Bronchial asthma is characterized by an increase of bronchial responsiveness to various stimuli. This can be demonstrated clinically by provocation of bronchospasm by acetylcholine or histamine inhalation. Thus it is critically important to study the causative factors of bronchial hyperresponsiveness in the study of pathogenesis of the bronchial asthma. Although numerous reports have been published recently, it was not well clarified yet. Autonomic derangement has been postulated as a possible pathogenetic bronchial factor in bronchial asthma. Studies on the muscarinic acetylcholine receptor (mACh-R) of vagal nerve and adrenoceptors of sympathetic nerve are now being undertaken. Our studies disclosed an increase of mACh-R, especially of M3 subtype of mACh-R in bronchial asthma. In studies of adrenoceptors, decrease of beta-2 adrenoceptors was noted in bronchial asthma. In the experimental allergic asthmatic model, the decrease of mRNA of beta-2 adrenoceptor was significantly lower in the bronchus than in the lung parenchyma. Another series of experiments was done from the stand point of airway inflammation. An increased number of eosinophils and neutrophils in the bronchoalveolar lavage fluid (BALF) was noted in experimentally induced asthmatic attack. Submucosal eosinophilic infiltration in the bronchial wall was also noted in these experiments. Bronchial ciliary beat was severely impaired and also bronchial responsiveness to inhaled histamine was significantly increased by eosinophils and platelet activating factor (PAF). Physical and mental stress challenge in experimental animals induced flux of eosinophils and neutrophils into the airway. Thus stress has close correlation with airway inflammation. Our recent studies on eosinophils and intercellular network and its relation with cytokines were also reported.

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As yet, the functional abnormalities of patients with various types of COPD have not been correlated with changes of airways in systematized pathological studies. The delay in this aspect of research is attributable to the lack, on the part of pathologists, of techniques for evaluating the distribution and degree of airway obstruction, tasks in which one cannot resort to the techniques of stereology. In this lecture I reviewed some recent attempts of our team to introduce new techniques of morphology : computer-aided 3-D structural analysis which aims at visualizing the distribution of obstruction, and airway morphometry that allows a comparison of airway diameter with its original state. The methods were effective in defining the exact place of obstruction in the airway tree in several types of COPD including diffuse panbronchiolitis and bronchobronchiolitis obliterans. Also, they contributed much to a better understanding of a type of COPD which, though poorly documented by pathologists, tumed out to correspond to what has been called small airways disease despite the lack of a firm pathological definition.

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The upper airway controls air inspiration, regulation of ventilatory volume and protection from noxious particles and gases by neural reflex and mucociliary function. The role of the lower airway is to modulate the inspired air-current for even diffusion and the optimal gas-exchange. Respiratory disturbance in the upper airway has manifold influence on sleep, respiro-circulatory and neuro-psychological functions in varying degress depending on the pathogenetic factor, severity and duration. Although the grade of disturbance in nasal breathing is the same, those with nasal sinusitis often have more damage to the lower airway than those without mucosal inflammation. Laryngeal stenoses elevate respiratory resistance and flatten the peak flow at MEFV-curves. Laryngectomized patients show a change in breathing pattern with increased FRC and decreased tidal volume. Postoperative MEFV-curve recordings showed a steep curve with a larger peak flow and downward convexity, compared with preoperative records. While asleep, patients with upper airway obstruction suffer from more severe disturbance of breathing manifested by loud snoring and apneic episodes than while awake. In a severely obstructed case, the airway is occluded and ventilation stops (sleep apnea). Enforcement of respiratory work and arousal reaction enable overcome the occlusion resulting in breathing, accompanied with snoring. Heavy respiratory intrathoracic pressure-change causes uneven ventilation, pulmonary overload, hypertension, sleep disturbance, daytime sleepiness and deterioration of social activities. Obesity itself disturbs cardio-respiratory functions by excessive fat deposit in various organs inside. When the upper airway is obstructed, it inflicts an additional heavy load on cardiorespiratory functions, which may develop into the Pickwick syndrome. Infants who have great trouble in nasal breathing can hardly breathe through the mouth, and this creates manifest respiratory disturbance, especially while they sleep. They have less tolerance against such respiratory disturbance. These factors may be one of the causes of sudden infant death syndrome. Properly selected treatment based on precise examination and diagnosis of the location, pathogenesis and severity of obstruction achieves satisfactory results subjectively and objectively.

