Search

A 34-year-old woman visited our hospital complaining of dry cough. Chest radiography and computed tomography showed bilateral multiple infiltrative shadows over the lung field. After an initial diagnosis of pneumonia, antibiotics were administered, but the therapy failed to improve the symptoms and abnormalities observed on the chest radiograph. The patient was then admitted to our hospital. The bronchoalveolar lavage fluid (BALF) was slightly bloody, but we were not able to make any specific findings in BALF. In order to confirm the pathological diagnosis, video-assisted thoracoscopic lung biopsy was performed aiming at the right middle and lower lobes. There were bleeding pulmonary infarctions in a biopsy specimen from the right middle lobe. Atypical cells positive for human chorionic gonadotropin (hCG) proliferated in the pulmonary arteries, and so a diagnosis of pulmonary embolic metastasis of choriocarcinoma was made. After the diagnosis, it became clear that urine and serum hCG values were very high. The patient has since received systemic chemotherapy in the gynecology unit at our hospital. Pulmonary embolic metastasis of choriocarcinoma diagnosed by video-assisted thoracoscopic lung biopsy has never been reported in the literature. However, early hCG measurement may have detected this syndrome in the earlier stages, and pulmonary metastasis of choriocarcinoma should be considered in the differential diagnosis of women with past pregnancy presenting with intractable multiple pulmonary shadows.

A 66-year-old man who had received a diagnosis of ankylosing spondylitis at the age of 50 was referred to our hospital for further evaluation of sleep apnea experienced for the last 3 years. Polysomnography yielded a diagnosis of obstructive sleep apnea syndrome with an apnea index of 41/hr. Computed tomographic scans demonstrated complete closure of the oropharynx during sleep at a site of marked ossification and hypertrophy of the cervical anterior longitudinal ligament. Nasal continuous positive airway pressure (nasal CPAP) with the use of chinstrap, but not nasal CPAP alone, dramatically decreased the patient's apnea index to 2.4/hr. We reported this case because, to the best of our knowledge, it is the first to demonstrate a causative association between ankylosing spondylitis and obstructive sleep apnea syndrome.

Helical-scan computed tomography (CT) is now widely utilized as a mass screening procedure for lung cancer. By adding 3 slices of high-resolution CT (HRCT) to the standard screening procedure, we were able to compare the efficacy of helical-scan CT and HRCT in detecting pulmonary emphysema. Additionally, the prevalence of emphysema detected by HRCT was examined as a function of patient age and smoking history. The subjects (106 men and 28 women) were all community-based middle-aged and older volunteers who participated in a mass lung cancer screening program. Based on visual assessments of the CT films, emphysema was detected in 29 subjects (22%) by HRCT, but in only 4 (3%) by helical-scan CT. Although the prevalence of emphysema was higher among subjects with a higher smoking index, no correlations with age were observed. We concluded that the efficacy of helical scan CT in detecting pulmonary emphysema can be significantly improved with the inclusion of 3 slices of HRCT, and confirmed that cigarette smoking is linked to the development of pulmonary emphysema.

A 25-year-old woman was admitted to our hospital because of dry cough, slight fever, and severe dyspnea 5 hrs after inhalation of waterproofing spray. She had used the spray indoors near an oil heater, and then had smoked with spray-contaminated fingers. Chest roentgenograms revealed diffuse interstitial shadows mixed with patchy alveolar infiltration, and computed tomographic (CT) scans confirmed diffuse infiltration in both lungs. Marked leukocytosis and severe hypoxemia were noted. A transbronchial lung biopsy performed 4 days later demonstrated extensive alveolitis characterized by edema in alveolar septa and marked neutrophil migration into alveoli as well as alveolar septa. Oxygen therapy and the administration of methylprednisolone (1 g/day) achieved a complete recovery in about 1 week. We speculated that acute lung injury in this patient may have been induced by direct inhalation not only of the waterproofing spray itself, but also of spray by-products resulting from heat-decomposition. When using waterproofing spray, precautions should be taken to avoid inhaling the spray fumes or the more toxic by-products of thermal degradation.

The prognostic value of hypercapnia and/or pulmonary hypertension differs in patients with sequela of pulmonary tuberculosis (TBseq) and those with chronic obstructive pulmonary disease (COPD) who are receiving home oxygen therapy (HOT). In an attempt to identify the factors, if any, that might explain this difference, we first compared nutritional status, respiratory function test results, dyspnea indexes, and other data for hypercapnic patients (PaCO2 > or = 45 Torr) and normocapnic patients (PaCO2 < 45 Torr) receiving HOT. Second, we examined the relationship between the degree of pulmonary hypertension and several respiratory function parameters for patients in each disease category. In 44 patients with TBseq, nutritional status estimated by body mass index and serum albumin was significantly better in the hypercapnic patients than in the normocapnic patients. However, this difference was not observed in 37 patients with COPD. In 30 patients with TBseq, the degree of pulmonary hypertension correlated significantly only with PaO2; in 32 patients with COPD, however, significant correlations were observed not only with PaO2 but also with PaCO2, %VC, and FEV1. These differences distinguishing groups of patients with the 2 diseases may provide an explanatory basis for the difference in prognostic value of hypercapnia and/or pulmonary hypertension in patients receiving HOT.

We report on a 59-year-old woman who presented with characteristic findings on lung computed tomographic (CT) scans and was therefore suspected to have chronic pulmonary thromboembolism. She visited our hospital because of worsening exertional dyspnea over the preceding year, and because she was dissatisfied with an earlier diagnosis made by another institution. Chest roentgenograms disclosed nonhomogeneous hyperlucency in both lungs associated with linear and bundle shadows, dullness of the right costophrenic angle, and dilatation of the descending branch of the right pulmonary artery. The patient experienced moderate hypoxemia even at rest. Pulmonary function tests demonstrated a restrictive ventilatory pattern associated with reduced diffusion capacity. The lung CT scans disclosed a mosaic pattern of attenuation in the lung parenchyma, which probably reflected scattered areas of low perfusion. The unique characteristics of such CT findings drew our attention to chronic pulmonary thromboembolism as a possible diagnosis. We eventually confirmed the diagnosis on the basis of enhanced CT scans, pulmonary perfusion and ventilation scintigrams, and digital subtraction angiography. In our view, chronic pulmonary thromboembolism should be kept in mind as a possible differential diagnosis of the mosaic patterns of attenuation on lung CT scans.

