Exercise and psychosocial factors modulate immunity to influenza vaccine in elderly individuals

BACKGROUND: Decreases in immune responsiveness with age contribute to the increased incidence and severity of infectious disease among elderly adults. The immune response to immunization also decreases with advancing age. Lifestyle factors (exercise, diet) have been established to play an important role in immunosenescence, and the practice of "healthy" behavior may minimize the age-associated decline of immune function. The objective of this study was to determine whether exercise, diet, and psychosocial factors were associated with altered immune response to influenza vaccine. METHODS: Adults aged 62 years and older were categorized into one of three groups: active (> or =20 min vigorous exercise three or more times per week), moderately active (regular exercise but with less intensity, frequency, and/or duration), or sedentary (no exercise). Two weeks postimmunization, serum was frozen for antibody analysis, and peripheral blood mononuclear cells (PBMC) were cultured in vitro with influenza vaccine to elicit antigen-specific responses (proliferation and cytokine [IL-2, IFN-gamma, IL-10] production). Cytokines and antibody were measured by enzyme-linked immunosorbent assay. RESULTS: The results demonstrated that anti-influenza IgG and IgM were greater in active as compared with moderately active or sedentary participants. PBMC proliferation was lowest in sedentary subjects. Perceived stress was a significant predictor of IL-2. Greater optimism and social activity were associated with greater IL-10. Daily multivitamin intake was significantly correlated with IL-2. CONCLUSIONS: These results suggest that lifestyle factors including exercise may influence immune response to influenza immunization. The practice of regular, vigorous exercise was associated with enhanced immune response following influenza vaccination in older adults.     

Clinical implications of T cell receptor repertoire analysis after allogeneic stem cell transplantation

Stem cell transplantation (SCT) constitutes a major challenge to the immune system. Long-term impairment of immunity against various common infectious stimuli leads to increased susceptibility to infectious diseases; in contrast, an immune response against the recipient may cause the devastating graft-versus-host disease (GvHD). Recovery of the immune system (both qualitative and quantitative) after SCT is perhaps the most important factor in determining the clinical outcome. Consequently, immune reconstitution has been extensively studied using different approaches, including quantitative analysis of immune cells as well as their phenotypic characterization. Analysis of diversity and clonality is an important tool in determining competence of the immune system, assuming that a broad diversity assures efficient response to different stimuli and clonal dominance reflects ongoing, potentially relevant immune responses. Detailed analysis of the immune repertoire through the flow cytometric and molecular study of the T cell receptor repertoire has been applied to gain quantitative and qualitative insights about the T cell immune competence and responsiveness. After SCT, a contraction of the T cell pool and a reduction in T cell receptor diversity is clearly associated with clinical immunodeficiency. Reconstitution of the immune system is often characterized by dominance of oligoclonal T cell populations, reflecting specific antigen-driven immune responses. Detailed characterization of T lymphocytes by T cell receptor analysis is possible, and may lead to the identification of individual clones involved in specific immune reactions, such as alloresponses in GvHD, the closely related graft-versus-leukemia effect and opportunistic viral agents such as CMV or EBV.     

Coronavirus: la emergencia geriátrica de 2020. Documento conjunto de la Sección de Cardiología Geriátrica de la Sociedad Española de Cardiología y la Sociedad Española de Geriatría y Gerontología

SARS-CoV-2 infection, also known as COVID-19 (coronavirus infectious disease-19), was first identified in December 2019. In Spain, the first case of this infection was diagnosed on 31 January, 2020 and, by 15 April 2020, has caused 18 579 deaths, especially in the elderly. Due to the rapidly evolving situation regarding this disease, the data reported in this article may be subject to modifications. The older population are particularly susceptible to COVID-19 infection and to developing severe disease. The higher morbidity and mortality rates in older people have been associated with comorbidity, especially cardiovascular disease, and frailty, which weakens the immune response. Due to both the number of affected countries and the number of cases, the current situation constitutes an ongoing pandemic and a major health emergency. Because Spain has one of the largest older populations in the world, COVID-19 has emerged as a geriatric emergency. This document has been prepared jointly between the Section on Geriatric Cardiology of the Spanish Society of Cardiology and the Spanish Society of Geriatrics and Gerontology.     

