[Airway inflammation in COPD].
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Bronchi↗
Biomedical subjects
M Yamaya
Publications and source records attributed to M Yamaya.
Relation between exhaled carbon monoxide levels and clinical severity of asthma.
Carbon monoxide (CO) can be detected in exhaled air and is increased in asthmatic patients not treated with corticosteroids. However, it is uncertain whether exhaled CO is related to severity of asthma. To study whether exhaled CO is related to severity of asthma in clinical courses, exhaled CO concentrations were measured on a CO monitor by vital capacity manoeuvre in 20 mild asthmatics treated with inhaled beta2-agonists alone, 20 moderate asthmatics treated with inhaled corticosteroids, and 15 stable asthmatics treated with high dose inhaled corticosteroids and oral corticosteroids once a month over 1 years. Exhaled CO concentrations were also measured in 16 unstable severe asthmatics who visited the hospital every 7 or 14 days for treatment with high dose inhaled corticosteroids and oral corticosteroids. The mean values of exhaled CO in severe asthma over 1 year were 6.7 +/- 9.5 p.p.m. (n = 31, mean +/- SD) and significantly higher than those of non-smoking control subjects (1.2 +/- 0.9 p.p.m., n = 20, P < 0.01). Exhaled CO concentrations in unstable severe asthmatics were significantly higher than those in stable severe asthmatics. However, exhaled CO concentrations in mild and moderate asthmatics did not differ significantly from those in non-smoking control subjects (P > 0.20). There was a significant relationship between the exhaled CO concentrations and forced expiratory volume in one second in all asthmatic patients. These findings suggest that exhaled CO concentrations may relate to the severity of asthma and measurements of exhaled CO concentrations may be a useful means of monitoring airway inflammation in asthma.
Adult↗
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.
Aged↗
Antithrombotic therapy for prevention of pneumonia.
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Aged↗
Type 2 rhinovirus infection of cultured human tracheal epithelial cells: role of LDL receptor.
To examine the role of the low-density lipoprotein (LDL) receptor on minor group human rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with a minor group (RV2) or a major group (RV14) RV. Viral infection was confirmed by showing with PCR that viral titers in supernatants and lysates from infected cells increased with time. RV2 and RV14 increased expression of mRNA and protein of the LDL receptor on the cells and the cytokine production. RV2 induced activation of transcription factors SP1 and nuclear factor-kappaB (NF-kappaB). An antibody to the LDL receptor inhibited RV2 infection and RV2-induced cytokine production without an effect on RV14 infection and RV14-induced cytokine production. These findings imply that RV2 upregulates LDL receptor expression on airway epithelial cells, thereby increasing susceptibility to minor group RV infection. LDL receptor expression and cytokine production may be mediated, in part, via activation of transcription factors by RV2. These events may be important in airway inflammation after minor group RV infection in asthma.
Aged↗
Bafilomycin A(1) inhibits rhinovirus infection in human airway epithelium: effects on endosome and ICAM-1.
To examine the effects of bafilomycin A(1), a blocker of vacuolar H(+)-ATPase, on rhinovirus (RV) infection in the airway epithelium, primary cultures of human tracheal epithelial cells were infected with RV14. Viral infection was confirmed by showing that viral RNA in the infected cells and the viral titers in the supernatants of infected cells increased with time. RV14 infection upregulated the production of cytokines and mRNA of intercellular adhesion molecule (ICAM)-1 in epithelial cells. Bafilomycin A(1) reduced the viral titers of RV14 and inhibited the production of cytokines and ICAM-1 before and after RV14 infection. Bafilomycin A(1) reduced susceptibility of epithelial cells to RV14 infection. RV14 increased activated nuclear factor-kappaB in the cells, and bafilomycin A(1) reduced the activated nuclear factor-kappaB. Bafilomycin A(1) decreased the number of acidic endosomes in the epithelial cells. These results suggest that bafilomycin A(1) may inhibit infection by RV14 by not only blocking RV RNA entry into the endosomes but also reducing ICAM-1 expression in the epithelial cells. Bafilomycin A(1) may therefore modulate airway inflammation after RV infection.
