Recently it has become recognized that a variety of pathognomonic lesions develop in the peribroncho-arterial interstitium. In accordance with this increasing numbers of studies have been performed concerning the structure and function of this area, and due to the development of CT imaging it is now possible to obtain some grasp of the radiologic pathologic correlation. As a result of analysis of Mycoplasma infection it has become understood that this is an important site of immunological reactions in the lung. This presentation reviews the various investigations that have been published concerning the peribroncho-arterial interstitium.

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Clara cells in terminal bronchioles are important in the production of surfactant, catabolysation and metabolic activation of various chemicals, and in the carcinogenesis of lung cancer. Many round mitochondria with decreased cristae and rich endoplasmic reticuli of the Clara cell suggest that the Clara cell has a function similar to that of the hepatic cell. Furthermore, the style of secretion of the Clara cell probably has a special function related to respiration. The air bladder of the Gar-pike fish shows a lung-like structure and has cells resembling the Clara cell and type II alveolar cells. Lungs of other animals also have Clara cells in their bronchioles with some individual differences. Mice Clara cells were activated by the beta-adrenergic stimulator, nicotine, and cold stimuli and were targets of paraquat and oxygen toxicity. Tumorigenesis by 4-nitroquinoline-1-oxide on mouse lung was increased by pretreatment with a beta-stimulator. The site of the location of the Clara cells was the focus of asbestosis, centrilobular emphysema, and respiratory distress syndrome in infants as well as adult. In cases of diffuse panbronchiolitis and alveolar proteinosis, alteration of the Clara cell was noticed. About 70% of human pulmonary adenocarcinomas resembled the Clara cell type in ultrastructure and showed characteristic clinical behaviour. In conclusion, the Clara cell is an important key to resolve the pathogenesis of peripheral lung disease, especially of peripheal lung cancer.

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Physico-chemical properties of sputum povide us the pathophysiological and clinical information concering respiratory diseases. It is possible to estimate the origin of the sputum and reasons for difficulty in expectoration by analyzing it chemically. Recently, it has become evident that characteristic properties of sputum in bronchial asthma contribute to the occurence of dysfunction of the mucociliary system, and it is now thought that the treatment of such sputum is very important in asthma. Based on the results of studies on the rheological properties of sputum, new types of expectorant drugs were developed. At present, the presence of elastase and of lipids in sputum has become a matter of great concern, and consequently, a new researches on respiratory failure and pulmonary infectious diseases have been commenced based on considerations of aspects of sputum.

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Recent advances in diagnostic imaging have made it possible to visualize horizontal slices of the lung, which can clearly show that in some diseases the lesions are not necessarily homogeneous in that particular plane. Many factors should be considered to clarify the etiology, including the branching patterns of bronchi. This study was conducted to estimate the contribution of branching patterns to the lack of homongeneity of the pathological changes with special reference to daughter branches and the areas supplied by them. An inflated and fixed lung prepared by Heitzman's method was used. A three-dimensional image analyzing system using a personal computer was employed to calculate the branching angles and the volumes of the areas supplied by the daughter or axial branches. The mean ratio between the typical daughter branch and its parent bronchus was 0.47, while that between the typical axial branch and its parent bronchus was 0.72, The mean branching angle of the typical daughter branch was 77°, while that of a typical axial branch was 48°. The volume of the area supplied by the daughter branch was about 30% greater than that supplied by the axial branch. The diameters of the daughter bronchi tend to become smaller as the order of their parent bronchi increases. No differences were observed among the branching angles of the daughter branches from 3rd to 6th order parent bronchi. The above morphological details are important because the precise geometry of branching is essential to understand the distribution of air flow and the deposition of aerosol within the airways. Most of the inner and middle layer of the lung is supplied by daughter branches, while about 80% of the outer layer is supplied by axial branches and the remainder by asymmetrical branches. This study suggests that the branching patterns of the bronchi is one of the keys to clarify the etiology of unhomongeneity in lesions of the horizontal plane.

