Abstract
Background:
Postoperative rehabilitation programs consisting of exercise training are considered effective for unselected lung cancer patients. However, whether postoperative exercise is beneficial to lung cancer patients comorbid with chronic obstructive pulmonary disease remains unknown.
Methods:
Eighty-four patients diagnosed with both lung cancer and chronic obstructive pulmonary disease were randomized into the exercise group and control group. Both groups were given standard postoperative rehabilitation for 1 week. After that, oxygen therapy (if needed) and nebulization were given to the control group, while patients in the exercise group started to participate in exercise programs on the basis of receiving oxygen therapy and nebulization as in the control group. The exercise programs consisted of 24 training sessions.
Results:
In both groups, the functional status and the results of the pulmonary function test decreased from baseline to the endpoint. However, after surgery and the intervention program, both the maximal oxygen consumption in the cardiopulmonary exercise test and walking distance in the 6-minute walk test in the exercise group were significantly better than those in the control group [15.5 (±1.4) mL/kg/min vs 13.1 (±1.3) mL/kg/min, P = 0.016; 437.4 (±48.6) m vs 381.7 (±40.5) m, P = 0.040]. Force vital capacity and forced expiratory volume in the first second in the exercise group were better than those in the control group, but the differences were not statistically significant [1798.1 (±298.9) mL vs 1664.0 (±329.7) mL, P = 0.254; 1155.7 (±174.3) mL vs 967.4 (±219.4) mL, P = 0.497]. The decline in the standard score of the QLQ-C30 (V3.0) was smaller in the exercise group, but the difference did not meet a statistically significant level [61.7 (±5.7) vs 58.4 (±9.3), P = 0.318].
Conclusion:
This study demonstrates that a short-term postoperative exercise training program can facilitate the recovery of functional capacity in lung cancer patients with comorbidities of chronic obstructive pulmonary disease.
Keywords: lung cancer, lung function, physical function, postoperative rehabilitation, quality of life
Strengths and limitations of this study: 1. The ingenious study design allows the subjects to participate more and reduces the sample shedding. 2. Both objective and subjective outcomes were collected to ensure a global participant assessment. 3. Assessor and statistician masking was used. 4. The limited intervention time may be the reason for the negative part of the study results.
1. Introduction
Chronic obstructive pulmonary disease (COPD) is an important comorbidity of lung cancer. COPD has been found to be an independent risk factor for lung cancer and is estimated to affect approximately 55% of lung cancer patients worldwide.[1] The prognosis of lung cancer is heavily affected by this comorbidity. Higher rates of postoperative pulmonary complications and poorer recovery from surgery in lung cancer patients are associated with chronic pulmonary obstructive disease.[2] Surgical resection remains the best treatment option for lung cancer patients in the early stage.[3] Surgical operation for lung cancer comorbid with chronic pulmonary obstructive disease can be challenging, as chronic pulmonary obstructive disease may increase postoperative morbidities and decrease the survival rate.[4] Even in patients with early-stage chronic pulmonary obstructive disease, the prevalence of postoperative pulmonary complications is higher than that in patients with normal spirometry.[5]
Fatigue and shortness of breath are the 2 most frequently mentioned postoperative complications associated with impaired physical capacity and pulmonary function and may result in reduced quality of life.[5,6] The beneficial effects of reducing fatigue and dyspnea and enhancing the recovery of postoperative rehabilitation have been studied recently.[7–9] Postoperative rehabilitation programs consisting of exercise training are considered effective for unselected lung cancer patients in 2 systematic reviews.[10,11] However, whether postoperative exercise is beneficial to lung cancer patients comorbid with COPD remains unknown. Therefore, the aim of this trial was to investigate whether postoperative exercise training can improve the physical function and quality of life of lung cancer patients comorbid with COPD.
2. Methods
This clinical study was a prospective, randomized controlled trial applying assessor blinding. The study was ratified by the Ethics Committee of West China Hospital, Sichuan University (No. 2021/1600) and was carried out in accordance with the Declaration of Helsinki. It was registered at the Chinese Clinical Trial Registry (ChiCTR2200056709). This trial was conducted from February 16, 2022 to August 26, 2022, at West China Hospital, Sichuan University, which is responsible for the integrity and conduct of the current study.
