Hirofumi Tsugeno

Influence of age and disease severity on high resolution CT lung densitometry in asthma

BACKGROUND Low attenuation areas (LAA) on computed tomographic (CT) scans have been shown to represent emphysematous changes in patients with chronic obstructive pulmonary disease (COPD). However, the significance of LAA is still controversial in patients with asthma. This study was undertaken to assess the usefulness of lung CT densitometry in the detection of airspace enlargement in association with asthma severity. METHODS Forty five asthmatic subjects and 15 non-smoking controls were studied to determine the influence of age, pulmonary function, and asthma severity on mean lung density (MLD) and the relative area of the lung showing attenuation values less than –950 HU (RA950) on high resolution CT (HRCT) scans. RESULTS In asthmatic patients both MLD and RA950 correlated with parameters of airflow limitation (%FEV1, FEV1/FVC, %FEF25–75) and lung volume (%TLC, %FRC, %RV), but not with lung transfer factor (%Tlco, %Tlco/VA). The results of HRCT lung densitometry also correlated with patient age and severity of asthma. CONCLUSIONS Decreased CT lung density in non-smoking asthmatics is related to airflow limitation, hyperinflation and aging, but not with lung transfer factor.

Decreased computed tomographic lung density during exacerbation of asthma

Recently, it was shown that both mean lung density (MLD) and the relative lung area with an attenuation of <-950 HU (RA950) are related to severity of asthma in nonsmoking asthmatics. The aim of the present study was to examine whether reduced computed tomography (CT) lung density during exacerbation could change after treatment. A cross-sectional study was performed to compare CT lung density in 30 stable asthmatics, 30 unstable asthmatics and 25 control subjects. In order to investigate longitudinally the effect of treatment on decreased CT lung density, 17 asthmatics with an exacerbation were followed at the initiation of treatment and 2 months after relief. The MLD was significantly lower and the RA950 significantly higher in unstable asthmatics than in controls and stable asthmatics. Both MLD and RA950 changed significantly with administration of systemic glucocorticoid therapy. The changes in forced expiratory volume in one second correlated significantly with those in both MLD and RA950. The changes in residual volume also correlated significantly with those in both MLD and RA950. It was concluded that decreased computed tomographic lung density during an asthma exacerbation is at least partially reversible, and changes in mean lung density and the relative lung area with a radiation attenuation of <−950 HU are related to the change in forced expiratory volume in one second and residual volume.

Vertebral Fracture and Cortical Bone Changes in Corticosteroid-Induced Osteoporosis

Abstract: Despite an intriguing understanding of trabecular bone dynamics, little is known about corticosteroid-induced cortical bone loss and fractures. Recently, we verified a steroid-induced decrease in cortical bone volume and density using peripheral quantitative computed tomography (pQCT) in adult asthmatic patients given oral corticosteroids. Subsequently, the pQCT parameters and presence of vertebral fractures were investigated to further clarify the role of cortical bone quality in fractures in 86 postmenopausal (>5 years after menopause) asthmatic patients on high-dose oral steroid (>10 g cumulative oral prednisolone) (steroid group) and 194 age-matched controls (control group). Cortical and trabecular bone was subjected to measurement of various parameters using pQCT (Stratec XCT960). Relative Cortical Volume (RCV) was calculated by dividing the cortical area by the total bone area. Strength Strain Index (SSI) was determined in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. Patients treated with high doses of oral steroid (>10 g cumulative oral prednisolone) were found to have an increased risk of fracture compared with control women receiving no steroid medication (odds ratio, 8.85; 95% CI, 4.21–18.60) after adjustment was made for years since menopause, body mass index and RCV. In both groups, the diagnostic and predictive ability of the pQCT parameters for vertebral fracture was assessed by the areas under their receiver operating characteristic (ROC) curves. All parameters were found to be significant predictors (p<0.0001) in the control group. In the steroid group, however, the cortical bone mineral density (BMD) (p= 0.001), RCV (p<0.0001) and SSI (p= 0.001) were found to be significant predictors, but not trabecular BMD (p= 0.176). For comparison between the two groups, thresholds of all parameters for vertebral fracture were also calculated by the point of coincidence of sensitivity with specificity in ROC testing and the 90th percentile value. Although a rise in fracture threshold in the steroid group was suggested, considerable difference in the values obtained by the two methods of calculation precluded any conclusion. High-dose oral steroid administration was associated with an increased risk of fracture. Cortical bone parameters obtained by pQCT could play a role as good predictors of future corticosteroid-induced vertebral fractures.

