Reviewer’s report  
 
Title: Tracheobronchitis in Ulcerative Colitis: a case of therapeut ic response with infliximab and 
review of the literature  
 
Version: 0 Date: 26 Jul 2019  
 
Reviewer: Ted Spiewak  
 
Reviewer's report:  
 
This is a case of a novel treatment for a rare and potentially life -threatening condition. This study 
further highlights and strengthens the literature regarding the high index of suspicio n one must 
have when encountering a patient with inflammatory bowel disease (IBD) and presenting with 
bronchopulmonary complaints. As reported, the bronchopulmonary extraintestinal 
manifestations (EIM) of IBD are rare and historically reported to be under recognized by 
gastroenterologists and pulmonologists. The literature stands to benefit from this case study as 
better outcomes will arise from increased recognition leading to more aggressive management.  
 
There is a paucity of evidence -based literature re garding treatment of these manifestations. 
Ulcerative colitis (UC) involvement of the lung parenchyma typically presents predominantly as 
bronchiolitis obliterans organising pneumonia (BOOP) or interstitial lung disease with varying 
pathological patterns. This case is one of only fifteen reported cases of UC related 
tracheobronchitis. Limited data does exist surrounding the use of infliximab for BOOP, but these 
are in the form of (~10) case reports. One caveat, is that most case reports describe the use of 
anti-TNF -α therapy for pulmonary manifestations in patients with active Crohn's disease. This 
could lead the reader to believe that resolution of the active disease is the prime driver of 
response to treatment and also justify use of therapy from the begin ning. The majority of studies 
currently published describe treatment with oral, inhaled and sometimes intravenous 
corticosteroids in addition to steroid sparing immunosuppressants like Azathioprine.  
 
This case report is an example of Infliximab treatment resulting in a dramatic positive effect on 
this patient's pulmonary inflammatory manifestations that were previously uncontrolled on 
glucocorticoid therapy, which is also rare and supported by the literature. This case report adds 
to the lack of evidence -based recommendations regarding treatment of corticosteroid failure. 
This therapeutic result was also in the setting of quiescent disease. This highlights the rare 
instances where highly active IBD luminal disease is not required for the emergence of an EIM  
of the disease and absence of luminal disease activity should not be relied on to make or exclude 
the diagnosis. In this instance, use of infliximab was solely targeting the pulmonary disease. As 
stated by the authors, there is limited evidence for anti -TNF-α therapy in this setting and this 
study adds to the slow growing number of pulmonary cases that have responded well. The use of 
Infliximab in pulmonary Crohn's disease is guided primarily by case reports supporting its 
efficacy. This case report descri bes the first trial of an anti -TNF monoclonal antibody for UC -
related tracheobronchitis with clinical benefit. This unique case provides valuable experiential 
support for a trial of infliximab in cases of UC -related tracheobronchitis proving dependent on 
high dose corticosteroids and poorly responsive to other steroid -sparing agents such as 
azathioprine.  
 
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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in t he manuscript:  
 
Acceptable  
 
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  
organization  that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organization  that may in any way gain or lose 
financially from the publication of this m anuscript, 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 for pat ents 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 wil l 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 und er 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: Tracheobronchitis in Ulcerative Colitis: a case of therapeut ic response with infliximab and 
review of the literature  
 
Version: 0 Date: 26 Jul 2019  
 
Reviewer: Ted Spiewak  
 
Reviewer's report:  
 
This is a case of a novel treatment for a rare and potentially life -threatening condition. This study 
further highlights and strengthens the literature regarding the high index of suspicio n one must 
have when encountering a patient with inflammatory bowel disease (IBD) and presenting with 
bronchopulmonary complaints. As reported, the bronchopulmonary extraintestinal 
manifestations (EIM) of IBD are rare and historically reported to be under recognized by 
gastroenterologists and pulmonologists. The literature stands to benefit from this case study as 
better outcomes will arise from increased recognition leading to more aggressive management.  
 
There is a paucity of evidence -based literature re garding treatment of these manifestations. 
Ulcerative colitis (UC) involvement of the lung parenchyma typically presents predominantly as 
bronchiolitis obliterans organising pneumonia (BOOP) or interstitial lung disease with varying 
pathological patterns. This case is one of only fifteen reported cases of UC related 
tracheobronchitis. Limited data does exist surrounding the use of infliximab for BOOP, but these 
are in the form of (~10) case reports. One caveat, is that most case reports describe the use of 
anti-TNF -α therapy for pulmonary manifestations in patients with active Crohn's disease. This 
could lead the reader to believe that resolution of the active disease is the prime driver of 
response to treatment and also justify use of therapy from the begin ning. The majority of studies 
currently published describe treatment with oral, inhaled and sometimes intravenous 
corticosteroids in addition to steroid sparing immunosuppressants like Azathioprine.  
 
