We studied 21 parameters of pulmonary function in 172 healthy Japanese adult smokers and non-smokers ranging from 18 to 83 years of age. Prediction formulas for each parameter were calculated in both linear and exponential form using multiple regression analysis with regard to sex, age, height and weight. The exponential form was superior to the linear form for V₂₅, V₅₀, PEF, FVC, VC, FEV_1.0, FEV_1.0%, TLC, D_LCO and D_L/V_A, namely, the parameters whose predictive value decreases with aging. In particular for V₂₅, only the exponential form of the predictive formula could be applied for subjects with advanced age. For PMI, LCI, IDI, pulmonary N₂ clearance delay, and single breath ΔN₂, indices for unevenness of intrapulmonary gas distribution, there has been no previous report about their predictive formulas and ours is the first. These predictive formulas all showed increasing values with aging, and showed higher predictive values in females than in males, except for ΔN₂. These parameters require further study with respect to their normal value ranges and differences between males and females.

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Elemental analysis of hilar and mediastinal lymph node tissues was performed to determine whether some inhaled atmospheric elements are inplicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). IPF was divided into two types; typical and atypical, according to our criteria. Lymph nodes were selected as the study material rather than lung tissue, because inhaled elements are concentrated in the hilar and mediastinal lymph nodes, and increase in lung weight due to fibrosis may influence the estimated values of element per unit weight of lung tissue. The hilar and mediastinal lymph nodes collected from 40 IPF cases and 43 non-IPF control cases were examined to determine the concentration of 13 elements in 100mg dry tissue, using the X-ray fluorescent analysis method. For aluminium, 50mg dry tissue was examined by an atomic absorption analysis method.
Among the 14 elements, Ni in IPF lymph nodes showed a significantly higher level than in control nodes (mean±SD: 8.2±21.3ppm versus 1.1±2.1ppm, respectively. p<0.01). No difference in each of the examined elements was noted between smokers and non-smokers or between typical and atypical IPF cases. Exogenous elements such as Ni may play a role as triggering substances in the pathogenesis of IPF.

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The superoxide generation of neutrophil NADPH oxidase was investigated in healthy subjects, patients with respiratory tract infections, and patients receiving effective antibiotic therapy. In adults, oxidase activity significantly increased during respiratory tract infections and decreased after treatment with effective antibiotics. In the elderly, no significant increase in oxidase activity was observed during respiratory tract infections, while the activity significantly decreased after therapy. Increases in white blood cell counts, neutrophil counts and C-reactive protein values in the elderly during respiratory tract infections were less marked than those in adults. These abnormalities in both adults and the elderly were restored to within normal limits after antibiotic therapy. In in vitro experiments, antibiotics, such as imipenem, ceftazidime and cefoperazone, at each therapeutic dose did not inhibit the superoxide generation of NADPH oxidase. These results suggest that in the elderly, defense activity against infections may be suppressed, and that these antibiotics may normalize neutrophil NADPH oxidase activity as a result of their bactericidal action and a possible biological action to normalize the peri-neutrophil environment of the body.

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It is known that tumor associated carbohydrate antigens are significantly increased in the serum of patients with diffuse panbronchiolitis (DPB). We investigated carbohydrate antigens (SLX, CA19-9) in bronchoalveolar lavage fluid (BALF) obtained from 24 patients with DPB. The concentrations of SLX and CA19-9 were significantly higher in BALF from patients with DPB than those from healthy subjects (7 cases) and patients with pulmonary sarcoidosis (16 cases). No significant correlation was observed between either SLX or CA19-9 concentrations in the serum and BALF, and no significant correlation was observed between the concentrations of these carbohydrate antigens in BALF and clinical findigns.
Immunohistochemical study of SLX and CA19-9 in open lung biopsy specimens obtained from patients with DPB showed expression of SLX and CA19-9 on the bronchiolar surface epithelial cells and mucinous exudates in air spances. These results indicate that carbohydrate antigens are presumably increased in the pulmonary lesions of patients with DPB, and this increase causes high levels of these antigens in the serum. Furthermore, we investigated the change of concentrations of SLX and CA19-9 in BALF obtained from patients with DPB after erythromycin (EM) treatment. The concentrations of these two antigens were decreased after EM treatment.

