We evaluated 240 consecutive subjects (aged 20-91) without cardiopulmonary, endocrine or, neuromuscular disease consecutively regarding pulmonary function (TLC, VC, FEV₁, RV) and static maximal inspiratory (PImax) and expiratory (PEmax) pressures. PImax and PEmax declined with advancing age. PImax correlated with grip strength, VC, FEV₁, height, weight, and RV/TLC. PEmax also correlated with grip strength, TLC, VC, FEV₁, height, and weight. Age, height, weight, and grip strength were entered stepwise into multiple linear regression models with PImax or PEmax as the dependent variable. Stepwise regression analysis revealed that grip strength was an independent predictor for both PImax and PEmax. However, age itself was not an independent predictor for PImax or PEmax. These results suggest that static maximal respiratory pressures decrease with aging, and that age-dependent changes in respiratory muscle function may depend on other factors, including lung volume, skeletal muscle status, and body composition.

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We tested the effects of a DNA topoisomerase inhibitor (camptothecin; CPT) on the transduction efficiency of AAV vectors in cultured human airway epithelial cells. The cells were treated with CPT for 24 hours, then exposed to AAV-CMV-LacZ for 1 hour at different multiplicities of infection (moi). Transduction efficiency of AAV vectors was assessed using X-gal staining as the percentage of LacZexpressing cells. The transduction efficiency was approximately 1.5 to 10 fold increased by treatment with CPT prior to AAV vector exposure. However, treatment with CPT after AAV vector infection did not enhance the transduction efficiency of the vectors. These results suggest that pre-treatment with CPT increases the transduction efficiency of AAV vectors, probably by nodulating cellular function.

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We studied the effect of intravenous administration of a dopamine (DA) agonist and antagonist on the hypoxic response of phrenic nerve activity in anesthetized, vagotomized and mechanically ventilated rabbits. The experiments were performed in both intact and carotid sinus denervated animals. In the intact animals, hypoxic challenge (FIO₂=0.10) increased the amplitude of integrated phrenic nerve activity (iPNA) without any alteration in respiratory frequency. In the carotid sinus denervated animals, the hypoxia progressively depressed iPNA. Neither the DA antagonist, haloperidol (0.5mg/kg i. v.), nor the DA agonist, apomorphine (0.3mg/kg, i. v.) changed the iPNA during normoxia in either the intact or denervated group. Administration of haloperidol enhanced iPNA response to hypoxia in the intact group. Apomorphine decreased the hypoxic response to iPNA. Although apomorphine did not change the control hypoxic response to iPNA in the denervated group, haloperidol augmented hypoxic respiratory depression in the carotid sinus denervated group. Therefore, we concluded that the effect of DA on peripheral chemoreceptors inhibits the hypoxic ventilatory response, but stimulates the hypoxic ventilatory response in the central nervous system.

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We investigated interstitial pneumonia associated with collagen vascular disease (IP-CVD) in association with lung cancer. Seventy-three cases of IP-CVD were included in this study. Nine (12%) of the 73 cases were associated with lung cancer, one of which had double lung cancers. The histological types of the cancers were adenocarcinoma (5 cases), epidermoid carcinoma (2 cases), small cell carcinoma, large cell carcinoma and large cell neuroendocrine carcinoma (one case each). The lesions were located in the central or peripheral lung in 3 and 7 of the ten cancers, respectively. Of the seven cases diagnosed as having IP-CVD followed by lung cancer, five had stage I disease, and one each of the remaining two cases was in stage IIIA and stage IV. Six of the seven peripheral cancer lesions which were resected or autopsied could be analyzed with regard to the topographical relationship between the primary site and fibrotic lesions. Only three cancers were encased by or in close proximity to, honeycomb lung, although most of the lung cancers arose in relation to fibrotic lesions. Moreover, the acute exacerbation of IP-CVD after operation or chemotherapy without thoracic irradiation shoud be monitored carefully.

