Vagus Nerve Preservation and Chronic Cough in Non-small Cell Lung Cancer Surgery
October 24, 2022 updated by: Kwhanmien Kim, Seoul National University Bundang Hospital
Prospective Randomized Controlled Study on the Effects of Vagus Nerve Pulmonary Branch Preservation During Video-assisted Thoracic Surgery Lobectomy in Non-small Cell Lung Cancer: Can it Decrease Postoperative Cough and Pulmonary Complications
Lung cancer is the leading cause of cancer death worldwide. Surgical resection is the main treatment for resectable non-small-cell lung cancer (NSCLC), and lobectomy with systemic mediastinal lymph node dissection is the standard surgical method. However, a significant number of patients experience postoperative chronic cough; it is observed in about 60% of patients during the first year of outpatient clinic follow-up, and persistently lasts in about 24.7-50% during the 5 year follow-up period.
Several studies showed the association between vagus nerve and chronic cough. The bronchopulmonary vagal afferent C-fibers are responsible for cough, chest tightness and reflex bronchoconstrictions. It is expected that during the mediastinal lymph node dissection, the inevitable injuries to the pulmonary branch of vagus nerve is largely responsible for development of chronic cough. In other words, preservation of pulmonary branch of vagus nerve may reduce the incidence of chronic cough and relevant detrimental effects on quality of life.
Therefore, this prospective, randomized and controlled clinical study, aims to evaluate the effect of vagus nerve preservation on postoperative chronic cough in patients undergoing lobectomy with mediastinal lymph node dissection. In addition, the feasibility and oncologic safety of preserving pulmonary branch of vagus nerve during mediastinal lymph node dissection with minimally invasive surgery compared with conventional mediastinal lymph node dissection with minimally invasive surgery will also be investigated.
This trial will provide a new basis for oncologically feasible, safe and effective new surgical technique for mediastinal lymph node dissection in patients with early lung cancer undergoing minimally invasive surgery. Furthermore, the preventive effect of vagus nerve preservation on incidence of chronic cough will be objectively be proven and thus help to broaden the current knowledge of the role of vagus nerve and postoperative chronic cough.
Study Overview
Status
Recruiting
Conditions
Study Type
Interventional
Enrollment (Anticipated)
214
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Kwhanmien Kim, MD. PhD
- Phone Number: +82-31-787-7130
- Email: kmkim0070@snubh.org
Study Locations
-
-
Bundang
-
Seongnam-si, Bundang, Korea, Republic of, 13620
- Recruiting
- Seoul National University
-
Contact:
- Beatrice C Shih, MD
- Phone Number: 821091094533
- Email: 82430@snubh.org
-
Principal Investigator:
- Kwhanmien Kim, MD.PhD.
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 80 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Subjects clearly understand the purpose of the study, are willing and able to comply with the requirements to complete the study, and can sign the informed consent.
- Clinically suspicious of non-small cell lung cancer or tissue confirmed preoperatively
- Clinical stage T1-3/N0-1/M0
- Preoperative ECOG performance status 0-1
- Preoperative ASA class I-III
- Preoperative pulmonary function test FEV1 ≥ 60%, DLCO ≥ 60%
- Patients expected to achieve R0 (complete resection) via simple lobectomy and mediastinal lymph node dissection
Exclusion Criteria:
- Patients who smoked within 2 weeks prior to operation
- Patients who received antitussives and expectorants 2 weeks prior to operation
- Patients who are pregnant or breast feeding
- Patients with severe or uncontrolled psychological disorders
- Patients with severe pulmonary adhesion
- Patients who are ineligible for minimally invasive surgery; thoracotomy conversion
- Patients diagnosed with other malignancies within 2 years prior to operation
- Patients who received chemotherapy or radiotherapy within 6 months prior to operation
- Patients suspicious of clinical N2 or received neoadjuvant therapy prior to operation
- Patients with cough-related diseases; COPD, asthma, ILD, GERD
- Patients suspicious of lymph node metastasis/invasion around vagus nerve during the preoperative clinical staging evaluation
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
Experimental: Pulmonary branch of vagus nerve preserved
Pulmonary branch of vagus nerve is preserved during the mediastinal lymph node dissection using minimally invasive surgery
|
During the mediastinal lymph node dissection using minimally invasive surgery, efforts to preserve the pulmonary branch of vagus nerve is made.