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We assessed pulmonary function and exercise tolerance in 10 BMT patients. Their underlying disorders were as follows; chronic myeloid leukemia 5 cases, acute lymphoblastic leukemia 2 cases, aplastic anemia, acute myeloid leukemia and non-Hodgkin's lymphoma one case each. Their mean age was 26±9 years old. When the patients were healthy and free of serious complications and anemia, arterial blood gas examination, pulmonary function tests and incremental treadmill exercise test were examined repeatedly. Although %VC and FEV_1.0% kept within normal range, PaO₂ at rest, %DLCO, VO₂max, VO₂max/kg and O₂-pulsemax remained low at one year after BMT. There were significant correlations between VO₂max and O₂-pulsemax [r=0.955 (p<0.001)], %VC [r=0.758 (p<0.02)], VE/VO₂max [r=-0.749 (p<0.02)] and ΔSaO₂/VO₂/kg [r=-0.731 (p<0.02)], suggesting that exercise intolerance in BMT patients may be based on both cardiac and gas exchange abnormalities. To evaluate cardiac dysfunction, we compared exercise parameters obtained at an exercise level of 75% predicted heart rate max in five age-matched normal subjects to those in six BMT patients who did not demonstrate desaturation during exercise. As a result, the mean values of VO₂max/kg and O₂-pulse/m² in BMT patients were significantly lower than those in normal subjects, suggesting that cardiac dysfunction may be due to insufficiency of stroke volume during exercise. It is concluded that exercise intolerance in BMT patients may be mainly due to cardiac dysfunction.

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To examine whether alteration of 7S collagen in the alveolar basement membrane is related to the condition and prognosis of diffuse interstitial lung diseases (idiopathic interstitial pneumonia: IIP, collagen vascular diseases, sarcoidosis, and hypersensitivity pneumonitis), we measured serum 7S collagen levels in 123 patients with diffuse interstitial lung disease and other lung diseases.
Patients with diffuse lung diseases (diffuse interstitial lung disease, pulmonary emphysema, and diffuse panbronchiolitis: DPB) showed significantly higher serum levels of 7S collagen than healthy normal controls. Serum 7S collagen levels in IIP and collagen vascular diseases were significantly higher than those in pulmonary emphysema and DPB. In cases of IIP, serum 7S collagen levels in the active stage were significantly higher than those in the inactive stage. Furthermore, the prognosis of patients with higher serum 7S collagen levels was significantly poorer than those of patients with lower serum 7S collagen levels. In infectious pulmonary diseases, serum 7S collagen levels of patients with adult respiratory distress syndrome (ARDS) were significantly higher than those of patients without ARDS.
Autopsy specimens obtained from patients with positive serum 7S collagen showed diffuse alveolar damage and/or diffuse pulmonary hemorrhage in the alveolar areas. Immunohistochemical staining for 7S collagen showed disruption and/or loss of the alveolar basement membrane.
The authors conclude that serum level of 7S collagen is useful for estimating the activity of diffuse interstitial lung diseases as an index of the destruction of alveolar structure.