Amiloride↗
Acid exposure stimulates the adherence of Streptococcus pneumoniae to cultured human airway epithelial cells: effects on platelet-activating factor receptor expression.
To examine the effects of acid exposure on the adherence of Streptococcus pneumoniae to cultured human tracheal epithelial cells, cells were exposed to acid at various pH levels, and various concentrations of S. pneumoniae were added to the culture medium. The number of S. pneumoniae adhering to cultured human tracheal epithelial cells increased after acid exposure. Y-24180, a specific inhibitor of the receptor for the platelet-activating factor (PAF) and PAF itself decreased the number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the activation of transcription factor nuclear factor (NF)-kappa B and the expression of protein and messenger RNA (mRNA) of the PAF receptor. The pyrrolidine derivative of dithiocarbamate (PDTC), an inhibitor of NF-kappa B, also decreased the number of S. pneumoniae adhering to the cultured human tracheal epithelial cells after acid exposure. Acid exposure increased the content of interleukin (IL)-1 alpha and IL-1 beta in the culture supernatants, but monoclonal antibodies to IL-1 alpha and IL-1 beta failed to inhibit the increased number of S. pneumoniae adhering to cultured human tracheal epithelial cells after acid exposure. These findings suggest that acid exposure stimulates the adherence of S. pneumoniae to the airway epithelial cells via increases in PAF receptors. Increases in PAF receptor expression may be, in part, mediated via activation of transcription factors and subsequent PAF receptor mRNA expression by acid exposure. Increased adherence of S. pneumoniae may be one of the reasons why pneumonia develops after gastric juice aspiration.
Aged↗
"Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases", summary of the ERS Research Seminar in Budapest, Hungary, September, 1999.
In recent years, there has been increasing interest in noninvasive monitoring of airway inflammation and oxidative stress. Several volatile and nonvolatile substances can be measured in exhaled breath and have been suggested as potential biomarkers of these events. Exhaled gases, including carbon monoxide (CO), alkanes (ethane, pentane), and substances measured in breath condensate, such as hydrogen peroxide (H2O2) and isoprostanes were all suggested as potential markers of oxidative stress in the lung. A European Respiratory Society (ERS) International Research Seminar entitled "Haemoxygenase-1 induction and exhaled markers of oxidative stress in lung diseases" was organized by the Airway Regulation and Provocation Group of the Clinical Allergy and Immunology Assembly in Budapest, Hungary in September, 1999 to integrate the latest knowledge on these issues and accelerate further improvement in this area. During this 2-day event several issues were raised about: the use and standardization of measurements in exhaled breath; problems of measuring expired H2O2 and other mediators in breath condensate; role and regulation of haemoxygenase (HO)-1 in the lung; and conditions and factors influencing exhaled CO. This report is a summary of the main presentations at the seminar, together with the current areas of research in this rapidly expanding field.
Antioxidants↗
Erythromycin and common cold in COPD.
