Understanding Comorbidity and SBAR

• Comorbidity refers to the simultaneous existence of two or more chronic diseases in an individual at any given time.
• Risk factors for comorbidities include age and lower socioeconomic status.
• The average life expectancy is about 80 years, with an estimated 50% needing treatment for multiple chronic conditions in their last 15 years.
• Comorbidities complicate treatment, increase healthcare costs, and reduce the quality of life.
• The Charlson Comorbidity Index (CCI) determines mortality risk in patients with multiple comorbidities.
• The Health Impact Index (HII) measures the impact of multiple comorbidities on self-reported health.

SBAR Format

• SBAR format facilitates the CEP's work with patients presenting with multiple comorbidities.
• SBAR stands for Situation, Background, Assessment, and Recommendation.
• SBAR is commonly used for transitions in care between healthcare providers.
• SBAR succinctly provides all necessary information for safe transitions.
• S (Situation): explains why the patient is here, and includes diagnosis, age, and gender.
• B (Background): includes pertinent medical history (PMH), history and physical/discharge summary from last hospitalization, MD office notes, and labs.
  • Labs examples: basic metabolic panel (BMP), lipids, complete blood count (CBC), arterial blood gases (ABG), lipids, hemoglobin A1c (HbA1c), brain natriuretic peptide (BNP), cardiac enzymes (creatinine kinase (CK), creatine kinase myocardial isozyme (CKMB), troponin), pulmonary function tests (PFT), echocardiogram (ECHO), cath reports, operative reports, 12-lead electrocardiogram (ECG), imaging, and stress test results.
• A (Assessment): Includes the clinical interview, exercise tests, and fall risk evaluation.
• R (Recommendation): exercise prescription.

Mechanisms of Pathophysiology

• Mechanisms of pathophysiology involved in multiple comorbidities that commonly occur in the adult population include shared mechanisms of pathophysiology like insulin resistance, low-grade inflammation, and oxidative stress that are related to environmental factors, genetics, lifestyle factors, and/or the aging process.
• Secondary effects or complications from a primary diagnosis or its treatment is another mechanism of pathophysiology.
• Insulin resistance, low-grade inflammation, and oxidative stress are shared pathophysiology in people with comorbidities.
• Lifestyle factors contribute to shared mechanisms of pathophysiology.
• One comorbidity can cause another.
• Treatment of a comorbidity can cause another comorbidity.

Lifestyle Factors

• Lifestyle factors can have pleiotropic downstream effects, leading to multiple comorbidities.
• Insufficient physical activity, poor dietary habits, smoking, chronic stress, and excessive alcohol intake increase the risk for CVD, metabolic disease, chronic respiratory disease, musculoskeletal degeneration, impaired immune system function, chronic inflammation, neurodegeneration, cognitive decline, and accelerated aging.
• Certain lifestyle choices can lead to the concurrent development of multiple chronic diseases.
• Environmental factors, genetics, and lifestyle factors contribute to the development of comorbidities by promoting systemic changes in cellular function that affect multiple organ systems.
• "Common soil" etiology of chronic disease includes cellular and systemic changes such as insulin resistance, chronic low-grade inflammation, obesity (characterized by accumulation and dysfunction of visceral and perivascular adipose tissue), oxidative stress, and mitochondrial dysfunction.
• Changes often co-occur in the aging process.
• Aging is also characterized by chronic inflammation, termed "inflammaging”.
• Multiple comorbidities become more common in older individuals.