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To assess the compensatory mechanisms involved in maintaining aerobic metabolism in various organs during exposure to acute hypoxia, five anesthetized and paralyzed dogs were ventilated with either normoxic (FI_O2: 0.21) or hypoxic gas mixture (FI_O2: 0.13). Under both conditions, we examined systemic and pulmonary hemodynamic parameters, and took samples of arterial and mixed venous blood as well as venous blood from various organs including the heart, brain splanchic organs (hepatic vein) and kidney. Based on P_O2 P_CO2 and pH values as measured with electrodes, we calculated O₂ and CO₂ contents in each blood sample. The values thus obtained were then used to estimate the O₂ extraction ratio (ER), gas exchange ratio (R) and difference of base excess between arterial and venous blood (avBE) in the whole body as well as in each organ. In addition, both O₂ delivery (D_O2) and O₂ consumption (V_O2) in the whole body were calculated. Although the whole body showed a decrease in D_O2 and an increase in ER during hypoxic gas breathing, other parameters including R, avBE and V_O2 did not change significantly. Higher ER values were found in the heart and brain than those in the splanchic organs and kidney, the qualitative trend being the same irrespective of FI_O2. On the other hand, increase in ER during hypoxic gas breathing was considerably larger in the splanchic organs and kidney than that in the heart and brain. There was no significant difference in R and avBE in any of the organs between normoxic and hypoxic conditions.
The experimental results of R and avBE were highly consistent with the maintenance of aerobic metabolism in a organs studied, even during exposure to acute hypoxia, indicating that V_O2 of an individual organ under hypoxia would be nearly identical to that under normoxia. Assuming that V_O2 in each organ was kept constant independent of FI_O2, we evaluated the relative change in perfusion of various organs when FI_O2 was changed from 0.21 to 0.13. The results showed that hypoxia significantly augmented blood flow to the heart and brain while concomitantly reducing flow to the splanchic organs.
In conclusion, O₂ extraction increases sufficiently to compensate for decreased O₂ delivery in the splanchic organs and kidney under acute hypoxia. However, O₂ extraction is not enhanced in the heart and brain, in which aerobic metabolism under acute hypoxia seems to be maintained by the redistribution of blood flow from the splanchic organs.

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We studied the hemodynamic effects of frequent inhalation of aerosolized procaterol hydrochloride (PRC) in the treatment of status asthmaticus.
Twenty patients were enrolled and divided into 2 groups; younger group (less than 55 years; n=11) and older group (more than 55 years; n=9). All patients were treated with intravenous hydrocortisone (4mg/kg/4h) and PRC inhalation (30μg; 0.3ml) every hour via a jet nebulizer with 3l/min oxygen for four consecutive days. Holter ECG monitoring was performed on the 1st, 4th, and 7th days of hospitalization to evaluate mean heart rate, tachycardiac incidence, and arrhythmias. Blood pressure, serum potassium levels, and peak expiratory flow rate (PEFR) were measured on the same day.
Even though the total dosage of inhaled PRC on the 1st day was 496.4±62.61μg for the younger group and 490.0±36.73μg for the older group (p=NS), total arrhythmic ratios were less than 1% in both group. Both blood pressure and heart rate decreased with improvement of symptoms and PEFR value. Serum potassium levels tended to decline according to the administered dosage of PRC (p<0.01); however, severe hypokalemia less than 3.0mmol/l was not observed.
We conclude that frequent inhalation of PRC (up to 500μg/day) via a jet nebulizer provides rapid relief from acute asthmatic attacks, and is safe clinically even in aged asthmatics receiving intravenous steroids.

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A 40-year-old man was admitted with high fever and cough. Pneumonic shadows of the left middle and lower lung fields increased rapidly, and his blood gases worsened. Initial treatment with cefmenoxime, piperacillin, and minocycline was ineffective. Administration of rifampicin was started for suspected legionella pneumonia, but it did not control the spread of the pneumonia shadows. After addition of an antifungal agent and trimethoprim-sulfamethoxazole, his symptoms gradually improved. Isolation of Legionella pneumophila from sputum specimens collected on the 4th day of admission confirmed the diagnosis on day 10. The patient was then given oral rifampicin plus cefmenoxime to prevent mixed infection, and showed a satisfactory improvement. Legionella pneumonia developed secondary to compamse of the patient's immunity due steroid therapy for MDS. After recovering from Legionella pneumonia, the patient subsequently developed tuberculous pleurisy and Pneumocystis carinii pneumonia, which were cured by antituberculous therapy and trimethoprim-sulfamethoxazole. However, acute hepatitis followed by hepatic fatlure developed, and he died on day 121 after admission.