Bone loss in Crohn's disease: exercise as a potential countermeasure

Crohn's disease (CD) is associated with a number of secondary conditions including osteoporosis, which increases the risk of bone fracture. The cause of metabolic bone disease in this population is believed to be multifactorial and may include the disease itself and associated inflammation, high-dose corticosteroid use, weight loss and malabsorption, a lack of exercise and physical activity, and an underlying genetic predisposition to bone loss. Reduced bone mineral density has been reported in between 5% to 80% of CD sufferers, although it is generally believed that approximately 40% of patients suffer from osteopenia and 15% from osteoporosis. Recent studies suggest a small but significantly increased risk of fracture compared with healthy controls and, perhaps, sufferers of other gastrointestinal disorders such as ulcerative colitis. The role of physical activity and exercise in the prevention and treatment of CD-related bone loss has received little attention, despite the benefits of specific exercises being well documented in healthy populations. This article reviews the prevalence of and risk factors for low bone mass in CD patients and examines various treatments for osteoporosis in these patients, with a particular focus on physical activity.     

Exercise and older patients: guidelines for the clinician

Sedentary persons who improve their physical fitness are less likely to die of all causes and of cardiovascular disease than are those who remain sedentary. There now exists a wealth of data demonstrating that physical activity and exercise may ameliorate disease and delay decline in function in the geriatric population. We review evidence that exercise can improve body composition, diminish falls, increase strength, reduce depression, reduce arthritis pain, reduce risks for diabetes and coronary artery disease, and improve longevity. However, many healthcare professionals do not feel adequately prepared to design and prescribe exercise programs for their patients. This review provides a basic overview of the benefits of exercise in the geriatric population and guidelines indicating how to prescribe and facilitate adherence to an exercise program. Healthcare providers are strongly encouraged to promote a less sedentary life style for their older patients, which may augment quality of life in these older individuals.     

Sudden death during exercise

Although death during exercise is rare, vigorous physical activity is associated with increased risk for fatality, particularly in individuals with overt cardiac disease or a high coronary risk profile. The mechanism of death is usually a lethal ventricular arrhythmia, but this may vary depending on the underlying cardiac condition. Cardiac disease is present in the great majority of individuals who die during exercise. In young persons, hypertrophic cardiomyopathy and congenital coronary anomalies are most frequent, whereas older victims usually have coronary artery atherosclerosis. Cardiac disease is typically unrecognized before the fatal event in young individuals; in the older group, most have overt coronary disease or identifiable risk factors. Screening asymptomatic subjects to identify increased cardiac risk during exercise is problematical in terms of logistics, expense and accuracy. However, careful evaluation, including exercise testing, is mandatory before a program of increased physical activity is initiated in cardiac patients. For other individuals, firm guidelines are lacking, and the extent of the evaluation must be determined on an individual basis.     

Physical activity,ethnicity and cardio-metabolic health: Does one size fit all?

A large and consistent body of epidemiological evidence indicates that low levels of physical activity, low levels of cardiorespiratory fitness and high levels of sedentary behaviour are associated with increased risk of cardio-metabolic diseases. However, most such studies have been undertaken in populations of White European descent. The available data from non-White populations suggests that physical activity is also protective in these groups, but the threshold level of activity needed to confer low risk, particularly for type 2 diabetes, may not be the same across all ethnic groups. In patients with impaired glucose regulation, lifestyle interventions, including physical activity as a component (often in combination with weight loss), are effective at reducing risk of incident diabetes across a range of ethnic groups. However, the optimal levels of physical activity for prevention of diabetes and cardiovascular disease amongst the general populations of different ethnic groups have not been firmly established. Emerging data suggest that innate differences in cardiorespiratory fitness levels and capacity for fat oxidation potentially contribute to ethnic differences in the cardio-metabolic risk profile and that ethnicity–specific physical activity guidelines may be conceptually warranted. More study is needed to understand how and why the dose–response relationship between physical activity and cardio-metabolic risk differs according to ethnicity and to determine the best approaches to promote physical activity in non-White ethnic groups.     