|
|
Experimental: Pulmonary branch of vagus nerve not-preserved
Pulmonary branch of vagus nerve is not preserved during the mediastinal lymph node dissection using minimally invasive surgery
|
During the mediastinal lymph node dissection using minimally invasive surgery, efforts to preserve the pulmonary branch of vagus nerve is not made/ can be severed.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Qualitative measurement of postoperative cough
Time Frame: Preoperative day
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Preoperative day
|
|
Qualitative measurement of postoperative cough
Time Frame: Postoperative day (discharge day, an average of 1 week)
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Postoperative day (discharge day, an average of 1 week)
|
|
Qualitative measurement of postoperative cough
Time Frame: Postoperative 1 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Postoperative 1 month follow up at outpatient clinic
|
|
Qualitative measurement of postoperative cough
Time Frame: Postoperative 2 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Postoperative 2 month follow up at outpatient clinic
|
|
Qualitative measurement of postoperative cough
Time Frame: Postoperative 6 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Postoperative 6 month follow up at outpatient clinic
|
|
Qualitative measurement of postoperative cough
Time Frame: Postoperative 12 month follow up at outpatient clinic
|
Cough Visual Analog Scale (VAS) will be used for survey.
The Cough VAS is a numeric scale from 0-10 scale, with 0 indicating that patient experiences no distress from cough and 10 indicating severe distress from cough.
|
Postoperative 12 month follow up at outpatient clinic
|
|
Quantitative measurement of postoperative cough
Time Frame: Preoperative day
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Preoperative day
|
|
Quantitative measurement of postoperative cough
Time Frame: Postoperative day (discharge day, an average of 1 week)
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Postoperative day (discharge day, an average of 1 week)
|
|
Quantitative measurement of postoperative cough
Time Frame: Postoperative 1 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Postoperative 1 month follow up at outpatient clinic
|
|
Quantitative measurement of postoperative cough
Time Frame: Postoperative 2 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Postoperative 2 month follow up at outpatient clinic
|
|
Quantitative measurement of postoperative cough
Time Frame: Postoperative 6 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Postoperative 6 month follow up at outpatient clinic
|
|
Quantitative measurement of postoperative cough
Time Frame: Postoperative 12 month follow up at outpatient clinic
|
The Korean version of the Leicester Cough Questionnaire will be used for survey.
Comparison of preoperative and and postoperative change in objective cough frequency and quality of life among patients using the Leicester Cough Questionnaire, which is a 7 point Likert scale with a minimum value of 1 indicating chronic cough impacts participant life all of the time and a maximum value of 7 indicating chronic cough impacts participant life none of the time.
|
Postoperative 12 month follow up at outpatient clinic
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
|
Serum TRPA1, TRPV1, bradykinin, PGE2 measurements
Time Frame: Preoperative day
|
Measurement of TRPA1 (ng/mL), TRPV1 (ng/mL), bradykinin (pg/mL), PGE2 (pg/mL) (released from C-fibers) via enzyme-linked immunosorbent assay (ELISA) test to quantitatively measure the injures of the vagus nerve during the mediastinal lymph node dissection.
|
Preoperative day
|
|
Serum TRPA1, TRPV1, bradykinin, PGE2 measurements
Time Frame: Postoperative 1 day
|
Measurement of TRPA1 (ng/mL), TRPV1 (ng/mL), bradykinin (pg/mL), PGE2 (pg/mL) (released from C-fibers) via enzyme-linked immunosorbent assay (ELISA) test to quantitatively measure the injures of the vagus nerve during the mediastinal lymph node dissection.