A Proton-Pump Inhibitor, Rabeprazole, Improves Ventilatory Function in Patients with Asthma Associated with Gastroesophageal Reflux

Background: Treatment of gastroesophageal reflux (GER) with proton-pump inhibitors (PPI) improves symptoms of asthma in some patients. However, the effects of a PPI on ventilatory function are still controversial. In this study, we measured ventilatory function in asthma patients treated with a PPI in order to identify those in whom a therapeutic effect on asthma can be expected from the acid suppression. Methods: From a cohort of 114 consecutive patients with bronchial asthma, 53 patients agreed to participate in the study and were treated with rabeprazole 20 mg daily for 8 weeks during an asymptomatic, stable period with no exacerbations of their asthma. Of the 53 patients, 22 were diagnosed as GER on the basis of the QUEST questionnaire and endoscopic examination. The patients were monitored for improvement in ventilatory function. Results: Four patients dropped out because of adverse drug reactions. All the patients with GER noted an improvement in reflux symptoms with PPI treatment. An improvement of more than 20% in peak expiratory flow (PEF) was observed in 8 of 21 GER patients but in none of the non-GER patients. Factors predictive of improvement in PEF with rabeprazole therapy were the QUEST score (odds ratio: 1.47, 95% CI: 1.06-2.04, P = 0.022) and steroid-dependency of asthma (odds ratio: 0.01, 95% CI: 0.001-0.31, P = 0.008). Conclusions: Treatment with rabeprazole is expected to ameliorate asthma in non-steroid-dependent patients who have symptomatic GER defined by the QUEST score.

Effects of Perilla Seed Oil Supplementation on Leukotriene Generation by Leucocytes in Patients with Asthma Associated with Lipometabolism

Background: Dietary sources of α-linolenic acid, such as perilla seed oil, may have the capacity to inhibit the generation of leukotrienes (LTs) by leucocytes in patients with asthma, as has been reported with the consumption of other long-chain n-3 fatty acids. Methods: The factors affecting the suppression of leukotriene (LT) C4 generation by leucocytes were examined by comparing the clinical features of patients with asthma who had been given dietary perilla seed oil (n-3 fatty acids). Group A consisted of patients in whom the leucocyte generation of LTC4 was suppressed by dietary perilla seed oil. Group B consisted of those in whom LTC4 generation was not suppressed. Results: LTC4 generation by leucocytes decreased significantly in group A after 2 (p < 0.05) and 4 weeks (p < 0.05); conversely, it increased significantly in group B after 4 weeks (p < 0.05). The two study groups differed significantly in terms of LTC4 generation by leucocytes after 4 weeks of dietary supplementation (p < 0.05). Ventilatory parameters such as peak expiratory flow (PEF), forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) increased significantly after 4 weeks of dietary supplementation in group A (p < 0.05). Values of PEF, FVC, FEV1 and maximum expiratory flow at 25% of the forced vital capacity (v̇25) differed significantly between groups A and B prior to dietary supplementation. Serum levels of total cholesterol, low-density lipoprotein (LDL) cholesterol and phospholipid were significantly decreased by dietary supplementation in group A after 4 weeks. Serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, LDL cholesterol and phospholipid differed significantly between the two study groups prior to dietary supplementation. Serum levels of triglyceride and LDL cholesterol differed significantly between the two study groups after 4 weeks of dietary supplementation. Conclusions: Dietary supplementation with perilla seed oil in selected patients with asthma suppresses the generation of LTC4 and is associated with clinical features such as respiratory function and lipometabolism.

Low-Attenuation Areas of the Lungs on High-Resolution Computed Tomography in Asthma

To investigate the low-attenuation areas of the lungs (LAA) in asthma, we compared the mean lung density (MLD) and the LAA in 22 asthmatics (12 ex-smokers and 10 nonsmokers) and 13 patients with chronic obstructive pulmonary disease (COPD) by high-resolution computed tomography. The MLD and the relative area of the lung with attenuation values lower than −950 Hounsfield Units at full inspiration (inspiratory RA950) were significantly different in nonsmoking asthmatics compared to patients with COPD and asthmatics with a smoking history. The MLD and the RA950 correlated significantly with the FEV1 in all groups and with the DLCO in patients with COPD and asthmatics with a smoking history but not in nonsmoking asthmatics. We concluded that the LAA in asthmatics with a smoking history indicates the presence of emphysema, but in nonsmoking asthmatics it reflects hyperinflation and nonemphysematous expiratory airflow limitation rather than emphysematous lesions.

