The fundamental importance of the lung in providing oxygen and eliminating carbon dioxide is well known. However the lung has another critical role as the site of numerous and important metabolic events. Some of these metabolic activities are essential to the normal performance of pulmonary gas exchange. Impairment of pulmonary metabolic activities can, therefore, have far-reaching repercussions on many organ systems.
Special features of pulmonary vascular beds which are helpful for the metabolism of various vasoactive substances through pulmonary circulation are described.
The lung can uptake or metabolize various vasoactive substances including acetylcholine, serotonin, bradykinin, prostaglandin E₂ (PGE₂), PGF_2α, leukotoriene C₄ (LTC₄), LTD₄ and LTE₄. On the other hand the lung can synthetize and release various vasoactive substances including histamine, serotonin, LTC₄, LTD₄, LTE₄, thromboxane A₄ (TXA₄), PGD₂, PGE₂, PGF_2α, PGI₂, LTB₄, and PAF (platelet activating factor).
We also investigated the metabolism of LTC₄ and LTD₄ through isolated perfused guinea pig lung lobes. And it is clarified that the infused LTC₄ was converted to LTD₄ and LTE₄, while the infused LTD₄ was converted to LTE₄.
Seventeen years ago, we demonstrated the release of prostaglandins from the lung during mechanical ventilation at large tidal volumes in anesthetized mongrel dogs. We thought this PG is PGE₂ which dilates pulmonary vasculatures. In the present study we investigated the release of PG from healthy volunteers by spontaneous hyperventilation. We demonstrated that serum levels of 6-keto PGF_1α and PGE₂ showed a marked increase following the spontaneous hyperventilation.
Various humoral factors related to the pulmonary vascular responses and various humoral factors which related to the tracheobronchial responses were also presented. Various chemical mediators and cells which synthesize and release these mediators were summarized.
It is well known that LTC₄ and LTD₄ deteriorate the circulation in coronary arteries (CA) and these substances are metabolized in the lung. Therefore, the influence of LTC₄ and LTD₄ on the coronary circulation through the lung was studied in anesthetized mongrel dogs. The coronary arthery blood flow was reduced by 90%.
It is well known that cigarette smoking has diverse effects not noly on the airway system but also on the pulmonary and systemic circulatory system. The acute effects of cigarette smoking are induced mainly by nicotine, the main alkaloid in tobacco. We demonstrated that peripheral venous blood levels of complement C3a and C5a showed a marked increase.
Bronchial asthma, idiopathic interstitial pneumonitis (IIP) and other diffuse interstitial lung diseases related to PG, LTS, disaturated phosphatidylcholine (DSPC) and SP-36 of 36KDa were also referred to.

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The most reasonable classification for diffuse interstitial pneumonia/fibrosis is described according to the clinical course, histopathological findings and responses to steroids. Idiopathic pulmonary fibrosis (IPF) represents the most prevalent, most chronic form of the disease with the worst prognosis. The histopathological findings of IPF are usual interstitial pneumonia (UIP) which microscopically is recognized as patchy lesions. In UIP diffuse alveolar inflammation does not change to diffuse alveolar fibrosis, rather the disease progresses via an increase in the number of localized fibrosis lesions.
Steroids are ineffective in the treatment of IPF. Lung transplantation is the only effective treatment. The question of when such transplantation should be undertaken constitutes the subject of further study.

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The authors recently encountered three cases of pulmonary dirofilariasis with unusual abnormalities on chest roentgenograms. In case 1, with right upper and lower lobe masses and right pleural effusion, the right lower lobe mass and pleural effusion spontaneously disappeared one month after admission. In case 2, chest roentgenograms and chest CT scanning revealed a small mass with cavity formation. In case 3, with a right lower lobe mass and pleural effusion, steroid therapy resulted in disappearance of the mass and a remarkable reduction of pleural effusion.
Human pulmonary dirofilariasis is a rare disease. In Japan, only 32, including our cases, have been reported in the literature of pulmonary dirofilariasis with unusual abnormalities on chest roentgenograms. The literature was reviewed.

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Two identical twin brothers and their sister who suffered from spontaneous pneumothorax (ages at onset, 18, 22 and 20 years) were admitted to our hospital.
Their symptoms and clinical courses were similar and all three were finally treated by thoracotomy. No other members of their family had any history of spontaneous pneumothorax.
None of these cases presented any abnormal level of serum ACE or α1-antitripsin.
In order to establish the monozygosity of the brothers more accurately, we examined restriction fragment length polymorphisms (RFLPs) which were shown as the band patterns of hypervariable minisatellite regions in human genomes.
However there have been few reports of spontaneous pneumothorax in identical twins, but the onset of the disease tends to be the same as in our cases, suggesting a genetical background of spontaneous pneumothorax.