Environmental and lifestyle influences on disorders of the large and small intestine: implications for treatment

There is growing evidence that many aspects of our lifestyle and the environment we now live in contribute to the development of disease. The luminal digestive tract is a clear target of the influence of dietary components, alcohol, microbial organisms, and other ingested materials. External factors including obesity, lack of physical exercise, and tobacco consumption also impact diseases of the luminal gastrointestinal (GI) tract. A growing understanding of the microbiome which forms an integral part of the human organism indicates that this is another important external force that impacts human health and disease. The luminal GI tract conditions that arise, at least in part, from these external factors range from malignancies (squamous cell esophageal cancer, Barrett's esophagus and associated esophageal adenocarcinoma, gastric cancer, and colorectal cancer), idiopathic inflammatory disorders such as inflammatory bowel diseases, and post-infectious syndromes including post-infectious irritable bowel syndrome, post-infectious dyspepsia and other functional GI disorders. Of particular interest, given their increase in prevalence in much of the world, are immune-mediated conditions in which food antigens are the driving force behind disease development. These entities include celiac disease, eosinophilic esophagitis, and food allergies. Celiac disease is a prime example of a condition mediated by dietary factors whose pathogenesis has only recently been determined, providing opportunities for developing treatment options beyond the gluten-free diet. While a genetic basis for this disease clearly exists, it is believed that environmental factors such as an increase in gluten in the human diet account for its rising prevalence, now roughly 1% of genetically susceptible populations in all continents. Proposed therapeutic strategies span from preventing disease by modulating the time of gluten introduction in infants, to reducing exposure to gluten by developing strains of wheat with lower levels of gluten, degrading ingested gluten peptides within the intestinal lumen via endopeptidases or modulating uptake of these peptides across intestinal tight junctions. Other novel treatments in development focus on interfering with the immune events that lead to disease once gluten accesses the lamina propria including altering the immune milieu from a Th1-predominant response via hookworm infection, inhibiting tissue transglutaminase, and blocking antigen presentation and/or T-cell responses to gluten peptides. While new treatment options for celiac disease reflect the complex interaction of diet, genetic factors and the host immune response, the implications for treatment of many conditions of the large and small intestine that arise from environmental and lifestyle are as basic as ensuring adequate nutrition, regular exercise and cessation of tobacco use. Much more needs to be learned about the microbiome, dietary and other factors and their interaction with the human host in order to develop potential new treatment strategies for diseases that result from the environment and lifestyle.     

A Potential Shift From Adaptive Immune Activity to Nonspecific Inflammatory Activation Associated With Higher Depression Symptoms in Chronic Heart Failure Patients

BackgroundChronic heart failure (CHF) patients with elevated depression symptoms are at greater risk of morbidity and mortality. The mechanisms linking symptoms of depression with disease progression in CHF are unclear. However, research studies have found evidence of alterations in immune activity associated with depression symptoms that may influence heart function. The present study sought to determine the relationship between depression symptoms and chemotaxis of peripheral blood mononuclear cells (PBMCs) in CHF patients, both at rest and in response to moderate exercise.Methods and ResultsSixty-five patients diagnosed with CHF (mean age, 59.8 ± 14.5 years) and 45 non-CHF control subjects (mean age, 52.1 ± 11.6) completed the Beck Depression Inventory (BDI) before undergoing a moderate 20-minute bicycle exercise task. Chemotaxis of PBMCs was examined in vitro to a bacterial peptide f-met leu phe (fMLP) and a physiologic chemokine, stromal cell derived factor-1 (SDF-1) immediately before and after exercise. CHF patients had reduced chemotaxis to SDF-1 (P = .025) compared with non-CHF subjects. Higher BDI scores were associated with reduced baseline chemotaxis to SDF-1 in both CHF and non-CHF subjects (P = .027). In contrast, higher BDI scores were associated with increased chemotaxis to fMLP (P = .049) and SDF-1 (P = .018) in response to exercise in the CHF patients.ConclusionThe present study suggests a shift in immune cell mobility in CHF patients with greater depression symptom severity, with reduced chemotaxis to a physiologically specific chemokine at rest but increased chemotaxis to both nonspecific and specific chemical attractants in response to physical activity. This could have implications for cardiac repair and remodeling in CHF patients and therefore may affect disease progression.     