A 54-year-old man was admitted for further investigation of multiple nodules disclosed by a chest roentgenogram. Adrenocorticotropic hormone (ACTH)-dependent Cushing's syndrome was diagnosed because serum ACTH and serum cortisol levels were elevated with a loss of diurnal rhythm. Because several extensive examinations, including inferior petrosal sinus sampling, did not detest ACTH-producing tumors, the patient was also given a diagnosis of occult ectopic ACTH syndrome. The nodules disclosed on chest roentgenograms increased gradually in size and number, and some were cavitary. Bronchial secretion samples obtained by fiberoptic bronchoscopy contained numerous Nocardia asteroides bacteria. After treatment with sulfamethoxazole-trimethoprim, the nodules gradually disappeared, leaving only scars. Although mitotane had been continuously administered to inhibit the synthesis of intrinsic corticosteroids, pulmonary nocardiosis relapsed in the patient following the termination of sulfamethoxazole-trimethoprim therapy.

Forty eight Japanese sleep apnea syndrome (SAS) patients, whose apnea-hypopnea index (AHI) was more than 30 times/hr. from 5 university hospitals (46 males, 2 females) were enrolled in this study to analyze the characteristics of the disorder and the effectiveness of nasal continuous positive airway pressure (nCPAP) effectiveness. Although the severity of excessive daytime sleepiness (EDS), depressive state, and ventricular premature beats caused by SAS seemed milder in Japanese than reported Caucasian patients, the prevalences of hypertension and glucose intolerance were quite high: 50 and 30% respectively. Treatment with nCPAP for 3 months was completed in 41 of 48 enrollees, a compliance rate of 85.4%, which was substantially higher than studies from Western countries. nCPAP treatment normalized about 50% of hypertensive patients and more than half of glucose intolerant patients. Moreover, EDS, driving ability, the severity of arrhythmia, and so forth were all improved with nCPAP. We, therefore, conclude that 1) SAS could differ between Japanese Caucasians in terms of clinical features resulting from SAS and 2) treatment with nCPAP is effective and should be considered as first-line treatment for patients with moderate to severe SAS, as reported in Western countries.

A 60-year-old woman was admitted for evaluation of an abnormal shadow in her chest X-ray. A chest roentgenogram revealed middle lobe atelectasis and a tomogram showed masses mainly in the right intermediate bronchus. In bronchoscopy, the bronchus was severely narrowed by irregularly surfaced masses. Microscopic examinations of transbronchial biopsy specimen showed the mucosal and submucosal tissue diffusedly infiltrated mainly by lymphocytes composed of small lymphocytes, centrocyte-like cells and monocytoid cells. The B-cell origin was suggested by a positive L-26 stain. Monoclonality of lymphocytes was proven by Southern blot analysis and in situ hybridization. The diagnosis was primary endobronchial lymphoma of mucosa-associated lymphoid tissue. The case was treated with chemotherapy protocol (CAMBO-VIP) and has been in complete remission for 20 months.

A case of cardiovascular Behçet's disease is reported. A 30-year-old man was admitted to our hospital with a high fever. Multiple nodular shadows were revealed on chest X-ray. Echocardiography revealed a mural thrombus in the right ventricle. A diagnosis of multiple pulmonary septic embolisms was made, and antibiotics were administered. The mural thrombus soon resolved, but later recurred in the same location. On the 90th day after admission. The mural thrombus was surgically removed. Histologically, the thrombus consisted of numerous neutrophils and fibrin. Examination of the endocardium attached to the thrombus revealed nonspecific inflammation, with fibrotic change and necrosing granulation present. A diagnosis of cardiovascular Behçet's disease was made based on the following findings: oral ulcerations, acneiform nodules, thrombophlebitis, bilateral uveitis, and positive HLA-B51. After treatment with steroid hormones and cyclosporine, the thrombus resolved completely, and inflammatory signs diminished. Though various clinical and pathological characteristics of cardiovascular Behçet's disease have been reported, it is rare for a mural thrombus to produce multiple pulmonary septic embolisms.

We report the case of a 48-year-old man with asthma and pulmonary eosinophilia. He presented with coughing, dyspnea, and wheezing that began 6 months after he began keeping a rabbit in his house. He was referred to our department for further examination of pulmonary infiltrative shadows. An inhalation test with rabbit-fur antigen induced both immediate and late asthmatic responses. In addition, infiltrative shadows appeared in the right segments 2, 8, and 9 on chest CT films after the antigen inhalation. Examination of fluid obtained by bronchoalveolar lavage from the right S9 showed an increase in the fraction of eosinophils. Examination of a specimen obtained by transbronchial lung biopsy from those segments revealed infiltration of inflammatory cells into the alveolar septa and alveolar spaces, which was consistent with eosinophilic pneumonia. Our diagnosis was asthma and pulmonary eosinophilia due to rabbit-fur antigen.

A 65-year-old man was admitted to the hospital because of an abnormal shadow on a chest roentgenogram. A diagnosis of mixed-type malignant mesothelioma was made after transcutaneous needle biopsy and thoracoscopic biopsy. The tumor was considered to be inoperable because it had diffusely invaded surrounding tissue, and therefore the patient was treated with chemotherapy only. About one year later, he died of acute pneumonia. At autopsy, a mesenchymal malignant mesothelioma that did not have an epithelial component was found. We know of no previous report of a case in which a tumor with a biopsy-proven epithelial component apparently changed to a purely sarcomatous type. No satisfactory explanation for this phenomenon has been offered.

