Lung surgical resection is the gold standard treatment for earlier stages of lung cancer patients. Nevertheless, postoperative pulmonary complications (PPC) are frequent, related to morbidity and mortality, increasing length of hospital stay (LOS), hospital costs, delaying adjuvant treatments, and patients suffering. The PPC often occurs on postoperative days, even after hospital discharge. Prehabilitation might reduce PPC, although few studies have compared the effectiveness of different training protocols, and no information is available regarding the possible benefits of expiratory muscle training. Moreover, there are no comparisons of the cost-benefits of other protocols in patients submitted to lung resection surgery. This project investigates the effectiveness of and compares four different prehabilitation protocols in reducing PPC and LOS in patients selected for lung cancer resections. Participants will be individuals referred to surgical resection due to lung cancer. Patients who meet the inclusion criteria will be invited to participate in the study. After clinical data collection, patients will be randomly allocated (simple method) into four groups \[Control - CG, receiving an education session; Inspiratory muscle training group (IMT-G) receiving education session plus inspiratory muscle training (IMT); expiratory muscle training group (EMT-G) receiving education session plus expiratory muscle training (EMT); global exercise training group (GET-G) receiving education session plus a general exercise training (GET)\], and evaluated for functional capacity (pulmonary function, respiratory muscle function, physical fitness, daily physical activity, dyspnoea, fatigue, quality of life, anxiety, depression, and a 24-hour food diary. Afterward, all patients will receive an education class and written information regarding healthy habits to follow before, during, and after hospital discharge. Patients allocated to exercise groups will start the prehabilitation intervention for two weeks. After the intervention, patient assessments will be repeated. After that, patients will be submitted to surgery, and anesthetic and surgical procedure data will be collected. During hospital recovery, all patients will receive physiotherapy and any etiological complications and the LOS will be recorded according to medical criteria. After hospital discharge, PPC will be monitored and recorded for 30 days; by then, patients will be submitted to the final assessment.
To achieve the project's aim, sample size was calculated using G\*Power 3.1.9.2, based on an effect size of 0.33 reported by Cavalheri \& Granger (2017) in a study of preoperative exercise training and pulmonary complications after lung resection. With α = 0.05 and 95% power, a sample of 180 patients (45 per group) was determined. Accounting for a 10% dropout rate, the estimated total sample size is 200 patients. The study was approved by the Ethical Committee from the Unidade Local de Saúde de São João (ULS São João), number (52/2024). All patients who meet the inclusion criteria, selected for pulmonary resections due to lung cancer, will be invited to participate in the study at the first preoperative appointment at the Cardiothoracic Department of the ULS São João. After signing the informed consent statement, a cod number will be attributed to the patients to protect his/her personal information. Participants will be randomized into one of the four groups: control group (CG), inspiratory muscle training group (IMT-G), expiratory muscle training group (EMT-G), and global exercise group (GET-G). Assessments will be conducted at three time points: after obtaining written informed consent (baseline), after completing the prehabilitation program (post-intervention), and 30 days post-discharge (follow-up). Each assessment will take two days. First day of assessments (data collection at the hospital): A physician will carry one a medical assessment and collect data regarding anthropometric, sociodemographic, medical history, and behavioral risk factors. Following the medical assessment, a researcher will provide to the patients an accelerometer to measure daily physical activity. The accelerometers will be worn during waking hours until completing the prehabilitation program. Additionally, the researcher will collect data regarding patient-related outcome measures through questionaries (modified Medical Research Council Dyspnoea Questionnaire, International Physical Activity Questionnaire - Short Form, the Fatigue Assessment Scale, the Hospital Anxiety and Depression Scale, the EuroQol 5D-5L, food intake report from the day before (1-day recall)\]. Only in the baseline assessment, it will be placing the evaluation of barriers for prehabilitation. The researcher will then schedule the second day of assessment within the next three or four days. Second day (data collection at Faculty of Sport of the University of Porto): In the second day, patients will be evaluated for pulmonary function, respiratory muscle function, and functional capacity and physical fitness. Pulmonary function and respiratory muscle function will provide information on respiratory dynamics, including the