This case report is an example of Infliximab treatment resulting in a dramatic positive effect on 
this patient's pulmonary inflammatory manifestations that were previously uncontrolled on 
glucocorticoid therapy, which is also rare and supported by the literature. This case report adds 
to the lack of evidence -based recommendations regarding treatment of corticosteroid failure. 
This therapeutic result was also in the setting of quiescent disease. This highlights the rare 
instances where highly active IBD luminal disease is not required for the emergence of an EIM  
of the disease and absence of luminal disease activity should not be relied on to make or exclude 
the diagnosis. In this instance, use of infliximab was solely targeting the pulmonary disease. As 
stated by the authors, there is limited evidence for anti -TNF-α therapy in this setting and this 
study adds to the slow growing number of pulmonary cases that have responded well. The use of 
Infliximab in pulmonary Crohn's disease is guided primarily by case reports supporting its 
efficacy. This case report descri bes the first trial of an anti -TNF monoclonal antibody for UC -
related tracheobronchitis with clinical benefit. This unique case provides valuable experiential 
support for a trial of infliximab in cases of UC -related tracheobronchitis proving dependent on 
high dose corticosteroids and poorly responsive to other steroid -sparing agents such as 
azathioprine.  
 
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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in t he manuscript:  
 
Acceptable  
 
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  
organization  that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organization  that may in any way gain or lose 
financially from the publication of this m anuscript, 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 for pat ents 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 wil l 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 und er 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: Tracheobronchitis in Ulcerative Colitis: a case of therapeut ic response with infliximab and 
review of the literature  
 
Version: 0 Date: 26 Jul 2019  
 
Reviewer: Ted Spiewak  
 
Reviewer's report:  
 
This is a case of a novel treatment for a rare and potentially life -threatening condition. This study 
further highlights and strengthens the literature regarding the high index of suspicio n one must 
have when encountering a patient with inflammatory bowel disease (IBD) and presenting with 
bronchopulmonary complaints. As reported, the bronchopulmonary extraintestinal 
manifestations (EIM) of IBD are rare and historically reported to be under recognized by 
gastroenterologists and pulmonologists. The literature stands to benefit from this case study as 
better outcomes will arise from increased recognition leading to more aggressive management.  
 
There is a paucity of evidence -based literature re garding treatment of these manifestations. 
Ulcerative colitis (UC) involvement of the lung parenchyma typically presents predominantly as 
bronchiolitis obliterans organising pneumonia (BOOP) or interstitial lung disease with varying 
pathological patterns. This case is one of only fifteen reported cases of UC related 
tracheobronchitis. Limited data does exist surrounding the use of infliximab for BOOP, but these 
are in the form of (~10) case reports. One caveat, is that most case reports describe the use of 
anti-TNF -α therapy for pulmonary manifestations in patients with active Crohn's disease. This 
could lead the reader to believe that resolution of the active disease is the prime driver of 
response to treatment and also justify use of therapy from the begin ning. The majority of studies 
currently published describe treatment with oral, inhaled and sometimes intravenous 
corticosteroids in addition to steroid sparing immunosuppressants like Azathioprine.  
 
This case report is an example of Infliximab treatment resulting in a dramatic positive effect on 
this patient's pulmonary inflammatory manifestations that were previously uncontrolled on 
glucocorticoid therapy, which is also rare and supported by the literature. This case report adds 
to the lack of evidence -based recommendations regarding treatment of corticosteroid failure. 
This therapeutic result was also in the setting of quiescent disease. This highlights the rare 
instances where highly active IBD luminal disease is not required for the emergence of an EIM  
of the disease and absence of luminal disease activity should not be relied on to make or exclude 
the diagnosis. In this instance, use of infliximab was solely targeting the pulmonary disease. As 
stated by the authors, there is limited evidence for anti -TNF-α therapy in this setting and this 
study adds to the slow growing number of pulmonary cases that have responded well. The use of 
Infliximab in pulmonary Crohn's disease is guided primarily by case reports supporting its 
efficacy. This case report descri bes the first trial of an anti -TNF monoclonal antibody for UC -
related tracheobronchitis with clinical benefit. This unique case provides valuable experiential 
support for a trial of infliximab in cases of UC -related tracheobronchitis proving dependent on 
high dose corticosteroids and poorly responsive to other steroid -sparing agents such as 
azathioprine.  
 
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.  
 
Not relevant to this manuscript  
 
Quality of written English  
Please indicate the quality of language in t he manuscript:  
 
Acceptable  
 
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  
organization  that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organization  that may in any way gain or lose 
financially from the publication of this m anuscript, 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 for pat ents 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 wil l 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 und er 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