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The Emargency Medical Personnel Law was approved last April. With this law it became possible for emergency medical technicians (EMTs), to give medical treatments once they obtain state qualification otherwise knwn as paramedics. Emergency tracheal intubation by the paramedics, however, is controversial. Examining the report on fire service in Japan in 1989 and other materials, the estimated number of cases in which intubation was necessary war 211, 791 and we could expect a 19.6% increase in survival rate. 81.8% of physicians to whom questionnaire was sent agreed to intubation by paramedics. The University of Washington School of Medicine offers the longest paramedic training program course in the world. In their 2, 500-hour program, lectures on intubation only take up 22 hours including practice on a mannequin. During field work, emergency room experience and internship, students performed 30∿40 actual intubations. After certification each paramedic is required to perform a minimum of 12 field endotracheal intubations. Even with this rather limited experiences no serious complication has been reported. From the above results it seems possible for paramedics to perform emergency endotracheal intubation in our country.

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We evaluated whether lavage cell findings are useful in diagnosing or managing interstitial lung diseases. Diagnostic sensitivity and specificity were calculated using lavage lymphocyte percentages and CD4^+/CD8^+ ratios, respectively. Results showed that the CD4^+/CD8^+ ratio has good diagnostic specificity in patients with pulmonary sarcoidosis. Two lavage cell patterns, both with lavage lymphocytosis, were found on the basis of their CD4^+/CD8^+ ratio : one had an elevated (CD4^+ cell dominant pattern) and the other a decreased ratio (CD8^+ cell dominant pattern). The latter pattern was found in patients with hypersensitivity pneumonitis, eosinophilic pneumonia or BOOP. The lavage lymphocyte percentage was a good index for disease activity in patients with BHL sarcoidosis, whereas lavage neutrophil or eosinophil percentages were good indices for prognosis in current smokers with idiopathic pulmonary fibrosis.

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The pathogenesis of bronchial asthma is not been fully understood, whereas atopic asthma is known to be based on type I allergic reaction. To clarify the multiple factors involved in asthmatic attacks, we applied the technique of bronchoalveolar lavage (BAL) to 97 asthmatics and 27 healthy subjects. Cell populations and leukotrienes were examined in BALF in the nonattack state and after bronchial responses by inhalation of house dust and Candida extract. In the non-attack state, several inflammatory cells, i. e. eosinophils, neutrophils and basophilmast cell systems, were frequently seen in the BALF of asthmatics in comparison to healthy subjects. Neutrophils as well as eosinophils increased in the BALF of non-atopic and late onset asthmatics. In asthmatic attacks, eosinophils, neutrophils and basophil-mast cell systems increased in BALF after late asthmatic response (LAR) in comparison to immediate asthematic response (IAR) by allergen inhalation. No severe side effect was seen, except for transient fever in approximately 30% of cases, I case of pneumonia and provoked asthmatic attack in less than 5% of asthmatics. These results shows that BAL is a useful and safety examination for analysis of the pathogenesis of bronchial asthma.

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Five cases of pulmonary involvement by non-Hodgkin's lymphoma in which immunophenotypic or gene rearrangement analysis in bronchoalveolar lavage supported the diagnosis are summarized. In a case of T-cell lymphoma, Southern blot analysis of T-cell receptor gene detected a monoclonal population of lymphoid cells in lavage fluid. In cases of B-cell lymphoma, a significant increase of CD19-positive B-lymphocytes bearing a single class of light chains was shown in lavage fluid. These findings were confirmed by histological and immunohistochemical studies of biopsied specimens. Discussion focuses on the significance of bronchoalveolar lavage in establishing a diagnosis of pulmonary non-Hodgkin's lymphoma.

