Ann Thorac Surg 2005;79:289-293
© 2005 The Society of Thoracic Surgeons
Original article: General thoracic
Persistent Cough Following Pulmonary Resection: Observational and Empiric Study of Possible Causes
Noriyoshi Sawabata, MDa,b,*,
Hajime Maeda, MDa,b,
Shin-ichi Takeda, MDa,b,
Masayoshi Inoue, MDb,
Masaru Koma, MDa,b,
Toshiteru Tokunaga, MDa,b,
Hikaru Matsuda, MDb
a Division of Surgery, Toneyama National Hospital, Osaka, Japan
b Department of Surgery (E-1), Osaka University, Graduate School of Medicine, Suita, Japan
Accepted for publication June 11, 2004.
* Address reprint requests to Dr Sawabata, Division of Surgery, Toneyama National Hospital, 5–1–1, Toneyama, Toyonaka, Osaka 560–8552, Japan (E-mail: nsawabata{at}m5.dion.ne.jp).
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Abstract
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BACKGROUND: Following thoracic surgery, patients often suffer from persistent coughing. There is speculation regarding the cause. However, since few studies of that following pulmonary resection have been reported, we conducted an observational and empiric study of this issue.
METHODS: A cross-sectional assessment of 240 patients who had undergone a pulmonary resection was performed using a questionnaire regarding postsurgical persistent coughing. Further, therapy based on empiric results was given to 20 patients who had undergone a lobectomy and mediastinal lymph node resection for nonsmall cell lung cancer.
RESULTS: Seventy patients were surveyed within 1 year following surgery (subchronic phase), of whom 35 (50%) suffered from coughing, as compared to 30 (18%) of 170 whose postoperative time was 1 year or more (p < 0.0001). Presence of lung cancer, mediastinal lymph node resection, and gastroesophageal reflux (GER) symptoms were significant factors in the group of subchronic patients. Of the 20 patients who received empiric therapy, 90% saw their coughing symptoms improve after the course of medication.
CONCLUSIONS: In the present patients, mediastinal lymph node resection may have contributed to coughing after the procedure, which tended to improve after 1 year following the operation. Further, a secondary change, such as GER, caused by surgical intervention may also be a contributing factor in the subchronic phase.
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Introduction
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Following thoracic surgery, patients often suffer from a persistent cough. Several reports have speculated that pulmonary C-fibers are responsible for coughing [1–4]; therefore, extraction of those from the tracheobronchial tract may explain the condition. Exposed end-bronchial sutures are another possible cause [5], as well as other anatomical contributions such as lymph node resection, hinging of the bronchus, elevation of the diaphragm, unilateral loss of lung volume, and deformity of the residual lobe. In addition, gastroesophageal reflux (GER) has also been proposed [6].
There is much speculation regarding coughing that occurs following a pulmonary resection, however, few known reports [7]. Therefore, we conducted observational and empiric studies with focus on this issue.
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Patients and Methods
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Observational Study
Using a cross-sectional survey, we assessed the cough status of 240 patients who had undergone a pulmonary resection at Toneyama National Hospital from 1992 to 2003 and were discharged in a healthy condition. During the same period, a total of 996 patients received a pulmonary resection, therefore, 24% of all pulmonary resection patients were assessed in the present study. The diseases involved were nonsmall cell lung cancer (NSCLC) in 196 cases (stage IA in 124, IB in 38, IIA in 5, IIB in 6, and IIIA in 23), benign solitary pulmonary nodule in 34 cases (tuberculosis in 12, benign pulmonary tumor in 7, intrapulmonary lymph node in 4, and others in 11), malignant lymphoma in the lung in 3 cases, bullous lung disease in 3 cases, solitary pulmonary metastatic lesion in 2 cases, and spontaneous pneumothorax in 2 cases. Patients with malignant lesions were diagnosed as having no relapse at the time of the survey. During all of the surgical procedures, the bronchial stumps were closed with mono-filament nylon thread.
The patients were initially recruited by an oral questionnaire shown in the appendix conducted by a staff member of the ambulatory section of our hospital, which was a modified version of the Division of Lung Disease/American Thoracic Society (ATS) questionnaire [8] used to assess the presence of persistent cough ("Do you usually experience persistent coughing?"). Patients were also asked about symptoms of GER as follows:
- (1) What symptom do you have apart from persisting coughing?