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We demonstrated that CD4⁺ αβ (CD4⁺) and γδ T cell subsets from healthy donors had similar effector functions (cytotoxicity and cytokine production) in response to mycobacterial antigens, despite differences in the antigens recognized. To elucidate the pathogenesis of pulmonary tuberculosis, this study was undertaken to compare T cell functions between patients with pulmonary tuberculosis with no complications and healthy controls.
Both resting and activated CD4⁺ and γδ T cells from the patient group proliferated in response to live BCG at a significantly lower rate than those from the control group. The cytotoxicity of BCG-pulsed monocytes and IFN-γ production in both the CD4⁺ and γδ T cells from patients was significantly lower than those of controls. In contrast to IFN-γ, significantly higher IL-10 production by both CD4⁺ and γδ T cells from patients was detected. The proliferative responses to BCG by CD4⁺ and γδ T cells from patients after antituberculous therapy were partially restored, but remained at lower levels compared with controls.
These results suggest that not only a general deterioration in CD4⁺ and γδ T cells effector functions, but also suppressive factors (such as IL-10) might be responsible for the pathogenesis of pulmonary tuberculosis, and that the low response to BCG by both CD4⁺ and γδ T cells in patients with tuberculosis is in part attributable to patient predisposition.

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We studied respiratory muscle endurance with an inspiratory threshold loading (ITL) device using Martyn's method (2-min incremental loading test) in 9 patients with chronic pulmonary emphysema (CPE patients) and in 9 elderly subjects with no lung disease (NE subjects), and their endurance was compared with that of 9 normal young subjects (NY subjects). In 11 cases (8 CPE patients and 3 NE subjects) a treadmill exercise test was performed and cardiopulmonary parameters obtained from the ITL and treadmill tests were compared. The maximum weight tolerated for 2 minutes (Wmax) and the mean peak inspiratory mouth pressure/maximum inspiratory mouth pressure ratio at the maximum load (Ppk/MIP at Max Load) were used as indices of respiratory muscle endurance. CPE patients had significantly decreased Wmax compared with those of NE and NY subjects. Wmax in all cases positively correlated with Ppk/MIP at Max Load, and endurance time of both the ITL and treadmill tests. During both tests, SaO₂ significantly decreased, and heart rate and mean blood pressure significantly increased. There was less change in SaO₂ and heart rate during the ITL test than during the treadmill test, and neither arrhythmias nor ST changes on ECG were observed during the ITL test. These results indicate that the ITL test can be easily and sefely employed in CPE patients and elderly subjects to estimate respiratory muscle endurance.

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A 51-year-old woman was admitted with fever, cough and dyspnea. She had been taking Sairei-to, a traditional Chinese medicine, for 2 months. On admission, chest X-ray revealed a ground-glass appearance in the lung fields bilaterally and serum LDH was elevated. A differential cell count of the bronchoalveolar lavage fluid (BALF) showed that lymphocytes were increased, with a decreased ratio of CD4/CD8 cells. A lymphocyte stimulation test (LST) for Sairei-to using the lymphocytes in BALF was a positive, although a test of peripheral blood was negative. Sairei-to-induced pneumonitis was diagnosed based on the clinical course, labolatory findings, BALF cell analysis and LST of BALF. Only 4 cases of pneumonitis due to Sairei-to have been reported. This case suggests that LST of BALF is useful for diagnosing drug-induced pneumonitis.

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We report a case of myiasis caused by Phaenicia sericata during mechanical ventilation. An 86-year-old woman with bronchiectasis was admitted to our hospital with severe respiratory failure. Treatment with mechanical ventilation and sedatives was initiated. On the 10th day of hospitalization, about 20 white larvae were found in the patient's oral or nasal cavities. The larvae were removed and identified as Phaenicia sericata. No mucosal injury was found in the patient's oral or nasal cavity by endoscopic examination. The patient died of multiple organ failure caused by sepsis that had no association with myiasis. From the clinical course and the fly's life cycle, it is considered that the fly laid eggs in the patient's oral or nasal cavity while she was sedated during mechanical ventilation. Myiasis can occur even in a hospital.