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Three familial cases of psittacosis presented with fever and arthralgia. The first case was a 54-year-old man whose chest X ray film showed ground glass appearance in left S6. Ga scintigraphy revealed stronger accumulation in left lower lobe. Bronchoalveolar lavage fluid was examined in 2 of the cases and activated helper T cells were increased in both of the cases. Lung function was studied in all 3 cases in different phases. Their basic lung functions were different, but there was a similar change in courses, i. e. decrease of small airway flow and the increase of RV. These findings suggest that lung lesion of psittacosis may be related to allergic reaction and diffuse lung disease.

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A new device, the BF-2.2T, has been designed to go through the 2.6mm channel of the conventional fiberoptic bronchoscope (Olympus BF-1T20). It measures 2.2mm in outer diameter; it has a visual angle of 75 degrees, a focal depth of 3 to 50mm, a working length of 1150mm, and a total length of 1400mm. It bends 120° in an upward direction and 120° in a downward direction. The tip, 2.2mm∅, of the BF-2.2T angulates like a conventional bronchofiberscope, and this is the main characteristic of this instrument.
The BF-2.2T yields clinically satisfactory observation and photography, as a method for determining morphological changes in peripheral type lung cancer.

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A case of multiple intracranial tuberculomas diagnosed by enhanced brain CT scan and MRI, which developed during the course of miliary tuberculosis under anti-tuberculous chemotherapy was experienced. Chemotherapy with an increased dose of each agent and corticosteroid was administered, and eventually intracranial tuberculomas nearly disappeared.
After 1970, there have been 29 reported cases of intracranial tuberculomas in Japan, which were diagnosed by brain CT and treated with anti-tuberculous agents.
Among them, 27 evaluable cases were classified into 3 groups. Group A: Intracranial tuberculomas were proved by CT before chemotherapy in 7 cases. Four of them enlarged during chemotherapy. Group B: During chemotherapy of tuberculous meningitis, neurological symptoms worsened or prolonged, and finally intracranial tuberculomas were found by CT in 9 cases. In 5 of them, after meningitis was improved by chemotherapy, neurological symptoms worsened and intracranial tuberculomas were found. Group C: During chemotherapy of pulmonary tuberculosis or miliary tuberculosis, neurological symptoms appeared and intracranial tuberculomas were found by CT in 11 cases (including our own case). Getting 3 groups together, intracranial tuberculomas seem to have worsened during chemotherapy in 24 out of 27 evaluable cases. In view of response to chemotherapy, these 24 cases can be divided into 2 categories: 1) non-responders to chemotherapy; 2) cases finally cured by chemotherapy (“transient worsening”).
Based on a review of the literature, the cause of non-responders can be attributed to the following: (1) anti-tuberculous agents do not penetrate well into tuberculomas because of their fibrous capsule, which is believed to be reflected on enhanced CT scans as ring-enhancement finding, (2) angitis is complicated and so local brain edema and tissue hypoxia is caused, and (3) intrathecal infiltration of anti-tuberculous agents is reduced once meningitis is improved.
Then, what is the cause of “transient worsening”? No previous reports have mentioned it. In our own case, during chemotherapy intracranial tuberculomas were supposed to have developed because headache worsened and right hemiplegia appeared. At the same time, pulmonary lesion of miliary tuberculosis also worsened. But eventually both of them were cured by continuation of chemotherapy. Similarly, in several reported cases, not only intracranial tuberculomas enlarged but pulmonary lesion worsened or hilar and cervical lymph nodes enlarged during chemotherapy, and eventually both of them were cured by chemotherapy.
Taking these clinical courses into consideration, it is suggested that the “transient worsening” of intracranial tuberculomas may be the same phenomenon as worsening of pulmonary lesions, appearance of pleural effusion, and enlargement of lymphnodes transiently seen in some cases of pulmonary tuberculosis during chemotherapy.