STUDY OBJECTIVES: To investigate whether erythromycin therapy lowers the frequency of the common cold and subsequent exacerbation in patients with COPD. DESIGN: Prospective, randomized, controlled, but not blinded, trial. PATIENTS: One hundred nine patients with COPD were enrolled into the study. Patients were randomly assigned to erythromycin therapy or to no active treatment in September 1997. Patients then were observed for 12 months, starting in October, during which time the risk and frequency of catching common colds and COPD exacerbations were investigated. Fifty-five patients received erythromycin at study entry (erythromycin group). The remaining 54 patients received no active treatment (control group). MEASUREMENTS AND RESULTS: The mean (+/- SE) number of common colds for 12 months was significantly lower in the erythromycin group than in the control group (1.24 +/- 0.07 vs 4.54 +/- 0.02, respectively, per person; p = 0.0002). Forty-one patients (76%) in the control group experienced common colds more than once, compared to 7 patients (13%) in the erythromycin group. The relative risk of developing two or more common colds in the control group compared with that in the erythromycin group was 9.26 (95% confidence interval [CI], 3.92 to 31.74; p = 0.0001). Thirty patients (56%) in the control group and 6 patients (11%) in the erythromycin group had one or more exacerbations. The relative risk of experiencing an exacerbation in the control group compared with that in the erythromycin group was 4.71 (95% CI, 1.53 to 14.5; p = 0.007). Significantly more patients were hospitalized due to exacerbations in the control group than in the erythromycin group (p = 0.0007). CONCLUSION: Erythromycin therapy has beneficial effects on the prevention of exacerbations in COPD patients.
Aged↗
[Detection of exhaled CO as a simple non-invasive tool for monitoring acute exacerbations of asthma in the elderly].
Exhaled carbon monoxide (CO) concentrations were measured on a CO monitor by vital capacity maneuvers in asthmatic patients either receiving or not receiving inhaled corticosteroids, and in nonsmoking healthy control subjects. CO was detectable and measured reproducibly in the exhaled air of all subjects. The exhaled CO concentrations were higher in asthmatic patients not receiving inhaled corticosteroids and similar in asthmatic patients receiving inhaled corticosteroids and nonsmoking healthy control subjects (Am J Respir Crit Care Med 1997: 156: 1140-1143). All patients with inhaled corticosteroid treatment had reductions in exhaled CO concentration and eosinophil cell counts in sputum that were accompanied by an amelioration of airway obstruction. These results showed that detection of exhaled CO could be a simple non-invasive tool for monitoring airway inflammation and acute exacerbation of asthma.
Aged↗
Depressive state and common cold.
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Aged↗
A rockwool fibre worker with lung fibrosis.
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Aged↗
Microsatellite polymorphism in the heme oxygenase-1 gene promoter is associated with susceptibility to emphysema.
Cigarette smoke, containing reactive oxygen species, is the most important risk factor for chronic pulmonary emphysema (CPE). Heme oxygenase-1 (HO-1) plays a protective role as an antioxidant in the lung. A (GT)n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and could modulate the level of gene transcription. To investigate the correlation between the length of the (GT)n repeat and susceptibility to the development of CPE, we screened the frequencies of alleles with varying numbers of (GT)n repeats in the HO-1 gene in 101 smokers with CPE and in 100 smokers without CPE. Polymorphisms of the (GT)n repeat were grouped into three classes: class S alleles (<25 repeats), class M alleles (25-29 repeats), and class L alleles (>/=30 repeats). The proportion of allele frequencies in class L, as well as the proportion of genotypic frequencies in the group with class L alleles (L/L, L/M, and L/S), was significantly higher in the smokers with CPE than in smokers without CPE. Moreover, we analyzed the promoter activities of the HO-1 gene carrying different (GT)n repeats (n=16, 20, 29, and 38), by transient-transfection assay in cultured cell lines. H2O2 exposure up-regulated the transcriptional activity of the HO-1 promoter/luciferase fusion genes with (GT)16 or (GT)20 but did not do so with (GT)29 or (GT)38. These findings suggest that the large size of a (GT)n repeat in the HO-1 gene promoter may reduce HO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting in the development of CPE.
Aged↗
Effects of dexamethasone on rhinovirus infection in cultured human tracheal epithelial cells.
