We studied cells and proteins in bronchoalveloar lavage fluid examined at the First Department of Internal Medicine of Shinshu University Hospital between 1990 and 1994. The samples came from 21 healthy subjects and from 216 patients with various diseases. Lymphocyte counts were abnormally high in patients with bronchiolitis obliterans organizing pneumonia, Sjögren's syndrome, sarcoidosis and hypersensitivity pneumonitis. Neutrophil counts were very high in the patients with diffuse panbronchiolitis and in those with high-altitude pulmonary edema, and eosinophil counts were high in those with eosinophilic pneumonia. The CD4:CDS ratio was significantly higher in the patients with stage I sarcoidosis than in the healthy subjects. The total protein concentration and the albumin concentration were significantly higher in the patients with eosinophilic pneumonia and in those with high-altitude pulmonary edema than in the healthy subjects, and these findings suggest that in those two conditions the permeability of the pulmonary microvasculature was abnormally high.

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The value of fiberoptic bronchoscopy in the diagnosis of solitary pulmonary nodules was studied. The subjects were 59 patients with chest-roentgenoraphic evidence of a solitary pulmonary nodule 2cm or less in diameter. Definitive diagnoses were made in 34 patients (57.6%). Primary lung cancer was diagnosed in 21 of 32 patients (65.6%), pulmonary tuberculosis in 7 of 12 (58.3%), metastatic lung cancer in 3 of 5 (60%), old lesions in 3 of 5 (60%), and pulmonary filariasis in 0 of 1 (0%). The diagnostic sensitivity of transbronchial biopsy was superior to that of curettage, and combining the two techniques further improved the diagnostic yield. Bronchial lavage was not effective for diagnosis of lung cancer, but was effective for diagnosis of pulmonary tuberculosis. Diagnostic yield was less for nodules in upper lobes than for those in other lobes, and most malignant tumors that were not diagnosed from the results of fiberoptic bronchoscopy were in upper lobes. We conclude that combining various fiberoptic bronchoscopic procedures can improve the diagnostic yield in patients with small pulmonary nodules. CT-guided needle biopsy and video-assisted thoracoscopic biopsy are two such procedures. Early diagnosis of small pulmonary nodules requires a skilled bronchoscopist who can choose the most appropriate method for biopsy.

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In a cross-sectional study, we evaluated success in the control of asthma as defined by criteria for symptoms, for FEV₁/FVC, and for peak flow rates. One hundred and three patients with chronic asthma who had been treated with inhaled steroids were studied. Chest tightness, dyspnea, wheezing, sputum production, and coughing were each scored from 1 (worst) to 5 (best). Symptoms were said to have been controlled if the symptoms scores for the preceding 4 weeks were greater than or equal to 20; FEV₁/FVC was said to be under control if it was greater than of equal to 70% when measured in the clinic; peak flow was said to have been controlled if the lowest peak flow in the preceding 4 weeks was greater than or equal to 80% of the highest measured value.
Symptoms were controlled in 72% of the patients, FEV₁/FVC was under control in 83%, and peak flow was controlled in 66%. The patients were grouped by severity of disease into four classes, and these percentages did not differ significantly among the classes. In 22 out of 74 (30%) patients in whom symptoms were controlled, peak flow was not controlled. Furthermore, in 18 out of 64 (28%) patients in whom symptoms and FEV₁/FVC were controlled, peak flow was not controlled. We concluded that in treating asthma, not should symptoms be controlled, but peak flow should also be measured each day to avoid undertreatment.