absolute and predicted values of forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), Tiffeneau index (TI); total lung capacity (TLC), diffusion lung capacity for carbon monoxide (DLCO) and DLCO per unit alveolar volume (DLCO/VA). Regarding respiratory muscle function, maximal voluntary ventilation (MVV), maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) will be measured. Thereafter, patients will be assessed for functional capacity / physical fitness \[aerobic endurance (6-minute walk test); lower body strength (30-second sit to stand), agility, coordination and dynamic balance (time up and go), balance (3 balance positions), speed walk (4 meters), lower body power (5-time sit to stand), handgrip strength\]. One week after the acceptance in participating in the study, the intervention program will start with an in-person education session for all patients, and those from the IMT-G, EMT-G and GET-G will thereafter start their 2-week training interventions at ULS São João. Detailed information of the training interventions is described in the Arms and Interventions section. Following the intervention, all patients will be reassessed using the same procedures as at baseline, and then they will undergo the surgery. Information on ASA classification, ARISCAT score, minimum oxygen saturation, surgical approach, total surgical time, and extent of resection will be registered by the surgical team. After surgery, all patients will receive standard care at the Cardiothoracic Department, including daily medical assessment, physiotherapy care, and analgesic protocol. Postoperative pulmonary complications (PPC) or from any other etiology, as well as the length of hospital stay (LOS), will be recorded. Any postoperative complication and hospital readmission in the next 30 days will be monitored and recorded. The criteria of PPC will be established according to the European Society of Thoracic Surgery and the Society of Thoracic Surgeons joint agreement and standardized definition (Fernandez et al., 2015). Following hospital discharge, patients will be referred for outpatient physiotherapy and nursing care. Three weeks post-discharge, patients will have a medical appointment at the Cardiothoracic Department and scheduled for the post-discharge assessment. At this appointment, patients will receive an accelerometer to wear for one week, after which a follow-up assessment will be conducted. At the end of data collection, a cost effective analysis will be perfumed aiming to achieve the real economic cost-benefit of each protocol.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
SUPPORTIVE_CARE
Masking
DOUBLE
Enrollment
200
The information that will be delivery is going to be focused on: * Lifestyle changes regarding nutrition and daily physical activity. * Abstinence of the additive behaviors smoking, alcohol, and drug consumption. * Personal hygiene care and hospital routines. * Importance of postoperative physiotherapy. A booklet summarizing the information provided at the education session will be delivered for all participants.
Education Session (described in the control group) Inspiratory muscle training (IMT) After the education session, patients will start the IMT program that will last two weeks. The IMT will be 5 days/ week, lasting 20 minutes, using the PowerBreath KH2 device. In the first week, the intensity of the PowerBreath KH2 will be set at 50% of the maximal inspiratory pressure (with 12 breaths per minute), and it will be increasing by 10% in the second week (with 15 breaths per minute). Patients will be continuously monitored by an oximeter and modified Borg scale
Education Session (described in the control group) Expiratory muscle training (EMT) After the education session, patients will start the EMT that will last two weeks, 5 days a week. The sessions will last 20 minutes and will be structured as follows: 4 minutes of total body stretching exercises 8 minutes of abdominal resistance exercises: 1. First week: 2 exercises, 4 sets of 8 repetitions 2. Second week: 2 exercises, 4 sets of 10 repetitions 8 minutes of specific EMT using the Philips Respironics Threshold PEP device (Load: 20 cmH2O; 10 expirations for minute) Patients will be continuously monitored by an oximeter and modified Borg scale.
The GET-G will be submitted to an education session (equal to the CG) plus 2-weeks of physical exercise, 3 sessions per week, 45-60 minutes. The structure is: Warm-up: 5 minutes of whole-body stretching exercises Main workout: -Aerobic: Week 1: 20 min of treadmill walking at 70% of the mean speed achieved on the 6-minute walk test and limited by 80% of the max theoretical heart rate. Week 2: 20 min of treadmill walking at 80% of the mean speed achieved on the 6-minute walk test and limited by 80% of the max theoretical heart rate. -Resistance Week 1: 8 exercises, 2 sets of 8-10 repetitions, using body weight and elastic bands. Week 2: 8 exercises, 2 sets of 10-12 repetitions, using body weight and elastic bands Coll-down: 5 min of whole-body stretching exercises, holding the point of feeling lightness discomfort for 15 seconds. Patients will be continuously monitored by an oximeter and modified Borg scale.
