Importance of Skeletal Muscle and Interdisciplinary Team Approach in Managing Pneumonia in Older People.

Pneumonia is the most frequent lower respiratory tract disease and a major cause of morbidity and mortality globally [...].

Comprehensive Approaches to Aspiration Pneumonia and Dysphagia in the Elderly on the Disease Time-Axis.

Pneumonia in the elderly has been increasing on an annual basis. To a greater or lesser extent, aspiration is a major contributor to the development of pneumonia in the elderly. Antimicrobials alone are not sufficient for the treatment of pneumonia, and the condition may become intractable or even recur repeatedly. In addition, some patients with pneumonia may have no problems with eating, while others are unable to receive the necessary nutrition due to severe dysphagia. It has recently been found that pneumonia decreases both the muscle mass and strength of the swallowing and respiratory muscles, a condition named pneumonia-associated sarcopenia. This contributes to a pathophysiological time-axis of aspiration pneumonia and dysphagia in the elderly, in which silent aspiration leads to the development of pneumonia, and further to dysphagia, malnutrition, and low immunity. Therefore, it is recommended that the treatment and prevention of developing pneumonia should also differ according to an individual's placement in the disease time-axis. In particular, approaches for preventing aspiration based on scientific findings are able to be implemented at home.

Medical aromatherapy in geriatric syndrome.

Geriatric syndromes are symptoms and signs, such as falls, incontinence, delirium, pressure ulcers, dysphagia and so on, that often threaten the independence of older adults, rather than the disease itself. Although the syndromes are very common in older people, it is difficult to treat those by modern medicine due to their complexity. To mitigate the intractable geriatric symptoms, we review the efficacy of aromatherapy, especially for dysphagia, dyspnea, cognitive dysfunction and falls in geriatric syndrome. Olfactory stimulation using a volatile black pepper oil on institutional residents improved the swallowing reflex, which is a crucial risk factor of aspiration pneumonia. Brain imaging study showed that olfactory stimulation using volatile black pepper oil activated cerebral regions of the anterior cingulate and the insular cortex, which play a role in controlling appetite and swallowing. Also, aromatherapy with volatile l-menthol decreased the sense of dyspnea and improved the efficacy of exercise therapy. The fragrance of the combination of rosemary and lemon oils in the morning, and the combination of lavender and orange oils in the night-time were reported to improve cognition and behavioural and psychological symptoms of dementia, respectively. Also, the combination of lavender and lemon balm oils was reported to be effective for irritability-related agitation in older adults. Furthermore, aromatherapy with lavender fragrance could improve both static and dynamic balance, resulting in a reduction in the number of fallers and the incidence rate in older people. Thus, aromatherapy is a promising remedy for geriatric syndrome. Geriatr Gerontol Int 2021; 21: 377-385.

Respiratory Muscle Weakness as a Risk Factor for Pneumonia in Older People.

INTRODUCTION: The respiratory muscle strength regulates the effectiveness of coughing, which clears the airways and protects people from pneumonia. Sarcopenia is an aging-related loss of muscle mass and function, the worsening of which is associated with malnutrition. The loss of respiratory and swallowing muscle strength occurs with aging, but its effect on pneumonia is unclear. This study aimed to determine the risks of respiratory muscle weakness on the onset and relapse of pneumonia in older people in conjunction with other muscle-related factors such as malnutrition. METHODS: We conducted a longitudinal study with 47 pneumonia inpatients and 35 non-pneumonia controls aged 70 years and older. We evaluated the strength of respiratory and swallowing muscles, muscle mass, and malnutrition (assessed by serum albumin levels and somatic fat) during admission and confirmed pneumonia relapse within 6 months. The maximal inspiratory and expiratory pressures determined the respiratory muscle strength. Swallowing muscle strength was evaluated by tongue pressure. Bioelectrical impedance analysis was used to evaluate the muscle and fat mass. RESULTS: The respiratory muscle strength, body trunk muscle mass, serum albumin level, somatic fat mass, and tongue pressure were significantly lower in pneumonia patients than in controls. Risk factors for the onset of pneumonia were low inspiratory respiratory muscle strength (odds ratio [OR], 6.85; 95% confidence interval [CI], 1.56-30.11), low body trunk muscle mass divided by height2 (OR, 6.86; 95% CI, 1.49-31.65), and low serum albumin level (OR, 5.46; 95% CI, 1.51-19.79). For the relapse of pneumonia, low somatic fat mass divided by height2 was a risk factor (OR, 20.10; 95% CI, 2.10-192.42). DISCUSSION/CONCLUSIONS: Respiratory muscle weakness, lower body trunk muscle mass, and malnutrition were risk factors for the onset of pneumonia in older people. For the relapse of pneumonia, malnutrition was a risk factor.