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A common side effect of radiotherapy is the development of fibrosis in the irradiated tissue. To study the effects of methylprednisolone on acute radiation-induced lung injury, we counted neutrophils, lymphocytes, and macrophages, and measured the expression on alveolar macrophages of lymphocyte function associated molecule-1 (LFA-1) in bronchoalveolar lavage fluid recovered from irradiated rat lungs. Twenty 10-week-old male Wistar rats were divided into 4 groups of 5 rats each: (1) a radiation group (R), which received 20 Gy of radiation from ⁶⁰Co to the left hemithorax in one fraction; (2) a methylprednisolone treatment group (RS), which received the same dose of radiation as the R group, along with 2.0mg·kg^-1 of methylprednisolone (6α methylprednisolone 21-acetate) by intramuscular injection 6 hours before and every 48 hours after irradiation; (3) an untreated control group (C); and (4) a methylprednisolone control group (S), which received the same dosage of methylprednisolone as the RS group. Rats were kept under specific-pathogen-free conditions. Bronchoalveolar lavage of the left lung was done in all 4 groups 2 week after irradiation. The number of neutrophils in the recovered fluid was significantly higher in the R and RS groups than in the C and S groups. The expression of LFA-1 on alveolar macrophages was significantly higher in the R group than in the RS, C, and S groups. The number of neutrophils in bronchoalveolar lavage fluid and the expression of LFA-1 on alveolar macrophages were significantly higher in the R group than in the RS groups. These results suggest that the increase in the expression of LFA-1 on alveolar macrophages and the increase in the number of neutrophils in bronchoalveolar lavage fluid are related to acute radiation-induced lung injury. Methylprednisolone suppressed the expression of LFA-1 on alveolar macrophages and the increase in the number of neutrophils measured in bronchoalveolar lavage fluid 2 weeks after irradiation.

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A thermistor flow-through system for measuring expiratory volume without a mouthpiece and a nose clip was developed. First, a thermostat and a large syringe were connected to a box used to simulate a subject's head. A carbon dioxide (CO₂) gas mixture was driven through the box, while the output of a thermistor sensor of the thermistor flow-through system was recorded. The correlation between the area under the temperature-time curve and the actual volume of gas driven through the box was computed. Second, the effects of driving time, gas temperature, and room temperature on the area under the temperature-time curve were measured. Third, corrections for expiratory time and for the temperature of exhaled gas were derived from regression analysis of the relation between the time taken to drive the CO₂ gas mixture and the area under the temperature-time curve, and between the temperature of the CO₂ gas mixture and the area under the temperature-time curve, respetively. Fourth, CO₂ production was computed from the area under the CO₂ concentration-time curve (obtained at the salve time as the temperature-time curve).
To measure the temperature-time curve and the CO₂-time curve for the simulator, the box was placed under the transparent hood of the thermistor flow-through system. To measure the temperature-time and CO₂-time curves for a subject, the head was placed in the hood while the subject was supine. The subject breathed with the mouth held slightly open, and the mixture of room air and expired gas was continuously drawn at a constant flow through an outlet at the top of the hood. The outlet was connected to a flow meter and to a constant-speed blower. The CO₂ concentration and the temperature in the hood exhaust were measured at the outlet, and were continuously recorded with a chart recorder. To measure the actual volume of CO₂, a Douglas bag was also used, and was connected to the blower.
Increases in driving time and in gas temperature caused increases in the area under the temperature-time curve of 9%/sec and 6%/°C, respectively; increases in room temperature caused it to decrease at 7%/°C. After the thermistor-derived expiratory volume was corrected for expiratory time and temperature, it correlated significantly with expiratory volume as measured with a respiratory inductance plethysmograph. The correlation coefficients were +0.904 for expiratory volume and +0.881 for tidal volume. A significant correlation (r=+0.992) was also found between the volume of CO₂ computed from the area under the CO₂-time curve and the actual volume of CO₂ delivered by the simulator. A similar correlation was found between CO₂ production computed from the area under the CO₂-time curve and the volume of CO₂ collected in the Dougls bag during breathing.
With corrections for expiratory time and temperature, and with the development of more advanced thermistor sensors, a thermistor flow-through method such as the one described here may be used to measure expired volume. Such a system may also be used to measure CO₂ production in the clinical pulmonary function laboratory.