We studied the relationship between the effectiveness of corticosteroid pulse treatment, clinical characteristics and outcomes in 17 patients with acute exacerbatin of idiopathic interstitial pneumonia. Acute exacerbation was defined as a decrease in PaO2 by more than 10 Torr, worsening of chest-radiographic findings, and deterioration of symptoms within 1 month. Effects of corticosteroid pulse treatment were judged 2 weeks and 3 months after the end of treatment. The change in AaD2 was computed and was used to determine whether the treatment had been effective, temporarily effective, or ineffective. The effects at three months were difficult to predict on the basis of those at two weeks. The treatment was often effective in patients who had not previously received steroids and in those with mild disease. Those in whom the treatment was effective at three months lived longer after the exacerbation than did those in whom it was ineffective, but the average lengths of survival through the whole clinical course were not significantly different among the three groups. We suggest that corticosteroid pulse treatment is effective in acute exacerbatins of idiopathic interstitial pneumonia and that effectiveness should be evaluated three months after treatment.

We examined the relationship between neutrophil elastase, elastin-derived peptides in bronchoalveolar lavage (BAL) fluid, and the development of pulmonary emphysema. The level of neutrophil elastase was higher in asymptomatic current smokers with emphysematous changes on computed tomographic scans than in current smokers without emphysematous changes, and was found to be correlated with the level of elastin-derived peptides in BAL fluid. Subjects with high levels of neutrophil elastase in BAL fluid had faster annual declines in FEV1. We conclude that the level of neutrophil elastase in BAL fluid can be used to differentiate asymptomatic cigarette smokers who are at risk for pulmonary emphysema from those who are not.

Clinically, threshold concentrations of agonist causing 20% decrease in FEV1 (PC20 FEV1) or 35% decrease in airway conductance (PC35Gaw) are usually used as parameters of airway hyperresponsiveness. In this session, what do these parameters mean was discussed based on theoretical analysis, experimental data and clinical observations. Theoretically, using these parameters, it seems very difficult to distinguish whether hyperresponsiveness is due to the change in sensitivity or maximum responses. Experimental and clinical observations suggest that these parameters are affected by multiple factors, for example, genetic vs. acquired factors and functional vs. structural factors. There may be differences in the degree of contributions of each factors on clinical parameters of airway responsiveness between asthmatics and control, and mild and chronic severe asthma. Clinically, considering such differences may be important in interpreting the changes of these parameters.

KL-6 is a mucinous glycoprotein expressed on Type 2 pneumonocytes, and serum levels of KL-6 are reported to be abnormally high in patients with interstitial pneumonia. A new assay kit for serum KL-6 (ED046) was used in the evaluation of patients with pneumonitis. To clarify whether KL-6 is a useful marker of pneumonitis activity, 649 subjects were studied, including 185 healthy controls, 187 patients with 3 types of interstitial lung diseases, and 277 patients with 4 types of non-interstitial lung diseases. The serum KL-6 level was significantly higher in the patients with pneumonitis (1285 +/- 1196 U/ml) than in the patients without pneumonitis (307 +/- 232 U/ml). The KL-6 level was also significantly higher in patients with clinically active pneumonitis (1708 +/- 1338 U/ml) than in those with inactive pneumonitis (820 +/- 796 U/ml) (p < 0.0001). Serum KL-6 levels correlated significantly with serum c-reactive protein, lactic dehydrogenase, and PaO2 values. These results suggest that the ED046 assay is useful for measuring KL-6 as a marker of pneumonitis activity.

Patient 1: A 64-year-old woman was admitted for further examination after reticulonodular shadows were found on a chest X-ray film. Idiopathic interstitial pneumonia (IIP) was diagnosed. Patient 2: The 60-year-old sister of patient 1 was admitted for further examination after reticulonodular shadows were found on a chest X-ray film. IIP was diagnosed. About half a year later, her proximal interphalangeal joints had become swollen and the result of a rheumatoid hemagglutination test was positive. Therefore, the pneumonia was suspected to have been caused by a collagen-vascular disease (CVD), rheumatoid arthritis. Patient 3: The 64-year-old brother of patient 1 was examined. A chest X-ray film revealed reticulonodular shadows that were strongly suggestive of IIP. The remaining three siblings were examined. In a 62-year-old sister, the chest X-ray film was normal, but the level of anti-nuclear antigen was elevated. The fact that the level of this antigen was high in these four siblings and that the 60-year-old sister later suffered from rheumatoid arthritis suggested the presence of a factor predisposing to CVD in these siblings. The interstitial pneumonia in these siblings may have been related to CVD.

The death rate among patients with asthma in Japan has been reported by Japan's Ministry of Health and Welfare to approximately 5/100,000 population. Over the past 15 years, this rate has remained relatively constant, but it is higher than that in western countries. To clarify recent trends in adult asthma mortality, the Japan Asthma Death Investigation Committee studied the clinical characteristics of 649 patients who died of asthma between 1986 and 1991. The annual number of deaths decreased slightly: from 145 in 1986 to 89 in 1991. There was a large difference between sexes: the male:female ratio was 3:2. Most patients ranged in age from 50 to 70 years old. It is noteworthy that in one third of the patients death was caused by asphyxic-type asthma, while status asthmaticus was the cause in only 23.7%. The number of patients with mild or moderate asthma was slightly increased, although patients with severe asthma accounted for at least 70% of all deaths. The main causes of fatal asthma attacks were airway infections, fatigue, and stress. Other responses on the questionnaires indicated the following areas of concern: deficiencies in patient education, delays in treatment with corticosteroids and other antiasthma drugs, and delays in provision of emergency treatment.

