Airway mucosa consists of several types of cells including ciliated cells, mucus secreting cells, basal cells and Clara cells. In this review, fine structures of these epithelial cells and intercellular junctions are demonstrated by scanning and transmission electron microscopy, and the proposed kinetics of cellular maturation and development are discussed.
Airway epithelium not only plays a role as a mechanical barrier at the airsurface interface but also possesses a wide variety of functions. Ciliary beating has been recognized to be one of the important determinants for mucociliary transport by clearing inhaled particles and bacteria from the airway. We found that the motility of cilia can be regulated by intracellular second messengers, such as Ca²⁺, cAMP, and protein kinase C. When ciliated epithelium is encountered by physicochemical stimuli, these signal transduction systems are activated through phosphatidylinositol turnover and/or Ca²⁺ channel opening, which subsequently modulate the synthesis of ATP, an energy source of ciliary beating. Airway epithelium contains the enzyme neutral endopeptidase which can degrade several peptides into inactive fragments, thus regulating the actions of tachykinins released from sensory C-fibers via axon reflex.
Ion transport across airway mucosa is determined by Cl secretion and Na absorption in airway epithelium. To elucidate the mechanism of airway hypersecretion under several conditions of respiratory diseases, the effects of chemical mediators, neuropeptides, and inflammatory mediators on electrical properties of canine cultured tracheal epithelium were studied. We also expanded this idea to human subjects and found that indomethacin inhalation was valuable in reducing the amounts of sputum production by inhibiting Cl and water secretion into the airway lumen.
In addition, airway epithelium can modulate contraction of airway smooth muscle by generating epithelium-attributable to the loss of airway epithelium with EpDRF.

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In order to study the effect of the decrease in P-Pi caused by low pH on hemoglobin-oxygen affinity, we measured P-Pi, 2, 3-diphoshoglycerate (2, 3-DPG), and oxygen tension at 50% saturation (P₅₀) in 36 cases with acute exacerbation of chronic respiratory failure with hypercapnia. The cases were classified into two groups by arterial blood pH values obtained on the day of admission. Group A: pH≤7.35 and Group B: pH≥7.36.
P₅₀ was calculated by a modification of Severinghaus' equation developed by Yusa and Kohsaka, and it was corrected by applying the carboxy-hemoglobin (COHb) coefficient.
On the day of admission (stage I), 2, 3-DPG and P₅₀ in both groups were slightly higher than in the control group.
In Group A, a week after admission (stage II), these values decreased and became significantly lower than they had been at stage I. Especially 2, 3-DPG in stage II was even lower than those of the control group. Approximately 14 days after admission, in stage III, it was found that these values had risen to the initial level at stage I.
In Group A, similar changes were also observed for P-Pi. The value of P-Pi was low in stage II and recovered to the initial value in stage III. On the other hand, we found that the urinary excretion of phosphorus (U-Pi) increased at stage I in Group A. It was supposed that the increase in U-Pi at stage I caused a decrease in P-Pi, which caused the decrease in 2, 3-DPG, in stage II. In Group B, U-Pi, P-Pi, 2, 3-DPG, and P₅₀ remained stable during these periods.
From the above results, we found that there was a difference in hemoglobinoxygen affinity between the two groups; In Group A, glycolysis in erythrocytes was depressed, but there was no significant decrease in P₅₀ and therefore we supposed that the oxygenation of tissues was not considerably inhibited. In group B, the hemoglobinoxygen affinity was supposed to be stable bacause P₅₀ showed a tendency to have a high value throughout the period and even increased.
Investigations of factors related to P₅₀ disclosed statistically significant positive correlations between P₅₀ and 2, 3-DPG in stage II, and between P₅₀ and PaCO₂ in stage III. It was shown that the single relationship between P₅₀ and 2, 3-DPG in stage II could explain 54.7% of the measured variance in P₅₀, and between P₅₀ and PaCO₂ in stage III could explain 41.7%. There was no correlation between P₅₀ and pH, nor between P₅₀ and COHb.
It was suggested that 2, 3-DPG and PaCO₂ were the most relevant of the variables examined affecting P₅₀ in this study.

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In the screening test of lung cancer, we found that there was a high prevalence of cases with pleural plaque recognized by chest X-ray film in inhabitants living in A town in Kumamoto Prefecture. We detected abnormal pleural plaque in 148 (41.5%) of 357 cases received lung cancer screening. These pleural plaques resulted in pleural thickening and calcification. Two or three mines of serpentine and an asbestos factory existed in this region from 1883 until 1970.
Although twelve cases had a history of factory work, none had fibrous changes in the lung fields on chest X-ray films. It was considered that the pleural plaque was probably resulted to exposure to low doses of asbestos in the atmosphere or contact with asbestos workers in their homes. The incidence of lung cancer in this region was not higher than that in other regions in Kumamoto Prefecture. There were no cases of malignant mesothelioma in our hospital during the past eleven years.