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A 70-year-old woman was hospitalized for status asthmaticus. The level of CRP was high and chest roentgenogram showed infiltrative shadows in the left middle lung field. Artificial respiration and continuous in fusion of methylprednisolone and aminophylline 750mg/24hr were performed. Eight hours after admission, seizures suddenly occurred. At this time, brain CT showed no abnormal findings. The seizures were thought to be induced by theophylline toxicity, since serum theophylline concentration was high at 69.9μg/ml. Because theophylline clearance of the patient in a clinically stable condition was normal, it was speculated that theophylline clearance was reduced during status asthmaticus. It is thought that this rare case of theophylline toxicity occurred due reduction of theophylline clearance during status asthmaticus associated with pneumonia.

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A 53-year-old male was admitted to our hospital because of an abnormal shadow in the left upper lung. Bronchofiberscopy revealed edematous mucosa and pus at the orifice of the left upper lobe bronchus. Pathological examination revealed bronchial inflammatory change with infiltration of eosinophils and also the existence of aspergillus in the pus. Mild eosinophilia and elevation of serum IgE level were observed in the peripheral blood, and serum precipitin agaisnt Aspergillus fumigatus was positive. Bronchogram showed central bronchiectasis, and the diagnosis of allergic bronchpulmonary aspergillosis (ABPA) was made. In cases of ABPA, bronchial asthma is usually present prior to presertation, but this patient had no history of asthma even though airway hyperresponsiveness to methacholine was confirmed.

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A 59-year-old male, born in Wakayama prefecture, was admitted to our hospital because of cervical lymph node swelling, huge mass lesions in both liver and head of the pancreas, and multiple nodular shadows in the left lung. Lymph node biopsy revealed a necrotic lesion containing tuberculous bacilli with no epithelioid cells or giant cells. Adult T-cell leukemia (ATL) was diagnosed by the presence of atypical lymphocytes with a convoluted nucleus and positive anti-ATL antibody. During successful treatment of Mycobacterium tuberculosis with ethambutol, isoniazid and rifampicin, ATL transformed to the blastic phase. The new pulmonary infiltrates improved after treatment with both combination chemotherapy for ATL and antibiotics. However, new infiltrative shadows appeared in both lungs, and were resistant to treatment and the patient died of acute respiratory failure. Histological examination of the lung at autopsy showed interstitial fibrosis with infiltration of leukemic cells and cytomegalovirus infection.

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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 bronchiole-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.

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A 64-year-old woman who was admitted with cough and dyspnea showed severe hypoxemia and interstitial lung shadows. The clinical diagnosis was idiopathic interstitial pneumonia (synonymous with idiopathic pulmonary fibrosis in the United States), since there were no specific immunological or bacteriological findings. No clinical signs or laboratory data compatible with collagen disease were observed. Methylprednisolone pulse therapy was given followed by prednisolone (0.8mg/kg) and azathiprine (15mg/kg). Marked improvement of hypoxia, chest X-ray and spirometry results was observed after five weeks. Histological examination of an cases of residual interstitial shadow obtained by open lung biopsy revealed usual interstitial pneumonia.
Tapering of the immunosuppressant drugs led to a recurrence 3 months later, which was controlled by reintroduction of the same regimen. Therefore, only prednisolone was tapered, and data obtained in an outpatient clinic 6 months after the recurrence were as follows: %VC 108%, %D_LCO 72%, PaO₂ 80 Torr. The value of this regimen for acute IPF or exacerbation of IPF is suggested because of its life-saving effects.

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A 29-year-old man presented with acute onset of high fever, chest pain and dyspnea. Chest X-ray film showed diffuse interstitial shadows, a cavitary lesion in the left upper lung field and cardiomegaly, but no lymphadenopathy. Abdominal CT scan showed hepatosplenomegaly and multiple small low density areas in the liver and spleen. Electrocardiogram demonstrated multifocal ventricular premature beats and ventricular tachycardia.Cardiac catheterization revealed left ventricular aneurysms. Sarcoidosis was confirmed by lung and liver biopsy. Drug therapy of prednisolone and mexiletine resulted in clinical improvement of symptoms, signs and chest X-ray film, but platelet count decreased gradually. It is suggested that an immune mechanism of sarcoidosis may have been the cause of this thrombocytopenia.

