Each session will include at least the following components:

• Resistance training of the lower limbs: Exercises for 6 muscle groups using minimal (e.g. ankle weights or elastic resistance bands) or no (body weight) equipment are foreseen. Each exercise will be performed in 3 series of 8 repetitions.
• Functional training: Sit to stand exercise and stair climbing. During the first 2 weeks of the exercise training program, at least 3 strength exercises and 1 functional exercise will be performed each session.

Starting from the 3rd week of the exercise training program, whole body exercise training (interval training for walking, cycling, stair climbing and high knees) will be added. From this moment on, at least 1-2 whole body exercises and 2-3 strength and functional exercises will be performed during each physiotherapy session. By doing this, each session will consist of a minimum of 4 exercises in total.

Isometric quadriceps strength of the right leg will be measured using the strain gauge device (Sauter Controls NV, Zellik, Belgium) with the hip and knee in 90° flexion. Four repetitions will be performed using standardized encouragement with the first attempt not being maximal and not counting as a possible best result. The best of the last three measurements will be used.

This will be evaluated using the SPPB. This test assesses lower extremity function and mobility. It consists of 3 subtests that are scored and points are added up:

• 4-meter gait speed: To evaluate the patient's functional gait speed. The test is repeated twice. The best time of the 2 attempts is used for the rating. Cut-off: <0.3 m/s or ≥0.3 m/s.
• 5 times sit to stand: This test quantifies the functional lower extremity strength. In this test, patients are asked to complete 5 cycles sit-to-stand as fast as possible from a 45 cm height chair. The participant may practice 1 repetition prior commencing the test. The time needed to perform 5 repetitions is noted. Cut-offs: ≤11.19 seconds (4 points); A higher score indicates a better functional performance.

Change in health related quality of life wil be measured by the Chronic Respiratory Disease Questionnaire (CRDQ-SAS) (dyspnea domain):

This disease specific questionnaire measures both physical and emotional aspects of the chronic respiratory disease. The questionnaire contains 20 items, spread over 4 domains (dyspnea, fatigue, emotional function and mastery). The MCID is reflected by a change in score of 0.5 on a 7-point scale for each of the CRDQ domains (28). Only the dyspnea domain will be used for this study. The self-administered standardized (CRDQ-SAS) version will be used. A higher score indicates a higher health related quality of life.

Change in health status will be measured using the COPD Assessment Test (CAT):

This validated 8-item questionnaire assesses the impact of the disease on a patient's health status. Scores range from 0 (good health status) to 40 (worse health status). The minimal clinical important difference (MCID) is a change of 2 points (19).

Change in patient experience of physical activity will be measured using the Patient Reported Outcome (PRO) -active (C-PPAC) questionnaire: a simple, valid and reliable 12-item questionnaire assessing PA from a patient's perspective reflecting on the past 7 days. The questionnaire investigates the experienced amount of and difficulty of PA as perceived by the patient. The 2 domain scores as well as the total score will be retrieved as outcomes. The clinical visit version will be used. A paper version of the questionnaire will be given along with the monitor. Subscores and total score are from 0 to 100, with higher score meaning less problems with daily life activities as reported by the patient

By taking a fasting blood sample of the patient

By taking a fasting blood sample of the patient

By taking a fasting blood sample of the patient

By taking a fasting blood sample of the patient and triglycerides) and blood pressure

By taking the systolic and diastolic blood pressure of the patient at rest

By taking the weight of the patient

The waist and hip circumference will be measured and risk factors fasting blood sample (glucose level, insulin Hba1c)

By taking a fasting blood sample of the patient

By taking a fasting blood sample of the patient

By taking a fasting blood sample of the patient

Change in day to day data of PA will be assessed by a wearable. The patient receives a step counter (Fitbit) that can be worn on the wrist. The device provides direct feedback, expressed as the number of steps taken per day. The patient is asked to wear the step counter every day during the intervention and is invited to frequently verify the number of steps per day against the agreed goals.

Number of AECOPD following the index AECOPD

By analysing muscle microbiopsies of the quadriceps muscle immunostaining of the myosin heavy chain, only for patients giving their specific consent.

By analysing muscle microbiopsies of the quadriceps muscle immunostaining of the myosin heavy chain, only for patients giving their specific consent.

By analysing muscle microbiopsies of the quadriceps muscle, only for patients giving their specific consent.

By analysing muscle microbiopsies with Pax7 immunostaining of the quadriceps muscle, only for patients giving their specific consent.

By analysing muscle microbiopsies with RT2 profiler PCR array skeletal muscle, Qiagen of the quadriceps muscle, only for patients giving their specific consent.

Change in minutes per day spent in at least moderate intense activities between baseline, 8 weeks and 52 weeks months post randomization in the intervention group as compared to the control group. Physical activity will be objectively measured for 1 week using a tri-axial accelerometer validated for use in patients with COPD. At least 4 valid weekdays (> 8 hours of wearing time during waking hours) is necessary to label the physical activity measurement as valid.

Change in mean daily walking time between baseline, 8 weeks and 52 weeks post randomization in the intervention group as compared to the control group. Physical activity will be objectively measured for 1 week using a tri-axial accelerometer validated for use in patients with COPD. At least 4 valid weekdays (> 8 hours of wearing time during waking hours) is necessary to label the physical activity measurement as valid.

Change in mean sedentary time between baseline, 8 weeks and 52 weeks post randomization in the intervention group as compared to the control group. Physical activity will be objectively measured for 1 week using a tri-axial accelerometer validated for use in patients with COPD. At least 4 valid weekdays (> 8 hours of wearing time during waking hours) is necessary to label the physical activity measurement as valid.

Change in daily mean step count between baseline and 8 weeks post randomization in the intervention group as compared to the control group. Physical activity will be objectively measured for 1 week using a tri-axial accelerometer validated for use in patients with COPD. At least 4 valid weekdays (> 8 hours of wearing time during waking hours) is necessary to label the physical activity measurement as valid.