- a Heartburn
- b Nausea
- c Central chest pain when swallowing
- d None
- (2) When does your symptom occur?
- a At any time
- b Within 2 hours of eating
- c At the same time regardless of eating habits
- d Unsure
- (3) How do the following affect your symptom?
- a More food than usual amount (WORSE, BETTER, STABLE)
- b Fat rich food (WORSE, BETTER, STABLE)
- c Spicy food (WORSE, BETTER, STABLE)
- d Coffee (WORSE, BETTER, STABLE)
- (4) How does bending over or lying down affect your symptom?
- a No change
- b Increase
- c Decrease
- d Unsure
- (5) How does lifting a heavy object affect your symptom?
- a No change
- b Increase
- c Decrease
- d Unsure
- (6) Does gastric juice or food you have eaten come back into your mouth?
- a Frequently
- b Sometimes
- c Never
- d Unsure
All patients who gave any answer that suggested GER were considered GER positive, which included: a, b, or c as answers to question 1; b to question 2; any "WORSE" type of answer to any part of question 3; b to question 4; b to question 5; and a or b to question 6. All questionnaires were evaluated by one of the authors on the same day as the questions were answered.
We defined the subchronic phase as within 1 year from the day of surgery, and grouped 70 patients into the subchronic phase and 170 patients into the chronic (> 1 year from the day of surgery) phase, as shown in Table 1. There were no significant differences in gender, age, preoperative smoking, side of operation, extent of resection, disease, or status of mediastinal lymph node resection between the 2 groups. A total of 65 (27%) patients in both groups suffered from cough and 43 (18%) complained of GER symptoms following surgery. These ratios were also compared between patients in the subchronic phase and those in the chronic phase.
Further analyses of the subchronic phase patients were conducted. The postoperative period was between 37 and 358 days, with a median of 178 days. Of the 70 patients, 31 (44%) were smokers before surgery and all quit postoperatively. Only 1 patient had a postoperative complication, which was postoperative bleeding. The duration of chest tube drainage ranged from 2 to 6 days, with a median of 4 days. Two patients underwent a pneumonectomy for lung cancer, 53 a lobectomy, and 15 an excision. Further, a thoracotomy was performed as a mini-thoracotomy in 15 cases of tumor excision and as an axillar thoracotomy in the remaining cases, while none underwent a formal thoracotomy. All patients were confirmed to be not suffering from postoperative pulmonary or pleural disease that could be the cause of coughing.
We analyzed the ratio of subchronic patients suffering from postoperative cough using age, preoperative smoking, gender, side of operation, extent of pulmonary resection, presence of lung cancer, mediastinal lymph node resection, and GER symptoms as variables. Multivariate analyses employing a logistic regression test were carried out using variables that were found to be significant in a uni-variate analysis. In addition, a 
2 test, Fisher's exact test, and t test were used as appropriate.
Empiric Study
The study design was self-controlled. The entry criteria were patients who had undergone a lobectomy and mediastinal lymph node resection for clinical stage IA or IB NSCLC. The total number of patients was 20, who were 8 males and 12 females, with a median age of 61 years old. The site of operation was right in 15 cases and left in 5 cases. The postoperative period was within 1 month in 17 cases, within 1 year in 2 cases, and greater than 1 year in 1 case. The pathological stages were stage IA in 15 cases, IB in 4 cases, and IIIA in 1 case. A persistent cough after pulmonary resection (CAP) was defined as follows: nonproductive coughing that occurred more than 2 weeks after the operation with stable chest roentgenogram results, with no evidence of PNDS, asthma, or ACE inhibitor administration.
The medication given was as follows: 30 mg/d of Lansoprazole was used as proton pomp inhibiter and 15 mg/d of Mosaprid in 3 doses was used as pro-kinetic agent. Assessment of CAP was performed using a visual analog scale (VAS), and was carried out just before receiving the medication and 2 weeks after the start of administration. The schema of the study is shown in Figure 1. The grade of coughing was defined by VAS using a minimum of 0 and a maximum of 10, and the scores were analyzed using a t test.
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Fig 1. Schema of the empiric study. The grade of coughing was defined using a VAS with a minimum of 0 and maximum of 10. (CAP = coughing after pulmonary resection; PPI = proton pump inhibitor; VAS = visual analog scale; Ws = weeks.)
