Background
Coughing is a common complication in patients with non-small cell lung cancer after undergoing surgery, as well as phlegm or throat discomfort, wheezing, shortness of breath, and chest pain. Further, it has been reported that approximately 25% of long term survivors (>5 years) suffer from a cough
Observational and empiric studies of coughing after pulmonary resection (CAP) have been conducted, and it has been proposed that some cases of persistent CAP are caused by acid regurgitation
Methods
Patients
Seventeen patients who had undergone a lobectomy were selected, of whom 13 had a persistent cough and 4 had no coughing. None of these patients had chronic bronchitis or a diagnosis of gastroesophageal reflux disease (GERD) before surgery, and all symptoms had become manifest after the pulmonary resection procedure. Persistent CAP was defined as non-productive coughing that occurred after the operation in patients with stable chest X-ray results, as well as no postnasal drip syndrome, asthma, or history of angiotensin converting enzyme inhibitor administration, as those are reported to be causes of chronic coughing
Characteristics of patients by status of post-operative cough.
Variables
Cough (+)
Cough (-)
Total no.
13
4
Onset
More than 7 days of OP
13
Age in years
Median (range)
66 (48–72)
66(36–68)
Gender
Male
6
2
Female
7
2
Disease
Lung cancer
13
4
Surgery
Lobectomy
13
4
Post-operative days
Median (range)
18 (15–26)
18(18–24)
Mediastinal lymph node resection
Yes
13
4
Operation side
Right
9
2
Left
4
2
Height (cm)
Median (range)
161 (149–172)
159(158–177)
Weight (kg)
Median (range)
56 (45–68)
50(45–75)
BSA (cm2)
Median (range)
1.6 (1.4–1.8)
1.5(1.4–1.9)
BMI
Median (range)
23.0 (18.2–25.9)
23.3(17.8–23.9)
OP: operation
24-hour esophageal pH monitoring
All of patients had stopped using proton pomp inhibitors and/or H2-blockers for more than 7 days. A 24-hour esophageal pH study was performed using a Disitrapper 550-1 (Meditoronic LA. USA). A pH electrode was placed 5 cm above the upper border of the lower esophageal sphincter through the nose. Coughing was chosen as the symptom to be recorded and each patient was instructed to push the record button when coughing occurred during the monitoring period. The time trends of esophageal pH (number of reflux occurrences and percentage of time that expectorant was at pH <4.0) and coughing were recorded by the machine. The recorded data were analyzed using computer software (POLYGRAM 98 pH testing system, Medtronic, Skovlunde, Denmark). Monitoring was also performed more than 1 year after the operation in 5 patients in the Type A group, as explained in the Results.
Symptom analysis
The severity of persistent CAP was analyzed using a visual analog scale (VAS), with a minimum of 0 and maximum of 10 for the number of coughs that occurred during an occurrence of coughing. We also assessed severity by the number of occurrences and duration of expectorant at pH <4. Symptom association probability was calculated using the POLYGRAM 98 software application.
Symptom association probability
To calculate symptom association probability, we used a contingency table
Statistical analysis
Measured values are expressed as the mean+/-significant difference. Comparisons between number of refluxes, percent of time at pH <4, VAS, and number of coughing occurrences at less than 4 weeks in all of the patients, and then again more than 1 year after surgery in 5 of the patients, were performed using unpaired t-tests. The results were considered to be significant when the p value was less than 0.05.
Results
Detailed information regarding the patients examined is shown in Table
Results of 24-hour pH monitoring in patients with CAP within 4 weeks of the operation.
Case
Age
Sex
Post-OP Cough
Height (cm)
Weight (kg)
BSA (cm2)
BMI (kg/m2)
OP site
OP
POD
Mediastinal LNRS
%FEV1.0
Smoking
1
48
F
YES
149
51
1.4
23.0
R
L
15
Yes
80.1
Never
2
70
F
YES
152
45
1.4
19.5
R
L
17
Yes
65.3
Never
3
64
F
YES
154
52
1.5
21.9
R
L
17
Yes
96.8
Never
4
69
M
YES
172
64
1.7
21.6
R
L
17
Yes
83.7
Never
5
62
M
YES
164
52
1.6
19.3
R
L
18
Yes
70.2
Never
6
63
F
YES
158
50
1.5
20.0
L
L
18
Yes
50.4
Former
7
66
F
YES
150
58
1.5
25.8
R
L
20
Yes
45.8
Former
8
72
M
YES
165
54
1.6
19.8
R
L
24
Yes
54.0
Current¶
9
53
F
YES
162
48
1.5
18.2
R
L
26
Yes
71.4
Never
10
52
F
YES
158
56
1.6
22.4
L
L
21
Yes
89.3
Never
11
66
M
YES
162
68
1.7
25.9
R
L
21
Yes
69.5
Never
12
68
M
YES
161
60
1.6
23.1
L
L
19
Yes
51.4
Former
13
72
M
YES
170
65
1.8
22.5
L
L
21
Yes
40.1
Former
14
66
F
NO†
158
50
1.5
20.0
R
L
21
Yes
88.7
Never
15
68
M
NO†
177
75
1.9
23.9
R
L
18
Yes
72.4
Former
16
68
M
NO†
159
45
1.4
17.8
L
L
24
No
50.8
Current¶
17
36
F
NO†
159
59
1.6
23.3
L
L
18
No
80.3
Never
†No diagnosis of or medication for gastroesophageal reflux disease, ¶No symptoms of chronic bronchitis
Results of 24-hour esophageal pH monitoring
Results of 24-hour esophageal pH monitoring. Based on the results, we divided the patients into 3 groups: type A had frequent acid regurgitation (>50 occurrences) and frequent coughing (>30 occurrences), type B had frequent acid regurgitation (>50 occurrences) and infrequent coughing (<30 occurrences), and type C had infrequent acid regurgitation (<50 occurrences) and infrequent coughing (<30 occurrences).