Pulsed doppler echocardiography is reported to be a reliable method for evaluating pulmonary hemodynamics in patients with cardiovascular diseases, but not with chronic obstructive pulmonary disease (COPD) because of the difficulty in obtaining an appropriate echo-window in such patients. We examined 23 patients with COPD by doppler echocardiography (Hewlett-Packard, HP77020CV) with a 2.5 MHz transducer via the subcostal approach in a supine position. The right side of the heart catheterization was performed simultaneously in sixteen of these patients. The remaining 7 patients received the same procedure within one week of the doppler echocardiography. Adequate ejection flow pattern from the right ventricle was obtained in all the patients. Significant negative linear relationships were found between pulmonary arterial pressure and acceleration time (r = -0.67) and ejection time (r = -0.52). These findings show that doppler echocardiography can be useful when evaluating pulmonary hemodynamics even in patients with COPD.

We examined the relationship between daytime symptoms and respiratory disturbance indices during sleep in 60 patients with sleep apnea syndrome who had an apnea index of more than 5/hr for at least one night. Daytime hypersomnolence, morning headache, and a history of traffic accidents did not correlated strongly with apnea index or with nocturnal desaturation. The same was true of daytime blood pressure and nocturnal micturition. Both hemoglobin concentration and the mean pulmonary arterial pressure in the daytime correlated significantly with indices of nocturnal desaturation and not with apnea index, but this might reflect the positive correlation between those variables and the base-line level of daytime PaO2, in which case it would not be a direct consequence of nocturnal desaturation. These data suggest that diagnostic criteria should not be based on apnea index or desaturation alone. Long-term follow-up data on Japanese patients is needed to establish more rational diagnostic criteria and stage classification for sleep apnea syndrome.

Genetic factors may contribute to the development of bronchial asthma. However, results of traditional epidemiological studies have not clarified exactly which genes are involved. Recent advances in molecular genetics have resulted in the discovery of some candidate genes. Although there is still only a little information about the role of these genes in the development of asthma, we attempted to classify asthma based on genetics and here we present one example of such a classification. Classification of asthma based on genetics may be useful in screening for people susceptible to asthma and in developing prophylactic procedures. It may also enhance our understanding of the mechanisms of asthma and may promote the development of new therapeutic strategies.

Persistent coughing and bloody sputum developed in a 75-year-old man with mycosis fungoides. Chest X-ray films on admission showed combined patterns of alveolar and interstitial shadows in both lung fields. Histological examination of the transbronchial lung biopsy specimen revealed patchy infiltration of mycosis fungoides cells in alveolar septa. VEPA chemotherapy was ineffective against skin lesions and caused bacterial pneumonia, but combined treatment with etoposide (200 mg, once a week) and prednisolone (30 mg, 3 days per week) resulted in remission. The patient has been taking oral etoposide and prednisolone regularly, and has been free of skin and pulmonary lesions for two years. Combined therapy with low-dose etoposide and prednisolone may be worth trying in cases of advanced mycosis fungoides with pulmonary involvement.

We studied the effects of the inhaled anticholinergic agent oxitropium bromide (Ox) on pulmonary hemodynamics in eleven patients with chronic obstructive pulmonary disease. All the patients underwent right heart catheterization and seven of them underwent an incremental ergometer exercise test while in the supine position. Pulmonary hemodynamics and arterial blood gases were measured at rest and during maximal exercise, before and 30 minutes after inhalation of 2 puffs (200 micrograms) of Ox. Inhalation of Ox did not significantly change pulmonary hemodynamics at rest. The mean pulmonary arterial pressure and the mean pulmonary capillary wedge pressure during exercise decreased significantly (from 40.3 +/- 4.6 to 37.7 +/- 3.9 mmHg, and from 20.4 +/- 3.5 to 17.1 +/- 2.7 mmHg, respectively, mean +/- SE). However, neither cardiac output nor pulmonary vascular resistance changed with inhalation of the drug, at rest or during exercise. We therefore conclude that this commonly used dose of Ox does not directly affect the pulmonary vascular system. The small but significant decreases in pulmonary arterial pressure and pulmonary capillary wedge pressure with Ox may have been indirect effects, caused by bronchodilation.

To evaluate the possibility that viral infections can trigger acute exacerbations of idiopathic interstitial pneumonia (IIP), we analyzed data from 105 patients with IIP. Acute exacerbation was defined as an increase in dyspnea, a decrease in PaO2 by more than 10 Torr, and worsening of chest radiographic findings within one month. Viral infection was said to be involved when patients had more than a 4-fold change in viral antibody titer or viral inclusion bodies in sputum during the acute exacerbation. Of the 105 patients with IIP, 30 had acute exacerbations. Among these 30 patients, viral infection was said to be involved in 11 (37%). Presumptive viruses were influenza virus (n = 6), parainfluenza virus (n = 1), herpes simplex virus (n = 1), RS virus (n = 1), and cytomegalovirus (n = 2). The levels of serum immunoglobulin A (IgA) before acute exacerbations were significantly lower (p < 0.05) in patients in whom viral infection was said to be involved. These results suggest that viral infection associated with a low value of serum IgA is an important trigger of acute exacerbations of IIP.

Acyclovir, an anti-herpes virus drug, has been reported to affect aspirin-induced asthma (AIA). Acyclovir was reported to decrease the sensitivity to aspirin in some AIA patients. Although the hypothesis that AIA is related to viral infection has been stated, there is no proof that patients with AIA are infected with a specific virus. Therefore, whether the effect of acyclovir on AIA is due to an antiviral effect is not clear. We hypothesized that acyclovir directly affects airway smooth muscle. To test this hypothesis, we examined whether acyclovir can directly contract or relax guinea-pig airway strips, and whether it can modify contraction or relaxation induced with several agents in vitro. Acyclovir did not directly affect basal smooth muscle tone and did not affect the responses to leukotriene D4, prostaglandin E2, carbachol, or KCl. We conclude that acyclovir has no direct effect on the function of guinea-pig airway smooth muscle.