Faculty of Sport - University of Porto
Porto, Porto District, Portugal
Occurrence of postoperative pulmonary complications from surgery to 30 days after discharge
PPC according to the European Society of Thoracic Surgery and the Society of Thoracic Surgeons (Fernandez et al., 2015): * Persistent air leak \> 5 days (thoracic drainage system Thopaz+ Medela) * Atelectasis needing bronchoscopy * Pneumonia * Adult respiratory distress syndrome * Bronchopleural fistula confirmed by CT scan or bronchoscopy * Pulmonary embolism confirmed by CT scan * Initial ventilator support \> 48 hours * Reintubation * Tracheostomy * Empyema confirmed by CT scan * Chylothorax confirmed by CT scan and pleural liquid analysis
Time frame: From the surgical procedure until 30 days after hospital discharge
Length of hospital stay
The number of days of postoperative hospitalization including hospital readmissions related to surgery, assessed in clinical data. This will be based on the patients´ clinical files.
Time frame: From the surgical procedure until 30 days after hospital discharge
Changes in pulmonary function from baseline at the day before surgery and for 1 week 30 days after hospital discharge
Absolute and relative values of Forced vital capacity (L) and (%); Forced Expiratory Volume in 1 second (L) and (%); Peak Expiratory Flow (L/s) and (%); Tiffeneau Index (%); Total Lung Capacity (L) and (%); Diffusion Lung Capacity for Carbon Monoxide (mmol/min/kPa) and (%); Diffusion Lung Capacity for Carbon Monoxide per unit alveolar volume (mmol/min/kPa/L) and (%) (MILLER et al., 2005). These informations will be captured using the equipment Quark PFT®, Cosmed (Rome, Italy)
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in respiratory muscle function from baseline at the day before surgery and for 1 week 30 days after hospital discharge
Absolute and relative values of Maximal Voluntary Ventilation (L/min) and (%); Maximal Inspiratory Pressure (cmH2O) and (%); Maximal Expiratory Pressure (cmH2O) and (%) ("ATS/ERS Statement on respiratory muscle testing," 2002). These informations will be captured using the equipment Quark PFT®, Cosmed (Rome, Italy) Baseline, day before surgery and 30 days after hospital discharge
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in aerobic endurance from baseline, at the day before surgery and 30 days after hospital discharge
Aerobic endurance will be assessed by the six-minute walk test (6-MWT), according to the American Thoracic Society (ATS) guidelines ("ATS statement: guidelines for the six-minute walk test," 2002). Distance (in meters), maximum and minimum oxygen saturation (%) and maximum and minimum heart rate (bpm) will be recorded. Both oxygen saturation and heart rates will be collected using the Spirodoc® (Rome, Italy).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in lower body strength from baseline, at the day before surgery and 30 days after hospital discharge
To measure lower body strength, participants will be required to perform the sit-to-stand test of the Senior Fitness Test (JONES, RIKLI \& BEAM, 1999). Patients will be instructed to sit and stand the maximum times for 30 seconds. The total number of repetitions will be recorded.
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes on handgrip strength from baseline, at the day before surgery and 30 days after hospital discharge
Handgrip strength will be assessed using the dynamometer Jamar Plus + Digital hand dynamometer (Sammons Preston Inc., Bolingbrook, Illinois, USA). Measurements will be carried out according to the American Society of Hand Therapists Recommendations (MacDermid et al., 2015). In brief, three measurements will be assessed in both arms, with 1 minute interval between attempts. The highest record for each arm will be used as the result.
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in balance from baseline, at the day before surgery and 30 days after hospital discharge
Balance will be measured by the balance test of the Short Physical Performance Battery. In brief, participants must stand for the maximum of 10 seconds with the two feet side by side, holding semitandem, or holding tandem (GURALNIK et al., 1994).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in speed walk from baseline, at the day before surgery and 30 days after hospital discharge
Speed walk will be measured according to the Short Physical Performance Battery. To measure speed walk, participants must walk along 4 meters using their usual speed. Procedure will be performed 3 times (GURALNIK et al., 1994).
Time frame: Baseline, day before surgery and 30 days after hospital discharge.
Changes in lower body power from baseline, at the day before surgery and 30 days after hospital discharge
Lower body power will be measured according to the Short Physical Performance Battery. Participants will be asked to stand up and sit down from an armless chair 5 times as fast as possible, and the time spend in the task will be record, and to (GURALNIK et al., 2000).