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With the wide application of X-ray CT techniques to pulmonary diseases, much interest in "bronchial daughter branches" ("daughter bronchi") has developed. "Daughter bronchi" have relatively smaller diameters, about half of in size of those of the parent stem at most right angles and usually give rise to a second wide-angled bifurcation. From the radiographs and macroscopic pictures of inflated and fixed lung specimens, we reconstituted a three-dimensional airway model including "daughter bronchi" and then analyzed air flow dynamics and aerosol particle movement. For comparison, we also made three kinds of single branching models ; 1) with equal daughter branch diameters and a symmetric branching angle (Weibel's type), 2) with unequal diameters and an asymmetric branching angle (Horsfield's type), 3) with other type of "daughter bronchi". Using these models, we performed the same calculation as in the model reconstituted from the radiographs of the lung specimens. The three-dimensional Navier-Stokes equation was calculated numerically by the finite element method. The equation of motion of the aerosol particles was calculated in this field. The result showed effective deceleration of air flow through the other type of "daughter bronchi". The deceleration was estimated to be equal to that of three or four generations of conventional Weibel's type branching. The shortening of air way through a "daughter bronchus" was estimated to be approximately 3 cm. This suggests possible lung space filling with less airway branching and without excessive air flow. The aerosol particle deposion pattern differed according to branching types. Fewer aerosol particles entered through the "daughter bronchus" than through other types of branching. The particle deposition pattern at each bifurcation of the model reconstituted from the radiographs of the lung specimen was similar to that of the single branching model of same type.

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Location of pulmonary lesions in relation to the deposition of insoluble partilces was discussed using human silicosis and rat exposed to diesel soot. Silicotic nodules were chiefly located around respiratogry bronchioles and both cortex and medulla of the lungs. In the rats exposed to diesel soot, reactive processes and lung tumor were both seen in the cortex and medulla of the lung. The area of the medulla is also important as for location of lesions.

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Increasing attention has been paid recently to the question of the extent and the direction of pathological changes in peripheral areas of the lung adjacent to the hilum. In terms of bronchial branching there are the principal axial bronchi and daughter bronchi, and while there have been studies to elucidate the difference between these roentgenologically and anatomically, there has been little understanding of this question in terms of imaging of respiratory physiology. Bronchography is one method by which it is possible to visualize daughter bronchi and the present study compared the results of preoperative bronchography with the resected fixed lung specimen to examine the results of bronchography in central daughter bronchi. As has previously been reported, bronchographic imaging of peripheral daughter bronchi extending from sites more central than the site of obstruction is good, and it was also satisfactory in cases without peripheral obstruction. High resolution imaging of central daughter bronchi is also possible. Furthermore, primary lesions in peripheral lung around the hilum were recognized.

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Bronchoscopic examination was performed in 30 cases with chronic bronchitis, including 7 cases of which had diffuse panbronchiolitis. In this study, endoscopical findings were classified into 4 types ; edematous, hypertrophic, transitional and atrophic. Transitional type was the most frequent pattern compared with the other types. The duration of disease history was less than 10 years in the edematous type and was more than 10 years in other types. The atrophic type was not developed with the duration of the disease. In relation to pulmonary function, the atrophic type was observed in cases with severe disturbance. Electron microscopic findings of bronchial cilia were investigated and divided into 2 groups ; poorly-regenerated and well-generated type. In the latter type, cilia regeneration was related to improvement in symptoms. Ultrastructural studies were clinically important to observe degeneration of cilia.