Prognostic factors of 90-day mortality in older people with healthcare-associated pneumonia.

AIM: The Quick Sequential Organ Failure Assessment, and confusion, urea, respiratory rate, blood pressure and age (CURB-65) scores have been used as prognostic factors of mortality related to healthcare-associated pneumonia. However, aspiration pneumonia remains unclear. METHODS: A cross-sectional, prospective cohort study was carried out with 130 inpatients aged ≥75 years at a Geriatric ward of Kyorin University Hospital, Japan. We investigated the utility of aspiration pneumonia-related factors, latency of swallowing reflex and cough reflex sensitivity, serum albumin levels, the neutrophil-to- lymphocyte ratio, and conventional scores of pneumonia severity, for predicting 30- and 90-day healthcare-associated pneumonia mortality. Patient demographics, cognition, physical activity (Barthel Index), eating ability (Food Intake Level Scale), dementia stage (Functional Assessment Staging Tool), performance status (Zubrod score), current medications and comorbidities were collected. Pneumonia severity was evaluated using the Quick Sequential Organ Failure Assessment, CURB-65 and Systemic Inflammatory Response Syndrome criteria scores. RESULTS: Age, Barthel Index, Zubrod, Functional Assessment Staging Tool and Food Intake Level Scale scores were significantly associated with mortality, whereas the conventional scores were not. The Kaplan-Meier method with the log-rank test using Cox proportional hazards analysis showed that serum albumin levels <2.75 and the comorbidity of atrial fibrillation were associated with a lower survival rate in deceased versus surviving individuals at 90 days. In addition, a deteriorated latency of swallowing reflex and a blunted cough reflex sensitivity were associated with 90-day mortality. CONCLUSIONS: Hypoalbuminemia, atrial fibrillation, deteriorated latency of swallowing reflex and blunted cough reflex sensitivity values were better predictors of 90-day mortality than traditional scores in older individuals with healthcare-associated pneumonia. Geriatr Gerontol Int 2020; 20: 1036-1043..

Cough reflex sensitivity and urge-to-cough deterioration in dementia with Lewy bodies.

Cough, an important respiratory symptom, predominantly involves the brainstem and the urge-to-cough (UTC) is modulated by the cerebral cortex. Lewy body disease is associated with decreased cough reflex sensitivity and central respiratory chemosensitivity. Additionally, the insula, associated with the UTC, shows decreased activation and atrophy in dementia with Lewy bodies (DLB). We investigated the relationships between cognition and cough reflex and the UTC and compared the differences in responses of patients with DLB and other dementia subtypes. We conducted a cross-sectional study within a geriatric ward of a university hospital involving elderly patients diagnosed with Alzheimer's disease (AD), DLB, or non-dementia (controls). The cough reflex sensitivities were estimated based on the lowest concentrations of inhaled citric acid that could induce ≥2 coughs (C2) or ≥5 coughs (C5). Subjects were asked to rate the UTC based on the threshold concentrations (Cu) using the modified Borg scale. C2, C5 and Cu were negatively correlated with cognitive function in female participants but not in males (p<0.01). The cough reflex sensitivities expressed as C2 and C5 were significantly higher in the DLB group than in the AD and control groups (p<0.01 adjusted for gender). The UTC threshold expressed as Cu was also significantly higher in the DLB group, while the UTC log-log slope was less responsive in the DLB group than in the other groups. The cough reflex sensitivity and perceived UTC deteriorated in the DLB group more than in the other groups. This result might be valuable in treating patients with DLB.

