Takae Ebihara

Capsaicin Troche for Swallowing Dysfunction in Older People

Objectives: To determine whether oral capsaicin troche supplementation with every meal upregulates the impairment of upper respiratory protective reflexes such as the swallowing reflex and the cough reflex.

A randomized trial of olfactory stimulation using black pepper oil in older people with swallowing dysfunction

OBJECTIVES: To determine the effect of olfactory stimulation with volatile black pepper oil (BPO) on risk factors for pneumonia.

Role of ephrinB2 in nonproductive angiogenesis induced by Delta-like 4 blockade.

Delta-like 4 (DLL4) is one of the Notch ligands and plays an important role in vascular development. DLL4 blockade inhibits tumor growth by promoting nonproductive angiogenesis, which is characterized by an increase in vascular density and decrease in tissue perfusion. However, a detailed mechanism remains unclear. In this study, newly developed neutralizing antibodies against mouse and human DLL4 were used to investigate the possible involvement of VEGF-DLL4-ephrinB2 cascade in nonproductive angiogenesis caused by DLL4 blockade. DLL4 blockade and soluble ephrinB2 treatment suppressed tumor growth and induced nonproductive angiogenesis. DLL4 was expressed in subcutaneous tumors, and DLL4 blockade suppressed ephrinB2 expression in the tumors. DLL4 blockade significantly promoted human umbilical vein endothelial cell (HUVEC) proliferation in vitro, and the effect was additive to that of VEGF. Both DLL4 blockade and VEGF significantly increased cord length and branch points in a tubular formation assay. Expression of ephrinB2 in HUVECs was enhanced by VEGF alone, and the enhancement was inhibited by DLL4 blockade. Moreover, when we studied the effect of ephrinB2 RNA interference on HUVEC tubular formation, knockdown of ephrinB2 mimicked the effect of DLL4. These results suggest that ephrinB2 plays a crucial role in nonproductive angiogenesis caused by DLL4 blockade.

Effect of temperature on swallowing reflex in elderly patients with aspiration pneumonia

To the Editor: We read with interest the study by Ricauda et al. describing a home hospital (HH) model of care for patients with acute stroke because it highlights important issues related to defining a HH. A wide variety of models of care has been described in the international literature under the HH umbrella, engendering controversy over the definition of HH and the effectiveness of the model. These models include the outpatient infusion centerwhere patients receive an intravenous infusion or other treatment; the physicians’ office intravenous service where patients predominantly self-infuse their medications and are reviewed in physicians’ offices; the delivery of home-based care by hospital, or hospital contracted, staff or in the United States by a home health agency to patients in their own homes; early discharge schemes, mostly for postsurgical patients in which patients early in the postoperative period are discharged home and receive postoperative nursing supervision and skilled therapies at home, again with little organized input from physicians; and a clinical unit model that delivers acute hospital-level medical care in the patient’s home and substitutes entirely for an acute hospital admission. Physician and nursing care are provided in the home, as well as appropriate diagnostic and therapeutic care and technologies. The study of HH for acute stroke by Ricauda et al. is an excellent example of a clinical unit model of HH. This HH model possessed three elements we consider to be key features that define a HH. (1) It provides care that substitutes entirely for an inpatient acute hospital admission. (2) It provides an intensity of care, including medical and nursing care, similar to that provided in the hospital appropriate to the severity of the illness treated. (3) It provides care that cannot be provided by usual community-based home care services. Defining HH in this manner relates to the underlying rationale of the model. The main reasons for developing HH include reducing iatrogenic complications including functional decline, honoring patients’ wishes for their care, and reducing expenses. Given this, substitution for an acute hospital inpatient stay is essential in satisfying the HH care model to its fullest extent. Postdischarge programs and nursing programs that do not substitute for a hospital admission entirely expose the patient to the acute hospital environment, may not satisfy patient preference to avoid the hospital, and probably are not as economically efficient as possible. To substitute entirely for an inpatient admission, HH should provide an intensity of care similar to that provided in the hospital to ensure proper evaluation and treatment of the acutely ill patient. This means that 24-hour access to hospital-level medical and nursing care and appropriate diagnostic and therapeutic modalities must be available to the care of the patient. This has generally not been available in the community setting or in many models claiming to be HH. Provision of HH needs to be care that typical community-based home care services cannot provide. HH programs that become blurred with other community-based programs run a high risk of subsequent failure, simply because the skills and organization are different from those required for non-HH community-based care provision. In terms of economics, labeling typical community-based home care services as HH care may simply undermine the economic rationale for the model if expensive HH care is provided to patients who do not require it. Finally, in terms of research and evaluation, blurred boundaries between HH and more typical home care services may result in substantial heterogeneity of patients and care requirements and ensure that outcome studies trend towards equivalence. We hope that focusing the definition of HH will facilitate further development and research on this emerging model of care.