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Nineteen patients with biopsy-proven diffuse panbronchiolitis (DPB) were examined by flexible bronchofiberscopy and the findings were compared to the clinical findings. Electron microscopic examinations were performed in a small number of patients. Most patients (84%) showed to have edematous change in bronchial mucosa and two patients had bronchial atrophic change. The severity of edematous changes increased in relation to the duration of the disease and was also related to the amount of intrabronchial mucus. Bronchial findings, however, were not related to cultured bacteria or age. Electron microscopic findings revealed severe impairment and recovery in peripheral airway epithelium and that there were large amounts of osmiophilic lamellated structures in epithelial surface fluid. These findings suggest that morphological changes occured in the central airways of patients with DPB, that these changes were related to airway secretions and that there was considerable injury in peripheral airways and possibly type II cells corresponding to abnormalitie in intralumenal osmiophilic lamellated structures.

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Forty-eight cases with bronchiectasis were classified into 3 different types ; cylindrical type-29, saccular type-8, and combined type-11, from the findings found on bronchograms. The clinical background and bronchofiberscopic findings of each type were studied. There were no significant differences of sexuality, mean age and mean age displaying the first symptom among the three types. However, all patients who became symptomatic at a young age belonged to the cylindrical type. Hemoptysis, bloody sputum and sputum were common symptoms in all three types. The cylindrical type patients had more severe complaints than those of the two other types. Major bronchofiberscopic findings of brnchiectasis were swelling, thickening and redness of the mucosa. The frequency of swelling and redness did not differ among these three types but thickening and atrophy were more frequently observed in the cylindrical type patients. Dilatation of the bronchial lumen which was supposed to be a direct sign of bronchiectasis was recognized in 5 cases. Differential diagnosis with other bronchial inflammatory diseases was difficult to ascertain from bronchofiberscopic findings because the intraluminal changes of bronchiectasis seems to be mainly caused by secondary inflammation.

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This study was carried out to investigate the bronchoscopic findings of the middle lobe (lingular) syndrome (n=48). The findings of the bronchial lumen, bifrucation and mucosa were mainly observed and compared with cases of lung cancer (n=10) and tuberculosis (n=2). In the middle lobe (lingular) syndrome, the positive rate of finding was less than 50%, however, in lung cancer and tuberculosis it was almost 100%. It was suggested that the middle lobe (lingular) syndrome might be separated into two groups, that is, the orifice dominant (B^4, B^5) and the lobe dominant (S^4, S^5) types.

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The pathogenic mechanisms of endoscopic lesions in RA and SjS were evaluated from clinical manifestations, chest X-ray findings, cellular and humoral profiles of SAB, TBLB, and BALF, and immunohistological observations. In the 55 patients with RA, BE was commonly observed, and endoscopic findings were characterized by marked atrophic changes and reddening. Respiratory symptoms preceded in 75%, in whom BO-BBO lesions were demonstrated by SAB examination. In patients exhibiting no or only slight lung involvement in chest X-rays, the lymphocyte fraction of BALF was increased, and TBLB study indicated severe alveolitis. In patients with advanced lung involvements, on the other hand, the neutrophil fractions was increased in BALF, and fibrotic tendency was observed, suggesting a greater role of NCA than smoking or the therapeutic agents in the pathogenesis of the lung lesions. The 12 SjS patients without RA showed mild atrophic changes with proliferation and dilatation of vessels. In these patients, no sicca was noted, lymphocytes were frequently increased, and OKT_4 cells were dominant, and immunohistological studies demonstrated OKT_4 cells in bronchioles and alveoli. These findings indicated differences in the pathogenic mechanism of lung involvement between the two conditions.

