Vagus Nerve Preservation and Chronic Cough in Non-small Cell Lung Cancer Surgery

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.


Eligibility Criteria:
Inclusion Criteria:

1. 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.
2. Clinically suspicious of non-small cell lung cancer or tissue confirmed preoperatively
3. Clinical stage T1-3/N0-1/M0
4. Preoperative ECOG performance status 0-1
5. Preoperative ASA class I-III
6. Preoperative pulmonary function test FEV1 ≥ 60%, DLCO ≥ 60%
7. Patients expected to achieve R0 (complete resection) via simple lobectomy and mediastinal lymph node dissection

Exclusion Criteria:

1. Patients who smoked within 2 weeks prior to operation
2. Patients who received antitussives and expectorants 2 weeks prior to operation
3. Patients who are pregnant or breast feeding
4. Patients with severe or uncontrolled psychological disorders
5. Patients with severe pulmonary adhesion
6. Patients who are ineligible for minimally invasive surgery; thoracotomy conversion
7. Patients diagnosed with other malignancies within 2 years prior to operation
8. Patients who received chemotherapy or radiotherapy within 6 months prior to operation
9. Patients suspicious of clinical N2 or received neoadjuvant therapy prior to operation
10. Patients with cough-related diseases; COPD, asthma, ILD, GERD
11. Patients suspicious of lymph node metastasis/invasion around vagus nerve during the preoperative clinical staging evaluation