Multidimensional Approach for COPD and High Complexity

Inclusion criteria

• Provide signed and dated informed consent form;
• Willing to comply with all study procedures and be available for the duration of the study;
• COPD diagnosis (according to "Global Initiative for Chronic Obstructive Lung Disease" (GOLD) 2020 Guidelines) or HF diagnosis (according to European Society of Cardiology (ESC) 2016 Guidelines for the diagnosis and treatment of acute and chronic heart failure);
• Diagnosis at least two other chronic diseases, in addition to COPD (Group A) or HF (Group B). If COPD and HF diagnoses are both present in the same subject, COPD or HF will be considered as the index pathology in view of the clinical relevance and ergo, the participant will be included in the group A or in the group B;
• Healthy subjects exclusively for Group C;
• Chronic diseases are considered the following:
• Type 1 or Type 2 Diabetes mellitus
• Essential hypertension
• Chronic Kidney Disease Stage 3b or worst (Glomerular Filtration Rate \< 44 mL/min/1.73 m\^2 estimated through the Cockcroft-Gault formule)
• Chronic Anemia of moderate level of lower (Haemoglobin levels ≤10.9 g/dl) according to World Health Organization (WHO) classification
• Chronic liver disease (every etiology)
• Obesity (Body Mass Index ≥ 30)

Exclusion criteria

• Active cigarette smoking;
• Need for continuous supportive oxygen therapy, regardless of the flow required;
• Distance covered during the 6 minutes walking test (6MWT) \< 300 meters;
• Unstable angina pectoris or angina pectoris at rest, a history of cardiac arrest, "New York Heart Association" (NYHA) Class III or IV congestive heart failure or severe left ventricular systolic dysfunction (EF \<30%), acute myocarditis, pericarditis or hypertrophic myocardiopathy, clinically significant aortic stenosis, cardiac defibrillator, heart transplant, history of aortic aneurysm of at least 7 cm in diameter or aortic aneurysm repair;
• Uncontrolled or partially controlled asthma despite optimal treatment; Sleep apnea syndrome; history of pulmonary fibrosis;
• Recent acute cardiac or cerebral event in the last six months;
• Child-Pugh B/C cirrhosis;
• Body Mass Index ≥ 35;
• Evidence of any arrhythmia (uncontrolled atrial fibrillation (heart rate of 100 beats per minute or more), left bundle branch block or cardiac pacemaker, etc.) that contraindicates or makes unsafe the fulfilment of the regular physical activity program, assessed on the basis of the clinical history, documentation presented and clinical and instrumental evaluation carried out at the time of enrollment;
• Resting heart rate less than 45 beats per minute or greater than 100 beats per minute;
• History of uncontrolled or partially controlled high blood pressure despite optimal treatment;
• Regular physical activity practice (the level of habitual physical activity practiced will be ascertained by administering specific questionnaires. Only sedentary participants will be eligible);
• Inability to perform the 24-weeks physical activity program for any cause (muscle, joint, respiratory, neurological, vascular, diabetes complications);
• Any acute or chronic disease, already known at the time of enrollment, capable of altering systemic inflammation biomarkers and cytokine profile (e.g. sepsis, infections, immune-rheumatological diseases, hematological diseases, etc.).
• Any muscle condition, inflammatory or not, capable of altering muscular myokines' release (polymyositis, rheumatic polymyalgia, fibromyalgia);
• Acute bleeding at the time of enrollment or any anemia that would have been required urgent transfusion within the past three months;
• Solid or hematological neoplasia under active (at the time of enrollment) or recent (ended less than 6 months earlier) chemo-radiotherapy treatment at the time of enrollment;
• Current diagnosis of schizophrenia, other psychotic disorders or bipolar disorder uncontrolled or partially controlled despite optimal treatment;
• Self-report of alcohol or substance abuse within the past twelve months, current consumption of more than 14 alcoholic drinks per week, and/or current acute treatment or rehabilitation program for these problems;
• Severe cognitive impairment or anything that would place the individual at increased risk or preclude the individual's full compliance with or completion of the study;
• Conditions not specifically mentioned above that may serve as criteria for exclusion at the discretion of the PI and study staff;