The participant inclusion criteria were as follows: age ≥ 18 years old; the pathological diagnosis was primary non-small cell lung cancer, and there were surgical indications according to the National Comprehensive Cancer Network clinical diagnosis and treatment guidelines for non-small cell lung cancer (2021 Edition); the diagnosis included COPD (according to the guidelines for the diagnosis and treatment of COPD, the ratio of forced expiratory volume per second/forced vital capacity < 0.7). The exclusion criteria were as follows: forced expiratory volume in the first second (FEV1) of patients in the pulmonary function test (PFT) was lower than 30% of the expected value; New York Heart Association cardiac function classification standards II, III and IV; inability to participate in sports training (such as lower limb dysfunction or hemiplegia); previous history of lung surgery; and refusal to sign the informed consent form of rehabilitation treatment in the Department of Rehabilitation Medicine.
After inclusion and exclusion, eligible patients were required to sign informative consent forms. Consenting participants were randomized to an exercise group (EG) and a control group (CG) by a nurse who was not involved in the later intervention and data collection process using a random number table generated by a computer.
Lung cancer patients with normal spirometry are usually hospitalized for no more than 1 week after surgery. However, for those comorbid with chronic pulmonary obstructive disease, the surgeons considered it risky to let those patients go home just after this short period and so transferred them to the Rehabilitation Medicine Center for ongoing postoperative rehabilitation and care.
After surgery, patients in both groups were given standard postoperative rehabilitation for 1 week in the surgery department, which included early mobilization, cough and deep-breath technique teaching, supplemental oxygen therapy and nebulization. After the first week with the participants of the 2 groups being transferred to the Rehabilitation Medicine Center and settled in 2 separate wards, patients in the CG received oxygen therapy (if needed) and nebulization as before, while patients in the EG started to participate in exercise programs on the basis of receiving oxygen therapy and nebulization as in the CG.
The exercise program consisted mainly of aerobic training. EG patients were asked to ride on cycle ergometers (Schiller, 911 S/L) for 30 minutes each session, twice daily, 6 days weekly. The exercise intensity was set at 20% of heart rate reserve at the beginning and gradually increased to 60% to 70% of heart rate reserve. Before each training session, participants had a 5-minute warmup. This 30-minute training can be broken down into two 15 minutes or three 10 minutes depending on the patients’ needs, with an interval rest of <5 minutes. Supplemental oxygen was available during exercise if needed. When patients feel dizziness, moderate chest discomfort and breathing difficulty, or peripheral oxygen saturation dropping for >4° during exercise, they should stop that training session. The exercise program was adapted from exercise training guidelines for cancer survivors by the American College of Sports Medicine and revised.[12] It lasted 2 weeks for each participant. Patients or the public were not involved in the design, or conduct, or reporting, or dissemination plans of our research.
3. Outcome measurements
Baseline and endpoint tests were carried out 3 days before surgery (baseline) and 1 day after the end of the exercise program (endpoint). Cardiopulmonary exercise test (CPET) and 6-minute walk test (6MWT) were used to assess the physical capacity.[13,14] Higher maximal oxygen consumption (peak VO2) in the CPET and longer walking distance in the 6MWT indicate better functional capacity. Data from PFTs, such as force vital capacity (FVC) and FEV1, were used to assess overall lung function.[15,16]
Daily walking step recordings by WeChat at baseline and endpoint were used to represent daily functional ability. The European Organization for Research on Treatment of Cancer quality of life scale QLQ-C30 (V3.0) Chinese version was used to assess the quality of life at both evaluation time points. A higher standard score (SS, range from 0 to 100) of the QLQ-C30 (V3.0) indicates better quality of life.
4. Statistical methods
The sample size was calculated on G*power software (Version 3.1.9.2) with α = 0.05 and statistical power = 0.80 according to the cardiopulmonary fitness measured by peak VO2 with lung cancer patients, which gave 70 as the minimum sample size.[17] In consideration of a 20% dropout rate, 84 was determined as a proper sample size to generate a statistically significant difference between groups.
Statistical software SPSS version 23.0 (SPSS, Inc., Chicago, IL) was used for data processing, and the Kolmogorov–Smirnov test was used for distribution patterns. Continuous data are presented as the mean and standard deviation, while categorical data are presented as frequencies (%). Intergroup differences were analyzed by a 2-sided unpaired t test, Mann–Whitney U test, or χ2 test where appropriate. All statistical tests were 2-sided and conducted at the 5% significance level.
5. Results
5.1. Study population
The flowchart of this trial is shown in Figure 1. A total of 154 patients diagnosed with both lung cancer and chronic pulmonary obstructive disease were screened for eligibility, of which 84 provided consent. After randomization, there were 40 in the CG and 44 in the EG. Twelve participants dropped out after the exercise program, 3 in the CG because of self-unwillingness and 9 in the EG because of postoperative pain interacting with training. The remaining 35 patients in the EG all completed 24 training sessions. All 84 patients underwent baseline assessment, while only 72 underwent endpoint assessment.
