Machine Learning Prediction of Respiratory Muscle Changes and Ventilatory Responses After Incretin-Based Therapy in Obesity

Maximum expiratory pressure (MEP) will be measured using an intraoral pressure measuring device (MicroRPM, Micro Medical; UK) in accordance with ATS and ERS criteria. Measurements will be performed with a nasal clip in place and in a seated position. To prevent the risk of infection, a disposable mouthpiece and filter will be used for each participant. Maximum expiratory pressure (MEP) will be measured by applying maximal exhalation for a few seconds and recording the values. Measurements will be repeated three times, and the best value that meets the measurement standard will be recorded in cmH2O. For the measurement to be considered valid, the difference between the two highest measurements must be less than 10%. When evaluating respiratory muscle strength, age and gender-specific reference ranges will be considered. Reference equations developed by Black and Hyatt will be used to interpret the measurements.

Forced vital capacity (FVC) will be assessed using pulmonary function tests (PFTs). The assessment will be performed using the "COSMED Spiropalm 6MWT" (COSMED; Italy) device and integrated PFT software, in accordance with ATS and European Respiratory Society (ERS) criteria (ATS\&ERS, 2002). The assessment will be conducted in a seated position with back support. To prevent the risk of infection, a disposable mouthpiece and filter will be used for each participant. Values will be recorded in liters and as a percentage (%) of the expected value. Measurements will be repeated three times, and the best value meeting the measurement standard will be recorded.

Forced expiratory volume in the first second (FEV1) will be assessed using pulmonary function tests (PFTs). The assessment will be performed using the "COSMED Spiropalm 6MWT" (COSMED; Italy) device and integrated PFT software, in accordance with ATS and European Respiratory Society (ERS) criteria (ATS\&ERS, 2002). The assessment will be conducted in a seated position with back support. To prevent the risk of infection, a disposable mouthpiece and filter will be used for each participant. Values will be recorded in liters and as a percentage (%) of the expected value. Measurements will be repeated three times, and the best value meeting the measurement standard will be recorded.

FEV1/FVC will be assessed using pulmonary function tests (PFTs), and the assessment will be performed according to ATS and European Respiratory Society (ERS) criteria using the "COSMED Spiropalm 6MWT" (COSMED; Italy) device and integrated PFT software (ATS\&ERS, 2002). The assessment will be performed in a seated position with back support. To prevent the risk of infection, a disposable mouthpiece and filter will be used for each participant. The values will be recorded in liters and as a percentage (%) of the expected value. Measurements will be repeated three times, and the best value that meets the measurement standard will be recorded.

Participants' respiratory muscle endurance will be assessed using an inspiratory muscle training device (POWERbreathe® K-SerieS-K3, POWERbreathe International Ltd, UK). Measurements will be taken in a seated position with the device placed in the mouth using a nose clip. The assessment will be conducted using an increasing threshold loading protocol. At the start of the test, the threshold pressure will be set to 20% of the individual's MIP (maximum inspiratory pressure). The individual will be asked to breathe 30 times over two minutes. Individuals who tolerate this level will proceed to the next step, gradually increasing the pressure to 40%, 60%, 80%, and 100% respectively. Oxygen saturation and pulse rate will be recorded before and after the test using a pulse oximeter.

Participants' exercise capacity will be assessed using the Spiropalm 6MWT (Cosmed, Italy) six-minute walk test (6MWT) according to American Thoracic Society (ATS) criteria. This device is a comprehensive system that includes an integrated pulse oximeter for monitoring oxygen saturation during the test and allows for measurement of heart rate, minute ventilation (VE), and respiratory pattern during walking. The Spiropalm 6MWT meets all technical criteria set by the ATS for the 6MWT and is also compliant with ATD/ASD spirometry standards. The test will be conducted in a 30-meter straight corridor in an enclosed area. Participants will rest for at least 10 minutes before starting the test. Following the rest period, heart rate, blood pressure, and oxygen saturation measurements will be taken. In addition, dyspnea and leg fatigue levels will be assessed using the Modified Borg Scale (0-10). Participants will be asked to walk at a pace faster than their normal walking

During the 6MWT will be measured using a Spiropalm device.

During the 6MWT, peak respiratory reserve (BRpeak) will be measured using a Spiropalm device.

During the 6MWT, peak ventilation (VEpeak) will be measured using a Spiropalm device.

During the 6MWT, inspiratory capacity (IC) will be measured using a Spiropalm device.

This will be calculated according to the following formula based on waist circumference and weight measurements.

Skeletal Muscle Mass Index (SMMI) is calculated by dividing an individual's total skeletal muscle mass (kg) by the square of their height in meters (m²) (kg/m²).

The Body Roundness Index (BRI) will be calculated using the individual's waist circumference (cm) and height (m) according to the standard formula defined in the literature. The BRI value will be evaluated as an indicator of body fat distribution and abdominal obesity level.

Participants' body muscle mass (kg) and body muscle percentage (%) will be measured using Bioelectrical Impedance Analysis (BIA). Individuals will be informed about the test protocol and instructed to fast for 8-12 hours before the measurement, to arrive with an empty bladder, and to avoid fluids, food, and strenuous physical activity. Measurements will be taken at a room temperature of 25°C, during the daytime, and participants will be asked to remove their shoes, socks, and all metal objects before stepping onto the device barefoot.

Participants' body fat mass (kg), body fat percentage (%) will be measured using Bioelectrical Impedance Analysis (BIA). Individuals will be informed about the test protocol and instructed to fast for 8-12 hours before the measurement, to arrive with an empty bladder, and to avoid fluids, food, and strenuous physical activity. Measurements will be taken at a room temperature of 25°C, during the daytime, and participants will be asked to remove their shoes, socks, and all metal objects before stepping onto the device barefoot.

Waist circumference will be measured with a non-stretch measuring tape. The measurement will be taken three times at the level of the navel with the patient in an upright position during exhalation, with both feet bearing equal weight. The average value will be recorded in centimeters (cm).

Participants' physical activity levels will be assessed using a wearable activity monitor. The device uses a six-axis sensor (accelerometer and gyroscope) to temporarily store data on the user's lifestyle and physical activity profile in its memory for the duration of wear. The wearable activity monitor will track participants' daily step counts. Participants will be asked to wear the activity monitor continuously on their left wrist for at least 72 hours, excluding sleep or bathing hours.

For the glucose profile of participants after 12 hours of fasting, fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) levels will be measured.

Participants will have their lipid profile measured after a 12-hour fast, including high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglyceride levels.