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A 55-year-old man was admitted to our hospital with of hemoptysis, progression of anemia and renal failure in February, 1996. Idiopathic interstitial pneumonia had been diagnosed and he had been followed at a regional hospital since 1988. On the third day after admission, he suffered from sudden and massive hemoptysis. Goodpasture's syndrome was diagnosed because anti-GBM antibody was detected in serum. A high titer of MPO-ANCA was also recognized simultaneously. Steroid pulse therapy, immunosuppressive therapy, and plasmapheresis were begun, but he died on the 28th hospital day because of severe hypoxemia and multi-organ failure. Histological examination after autopsy revealed crescentic glomerulonephritis with linear deposition of IgG in the glomerular capillary wall, and interstitial pneumonia accompanied by massive alveolar hemorrhage. It was suggested that in this patient, not only anti-GBM antibody but also circulating MPO-ANCA might have participated in the progression of the crescentic glomerulonephritis and alveolar hemorrhage observed in Goodpasture's syndrome.

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We report a case of severe legionella pneumonia with acute respiratory failure, successfully managed with veno-venous extracorporeal membrane oxygenation (VV-ECMO). The patient presented with 4-day history of fever and cough. He was in critical condition, with exacerbated respiratory failure. Mechanical ventilation, volume replacement and antibiotic therapy were initiated. Despite increasing mechanical ventilatiory support (FiO₂ 100%, TV 10ml/kg, f 30min, PEEP 5cmH₂O), PaO₂ fell below 40Torr and life sustaining measures were undertaken. VV-ECMO (flow 30ml/kg/min) was commenced, and the patient responded well, with an elevation of PaO₂. Erythromycin therapy was effective against the pneumonia. VV-ECMO was maintained for 92 hours, mechanical ventilation was successfully discontinued 11days after and the patient was discharged 82 days after cessation of ventilator support. Serum antibody examination proved legionella infection. VV-ECMO may have a role in the management of patients with acute respiratory failure caused by bacterial pneumonia.

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We report a case of sero-negative tsutsugamushi disease diagnosed by polymerase chain reaction (PCR). A 54-year-old man who worked in Nagano prefecture presented with flu-like symptoms that did not respond to cephalosporin therapy. On admission to another hospital, chest roentgenography revealed abnormal shadows; liver dysfunction was also present. Despite therapy, the patient's condition gradually worsened and he was transferred to our intensive care unit. Erythema on all extremities and scabs on the right medial femoral region and the dorsum of the left foot suggested a diagnosis of tsutsugamushi diesase. We administered minocycline and gave percutaneous cardiopulmonary support for adult respiratory distress syndrome. Despite all efforts, the patient died. Although serologic tests were not positive, Karp strains of R. tsutsugamuschi were identified on PCR amplification. Autopsy revealed evidence of acute hemorrhagic pancreatitis, which has not been reported previously in tsutsugamushi disease. We conclude that PCR techniques may be useful in confirming a diagnosis of early tsutsugamushi disease.

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A 16-year-boy who had taken a common over-the-counter cold remedy containing Sho-saiko-to, presented with fever, severe cough, sputum and dyspnea. Two days later, he was admitted because a negative density, pulmonary edema-like shadow was noted on chest X-ray. A diagnosis of drug-induced pneumonia was strongly suspected, because an arterial blood gas analysis showed severe hypoxemia and leukocytosis with eosinophilia, and the chest X-ray showed a diffuse negative density pulmonary edema like shadow bilaterally. The findings on microscopic examination of transbronchial lung biopsy specimens were compatible with eosinophilic pneumonia. The eosinophil percentage in the bronchoalveolar lavage fluid was high. The result of a lymphocyte-stimulation test was positive for Sho-saiko-to, and Sho-saiko-to-induced pneumonia was strongly suspected. The patient ceased taking the cold remedy, and prednisolone was given. The clinical symptoms, severe hypoxemia, and chest X-ray findings markedly improved. To the best of our knowledge, there have been no previous reports of acute eosinophilic pneumonia induced by Sho-saiko-to.

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A 50-year-old man resented at a local medical clinic with nasal obstruction. He was treated but did not improve. He then consulted our institution. Chest X-ray disclosed infiltrative shadows in the basal region of the left lung. A computed tomography scan of the lung showed marked thickening of the airway walls exterding from the trachea to both bronchial trees and obstructive changes in the left lower lobe of the lung. On bronchoscopic examination the bronchial mucosa was reddened and edematous with a pinhole bronchial obstruction in one region. Congo red staining of biopsy samples taken from the bronchial mucosa showed deposition of an amorphous substance. Tracheobronchial amyloidosis was diagnosed. The amyloid material was resistant to potassium permanganate and tested positive for λ-chain of L immunoglobulin. Otorrhinolaryngological examination disclosed a tumor in the inferior nasal concha as the cause of his nasal obstruction. The nasal tumor was resected and ALλ-type amyloidosis was diagnosed pathologically. Tracheobronchial and inferior nasal concha amyloidosis is an extremely rare pathological condition. The patient was followed for one year and remgine asymptomatic without treatment.