The results of 24-hour esophageal pH monitoring, coughing occurrence, and VAS for these patients are shown in Table
Results of 24-hour pH monitoring.
Case
No. of reflux occurrences#
Time pH <4 (min)#
Time pH <4 (%)
Coughing (VAS)
No. of coughing occurrences#
Result of pH monitor (group)
SAP
1
57
15
1
6
43
A
97.0
2
86
63
4
10
89
A
100.0
3
126
49
3
6
86
A
99.9
4
263
143
10
10
58
A
100.0
5
195
472
33
3
40
A
97.5
6
443
572
40
4
186
A
99.9
7
110
98
7
6
46
A
97.5
8
193
207
14
3
43
A
100.0
9
310
145
10
5
95
A
99.9
10
227
153
11
8
156
A
99.7
11
131
29
2
5
20
C
80.6
12
43
58
4
3
8
B
60.1
13
38
41
3
3
7
B
61.4
14
285
273
19
0
1
B
69.9
15
256
223
15
0
1
B
69.9
16
413
659
46
0
0
B
0.0
17
441
518
36
1
10
B
81.1
#In 24-hour period, VAS: visual analog scale, SAP: symptom association probability,
Five patients in the Type A group also underwent 24-hour esophageal pH monitoring more than 1 year after the operation. Comparisons between the results obtained within 4 weeks of the operation and those from more than 1 year after surgery are shown in Table
Results of 24-hour esophageal pH monitoring more than 1 year after surgery in patients with CAP originally observed within 4 weeks after the operation.
Case
No. of reflux occurrences#
Time pH <4 (min)#
Time pH <4 (%)
Coughing (VAS)
No. of coughing occurrences#
Result of pH monitor (group)
3
133
53
3.7
0
1
B
5
180
382
28.9
0
0
B
6
422
188
13.1
0
2
B
7
197
150
10.5
0
0
B
9
214
207
14.4
1
18
B
#In 24-hour period, VAS: visual analog scale, SAP: symptom association probability,
Comparisons of results of 5 patients with coughing within 4 weeks and more than 1 year after undergoing a pulmonary resection procedure
Comparisons of results of 5 patients with coughing within 4 weeks and more than 1 year after undergoing a pulmonary resection procedure. The number of reflux occurrences was 236+/-136 in the patients within 4 weeks after the operation and 229+/-112 at more than 1 year after the operation (p = 0.9). The %pH <4.0 values were 18.7+/-16.8% within 4 weeks after the operation and 14.1+/-9.2% at more than 1 year after the operation (p = 0.6). The visual analog scale results were 4.8+/-1.3 within 4 weeks after the operation and 0.2+/-0.4 at more than 1 year after the operation (p < 0.0001). The numbers of coughing occurrences were 80.0+/-60.2 within 4 weeks after the operation and 4.2+/-7.8 at more than 1 year after the operation (p = 0.03).
Discussion
There are some negative aspects of patient condition following a pulmonary resection, including loss of lung volume
The major symptoms of gastro-esophageal reflux disease (GERD) are heartburn and acid regurgitation, though some patients have only minor forms of those symptoms
Coughing after a pulmonary resection has some characteristics, such as delayed onset and non-productive coughing, and occurs in preparing to speech. Observational and empiric investigations in our previous study
One of the most definitive examinations of acid regurgitation is 24-hour esophageal pH monitoring
These observations can explain the results of our previous observational and empiric study of persistent CAP
The opposing viewpoint must also be considered, i.e. coughing augments acid regurgitation, thus acid regurgitation could be caused by coughing. However, the severity of acid regurgitation in the present patients with a persistent cough after pulmonary resection and frequency of acid regurgitation within 4 weeks of the initial operation did not change when monitored 1 year or more after the operation, regardless of any improvement in coughing severity. In addition, 4 patients with no coughing after the lobectomy procedure also reported acid regurgitation. Thus, there seems to be only a scant contribution by coughing to acid regurgitation.
Improvement of coughing 1 year after surgery is a crucial issue. From our results, it is difficult to conclude that an improvement in acid regurgitation is a contributor to improvement in coughing, as there was little difference in the severity of acid regurgitation seen soon after surgery and more than 1 year later. In addition, degeneration could also be a cause of coughing, such as injury of the vagus, injury of the tracheobronchial area, exposed bronchial suture ends, lymph node resection, hinging of the bronchus, elevation of the diaphragm, unilateral loss of lung volume, and deformity of the residual lung. Therefore, it is important to study the cause of improvement in CAP with multi-focal observations, including acid regurgitation.
This study has some limitations. Owing to irritability caused by trans-nasal insertion of the thin fiber, autonomic nerve conditions may have changed during the examination
Conclusion
Although there are many possible causes of CAP that should be investigated, a relationship between coughing and acid regurgitation soon after a lobectomy procedure was observed in the present study using a physiological technique with 24-hour esophageal pH monitoring.
Abbreviations
GERD, gastroesophageal reflux disease
CAP, coughing after pulmonary resection
Competing interests
The author(s) declare that they have no competing interests.
Authors' contributions
N.S.; Attending physician, patient observations, esophageal pH monitoring, conducted the study, and wrote the manuscript
S.T.; Attending physician and patient observations
T.T.; Attending physician, patient observations, and esophageal pH monitoring
M.I.; Attending physician and patient observations
H.M.; Attending physician, patient observations, and coordination of the study