"Common Soil"

• Insulin Resistance is considered "common soil"
• Chronic Low-Grade Inflammation is considered "common soil"
• Obesity is considered "common soil"
• Oxidative Stress is considered "common soil"
• Mitochondrial Dysfunction is considered "common soil"

Insulin Resistance

• Skeletal muscle insulin resistance contributes to multiple conditions like type 2 diabetes, obesity, dyslipidemia, and hypertension.
• Insulin resistance in the brain can lead to neurodegeneration and dementia.
• Loss of insulin signaling in the skeletal system can lead to loss of bone mass and increased risk for osteopenia in those with diabetes.
• Insulin resistance causes a compensatory increase in insulin production by the β cells of the pancreas, causing hyperinsulinemia.
• Hyperinsulinemia leads to the pathogenesis of cancer.
• Vascular endothelium insulin resistance causes diseases of the cardiovascular system, eyes, nervous system, and renal system.
• Insulin resistance has effects on skeletal muscle and the brain.
• Factors that may lead to the development of insulin resistance include inflammatory signaling, particularly tumor necrosis factor alpha (TNF-α) signaling, mitochondrial insufficiency and dysfunction, impaired glycogen synthesis, mainly from reduced glycogen synthase activity, endoplasmic reticulum stress, impaired lipid metabolism, and accumulation of intramuscular and intrahepatic lipids and lipid metabolites like diacylglycerol, long-chain fatty acyl-CoAs, and ceramides.
• Genes play a role in the development of insulin resistance, as being obese, sedentary, and older can increase insulin resistance, which increases insulin secretion, causing conditions like CVD, HTN, stroke, lipid disorders, IFG, IGT, and T2DM.

Chronic Low-Grade Inflammation

• Chronic low-grade inflammation is characterized by a continual low-grade activation of the immune system which is evidenced by elevated levels of inflammatory markers.
• C-Reactive Protein (CRP), TNF-α, monocyte chemotactic protein-1 (MCP-1), interleukin-8 (IL-8), and interleukin-6 (IL-6) are examples of the elevated levels of inflammatory markers in the immune system.
• C-Reactive Protein is produced by the liver and is a general marker of low-grade inflammation.
• Important factors in the pathophysiology of several chronic conditions: insulin resistance, diabetes, obesity, atherosclerosis and CVD, neurodegenerative diseases, stroke, chronic obstructive pulmonary disease (COPD), cancer, sarcopenia, and autoimmune conditions.
• COPD pathophysiology involves lung tissue and systemic oxidative stress and inflammation.

Obesity

• Obesity, particularly the accumulation of adipose tissues in the visceral region, abdominal cavity, and chest wall (i.e., central obesity), may lead to multiple chronic cardiovascular, metabolic, respiratory, and musculoskeletal conditions.
• Central obesity leads to chronic inflammation by the secretion of proinflammatory cytokines.
• Visceral adipose tissue (VAT) secretes various hormones and cytokines, termed adipokines, which have systemic effects on inflammation, insulin sensitivity, and metabolism.
  • Adipokine is a cytokine produced by adipose tissue.
• VAT is more lipolytic than subcutaneous adipose tissue and releases nonesterified fatty acids (NEFAs), which interfere with insulin signaling and promote the intracellular accumulation of lipid metabolites, which may lead to insulin resistance.
• Metabolic syndrome and central obesity harm the brain, heart, and pancreas.
• Accumulation of adipose tissue in the abdominal and chest cavity may impair respiratory mechanics and lung function, leading to respiratory conditions (e.g., exertional and resting dyspnea, obstructive sleep apnea, and obesity hypoventilation syndrome).
• May also exacerbate symptoms or increase mortality from existing respiratory conditions.
• Obesity may also contribute to the development or accelerate the progression of existing musculoskeletal conditions such as osteoarthritis of the knee and hip, gait disturbances, plantar fasciitis, and low back pain.
• The link between abdominal obesity, inflammation, and insulin resistance may explain much of the relationship between obesity and chronic disease.
• Physical inactivity predisposes someone to metabolic susceptibility, and physical activity predisposes someone to metabolic syndrome.

