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 (RA(950)) on high resolution CT (HRCT) scans. RESULTS: In asthmatic patients both MLD and RA(950) correlated with parameters of airflow limitation (%FEV(1), FEV(1)/FVC, %FEF(25-75)) 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.

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 DL(CO) 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.

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.

A patient with severe palindromic rheumatism and frequent episodes of pain.

A 44-year-old man began to experience episodes of joint pain with erythema in his knees, elbows, shoulders, and hands in April 1996. He was diagnosed as having palindromic rheumatism. Due to the increasing frequency and severity of these episodes, he was admitted to our hospital in May 1999. Heat therapy to the affected area produced a rapid improvement in symptoms. In addition, the continued use of physical therapy during symptom-free periods tended to reduce the frequency and severity of pain attacks. We present this case and discuss treatment options in patients with palindromic rheumatism.

Enhanced production of leukotrienes by peripheral leukocytes and specific IgE antibodies in patients with chronic obstructive pulmonary disease.

BACKGROUND: How leukotrienes (LTs) and IgE-mediated allergy reflect clinical features in patients with chronic obstructive pulmonary disease (COPD) remains unclear. OBJECTIVE: Our goal was to determine whether LTB4 and LTC4 would correlate with airway obstruction and whether IgE-mediated allergy would influence the generation of LTs and bronchial hyperresponsiveness in patients with COPD. METHODS: We measured the pulmonary function, methacholine bronchial hyperresponsiveness, and generation of LTB4 and LTC4 from peripheral leukocytes stimulated with calcium ionophore A23187 in relation to the presence of specific IgE antibodies against inhalant allergens. RESULTS: The leukocytes of patients with COPD generated significantly more LTB4 (with allergy, P <.001; without allergy, P <.001) and LTC4 (with allergy, P <.001; without allergy, P <.01) than the leukocytes of the control subjects. LTC4 production was significantly higher in the allergic COPD subjects than in the nonallergic COPD patients (P <.01), but the amount of LTB4 generated was not significantly different. FEV(1) significantly correlated with the level of both LTB4 (with allergy, r = -0.556, P =.0375; without allergy, r = -0.731, P =.0046) and LTC4 (with allergy, r = -0.764, P =.0043; without allergy, r = -0.526, P =.0414) generation in COPD. The log(10) of the minimum dose of methacholine was significantly higher in COPD patients without allergy than in those with allergy (P <.05). CONCLUSION: Enhanced LT generation from peripheral leukocytes is observed in patients with COPD, and the presence of specific IgE antibodies against inhalant allergens enhances LTC4 generation, bronchial hyperresponsiveness, and the relationship between LTC4 generation and airway obstruction.

Basic study on radon effects and thermal effects on humans in radon therapy.

Because most of the diseases to which radon (222Rn) therapy is applied are related to activated oxygen, in this study the effect of the radioactivity of radon and the thermal effect were compared under a room or a hot spring condition with the same chemical component using as the parameters the activity of superoxide dismutase (SOD), which is an oxidation inhibitor, and lipid peroxide and low density lipoprotein (LDL)-cholesterol, which are closely involved in arteriosclerosis. Results show that the SOD activity was significantly increased, and the lipid peroxide and LDL-cholesterol levels were significantly decreased on days 6 and 7 of study. The results were about 2-fold larger in the radon group than in the thermo group. This suggests that the anti-oxidation function was more enhanced by radon therapy than by thermo therapy, and suggests that radon therapy may help to prevent the causes of life style-related diseases such as arteriosclerosis. These findings are important in understanding the mechanism of diseases in which radon therapy is used as treatment, and most of which are called activated oxygen-related diseases.

Enhanced peripheral leukocyte leukotriene production and bronchial hyperresponsiveness in asthmatics.

Leukotrienes (LTs) are pro-inflammatory mediators that contribute to the pathophysiological features of asthma. The relationship between the amounts of LTB4 and LTC4 produced by the leukocytes of asthmatic patients on the one hand and immunoglobulin E (IgE)-mediated allergy, asthma exacerbations and bronchial hyperresponsiveness was studied. Leukocytes were obtained from peripheral blood drawn from 29 atopic and 27 nonatopic asthmatics during exacerbations and clinically controlled periods, as well as from 20 control individuals. The leukocytes were stimulated with calcium ionophore A23187 to induce LTB4 and LTC4 production. Allergy was assessed by means of specific serum IgE or by positive skin tests, whereas bronchial hyperresponsiveness was measured by methacholine challenge. The leukocytes of the asthmatics generated significantly more LTB4 (p<0.05) and LTC4 (p<0.01) than those of controls. The leukocytes of patients with atopic asthma generated significantly more LTC4 than those of patients with nonatopic asthma (p<0.01). Significantly more LTC4 was produced by leukocytes obtained during exacerbations, than by those obtained during clinically controlled periods (p<0.01). In addition, there was a significant correlation between LTB4 generation by leukocytes and the degree of bronchial hyperresponsiveness to methacholine (r=-0.792, p<0.0001). These results suggest that leukotriene C4 production by leukocytes is associated with immunoglobulin E-mediated allergy and asthma exacerbations, and further that generation of leukotriene B4 is closely related to bronchial hyperresponsiveness in patients with asthma.

