Effects of a synthetic protease inhibitor (gabexate mesilate) and a neutrophil elastase inhibitor (sivelestat sodium) on acid-induced lung injury in rats

The present study was designed to examine the combined effects of a synthetic protease inhibitor, gabexate mesilate, with a specific neutrophil elastase inhibitor, sivelestat sodium, on acid-induced lung injury. Adult male Sprague-Dawley rats weighing 300-350 g were anaesthetised intraperitoneally with pentobarbitone sodium and the right jugular vein was cannulated. Following tracheostomy, rats were ventilated mechanically and underwent intratracheal instillation of hydrochloric acid (HCl, 0.1 N 1.5 ml/kg) or normal saline. Gabexate mesilate (10 mg/kg, i.p.) and/or sivelestat sodium (10 mg/kg/h, i.v.) were administered 30 min before HCl instillation. Bronchoalveolar lavage fluid samples were obtained 5 h after HCl instillation. in bronchoalveolar lavage fluid, the HCl-induced increases in total nucleated cell counts, neutrophil counts, optical density at 412 nm as an index of pulmonary haemorrhage, concentrations of albumin and cytokine-induced neutrophil chemoattractant (CINC) were significantly attenuated by either gabexate mesilate or sivelestat sodium treatment. Gabexate mesilate or sivelestat sodium treatment also significantly attenuated the wet to dry weight ratio induced by HCl. However, combined treatment with both gabexate mesilate and sivelestat sodium did not show additive effects on HO-induced lung injury, compared with single treatments. These findings suggested that gabexate mesilate and sivelestat sodium each exhibited protective effects on acid-induced lung injury, but that synergistic effects of both agents are limited in this acid-induced lung injury model.ArticleEUROPEAN JOURNAL OF PHARMACOLOGY. 641(2-3):220-225 (2010)journal articl

Sputum eosinophilia can predict responsiveness to inhaled corticosteroid treatment in patients with overlap syndrome of COPD and asthma

Background: Chronic obstructive pulmonary disease (COPD) and asthma may overlap and converge in older people (overlap syndrome). It was hypothesized that patients with overlap syndrome may have different clinical characteristics such as sputum eosinophilia, and better responsiveness to treatment with inhaled corticosteroid (ICS). Methods: Sixty-three patients with stable COPD (forced expiratory volume in 1 second [FEV1] <= 80%) underwent pulmonary function tests, including reversibility of airflow limitation, arterial blood gas analysis, analysis of inflammatory cells in induced sputum, and chest high-resolution computed tomography. The inclusion criteria for COPD patients with asthmatic symptoms included having asthmatic symptoms such as episodic breathlessness, wheezing, cough, and chest tightness worsening at night or in the early morning (COPD with asthma group). The clinical features of COPD patients with asthmatic symptoms were compared with those of COPD patients without asthmatic symptoms (COPD without asthma group). Results: The increases in FEV1 in response to treatment with ICS were significantly higher in the COPD with asthma group. The peripheral eosinophil counts and sputum eosinophil counts were significantly higher. The prevalence of patients with bronchial wall thickening on chest high-resolution computed tomography was significantly higher. A significant correlation was observed between the increases in FEV1 in response to treatment with ICS and sputum eosinophil counts, and between the increases in FEV1 in response to treatment with ICS and the grade of bronchial wall thickening. Receiver operating characteristic curve analysis revealed 82.4% sensitivity and 84.8% specificity of sputum eosinophil count for detecting COPD with asthma, using 2.5% as the cutoff value. Conclusion: COPD patients with asthmatic symptoms had some clinical features. ICS should be considered earlier as a potential treatment in such patients. High sputum eosinophil counts and bronchial wall thickening on chest high-resolution computed tomography might therefore be a good predictor of response to ICS.ArticleINTERNATIONAL JOURNAL OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. 7:283-289 (2012)journal articl

Comparison of acid-induced inflammatory responses in the rat lung during high frequency oscillatory and conventional mechanical ventilation

The present study was performed to compare the effects of high frequency oscillatory ventilation (HFOV) with conventional mechanical ventilation (CMV) on pulmonary inflammatory responses in a rat acid-induced lung injury model. Anesthetized rats were instilled intratracheally with HCl (0.1 N, 2 mL/kg) and then randomly divided into three mechanical ventilation settings: HFOV (an oscillatory frequency of 15 Hz, mean airway pressure (MAP) of 9 cmH(2)O), CMV at tidal volume of 12 and 6 mL/kg for 5 h. After HCl instillation, HFOV significantly attenuated the increases in neutrophil infiltration and TNF-alpha concentration in bronchoalveolar lavage fluid compared with the CMV groups. During HFOV, there was an inhibition of an increase in TNF-alpha mRNA expression and a decrease in SP-A mRNA expression induced by acid instillation. This animal study demonstrates that HFOV is a suitable form of mechanical ventilation to prevent inflammatory responses in acid-induced lung injury.ArticleINFLAMMATION RESEARCH. 59(11):931-937 (2010)journal articl