Oxidative Stress

• Generation of reactive oxygen species (ROS) is a normal and vital aspect of cellular function.
• Generation of ROS from the mitochondria is an important signal for adaptations to training, such as mitochondrial biogenesis and cellular apoptosis.
• However, generation of ROS in excess of the cellular mechanisms available to neutralize them (antioxidant vitamins and enzymes) leads to oxidative stress.
• Increased oxidative stress can interfere with cellular function, leading to deoxyribonucleic acid (DNA) damage, endothelial dysfunction, and other detrimental effects.
• If there are too many ROS, it leads to oxidative stress.
• If the ability to neutralize is unable and the ROS levels get too high, it leads to oxidative stress.
• One well-known example is the role of ROS in the vascular complications of diabetes.
• Hyperglycemia = uptake of glucose by noninsulin-dependent tissues, such as endothelial cells = increased production of ROS = activates inflammatory pathways and is thought to be a major factor linking hyperglycemia to vascular disease.
• Oxidative stress is a component of common soil.
• ROS is an abbreviation for oxidative stress.
• An increased amount of glucose in blood (hyperglycemia) leads to an increase in the uptake of glucose by endothelial cells, which increases the production of ROS, which activates inflammatory pathways and links hyperglycemia to vascular disease.
• Hyperglycemia can cause increased production of ROS, which can lead to inflammation.
• The development of oxidative stress caused by overproduction of reactive oxygen species (ROS) and reactive nitrogen oxide species (RNOS) can overwhelm antioxidant defenses in the cell and contribute to chronic disease.
• Oxidative stress occurs if the cell defenses (antioxidant enzymes) are not enough and if there are too many ROS and RNOS.
• Too many ROS & RNOS causes oxidative stress, which creates an imbalance.

Mitochondrial Dysfunction

• Reduced mitochondrial capacity for oxidative metabolism, such as a reduced number of mitochondria or inadequate oxidative enzyme levels, is a key feature of mitochondrial dysfunction.
• Mitochondrial dysfunction contributes to chronic disease through impaired fatty acid metabolism (accumulation of lipid metabolites) and by increasing the generation of ROS and by reducing antioxidant capacity.
• Mitochondrial dysfunction in skeletal muscle is linked to insulin resistance, pathophysiology of endothelial dysfunction, and cardiotoxicity from chemotherapy.
• Individuals with obesity and T2DM vs. healthy controls demonstrate reduced activity of oxidative enzymes, mitochondrial activity, and mitochondrial size in skeletal muscle.
• T2DM vs. nondiabetic individuals have greater impairments in mitochondrial structure and function.
• Activity of oxidative enzymes was correlated with insulin sensitivity.
• If the mitochondria are not functioning properly, it can lead to insulin resistance.
• Individuals with obesity & T2DM have reduced activity of oxidative enzymes, mitochondrial activity, and mitochondrial size in skeletal muscle.
• Individuals with T2DM have greater impairments in mitochondrial structure and function.
• It appears mitochondrial dysfunction can lead to many different health issues.

Comorbidities Resulting From a Primary Diagnosis

• Multiple comorbidities can result as a complication from a primary diagnosis or its treatment.
• Metabolic and cardiovascular pathologies are interrelated and may exacerbate each other through a feed-forward mechanism involving inflammation, hyperglycemia, oxidative stress, and endothelial dysfunction.
• Long-term diabetes is associated with well-known vascular complications, including an increased risk for large artery disease (coronary artery disease, peripheral artery disease) and microvascular complications (retinopathy, nephropathy, neuropathy).
• Hyperglycemia leads to macro- and microvascular damage through increased production of ROS, reduced nitric oxide (NO) bioavailability, activation of inflammatory pathways, and endothelial dysfunction.
• Nitric oxide (NO) is a potent vasodilator.
• Metabolic diseases like obesity and diabetes are associated with an increased risk for neurological disorders such as Alzheimer disease, vascular dementia, and Parkinson disease.
• The relationship appears mediated by inflammation, insulin resistance, and mitochondrial dysfunction.
• Physical exercise has pleiotropic benefits, while a lack of bodily activity may lead to multiple downstream pathologies.
• Oxidative stress from poor glucose control can lead to microvascular complications associated with diabetes and can also lead to cardiovascular complications.
• Insulin action in skeletal muscle, liver, and the vascular endothelium is impaired in metabolic syndrome leading to vascular dysfunction and impaired blood glucose regulation.