Effects of perilla seed oil supplementation on leukotriene generation by leucocytes in patients with asthma associated with lipometabolism.

BACKGROUND: Dietary sources of alpha-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 (FEV(1)) increased significantly after 4 weeks of dietary supplementation in group A (p < 0.05). Values of PEF, FVC, FEV(1) and maximum expiratory flow at 25% of the forced vital capacity (V(25)) 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.

IgE-mediated and age-related bronchial hyperresponsiveness in patients with asthma. relationship to family history of the disease.

OBJECTIVE: to uncover any differences in the age-related and IgE-mediated pathophysiology of the airways in asthmatics. METHODS: we examined the relationship of both IgE-mediated bronchial hyperresponsiveness and the cell content of bronchoalveolar lavage fluid with a family history of asthma in 263 patients with asthma classified according to age at onset. RESULTS: bronchial hyperresponsiveness decreased significantly as age at onset increased in those without a family history. Responsiveness was significantly higher in patients who were > or = 60 years of age at onset who had a family history than in those who did not (P < 0.05). The proportion of lymphocytes in bronchoalveolar lavage fluid was significantly higher in patients between 50 and 59 years old at onset who had a family history than those who did not (P < 0.05). These results suggest that bronchial hyperresponsiveness and the proportion of bronchoalveolar lavage lymphocytes differ according to the presence or absence of a family history, a finding which is closely related to IgE-mediated allergy in elderly patients at onset. CONCLUSIONS: our findings suggest (i) the possibility of asthma induced by non-IgE-mediated allergy in elderly patients and (ii) that bronchial responsiveness is also influenced by IgE-mediated allergy and age at onset.

Effects of dietary supplementation with n-3 fatty acids compared with n-6 fatty acids on bronchial asthma.

OBJECTIVE: The effects of perilla seed oil (n-3 fatty acids) on bronchial asthma were compared with the effects of corn oil (n-6 fatty acids) in relation to the pulmonary function and the generation of leukotriene B4 (LTB4) and C4 (LTC4) by leucocytes. METHODS AND SUBJECTS: 14 asthmatic subjects were divided randomly into two groups: one group (7 subjects) consumed perilla seed oil-rich supplementation and the other group (7 subjects) consumed corn oil-rich supplementation for 4 weeks. Generation of LTs by leucocytes and respiratory function were compared between the two groups. RESULTS: The generation of LTB4 and LTC4 by leucocytes tended to increase in subjects (N=7) with corn oil-rich supplementation, and decrease in subjects (N=7) with perilla seed oil-rich supplementation. Significant differences between the two groups were observed in the generation of LTB4 at 2 weeks (p<0.05) and LTC4 at 2 weeks (p<0.05) after dietary supplementation. Significant increases in the value of PEF (p<0.05), FVC (p<0.01), FEV(1.0) (p<0.05) and V(25) (p<0.05) were found in subjects who received perilla seed oil supplementation for 4 weeks. And significant differences in the value of FVC (p<0.05) and FEV(1.0) (p<0.05) were observed between the two groups after 4 weeks of dietary supplementation. CONCLUSION: These results suggest that perilla seed oil-rich supplementation is useful for the treatment of asthma in terms of suppression of LTB4 and LTC4 generation by leucocytes, and improvement of pulmonary function.

Bone mineral density in steroid-dependent asthma assessed by peripheral quantitative computed tomography.