A 62-year-old woman was admitted to our institution for abnormal shadows on a screening chest roentgenogram. An immunoelectrophoresis test on admission revealed a polyclonal gammopathy. In her bronchoalveolar lavage fluid, the percentage of lymphocytes was found to be high: 47%. These results indicated an abnormal immunological state. A chest X-ray film showed multiple patchy shadows in both lungs. A chest CT scan revealed that the shadows were distributed peripherally, and abutted the pleura. Before treatment, the lesions enlarged toward the hilum concentrically, and cleared from the pleural side. This change is characteristic of cryptogenic organizing pneumonitis. The pathological finding at open lung biopsy was organizing pneumonitis. Bronchiolitis obliterans was not pathologically recognized. The shadows on the chest X-ray film almost completely disappeared after treatment with predonisolone at a daily dose of 30 mg. We diagnosed this as a case of cryptogenic organizing pneumonitis with typical shadows.

A 38-year-old man was found to have an abnormal shadow in his chest X-ray film during a general medical examination. A nodule with a homogeneous density and a clear margin was seen in the upper lobe of the right lung. Since this shadow gradually enlarged during a five-year follow-up period, he was admitted to our hospital. Chest contrast and dynamic CT scans and aortography showed characteristics of a benign tumor with somewhat rich vascularity. The doubling time of this tumor was about 430 days. Transbronchial brushing for cytologic study and a transbronchial biopsy showed no malignancy. However, the tumor was surgically resected because of its gradual growth over the five years. The resected tumor was histologically diagnosed as a benign clear cell tumor of the lung. This disease was first described by Leibow and Castleman in 1963, as a benign pulmonary tumor similar to metastatic renal cell carcinoma. This disease is extremely rare and only 61 cases have been reported: twenty cases, including the present case, in Japan and 41 in other countries.

We examined patterns of airway response of thirty nine asthma patients who had positive responses on allergen inhalation tests. Six types of inhaled allergens were used: house dust mite, animal, pollen, plant, mold, and others. Three patterns of responses were found: isolated immediate asthmatic response (IAR), immediate and late response (Dual), and isolated late asthmatic response (LAR). No relationship was found between the pattern of response and pulmonary function, airway sensitivity, IgE RIST titers, numbers of eosinophils, or concentration of inhaled antigens. Animal antigens tended to cause a dual response, and molds did only rarely. Ten of 39 challenged patients had an isolated LAR, half of which were caused by mold antigen inhalation. RAST scores were lower in isolated LAR than in other responses. Changes in the number and proportion of peripheral leukocytes during the challenge tests were also studied. Total leukocyte count had increased significantly in the isolated LAR group by 24 hours after the inhalation. These results suggest that the pattern of airway response after inhalation depended in part on the type of inhaled antigen, and that non-IgE mediated immune reactions have some role in the isolated LAR.

The effects of supplemental oxygen on exercise tolerance and exercise-induced dyspnea in patients with chronic obstructive pulmonary disease (COPD) and an arterial oxygen tension (PaO2) over 60 Torr were studied. Twenty two men who met the criteria stated above underwent three 6-minute walk tests while breathing room air, compressed air, or supplemental oxygen, in a double-blind randomized crossover fashion. The distance walked in 6 minutes was recorded, and the degree of dyspnea during exercise was quantified on a visual analog scale with a questionnaire that had eight descriptors of dyspnea sensations. The distances walked were: 535 +/- 27 (SE) for room air, 545 +/- 27 for compressed air, and 563 +/- 23 m for O2. These data indicate a significant placebo effect and an effect of supplemental oxygen. The data regarding dyspnea also indicated both a significant placebo effect and an effect of supplemental oxygen, but the descriptors for the placebo effect differed from those for the effect of supplemental oxygen. Patients in whom arterial desaturation (below 88%) developed during exercise with compressed air benefited from supplemental oxygen: they walked significantly farther and their dyspnea scores for two of the eight descriptors were significantly lower. However, patients in whom arterial desaturation (below 88%) did not develop during exercise with compressed air did not benefit from supplemental oxygen. Nonetheless, the degree of dyspnea during exercise with compressed air could not be used to predict the beneficial effect of supplemental oxygen.

Although inhaled nitric oxide (NO) has attracted attention as a pulmonary vasodilator, little heed has been given to its potential toxicity. Nitric oxide is known to be rapidly oxidized to nitrogen dioxide (NO2), which may damage pulmonary tissue. We examined the effects of temperature and humidity on the production of NO2 from NO. We also evaluated the amount of NO2 absorbed by soda lime, which is usually placed in the inspiratory line. For this purpose, we measured changes over time in the concentrations of NO and NO2 in mixtures that included NO, oxygen, and nitrogen in various concentrations, and at different temperatures and humidities. We confirmed that the formation of NO2 from NO follows the equation: -d[NO]/dt = 2 k[NO]2 [O2], where k is the rate constant. We found that k was significantly smaller at 37 degrees C than at 25 degrees C but was not influenced by humidity (0%, 40% or 90%). Although soda lime was very effective in absorbing NO2 from the inspiratory line, NO was simultaneously absorbed at the same molar ratio when the two gases existed together in the line. We thus conclude that inhalation of NO at 37 degrees C is more desirable than inhalation at room temperature, to suppress the production of NO2. When soda lime is used in the inspiratory line, attention should be paid to the reduction in the concentration of NO in the line.

A 43-year-old woman was referred for examination because of an abnormal shadow on a chest X-ray film. She had a 12-year history of seropositive rheumatoid arthritis. Chest X-ray films and CT scans showed a pleurabased solitary nodule without a cavity. Cytological examination of a transbronchial biopsy specimen did not lead to a diagnosis, so thoracoscopic enucleation was performed. Histologically, the nodule consisted of lymphocytes and fibroblasts surrounding a central necrotic area, which indicated that it was a rheumatoid nodule. This solitary necrobiotic nodule was radiographically indistinguishable from lung adenocarcinoma, so histologic confirmation was necessary.

