Biomedical subjects

Hiroyuki Ohbayashi

Publications and source records attributed to Hiroyuki Ohbayashi.

10 recordsLinked to original sources

PubMed2006

One-year evaluation of the preventative effect of hydrofluoroalkane-beclomethasone dipropionate on eosinophilic inflammation of asthmatic peripheral airways.

BACKGROUND: In asthmatic patients with eosinophilic inflammation of the peripheral airways, appropriate drug delivery to the affected area is required. OBJECTIVE: It was the aim of this study to assess persistent eosinophilic inflammation of the peripheral airways in asthmatic patients, stabilized by the long-term use of dry powder type inhaled steroids, and to evaluate the clinical efficacy of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) over 1 year. METHODS: Seventy-four outpatients with moderate stable asthma were studied for at least 6 months, 37 treated with fluticasone propionate Diskus (FP-DK) and 37 with budesonide Turbuhaler (BUD-TH). The eosinophil count, eosinophil cationic protein (ECP), eotaxin and RANTES levels in 10% hypertonic saline-induced sputum were examined before treatment, as well as 4 weeks, 8 weeks, 6 months and 1 year after switching patients to HFA-BDP. RESULTS: Fifteen patients (40.5%) in the FP-DK group and 12 (32.4%) in the BUD-TH group had eosinophils in induced sputum. The sputum ECP in the eosinophil-positive and the eosinophil-negative groups was 1,510.1 +/- 2,009.3 versus 426.6 +/- 464.1 microg/l (p = 0.037) in the FP-DK group, and 3,850.0 +/- 5,486.2 versus 492.0 +/- 1,150.7 microg/l (p = 0.011) in the BUD-TH group, respectively. Four weeks after the switch to HFA-BDP, the number of eosinophil-positive patients decreased in both groups. Significant reductions in sputum ECP and eotaxin were observed at 8 weeks, and their concentrations continued decreasing for 1 year. CONCLUSION: There is a certain proportion of asthmatic patients for whom long-term treatment with dry powder type steroids may not be suitable; however, their peripheral airway inflammation improved after switching them to HFA-BDP, suggesting its excellent delivery.

Administration, Inhalation↗

PubMed2006

[Results of a survey questionnaire concerning smoking conditions in 54 major Japanese pharmaceutical companies and among their employees].

BACKGROUND: Despite progress in the prohibition of smoking in many hospitals, some medical representatives (MRs) still visit hospitals smelling of tobacco smoke. As few broad studies of the actual smoking conditions in pharmaceutical companies and among their employees have been conducted, this issue warrants investigation. METHODS: A total of 54 area offices. 155 branch offices, and 4610 employees of 54 major Japanese pharmaceutical companies that conduct business in the Tohno area of Gifu Prefecture were investigated using a questionnaire survey regarding smoking conditions. RESULTS: The results of the survey questionnaire distributed to pharmaceutical companies (response rate, 100.0%) indicated that 12.4% and 43.5% of offices have already prohibited smoking in the entire building or in offices, respectively. In addition, 31.6% of the offices have established separate smoking areas. The results of the individual employee questionnaire (response rate, 98.2%) indicated that 1805 employees (39.9%) smoke (including 1759 male smokers, 44.8%). The smoking rate among MRs (41.0%) was significantly higher than among non-MRs (31.1%) (p< 0.0001), while the smoking rate among managers (42.8%) was also higher than among non-managers (39.1%) (p = 0.0041). Tobacco is most frequently consumed by MRs in their business cars (57.8%) and while driving (42.1%). CONCLUSION: 87.5% of the companies have already established efficacious non-smoking conditions. However, the smoking rate among employees of major Japanese pharmaceutical companies, including MRs, remains high, suggesting that appropriate actions should be taken in order to promote smoking cessation of all smokers.

Adult↗

PubMed2005

Matrix metalloproteinase-9 and airway remodeling in asthma.