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In order to examine to diagnostic and clinical significance of cells and bacterial flora directly obtained from the lower airway by bronchofiberscopy in chronic airway infection, we compared the cellular components and bacterial flora of tracheal aspirate, bronchial lavage fluid (BLF) and bronchoalveolar lavage fluid (BALF) from patients with chronic airway diseases with those from normal subjects and control patients. Analysis of the cellular components showed that the predominant change in cell profiles of the lavage fluids from patients with chronic airway infection is increase of polymorphonuclear leukocytes, especially neutrophils. The BALF and BLF showed almost the same cellular change in patients with chronic airway infection. It was concluded that analysis of the cellular components of the lavage fluids from lower airway is useful for diagnosis of disease activity of chronic airway infection. The normal bacterial flora present in the upper airway were detectable in the BLF of both normal subjects and patients with chronic airway infection. The normal bacterial flora content of the BLF from patients were larger than that from normal subjects and decreased to the latter level after therapy with antibacterial agents. In some patients with chronic airway diseases such as DPB, same pathogenic bacterial flora were detectable in the test samples, and in other patients with CB, pathogenic bacterial flora detectable in the sputum and TA were different from those in the BALF and BLF or not detectable in the latter samples. Those results suggest that analysis of bacterial flora of samples obtained directly from airway by bronchofiberscopy is useful to clarify specific pathogenic bacteria, and the extent and localization of infection in the lower airway.

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A 65 year-old female case of paratracheal cavernous hemangioma in the mediastinum was reported. She had suffered from hoarseness repeatedly for 3 years. Bronchofiberscopy disclosed a lusterless and erosive mucosa, loss of folds with bleeding tendency from below the vocal cord to the left main bronchus. A gray coarse nodule was located in the upper trachea below the vocal cord. These findings raised the very strong suspicion of primary malignant tracheal tumor or malignant invasion from the mediastinum. CT scan demonstrated a paratracheal mass with a calcification nodule. Bronchioarteriography showed increased vascularity and pooling of the contrast media along the trachea. No malignant cells were found in several cytological examinations of sputum. A biopsy of the tracheal mucosa displayed metaplastic changes. Mediastinoscopy and open biopsy were performed. Fat-like shrunk tissue with a strong bleeding tendency surrounded the trachea, and the tissue could be removed easily from the trachea. Microscopically the tissue consisted of wide cavernous spaces with a monomorph endthelial lining. This case was diagnosed as mediastinal cavernous hemangioma. Cavernous hemangioma is rare with a low incidence of approximately 1-1.5% of all mediastinal tumors.

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A bronchofiberoptic examination was performed to a 63-year old woman with collapsed right middle lobe on chest X-ray films. The endoscopic finding of the right middle lobe bronchus showed a flattened deformity of orifice, a low polypoid elevation on the lateral wall, thickening and redness of mucosa. For differential diagnosis of the polypoid lesion transbronchial needle aspiration (23 G 4 mm-length needle for endoscopy) was performed, but just after pulling out needle from polypoid lesion spouting bleeding came out vigorously. Fortunately the bleeding stopped spontaneously in several minutes at that time, but massive bleeding recured 3 days later and the patient was saved by emergency resection of right middle lobe. According to anatomical appearance at operation and pathohistological findings of resected material, we presumed that the bleeding had occured accidentally because the needle had penetrated through weakened site of bronchial wall and then punctured a dilated bronchial artery running along with bronchus.

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A 46 year-old woman who had a past history of lung tuberculosis visited our hospital with a complaint of recurrent fever. Chest X-ray showed an infiltration shadow in the right upper lobe and a shadow of calcification in the right hilar region. Bronchofiberscopy revealed a yellowishgray stone at the orifice of right B^1. We recognized its mobility both on chest X-ray and bronchofiberscopy. After bronchoscopic extirpation her reccurent fever and cough improved, and her roentgenological findings disapperared. Broncholithiasis is an uncommon disease and the usual method of treatment is surgical operation. This rare case of extirpation of a stone by bronchofiberscopy was discussed with reference to the literature.

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A 74-year-old female was admitted to our hospital with fever, yellowish sputum and cough. Chest X-ray showed infiltrative shadows in the right middle lobe and the left lower lobe, and significant widening of the trachea. Bronchoscopic findings showed marked dilatation of the trachea and bronchi. The diagnosis was confirmed to be tracheobronchomegaly. The survival of cases of tracheobronchomegaly to such an elderly age is rare.

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