To evaluate the role of gamma delta T cells in atopic asthma, we examined the relationship among atopy bronchial asthma, and genetic polymorphism of the gamma chain of T cell receptors (TCR) in families through atopic asthmatic probands. We recruited 5 families (69 subjects). Total serum IgE levels were estimated by a radioimmunosorbent test (IgE RIST). Skin prick tests were done with inhaled allergens consisting of house dust, grass and tree pollens, common molds, and animal danders. Antigen-specific IgE levels in response to these allergens were also measured by multiple antigen simultaneous test (IgE MAST). The atopic phenotype was determined by the presence of a positive skin test, an elevated antigen specific IgE value, an elevated total IgE level, or some combination of these. Although linkage of atopy or bronchial asthma to the gene encoding the gamma chain of TCR was excluded, the lod score between this gene and molds-specific IgE responses was 0.42 at the recombination fraction of 0.1. In an association study, a 19 kb allele of the gamma chain of the TCR gene was found more frequently in asthmatic subjects than in non-asthmatic subjects (p = 0.068). Also, molds-specific IgE responses were significantly associated with this allele (p = 0.018). These findings suggest that molds-specific IgE responses underlying atopic asthma are partly regulated by the gene encoding the gamma chain of the TCR.

The present status of idiopathic interstitial pneumonia (IIP) was evaluated from data collected as part of the Financial Support Program for patients with IIP, conducted in Hokkaido since 1979. The prevalence of IIP in 1992 was 4.08/100,000, and the yearly incidence was 1.23/100,000. The ratio of men to women was 1.85/1.0. Under age 55, women were more numerous than men, and over age 55, men were more numerous than women. Clinical and epidemiological analyses of the patients with IIP, with collagen vascular disease-interstitial pneumonia suggested possible contribution of dust inhalation to the etiology IIP. A prospective study revealed that about 20% of the subjects had systemic signs and symptoms of collagen diseases from 2 months to 10 years after the diagnosis of IIP. In addition, about 15% of the subjects with IIP developed lung cancer during the follow-up period. This incidence was significantly higher than that in the patients with chronic obstructive pulmonary diseases and the same smoking history, which suggests that IIP itself is a risk factor for lung cancer.

The clinical usefulness of 24 hr home monitoring of oxygen saturation (SaO2) with pulse oximeter was studied in 48 outpatients with COPD. In addition, doppler echocardiography for measurement of acceleration time (AcT), which inversely correlates with mean pulmonary arterial pressure, a 6-minute walk test, and an exercise study on a bicycle ergometer were performed in 26, 17, and 14 patients, respectively. Nadir SaO2 and the total time during which SaO2 was below 90% were calculated to estimate diurnal and nocturnal oxygen desaturation (diurnal nadir SaO2, diurnal TSaO2 < 90%, nocturnal nadir SaO2, and nocturnal TSaO2 < 90%). Relations between the indices of desaturation measured during home monitoring and dyspnea grade (Fletcher-Hugh-Jones), awake PaO2, AcT, Hb, Ht, and oxygen desaturation during the exercise tests were also studied. Diurnal nadir SaO2 was lowest and diurnal TSaO2 < 90% was longest in the group with dyspnea grade IV. In the other groups, various degrees of oxygen desaturation were observed, even within groups. Diurnal nadir SaO2 and nocturnal nadir SaO2 correlated with awake PaO2, but not with diurnal TSoO2 < 90%. Diurnal nadir SaO2 was similar to nadir SaO2 during the exercise tests. AcT, hemoglobin, and hematocrit correlated with diurnal oxygen desaturation but not with nocturnal oxygen desaturation. From the above findings, we conclude that pulmonary hypertension may be associated with diurnal oxygen desaturation, and that home monitoring of SaO2 is useful for the detection of oxygen desaturation not predicted from dyspnea grade and PaO2 while awake.

It is known that the prognosis of patients with chronic obstructive pulmonary disease (COPD) is related to some indices of pulmonary function tests representing airway obstruction and/or the level of arterial oxygenation. Although the grade of exertional dyspnea, which is a common complaint of such patients, has also been claimed by some to be an important prognostic factor, it is not certain whether dyspnea grade is independent of other objective indices. In this study, we examined the prognosis of 97 patients with COPD in a retrospective fashion by Kaplan-Meyer's method and compared the survival time according to the dyspnea grade. As a whole, the survival time in those patients (n = 22) whose dyspnea grade initially was 4 or 5 was shorter than in patients with dyspnea grade 1 or 2 (n = 40) and dyspnea grade 3 (n = 30) (dyspnea grade 4-5 vs. dyspnea grade 1-2 and 3, p < 0.001). Since patients with higher dyspnea grades are associated with lower pulmonary function, we selected the patients whose PaO2 and forced expiratory volume in 1 second were in the same range. Dyspnea grade varied even among these subjects, and again was significantly related to the survival time. We therefore conclude that dyspnea grade, even though a subjective complaint, is an independent prognostic factor in patients with COPD.

Questionnaires were answered by 3,243 presumably healthy subjects who underwent regular medical checkups in four cities. The prevalences of risk factors for sleep-disordered breathing (SDB) were as follows; habitual snoring was reported by 13-16%, excessive daytime sleepiness by 8-9%, insomnia by 7-13% and systemic hypertension by 5-13%. Polysomnographic studies performed on some possible SDB cases who were selected by the presence of risk factors estimated that the average prevalence of SDB in the present population would be in the range of 1.14-1.94%. Secondly, questionnaires were sent to the main hospitals and institutes involved in the management of patients with SDB, asking about diagnostic criteria, number of SDB patients, management, effectiveness of treatment, etc. The total number of patients registered at those hospitals was 2,751 in 1991. Of the 132 patients who were followed for more than six months, the efficacies of body weight loss, medications, nasal CPAP and UPPP were compared. Based on the analyses of the 279 patients examined some tentative vriteria for diagnosis and for treatment are proposed.

