Takashi Ohrui

Oral Care Reduces Pneumonia in Older Patients in Nursing Homes

Aspiration of oral secretions and their bacteria is increasingly being recognized as an important factor in pneumonia. We investigated whether oral care lowers the frequency of pneumonia in institutionalized older people.

Interventions to Prevent Pneumonia Among Older Adults

Pneumonia is a common cause of death in older people. Antimicrobial drugs do not prevent pneumonia and, because of increasingly resistant organisms, their value in curing infection will become more limited. Establishing new strategies to prevent pneumonia through consideration of the mechanisms of this devastating illness is essential. The purpose of this review is to discuss how pneumonia develops in older people and to suggest preventive strategies that may reduce the incidence of pneumonia among older adults. Aspiration of oropharyngeal bacterial pathogens to the lower respiratory tract is one of the most important risk factors for pneumonia; impairments in swallowing and cough reflexes among older adults, e.g., related to cerebrovascular disease, increase the risk for the development of pneumonia. Thus, strategies to reduce the volumes and pathogenicity of aspirated material should be pursued. For example, since both swallowing and cough reflexes are mediated by endogenous substance P, pharmacologic therapy using angiotensin‐converting enzyme inhibitors, which decrease substance P catabolism, may improve both reflexes and result in the lowering of the risk of pneumonia. Similarly, since the production of substance P is regulated by dopaminergic neurons in the cerebral basal ganglia, treatment with dopamine analogs or potentiating drugs such as amantadine (and, of course, prevention of cerebral vascular disease, which can result in basal ganglia strokes) should affect the incidence of pneumonia. The purpose of this review is to consider promising pharmacologic treatments as methods of preventing pneumonia in older adults and to review other proven strategies, e.g., infection control and cerebrovascular disease prevention that will lessen the incidence of pneumonia.

Effects of brain-penetrating ACE inhibitors on Alzheimer disease progression.

There is evidence that certain components of the renin-angiotensin system (RAS) may have a crucial role in learning and memory processes.1,2⇓ Angiotensin-converting enzyme (ACE) is overexpressed in the hippocampus, frontal cortex, and caudate nucleus of patients with Alzheimer disease (AD).1 In an animal model with AD, brain-distributing ACE inhibitors are reported to rescue neuronal damage and improve behavior.2 Furthermore, we have shown that brain-penetrating ACE inhibitors can reduce the incidence of AD in elderly hypertensive patients.3 In the present study, we tested the hypothesis that treatment with brain-penetrating ACE inhibitors3 would slow the rate of cognitive decline in mild-to-moderate AD patients with hypertension. We performed a randomized, prospective, parallel group trial with 1-year exposure to study medications. Participants were recruited from three long-term care facilities in Sendai, Japan. Patients eligible for this study had a diagnosis of mild to moderate AD,4,5⇓ were aged 65 years and older, had Mini-Mental State Examination (MMSE) scores within the range of 13 to 23, showed no evidence of stroke; insulin-dependent diabetes mellitus, or other endocrine disorders, or asthma or obstructive pulmonary disease, and had a blood pressure of higher than 140 mm Hg systolic or 90 mm Hg diastolic. The diagnosis of probable AD was made according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria with no clinical or laboratory evidence of a cause other than AD for dementia.5 Brain MRI was obtained in all participants within 3 months prior to the study enrollment to exclude patients with possible or probable vascular dementia and other neurodegenerative dementias. Patients …

Rhinovirus infection of primary cultures of human tracheal epithelium: role of ICAM-1 and IL-1β