Clinical characteristics of combined pulmonary fibrosis and emphysema

The definitive version is available at www.blackwell-synergy.comBackground and objective: Patients with combined pulmonary fibrosis and emphysema (CPFE) are sometimes seen, and we speculate that these patients have some different clinical characteristics from COPD patients. This study clarifies the clinical characteristics of CPFE patients. Methods: This was a retrospective study of 47 stable patients with concurrent emphysema and diffuse parenchymal lung disease with fibrosis, based on the findings of chest CT (CPFE patients). The clinical characteristics of CPFE patients were compared with those of emphysema-dominant COPD patients without parenchymal lung disease (COPD patients). Results: Forty-six of the 47 CPFE patients were male. Paraseptal emphysema was particularly common in the CPFE group. Honeycombing, ground-glass opacities and reticular opacities were present in 75.6%, 62.2% and 84.4% of CPFE patients, respectively. Twenty-two of the 47 CPFE patients (46.8%) had lung cancer. Pulmonary function tests showed that the CPFE group had milder airflow limitation and lower diffusing capacity than the COPD group. Desaturation during 6-min walking test in CPFE patients tended to be more severe than in COPD patients, if the level of FEV1 or 6MWD was equal. Conclusions: CPFE patients had some different clinical characteristics in comparison with COPD patients and may also have a high prevalence of lung cancer.ArticleRESPIROLOGY. 15(2):265-271 (2010)journal articl

Diffuse Endobronchial Wall Spread of Metastatic Breast Cancer

We present here a case of diffuse tracheobronchial wall spread of metastatic breast cancer who was successfully treated with trastuzumab plus vinorelbine chemotherapy. The patient had a left radical mastectomy for breast cancer in March 2000 and developed persistent cough and dyspnea in November 2006. Pulmonary function test demonstrated an obstructive pattern. Chest computed tomography showed a wall thickening of trachea and right side bronchus, but radiographic findings including 18F-fluorodeoxyglucose positron emission tomography failed to detect the locations of disease in the lung. The findings on bronchofiberscopy showed edematous tracheobronchial mucosa, but also failed to visually detect direct masses. Transbronchial biopsy specimens revealed involvement of metastatic breast cancer. The patient was treated with trastuzumab plus vinorelbine chemotherapy and the wall thickening of bronchial tree and clinical symptoms were improved. Although endobronchial metastasis in metastatic breast cancer is not uncommon, diffuse spread without forming intraluminal mass is extremely rare. The pattern of endobronchial metastasis should be considered in patients with malignancies even when radiographic abnormalities are undetectable

Usefulness of the Measurement of Fractional Exhaled Nitric Oxide in Asthmatic Patients :Correlation with Pulmonary Function, Asthma Control and Health Status

Background and objective:This study was conducted to investigate whether or not FeNO correlates with lung function tests, the Asthma Control Test (ACT) for assessing asthma control or the Asthma Health Questionnaire (AHQ-33) for evaluating the health status in asthmatics. Methods :FeNO was compared with the results of spirometry,ACT and AHQ-33 in 57 non-smoking patients with asthma and 17 healthy individuals without pulmonary diseases who had never smoked. Sixteen of 57 asthmatics treated with inhaled corticosteroid (ICS)underwent step-down therapy if they showed good/total control or step-up therapy if they showed poor control, and were evaluated by spirometry, ACT and AHQ- 33 prior to and more than one month after starting step-down or step-up therapy. Results :FeNO in asthmatics was significantly higher than that in the control group.There were no significant correlations between FeNO and FEV1, ACT score or AHQ-33 scores. However, there were significant correlations between the changes in FeNO and changes in FEV1, ACT score or AHQ-33 scores following stepdown or step-up therapy. Conclusion :FeNO is a useful marker not only for the diagnosis of asthma but also for asthma control and determining the health status in an individual patient, although it is variable without any correlation with symptoms and lung function among asthmatics. Shinshu Med J 59 : 239 ―247, 2011Article信州医学雑誌 59(4): 239-247(2011)departmental bulletin pape

Annual changes in pulmonary function in combined pulmonary fibrosis and emphysema: Over a 5-year follow-up