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It is well known that patients with diffuse panbronchiolitis (DPB) have various immunological abnormalities. The authors evaluated the peripheral lymphocyte subsets using two-color analysis by FACS. Convening percentages of activated CD3⁺, CD8⁺, and CD4⁺ cells in DPB patients, all, especially that of CD8⁺ cell, were greater in number before therapy compared to healthy controls. After erythromycin therapy, all three parameters decreased in all patients. Therapy with other antibiotics did not obtain any effects.
These results suggested that patients with DPB had some immunological hyperreactivity and that erythromycin was effective in these patients by suppressing this activity. From these results, together with the fact that DPB is a type of sino-bronchial syndrome, the possible pathogenesis of DPB was thought to be related to some immunological defect and hyperreactivity in the respiratory system.

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The pattern of relapse was analyzed in patients with small cell lung cancer (SCLC). Of 180 patients treated with intensive combination chemotherapy between 1976 and 1987, 75 achieved complete response (CR). Of 47 patients with limited disease (LD), 20 (43%) initially relapsed in the chest and 7 (15%) in the brain. Among 27 patients with extensive disease (ED), the chest was also the most frequent site of relapse (44%) followed by the brain (19%). In LD patients who had received chemotherapy plus chest irradiation, the initial relapse rate and the cumulative relapse rate in the chest at 2 years were only 29% and 35.4%, respectively. These rates were significantly lower compared with the rates of 69% and 76.5% for patients who had received chemotherapy alone (p<0.05). Survival was improved to some extent by the addition of chest irradiation, but not significantly, however, the long-term survival rate favored those receiving chest irradiation. Prophylactic cranial irradiation (PCI) reduced the frequency of brain relapse and significantly improved the survival of SCLC patients achieving CR. The median survival time and 5-year survival rate of patients who received PCI were 23.1 months and 26.7%, which these figures were only 14.0 months and 8.3% for those who had not respectively. Analysis using Cox's proportional hazard model showed that PCI was the greatest prognostic factor favoring the SCLC patients achieving CR. These results indicate that chest irradiation and PCI in conjunction with intensive combination chemotherapy are effective for cases of SCLC with CR.

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In seven normal adult males the authors studied diaphragmatic fatigue by analysis of the power spectrum of the diaphragmatic electromyogram obtained with an esophageal electrode, and of the change of transdiaphragmatic pressure. Diaphragmatic fatigue was produced by inspiring through a resistive load, and mean value of the index of the tension time of the diaphragam (TTdi) maintained until fatigue was 0.33±0.09, which has been known to produce fatigue. The mean value of ratios of power at high frequencies to power at low frequencies (H/L) decreased to 61.2±16.8% of the initial value at just before breaking time. Breaking time was 4.88±1.37 minutes in average.
The selection of low and high band widths for analysis of H/L ratio has differed slightly in the literature, but such differences do not have any substantial influence on the estimation of the changes of H/L ratio.

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Although there have been many reports on the airway area measured by breathing 80% He-20% O₂ (He-O₂) using the acoustic reflection technique (ART), there have been no reports on that by breathing room-air (Air) because of the lack of accuracy in evaluating the trachea. When measuring with He-O₂, accidental introduction of Air into the airway makes the measurement inaccurate. Moreover, it is a time-consuming method and is hardly applicable to dyspneic patients. Therefore, we tried to assess whether the airway area, especially the upper airway, can be measured while breathing Air. In order to compare the areas determined by the two methods, area-distance functions from the pharynx to the trachea were arbitrarily divided into 9 divisions at interval of 2.8cm. Each of these divisions was respectively compared. We took averages of the pharyngeal, tracheal areas in 8 normal subjects. We found no significant difference between the oropharyngeal area measured by breathing Air and that measured by breathing He-O₂, and found a significant correlation between them. There was a significant correlation between the hypopharyngeal areas when using the two methods. The average tracheal area by breathing Air is 4.96±0.50cm², which is 40% above that when measured using He-O₂ (3.55±0.32cm²). In contrast, the average pharyngeal area when breathing Air is 4.13±0.93cm₂, which overestimates that by breathing He-O₂, namely 3.54±0.84cm₂ by only 17%. In conclusion, it is possible and useful to estimate the pharyngeal area by breathing Air.

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To evaluate the usefulness of serum lipid-bound sialic acid (LSA) as a tumor marker in patients with lung cancer, its serum levels was determined in 85 patients with primary lung cancer, 42 patients with benign pulmonary diseases and 22 healthy controls by the method developed by Katopodis and Stock. The mean serum LSA concentration was significantly higher in the patients with primary lung cancer [32.4±16.4 (SD) mg/dl] than that in the patients with benign pulmonary diseases (22.4±12.4mg/dl) or in healthy controls (17.2±4.5mg/dl). The serum LSA level was elevated above the mean value plus 2 SD for the healthy controls (26.0mg/dl) in 60% of all cases with primary lung cancer including 1 of 9 (11.1%) in stages I and II and 50 of 76 (65.8%) in stages III and IV and 35.4% of the patients with benign pulmonary diseases. No significant difference was observed in serum LSA concentration among each cell type of lung cancer. Serum carcinoembryonic antigen (CEA) was elevated (>5.0ng/ml) in 39.8% of the patients with lung cancer. As there was poor correlation between serum LSA and CEA levels, when these two markers were used in combination, 71.1% of the cases with lung cancer in this study showed elevated levels of either serum LSA or CEA, or both. Moreover, in the patients with small cell lung cancer followed up during intensive chemotherapy, serum LSA levels changed almost parallel with the clinical course. These results indicate that serum LSA may be a useful biochemical marker in lung cancer patinets.