Airway remodeling is a major change responsible for irreversible asthmatic airflow restriction. The Th-2 cytokines-dominant eosinophilic inflammatory mechanism cannot fully explain the progressive subepithelial fibrosis and structural changes in the extracellular matrix (ECM). Matrix metalloproteinases (MMPs) are the key enzymes responsible for ECM degradation. MMPs are normally produced and secreted under the tight regulation of, at least, 3 different levels: the gene transcriptional level, the activation of the latent form of enzyme, and the inactivation by specific endogenous inhibitors. In asthmatic condition, as shown by the large amount of accumulated evidence in this review, MMP-9 is the most relevant among the 23 kinds of human MMPs at present detected. Although the mechanism is still under investigation and not accurately known, the imbalance between MMP-9 and tissue inhibitor of metalloproteinase-1 is considered a major theory to explain the progression of asthmatic airway remodeling. Various inflammatory cytokines including TGF beta and growth factors play a pivotal role in MMP-9 production and secretion. This review mainly focuses upon the pivotal role of MMP-9 in airway remodeling, and also upon major cellular source of MMP-9 in asthma such as eosinophils, neutrophils, epithelial cells and alveolar macrophages. This review also refers to the partial contribution of nitric oxide to MMP-9 in asthma.

Animals↗

PubMed2005

[The small airway inflammation of asthmatic patients who have used dry powder type inhaled steroid for moderate-long term evaluated by induced sputum and the efficacy of HFA-BDP (QVAR) inhalation].

UNLABELLED: Although the dry powder type inhaled steroids, such as Fluticasone Propionate Diskhaler (FP-DH), FP Diskus (FP-DK), Budesonide Turbuhaler (BUD-TH), are widely distributed in daily clinical fields, we clinicians are required to evaluate whether it is effectively inhibiting inflammation of distal airway or not. We also investigated the effect of Hydrofluoroalukan-beclomethasone dipropionate (HFA-BDP), a new type of inhaled steroid which forms super micro aerosol particles, in the distal small airway. METHOD: 85 patients with moderate asthma, who daily used dry powder type inhaled steroid for at least more than 6 months with stable asthmatic condition, were the subject of this study. All subjects underwent sputum induction with the inhalation of 10% of hypertonic saline solution for 15 min and eosinophil counts and eosinophil cationic protein (ECP) in individual induced sputum were measured. Then, patients who had eosinophils detected in their induced sputum changed their previously inhaled steroid to HFA-BDP inhalation (400 i.g./day). Their eosinophil counts and the values of eosinophil cationic protein (ECP), Eotaxin, RANTES and neutrophil elastase (PMN-E) in their induced sputum were also examined before and 4weeks after changing HFA-BDP inhalation. RESULT: Increased eosinophils were found in the induced sputum of 40.5% patients of the FP-DK group, 36.3% of the FP-DH group and 32.4% of the BUD-TH group, respectively. Compared with group of patients in which no sputum eosinophil were detected, the sputum ECP values, in which sputum eosinophils were detected, were significantly high. 4 weeks after changing to HFA-BDP inhalation, eosinophil counts, ECP, Eotaxin, RANTES and PMN-E in their induced sputum were decreased in every group. CONCLUSION: Compared with the ordinary dry powder type inhaled steroids, HFA-BDP can effectively diminish distal airway inflammation, suggesting the possibility that HFA-BDP can effectively reach to the distal small airway by forming super micro aerosol particles.

Administration, Inhalation↗

PubMed2005

[A case of severe persistent bronchial asthma who showed significant improvement by switching to hfa-bdp, with reducing the dosage of oral steroids].