Diabetes mellitus and geriatric syndromes

Diabetes mellitus is associated with an increased prevalence and incidence of geriatric syndrome: functional disabilities, depression, fall, urinary incontinence, malnutrition and cognitive impairment. Geriatric syndrome not only leads to frailty, loss of independence and low quality of life, but also becomes a major obstacle in the treatment and care of diabetic people. The risk factors or contributing factors of geriatric symptoms are micro- and macrovascular complications, age-rated comorbid disease and aging per se. Comprehensive geriatric assessment of geriatric syndrome, including basic activities of daily living, instrumental activities of daily living, gait and balance, visual acuity, the Mini-Mental State Examination, depression scores, history and risk of fall, urination and nutrition, should be performed as part of the care of elderly diabetic patients, in particular old-old patients. Because geriatric syndromes are multifactorial and share risk factors, diabetic people with any geriatric symptoms should be treated with a common concentric strategy, such as supervised exercise therapy including muscle-strengthening training, psychological support, social support for adherence, and good glycemic control with avoidance of hypoglycemia.     

Psychoneuroimmunology update

Psychoneuroimmunology is the scientific field that investigates linkages between the brain, behavior, and the immune system and the implications of these linkages for physical health and disease. Recent evidence suggests that both naturalistic and laboratory stressors can alter enumerative and functional aspects of the human immune system. Chronic stress may increase vulnerability to infectious disease; however, the role of stress in the course of inflammatory bowel disease remains unclear. Because there are large individual differences in psychological response to stress, it is important to consider the role of cognitive and affective responses to stress. Depression has been associated with functional immune decrements and immune overactivation. Cognitive states such as perceived control, views of the self, and views of the future have been associated with immune parameters and health in some studies. Very few controlled clinical trials have been conducted to determine if psychosocial interventions can impact the immune system and the progression of medical conditions. There is suggestive evidence for the health benefits of relaxation training, cognitive-behavioral stress management, and support groups; but, there is little research on many other psychosocial interventions in widespread use for medical conditions. An evidence-based discussion of this research literature with interested patients may help them make informed decisions regarding adjunctive treatments.     

Exercise and sudden death

Sudden death during exercise is rare, but limited data suggest that vigorous physical activity is associated with an increased risk for this event, particularly in individuals with overt cardiac disease or a high coronary risk profile. The mechanism of exercise-associated sudden death is usually a lethal arrhythmia; however, this may vary depending on the underlying cardiovascular disease. In the great majority of cases, cardiovascular disease is present in persons who die during exercise. In young individuals (less than 35 years old) hypertrophic cardiomyopathy and congenital coronary anomalies are the most common conditions, whereas older victims usually have coronary artery disease. Cardiac disease is typically unrecognized prior to death in young persons; in the older population, most have overt coronary disease or recognizable coronary risk factors. Screening asymptomatic individuals to identify increased risk of a cardiac event during exercise presents major problems in terms of logistics, expense, and accuracy, but careful evaluation, including exercise testing, is mandatory before a program of increased activity in patients with overt cardiac disease. In other cases, the extent of any evaluation must be determined on an individual basis.     

An innovative educational clinical experience promoting geriatric exercise

ABSTRACT

Formal educational training in physical activity promotion is relatively sparse throughout the medical education system. The authors describe an innovative clinical experience in physical activity directed at medical clinicians on a geriatrics rotation. The experience consists of a single 2 1/2 hour session, in which learners are partnered with geriatric patients engaged in a formal supervised exercise program. The learners are guided through an evidence-based exercise regimen tailored to functional status. This experience provides learners with an opportunity to interact with geriatric patients outside the hospital environment to counterbalance the typical geriatric rotation in which geriatric patients are often seen in clinics or hospitals. In this experience, learners are exposed to fit and engaged geriatric patients successfully living in the community despite chronic or disabling conditions. A survey of 105 learners highlighted positive responses to the experience, with 96% of survey respondents indicating that the experience increased their confidence in their ability to serve as advocates for physical activity for older adults, and 89.5% of responders to a follow-up survey indicating that the experience changed their perception of geriatric patients. Modifications to the experience, implemented at partnering facilities are described. The positive feedback from this experience warrants consideration for implementation in other settings.     