|
Postoperative 1 day
|
|
Serum TRPA1, TRPV1, bradykinin, PGE2 measurements
Time Frame: Postoperative 2 month follow up at outpatient clinic
|
Measurement of TRPA1 (ng/mL), TRPV1 (ng/mL), bradykinin (pg/mL), PGE2 (pg/mL) (released from C-fibers) via enzyme-linked immunosorbent assay (ELISA) test to quantitatively measure the injures of the vagus nerve during the mediastinal lymph node dissection.
|
Postoperative 2 month follow up at outpatient clinic
|
|
Pulmonary function test
Time Frame: Preoperative day
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Preoperative day
|
|
Pulmonary function test
Time Frame: Postoperative 1 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 1 month follow up at outpatient clinic
|
|
Pulmonary function test
Time Frame: Postoperative 2 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 2 month follow up at outpatient clinic
|
|
Pulmonary function test
Time Frame: Postoperative 6 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 6 month follow up at outpatient clinic
|
|
Pulmonary function test
Time Frame: Postoperative 12 month follow up at outpatient clinic
|
Routine PFT (FEV1%, FEV1/FVC%) check to evaluate the effects of vagus nerve preservation in pulmonary function
|
Postoperative 12 month follow up at outpatient clinic
|
|
Incidence of postoperative pulmonary complications, hospital stay and readmission, ICU care
Time Frame: from admission for operation to until the date of first documented postoperative complication or readmission, whichever came first), assessed up to 30 days
|
from admission for operation to until the date of first documented postoperative complication or readmission, whichever came first), assessed up to 30 days
|
|
|
Histopathologic review of the total number of mediastinal lymph node dissected
Time Frame: through study completion, an average of 1 year
|
Total number of dissected mediastinal lymph nodes and metastatic lymph nodes will be analyzed.
Patient's preoperative clinical N stage and pathologic N stage will be compared; if pathologic N stage is higher than that of the clinical N stage, it will be considered as nodal upstaging.
|
through study completion, an average of 1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Kwhanmien Kim, MD. PhD, Department of Thoracic and Cardiovascular Surgery, Seoul National University Bundang Hospital
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Zhu YF, Wu SB, Zhou MQ, Xie MR, Xiong R, Xu SB, Xu GW. Increased expression of TRPV1 in patients with acute or chronic cough after lung cancer surgery. Thorac Cancer. 2019 Apr;10(4):988-991. doi: 10.1111/1759-7714.13042. Epub 2019 Mar 18.
- Sarna L, Evangelista L, Tashkin D, Padilla G, Holmes C, Brecht ML, Grannis F. Impact of respiratory symptoms and pulmonary function on quality of life of long-term survivors of non-small cell lung cancer. Chest. 2004 Feb;125(2):439-45. doi: 10.1378/chest.125.2.439.
- Kwon JW, Moon JY, Kim SH, Song WJ, Kim MH, Kang MG, Lim KH, Lee SH, Lee SM, Lee JY, Kwon HS, Kim KM, Kim SH, Kim SH, Jeong JW, Kim CW, Cho SH, Lee BJ; Work Group for Chronic Cough, the Korean Academy of Asthma, Allergy and Clinical Immunology. Reliability and validity of a korean version of the leicester cough questionnaire. Allergy Asthma Immunol Res. 2015 May;7(3):230-3. doi: 10.4168/aair.2015.7.3.230. Epub 2014 Dec 18.
- Al-Shamlan F, El-Hashim AZ. Bradykinin sensitizes the cough reflex via a B2 receptor dependent activation of TRPV1 and TRPA1 channels through metabolites of cyclooxygenase and 12-lipoxygenase. Respir Res. 2019 Jun 6;20(1):110. doi: 10.1186/s12931-019-1060-8.