Association between sarcopenia and pneumonia in older people.

Pneumonia is a major cause of death in older people, and the number of such deaths is increasing. Present guidelines for pneumonia management are based on a pathogen-oriented strategy that relies on the optimal application of antibiotics. Older pneumonia inpatients show the high incidence of aspiration pneumonia. The main cause of aspiration pneumonia is an impairment in the swallowing and cough reflexes. These facts suggest a limitation of present management strategies and a requirement for new strategies for aspiration pneumonia. Sarcopenia is the loss of muscle strength and mass, and declining physical function with aging. Recently, a decrease in the mass or strength of the swallowing muscles was suggested to be associated with reduced swallowing function. Accordingly, dysphagia caused by sarcopenia of the systemic and swallowing-related muscles was named sarcopenic dysphagia. Presently, few studies have shown associations between aspiration pneumonia and sarcopenic dysphagia. As for the cough reflex, strong cough prevents aspiration pneumonia, and its strength is regulated by respiratory muscles. A few studies have reported a relationship between muscles and pneumonia in older people. Sarcopenia is a risk factor for pneumonia in older people, and aspiration pneumonia inpatients with low muscle mass show high mortality rates. Aspiration pneumonia induced muscle atrophy in respiratory, swallowing, and skeletal muscles in an animal model and humans. Associations between respiratory muscle strength and pneumonia are currently under investigation. Evaluation and management of sarcopenia could potentially become a new strategy to prevent and treat pneumonia in older patients, and research has only recently been launched. Geriatr Gerontol Int 2020; 20: 7-13.

The association between eating difficulties and biliary sludge in the gallbladder in older adults with advanced dementia, at end of life.

OBJECTIVES: In clinical settings, untreatable biliary sludge in the gallbladder can be observed in older adults with advanced dementia. The underlying cause of biliary sludge existence in patients with dementia is currently unknown. Therefore, we aimed to investigate the prevalence, risk factors, and related outcomes of biliary sludge formation in the gallbladder of older adults with dementia. DESIGN: Cross-sectional study. SETTING: Geriatric ward of University Hospital in Japan. PARTICIPANTS: Inpatients aged 80 and older living with dementia. MEASUREMENTS: We evaluated the presence of biliary sludge by diagnostic ultrasonography and collected data regarding patient demographic information, cognition (mini-mental state examination [MMSE]), physical activity (Barthel Index), oral food intake (food intake level scale [FILS]), clinical stage of dementia (functional assessment staging [FAST] of dementia), and patient performance status (Zubrod/ Karnofsky score). RESULTS: Male sex, larger gallbladder volume and calories from oral intake were significantly associated with the presence of biliary sludge (P = .02, .02, .002, respectively). There was a significant negative correlation between the FAST stage and the FILS level in all patients (P < .001). More advanced dementia and dysphagia was more likely to be found in patients with Alzheimer disease (AD) with biliary sludge, compared to patients with AD without biliary sludge (FAST 7a, FILS II and FAST 6c, FILS V, respectively, P = .06, 04). A logistic regression analysis revealed that the eating status of FILS I and II, generally called "fasting or anorexia", was a significant risk factor for forming biliary sludge in older adults with dementia (P = .031, odds ratio: 5.25, 95% confidence interval: 1.16-23.72). CONCLUSIONS: Fasting status may be associated with the existence of biliary sludge in older adults with dementia. Therefore, supportive care for eating might be an important solution to comfortable end-of-life care for older adults with advanced dementia.

Aspiration pneumonia induces muscle atrophy in the respiratory, skeletal, and swallowing systems.