We report a case of interferon-alpha-induced pneumonitis. A 61-year-old man was diagnosed as having recurrence of renal cell carcinoma and treated with 3 x 10(6) unit of interferon-alpha daily for 8 weeks. On the 55th injection, he presented with a high fever and mild dyspnea, and his chest CT films revealed diffuse reticulonodular shadows in both lung fields. We suspected interstitial pneumonitis due to interferon-alpha, and started steroid therapy. He showed rapid improvement of symptoms and diffusing capacity, and the pulmonary infiltrates in his chest CT were markedly reduced. Transbronchial lung biopsy (TBLB) revealed slightly thickened alveolar walls and small granulomatous-like lesions. These granulomatous-like lesions showed marked accumulation of macrophages. To our knowledge, this is the first report of interferon-alpha-induced pulmonary injury in Japan.

The efficacy of conventional CT in the diagnosis of pulmonary emphysema (PE) was studied in 122 patients with miscellaneous diseases including 26 patients with PE. The density and the distribution of low attenuation area (LAA) were evaluated by six independent physicians. Analysis with kappa statistics showed a good inter-observer agreement in the detection of LAA. The grading of LAA correlated well with FEV1/FVC, DLCO/VA, and lung volumes, which indicated that PE could be detected by conventional CT by the evaluation of LAA. The agreement was poor, however, for the detection of low grade LAA and there were some false positives, and there was no specific pattern in the distribution of LAA in PE compared to other pulmonary diseases. We conclude that the evaluation of LAA by conventional CT is simple and effective in the screening of PE.

A 58-year-old woman was admitted with cough, dyspnea on effort and diffuse micronodular and patchy shadows on her chest roentgenograms. Two weeks later, acute pulmonary hemorrhage developed with low levels of complement and positive immune complexes. She was diagnosed as having systemic lupus erythematosus (SLE) with positive anti-nuclear antibody, positive anti-DNA antibody, biologically false positive Wassermann reaction, auto-immune hemolytic anemia and photosensitive dermatoses. In addition, anti-glomerular basement membrane antibody (anti-GBM antibody) was positive in serum, but pulmonary hemorrhage was thought to be secondary to SLE, since the renal biopsy showed lupus nephritis. Cases of SLE with positive anti-GBM antibody are seldom confirmed. It was assumed that the basement membrane of the lung or kidney was damaged first by interstitial pneumonitis due to SLE or lupus nephritis, basement membranes antigens were exposed, with secondary production of anti-GBM antibody.

We studied the effects of inhaled anticholinergic (oxitropium bromide, 0.2 mg) and beta-adrenergic (fenoterol 0.4 mg) drugs on respiratory function and arterial blood gases in fourteen male patients with pulmonary emphysema (age 63 +/- 8 years; FEV1/FVC 1.41 +/- 0.73 L) using a three day, randomized, double-blind placebo-controlled design. Each day, spirometry and arterial blood gas analyses were performed before and 45 min after inhalation. Both fenoterol and oxitropium bromide significantly improved FEV1 by 21% and 16%, respectively, although there was no significant difference between the two drugs. However, the mean value of PaO2 significantly decreased from 74.5 +/- 2.6 to 69.3 +/- 2.7 Torr with fenoterol, but not with oxitropium and placebo. Change of PaO2 with fenoterol was significantly correlated with %FRC, but not with FEV1 nor change of FEV1. We therefore conclude that an anticholinergic inhalant bronchodilator is more favorable for patients with COPD than a beta-adrenergic agent.

Recently, the role of activated T-cell derived cytokines in the pathophysiology of asthma has been recognized. In this study, we evaluated the effects of interleukin-2 (IL-2) and gamma interferon (IFN-gamma) on contractile and relaxing responses of guinea-pig tracheal strips in isometric tension measurement system. IL-2 enhanced carbachol (Carb)- and KCl-induced contraction, and attenuated isoproterenol (Iso)-induced relaxation. IFN-gamma had little effect on Carb and KCl contraction, but enhanced Iso relaxation. These effects of cytokines were abolished by denuding epithelium from tracheal strips. These results suggest that IL-2 and IFN-gamma are able to affect functions of non-immune cells in the airway, and that the airway epithelium has some role in the effects of cytokines on airway responses.

We measured intracytoplasmic free calcium ion concentration ([Ca3+]i) of alveolar macrophages (AMs) in order to elucidate the mechanism(s) of lipopolysaccharide (LPS)-hyperresponsiveness of AMs in patients with sarcoidosis at the second messenger level. Resting [Ca2+]i was higher in patients with sarcoidosis than in normal subjects. [Ca2+]i increase responses were also elevated in patients with sarcoidosis when AMs were stimulated with either anti-CD14 (a LPS/LPS-binding protein complex receptor) antibody, anti-CD64 (Fc gamma receptor I), antibody or platelet activating factor. After incubation with interferon-gamma, resting [Ca2+]i and increase in [Ca2+]i induced by anti-CD14 antibody stimulation were higher in patients with sarcoidosis as compared with values before incubation. Thus, these data suggest that activation of AMs at the second messenger level induced by IFN gamma, at least in part, accounts for LPS-hyperresponsiveness in sarcoidosis.

We prospectively elucidated the effect of home oxygen therapy (HOT) on the prognosis of patients with chronic pulmonary disease associated with pulmonary hypertension. One hundred and twenty-seven patients with pulmonary hypertension (mean pulmonary arterial pressure > or = 20 Torr) participated in this study. Fifty-four patients had chronic pulmonary emphysema, 5 chronic bronchitis, 19 diffuse panbronchiolitis, 29 old tuberculosis, 8 pulmonary fibrosis, and 12 other diseases. Fifty-one patients died of respiratory failure. The survival curve of patients who received HOT was not different from that of patients who did not receive HOT, although FEV1 and PaO2, both prognostic factors, were significantly worse in the patients who received HOT than in the patients who did not receive HOT. In the patients with COPD, the survival rate of patients who received HOT was significantly higher than that of those who did not receive HOT. The mean survival time of the patients who received HOT was significantly longer than that of the patients who did not received HOT (1971 +/- 217 SEM days and 978 +/- 156 days, respectively). From these data, we conclude that HOT improves the survival of patients with chronic pulmonary disease, especially COPD, associated with pulmonary hypertension.