Background: Combined pulmonary fibrosis and emphysema (CPFE) is a unique disorder that has been previously described, and the distinct features of CPFE in comparison with chronic obstructive pulmonary disease (COPD) have been reported. However, the yearly dynamics of pulmonary function parameters in CPFE patients compared with those in COPD patients have not yet been reported. Methods: We retrospectively enrolled patients with CPFE and COPD who had undergone pulmonary function tests more than five times during a follow-up period of more than five years. The baseline clinical characteristics and the annual changes in pulmonary function during the follow-up period in 16 stable CPFE patients were compared with those in 19 stable COPD patients. Annual changes in pulmonary function were estimated from linear regressions, with assumptions for time-dependency and linearity. We analyzed the time-dependent fluctuations in pulmonary function for the two disorders. Results: Annual decreases in VC and FVC in the CPFE group were significantly higher than those in the COPD group. Annual decrease in FEV1/FVC in the COPD group was significantly higher than in the CPFE group. During the follow-up period, FEV1/FVC in the CPFE group appeared to improve because of annual decrease in FVC. Annual decreases in DLco and DLco/VA in the CPFE group were significantly higher than those in the COPD group. Conclusion: This is the first report showing the yearly dynamics of pulmonary function parameters in CPFE patients compared with those in COPD patients during a follow-up period of more than five years. This study revealed that the physiologic consequences of CPFE including the rate of progression of pulmonary function impairment were different from those of COPD. (C) 2013 Elsevier Ltd. All rights reserved.ArticleRESPIRATORY MEDICINE. 107(12):1986-1992 (2013)journal articl

Additive efficacy of short-acting bronchodilators on dynamic hyperinflation and exercise tolerance in stable COPD patients treated with long-acting bronchodilators

The purpose of this study was to clarify the additive efficacy of short-acting beta(2)-agonists (SABA) or muscarinic antagonists (SAMA) on dynamic hyperinflation and exercise tolerance in patients with chronic obstructive pulmonary disease (COPD) who had been treated with long-acting bronchodilators. Thirty-two patients with stable COPD who had been treated with long-acting bronchodilators, including long-acting muscarinic antagonists (LAMA), were examined by pulmonary function tests, dynamic hyperinflation evaluated by the method of step-wise metronome-paced incremental hyperventilation, and the incremental shuttle walking test before and after inhalation of SABA or SAMA. The additive efficacy of the two drugs was analyzed. Inhalation of SABA and SAMA improved airflow limitation and dynamic hyperinflation in stable COPD patients who had been treated with LAMA. Inhalation of SABA decreased respiratory resistance and the difference in respiratory resistance at 5 Hz and 20 Hz. On the whole, the additive efficacy of SABA on airflow limitation and dynamic hyperinflation was superior to that of SAMA. Furthermore, inhalation of SABA resulted in relief of breathlessness during exercise and significant improvement in exercise capacity. Inhalation of SABA resulted in significant improvement in exercise tolerance, which may have been due to improvement in dynamic hyperinflation. Single use of SABA before exercise, in addition to regular treatment with LAMA, may therefore be useful in stable COPD patients.ArticleRESPIRATORY MEDICINE. 107(3):394-400 (2013)journal articl

Clinical characteristics and outcomes of patients with small cell lung cancer detected by CT screening

The present study was performed to evaluate the clinical characteristics and survival outcomes in patients with small cell lung cancer (SCLC) detected by low-dose computed tomography (CT). We retrospectively reviewed clinical records of patients with SCLC treated at our hospital between 1997 and 2011 and selected patients with SCLC detected by CT screening. We identified 12 patients (male/female 11/1; mean age 67.8 years old. Nine patients had limited disease (LD), and 3 had extensive disease (ED). Five LD patients underwent thoracic surgery, and the pathological staging information included stage IA (n = 1), IB (n = 1), IIA (n = 1), and IIIB (n = 2). Although 2 patients with pathological stages IA and IB had >10-year survival, the median survival times (MST) in LD and ED were 25 months (95 % CI 17.0-32.9) and 16 months (95 % CI; not evaluated), respectively. In addition, MST in 12 patients was not significantly different from that in SCLC patients in general care in our hospital. This analysis suggested that CT screening contributes to the detection of early-stage SCLC in patients that are potentially suitable for surgery, but it remains unclear how to improve clinical outcome in patients with SCLC.ArticleMEDICAL ONCOLOGY. 30(3):623 (2013)journal articl

Phase II Trial of Biweekly Paclitaxel and Gemcitabine as Second-Line Chemotherapy for Non-Small Cell Lung Cancer Previously Treated with Platinum-Based Chemotherapy

A phase II study was conducted to evaluate the feasibility and efficacy of biweekly administration of paclitaxel and gemcitabine in patients with non-small cell lung cancer (NSCLC) who had been treated previously with platinum-based chemotherapy. Paclitaxel (150 mg/m2) and gemcitabine (1,000 mg/m2) were administered biweekly for at least 4 cycles. Thirty-one patients with a median age of 64 years (39-75 years) were enrolled in this study(stage IIIB/IV :11/20,PS 0/1/2:13/16/2).Partial response was observed in 7 cases (23%), and stable disease was seen in 18 cases (58%).Median survival time was 8.8 months with a one-year survival rate of 41.9 %.Hematological toxicities were mild and neutropenia of grade 3 or above was observed in one patient (3%). Non-hematological toxicities were also mild, including neurotoxicity (3%). Biweekly paclitaxel and gemcitabine combination chemotherapy was effective and tolerated well as second-line therapy against NSCLC.Article信州医学雑誌 59(6): 411-418(2011)departmental bulletin pape