BACKGROUND: Repetition of the onset of aspiration pneumonia in aged patients is common and causes chronic inflammation. The inflammation induces proinflammatory cytokine production and atrophy in the muscles. The proinflammatory cytokines induce muscle proteolysis by activating calpains and caspase-3, followed by further degradation by the ubiquitin-proteasome system. Autophagy is another pathway of muscle atrophy. However, little is known about the relationship between aspiration pneumonia and muscle. For swallowing muscles, it is not clear whether they produce cytokines. The main objective of this study was to determine whether aspiration pneumonia induces muscle atrophy in the respiratory (the diaphragm), skeletal (the tibialis anterior, TA), and swallowing (the tongue) systems, and their possible mechanisms. METHODS: We employed a mouse aspiration pneumonia model and computed tomography (CT) scans of aged pneumonia patients. To induce aspiration pneumonia, mice were inoculated with low dose pepsin and lipopolysaccharide solution intra-nasally 5 days a week. The diaphragm, TA, and tongue were isolated, and total RNA, proteins, and frozen sections were stored. Quantitative real-time polymerase chain reaction determined the expression levels of proinflammatory cytokines, muscle E3 ubiquitin ligases, and autophagy related genes. Western blot analysis determined the activation of the muscle proteolysis pathway. Frozen sections determined the presence of muscle atrophy. CT scans were used to evaluate the muscle atrophy in aged aspiration pneumonia patients. RESULTS: The aspiration challenge enhanced the expression levels of proinflammatory cytokines in the diaphragm, TA, and tongue. Among muscle proteolysis pathways, the aspiration challenge activated caspase-3 in all the three muscles examined, whereas calpains were activated in the diaphragm and the TA but not in the tongue. Activation of the ubiquitin-proteasome system was detected in all the three muscles examined. The aspiration challenge activated autophagy in the TA and the tongue, whereas weak or little activation was detected in the diaphragm. The aspiration challenge resulted in a greater proportion of smaller myofibers than in controls in the diaphragm, TA, and tongue, suggesting muscle atrophy. CT scans clearly showed that aspiration pneumonia was followed by muscle atrophy in aged patients. CONCLUSIONS: Aspiration pneumonia induced muscle atrophy in the respiratory, skeletal, and swallowing systems in a preclinical animal model and in human patients. Diaphragmatic atrophy may weaken the force of cough to expectorate sputum or mis-swallowed contents. Skeletal muscle atrophy may cause secondary sarcopenia. The atrophy of swallowing muscles may weaken the swallowing function. Thus, muscle atrophy could become a new therapeutic target of aspiration pneumonia.

Relationship between the severity of cerebral white matter hyperintensities and sympathetic nervous activity in older adults.

AIM: White matter hyperintensities (WMH), visualized on brain magnetic resonance imaging, represent an abnormality related to the development of geriatric syndromes. Recently, it has been found that low sympathetic nervous activity might be associated with physical and cognitive dysfunction in older adults. Therefore, we investigated the relationship between the severity of cerebral WMH and sympathetic nervous activity, measured by the heart rate variability. METHODS: We carried out a cross-sectional study of 39 older patients. Holter recording was carried out for 30 min. From the RR intervals on the electrocardiogram, the standard deviation of the normal-to-normal intervals, the standard deviation of all normal-to-normal intervals in all the five segments of the entire recording, low frequency (LF), high frequency (HF) and LF/HF were calculated. In regard to the WMH, periventricular hyperintensities and deep white matter hyperintensities (DWMH) were rated according to the Fazekas classification. The WMH were also rated semiquantitatively according to the methods developed by Junque (periventricular hyperintensities) and de Groot (DWMH). RESULTS: The LF/HF showed significant negative correlations with the total and regional periventricular hyperintensities, as well as DWMH. Multiple regression analysis showed that the negative associations remained significant between the LF/HF and DWMH (total, temporal, occipital). Furthermore, fall risk index significantly correlated with the LF/HF, total and the occipital DWMH. CONCLUSIONS: The severity of the DWMH was associated with the LF/HF and the fall risk, one of the important geriatric syndromes, suggesting that WMH, sympathetic nervous dysfunction and geriatric syndrome are interrelated to each other. Geriatr Gerontol Int 2018; 18: 569-575.