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A 61-year-old man with superficial bladder cancer, which was detected after he complained of hematuria, was treated three times with intravesical BCG administration. Since liver dysfunction was detected thereafter, he was admitted to our hospital. Three days after admission, he complained of dyspnea on exertion associated with severe hypoxemia, as well as abnormal findings on chest X-ray, i. e. extensive bilateral lung densities. We performed bronchoscopic examination and obtained bronchoalveolar lavage fluid (BALF) and lung biopsy specimens (TBLB). In the BALF, a marked increase in the total cell number, particularly lymphocytes with a high CD4/CD8 ratio was noted. TBLB specimens revealed the lesions to be numerous non-caseating granulomas. We failed to obtain definite evidence of BCG in the sputum, urine, blood, and BALF. Instead, we found that a lymphocyte stimulation test for BCG (DLST) was strongly positive. Based on these findings, severe interstitial pneumonia probably induced by hypersensitivity against BCG, was diagnosed. Anti-tuberculous agents, and steroid-pulse therapy followed by oral administration of relatively low dose of steroid ameliorated the abnormal conditions, including chest X-ray film findings and hypoxemia. The population of lymphocytes and CD4/CD8 ratio in the BALF were reduced as well. Serious interstitial pneumonia was induced by the intravesical administration of BCG, which resulted in transitional changes in the BALF cell component.

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Langerhans cell granulomatosis, once called histiocytosis X, is a rare disease. A case of multifocal Langerhans cell granulomatosis in the bone, lymph nodes, skin and lungs of an 18-year-old man is described. Head CT and MRI showed a soft tissue mass of the left temporal bone. Lymph node and skin biopsies substantiated a diagnosis of Langerhans cell granulomatosis. A High resolution CT scan of the lung revealed a small cystic lesion, and bronchoalveolar lavage (BAL) showed an increased number of S-100 positive cells. Steroid therapy resulted in complete resolution, and no S-100 positive cells were obtained in the follow-up BAL study.

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We describe the first case, to the best of our knowledge, of non-specific interstitial pneumonia associated with psoriasis vulgaris and polymyalgia rheumatica (PMR).
A 50-year-old woman was admitted with a dry cough and a bilateral basilar reticulonodular shadows on chest X-ray. Bronchoalveolar lavage fluid analysis revealed lymphocytosis and a decreased CD4/CD8 ratio. A thoracoscopic lung biopsy specimen showed evidence of non-specific interstitial pneumonia.
During her clinical course, she began suffering from psoriasis vulgaris and polymyalgia rheumatica.
Corticosteroid therapy had no effect, but maintained a stable condition during a follow-up period of 4 years.

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A 20-year-old man visited our hospital complaining of headache and a dry cough. Chest X-ray and chest CT showed bilateral hilar and mediastinal lymphadenopathy, multiple cavitations with thin, smooth walls, and diffuse granular shadows. A transbronchial biopsy specimen revealed sarcoid granuloma. Primary acute pulmonary cavitation of sarcoidosis was diagnosed, since there was no evidence of infection, emphysematous change, fibrotic or cystic bronchiectatic change on chest X-ray.
EEG, contrast enhancement of brain CT scans and MRI were performed because the patient complained of headache. EEG showed a high voltage paroxysmal slow wave and giant build-up, whereas brain CT showed no abnormalities. T₁-weighted MRI with gadolinium enhancement showed mutiple high intensity nodules in the convexity, brain stem, and spinal cord. Corticosteroid therapy (60mg/day) was started. After 1 week of treatment, the headache ceased. After 2 weeks of treatment, both the cavities in the lung field's and the nodules in the central nervous system disappeared. Therefore, the dose of corticosteroids was gradually reduced to a maintenance dose of 5mg/day, and no relapse was noted. We report a very rare case of primary acute pulmonary cavitation in sarcoidosis complicated by multiple nodular lesions in the central nervous system.