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To evaluate the role of alveolar macrophages in pulmonary granuloma formation, production and modulation of tumor necrosis factor(TNF) from alveolar macrophages were investigated in granulomatous lung diseases. Spontaneous TNF production was observed in four cases out of ten with collagen vascular disease. Pulmonary alveolar macrophages from patients with summer type hypersensitivity pneumonitis have statistically significantly diminished ability to produce TNF. TNF production from alveolar macrophages of normal donors was suppressed with the addition of culture supernatant from alveolar macrophage with summer type hypersensitivity pneumonitis. However, this effect was abolished by addition of anti-TGF-β antibody. Addition of indomethacin resulted in complete inhibition of PGE_2, but no increased ability to produce TNF. It is postulated that the decrease in ability to produce TNF seen in pulmonary alveolar macrophages from patients with summer type hypersensitivity pneumonitis is mediated by down-regulation due to TGF-β.

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An enzyme-linked immunoabsorbent assay enabled measurement of soluble interleukin-2 receptor (S-IL-2R) in culture supernatant of Tlymphocytes or serum of clinical samples. The release of S-IL-2R appears to be a characteristic marker of T lymphocyte activation and might be related to immunoregulatory function during cell growth and differentiation. Clinically it has been reported that the level of S-IL-2R in serum is a useful marker to follow disease activity. In this study we measured S-IL-2R levels in serum and bronchoalveolar lavage fluid (BALF) of summer-type hypersensitivity pneumonitis (S-HP) patients. S-IL-2R levels in serum of S-HP patients were significantly increased compared to those of normal controls. However, no mean difference in BALF S-IL-2R levels was detected when these levels were expressed per milligram albumin between S-HP patients and normal controls. Moreover, in our in vitro study, the expression of IL-2R mRNA with various stimuli was significantly decreased in BAL T lymphocytes compared to that of peripheral blood T lymphocytes.

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To investigate possible roles of colony-stimulating factor (CSF) in the formation of sarcoid lesions of the lung, the expression of CSF mRNAs was examined by a reverse transcription-polymerase chain reaction (RT-PCR) method. Macrophage-CSF mRNA was detected in bronchoalveolar lavage cells from all normal subjects and patients with pulmonary sarcoidosis or farmer's lung disease, however, that of IL-3 was detected in none. Granulocyte macrophage-CSF (GM-CSF) mRNA was specifically expressed in 15 of 20 sarcoid patients. Moreover, its expression was well correlated with the clinical activity and course of pulmonary sarcoidosis and with bronchoalveolar lavage findings. These observations substantiated the actual roles of GM-CSF in the pathogenetic mechanism of pulmonary sarcoidosis.

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The authors report results of biochemical analysis of bronchoalveolar lavage fluid (BALF). In BALF from patients with idiopathic interstitial pneumonia, the content of pulmonary surfactants decreased and the content of arachidonic acid metabolites increased. In patients with sarcoidosis, the production of leukotriene B4 from alveolar macrophages increased. On the other hand, the production of leukotriene B4 decreased in smokers. Investigations of arachidonic acid metabolites from alveolar macrophages will become more important to elucidate the mechanisms of various lung diseases including lung fibrosis and other diffuse interstitial lung diseases.

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To determine which type of anesthesia is safest for use in bronchoscopy, we compared of several types of anesthesia in terms of blood gas analysie and measurements of respiratory function. The cases were divided into three groups : Group A given topical anesthesia, Group B given intravenous anesthesia, and Group C given general anesthesia. Arterial oxygen tension, arterial oxygen saturation, cardiac output, and mixed venous oxygen saturation before examination, after anesthesia, during observation by bronchoscopy, during biopsy, and after examination were measured. The cases given general anesthesia had significantly less ventilation disturbance and maintained a good balance between demand and supply as compared with those given the other types of anesthesia. Thus, it seems best to supply oxygen as an aid in other types of anesthesia.