Dysphagia, dystussia, and aspiration pneumonia in elderly people.

Despite the development and wide distribution of guidelines for pneumonia, death from pneumonia is increasing due to population aging. Conventionally, aspiration pneumonia was mainly thought to be one of the infectious diseases. However, we have proven that chronic repeated aspiration of a small amount of sterile material can cause the usual type of aspiration pneumonia in mouse lung. Moreover, chronic repeated aspiration of small amounts induced chronic inflammation in both frail elderly people and mouse lung. These observations suggest the need for a paradigm shift of the treatment for pneumonia in the elderly. Since aspiration pneumonia is fundamentally based on dysphagia, we should shift the therapy for aspiration pneumonia from pathogen-oriented therapy to function-oriented therapy. Function-oriented therapy in aspiration pneumonia means therapy focusing on slowing or reversing the functional decline that occurs as part of the aging process, such as "dementia → dysphagia → dystussia → atussia → silent aspiration". Atussia is ultimate dysfunction of cough physiology, and aspiration with atussia is called silent aspiration, which leads to the development of life-threatening aspiration pneumonia. Research pursuing effective strategies to restore function in the elderly is warranted in order to decrease pneumonia deaths in elderly people.

Chemical Senses Affecting Cough and Swallowing.

BACKGROUND: Dysfunction of swallowing and coughing leads to life-threatening aspiration pneumonia, especially in the elderly. In order to induce the cough and swallowing reflexes efficiently, sensory inputs to trigger the reflexes are essential. METHODS: Both the cough and swallowing reflexes respond to mechanical and chemical stimuli. However, the mechanisms of action of the two reflexes are not homogeneous. Some substances stimulate both reflexes, but others stimulate one of the reflexes and inhibit the other one. RESULTS: Capsaicin, a TRPV1 agonist, stimulates both the cough and swallowing reflexes. Menthol, a TRPM8 agonist, stimulates the swallowing reflex, but it inhibits the cough reflex, especially if applied to the nose. Acid stimulates the cough reflex but its effect on the swallowing reflex is complicated. Theophylline inhibits the cough reflex by decreasing the excitability of sensory nerves, whereas it stimulates the swallowing reflex by antagonizing adenosine receptors. In smoking, cigarette smoke and nicotine have different effects. Cigarette smoke stimulates the cough reflex, while it inhibits the swallowing reflex. Nicotine inhibits the cough reflex but does not affect the swallowing reflex. CONCLUSION: Whenever you prescribe for an abnormality of one of the reflexes, you should think about the effect of the prescription on the other reflex.

Chronic inflammation, lymphangiogenesis, and effect of an anti-VEGFR therapy in a mouse model and in human patients with aspiration pneumonia.

Chronic inflammation induces lymphangiogenesis and blood vessel remodelling. Since aged pneumonia patients often have repeated episodes of aspiration pneumonia, the pathogenesis may involve chronic inflammation. For lymphangiogenesis, VEGFR-3 and its ligand VEGF-C are key factors. No previous studies have examined chronic inflammation or vascular changes in aspiration pneumonia or its mouse models. In lung inflammation, little is known about the effect of blocking VEGFR-3 on lung lymphangiogenesis and, moreover, its effect on the disease condition. This study aimed to establish a mouse model of aspiration pneumonia, examine the presence of chronic inflammation and vascular changes in the model and in patients, and evaluate the effect of inhibiting VEGFR-3 on the lymphangiogenesis and disease condition in this model. To induce aspiration pneumonia, we repeated inoculation of pepsin at low pH and LPS into mice for 21-28 days, durations in which bronchioalveolar lavage and plasma leakage in the lung suggested the presence of exaggerated inflammation. Conventional and immunohistochemical analysis of tracheal whole mounts suggested the presence of chronic inflammation, lymphangiogenesis, and blood vessel remodelling in the model. Quantitative RT-PCR of the trachea and lung suggested the involvement of lymphangiogenic factor VEGF-C, VEGFR-3, and pro-inflammatory cytokines. In the lung, the aspiration model showed the presence of chronic inflammation and exaggerated lymphangiogenesis. Treatment with the VEGFR inhibitor axitinib or the VEGFR-3 specific inhibitor SAR131675 impaired lymphangiogenesis in the lung and improved oxygen saturation in the aspiration model. Since the lung is the main site of aspiration pneumonia, the changes were intensive in the lung and mild in the trachea. Human lung samples also showed the presence of chronic inflammation and exaggerated lymphangiogenesis, suggesting the relevance of the model to the disease. These results suggest lymphatics in the lung as a new target of analysis and therapy in aspiration pneumonia.