Exercise and diabetes

As rates of diabetes mellitus and obesity continue to increase, physical activity continues to be a fundamental form of therapy. Exercise influences several aspects of diabetes, including blood glucose concentrations, insulin action and cardiovascular risk factors. Blood glucose concentrations reflect the balance between skeletal muscle uptake and ambient concentrations of both insulin and counterinsulin hormones. Difficulties in predicting the relative impact of these factors can result in either hypoglycemia or hyperglycemia. Despite the variable impact of exercise on blood glucose, exercise consistently improves insulin action and several cardiovascular risk factors. Beyond the acute impact of physical activity, long-term exercise behaviors have been repeatedly associated with decreased rates of type 2 diabetes. While exercise produces many benefits, it is not without risks for patients with diabetes mellitus. In addition to hyperglycemia, from increased hepatic glucose production, insufficient insulin levels can foster ketogenesis from excess concentrations of fatty acids. At the opposite end of the glucose spectrum, hypoglycemia can result from excess glucose uptake due to either increased insulin concentrations, enhanced insulin action or impaired carbohydrate absorption. To decrease the risk for hypoglycemia, insulin doses should be reduced prior to exercise, although some insulin is typically still needed. Although precise risks of exercise on existing diabetic complications have not been well studied, it seems prudent to consider the potential to worsen nephropathy or retinopathy, or to precipitate musculoskeletal injuries. There is more substantive evidence that autonomic neuropathy may predispose patients to arrhythmias. Of clear concern, increased physical activity can precipitate a cardiac event in those with underlying CAD. Recognizing these risks can prompt actions to minimize their impact. Positive actions that are part of exercise programs for diabetic patients emphasize SMBG, foot care and cardiovascular functional assessment. SMBG provides critical information on the impact of exercise and is recommended for all patients before, during and after exercise. More frequent monitoring (and for longer periods following exercise) is recommended for those with hypoglycemia unawareness or those performing high-intensity exercise. Preventing the sequelae of an exercise-induced severe hypoglycemic reaction can be as simple as carrying glucose tablets or gel, a diabetic identification bracelet or card, or exercising with an individual who is aware of the circumstances. In addition to blood glucose concentrations, proper foot care is critical to people with diabetes who exercise and includes considering type of shoe, type of exercise, inspection of skin surfaces and appropriate evaluation and treatment of lesions (calluses and others). Those with severe neuropathy can consider alternatives to weight-bearing exercises. Precipitation of clinical CAD is of great concern for all diabetic patients participating in exercise activities. Although a sufficiently sensitive and specific screening test for coronary disease has not been identified, those planning an exercise program of moderate intensity or greater should be evaluated. Initial cardiac assessment should include exercise testing as well as identifying risk for autonomic neuropathy. In addition to noting maximal heart rate and blood pressure as well as ischemic changes, exercise tolerance testing can identify anginal thresholds and patients with asymptomatic ischemia. Those without symptoms should be counseled regarding target pulse rates to avoid inducing ischemia. Ischemic changes need to be evaluated for either further diagnostic testing or pharmacological intervention. For patients with diabetes mellitus, the overall benefits of exercise are clearly significant. Clinicians and patients must work together to maximize these benefits while minimizing risks for negative consequences. Identifying and preventing potential problems beforehand can reduce adverse outcomes and promote this important approach to healthy living.     

Moving against frailty: does physical activity matter?

Frailty is a common condition in older persons and has been described as a geriatric syndrome resulting from age-related cumulative declines across multiple physiologic systems, with impaired homeostatic reserve and a reduced capacity of the organism to resist stress. Therefore, frailty is considered as a state of high vulnerability for adverse health outcomes, such as disability, falls, hospitalization, institutionalization, and mortality. Regular physical activity has been shown to protect against diverse components of the frailty syndrome in men and women of all ages and frailty is not a contra-indication to physical activity, rather it may be one of the most important reasons to prescribe physical exercise. It has been recognized that physical activity can have an impact on different components of the frailty syndrome. This review will address the role of physical activity on the most relevant components of frailty syndrome, with specific reference to: (i) sarcopenia, as a condition which frequently overlaps with frailty; (ii) functional impairment, considering the role of physical inactivity as one of the strongest predictors of physical disability in elders; (iii) cognitive performance, including evidence on how exercise and physical activity decrease the risk of early cognitive decline and poor cognition in late life; and (iv) depression by reviewing the effect of exercise on improving mood and increasing positive well-being.     