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Since 1974, we have performed bronchoscopy under general anesthesia to increase diagnostic rate of lung cancer and to perform it more safely. In this paper, 167 cases of lung cancer examined from 1986 to 1990 were evaluated. Of the 167 cases, 131 (78.4%) were diagnosed as lung cancer endoscopically. Examination of 3 cases were discontinued due to severe cardiac arrhythmias. Supervision by anesthesiologists permitted early recognition and control of various complications caused by bronchoscopy.

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The TBB obtained from fibreoptic bronchoscopy performed under fluoroscopic guidance were evaluated in a diagnosis study of 561 patients with a peripheral lung lesions. Transbronchial curettage (TBC), transbronchial biopsy by forceps (TBB) and cytology after transbronchial biopsy (TBB-C) included TBTB were compared for thier diagnostic sensitivity. In 561 patients, the diagnostic yield was 84%, including 277 primary lung cancers (83%), 15 secondary lung cancers (47%), and 209 benign tumors (53%). At primary lung cancer, there was no difference in positive rate between tumor size of &le; 2cm and 2cm <. For 35 patients with the primary lung cancer which are smaller than 2cm, the positive diagnosis was made in 21% by one of all three methods. Therefor, all three methods should be used in combination to obtain the higher diagnostic yield.

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In order to investigate the applications and diagnostic values of transbronchial lung biopsy (TBLB), cases of diffuse pulmonary diseases in which TBLB was performed were reviewed. Also, the usefulness of bronchoalveolar lavage (BAL) for diagnosis was evaluated. The subjects consisted of 139 patients and included idiopathic interstitial pneumonia (IIP, 36 cases), hypersensitivity pneumonitis (HP, 10 cases), sarcoidosis (30 cases), pneumoconiosis (10 cases) and diffuse panbronchiolitis (DPB 10 cases). Biopsy results in IIP indicated fibrosis or interstitial pneumonia, but it was not possible to make a definitive histologic diagnosis. BAL was not useful for the diagnosis of IIP. In sarcoidosis and HP, both of which have specific findings histologically, a definitive histologic diagnosis was obtained in approximately 50%, BAL contributed to diagnosis. In pneumoconiosis, TBLB was useful to obtain the definitive diagnosis. In DPB, it was difficult to obtain a definitive diagnosis by TBLB due to the difficulty of obtaining satisfactory specimens. TBLB might be considered to be the first procedure of choice to obtain histological information concerning diffuse lung diseases, but we must consider the applications and limits of TBLB.

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Recently, in our hospital, we experienced some cases of bacterial contamination involving fiberoptic endoscopes and an automatic endoscope washer with atypical mycobacteria, such as M. chelonae, and M. gordonae, as well as non-fermentative Gram negative bacilli, mainly belonging to Pseudomonas aeruginosa. On the basis of these findings, some experiments concerning the bacteriocidal effect of disinfectants to be used on the mycobacteria and other bacteria related to contamination were designed, and the decrease of concentration of the disinfectant solution in the automatic endoscope washer by dilution during washing, in addition to periodical surveys of bacterial contamination of the automatic endoscope washer were investigated. Besed on the results the following decontamination procedures were suggested ; (1) careful, rigorous and thorough brushing of the biopsy channel in the fibroptic endoscope and (2) the use of 3% glutaraldehyde solution as a sufficient disinfectant. After these procedures were adopted, bacterial contamination of endoscopes and the automatic washer dramatically decreased.