- Chen S, Huang S, Yu S, Han Z, Gao L, Shen Z, Kang M. The clinical value of a new method of functional lymph node dissection in video-assisted thoracic surgery right non-small cell lung cancer radical resection. J Thorac Dis. 2019 Feb;11(2):477-487. doi: 10.21037/jtd.2019.01.15.
- Huang J, Luo Q, Tan Q, Lin H, Qian L, Ding Z. Evaluation of the surgical fat-filling procedure in the treatment of refractory cough after systematic mediastinal lymphadenectomy in patients with right lung cancer. J Surg Res. 2014 Apr;187(2):490-5. doi: 10.1016/j.jss.2013.10.062. Epub 2013 Nov 5.
- Lin R, Che G. Risk factors of cough in non-small cell lung cancer patients after video-assisted thoracoscopic surgery. J Thorac Dis. 2018 Sep;10(9):5368-5375. doi: 10.21037/jtd.2018.08.54.
- Liu Z, Liu Y, Xie C, Yang J, Zeng B, Yeung SJ, Cheng C. Vagus nerve and phrenic nerve guided systematic nodal dissection for lung cancer. J Thorac Dis. 2019 Sep;11(9):4021-4027. doi: 10.21037/jtd.2019.08.80. No abstract available.
- Poghosyan H, Sheldon LK, Leveille SG, Cooley ME. Health-related quality of life after surgical treatment in patients with non-small cell lung cancer: a systematic review. Lung Cancer. 2013 Jul;81(1):11-26. doi: 10.1016/j.lungcan.2013.03.013. Epub 2013 Apr 4.
- Sawabata N, Maeda H, Takeda S, Inoue M, Koma M, Tokunaga T, Matsuda H. Persistent cough following pulmonary resection: observational and empiric study of possible causes. Ann Thorac Surg. 2005 Jan;79(1):289-93. doi: 10.1016/j.athoracsur.2004.06.045.
- Spinou A, Birring SS. An update on measurement and monitoring of cough: what are the important study endpoints? J Thorac Dis. 2014 Oct;6(Suppl 7):S728-34. doi: 10.3978/j.issn.2072-1439.2014.10.08.
- Watanabe A, Nakazawa J, Miyajima M, Harada R, Nakashima S, Mawatari T, Higami T. Thoracoscopic mediastinal lymph node dissection for lung cancer. Semin Thorac Cardiovasc Surg. 2012 Spring;24(1):68-73. doi: 10.1053/j.semtcvs.2012.03.002.
- Yang P, Cheville AL, Wampfler JA, Garces YI, Jatoi A, Clark MM, Cassivi SD, Midthun DE, Marks RS, Aubry MC, Okuno SH, Williams BA, Nichols FC, Trastek VF, Sugimura H, Sarna L, Allen MS, Deschamps C, Sloan JA. Quality of life and symptom burden among long-term lung cancer survivors. J Thorac Oncol. 2012 Jan;7(1):64-70. doi: 10.1097/JTO.0b013e3182397b3e.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 1, 2021
Primary Completion (Anticipated)
June 30, 2023
Study Completion (Anticipated)
June 30, 2023
Study Registration Dates
First Submitted
May 23, 2021
First Submitted That Met QC Criteria
June 6, 2021
First Posted (Actual)
June 11, 2021
Study Record Updates
Last Update Posted (Actual)
October 26, 2022
Last Update Submitted That Met QC Criteria
October 24, 2022
Last Verified
October 1, 2022
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Nervous System Diseases
- Respiratory Tract Diseases
- Neoplasms
- Respiration Disorders
- Lung Diseases
- Neoplasms by Site
- Wounds and Injuries
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Craniocerebral Trauma
- Trauma, Nervous System
- Signs and Symptoms, Respiratory
- Cranial Nerve Diseases
- Vagus Nerve Diseases
- Cranial Nerve Injuries
- Lung Neoplasms
- Cough
- Vagus Nerve Injuries
Other Study ID Numbers
- B-2007-625-007
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.