Exacerbations of asthma are often associated with respiratory infection caused by rhinoviruses. To study the effects of rhinovirus infection on respiratory epithelium, a primary target for respiratory viruses, human rhinovirus (HRV)-2 and HRV-14 were infected to primary cultures of human tracheal epithelial cells. Viral infection was confirmed by showing that viral titers of supernatants and lysates from infected cells increased with time and by polymerase chain reaction. HRV-2 and HRV-14 infections upregulated the expression of intercellular adhesion molecule-1 (ICAM-1) mRNA, the major rhinovirus receptor, on epithelial cells, and they increased the production of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in supernatants. Antibodies to ICAM-1 inhibited HRV-14 infection of epithelial cells and decreased the production of cytokines after HRV-14 infection, but they did not alter HRV-2 infection-induced production of cytokines. IL-1β upregulated ICAM-1 mRNA expression and increased susceptibility to HRV-14 infection, whereas other cytokines failed to alter ICAM-1 mRNA expression. Furthermore, a neutralizing antibody to IL-1β significantly decreased viral titers of supernatants and ICAM-1 mRNA expression after HRV-14 infection, but a neutralizing antibody to TNF-α was without effect. Immunohistochemical studies revealed that both HRV-14 infection and IL-1β increased ICAM-1 expression on cultured epithelial cells. These findings imply that HRV-14 infection upregulated ICAM-1 expression on epithelial cells through increased production of IL-1β, thereby increasing susceptibility to infection. These events may be important for amplification of airway inflammation after viral infection in asthma.

Risk Factors of Aspiration Pneumonia in Alzheimer’s Disease Patients

Background: Pneumonia is the reported cause of death of a high proportion of Alzheimer’s disease (AD) patients. Objectives: This study assessed swallowing function to explore the potential risk factors of aspiration pneumonia in AD patients. Methods: Data were gathered on 121 AD patients (mean age 78.2, SD 7.5, male/female ratio = 48/73) treated in two psychiatric hospitals. Multiple logistic regression analysis was used to estimate odds ratios for the risk of aspiration pneumonia. The following risk factors were considered: age, severity of dementia, silent brain infarction (SBI) in the basel ganglia, use of psychotropic drugs (neuroleptics and benzodiazepines), and gender. The latency time of the swallowing reflex was analyzed (1) among groups based on the severity of dementia; (2) between groups with and without SBI in the basal ganglia; (3) before and after the use of psychotropic drugs in the group without SBI in the basal ganglia, and (4) between males and females. Results: Aspiration pneumonia in ambulatory AD patients was significantly and independently associated with severe dementia, presence of SBI in the basal ganglia, intake of neuroleptics, and the male gender. The mean latency of the swallowing reflex in the severe AD group was significantly longer compared to that in the mild-to-moderate AD group. The mean latency of the swallowing reflex after the intake of neuroleptics was significantly prolonged compared to that obtained before any neuroleptic intake, whereas there was no significant difference in the mean latency of the swallowing reflex before and after benzodiazepine intake. Conclusion: We recommend the use of the smallest efficacious dosage of neuroleptics especially in treating severely demented AD patients with basal-ganglia infarction. As soon as the behavioral and psychiatric problems are resolved, drug tapering or discontinuation should be considered in order to prevent life-threatening aspiration pneumonia.

Adiponectin in plasma and cerebrospinal fluid in MCI and Alzheimer's disease.

Background and purpose:  Life style‐related disorders such as hypertension, diabetes, dyslipidemia, and obesity are reported to be a great risk of dementia. Adipocytokines released from adipose tissue are thought to modulate some brain functions including memory and cognition. We here analysed adiponectin, one of the most important adipocytokines, in plasma and cerebrospinal fluid (CSF) from cognitive normal controls (NC), mild cognitive impairment (MCI) subjects, and patients with Alzheimer’s disease (AD) and discussed if/how adiponectin could relate to the pathogenesis of AD.

Increased blood carboxyhaemoglobin concentrations in inflammatory pulmonary diseases.