To examine the effects of glucocorticoid on rhinovirus (RV) infection, primary cultures of human tracheal epithelial cells were infected with either RV2 or RV14. Viral infection was confirmed by demonstrating that viral RNA in infected cells and viral titers of supernatants and lysates from infected cells increased with time. RV14 infection upregulated the expression of mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, on epithelial cells, and it increased the production of interleukin (IL)-1beta, IL-6, IL-8, and tumor necrosis factor-alpha in supernatants. Dexamethasone reduced the viral titers of supernatants and cell lysates, viral RNA of infected cells, and susceptibility of RV14 infection in association with inhibition of cytokine production and ICAM-1 induction. In contrast to RV14 infection, dexamethasone did not alter RV2 infection, a minor group of RVs. These results suggest that dexamethasone may inhibit RV14 infection by reducing the surface expression of ICAM-1 in cultured human tracheal epithelial cells. Glucocorticoid may modulate airway inflammation via reducing the production of proinflammatory cytokines and ICAM-1 induced by rhinovirus infection.
Aged↗
Cough syncope treated with imidapril in an elderly patient with dysphagia.
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Aged↗
[The pathogenesis and therapy of virus infection-induced senile bronchial asthma].
We investigated the pathogenesis and therapy of virus infection-induced senile bronchial asthma in vitro. To examine the effects of rhinovirus infection on the production of cytokines and intercellular adhesion molecule-1 (ICAM-1), human tracheal epithelial cells and submucosal gland cells were cultured, and infected with human rhinovirus. Rhinovirus upregulated the production of interleukin (IL)-1 beta, IL-6, IL-8, tumor necrosis factor (TNF)-alpha in supernatants of epithelial cells and submucosal-gland cells, and IL-1 alpha and granulocyte macrophage colony-stimulating factor (GM-CSF) in supernatants of submucosal gland cells. Rhinovirus upregulated the expression of ICAM-1 mRNA. Rhinovirus infection also increased epithelial permeability. These events may be important for the spread of airway inflammation after rhinovirus infection. Furthermore, we studied the effects of dexamethasone and erythromycin on the modulation of virus infection and induction of cytokines and ICAM-1 in tracheal epitherial cells. Both of them reduced viral titers of rhinovirus type 14, a major group rhinovirus, and cytokine production of supernatants, and ICAM-1 mRNA expression in the cells. Because it is known that acidic conditions by proton pumps are needed for rhinovirus entry into the cells, we studied the effects of H+ ATPase inhibitor bafilomycin A1. Bafilomycin A1 reduced the virus titers of both rhinovirus type 2 and 14 in supernatants. These findings in our in vitro study suggest that dexamethasone, erythromycin and bafilomycin A1 may inhibit rhinovirus infection and modulate airway inflammation induced by rhinovirus infection.
Aged↗
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.
Adolescent↗
Kinin and histamine stimulate Cl- secretion in gerbil middle ear epithelium: connection to otitis media.
The effects of bradykinin (BK) and histamine on transepithelial ion transport in primary cultures of gerbil middle ear epithelium were investigated. Lysyl-bradykinin (lys-BK) elicited a transient increase in short-circuit current (I(sc)) when added to apical or basolateral surfaces. Lys-BK had a larger effect than BK or des-arg9-BK on both epithelial surfaces. Histamine induced a transient increase in I(sc) only when added to the basolateral surface. Mepyramine, an H1 histamine antagonist, greatly reduced the histamine-induced I(sc). The H2 and H3 histamine antagonists were both ineffective for inhibiting the I(sc) responses to histamine. Diphenylamine-2-carboxylate or 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid, Cl- channel blockers, significantly blocked the I(sc) responses to lys-BK or histamine. The Ca2+-mobilizing action of lys-BK and histamine was also investigated in single middle ear epithelial cells. BK and histamine induced an increase in the intracellular Ca2+ concentration. 1,2-Bis-(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester, a calcium chelator, greatly reduced the increase in the I(sc) responses to lys-BK or histamine. These data indicate that BK and histamine activate intracellular Ca2+-dependent mechanisms, leading to apical Cl- secretion in the cultured gerbil middle ear epithelium via B2 BK receptors and H1 histamine receptors.
Animals↗