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Artificial surfactant is used to treat patients with the adult respiratory distress syndrome; we studied its effects on neutrophil function. Neutrophils were isolated from healthy volunteers and their adherence to plastic surfaces was used as an index of their function. Surfactant TA (S-TA, 0.16-5mg/ml) dose-dependently inhibited neutrophil adherence stimulated by n-formyl-methionyl-leucyl-phenyl-alanine, phorbol myristate acetate, and tumor necrosis factor. This inhibition was observed whether untreated S-TA or heated S-TA was used. Electron microscopy revealed an increase in the number of apoptotic neutrophils with pyknotic nuclei and smooth cell surfaces after treatment with S-TA which suggests that neutrophil apoptosis was increased. The number of apoptotic neutrophils increased with incresing time of incubation with S-TA, and was also high in the presence of G-CSF, which inhibits neutrophil apoptosis. These results show that S-TA can inhibit neutrophil function, and they suggest that S-TA therapy for the adult respiratory distress syndrome not only corrects the surface-tension abnormality, but can also inhibit infiltration of neutrophils.

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To evaluate the long-term effect of a beta-adrenergic agonist on Na⁺-channel function in cultured rat alveolar type II cells, we measured ²²Na⁺ uptake into type II cells cultured in the presence and absence of 0.1mM terbutaline for up to 5 days. Terbutaline did not influence the growth, morphology, or protein content of the cells. Terbutaline increased amiloride-inhibitable ²²Na⁺ uptake into the cells at day 2 in culture, but there was no significant difference at day 5. Because amiloride-inhibitable ²²Na⁺ uptake reflects Na⁺-channel function, these data indicate that terbutaline may transiently upregulate Na⁺-channel function. This study provides direct evidence of a long-term effect of a beta-adrenergic agonist on Na⁺-channel function in alveolar type II cells.

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To evaluate the usefulness of expandable metallic stens (EMS) in patients with superior vena cava (SVC) syndrome, we compared venographic findings obtained before EMS insertion with findings at autopsy. Stents were inserted into the SVC in 10 patients. An autopsy was done in 7 of the 10 patients. At autopsy, the lumen of the SVC was patent in 4 patients; in those 4 patients venography before EMS insertion showed that the SVC was obstructed by extramural compression. These results suggest that extramural compression without direct invasion of the tumor is the best indication for insertion of an EMS. At autopsy, the lumen of the SVC was obstructed by direct invasion of a tumor in 2 patients; in those 2 patients venography showed wall irregularity and lumen narrowing caused by tumor invasion. However, in those 1 patients SVC syndrome either did not recur or recurred in only a mild form after EMS insertion. The results in these 2 patients suggest that if collateral circulation does not develop, insertion of an EMS is indicated also in patients in whom the SVC is obstructed by direct invasion of a tumor. In the remaining patient, the lumen of the SVC was found at autopsy to be obstructed by a thrombus. SVC syndrome developed in this patient 430 days after EMS insertion. In 1 of the 7 patients, an EMS was inserted into the left innominate vein and also into the SVC. Venography before EMS insertion showed that the vein was obstructed by extramural compression without direct invasion of the tumor, but the EMS was found at autopsy to be completely obstructed by a thrombus. This suggests that insertion of an EMS into the left innominate vein is not indicated this vein is easily obstructed by thrombi because of its anatomical location.

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A 77-year-old man with diabetes mellitus who was being treated as an outpatient had abnormal shadow in the right lower lobe on a chest roentgenogram in June 1993. In July 1994, a productive cough developed, and subsequent dyspnea obliged him to enter our hospital. Reterntion of pleural fluid led us to suspect tuberculous pleurisy and to perform a pleural biopsy and a thoracentesis to remove pleural fluid, but no final diagnosis was reached. About 14 months later he died of dyspnea with a rapidly growing, tumor. An autopsy disclosed a giant tumor that occupied the right pleural cavity, excluding the lung. The tumor was well-defined between the lung and had infiltrated into the mediastinum. The histopathological diagnosis was primary malignant mesothelioma, sarcomatous type, of the visceral pleura.

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A 75-year-old man with multiple myeloma presented with fever and respiratory symptoms. A chest roentgenogram showed interstitial shadows and transbronchial lung biopsy revealed diffuse infiltration of amyloid in the alveolar walls. Analysis of bronchoalveolar lavage fluid showed the presence of an IgA-λ paraprotein, and the IgA/albumin ratio was similar to that in serum. However, plasma cells could not be detected in the cells obtained by lavage. We know of no previous case in Japan in which bronchoalveolar lavage fluid was examined in a case of diffuse alveolar septal amyloidosis.