Figure 1.
. Flowchart of the study.
Demographic data are shown in Table 1. The 2 groups did not have significant differences regarding sex, age, body mass index, marital status, education length, history of cardiovascular disease, history of COPD, COPD stage or preoperative anticancer treatment. In both groups, the age of participants was 68.7 ± 6.5 years old, with oldest 84 and youngest 57. Twenty-seven participants (32.1%) were female, and the average length (standard deviation) of COPD history was 11.32 ± 3.1 years.
Table 1.
Demographic data and clinical characteristics between groups.
| Control group (n = 40) | Exercise group (n = 44) | P value | |
|---|---|---|---|
| Male sex | 28(70.0) | 29(65.9) | .611 |
| Age (yr) | 69.6(4.8) | 68.3(4.3) | .875 |
| BMI (kg/m2) | 22.8(2.9) | 23.6(2.8) | .739 |
| Married | 34(85.0) | 35(79.5) | .842 |
| Education length (yr) | 4.6(1.9) | 5.5(2.4) | .209 |
| Diabetes mellitus | 4(10.0) | 3(6.8) | .313 |
| Coronary artery disease | 4(10.0) | 5(11.4) | .327 |
| Hypertension | 15(37.5) | 18(40.9) | .407 |
| COPD history (yr) | 10.9(2.9) | 11.8(3.3) | .377 |
| Stages of COPD | .179 | ||
| GOLD I | 18(45.0) | 24(54.5) | |
| GOLD II | 20(50.0) | 19(43.2) | |
| GOLD III | 2(5.0) | 1(2.3) | |
| GOLD IV | 0(0.0) | 0(0.0) | |
| Preoperative treatment | 9(22.5) | 11(25.0) | .430 |
BMI = body mass index, COPD = chronic obstructive pulmonary disease, GOLD = consensus of the Global Initiative for Chronic Obstructive Lung Disease, with classification of COPD stages I–IV based on ratio of FEV1 to predicted value.
Surgical characteristics are summarized in Table 2. The surgery type and resection sites did not differ significantly, nor did ventilation parameters during surgery procession and postoperatively.
Table 2.
Surgical characteristics and perioperative data.
| Control group (n = 40) | Exercise group (n = 44) | P value | |
|---|---|---|---|
| Resection sites | .639 | ||
| Segmentectomy | 15(37.5) | 14(31.8) | |
| Lobectomy or bilobectomy | 25(62.5) | 29(65.9) | |
| Pneumonectomy | 0(0.0) | 1(2.3) | |
| Surgery types | .603 | ||
| VATS | 28(70.0) | 33(75.0) | |
| Thoracotomy | 12(30.0) | 11(25.0) | |
| Duration of surgery, min | 167.6(43.8) | 175.1(47.9) | .752 |
| Duration of anesthesia, min | 243.4(65.3) | 265.7(72.6) | .456 |
| VT during TLV, mL/kg PBW | 8.0(1.8) | 8.1(1.9) | .771 |
| PEEP during TLV, cm H2O | 5.4(2.1) | 5.7(1.7) | .545 |
| FIO2 during TLV, % | 54.5(13.6) | 57.1(11.8) | .819 |
| VT during OLV, mL/kg PBW | 6.2(1.3) | 6.5(1.6) | .391 |
| PEEP during OLV, cm H2O | 6.5(1.9) | 6.9(2.6) | .614 |
| FIO2 during OLV, % | 61.9(16.5) | 64.6(18.7) | .348 |
| PaO2/FIO2 on POD1, % | 346.6(15.8) | 317.1(17.9) | .267 |
FIO2 = fraction of inspiratory oxygen, OLV = one-lung ventilation, PaO2/FIO2 = ratio of partial oxygen pressure to inspiratory fraction of oxygen, PBW = predicted body weight, PEEP = positive end-expiratory pressure, POD1 = first postoperative day, TLV = two-lung ventilation, VATS = video-assisted thoracic surgery, VT = tidal volume.