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Three weeks prior to admission, cough and dyspnea developed in a 49-year-old man and progressed to acute respiratory failure. The patient was treated with a mechanical ventilator. Open lung biopsy revealed diagnosis of BOOP. With corticosteroid therapy, the patient recovered dramatically.

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A 43-year-old man, who came to our hospital for further examination of a thoracic abnormality pointed out on a check-up examination. Chest X-ray revealed a protruding tumor shadow on the right diaphragm. The patient had a history of right precordial contusion due to a traffic accident about 2 years previously, and after the injury a shadow appeared which gradually became larger, suggesting traumatic right diaphragmatic rupture-induced hernia. Chest CT scan revealed middle hepatic vein within the tumor without changes such as deviation and/or stenosis and hepatoparenchymatous tumor. Ultrasonography revealed the tumor to comprise a part of the liver (S₄, S₈) with the normal internal echo and the right diaphragm dividing the liver parenchyma in two, intrathoracically and intraperitoneally. The above led to the diagnosis of right diaphragmatic hernia, which probably was caused by the traffic injury and gradually increased during approximately 2 years. In cases of suspected traumatic right hemidiaphragmatic hernia, ultrasonography is regarded as useful.

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Two cases of pulmonary alveolar proteinosis with increased serum CEA were reported. In both cases, the clinical diagnosis of pulmonary alveolar proteinosis was confirmed by transbronchial lung biopsy (TBLB).
Immunohistochemical study of the lung biopsy specimen showed that CEA staining was present in the region of alveoli where type II alveolar epithelial cells proliferate. It was suggested that proliferative type II cells produced CEA in pulmonary alveolar proteinosis.
The study of cell surface markers in their bronchoalveolar lavage fluid (BALF) revealed increase of CD8 and Leu7 positive cells and decrease of CD4 positive cells. In the case 2, there was significant increase of B lymphocytes marker positive cells. These results suggested that there may be abnormal regulation of both T and B lymphocytes and NK cells, leading to dysfunction of the pulmonary alveolar macrophage in pulmonary alveolar proteinosis.

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A 72-year-old female with malignant lymphoma, receiving oral cyclophosphamide (CPA) and prednisolone, developed severe pulmonary insufficiency 56 days after the start of CPA (total dosages 8.5g). A chest roentogenogram showed a diffuse interstitial shadow throughout both lungs, and CT scan revealed increased density, most prominent in the central zones, and a thickening of bronchovascular bundles. She was diagnosed from the clinical course and the postmortem examination as having cyclophosphamide-induced interstitial pneumonia. Interstitial pneumonia as a side-effect of cyclophosphamide is very rare in Japan. The clinical and pathological findings in this case and a review of the literature on 38 other cases world-wide are reported.

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A 55-year-old male was admitted with fever, productive cough and dyspnea for a month. Chest X-ray revealed infiltration in the right lower lung field and right pleural effusion. Cultures of sputum, bone marrow and peripheral blood disclosed mycobacterium avium-intracellulare complex. The specimens of the liver, gallbladder wall and mesenterium obtained on cholecystectomy revealed epithelioid granulomas. Fifteen months after the admission, bronchoscopic finding showed a pedunculated polyp in the right main bronchus, and three other bronchial polyps in the truncus intermedius, right basal bronchus and B⁶. These bronchial lesions improved with combination chemotherapy containing cycloserine (CS) and other antituberculosis drugs. He was discharged 36 months after the admission. Perforation of the involved hilar lymph-nodes was considered to play an important role in the development of the multiple bronchial polyps. Cases of disseminated atypical mycobacteriosis accompanied with multiple bronchial polyps are extremely rare.

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A 32-year-old woman was referred to our division because of abnormal shadow on a chest X-ray film taken at an annual health survey. Chest X-ray films and chest CT scanning revealed a smooth-surface mass at the left hilus. A bronchoscopic examination revealed severe extraluminal compression in the left basal bronchus but no visible tumors. Surgical treatment was performed on the suspicion of lung cancer. Since the intraoperative frozen section examination revealed a benign tumor, the tumor mass was resected. Based on intraoperative and pathological findings, benign intrapulmonary schwannoma associated with the left basal bronchus was diagnosed. Only 15 cases of intrapulmonary schwannoma have been reported in Japan.

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