Effect of Aging on Cough and Swallowing Reflexes: Implications for Preventing Aspiration Pneumonia

The impairment of airway protective reflexes, i.e., swallowing and cough reflexes, is thought to be one of the major causes for aspiration pneumonia in older people. Restoration of cough and swallowing reflexes in the elderly is key to preventing aspiration pneumonia in the elderly. Although, the medical literature has asserted that cough and swallowing are controlled primarily by the brainstem, recent advances in human brain imaging has provided evidence that cortical and subcortical structures play critical roles in cough and swallowing control. Because of their nature, reflexive cough and swallowing activate both sensory and motor areas in the cortex. In both protective reflexes, the sensory component, including sensory cortex in reflexive circuits, seems to be more vulnerable to aging than the motor component, including the motor cortex. Therefore, the strategy to restore cough and swallowing reflexes should be focused on compensations of sensory components in these reflexive circuits. Remedies to enhance sensory nerve terminals and sensory cortical areas related to these reflexes might be useful to prevent aspiration pneumonia in the elderly.

Impaired urge-to-cough in elderly patients with aspiration pneumonia

BackgroundThe down-regulation of the cough reflex in patients with aspiration pneumonia can involve both cortical facilitatory pathways for cough and medullary reflex pathways. In order to study the possible involvement of the supramedullary system in the down-regulation of cough reflex, we evaluated the urge-to-cough in patients with aspiration pneumonia.MethodsCough reflex sensitivity and the urge-to-cough to inhaled citric acid were evaluated in patients with at least a history of aspiration pneumonia and age-matched healthy elderly people. The cough reflex sensitivities were defined as the lowest concentration of citric acid that elicited two or more coughs (C2) and five or more coughs (C5). The urge-to-cough scores at the concentration of C2 and C5, and at the concentration of two times dilution of C2 (C2/2) and C5 (C5/2) were estimated for each subject.ResultsBoth C2 and C5 in the control subjects were significantly greater than those for patients with aspiration pneumonia. There were no significant differences in the urge-to-cough at C2 and C5 between control subjects and patients with aspiration pneumonia. However, the urge-to-cough scores at both C2/2 and C5/2 in patients with aspiration pneumonia were significantly lower than those in control subjects. The number of coughs at C5/2 was significantly greater in the control subjects than those in the patients with aspiration pneumonia whereas the number of coughs at C2/2 did not show a significant difference between the control subjects and the patients with aspiration pneumonia.ConclusionThe study suggests the involvement of supramedullary dysfunction in the etiology of aspiration pneumonia in the elderly. Therefore, restoration of the cough motivation system could be a new strategy to prevent aspiration pneumonia in the elderly.

Sensory Stimulation to Improve Swallowing Reflex and Prevent Aspiration Pneumonia in Elderly Dysphagic People

Morbidity and mortality from aspiration pneumonia continues to be a major health problem in the elderly. A swallowing disorder, such as a delayed triggering of the swallowing reflex, exists in patients with aspiration pneumonia. We found that the swallowing reflex in elderly people was temperature-sensitive. The swallowing reflex was delayed when the temperature of the food was close to body temperature. The actual swallowing time shortened when the temperature difference increases. The improvement of swallowing reflex by temperature stimuli could be mediated by the temperature-sensitive transient receptor potential (TRP) channel. The administration of a pastille with capsaicin as an agonist stimulus of TRPV1, a warm-temperature receptor, decreased the delay in swallowing reflex. Food with menthol, an agonist of TRPM8, 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 activity of daily living (ADL) levels or with decreased consciousness. Oral care also shortened the latent time of swallowing reflex presumably due to stimulating the nociception of the oral cavity. A combination of these sensory stimuli may improve the swallowing disorders and prevent aspiration pneumonia.

Perception of urge-to-cough and dyspnea in healthy smokers with decreased cough reflex sensitivity

BackgroundAlthough cigarette smoking has been implicated as an important risk factor for the development of respiratory symptoms, the perceptional aspects of two symptoms in smokers have not been fully elucidated. Therefore, we simultaneously evaluated the cough reflex sensitivity, the cognition of urge-to-cough and perception of dyspnea in both healthy smokers and non-smokers.MethodsFourteen male healthy never-smokers and 14 age-matched male healthy current-smokers were recruited via public postings. The cough reflex sensitivity and the urge-to-cough were evaluated by the inhalation of citric acid. The perception of dyspnea was evaluated by Borg scores during applications of external inspiratory resistive loads.ResultsThe cough reflex threshold to citric acid, as expressed by the lowest concentration of citric acid that elicited two or more coughs (C2) and the lowest concentration of citric acid that elicited five or more coughs (C5) in smokers was significantly higher than in non-smokers. The urge-to-cough log-log slope in smokers was significantly milder than that of non-smokers. There were no significant differences in the urge-to-cough threshold between non-smokers and smokers. There were no significant differences in perceptions of dyspnea between non-smokers and smokers.ConclusionsThe study showed that decreased cough reflex sensitivity in healthy smokers was accompanied by a decreased cognition of urge-to-cough whereas it was not accompanied by the alternation of perception of dyspnea. Physicians should pay attention to the perceptual alterations of cough in smokers.