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The CT findings of pulmonary alveolar proteinosis were studied. The subjects consisted of five cases; 4 men and 1 woman with an average age of 47.4 years old. The total of 19 CT views were analyzed with a mean follow-up duration of 5.7±1.2 years. The interval from the estimated onset to the first CT examination day was considered to be 6.0±3.1 years.
The purposes of this report were; 1) Whether one could obtain useful imformation for the diagnosis by initial CT? 2) What were the changes of imaging with the passage of time on CT? 3) How one could predict the prognosis of the patients by CT?
From the results of initial CT, pulmonary alveolar proteinosis showed diffuse, non-segmental densities with a mixture of various degrees of consistency, with peripheral clear zone which could be detected under posterior and lateral chest wall and/or interlobar area, and occasional air bronchograms. Irregular shaped patchy densities attached to the anterior chest wall were detected in 4 cases. These densities made the anterior pleural line irregular.
In two cases, densities which were thought to represent the deposition of protein-like material in alveolar spaces decreased in the clinical course. Interstitial changes of the lung field were thought to cause the loss of lung volume, dilatation of bronchi and bronchioles, resulting in cystic changes and respiratory difficulty increased. In another case, the densities spontaneously disappeared during a period of one year.
In cases showing deterioration, the first CT showed localized decrease of lung volume, but in a case with spontaneous improvement, diminished lung volume could not be detected on the initial CT. These differences between worsened cases and improved case might provide a clue to estimate the patient's prognosis at the first consultation.
As a result of our experience in a small number of cases, CT may be more useful for the diagnosis and estimation of the prognosis in pulmonary alveolar proteinosis than conventional radiography.

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Fourteen inflammatory disease cases in which differential diagnoses from tumorous lesions had been difficult and which were confirmed by thoracotomies, were studied. They included 4 plasma cell granulomas, 3 pulmonary abscesses, 2 fungal diseases, and one case of pseudolymphoma, lymphocytic interstitial pneumonia, Wegener's granulomatosis, round atelectasis, organized pneumonia, respectively.
In some cases with plamsa cell granuloma, lymphoproliferative disease, Wegener's granulomatosis and round atelectasis, it might be possible to correctly diagnose the cases preoperatively, on chest X-ray, clinical symptoms and blood examinations.
However in cases with plasma cell granuloma in aged patients, fungal disease, pulmonary abscess and organized pneumonia, there were few characteristic findings for differentiation from benign or malignant tumors. Therefore open thoracotomy will be inevitable for correct diagnosis.

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Production of fibronectin (Fn) and prostaglandin E₂ (PGE₂) by human alveolar macrophages (AM) which were obtained by bronchoalveolar lavage was studied in vitro. AM obtained from patients with idiopathic interstitial pneumonia (IIP) produced much more Fn than those from normal volunteers but produced less amounts of PGE₂. We also tested the effect of lipopolysaccharide (LPS), phorbol 12-myristate 13-acetate (PMA), zymosan and albumin-anti albumin complex (alb-anti alb) on production of Fn and PGE₂ from AM. LPS, PMA and zymosan suppressed Fn production but stimulated PGE₂ production by AM from patients with IIP but indomethacin reversed the suppressve effect of LPS, PMA and zymosan on Fn production.
On the contrary, alb-anti alb stimulated Fn production by AM. Furthermore, exogeneous PGE₂ suppressed Fn production by AM from patients with IIP in a dose-dependent manner. These data suggest that Fn production by AM may be changed by different stimuli or different states of disease, and there is close relationship between the production of Fn and PGE₂ by AM.

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A 26-year-old man admitted to Nishinomiya Municipal Hospital for further evaluation for abnormal shadows on the chest film in a mass examination. He had no subjective complaints; for example, cough, sputum or dyspnea. His past history and physical examinations yielded no significant findings. The chest film revealed the multiple cavities accompanied with a little infltration throughout several loves bilaterally. The inflammatory reactions; such as, CRP and ESR, were all intact, but the titer of the serum cryptococcal antigen was high. He was not immunocompromised. Although bronchoscopy and transbronchial lung biopsy were performed twice during admission, they revealed no pathogenic findings both bacteriologically and histologically. The elevation of the serum cryptococcal antigen titer suggested that this disease is the primary pulmonary cryptococcosis. The titer decreased with spontaneous disappearance of the abnormal shadows on the chest film. This test has a sensitivity of 90% for cryptococcal infection, but in rheumatoid arthritis, a small percentage of false positive results have been reported. Therefore, if the rheumatoid factor is eliminated, the test is more specific for cryptococcal infection. On the other hand, some authors have reported the false positive results in Trichosporon beigelii infection by this method. But this disease is negligible for its frequency in clinical features in our country.
We emphasized that this non-invasive test is more useful for the diagnosis of the primary pulmonary cryptococcosis.