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A 34-year-old female was admitted on June 25, 1990, for the evaluation of alveolar hypoventilation which worsered after her second delivery. She showed impairment of both hypercapnic and hypoxic ventilatory responses, and marked desaturation due to hypopnea and apnea during sleep. Although administration of methylxanthine and medroxyprogesterone was not very effective, after treatment with low flow oxygen, there was a marked decrease in the frequency and duration of desaturation during sleep and improvement of arterial daytime blood gases, which suggested the existence of hypoxic ventilatory depression in the pathophysiology of her nocturnal desaturation. Furthermore, the use of a negative pressure ventilator for 3 hours in the daytime for 10 days resulted in markedimprovement of symptoms, arterial blood gases, respiratory muscle strength, and the frequency and duration of sleep desaturation. These findings suggest that both low flow oxygen therapy during sleep, and daytime negative pressure ventilation may be beneficial in patients with primary alveolar hypoventilation and central sleep apnea syndrome.

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A case of endobronchial minute leiomyoma successfully treated by bronchoscopically directed forceps biopsy is described. A 42-year-old male with a 20 pack-year smoking history was admitted for dry cough occurring at night. Chest X-ray showed no abnormal shadows. The tumor, measuring 2 by 2mm, was located in the right B7.
The clinical characteristics of the 66 cases of endotracheal and endobronchial leiomyoma reported in Japan are also discussed. The male to female ratio of this disease was 2:3. Middle-aged people were most, commonly affected. Usually, obstructive pneumonia or atelectasis, which develops distal to the lesion, causes respiratory symptoms and chest X-ray abnormality. However, 10% of cases were asymptomatic and 30% had a negative chest X-ray. There were 7 cases of endobronchial minute leiomyoma, measuring less than 10mm in diameter. Of these, three cases had only hemoptysis and had no chest X-ray abnormality. In such cases fiberoptic bronchoscopy is may be the only useful procedure for the diagnosis of this disease.

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A 47-year-old woman was admitted to our hospital because of dry cough and throat discomfort. Chest X-ray film showed reticular shadows with Kerley B line and scattered nodular shadows.
Blood examination revealed normal WBC count (5100/mm³) with eosinophilia (21%), negative CRP, elevated ESR (49mm/1hr), normal IgE level and positive antinuclear antibody with speckled pattern. Skin tests and precipitating antibodies for common allergens were negative. Results of arterial blood gas analysis and respiratory function test were almost normal. Bronchoalveolar lavage fluid yields 85.7% eosinophils, which suggested eosinophilic lung disease.
To establish the diagnosis, thoracotomy was performed and lung specimens were obtained from S³a and S⁸a. In the area of the nodule, the alveolar spaces were filled with eosinophils and mononuclear cells, with no evidence of vasculitis, granuloma or parasites. Alveolar spaces were almost preserved in residual areas. The walls of air ways, pleura and lobular septa were heavily infiltrated with eosinophils and mononuclear cells. Thus, open lung biopsy confirmed the diagnosis of idiopathic eosinophilic pneumonia. The areas of intraalveolar filling with eosinophils and mononuclear cells were found to correspond to the nodular shadows on chest X-ray film. The relationship between the findings of chest X-ray films and lung histology are discussed.

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Two cases of familial pulmonary arteriovenous fistula are reported.
Case 1: A 54-year-old woman was admitted with exertional dyspnea. An a abnormal shadow on chest X-ray had been noted since the age of 37 years. Pulmonary angiography demonstrated bilateral pulmonary arteriovenous fistulas.
Case 2: A 25-year-old man, the son of Case 1, was admitted for operation for the same disease. The mother and son both suffered from repeated epistaxis due to Rendu-Osler-Weber disease. In order to reserve pulmonary function, fistulectomy was performed in both cases, and their subsequent clinical courses were good.

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