5.2. Primary outcome
The functional status and the results of the PFT from baseline to endpoint are shown in Table 3. All parameters were comparable at baseline (P ≥ .05). After surgery and the intervention program, both the peak VO2 in the CPET and walking distance in the 6MWT in the EG were significantly better than those in the CG [15.5 (±1.4) mL/kg/min vs 13.1 (±1.3) mL/kg/min, P = .016; 437.4 (±48.6) m vs 381.7 (±40.5) m, P = .040]. FVC and FEV1 in the EG were better than those in the CG, but the differences were not statistically significant [1798.1 (±298.9) mL vs 1664.0 (±329.7) mL, P = .254; 1155.7 (±174.3) mL vs 967.4 (±219.4) mL, P = .497]. The daily walking step record by WeChat did not differ much at baseline. However, patients in EG walked significantly more steps than those in CG after the exercise program [4391(±393) vs 3491(±357), P = .008]. The changes in assessment results before and after intervention were analyzed in Table 4. The results indicate that the EG demonstrated a smaller decline in the maximum oxygen uptake during CPET, distance covered in the 6MWT, FVC, and daily walking steps compared to the CG (P < .05).
Table 3.
Functional status and QoL score of the baseline and endpoint assessment.
| Control group (n = 37) | Exercise group (n = 35) | P value | |
|---|---|---|---|
| Baseline | |||
| CPET (mL/kg/min) | 16.3(1.7) | 16.7(1.9) | .694 |
| 6MWT (m) | 464.8(52.8) | 486(57.9) | .701 |
| FVC (mL) | 2241.7(547.3) | 2176.4(496.2) | .372 |
| FEV1 (mL) | 1356.9(324.6) | 1474.5(390.4) | .794 |
| SS of QLQ-C30 (V3.0) | 66.8(11.3) | 68.7(12.5) | .641 |
| Daily walking step record | 6348(641) | 6279(563) | .781 |
| Endpoint | |||
| CPET (mL/kg/min) | 13.1(1.3) | 15.5(1.4) | .016 |
| 6MWT (min) | 381.7(40.5) | 437.4(48.6) | .040 |
| FVC (mL) | 1664.0(329.7) | 1798.1(298.9) | .254 |
| FEV1 (mL) | 967.4(219.4) | 1155.7(174.3) | .497 |
| SS of QLQ-C30 (V3.0) | 58.4(9.3) | 61.7(5.7) | .318 |
| Daily walking step record | 3491(357) | 4391(393) | .008 |
6MWT = 6-minute walk test, CPET = cardiopulmonary exercise test, FEV1 = forced expiration volume in the first second in the pulmonary function test, FVC = forced vital capacity in pulmonary function test, QLQ = quality of life questionnaire from European Organization for Research on Treatment of Cancer, QoL = quality of life, SS = standard score.
Table 4.
Change of Functional status and QoL score.
| Control group (n = 37) | Exercise group (n = 35) | P value | |
|---|---|---|---|
| CPET (mL/kg/min) | −3.2(0.3) | −1.2(0.2) | .043 |
| 6MWT (m) | −83.1(9.2) | −48.6(6.0) | .029 |
| FVC (mL) | −577.7(136.2) | −378.3(111.6) | .034 |
| FEV1 (mL) | −389.5(89.4) | −318.8(114.3) | .213 |
| SS of QLQ-C30 (V3.0) | −8.4(1.6) | −7.0(2.1) | .464 |
| Daily walking step record | −2857(289) | −-1888(313) | .002 |
6MWT = 6-minute walk test, CPET = cardiopulmonary exercise test, FEV1 = forced expiration volume in the first second in the pulmonary function test, FVC = forced vital capacity in pulmonary function test, QLQ = quality of life questionnaire from European Organization for Research on Treatment of Cancer, QoL = quality of life, SS = standard score.
Negative values indicate a decline in patients’ functional assessment data and quality of life from preoperative to postoperative and intervention periods.
5.3. Secondary outcome
The standard score (SS) of the QLQ-C30 (V3.0) from baseline to endpoint is also shown in Table 3. The decline in the SS of the QLQ-C30 (V3.0) was smaller in the EG, but the difference did not meet a statistically significant level [61.7 (±5.7) vs 58.4 (±9.3), P = .318].
6. Discussion
This study demonstrates that a short-term postoperative exercise training program can facilitate the recovery of functional capacity in lung cancer patients with comorbidities of COPD. Patients with more postoperative exercise also walk more steps than those without additional exercise. Postoperative lung function and quality of life appeared superior in patients who participated in exercise training and only failed to reach a statistically meaningful level. To our knowledge, this is the first randomized controlled trial investigating the effect of postoperative exercise on lung cancer patients comorbid with chronic pulmonary obstructive disease.