Background: Exhaled carbon monoxide has been reported to increase in inflammatory pulmonary diseases and to be correlated with blood carboxyhaemoglobin (Hb-CO) concentration. A study was undertaken to determine whether arterial blood Hb-CO increases in patients with inflammatory pulmonary diseases. Methods: The Hb-CO concentration in arterial blood was measured with a spectrophotometer in 34 normal control subjects, 24 patients with bronchial asthma, 52 patients with pneumonia, and 21 patients with idiopathic pulmonary fibrosis (IPF). Results: The mean (SE) Hb-CO concentrations in patients with bronchial asthma during exacerbations (n=24, 1.05 (0.05)%), with pneumonia at the onset of illness (n=52, 1.08 (0.06)%), and with IPF (n=21, 1.03 (0.09)%) were significantly higher than those in control subjects (n=34, 0.60 (0.07)%) (mean difference 0.45% (95% confidence interval (CI) 0.23 to 0.67), p<0.01 in patients with bronchial asthma, mean difference 0.48% (95% CI 0.35 to 0.60), p<0.0001 in patients with pneumonia, and mean difference 0.43% (95% CI 0.26 to 0.61) p<0.001 in patients with IPF). In 20 patients with bronchial asthma the Hb-CO concentration decreased after 3 weeks of treatment with oral glucocorticoids (p<0.001). In 20 patients with pneumonia the Hb-CO concentration had decreased after 3 weeks when patients showed evidence of clinical improvement (p<0.001). The values of C-reactive protein (CRP), an acute phase protein, correlated with Hb-CO concentrations in patients with pneumonia (r=0.74, p<0.0001) and in those with IPF (r=0.46, p<0.01). In patients with bronchial asthma changes in Hb-CO concentrations were significantly correlated with those in forced expiratory volume in 1 second (FEV1) after 3 weeks (r=0.67, p<0.01). Exhaled carbon monoxide (CO) concentrations were correlated with Hb-CO concentrations (n=33, r=0.80, p<0.0001). Conclusions: Hb-CO concentrations are increased in inflammatory pulmonary diseases including bronchial asthma, pneumonia, and IPF. Measurement of arterial Hb-CO may be a useful means of monitoring pulmonary inflammation.

A Randomized, Single-Blind Study of Lansoprazole for the Prevention of Exacerbations of Chronic Obstructive Pulmonary Disease in Older Patients

OBJECTIVES: To investigate whether proton pump inhibitor (PPI) therapy reduces the frequency of common colds and exacerbations in patients with chronic obstructive pulmonary disease (COPD).

ACE inhibitors and protection against pneumonia in elderly patients with stroke

Pneumonia is the most common cause of death from nosocomial infection in the elderly. The increased incidence of pneumonia and the high mortality are consequences of a number of age-related factors, including coexisting illnesses, therapeutic interventions, and the aging process itself.1 Pneumonia has been estimated to occur in about one third of patients with stroke.2 The most important factor contributing to the risk of pneumonia in patients with stroke is suggested to be dysphagia with aspiration.1 Angiotensin-converting enzyme (ACE) inhibitors have been shown to improve silent aspiration3 and prevent pneumonia in elderly patients with stroke.4 However, little is known about whether ACE inhibitors have a beneficial role in reducing the risk of pneumonia as compared to other classes of antihypertensive drugs in elderly patients with stroke. Thus, we investigated whether ACE inhibitors can reduce the risk of pneumonia …

Prevention of severe premenstrual asthma attacks by leukotriene receptor antagonist.

BACKGROUND The etiology and treatment of premenstrual exacerbations of asthma (PMA) remain uncertain. OBJECTIVE We investigated the role of cellular mediators released from inflammatory cells in the airflow limitation during PMA. METHODS Serum levels of leukotriene (LT) B(4), LTC(4), platelet- activating factor, histamine, IL-1beta, IL-4, IL-5, IL-6, and GM-CSF were measured at different time points, first just before or during menstruation when the peak expiratory flow rate (PEFR) began to decrease precipitously and second during the menstrual midcycle week (days 10-16) when the PEFR returned to baseline values in patients with PMA and in age-matched asthma patients without PMA at the same intervals. RESULTS Serum levels of LTC(4) were significantly higher during exacerbations of asthma than after recovery (69.0 +/- 16.0 pg/mL vs 24.0 +/- 9.5 pg/mL, P <.05), whereas those of IL-1beta, IL-4, IL-5, IL-6, GM-CSF, histamine, LTB(4), and platelet-activating factor did not differ between 2 periods in 5 patients with PMA. In contrast, in 5 asthmatic patients without PMA serum levels of cellular mediators did not differ between corresponding periods. Oral administration of pranlukast, an LT receptor antagonist (225 mg twice daily), significantly reduced decreases in PEFR from the baseline values (110 +/- 21 L/min with pranlukast vs 233 +/- 20 L/min without pranlukast, P <.01) in association with an improvement of asthma symptom scores (6.5 +/- 1. 1 with pranlukast vs 9.8 +/- 0.7 without pranlukast, P <0.05) in 5 patients with PMA. CONCLUSION LTs are partly involved in the pathogenesis of PMA, and LT receptor antagonists may be useful for preventing airflow obstruction in patients with PMA.