Chronic use of systemic glucocorticoids results in progressive bone loss and pathologic fractures. This study identified the predictive variables for bone loss and used peripheral quantitative computed tomography (pQCT) to measure changes in cortical and trabecular bone in patients receiving systemic glucocorticoid therapy of prednisone 15.4 g. Eighty-four asthmatic patients were included in the study. Vertebral fractures were diagnosed via plain spinal radiograms. pQCT was used to measure cortical and trabecular bone mineral density. Multiple regression analysis identified variables with predictive value. The cumulative dose of glucocorticoid correlated with the bone mineral density (p<0.05) and the trabecular bone density (p<0.01). Among patients > or = 65 yrs of age, the cumulative dose of glucocorticoid correlated with the occurrence of vertebral fractures (p<0.05), total bone mineral density (p<0.01) and cortical bone mineral density (p<0.01). Bone mineral density in the distal radius measured by pQCT and the vertebral bodies by axis QCT were correlated, regardless of whether systemic glucocorticoids were administered. Glucocorticoid administration not only decreases trabecular but also cortical bone mineral density. Since cortical bone provides strength and stiffness, it appears that the loss of cortical bone is responsible for the increased incidence of fracture seen in patients receiving systemic glucocorticoid therapy.

Giant cell arteritis associated with rheumatoid arthritis monitored by magnetic resonance angiography.

A 57-year-old Japanese woman with well controlled rheumatoid arthritis visited our hospital with a severe bitemporal headache and marked fatigue. Based on the classification criteria by the American College of Rheumatology, she was diagnosed as having giant cell arteritis. Magnetic resonance (MR) angiography was performed, from which stenotic changes in the bilateral superficial temporal arteries were strongly suspected. Corticosteroid therapy was quickly started. The patient followed an uneventful course with no complications. Therapeutic effect was confirmed by MR angiographic findings obtained 4 weeks after the initiation of therapy.

[Age-related changes of IgE-mediated allergic reaction in patients with late onset asthma--relationship between IgE-mediated allergy and age at onset].

We examined age-related changes in the IgE-mediated allergic reaction in patients with late onset asthma, whose asthma first occurred at over 40 years. 1. The number of patients with a high serum IgE level (over 300 IU/ml) was larger in patients with an age of onset between 40 and (40-49 years group) and in patients older than 60 at age of onset (60-year group) than in patients with an age of onset between 50 and 59 (50-59 year group). 2. A positive RAST score to house dust mite (HDm) allergen was more frequently found in the 40-49 year group and in the 60- year group than in the 50-59 year group. Frequency of positive RAST score to HDm in the 50-59 year group was significantly lower (p < 0.01) than in early-onset asthma patients (age at onset less than 39 years). 3 Frequency of family history of asthma in the 50-59 years group was high, being equal to that of early-onset asthma patients. 4 In the 50-59 year group, the frequency of severe asthma was comparatively higher than that of the other groups. The frequency of IgE-mediated allergic reaction changed in regard to age of onset of asthma, and allergic reactions in late-onset asthma partially resembled those of early-onset asthma. These results suggest that an atopic constitution is related to the onset of bronchial asthma in the elderly.

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.

[Psychological investigation on spa therapy in patients with bronchial asthma].

To evaluate the effects of complex spa therapy (swimming training in a hot spring pool + fango therapy + inhalation of iodine salt solution) on psychological factors, three psychological examinations; CMI (Cornell Medical Index), SDS (Self-Rating Depression Scale) and CAI (Comprehensive Asthma Inventory); were given 25 patients with bronchial asthma (10 male, 15 female, mean age 60 years), and the results of these examinations were compared before and after spa therapy. 1. Physical symptoms, respiratory system and CIJ symptoms by CMI were significantly improved after spa therapy, however the improvement of psychical symptoms was not significant. 2. In SDS, 11 of 25 patients showed more than 40 points, indicating depressive state. The number of such patients decreased from 11 to 2 and the mean SDS score significantly improved from 38.7 to 34.2 after spa therapy. 3. Conditioning, suggestion, fear of expectation, frustration, flight into illness, negative attitudes towards prognosis, and decreased motivation towards therapy by CAI were significantly reduced after spa therapy, with the reduction in negative attitudes towards prognosis and decreased motivation towards therapy being relatively large. Furthermore, CAI score, which is the average of the categories in CAI, was also significantly decreased from 37.9 to 28.4 after spa therapy. These results suggested that complex spa therapy improves psychological factors in patients with bronchial asthma.

Topographic differences of 1H-NMR relaxation times (T1, T2) in the normal intervertebral disc and its relationship to water content.