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A 46-year-old man who had worked in a paint processing plast for over 29 years was admitted to our hospital with complaints of nocturnal dyspnea and dry cough. A chest X-ray film showed diffuse granular shadows in bilateral lungs. Pulmonary function tests revealed reduction of diffusing capacity and restrictive impairments. Hypersensitivity pneumonitis (HP) due to isocyanates was speculated from his occupational history and clinical course.
Positive skin tests against TDI-HSA and MDI-HSA, precipitating antibody against TDI-HSA, and negative lymphocyte stimulating tests of peripheral blood and bronchoalveolar lavage fluid were also noticed. Environmental provocation test was positive. Histological findings of transbronchial lung biopsy specimens showed diffuse alveolitis and Masson body, but no granulomas. According to these results, the patient was diagnosed as HP due to TDI.
Type III allergy of Gell-Coombs seems to participate in this case. The granulomatous lesion is seen less frequently in isocyanate-related HP than in HP induced by organic dusts, which suggests the difference in immunological and histological reactions between both types of HP.

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Two cases of inflammatory pseudotumor of the lung were reported.
Case 1. A 68 year-old man was referred to our hospital because of an abnormal shadow on chest X-ray. He had a history of pneumonia in the right upper lobe five months before. The chest X-ray film revealed a coin lesion in the right upper lung field (S1), the same segment as the previous pneumonia. Although RPF and INH were administered for three months, the shadow did not change, and cough and sputum continued. In order to confirm the diagnosis, open thoracotomy was performed and microscopic findings of the resected tumor showed inflammatory pseudotumor; proliferation of fibrous tissue with infiltration by inflammatory cells (plasma cells, lymphocytes and a few neutrophils).
Case 2. A 35 year-old man was admitted to our hospital because of an abnormal shadow on chest X-ray, i. e. a coin lesion with vascular indentation in the left lower lung field (S8). A wedge resection including the mass was performed, and histopathologic examination revealed inflammatory pseudotumor, or plasma cell granuloma; proliferation of fibrous connective tissue with infiltration by predominantly mature plasma cells. Both patients have been doing well after the operation.
We also reviewed 46 cases reported in the Japanese literature and discussed various aspects of this disease. Of 10 patients who had a history of previous respiratory tract infection, 8 had histopathologic features with various inflammatory cells, including many lymphocytes, as in our Case 1. Although the common etiology of inflammatory pseudotumor is obscure, we suppose that in some cases the lesion may be a result of postinflammatory repair process.

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A 42-year-old male was admitted to Tokyo University Hospital because of confusion, aphasia and right hemiparesis. Cranial computed tomography and cerebral angiography demonstrated cerebral infarction due to occlusion of the left middle cerebral artery, while chest roentgenography disclosed a nodular shadow in the right upper lobe and swelling of right hilar and paratracheal lymph nodes. These findings suggested carcinoma of pulmonary origin and tumor-associated cerebral thrombosis, but a possibility of gastric cancer was raised by the finding of cervical lymph node biopsy which revealed signet ring cells in metastatic adnocarcinoma. He developed disseminated intravascular coagulation syndrome and died on the 83rd hospital day. Autopsy revealed adenocarcinoma of the lung with signet ring cells and non-bacterial thrombotic endocarditis which appeared to be responsible for the cerebral infarction. The relationship between adenocarcinoma of the lung with signet ring cells and non-bacterial thrombotic endocarditis was discussed.

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A female case of Japanese summer-type hypersensitivity pneumonitis who was a smoker developed in chronic respiratory failure several years later. Biopsy specimen on first admission showed findings of granulomatous bronchioloalveolitis distributed in the center of secondary lobules. Pulmonary function studies demonstrated restrictive disease with high RV% and low airway conductance. In spite of steroid therapy, dyspnea persisted and the same symptoms were found on next summer. Six years later symptoms of chronic respiratory failure and cor pulmonale developed. Chest X-Ray showed dilated pulmonary artery, cardiomegaly and overinflation without apparent fibrosis. Hypoxemia and hypercapnia were also seen on blood gas analysis. Pulmonary function was unchanged compared to the findings on first admission. Since then long term oxygen therapy was started.
It was thought that irreversible small airway disease caused by hypersensitivity pneumonitis was attributable to cor pulmonale and chronic respiratory failure because of her smoking habit and long period of exposure to antigen. As a patient with summer type hypersensitivity pneumonitis always has a possibility of chronic disease developing after long term exposure to antigen, such as a farmer's lung, the cessation of exposure to antigen by complete cleaning up of the patient's enviroment or moving out were considered to be important.