Gender differences in the effect of urge-to-cough and dyspnea on perception of pain in healthy adults.

Previous studies have reported that respiratory sensations, such as urge-to-cough and dyspnea, have an inhibitory effect on pain. Considering the existence of gender differences in both urge-to-cough and pain, it is conceivable that a gender difference also exists in the analgesia induced by urge-to-cough. In this study, we evaluated gender differences in the pain perception response to urge-to-cough, as well as to dyspnea. Twenty-seven male and 26 female healthy nonsmokers were originally enrolled. Citric acid challenge was used to induce the urge-to-cough sensation, and dyspnea was elicited by inspiratory loaded breathing. Before and during inductions of these two respiratory sensations, perception of pain was assessed by the thermal pain threshold, and differences between men and women were compared. The thermal pain threshold in women (43.83 ± 0.17°C) was significantly lower than that in men (44.75 ± 0.28°C; P < 0.05) during the baseline period. Accompanying increases in both citric acid concentration and inspiratory resistive load, thermal pain threshold values significantly increased in both men and women. The average thermal pain threshold changes for comparable increases in the urge-to-cough Borg score were parallel between men and women. Furthermore, the mean value of the thermal pain threshold plotted against the dyspnea Borg score also showed no significant gender difference. These results demonstrate that although gender differences exist in respiratory sensations, that is, urge-to-cough and dyspnea, the inhibitory effects of these respiratory sensations on the perception of pain are not significantly different between the sexes.

Thermal taste and anti-aspiration drugs: a novel drug discovery against pneumonia.

Despite the development of strong antibiotics, the pneumonia death is increasing all over the world in these decades. Among the people who died of pneumonia, the majority were 65 years old or over. Although pneumonia is recently categorized into several entities, aspiration pneumonia includes all entities. Therefore, targeting dysphagia and aspiration to treat pneumonia is a promising strategy and anti-aspiration drugs will be a part of pneumonia treatment. The swallowing reflex in elderly people was temperature-sensitive and the improvement of swallowing reflex by temperature stimuli could be mediated by the thermosensing TRP channels at pharynx. The administration of capsaicin as an agonist stimulus of TRPV1, a warm temperature receptor, decreased the delay in swallowing reflex. Red wine polyphenols improved swallowing reflex by enhancing TRPV1 response. Food with menthol, agonist of TRPM8 which is a cold temperature receptor, also decreased the delay in swallowing reflex. Olfactory stimulation such as black pepper was useful to improve the swallowing reflex for people with low ADL levels or with decreased consciousness. Thus, recent advancement of geriatrics found several anti-aspiration drugs such as thermosensing TRP channel agonists, black pepper odor, amantadine, cilostazol, theophylline and angiotensin- converting enzymes inhibitors. Thermosensing TRP channel agonists include capsaicin, capsiate, menthol, and red wine polyphenols. Controls of swallowing are mediated by various stages of neural system from peripheral sensory nerves to the entire cerebral cortex. Each anti-aspiration drug acts on various sites of neural axis of swallowing reflex. The combination of various anti-aspiration drugs may improve dysphagia and prevent aspiration pneumonia.