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Pulmonary lymhangiomyomatosis is a rare disorder that affects only women of reproductive age. The lung shows numerous cystic changes and striking proliferation of smooth muscle around the airways, blood vessels, and lymphatic channels.
We encountered a patient with pulmonary lymphangiomyomatosis who had repeated pneumothorax and bloody sputum over 10 years. The patient also had other lesions, including intracranial calcification, renal angiomyolipoma and endolymphatic stromal myosis of the uterus. The first two findings are known as tuberous sclerosis, and lymhangiomyomatosis is considered to be a forme fruste of tuberous sclerosis. However, we know of no previous reports of uterine lesions in this disease. Lymphangiomyomatosis may be a systemic disorder of smooth muscle.

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A 54-year-old man was referred to our hospital because of hemoptysis. Fiberoptic bronchoscopy revealed irregular mucosa of the right B¹, B², B³, B⁸, B⁹, and B¹⁰, and the left B¹⁺² and B³. Bronchoscopic and histological findings indicated bronchial varices.

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A 60-year-old man presented with sudden palpitations in September 1993, and was admitted to hospital with a diagnosis of atrial fibrillation and heart failure. The patient was suspected of having collagen disease, because of a positive test for antinuclear antibodies and a high sedimentation rate. He was referred to lou hospital. Chest radiographic findings were suggestive of cardiomegaly and cardiac murmurs were audible, which indicated the presence of heart disease. A chest Ct scan revealed a lesion surrounding the intrainediastinal large vessels and the heart from the level of the confluence of the left brachiocephalic vein and the superior vena cava. Suspicion of a mediastinal tumor led the patient to be admitted to the respiratory department. Percutaneous needle biopsy with a Trucut needle revealed non-specific chronic inflammation. An abdominal CT scan showed that the lesion surrounding the descending aorta traversed the diaphragm, reached the renal pelvis along both renal arteris, and caused narrowing of the ureter and left hydronephrosis. Based on these findings, retroperitoneal fibrosis was diagnosed. Treatment with steroids caused the lesion to shrink.

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A 39-year-old woman, who suffered from a sudden episode of severe left-sided back pain, was admitted to our hospital because of hemothorax. Chest CT scans revealed a mass extending from the left hilum to the posterior thoracic wall. The mass occluded the left pulmonary artery at the left main bronchus. Examination of a frozen section of a specimen obtained during a thoracotomy showed a sarcomatous tumor. A left pneumonectomy was then performed. Microscopic examination of a specimen revealed that the tumor was composed of spindle cells with cellular atypia and mitosis forming fascicles and storiform arrays. Malignant fibrous histiocytoma (storiform-pleomorphic pattern) was diagnosed. Chemotherapy was carried out six times during the year after surgery. No recurrence of the tumor has been seen during 20 months of follow-up.

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A 73-year-old man was admitted to our hospital with pneumonia in the right S⁶ induced by Streptococcus milleri and with left pleural thickening. He had histories of diabetes mellitus for 30 years and pulmonary tuberculosis 35 years ago. The pneumonia resolved completely after administration of ceftazidime and clindamycin for 10 days, but the pleural thickening remained and computed tomography revealed that it was an encapsulated effusion without calcification. An aspirate was turbid yellow with a high concentration of lipids, and consisted of dominant crystals and scattered cells, 80% of which were yeasts and 20% of which were macrophages phagocytizing them. Only Candida parapsilosis developed in culture. The same silent pleural shadow was identified on chest X-ray films obtained over the previous 7 years. The persistent pleuritis was diagnosed as saprophytic infection with C. parapsilosis.