Effect of cigarette smoking on cough reflex induced by TRPV1 and TRPA1 stimulations

BACKGROUND Recent studies have shown that neurogenic inflammation induced by cigarette smoke is inhibited by TRPA1 antagonist, but not by TRPV1 antagonist. Since cough reflex sensitivity is known to be modified by smoking status, we investigated the effects of cigarette smoking on TRPA1- and TRPV1-induced cough and urge-to-cough in healthy males. METHODS Twenty-six healthy never-smokers and 30 healthy current smokers were recruited via public postings. Cough reflex thresholds and urge-to-cough were evaluated by inhalation of capsaicin, a TRPV1 agonist, and cinnamaldehyde, a TRPA1 agonist. The cough reflex thresholds were defined as the lowest concentrations of capsaicin and cinnamaldehyde that elicited two or more coughs (C(2)) and five or more coughs (C(5)), respectively. The urge-to-cough was evaluated using the modified Borg scale. RESULTS In capsaicin-induced cough, the cough reflex thresholds, as expressed by C(2) and C(5), in current smokers were significantly higher than those in never-smokers (p<0.01 and p<0.001, respectively). The urge-to-cough log-log slopes in current smokers were significantly lower than those of never-smokers (p<0.001). There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. In cinnamaldehyde-induced cough, there were no significant differences in cough reflex thresholds in C(2) and C(5) between never-smokers and current smokers, nor were there any significant differences in urge-to-cough log-log slope between never-smokers and current smokers. There were no significant differences in the thresholds of the urge-to-cough between never-smokers and current smokers. CONCLUSION The study suggests that smoking has a differential effect on cough responses between TRPV1 and TRPA1 stimulations.

Effects of capsiate on the triggering of the swallowing reflex in elderly patients with aspiration pneumonia

Morbidity and mortality from aspiration pneumonia continue to be major health problems in the elderly. Dysphagia, such as delayed triggering of the swallowing reflex, an important respiratory defense mechanism, predisposes subjects to aspiration pneumonia. Triggering of the swallowing reflex could be accelerated if swallowed material was warmed up, even in dysphagic patients. Moreover, it has been reported that capsaicin accelerated the swallowing reflex in patients with aspiration pneumonia. Because the hot sensation is sensitized through transient receptor potential vanilloid 1 (TRPV1), the results indicate that TRPV1 stimulation together with laryngeal food stimuli accelerate swallowing reflex in the elderly. Although capsaicin is a wellknown and efficient TRPV1 agonist, its pungency is sometimes unacceptable to elderly people. Capsiate is obtained from the non-pungent cultivar of red peppers named CH-19 Sweet. CH-19 Sweet is a fixed cultivar that was selected and cultivated from a pungent cultivar, CH-19, of pepper. Capsiate is known to activate TRPV1, and, despite non-pungency, increases adrenaline secretion and oxygen consumption like capsaicin. Hence, capsiate may have a capability to accelerate the swallowing reflex without inducing a pungent sensation in elderly people. Therefore, we examine herein the effect of capsiate in elderly patients with aspiration pneumonia. Twelve elderly patients with aspiration pneumonia were recruited from those referred and admitted to the Geriatric Unit, Tohoku University Hospital for treatment of pneumonia from May 2006 to April 2007. Pneumonia was diagnosed by the presence of pulmonary infiltration on chest radiograph and computed tomography (CT) and according to systemic inflammation as determined by white blood cell (WBC) count and C-reactive protein (CRP). The criteria for pneumonia were established according to the pneumonia guidelines of the Japanese Respiratory Society. In the current study, aspiration was defined according to the Japanese Study Group on Aspiration Pulmonary Disease as pneumonia in a patient with a predisposition to aspiration because of dysphagia or swallowing disorders. We studied the swallowing reflex in 12 patients (seven men and five women) as they recovered from treatment such as antibiotic drip infusion. Informed consent was obtained from all subjects or their families. The patients fed themselves or needed help in eating. Patients had neither feeding tube nor percutaneous endoscopic gastrostomy. The protocol was approved by the Institutional Review Board of the Tohoku University Ethics Committee and it conformed to the provisions of the Declaration of Helsinki. The swallowing reflex was induced by a bolus injection of 1 mL distilled water into the pharynx through a nasal catheter (8-Fr). The subjects were unaware of the actual injection. Swallowing was identified by sub-mental electromyographic (EMG) activity and/or visual observation of characteristic laryngeal movement. EMG activity was recorded from surface electrodes on the chin. The swallowing reflex sensitivity of elderly patients was evaluated as a latent time of swallowing reflex (LTSR), timed from the injection to the onset of swallowing. Capsiate was extracted from CH-19 Sweet (kind gift from Ajinomoto, Kawasaki, Japan). Harvested chili peppers (CH-19 Sweet) were washed and dried. Then, the crude oil was extracted from the dried chili peppers using n-hexane. The crude oil was refined by distillation and column chromatography. Finally, in order to adjust the concentration, the refined oil was diluted with medium-chain Geriatr Gerontol Int 2010; 10: 107–109