A case, 54-year-old female teacher, has been treated for severe persistent asthma mainly with an inhaled corticosteroid, budesonide (BUD), 600 microg/day. The higher dose was considered inappropriate due to the adverse effects including hoarseness, thus, prednisolone (PSL) was frequently given when needed. In this situation, administration of hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP), 400 microg/day, was started instead of BUD, and then improvement of the clinical symptoms, PEF and pulmonary function were observed promptly, followed by reduction in the dosage of PSL and a short-acting beta-stimulant. With higher doses of HFA-BDP, her pulmonary condition improved more remarkably. The levels of ECP, Eotaxin and RANTES in induced sputum obtained by inhalation of 10%-hypertonic saline were measured prior to the medication change and after one year, and all of the levels were found to be decreased, from 19000 to 96.0 microg/L, from 410 to 319 pg/ml, and from 281 to 85.1 pg/ml, respectively, indicating improvement of the condition. The overall score of Asthma Quality of Life Questionnaire by Juniper also improved from 5.3 to 6.6 points after one year. In this case study, it was suggested that HFA-BDP may reduce eosinophilic inflammation remained in the peripheral airway, and may be effective in supplementing the activity of PSL which must be taken orally by severe asthmatic patients.

Administration, Inhalation↗

PubMed2003

[An evaluation of the acceptance of budesonide turbuhaler by older Japanese patients with bronchial asthma when changed from fluticasone propionate (FP) or beclomethasone dipropionate (BDP)].

UNLABELLED: Although the clinical reputation of the inhaled steroid budesonide(R) (BUD) has become well established in Europe and the USA, we found that in clinical practice many older Japanese patients were resistant to changing to this form of inhaled steroid from fluticasone propionate (FP) or beclomethasone dipropionate (BDP). This study was accordingly designed to evaluate the acceptability and clinical efficacy of budesonide in older Japanese patients with bronchial asthma. METHODS: Forty-five Japanese asthma patients aged over 65 (22 using FP and 23 using BDP) were changed to BUD inhalation from their existing inhaled steroid. After two weeks, patients were questioned as to their acceptance of BUD, their inhalation technique was checked, and the duration of inhalation required to dispense the drug and peak expiratory flow (PEF) was measured. The rate of pharyngeal candidiasis was also assessed, both before and after changing to BUD. RESULTS: Most of the patients in both groups considered BUD inhalation to be easy and could quickly learn to use the Turbuhaler. However, as no sensation of drug inhalation was generally experienced, over 70% of patients felt anxious about whether they had successfully inhaled the medication. Furthermore, there were various misunderstandings in correct inhaler technique. Although there were no significant differences in PEF or in the rate of pharyngeal candidiasis before and after changing to BUD administration, side effects occurred in about 40% of both groups. In patients aged 65-74, 50.0% of patients who had previously been taking FP and 38.9% of those who had previously been taking BDP intended to continue BUD inhalation, while in patients over 75, only 8.3% of former users of FP and 20.0% of former users of BDP intended to continue using BUD. CONCLUSION: In older patients, factors influencing satisfaction with inhaled medication include not only ease of use and time needed to become accustomed to a new delivery method, but also the important issue of satisfaction with the sensation of drug inhalation.

Administration, Topical↗

PubMed2002

Neutrophil elastase inhibitors as treatment for COPD.

Chronic obstructive pulmonary disease, characterised by a slowly progressive, irreversible airways limitation, is a major worldwide cause of chronic morbidity and mortality. The imbalance between human neutrophil elastase and endogenous antiproteases may cause excess human neutrophil elastase in pulmonary tissues, which may be considered a major pathogenic factor in chronic obstructive pulmonary disease. Great effort has been devoted to finding a method to restore the balance, resulting in the discovery of potent two-typed small-molecular-weight human neutrophil elastase inhibitors. In the application of chronic obstructive pulmonary disease therapy, the human neutrophil elastase inhibitors mainly focused upon include ONO-5046, MR-889, L-694,458, CE-1037, GW-311616 and TEI-8362 as the acyl-enzyme inhibitors; and ONO-6818, AE-3763, FK-706, ICI-200,880, ZD-0892 and ZD-8321 as the transition-state inhibitors. In this review, various problems that remain to be solved in the clinical use of human neutrophil elastase inhibitors are discussed.

Humans↗

PubMed2002

Matrix metalloproteinases in lung diseases.