In an attempt to elucidate the role of cholinergic mechanism in respiratory chemosensitivity to CO2 in humans, we examined 17 healthy male volunteers for ventilatory responses to hyperoxic progressive hypercapnia and isocapnic progressive hypoxia on three separate days in a randomized, double-blind fashion. Pirenzepine, a M1 muscarinic antagonist which does not cross the blood-brain barrier, biperiden, another M1 muscarinic antagonist which is expected to penetrate into the central nervous system, or placebo was intravenously preinjected before the measurement of ventilatory responses. There were no significant differences in the mean magnitude of ventilatory responses among the three experimental days. However, despite the poor correlation between the magnitude of ventilatory response to hypercapnia in the placebo and pirenzepine studies, there was a significant correlation between them when the value in the pirenzepine study was expressed as % of control, value i.e., subjects with greater hypercapnic ventilatory response in the placebo study showed greater declines with biperiden. Since these relations were seen only for the ventilatory response to hypercapnia with biperiden, we suggest that a cholinergic mechanism, particularly the M1 muscarinic receptor, may be involved in chemoreception to CO2 in the central nervous system and constitute the neurochemical background for the interindividual variation in hypercapnic ventilatory response in humans.

Familial aggregations and genes for atopy, airway hyperresponsiveness, and serum IgE were studied in 69 members of five atopic asthmatic families spanning three generations. Atopy was found in 68%, bronchial asthma in 26%, airway hyperresponsiveness in 45%, and positive mite allergen in 59%. Both atopy and airway hyperresponsiveness were inherited in an autosomal dominant fashion, but were not related to each other. No linkage was found of HLA with atopy and mite positivity. T cell gamma receptor gene (7p15), IL-3, IL-4, and IL-5 genes (5q23), and postulated atopic gene (11q13) were all not linked to atopy. However, alle 2.5 kb of 11q13 showed an association with serum IgE level. The beta 2 adrenergic receptor gene (5q31-32) was linked to airway responsiveness to inhaled beta 2 adrenergic agonist, and was associated with the occurrence of bronchial asthma.

Fluorescent in situ hybridization (FISH) with biotinated chromosome-specific repetitive DNA probes was used for the cytogenetic study of lung tumors and three cell lines of human lung cancer. The authors utilized a set of satellite DNA probes, specific for chromosomes 7, 17, X, Y in order to detect numerical chromosome aberrations in tumor cell nuclei. Normal diploid human lymphocyte nuclei, which served as the control, have have two signal spots in 95% of nuclei in response to 7, 17 chromosome probes. However, lung cancer cells have numerical heterogeneity, and copy numbers as determined by FISH were not definite with each probe. Discrepancies between cytogenetic and flow cytometric studies in the detection of aneuploidy in some tumors were shown. The number of FISH spots showed a correlation only with the Ki-67 labeling index expressed in proliferating cells. Loss of the Y chromosome in a high percentage of cells was seen by FISH in some tumors from male patients. These data indicate that FISH with chromosome-specific repetitive DNA probes can serve as a cytogenetic tool for the analysis of interphase nuclei of lung tumors with respect to the detection of numerical chromosome abnormalities.

Three cases of chronic respiratory tract lesions as a complication of adult T-cell leukemia (ATL) are reported. Case 1 was seropositive for HTLV-1 on recent examination following treatment of bronchiolitis. Chest radiograph revealed over inflation of the lungs and bilateral diffuse small nodular shadows. Pulmonary function test resulted hypoxemia and mixed ventilation disorder. Pathological examination confirmed lymphocytic infiltration of the bronchiolar wall. Both clinically and pathologically the patient was diagnosed as having diffuse panbronchiolitis (DPB). Therefore, this case was considered to be the bronchiolar type of HTLV-1 associated bronchiolo-alveolar disorder (HABA). The other two cases with smoldering or chronic ATL presented with long-standing symptoms of productive cough due to chronic respiratory lesions. We consider that all three cases had HTLV-1 virus associated pulmonary lesions, but with different clinical and pathological presentations. Among 12 cases of bronchiolitis experienced at our hospital, three were positive for HTLV-1.

A 59-year-old female was admitted for spontaneous pneumothorax. After evacuation, the chest X-ray film showed a round mass lesion at the left hilum. Following curettage and bronchoalveolar lavage of the left B3c, the mass became smaller, suggesting the diagnosis of round atelectasis. This is the first report of round atelectasis complicated by spontaneous pneumothorax. The mechanism of this case is suggested to resemble that of round atelectasis associated with pleural effusion.

The clinical importance of ras oncogene product p21 was evaluated in surgically treated non-small cell lung cancer patients. Paraffin sections of tumors were analysed immunohistochemically using anti-ras p21 monoclonal antibody rp35. The ras p21 expression was correlated with clinicopathological parameters and survival. Survival analysis demonstrated significantly longer survival times in patients with p21-negative tumors than those with p21-positive tumors. In Cox's multivariate analysis, ras p21 expression was a major and independent prognostic determinant of survival. On the other hand, in small cell lung cancer, L-myc gene is known to be frequently amplified and overexpressed. Immunoprecipitation analysis of two small cell lung cancer cell lines (classic type) revealed three major L-myc proteins (p60, p66 and p68), all of which were derived from extensive phosphorylation of a p59 protein. Expression and phosphorylation of L-myc protein, as well as the autocrine growth mechanism of gastrin-releasing peptide (GRP), is thought to be involved in the malignant behavior of small cell lung cancer.