Time frame: Baseline, day before surgery and 30 days after hospital discharge.
Changes in agility, coordination and dynamic balance from baseline, at the day before surgery and 30 days after hospital discharge
Agility, coordination and dynamic balance will be measured by the time up and go test presented in the Vivifrail battery (IZQUIERDO et al., 2016). The test will start with the participant sitting in a chair. At the evaluated sign, the participants will stand up, walk 3 meters, and turn back to the chair. The time to accomplish this task will be recorded.
Time frame: Baseline, day before surgery and 30 days after hospital discharge.
Changes in dyspnea from baseline, at the day before surgery and 30 days after hospital discharge
The modified Medical Research Council Dyspnea Questionnaire will be used to observed dyspnea. The questionary contains 5 sentences about daily activities that might promote dyspnea, and the participants will classify their self-perception of dyspnea according to a score ranging from 0 to 4 points (RIBEIRO et al., 2022).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in fatigue from baseline, the day before surgery and 30 days after hospital discharge
Fatigue will be determined through the Fatigue Assessment Scale, which is composed by 10 questions related to physical and mental fatigue, with a Lickert scale (1 to 5). The total score ranges from 10 to 50, which higher results indicating a more severe fatigue profile (MICHIELSEN et al., 2004).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in anxiety and depression from baseline, the day before surgery and 30 days after hospital discharge
Anxiety and depression will be evaluated with The Hospital Anxiety and Depression Scale. This scale consists of two subscales, one for anxiety and the other for depression. Higher results will indicate a potential presence of anxiety and depression (PAIS-RIBEIRO et al., 2007).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in quality of life from baseline, the day before surgery and 30 days after hospital discharge
Health-related quality of life will be observed with the EuroQol 5D-5L. This questionnaire contains the dimensions of mobility, self-care, usual activities, pain/discomfort and anxiety/depression, and participants also classified their perception of general health status (FENG et al., 2021).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in objectively daily physical activity from baseline at the day before surgery and for 1 week 30 days after hospital discharge
Daily physical activity data will be objectively collected using GT3X+ accelerometers (ActiGraph®, LLC, Pensacola, FL, USA). The devices will be wearing for 8 hours during the waiting time for surgery and during 7 days after 30 days of hospital discharge. Data will be processed using the ActiLife software (ActiLife®, LLC, Pensacola, FL, USA).
Time frame: From baseline to the day before surgery and for 1 week 30 days after hospital discharge
Changes in subjective daily physical activity from baseline, at the day before surgery and 30 days after hospital discharge
The Physical Activity Questionnaire - Short Form (IPAQ-SF) will be used to report subjective daily physical activity. Questions covering information about the weekly volume spent at vigorous, moderate and light physical activity, and the amount of time spending in the sitting position will be collected during the waiting time for surgery and during 7 days after 30 days of hospital discharge (CRAIG et al., 2003).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Change from Baseline on body composition at the day before surgery and 30 days after hospital discharge
Body composition variables (body mass (kg), fat-free mass (kg) and fat mass (kg)) will be analyzed with a bioimpedance (InBody 770®, InBody Co. Ltd., Seoul, South Korea).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in body mass index from baseline at the day before surgery and 30 days after hospital discharge
Body mass index will be calculated by the formula: weight divided by squared height. Weight will be assessed with the scale InBody 770 ®, InBody Co. Ltd., Seoul, South Korea) and height with a wall mounted stadiometer.
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in food intake from baseline at the day before surgery and 30 days after hospital discharge
Registration of food intake, including alcohol consumption, will be determined with the 1-day food record. Data will be analyzed using the Food Processor Software®.
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Changes in tabaco smoking habits from baseline at the day before surgery and 30 days after hospital discharge
Registration of smoking habits as "never smoker", "former smoker" or "smoker". For the "former smoker" and "smoker", it will be calculated the tabaco consumption by the number of pack year unity using the formula: number of cigarettes per day / 20 X number of smoking years (BERNAARDS et al., 2001).
Time frame: Baseline, day before surgery and 30 days after hospital discharge
Economic impact
Specific costs attributed to each intervention and comparison cost-effectiveness of each program.
Time frame: Surgical procedure until 30 days after hospital discharge
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