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Results
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Observational Study
Fifty percent of patients in the subchronic phase had a cough, compared with 18% in the chronic phase (p < 0.0001). Further, 33% of those in the subchronic phase had GER symptoms in contrast to 13% in the chronic phase (p = 0.003; Table 2). In addition, as illustrated in Figure 2, 23 (67%) of 35 patients in the subchronic phase with a cough following the pulmonary resection had GER symptoms, whereas 9 (30%) of 30 patients in the chronic phase had both GER symptoms and a cough (p = 0.006).
Patient characteristics by status of postoperative cough are shown in Table 3. The incidence of coughing in patients with lung cancer, mediastinal lymph node resection, and GER symptoms was higher than in those who reported the other variables. Results from a multivariate analysis using logistic regression tests are shown in Table 4, in which GER symptoms was the only independent variable found.
Empiric Study
Results of the empiric therapy are depicted in Figure 3. Coughing did not worsen in any of the patients. In 18 patients, the coughing improved, although the symptoms did not change in 2. The average VAS score was 6.5 ± 2.5 before starting therapy and 2.3 ± 2.6 after therapy (p < 0.0001).
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Fig 3. Empiric therapy study results. Coughing did not worsen in any of the patients. In 18 patients, the coughing improved, whereas symptoms did not change in 2. The average visual analog scale (VAS) score was 6.5 ± 2.5 before starting therapy and 2.3 ± 2.6 posttherapy.
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Comment
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A cough is a common complication in patients with nonsmall cell lung cancer who have received surgery. Sarna and colleagues [9] reported that approximately 25% of those patients who were long-term (>5 years) survivors suffered from a cough. The cause of coughing following thoracic surgery may be excision of pulmonary C-fibers from the tracheobronchial tract, which might be responsible for coughing [1–4], after which afferent signals regarding coughing may occur regularly. For example, subcarinal lymph nodes are usually removed en block or as a sample. During this intervention, it is very difficult to avoid cutting or damaging branches of the vagus that extend to all lobes. Therefore, lymph node resection may be a cause of cough following thoracic surgery, as portions of the tracheobronchial tract, such as the pulmonary C-fibers, are often damaged with excision of the vagal nerve.
The ratio of patients who suffered from a cough decreased in the chronic phase (> 1 year from the day of surgery) compared with those in the subchronic phase (< 1 year). This phenomenon may have been due to healing following the excision, such as of the pulmonary C-fibers. In our analysis of subchronic patients, lymph node resection was a factor following pulmonary resection, which may highlight the contribution of the excised vagal nerve to postoperative coughing. Lymph node resection was not an independent factor in the multivariate analysis, as 52 (88%) of 54 of the present patients with NSCLC underwent a mediastinal lymph node resection.
Gastroesophageal reflex can also be the cause of coughing [6]. Another study found that elevation of the diaphragm or loss of lung volume could cause GER symptoms, such as subclinical regurgitation of gastric juice from the stomach to the esophagus [10]. However, to verify its contribution, a study of the relationship between coughing and GER, such as with a 24-hour esophageal pH monitor [11], is needed, as the results of the present observational study only emphasize the contribution of GER to a cough following a pulmonary resection, because the ratios of both cough and GER symptoms decreased in the chronic phase patients. However, the results of the empiric therapy given in the present study might demonstrate the contribution of GER to persistent coughing. Further, the ratio of patients who suffered from GER symptoms and persistent cough was significantly higher in the subchronic phase than in the chronic phase. It is possible that improvement of persistent coughing can be attributed to resolution of coughing sensitivity due to excision of the vagal nerve system and improvement of gastroesophageal functions.
Other possible contributions to coughing must also be considered, such as postnasal drip syndrome associated with a rhinosinus condition [12], asthma [13], angiotensin-converting enzyme inhibiter [14], nonasthmatic eosinophilic bronchitis [15], suppurative airway disease, or a psychogenic disorder [16]. These would first need to be ruled out in order to establish that GER is the primary cause of a persistent cough following thoracic surgery. Specific examinations to diagnose their contributions were not carried out in the present study, however, our clinical observations and empiric therapy may aid physicians when considering the cause of a cough that occurs following a pulmonary resection procedure.
In conclusion, from the present results we speculated that mediastinal lymph node resection may contribute to a postoperative cough, whereas a secondary factor, such as GER, caused by surgical intervention may also be a contributing factor in the subchronic phase. Further study is required to investigate this issue more thoroughly.
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References
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Abstract
Introduction
= GER negative; 
= GER positive.