1H-nuclear magnetic resonance studies, in vitro, on normal intervertebral discs dissected from adult bovine (3- or 4-year-old) coccygeal vertebrae were performed to clarify topographic differences in relaxation times (T1, T2) and relationships between the relaxation times and water content. Immediately after death, intervertebral discs were dissected from 1st/2nd and 2nd/3rd coccygeal vertebrae and divided into three specimens: the nucleus pulposus, inner anulus fibrosus, and outer anulus fibrosus. T1, T2, and water content were measured for the specimens collected from 15 intervertebral discs (untreated group). Secondly, specimens were similarly collected from 12 intervertebral discs and were treated to changed water contents (dehydrated group and hydrated group). For each treated specimen, T1, T2, and water content were measured. The results showed highly significant differences (P < 0.01) in T1 values among the nucleus pulposus, inner anulus fibrosus, and outer anulus fibrosus, and also in T2 values between the nucleus pulposus and anulus fibrosus. In each of the nucleus pulposus and anulus fibrosus, a positive linear relationship (r = 0.97, P < 0.01) was found between T1 and water content. The respective regression lines for the nucleus pulposus and anulus fibrosus had different slopes, and the slope of the nucleus pulposus was significantly greater than that of the anulus fibrosus. Thus, the decrease in water content shortens the T1 in intervertebral discs, and changes in water content have a greater influence on T1 in the nucleus pulposus than in the anulus fibrosus.(ABSTRACT TRUNCATED AT 250 WORDS)

IgE-mediated allergic reaction in drug-induced asthma.

Immunoallergological studies were carried out to clarify the differences between 24 patients with drug-induced asthma (DIA) and 240 with non-drug-induced asthma (non-DIA). The mean values of age, skin reaction to Candida albicans (C. albicans), serum IgE levels, specific IgE antibodies to house dust (HD) and C. albicans, bronchial sensitivity and leukotriene B4 (LTB4) synthesis from peripheral venous blood in patients with DIA were not significantly different from those in patients with non-DIA. In contrast, the frequency of positive skin reaction to HD and histamine release from peripheral basophils by anti-IgE were significantly lower in DIA than in non-DIA. These results agree with the reports that DIA was often observed in non-atopic asthma. But, the mean value of serum IgE was very high in DIA as well as in non-DIA. This result suggests that IgE mediated reaction in DIA is important. Furthermore, the proportion of neutrophils in bronchoalveolar lavage fluid (BALF) was significantly lower in DIA than in non-DIA. Our findings suggest that a decrease of intrapulmonary neutrophils might play an important role in the pathophysiology of DIA.

Chemical mediator and cellular reaction in the bronchoalveolar lavage fluid of patients with steroid-dependent intractable asthma (SDIA).

The effects of long-term glucocorticoid therapy on chemical mediator and cellular reaction in the airways were examined in 69 patients with bronchial asthma. The histamine release induced by Ca ionophore A23187 from cells in the bronchoalveolar lavage (BAL) fluid of atopic asthmatics was significantly lower in the subgroup with steroid-dependent intractable asthma (SDIA) than in non-SDIA patients (p < 0.05). In contrast, histamine release in nonatopic SDIA patients did not differ from nonatopic non-SDIA patients. The release of leukotriene C4 (LTC4) was significantly lower in atopic patients with SDIA (p < 0.02). However, there was no significant difference in LTC4 release between nonatopic patients with SDIA and without SDIA. The proportion of BAL lymphocytes was significantly lower in atopic patients with SDIA than in those without it (p < 0.05), although there was no significant difference between the nonatopic patients with and without SDIA. These results show that glucocorticoids affect humoral and cellular events in the airways of atopic asthmatics more than in those of nonatopic asthmatics.

Cell-mediated immunity in bronchial asthma evaluated by purified protein derivative- and Candida albicans-skin reaction.

Cell-mediated immunity was examined in 45 patients with bronchial asthma by observing the delayed cutaneous reaction to purified protein derivative (PPD) and Candida albicans (C. albicans). The delayed skin reaction to PPD showed a decrease with age starting between 50 and 59 years old. The delayed reaction to PPD decreased more prominently with aging, being significantly depressed in the patients aged over 70 years than in those aged between 30 and 49 years (induration, p < 0.02; flare, p < 0.01). The C. albicans-induced skin reaction was significantly lower in the patients aged over 70 years than in those between 60 and 69 years old (induration, p < 0.01; flare, p < 0.05). The delayed skin reaction to PPD and C. albicans was significantly depressed in the patients with a serum IgE level over 1001 IU/ml. Delayed skin reaction to PPD and C. albicans was more depressed with aging and an elevated serum IgE, and the age (50-59 years) at the initiation of depression in the PPD-induced delayed skin reaction was younger than that (over 70 years) in the C. albicans-induced reaction.