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Patient 1; An 18-year-old woman was admitted to our hospital with pneumothorax. She had no history of smoking. Chest CT showed multiple cysts, and pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. She recovered without therapy 3 months later and a chest CT taken at that time was normal. She began smoking, 3 years later, and bore two children. She is withont recurrence after 8 years.
Patient 2; A 23-year-old man was admitted to our hospital with pneumothorax. He had a smoking history (index=180). Chest CT showed multiple cysts, and pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. He stopped smoking and recovered without therapy one month later, and subsequently, his CT findings returned to normal. Two years later, he began smoking again, but has no relapse.
Patient 3; A 21-year-old man was admitted to our hospital with pneumothorax. He had no history of smoking. A chest CT showed multiple cysts, and pulmonary eosinophilic granuloma was diagnosed by open lung biopsy. Diabetes insipidus was subsequently noted. Dyspnea persisted, and he recovered 4 months later after steroid treatment. He was without relapse 2 years later but the multiple cysts remained.
We report three cases of pulmonary eosinophilic granuloma, and discuss their pertinent clinical features.

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A 51-year-old woman was referred to our hospital with dyspnea. Chest roentgenogram on admission showed dilation of the pulmonary arteries and hyperlucency in the lung fields. An ultrasonic cardiographic examination showed that the right atrium and ventricle were dilated. Pulmonary thromboembolism due to left popliteal vein thrombosis was diagnosed by perfusion scintigram of the lung, which showed multiple wedge-shaped defects, and by digital subtraction angiogram, which showed a filling defect in the left popliteal vein. Antiphospholipid syndrome was diagnosed after IgG anticardiolipin antibody was detected. Scleroderma was subsequently diagnosed because the patient exhibited Raynaud's phenomenon and proximal scleroderma. Although closely associated with lupus erythematosus and other lupus variants, antiphospholipid syndrome has not been recognized as a common complication of scleroderma. This is the first report of a patient with pulmonary thromboembolism associated with antiphospholipid syndrome and scleroderma.

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A 66-year-old woman was admitted to our hospital with a cough, wheezing, and expectoration. Chest X-ray and CT scanning revealed atelectasis and infiltration of the middle lobe, but no central bronchiectatic change. The patient had eosinophilic infiltration elevated serum IgE, RAST against Aspergillus) (A.) fumigatus, a positive immediste skin reaction, and a positive test for antibodies agaisnt A. funmigatus. Bronchoscopy demonstrated mucoid impaction that plugged the middle lobe bronchus. The mucoid plug contained A. terreus and numerous eosinophils. Because the level of the precipitating antibody for counter immunoelectrophoresis agaisnt A. terreus was higher than that at A. fumigatus, allergic bronchopulmonary aspergillus caused be A. terreus was diagnosed. Oral and inhalation therapy of corticosteroids ameliorated the symptoms and abnormal laboratory findings.

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A 39-year old female was found to have Intralobar pulmonary sequestration with a high serum level of the tumor markers, CA19-9, CA125 and NCC-ST-439. The lesion was located in the left S¹⁰ and an aberrant artery from the aorta was noted. After partial resection of the left lower lobe, serum levels of the tumor markers (CA19-9 2418U/ml, CA125 50.3U/ml, NCC-ST-439 13.0U/ml) gradually returned to normal. The half-life of serum CA19-9 was about 7 days. Immunohistochemical analysis revealed that CA19-9 was being produced in the bronchial epithelium of the sequestered lung. Increased serum levels of CA19-9 may be helpful in diagnosing pulmonary sequestration.

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A 60-year-old female had old pulmonary tuberculosis. Chest radiographs taken in 1980 revealed a small cavitary lesion due to old lung tuberculosis in the right upper lung fields. Chest radiographs taken in 1984 revealed a fungus ball in the cavity and the adjacent pleura was thickened. Chest radiographs taken in 1994, revealed that the margin of the fungus ball had become ill-defined, and infiltrative shadows surrounded the cavity. A test for aspergillus antigen was positive and toxicolor test^®was elevated in serum.
Chest radiographs taken in 1996 revealed that the fungus ball had enlarged substantially.
We consider this case to be a semi-invasive pulmonary aspergillosis which spread by direct invasion from an aspergilloma to the surrouding cavitary wall.

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