This clinical study was a prospective, randomized controlled trial applying assessor blinding and intention-to-treat analysis. The study was ratified by the Ethics Committee of West China Hospital, Sichuan University (No.201264), and was carried out in accordance with the Declaration of Helsinki. It was registered at Chinese Clinical Trial Registry (ChiCTR2100042867). This trial was conducted from February 01, 2021 to April 30, 2021 in West China Hospital, Sichuan University, which is responsible for the integrity and conduct of the current study.
The participant inclusion criteria were: 1) patients aged above 18-year old; 2) patients with proven or suspected lung cancer waiting for resection surgery; 3) the diagnosis including chronic obstructive pulmonary disease (forced expiratory volume in 1 second [FEV1]＜80% of the predicted value and FEV1 /forced vital capacity [FVC] ratio＜0.7). The exclusion criteria were: 1) uncontrolled respiratory or cardiovascular disease; 2) mental or psychiatric disease; 3) unable to participate in exercise (e.g. lower limb bone fracture or hemiplegia) 4) thoracic surgery medical history before this trial.
After inclusion and exclusion, eligible patients were required to sign informative consents. Consenting participants were randomized to an exercise group (EG) and a control group (CG) by a nurse who was not involving in the later intervention and data collection process using a random number table generated by computer.
Lung cancer patients with normal spirometry are usually hospitalized for no more than 1 week after surgery. But 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 one 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 participant being transferred to the Rehabilitation Medicine Center and settled in two separate wards, patients in control group received oxygen therapy (if needed) and nebulization as before, while patients in exercise group started to participate in exercise programs on the basis of receiving oxygen therapy and nebulization as same as in control group.
The exercise program consisted mainly of aerobic training. Exercise group patients were asked to ride on cycle ergometers (Schiller, 911S/L) for 30 minutes each session, twice daily, six days weekly. The exercise intensity was set at 20% of heart rate reserve (HRR) at the beginning, and gradually increased to 60%-70% of heart rate reserve. Before each training session, participants had a 5-minute warmup. This 30-minute training can be break down into two 15 minutes or three 10 minutes depending on patients’ need, with interval rest less than 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 more than 4 degrees during exercise, they should stop that training session. The exercise program was adapted from exercise training guidelines for cancer survivors by American College of Sports Medicine and revised. It lasted two weeks for each participant.
Baseline and endpoint tests were carried out 3 days before surgery (baseline) and 1day after end of 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 (peakVO2) in cardiopulmonary exercise test and longer walking distance in 6-minute walk test means better functional capacity. Data in pulmonary function test (PFT) like force vital capacity (FVC) and forced expiratory volume in first second (FEV1) were used to assess the overall lung function[15, 16].
The primary outcomes were the change in physical capacity, and the second outcomes were the change in pulmonary function test.
Sample size was calculated on G*power software (Version 188.8.131.52) with α=0.05 and statistical power=0.80, which gave 56 as minimum sample size. In consideration of a 20% dropout rate, 70 was determined as a proper sample size to generate statistically significant difference between groups.
Statistical software SPSS version 23.0 (SPSS, Inc., Chicago, IL) was used for data processing, and Kolmogorov-Smirnov test for distribution pattern. Continuous data were presented as mean and standard deviation (SD), while categorical data as frequency (percentage). Intergroup differences were analyzed by a two-sided unpaired t-test, Mann-Whitney U test, or χ2 test where appropriate. All statistical tests were two sided and conducted at the 5% significance level.