Matrix metalloproteinases (MMPs) are a pivotal family of zinc enzymes responsible for degradation of the extracellular matrix (ECM) components including basement membrane collagen, interstitial collagen, fibronectin, and various proteoglycans, during normal remodeling and repair processes. The potent proteolytic activities of MMPs is mainly regulated by the balance with specific tissue inhibitors of Matrix metalloproteinases (TIMP). Excessive or inappropriate expression of MMP may contribute to the pathogenesis of tissue destructive processes in a wide variety of diseases including lung diseases. Although the precise mechanisms are still unknown, the contribution of individual MMPs are worth investigating in seeking the pathogenesis of various lung diseases such as lung cancer, bronchial asthma, chronic obstructive pulmonary disease, acute lung injury, pulmonary hypertension and interstitial lung diseases. In particular, the close association of each lung disease with the destructive effects of gelatinase A and B (also called MMP-2 and MMP-9) on the basement membrane in early alveolar remodeling, and that of collagenase-1 (MMP-1) on the major interstitial structural protein of ECM have received considerable attention. The interaction of MMPs with chemical mediators and inflammatory cytokines has also been reported in some recent studies. Several promising therapeutic approaches to inhibit MMPs have just started in the field of oncology, while more specific MMP inhibitors may be required for further investigation in other fields of lung diseases. In this review, the main focus is on the recent clinical and experimental findings and the contributions of MMPs and/or TIMPs in the lung diseases.

Extracellular Matrix↗

PubMed2002

[The evaluation of the relationship between the residual fluticasone propionate dry powder after inhalation and maximum peak inspiratory flow].

UNLABELLED: We often find some residual Fluticasone propionate (FP) dry powder after using a specialized inhalant instrument (Diskhaler) in daily clinical use. In this study, we evaluated the relationship between residual powder and peak inspiratory flow (PIF), and the therapeutic necessity of using the reductive method of the residual powder. METHOD: 70 patients with bronchial asthma including 18 patients concurrently with COPD were measured for their maximum PIF, the residual dose of FP dry powder and FP content of the residual powder after inhalation. We also investigated effective methods to reduce residual powder. RESULT: The residual powder volume may be dependently affected by maximum PIF. More than 50% residual powder after 1 inhalation occurred in asthmatic patients with a PIF of less than 50 L/min. Discovering almost the same FP content of dry powder residues as before inhalation, we recognized the therapeutic significance of the decreased residual dry powder. Although the method of increased inhalation frequency alone was limited, the combined use of nail-tapping vibration of the Diskhaler and increased inhalation frequency may significantly decrease the residual dry powder. After carrying out the nail-tapping vibration method over 3 months, we obtained significant increases in daily Peak expiratory flow values with no increased pharyngeal Candidiasis. Oral abnormal dry sensation was found in one person as an additional side effect. CONCLUSION: We showed the quantitative evaluation of the relationship between PIF and residual FP dose, while making clear the therapeutic meaning of the reduction of residual powder. Our nail-tapping method may be a clinically effective method to reduce risidual FP dry powder.

Aged↗

PubMed2002

Novel neutrophil elastase inhibitors as a treatment for neutrophil-predominant inflammatory lung diseases.

Acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF) are progressive and frequently fatal disorders, which have, at present, few effective therapeutic methods. The pathogenesis of these lung diseases is characterized by a neutrophil-predominant inflammation associated with excessive release of neutrophil proteases, including neutrophil elastase (NE), a terminal pulmonary tissue destroyer. Although precise pathogenic mechanisms have been under debate, the NE-mediated severe pulmonary tissue damage, based upon the protease-antiprotease imbalance hypothesis, may be a major pathogenic determinant of these diseases, in particular COPD. Novel aggressive therapeutic approaches to these lung disorders are required, and prevention of NE release may be considered as a promising strategy for disease outcome. This review mainly focuses upon the pathogenic contribution of NE to these neutrophil-predominant inflammatory lung diseases, and evaluates the experimental and clinical efficacies of the two-types of appropriate small molecular weight human neutrophil elastase (HNE) inhibitors: acyl-enzyme inhibitors and transition-state inhibitors. While much progress has been made in the investigation of these disorders and the contribution of HNE inhibitors, several fundamental questions remain to be answered, and so further studies are required.

Journal Article↗