - I 
suggest speculation in the discussion on why this might have been the case in this cohort (did it, 
for example, predict typical GERD symptom outcomes in the cohort, if this information is 
available?). ARS  was performed in some of these patients without pathologic AET (presumably, 
off PPI?) and without positive cough -reflux association - can you provide insight into what 
prompted this approach (in our practice, these types of patients are rarely sent for AR S in this 
setting)?  
 
-Discussion: would start with several sentences summarizing the major findings, before 
exploration of pertinent prior literature  
 
-Discussion: there are multiple newer GERD guidelines/consensus statements since 2007, 
including ACG, refer ence these  
 
-Discussion: good use of other references on the topic, but the page -long paragraph on page 7 
can be difficult to get through - suggest clarifying/streamlining this part of the discussion to make 
it easier for readers to comprehend, can also incl ude work from Vaezi's group on the drawbacks 
of symptom -reflux association parameters  
 
-Discussion: inclusion of multivariate analyses, consistency testing should be discussed in results 
in first  
 
 
Are the methods appropriate 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.  
 
Unable to assess  
 
Are the conclusions drawn 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 before 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 recei ved reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for 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 peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Typical symptoms and not positive reflux -cough correlation predict cure of 
gastroesophageal  reflux disease related chronic cough after laparoscopic fundoplication: a 
retrospective  study  
 
Version: 0 Date: 30 Nov 2018  
 
Reviewer: Amit  Patel  
 
Reviewer's report:  
 
The authors of this manuscript, "Typical symptoms and not positive reflux -cough correlation 
predict cure of GERD related chronic cough after laparoscopic fundoplication," should be 
congratulated on their efforts. In this retrospective investigation of 79 p atients with chronic 
cough who underwent antireflux surgery (ARS), the authors found that nearly three -fourths of 
patients had significant improvement or cure in their cough symptoms with ARS at median 
follow -up of almost 3 years. Concomitant typical GERD symptoms and numbers of impedance -
detected reflux events were significantly associated with resolution of cough after ARS, but not 
esophageal acid exposure or cough -reflux association.  
 
 
Suggestions:  
 
-Background: nice concise introduction; consider includi ng the more recent Lyon GERD 
consensus group statements as reference(s) (Roman, Gyawali, Savarino)  
 
-Background: suggest clarifying that GERD symptom response rates for ARS vary based on 1) 
evidence for GERD, as in ambulatory reflux monitoring metrics/GERD phenotypes, and 2) the 
particular symptom (which you acknowledge)  
 
-Background: reasonable to mention prior work suggesting value of symptom -reflux association 
on 24 -hr pH -impedance monitoring in prediction of symptomatic improvement with antireflux 
therapy  (there is data in both directions) in background or discussion  
 
-Methods: was pH -impedance monitoring performed on or off PPI?  
 
-Methods: were major esophageal motor disorders on HRM excluded from the study?  
 
-Methods: mention that reflux events were collect ed from pH -impedance monitoring  
 
-Methods: were Likert scales/any numeric scales used for patient -reported symptomatic 
outcomes beyond the cured/excellent/fair/poor categories described here?  
 
-Figure 1: nice diagram, but end it with the study cohort N=79 in stead of N=97 (unable to be 
contacted via telephone for follow -up, patients passed away)  
-Table 1: this can be folded into the text to allow room for another Table or Figure (as below)  
 
-Results: include breakdown of cohort, by symptom, into cured/excellent /fair/poor outcome 
categories (can perhaps replace Table 2 with this)  
 
-Table 3: was BMI/obesity not included in univariate model?  
 
-Results: why were patients selected for different surgical procedures (HRM findings?)  
 
-Results: it is surprising that AET was  not associated with symptom response after ARS - I 
suggest speculation in the discussion on why this might have been the case in this cohort (did it, 
for example, predict typical GERD symptom outcomes in the cohort, if this information is 
available?). ARS  was performed in some of these patients without pathologic AET (presumably, 
off PPI?) and without positive cough -reflux association - can you provide insight into what 
prompted this approach (in our practice, these types of patients are rarely sent for AR S in this 
setting)?  
 
-Discussion: would start with several sentences summarizing the major findings, before 
exploration of pertinent prior literature  
 
-Discussion: there are multiple newer GERD guidelines/consensus statements since 2007, 
including ACG, refer ence these  
 
-Discussion: good use of other references on the topic, but the page -long paragraph on page 7 
can be difficult to get through - suggest clarifying/streamlining this part of the discussion to make 
it easier for readers to comprehend, can also incl ude work from Vaezi's group on the drawbacks 
of symptom -reflux association parameters  
 
-Discussion: inclusion of multivariate analyses, consistency testing should be discussed in results 
in first  
 
 
Are the methods appropriate 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.  
 
Unable to assess  
 
Are the conclusions drawn 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 before 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 recei ved reimbursements, fees, funding, or salary from an organization that 
holds  or has applied for 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 peer review policy of the journal  
assistant