Chronic Illness and Mental Health

• Physical and mental health share a bidirectional relationship.
• Diagnosis with a chronic disease can lead to anxiety and depression.
• Mental illness (including depression or anxiety disorders) can lead to unhealthy behaviors like low levels of physical activity.
• Chronic stress and chronic disease also share a bidirectional relationship.
• Chronic stress, through modulation of autonomic nervous system activity and the hypothalamic-pituitary axis, can alter immune function, affect hemodynamics, lead to chronic inflammation, prompt endothelial dysfunction, and create a prothrombotic environment.
• Chronic stress may also contribute to metabolic perturbations, hypertension, and neurodegenerative, cognitive, and psychological disorders.
• Mental health can affect physical health and vice versa.
• Chronic stress may contribute to metabolic perturbations (insulin resistance, abdominal obesity, hyperglycemia), hypertension, and neurodegenerative, cognitive, and psychological disorders such as anxiety and depression.
• Chronic stress affects the cardiovascular system and may increase the risk for CVD and cardiac events.
• Consider the relationship between physical and mental health, considering the effects of chronic disease and mental illness on lifestyle choices, and potential issues like persistent high stress levels.

Comorbidities and Exercise Prescription

• The CEP must be aware of the relationship between conditions, including potential complications from a primary diagnosis, and how the treatment or management of one condition may influence another.
• Such awareness is essential for writing safe and effective exercise prescriptions for an increasingly prevalent population: those with comorbidities.

Exercise Prescription - The First Step

• Obtain appropriate provider referrals, requirements vary by state depending on practice acts in a particular area.
• Some states allow advanced practice professionals (APPs), including physician assistants and nurse practitioners, to make referrals.
• In all states, physicians (MD, DO) can make referrals.
• Referral is necessary before beginning the exercise program for clinically complex patients to ensure patient safety.

Exercise Prescription - The Second Step

• Once necessary referrals are obtained, the CEP reviews available medical records.
• Key records to be obtained at a minimum include the discharge summary from the last hospitalization (or the most recent clinic visit note) and a current medication list, and additional records addressing any questions that remain.

Exercise Prescription - The Third Step

• Prioritize concerns: pulmonary or hemodynamic instability (if the patient cannot maintain adequate oxygenation and peripheral perfusion at rest, activity will be poorly tolerated and unsafe).
• Examples include heart failure, aortic stenosis, pulmonary hypertension, angina, uncontrolled cardiac dysrhythmias, undertreated hypertension, and symptomatic hypotension.
• Metabolic imbalances are also priority concerns, and examples include high or low blood glucose levels, electrolyte abnormalities, anemia, and severe endocrine disorders such as hyperthyroidism.
• Patients with neurological or mental disorders may have difficulty communicating or following instructions, resulting in an unsafe setting.
• Dementia, severe depression, bipolar disorder, anxiety disorders, untreated psychosis, or severe personality disorders are examples.
• Patients with infectious or inflammatory conditions are precluded from participation in physical activity until their condition is resolved, which could include sepsis, myocarditis, pericarditis, or an acute infectious process.
• Other concerns could include orthopedic impairment that activity could aggravate, or a suspected or known dissecting aneurysm.

Exercise Prescription - The Fourth Step

• Conduct a clinical interview to review organ systems and patient goals.
• It's important to conduct an assessment of the disease burden and the functional status to compare the patient's baseline functional status to the patient's functional status one year preceding the major event that led to referral to the medical facility.
• Main issue for which the patient is referred is significant to consider.
• When reviewing the exercise history, patients with little to no experience with physical activity often do not understand how to rate their effort or exertion level, while patients with a strong history of activity may not understand that they can no longer perform as they did previously, whether because of deconditioning or an event that results in functional limitation.
• When reviewing goals of the exercise program, the CEP addresses whether the patient is able to perform the physical tasks required by work, activities of daily living (ADLs), and recreational pursuits.
• It is important to determine the metabolic equivalent (MET) level required for the patient to return to pre-event level of function.
• Patients with a high disease burden or significant limitation of function likely cannot resume a high level of activity.
• An example is a firefighter who had a large MI, as subsequent impact to LV function will typically not be able to resume his/her chosen occupation.