Oral Glucocorticoid-Induced Fall in Cortical Bone Volume and Density in Postmenopausal Asthmatic Patients

Abstract: Despite a deepening understanding of the influence of glucocorticoids (GC) on trabecular bone, little is known about GC-induced cortical bone loss. To elucidate the mechanism of GC-induced loss of cortical bone strength with particular reference to cortical bone loss, changes in cortical density, relative cortical volume, and the Strength Strain Index (SSI) based on biomechanical analyses of the geographic distribution of cortical bone material were measured. These parameters were compared, using peripheral quantitative computed tomography (pQCT), among the following age-matched groups: 68 postmenopausal asthmatic patients receiving high-dose oral GC in addition to inhaled GC (oral GC group), 68 postmenopausal asthmatic patients receiving only inhaled GC (inhaled GC group) and 69 postmenopausal controls without asthma or GC therapy (control group). Cortical bone mineral density (BMD) was measured, relative cortical volume was obtained by dividing the cortical area by the total bone area using pQCT (Stratec XCT960), and the Strength Strain Index (SSI) was calculated in the radius based on the density distribution around the axis. Spinal fracture was assessed on lateral radiographs. The number of vertebral fractures per patient correlated highly with cortical BMD, relative cortical volume and SSI values at the radius. The number of vertebral fractures per patient and the number of patients with fracture were similar between the control and inhaled GC group, both being significantly lower than those in the oral GC group. Total BMD, trabecular BMD, cortical BMD, relative cortical volume and SSI were similar between the first two, being significantly higher than in the last group. The slopes of cortical volume–density relationship, however, were identical among the three groups, indicating the persistence of cortical bone remodeling and a similar degree of calcification regardless of GC administration.

Quantitative analysis of wild-type and precore mutant hepatitis B virus in carriers

In the present study, we have analyzed the amount of precore wild-type hepatitis B virus (HBV) (wild-type) and precore mutant HBV (nt 1896: G-->A) (precore mutant) of HBV carriers; 31 asymptomatic healthy carriers (ASC) and 28 patients with chronic hepatitis (CH). Wild-type and precore mutant were quantified using sensitive and specific quantification methods: competitive wild-type-sequence-specific assay and competitive mutation-site-specific assay with different sets of specific primers and internal controls. Median serum levels of wild-type and precore mutant were 9.60 and 8.60 log copies/ml (median percentages of precore mutant in total HBV-DNA: 11.7%) in HBeAg(+) ASC, 8.48 and 8.00 (33.3%) in HBeAg(+) CH, and 6.30 and 6.85 (84.7%) in anti-HBe(+) CH, respectively, showing higher levels of the relative amount of precore mutant to wild-type along with HBeAg/anti-HBe status. Only precore mutant, but not wild-type was detected in anti-HBe(+) ASC. Although median percentages of precore mutant at the anti-HBe(+) ASC and CH stages were much higher than those at the HBeAg(+) ASC and CH stages, a substantial amount of precore mutant was found even at the HBeAg(+) stages. Existence of a substantial amount of precore mutant even in HBeAg(+) ASC suggests that the occurrence of precore mutant is not always closely associated with seroconversion from HBeAg to anti-HBe.

Different Roles of Histamine and Leukotriene C4 in the Airways Between Patients with Atopic and Nonatopic Asthma

The release of histamine and leukotriene C4 (LTC4) from bronchoalveolar lavage (BAL) cells and peripheral blood stimulated with Ca ionophore A23187 was compared between atopic and nonatopic asthma. The proportion of basophilic cells in BAL fluid was significantly higher in atopic than in nonatopic asthma (p < 0.01); however, no significant differences were present in the other BAL cells between the two asthma types. The concentration of histamine in BAL fluid was significantly higher in younger patients (20-59 years) with atopic than in nonatopic asthma (p < 0.01). In contrast, the concentration of LTC4 was significantly higher in nonatopic than in younger patients with atopic asthma (p < 0.01). The release of histamine from BAL cells (p < 0.001) and peripheral blood (p < 0.01) was significantly larger in younger patients with atopic than in nonatopic asthma. The generation of LTC4 by BAL cells was significantly larger in nonatopic than in younger (p < 0.01) and older patients with atopic asthma (60+ years) (p < 0.05). These results suggest that both histamine and LTC4 participate in the onset mechanism of atopic asthma, and only LTC4 participates in that of nonatopic asthma.

Immunohistochemical observation of Fas in the human liver: light and electron microscopic observation by immuno-peroxidase method

Abstract The expression of Fas was examined in liver specimens from 18 patients with various liver diseases (8 type B chronic hepatitis, 7 type C chronic hepatitis, 2 autoimmune hepatitis and one fatty liver) and normal liver specimens obtained from 2 patients under surgical treatments for metastatic liver cancer, by light and electron microscopy using the indirect peroxidase-labelled antibody method. Fas was detected on the surface of hepatocytes in all cases. By immunoelectron microscopy, dense reaction products were observed on the plasma membrane facing both the Disses and intercellular spaces, as well as in some membranes of the endoplasmic reticulum. In patients with severe or moderate chronic liver inflammation, strongly Fas-positive hepatocytes were distributed diffusely throughout the lobules. On the other hand, in patients with minimal hepatic inflammation, Fas expression was weak, and localized mainly in hepatocytes of the centrilobular area. These findings confirm the localization of Fas on the plasma membrane of hepatocytes, and suggest that Fas expression may increase with increasing degree of intrahepatic inflammation.