Surgical resection causes a 15% to 30% decrease in the VO2 peak, and the presence of chronic pulmonary obstructive disease may further decrease the peak VO2.[18] Perioperatively speaking, the decrease in CPET and 6MWT results of both groups were obvious in both groups, as the data above showed. However, comparison between groups suggests that patients in the EG had a substantially smaller decrease in physical capacity. Before our study, Edvardsen et al[19] reported that high-intensity endurance and strength training can induce clinically significant improvements in peak oxygen uptake and functional fitness. Salhi et al[20] reported that a rehabilitation program in patients with lung cancer significantly improved exercise capacity and muscle strength. This trial extends their findings to reach a conclusion that lung cancer patients comorbid with chronic pulmonary obstructive disease can also gain physical benefit from postoperative exercise training.
The comparison of lung function tests between groups from baseline to endpoint showed an improvement in clinical data, but that failed to reach a statistically significant level. This result coincided with another trial investigating the effect of postoperative exercise plus inspiratory muscle training on lung cancer patients, in which respiratory muscle strength did not improve to a significant level after intervention, but the trend was favorable.[21]
Compared with patients with normal spirometry, lung cancer patients comorbid with COPD are usually expected to have a longer recovery process, worse exercise tolerance and dyspnea more frequently in daily activities. These patients usually have a longer postoperative hospital stay. Even so, if patients leave the surgery department and directly go home, postoperative recovery and adaptation may be greatly delayed, eventually resulting in decreased quality of life. Postoperative rehabilitation exercise training can improve patients’ physical fitness and accelerate the postoperative recovery process. It can also improve lung function to a certain extent. Postoperative rehabilitation exercise training is demonstrated to help lung cancer patients comorbid with COPD return to their preoperative living or working state.
There are some limitations of our study. First, chronic pulmonary obstructive disease is not the only comorbidity that may interfere with the recovery of postoperative lung cancer patients. Future studies should enlarge the high-risk patient group, such as patients with coronary disease. Second, although participants in the 2 groups were hospitalized in 2 separate wards, communication between groups was still impossible to totally prohibit. Sample contamination is possible, leading to a reduced intergroup difference.
Postoperative rehabilitation is underestimated by medical staff working with lung cancer patients, and the evidence regarding it is very scarce compared with preoperative rehabilitation, which has been heavily studied in recent years. Not just for patients at high risk, patients who were considered to be at low risk before surgery may still have the possibility of developing very serious complications postoperatively. Postoperative rehabilitation can serve as a remedy and improve this situation.
Author contributions
Zhonghua Yu contributed to the conception of the study; Zhonghua Yu, Guosheng Xie, and Changlong Qin performed the experiment; Zhonghua Yu contributed significantly to analysis and manuscript preparation; Zhonghua Yu performed the data analyses and wrote the manuscript; Hongchen He and Quan Wei helped perform the analysis with constructive discussions. All authors reviewed the manuscript.Conceptualization: Zhonghua Yu, Hongchen He.
Formal analysis: Zhonghua Yu.
Investigation: Guosheng Xie, Changlong Qin.
Methodology: Zhonghua Yu, Hongchen He.
Resources: Guosheng Xie.
Project administration: Quan Wei.
Software: Zhonghua Yu.
Supervision: Hongchen He, Quan Wei
Validation: Zhonghua Yu
Writing—original draft: Zhonghua Yu.
Writing—review & editing: Zhonghua Yu.
Abbreviations:
- 6MWT
- 6-minute walk test
- CG
- control group
- COPD
- chronic obstructive pulmonary disease
- CPET
- cardiopulmonary exercise test
- EG
- exercise group
- EORTC
- european organization for research on treatment of cancer
- FEV1
- forced expiratory volume in the first second
- FVC
- force vital capacity
- peak VO2 =
- maximal oxygen consumption
- PFTs
- pulmonary function tests
- QLQ-C30
- The European Organization for Research on Treatment of Cancer quality of life scale
- QLQ
- quality of life questionnaire
- SS
- standard score of QLQ-C30
QW and HH contributed equally to this work.
The work was supported by the National Key R&D Program of China (Grant Nos. 2023YFC3603800 and 2023YFC3603801), the National Natural Science Foundation of China (Grant Nos. 82172534 and 82372574), the Natural Science Foundation Innovation Group of Sichuan Province (Grant No. 2023NSFSC1999).
This study involves human participants and was approved by Ethics Committee of West China Hospital, Sichuan University (No. 2021/1600). Participants gave informed consent to participate in the study before taking part.
The authors have no conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Yu Z, Xie G, Qin C, He H, Wei Q. Effect of postoperative exercise training on physical function and quality of life of lung cancer patients with chronic obstructive pulmonary disease: A randomized controlled trial. Medicine 2024;103:10(e37285).
Contributor Information
Zhonghua Yu, Email: 1850549417@qq.com.
Guosheng Xie, Email: 769602954@qq.com.
Changlong Qin, Email: qinyueming@163.com.
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