Goals of Exercise Prescription

• The primary goal is to return the patient to their pre-event functional status.
• The secondary goal is to return the patient to their level of function from one year previously.
• The tertiary goal is to return the patient to a level of function that meets all of the patient's goals.
• To attain more general goals, consider the 3 main general categories: Functional, Occupational, & Recreational.
• Functional exercises focus on performing all of the necessary activities of daily living (ADL); examples include bathing, meal prep, housework, and caring for others.
• Occupational examples would be can they carry laundry up and down two flights of stairs at their apartment.
• Can vary widely, The United States Department of Labor publishes a list of occupations and the associated metabolic demand for each job class
• Recreational exercises can vary widely, remember basic exercise physiology principles such as specificity of training, overload, and progression.
• The essence of writing an exercise prescription: Individualization of the program and creativity in crafting a program that meets the patient's goals, provides an adequate training effect, and safely accommodates the individual's clinical restrictions.
• Step 4 involves goals! When you do the clinical interview and determine goals, break goals down into functional (can they take care of themselves), occupation (what was your occupation & do you want to get back to that), and recreational (how recreational are you).
• There are 3 major areas you might want to consider in making goals for the individual, as well as examples of the types of goals.

Exercise Testing for Patients with Comorbidities

• After the clinical interview, exercise testing should be performed.
• Testing should be individualized to the functional capacity of the patient.
• Fall risk should be assessed using functional tests, such as the Timed-Up & Go (TUG) test, 30-second chair sit-to-stand, and 4-stage balance test.
• The STEADI Algorithm for Fall Risk Assessment & Interventions may be used to classify fall risk.
• • These functional tests are examples of tests to determine their risk of falling^, assess the risk of falling.

Exercise Prescription

• The initial exercise prescription should include cardiovascular, strength, and flexibility components and a progression plan.
• Potential side effects are key to mitigate
• It is important to consider alternative activities in the event that the initial program is poorly tolerated.
• Start off slowly and progress gradually.
• Medically complex patients tend to have poor exercise histories, may be intimidated by exercise, and may be less tolerant of the unpleasant sensation of delayed onset muscle soreness or fatigue.
• At some point, the patient can move to a "maintenance dose" of exercise.
• Maintenance dose means you can stay at a level of exercise, as you are maintaining what you gained and you are no longer applying progressive overload.

Chapter 9: Respiratory Diseases - Introduction

• Breathing provides oxygen and removal of carbon dioxide.
• Respiratory diseases occur if the lung is disproportionally ventilated with respect to the amount of blood flow they receive, thereby diminishing the efficiency of oxygen and carbon dioxide transport (gas exchange) across the alveolar-capillary interface. Extend beyond the lungs to contribute to skeletal muscle dysfunction and alter the perception of physical effort, making physical activity feel disproportionally difficult for the actual intensity .
• Burdens the sufferer with dyspnea and fatigue, anxiety, activity avoidance, and physical deconditioning and quality of life is diminished.

Respiratory Diseases

• COPD - Chronic Obstructive Pulmonary Disease includes Chronic Bronchitis and Emphysema.
• Asthma is a respiratory disease.
• Asthma-COPD is a hybrid form of respiratory disease.

Epidemiology of COPD

• COPD is the third leading cause of death in the United States.
• COPD is thought to evolve from a complex interaction between genetics and the environment. "... a common, preventable and treatable disease that is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases". Frequent exposure to tobacco smoke, and environmental or occupational exposure to organic and inorganic dusts, chemical fumes, and pollution are recognized contributors.
• The Exposure to noxious substances provokes an enhanced inflammatory response that affects the large and small airways as well as the lung parenchyma (the acini or respiratory bronchioles, alveolar ducts, and alveoli) such as Chronic bronchitis or Emphysema.
  • Chronic bronchitis involves hypersecretion of mucus from hypertrophied submucosal glands and goblet cells, which leads to chronic cough and sputum production.
  • Emphysema involves chronic inflammation increases small airway resistance through airway narrowing, and destroys the lung parenchyma, reducing both the lung's elastic recoil and the tethering between the acini and small airways.