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Bronchoscopes include rigid scopes and fiberscopes, the latter being maily used at present. As the scope is inserted into the bronchus there is a certain limit in its diameter. As it is dificult to achieve all examination purposes with one fiberscope, several kinds of fiberscopes must be used : for general purposes, for biopsy, for recording and for peripheral region. Several accessory instruments have been developed to collect speciments of tissue and cells, such as biopsy forceps, cytology brushes, small curettes and suction needles, which may be selected according to the nature and location of the lesion. For recording endoscopic images still photography is performed with 16mm or 35mm color slide films, while for recording dynamic images motion pictures or VTR is used. The motion picture is excellent in image resolution, and the VTR has the merit of reproduction immedately after recording. Regarding the endoscopic light sources many models, from a small portable one to a large powerful unit, are available at present, and for the motion picture and VTR it is recommended to use light sources with maximum, brightness. Presently the development of the bronchial TV endoscope with a small CCD chip in its tip has been promoted. This system offers the digitization of clinical information, which makes possible the image processing and long-term storage of the image without deterioration.

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Data on fiberoptic bronchoscopy performed in 44 asthmatics was studied to evaluate the likelihood of bronchial attacks ; bronchoalveolar lavage (BAL) was performed in 12 asthmatics and 10 healthy subjects to compare the changes of saturation O_2 (SaO_2), peak flow rate (PEFR) and heart rate (HR). A bronchoscope was inserted under 2% lidocaine local anesthetic. No bronchodilator drugs were administered before the bronchoscopy. In 44 cases, only 3 (6.8%) could not continue the bronchoscopy because of severe attacks ; 93.2% of the cases completed the bronchoscopy. Of these 41 cases, 27 (65.9%) revealed slight stridor and/or attacks, and 17 (41.5%) had no symptoms during the bronchoscopy. In all healthy subjects, BAL was performed successfully, but only in 8 out of 12 asthmatics (66.7%) completed the BAL without asthmatic attacks prevented completion of the procedure. Their SaO_2 and PEFR decreased for over 2 hours, and HR increased significantly after the BAL. In conclusion, the bronchoscopy can be performed safely in asthmatics, but special care must be taken when performing.

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The author measured bronchial hyperresponsiveness by Bronchoscreen (BOS, Erich Jeager Co.) which was designed to measure the airway resistance using the occlusion pressure method and included a quantitive inhalation system. Our experience with this apparatus and its evaluated utility were described. Localization of airway response was studied by calculating the peripheral resistance after methacholine inhalation and central airway resistances from shoutter curves. Five of 8 cases dominated by peripheral airway response were found, and those patients had experienced severe asthma attacks.

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Light and electron microscopic observations were carried out on the airway epithlium of patients with asthma. The tracheal epithelium showed obvious morphological changes such as desquamation and degenerative changes in cytoplasm, whereas peripheral airway epithelium appeared normal. In experimental studies of sulfuric acid exposure to guinea pigs, the severity of epithelial injury such as disappearance of tracheal cilia was related to an increase in bronchial hyperreactivity. These findings suggest that the alteration in the central airway epithelium is involved in airway hyperreactivity, one of characteristic features of bronchial asthma.

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Aerosol is widely used for the evaluation of bronchial hyperresponsiveness. Aerosol antibiotic inhalation therapy is also employed for the high concentration delivery to the microvirous airways with microviral infection. The differences of most commonly used bronchoconstricting agents, acethylcholine (ACh) and methacholine (MCh) in measuring airway responsiveness were determined. A total of 16 normal and 20 asthmatic subjects were studied to determine the bronchoconstricting threshold to ACh and MCh using an Asthograph (TCK-6000CV, Chest MS) on separate days. There was no significant difference in airway responsiveness between ACh and MCh data when expressed as a weight volume concentration. However, there was a significant correlation between ACh and MCh data in Dmin (y=0.70x+0.35, r=0.75, p<0.01). Next, biochemical activities of the antibiotic solutions and modified effects of ultrasonic nebulization on the activities were studied. Several kinds of antibiotics selected and were dissolved in saline or phosphate buffer solution and put in an ultrasonic nebulizer chamber (Omuron NEU06J, Tateishi Denki Co, Ltd.). The pH of the solutions varied from 2.50, minocycline to 8.90, ampicillin, and osmotic pressure ranged from 283 Osm of Tobramycine to 2200 Osm of Fosfomycine, which would possibly increase bronchial constrictive tone via vagal reflex, if the aerosol was inhaled. It has been pointed out that airway responsiveness estimated by PD20 FEV1 was increased when higher or lower osmotic saline solutions more than 0.9% NaCl was inhaled (BMJ, 1981 283 : 1285), so that a correction of osmotic pressure will be required for therapeutic inhalation. Aerosolization for 4 to 5 hours did not significantly change the pH or osmotic pressure. Higher concentration of the antibiotics may decrease aerosolizaion of the solution. The bacteriocidal activity was decreased by as much as 40% when they were exposed to conditions of around 50℃ for 20 min. Then, we concluded that high temperature should be avoided to prevent decrease in bacteriocidal activities.