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A 63-year-old female was admitted with dyspnea on exertion. She had previously suffered from a large amount of epistaxis. Chest X-ray showed the bilateral diffuse granular infiltrates. Arterial blood analysis revealed severe hypoxemia and pulmonary function test showed reduced function of diffusing capacity. Dynamic radionuclide perfusion scintigraphy performed with ^99mTc-labeled MAA demonstrated passage of microspheres through the pulmonary vasculature into the systemic circulation, indicating a right-to-left shunt.
Although selective pulmonary wedge angiography did not directly demonstrate pulmonary arteriovenous fistulae, the histopathological findings of TBLB specimens revealed multiple dilatated alveolar vessels that microspheres could pass through. In addition, chronic hepatitis, dilatation of splenic vein and spleno-renal anastomosis had been present. This type of pulmonary arteriovenous fistula is said to be a rare dispersed telangiectasic type, associated with a part of Rendu-Osler-Weber syndrome and a cause of hypoxemia in liver cirrhosis. We consider that in this case, the chronic hepatitis may have played an important role of developing multiple small pulmonary arteriovenous fistulas.

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A case of mediastinitis and left pyopneumothorax complicating a laryngeal phlegmon caused by Candida albicans is described.
A 64-year-old woman was admitted complaining of pharyngeal pain, hoarseness, dysphagia, and pain behind the left angle of the mandible. In that hospital, she was diagnosed as having a laryngeal phlegmon. She was known to be diabetic and hypertensive since 54 years of age. After admission, she became dyspneic, and chest X-rays revealed left atelectasis, left pleural effusion and left pneumothorax. After a drain was inserted into the left thoracic cavity, she was transferred to our hospital. Chest X-rays showed widening of the mediastinum, an enlarged cardiac shadow, mediastinal emphysema, left pneumothorax and bilateral pleural effusion. A thoracic CT also showed extensive mediastinal emphysema. On March 19, 1988 we incised the abscess behind the left angle of the mandible and inserted drains into both the mediastinum and left thoracic cavity under general anesthesia. Candidiasis was diagnosed based on culture of pus obtained from the abscess behind the left angle of the mandible. She was treated with antibiotics intravenously and through both drainage tubes for about 1 month. She was cured and discharged after 5 months of hospitalization.

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A 37-year-old woman, who presented with low grade fever and productive cough, was admitted for evaluation of an abnormal shadow on chest X-ray film. On physical examination, she had bilateral hallux valgus and funnel chest, the center of which was at the fifth rib on the right edge of the sternum. Since chest CT scan, selective bronchography, pulmonary arteriography and aortography revealed that she had pulmonary sequestration in the right cardiophrenic region associated with localized cystic bronchiectasis in the right S⁷b, she received right lower lobectomy. Histological examination showed the cystic change of bronchioli and a small number of emphysematous alveoli in the right S⁷b adjacent to the sequestered lung. The bronchopulmonary structure of right S⁷a was almost intact.
It might be speculated that the existence of the sequestered lung constituted to the deterioration of the development of the lung and the rib cage adjacent to it.

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A 70-year-old woman was admitted complaining of gait disturbance and difficulty in urination. Neurological examination showed myelopathy and both serum and CSF anti ATLA antibodies were positive. A diagnosis of HTLV-associaged myelopathy (HAM) was made and steroid therapy was initiated. Chest X-ray film on admission showed no abnormality, but three months later, diffuse fine nodular and reticular shadows appeared in both lung fields. The patients had no respiratory symptom. The results of pulmonary function tests were normal, aside from a mild obstructive defect as indicated by reduced V25. Arterial blood gas was also normal. Bronchoalveolar lavage studies showed increased total cell counts and an increased proportion of T-cells. The histological findings of the transbronchial lung biopsy specimen were bronchiolitis and alveolitis. Subsequently, within the next eight months the abnormal shadows on chest X-ray cleared gradually on maintenance dosage of prednisolone, 10mg/day. Possible relationships between HAM and the pulmonary lesions were discussed.

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