Epidemiology of Asthma

• Asthma is a heterogeneous disease that characterized by chronic airway inflammation.
• Asthma involves a complex interaction between host genetics and a wide range of environmental factors.
• such as the development of airflow obstruction, bronchial hyperresponsiveness, and inflammation. Dominant aspect of the disease that produces clinical symptoms is airway smooth muscle constriction and inflammation, both of which lead to airway narrowing and obstruction and make ventilation of the lungs more difficult
• In arterial blood gases and acid-base status during progressive steady-state increases in work rate, the fall in pH at the two highest work rates was caused by a rise in the concentration of lactic acid and a reduction in plasma bicarbonate in arterial blood. PaCO2 is fairly constant over the first four work rates but falls commensurately with the metabolic acidosis at the two heaviest work rates.
• You produce more lactic acid while exercising, the more hydrogen you have, the lower your pH.
• . Bicarbonate buffering system - HCO3- becomes H2CO3 breaks down into H2O and CO2
• Exhale removes excess CO2, consequently increasing exhalation of CO2
• They decrease together because we are buffering the lactic acid

COPD: Pathology

• Central pathology of COPD is an exaggerated inflammatory response due to chronic exposure to noxious gases and particulate
• Overproduction of mucus from hypertrophied submucosal glands and enlarged goblet cells leads to productive cough, and the inability to clear excess mucus provides an environment to promotes microbial infection Characteristic airflow limitation of COPD arises primarily from small airways less than 2 mm in diameter which an increasing the airflow resistance
• .Emphysema results when the alveoli, alveolar ducts, and respiratory bronchioles become irreversibly damaged with an increasing Inflammatory driven destruction of the lung parenchyma results in the loss of structural interdependence of the alveolar units and the alveolar attached to small airways. The tethering effect of the alveoli on each other and on smaller airways to hold them open during exhalation is lost.
• Collapsed airways are more difficult to reinflate and offer increased resistance to expiratory airflow; therefore, greater expiratory muscle effort is required to empty the lung.
• Typically see increases in total lung capacity (TLC)
• Airway narrowing and collapse during exhalation increases how long it takes to empty a tidal breath from the lung Dynamic lung hyperinflation develops because the expiratory airflow limitation slows emptying of the lungs and the shorten expiratory time invariably leads to a progressive increase in air trapping and end expiratory lung volume
• Dyspnea (most distressing symptom of COPD) is a multidimensional sensation described as air hunger, increased effort, or chest tightness
• Lung hyperinflation also affects cardiovascular function leading to increases High intrathoracic pressure and Elevated pulmonary vascular resistance
• Ventilation and perfusion of the lung is compromised, causing regional VA/Q mismatching that can result in hypoxia, hypercapnia, or both at rest and during exercise Skeletal muscle dysfunction is the most common extrapulmonary manifestation of COPD The upper panel (i) depicts a normal healthy bronchial tube, whereas the lower panel (ii) depicts a bronchial tube of a patient with chronic bronchitis. Irritant-induced inflammation leads to mucus production that over time becomes excessive due to goblet cell hypertrophy and hyperplasia. Reduced mucociliary clearance leads to blocked airways that have been narrowed by inflammation-induced airway remodeling.
• The left panel (i) depicts normal elastic recoil in a healthy alveolus. The end inspiration volume is shown by the dotted line, and alveolar volume decreases with exhalation. Panel (ii) shows how the loss of alveolar elastic recoil due to emphysema leads to a larger end expiratory alveolar volume and air trapping and excess mucus causes cilia to not work like they are supposed to
• The hallmark characteristic of Asthma is an exaggerated inflammatory response following exposure of the airway to triggering stimuli such as dust or pollen, viral infection, or airway drying.