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It has not been understood how the bronchial lesion develops in cases of sinobronchial syndrome (SBS). In the present study, pulmonary function and airway hyperresponsiveness (AHR) were examined in 30 cases of chronic sinusitis (CS) and 40 cases of SBS to determine the factors influencing the development of bronchial diseases. In cases of CS, routine pulmonary function tests were all within normal and about 10% of cases revealed peripheral airway obstruction which was correlated with the AHR. In cases of SBS, FEV_<1.0>% was reduced in 60% of cases. Peripheral airway obstruction tended to precede the reduction of FEV_<1.0>% and the severity of obstructive change may be related to AHR.

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Thirty seven patients (a total of 39 carcinoma lesions) with stage 0 or I central type lung cancer were treated by photodynamic therapy (PDT) at National Kinki Central Hospital for Chest Diseases. A complete remission (CR) was obtained in 22 patients. To evaluate pretreatment factors which influence results, we evaluated 5 factors : endoscopic appearance, length of tumor, visibility of peripheral area of tumor, tumor location and appearance in chest X-ray. Multiregression analysis revealed that the length of tumor is the most significant factor in achieving CR of tumor. The lack of visibility of the distal margin of the tumor is a significant factor related to relapse. It is expected that PDT combined with operation, chemotherapy or radiation is useful in more advanced cases. In the future, new photosensitizers or new laser equipments may achieve CR in more advanced central type lung cancer.

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An applicator for intraluminal afterloading irradiation using ^<192>Iridium thin wires was devised and applied to 20 patients with lung cancer which had residual endobronchial tumor after external radiation therapy. No residual cancer was found in the treated airway of any of the 20 patients, but two patients had recurrence of the disease in the extrabronchial region and/or untreated airway. No particular complication was experienced. Characteristics of this applicator are : (1) it can be inserted selectively into upper lobe or peripheral bronchi, (2) the radiation source can be put at the central part of bronchus to give uniform dose distribution over the bronchial wall as wings are provided at the top of the applicator that contains the radiation source and serve as a spacer, (3) the soft silicon material of the applicator does not injure the bronchial mucosa. It was concluded that this method is very useful for patients with early central type lung cancer which cannot be subjected to sufficient external radiation therapy because of poor pulmonary function or performance status.

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Bronchofiberscopic polypectomy was performed by electrosurgery using a semicircular snare in 11 tracheal and bronchial tumors (5 benign and 6 malignant tumors), and the usefulness of this procedure was evaluated. The intraluminal tumors were safely resected without bleeding. This procedure was thought to be valuable in the treatment of polypoid tumors originating from the trachea and bronchus.

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We report the use of a metallic stent used in conjunction with contact YAG-laser therapy for the management of malignant tracheobronchial obstruction in 8 patients, which included tracheal stenosis in 4, bronchial in 3 and both combined in one. Five of the 8 showed clinical improvement. The other 3 patients did not improve, because of tumor protrusion after placement of the stent in one, unsuitable stent location in another, and too small a stent in the other. The use of metallic stent provides good quality of living for respiration-compromised patients.

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