Rehabilitation of the elderly patient on dialysis

Rehabilitation for geriatric patients, as well as rehabilitation for patients with a chronic disease, strives to mobilize individuals' residual capacity for optimal function in their usual environment. It is clear from observational studies that chronic dialysis patients often experience marked limitations in physical functioning, and these limitations tend to increase with patients' age. However, both prospective studies and controlled trials conducted with elderly persons demonstrate that muscle strengthening and cardiovascular exercise are related to improved physical functioning, and there is evidence that dialysis patients can also benefit from many of these interventions. Inpatient rehabilitation in a specialized geriatric unit has been shown to be associated with better functional outcomes and decreased need for institutionalization among elderly persons; the process of comprehensive geriatric assessment may also have beneficial outcomes. More controlled studies are needed in order to better specify the effectiveness of various geriatric interventions, for elderly subjects in general and for elderly dialysis patients specifically.     

Hypertension and exercise

Levels of physical activity in modern urbanized society are clearly insufficient to maintain good health, and to prevent cardiovascular and other disease. Aerobic exercise is almost completely free of secondary effects, and is a useful adjunctive therapy in treating hypertension. There are several possible mechanisms to account for the beneficial effects of exercise in reducing blood pressure, the resulting physiological effects usually being classified as acute, post-exercise or chronic. Variations in genetic background, hypertension etiology, pharmacodynamics and pharmacokinetics may explain the different blood pressure responses to exercise among hypertensive patients. The present review discusses the different pathophysiological aspects of the response to exercise in hypertensives, including its modulators and diagnostic and prognostic usefulness, as well as the latest guidelines on prescribing and monitoring exercise regimes and drug therapy in the clinical follow-up of active hypertensive patients.     

New insights on the pathomechanisms of inflammatory bowel disease

Pathogenesis of inflammatory bowel disease (IBD) remains an enigma on whether germs, genes or a combination of these two with excessive immune responses to gut‐associated bacteria explicates its pathomechanisms. The incidence of IBD is 0.76747 per 100 000 in Central Indonesia, as shown in the Project Indonesian IBD ACCESS 2012 progress report. This result, together with other epidemiological studies in Asia, may conclusively reflect increased rates of the disease, while its pathogenesis still undoubtedly obscured. However, knowledge of the pathophysiology of IBD is rapidly growing, abreast with new developments. A series of recent updates in core pathomechanisms such as bacterial, endoplasmic reticulum stress, new immune cell populations, T‐cell differentiation and function, mucosal immune defenses and oxidative stress are relevant pathomechanism keypoints in IBD.     

Left ventricular hypertrophy in athletes: morphologic features and clinical correlates

The athlete's heart is a constellation of cardiac morphologic changes, including increased left ventricular volume, increased left ventricular mass, increased left atrial volume, and right ventricular structural changes as a physiologic response to exercise training. These structural changes fall within the normal reference ranges of appropriately matched control subjects for most trained individuals; however, there are significant numbers of athletes who have "abnormal" measurements. The ability to distinguish between physiologic changes associated with the athlete's heart and structural abnormalities that may represent underlying cardiac disease is of paramount importance. Structural heart disease significantly increases risk for morbidity, mortality, and sudden death, especially during exercise or physical stress. This article reviews the morphologic changes associated with the athlete's heart.     

Impact of age-related immune dysfunction on risk of infections

The elderly have clearly been found to have both increased risk and severity of infections. Immunosenescence, the state of dysregulated immune function with aging, is felt to be a significant contributor to this increased risk. Extensive studies on inbred laboratory animals and in very healthy elderly humans have identified changes in immunity and have identified primarily phenotypic and functional changes in the T cell component of adaptive immunity. However, no compelling scientific evidence has shown that these changes have direct relevance to the common infections seen in the aged population. This perspective will attempt to shed light on this dilemma. First, it will review clinically relevant infections in the elderly, focusing on influenza and influenza vaccination and how chronic illness contributes to increased risk and severity of infection/failed vaccine response. Next, key changes in immunity will be reviewed, keeping perspective of the impact of confounding variables such as nutrition. If the goal is to prevent serious infections in the elderly, it appears that the field of geriatric immunology/infectious disease is faced with the tremendous challenge of studying a very diverse population of chronically ill individuals in addition to the study of the very healthy elderly. Grouping individuals by disease severity or by level of impairment of specific components of immunity may assist in advancing our ability to improve host defense in an at risk population.