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A 25-year-old man with acute lymphoblastic leukemia (FAB:L2) received an allogeneic bone marrow transplant from an HLA-identical sibling during the first remission. Despite administration of adequate immunosuppressant drugs, active chronic graft-versus-host disease developed and continued. The patient complained of progressive dry coughing and breathlessness on exertion 18 months after the transplant and severe hyperlucency and multiple bullae were observed on a chest X-ray film. Three years after the transplant, recurrent bilateral pneumothorax developed and lung cysts were resected twice. Histological examination revealed bronchiolitis obliterans. We speculate that post-transplant bronchiolitis obliterans caused multiple bullae to form by a check-valve mechanism, which then led to recurrent bilateral pneumothorax.

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A 25-dear-old woman complained of coughing for over 8 weeks. The coughing was not relieved by a bronchodilator (β₂-adrenoceptor agonist; clenbuterol), an anti-allergic agent (azelastine), or an inhaled corticosteroid. The thromboxane synthetase inhibitor ozagrel completely abolished her cough. In this case, tromboxane A₂ may have contributed to the coughing.

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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 examieed. 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

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A 52-year-old man presented with BOOP-like recurrent bilateral pulmonary infiltrates. In 1989 a chest X-ray film showed an infiltratioe shadow in the right S⁶ region which disappeared after administration of prednisolone. Thereafter, bilateral patchy infiltrates recurred many times, and each time they resolved rapidly with steroid therapy. Skin eruptions on the face recurred. In October 1994 the patient underwent an open-lung biopsy of the infiltrate in the left S⁶ region. The pathological findings were consistent with BOOP, except for the moderate-to-marked infiltration of lymphocytes. A lymphoproliferative disorder was suspected, and Southern blot analysis of the specimen revealed a rearrangement of the TCR-β gene, which led to the diagnosis of T cell lymphoma. Ten months after the diagnosis, no recurrence of the lymphoma had been detected. In this case a gene analysis of the biopsy specimen was very useful for the diagnosis of T cell lymphoma.

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A 44-year-old woman with malignant T-cell lymphoma and secondary leukemia recieved an allogeneic bone marrow transplant (BMT). She had received BMT conditioning treatment with total body irradiation and chemotherapy. Hemoptysis and progressive dyspnea developed 11 days after the transplant. A chest roentgenogram showed bilateral diffuse infiltrates. Bronchoalveolar lavage fluid was bloody, and diffuse alveolar hemorrhage (DAH) was diagnosed. Respiratory failute progressed despite mechanical ventilation and administration of corticosteroids. The patient died 58 days after the transplant DAH after BMT has been recognized in western countries as a syndrome with high mortality. We draw attention to the fact that DAH is a serious early pulmonary complication of BMT also in Japan.

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A 77-year-old woman with a productive cough and fever was admitted to the hospital. Pulmonary and endobronchial tuberculosis, pneumonia of the left upper lobe, and stenosis of the left main bronchus were diagnosed. She was given the antimycobacterial drugs isoniazid, rifampin, and streptomycin, and her condition improved. Two months later, bronchoscopy revealed semilunar-shaped stenosis of the left main bronchus, and auscultation revealed wheezing in the middle-end expiratory phase. A continuous flow murmur (Levine III) was also heard at the left anterior chest wall. Cardiac catheterization with subclavian arteriography revealed two left subclavian-pulmonary shunts. In a case of systemic-pulmonary shunt such as this, the bronchical stenosis could be surgically repaired, but the result would be an increase in dead space. If left untreated, the pulmonary hypertension would progress and symptoms of pulmonary disease would become more severe. Subclavian-pulmonary artery shunt is a very rare complication of pulmonary tuberculosis. Surgical treatment should consist of open bronchoplasty along with lobectomy and removal of the shunt, rather than embolization of the shunt and endoscopic bronchoplasty.

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A 50-year-old man was admitted to our hospital because of slowly progressing ataxia. After the neurological examination and after observation of the clinical course, paraneoplastic cerebellar degeneration was suspected. Extensive examination revealed a malignant tumor in the right upper lobe of the lung. Immunoblotting with rat cerebellum revealed a 68KDa protein in the patient's serum, which suggested that paraneoplastic cerebellar degeneration was caused by an auto-antibody. Anti-cancer drugs and radiation therapy were begun 4 months after the onset of symptoms. After 4 months of therapy, the lung cancer had shrunk, but the neurological symptoms had become more severe.

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