Chronic respiratory failure is defined as the condition in which hypoxemia (Pa_O2≤60Torr) continues over one month. The pathogenesis and prognosis of chronic respiratory failure were studied.
The incidence of chronic respiratory failure in the past 10 years is 27.3%, and 60.4% of them are type II (Pa_CO2>45Torr). The death rate is 53%, which is higher than that of acute respiratory failure (24.2%). This high death rate is related to continuous hypoxemia, because no difference of death rate between type I (Po_CO2≤45Torr) and II is observed, in addition mean Pa_O2 at exacerbation in chronic respiratory failure (43Torr) is significantly lower than in acute respiratory failure (52.3Torr). Incidence of respiratory infection and heart failure is 75% in cases of acute exacerbation, and they also are related to mortality. These factors affected the prognosis of chronic respiratory failure.
The frequently observed underlying diseases of chronic respiratory failure are pulmonary tuberculosis, chronic pulmonary emphysema, chronic bronchitis, idiopathic interstitial pneumonitis, and lung carcinoma. These diseases are complicated by different kinds and degrees of severity of multiorgan failure, furthermore, the causes of acute exacerbation and death are different in these diseases. The prognosis of chronic respiratory failure also depends on these underlying diseases.

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The majority of patients with lung cancer already have invisible micrometastatic disease at the time of diagnosis. Therefore we should use combined modality treatment, especially systemic chemotherapy, for lung cancer.
A total of 118 patients with small cell lung cancer were treated at our institution. Twenty-five patients underwent surgical resection followed by combination chemotherapy except one. The remaining 93 non-operated patients were treated with combination chemotherapy and radiation therapy.
The 5-year survival rate for 13 patients with stage I disease undergoing surgical resection was 64.2%. In all 25 resected patients, the 5-year survival rate was 37.2%.
In non-resected patients, only those with complete response had long-term survival, for whom 5-year survival rate was 11.9%. We consider that surgical resection is definitely indicated in patients with stage I small cell lung cancer.
For patients with non-small cell tumors that are potentially resectable, operation is still the best approach for longterm survival., In our series of 380 resected patients with non-small cell tumors, the 5-year survival rate was 45.6%. But until now no evidence of improved survival or delayed recurrence of disease was seen in patients treated with intensive adjuvant chemotherapy.
In our randomized study of chemotherapy for advanced non-small cell lung cancer, patients who were treated with intensive chemotherapy consisting of the CAP-M regimen survived longer than those who were treated with mild chemotherapy with the MFC regimen. Of paramount importance is the discovery of new active drugs that may improve the results of treatment for lung cancer.

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Since 1986, the authors have tried to clarify the factors related to the persistency of sarcoidosis and its pathogenesis. Forty-five cases of clinicopathologic features compatible with sarcoidosis and with concomitant chronic tonsillitis (CT) were studied concerning whether CT was associated with a protracted or progressive course of the disease. In 77% of tonsillectomized cases BHL tended to become smaller in size, while in 85% of non-tonsillectomized patients BHL was unchanged or progressive in the course. In CT lesions, microbial examinations revealed α-streptococcus to be mostly responsible for tonsillitis.
In three cases, swollen tonsils and regional lymphadenopathy were recognized. The histological findings showed many epithelioid granulomas (EGs) both in the tonsillar follicles and regional lymph nodes, which indicated these lesions to be primary tonsillar sarcoid lesions. The chest radiographs showed no abnormalities.
Furthermore, the significance of rest during the course of sarcoidosis was assessed and in most cases serum angiotension converting enzyme (ACE) lowered during hospital, admission except in cases of cconcomitant tonsillitis.
A sterile suspension of sonically disrupted α-streptococcus cultured from CT of a sarcoid patient was injected into the footpads of rats which were killed at 6 weeks and EGs in regional lymph nodes and lungs were examined. One of the causes of sarcoidosis is also considered to be related to predisposition. As indicated in other granulomatous disease by Sasazuki, low responsiveness to antigen is controlled by the HLA-linked dominant gene which he designated as an immune suppression gene. Immune responsiveness to the streptococcal cell wall (SCW) antigen was examined in sarcoid patients. Patients with low circulating immune complex (CIC) showed high response, while those with high CIC showed low response. Low responders improved in clinical course, whereas high responders did not. Raised levels of CIC were associated with low numbers of Fcy-receptor positive lymphocytes and with increased numbers of OKT-8 cells.
Concomitant measurement of serum ACE, lysozyme (LZ) and β-glucuronidase provided an index for differential diagnosis of sarcoidosis and tuberculosis (allergic), especially in cases of uveitis without BHL, and for monitoring disease activity and therapeutic effects. Determination of ACE activity in tears was also a non-invasive test for evaluation of ocular sarcoidosis. In evaluation of these enzymes, assessment of serum ACE and LZ is necessary in renal disorders and in alcoholic liver disease while remission of the disease appears better in cases with negative gallium-scan and those maintaining low ACE in the lower half of the normal range for more than a year.
These results suggest that SCW in the upper respiratory tract seem to present antigens in the lower respiratory tract and sarcoid patients show a predisposition towards immune suppression, and raised levels of CIC modify the immune responsiveness to SCW antigen. Differential diagnosis of the disease and evaluation of disease activity should be performed by careful assessment of these three enzymes.

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Asthmatic attacks in normal guinea pigs provoked by intravenous injection (i. v.) of antibodies to guinea pig IgE were examined by Mead's apparatus which was able to measure pulmonary function without operation or anesthesia. The asthma showed similar changes of pulmonary pattern or pulmonary resistance with asthma provoked by inhalation of antigens to normal guinea pigs passively sensitized with IgE antibodies to the antigens.
Following a 2-minute inhalation of 25mg/ml or 10mg/ml disodium cromoglycate (DSCG) solution, 4 out of 5 guinea pigs showed no sign of asthma after anti IgE i. v. injection which was performed 15 minutes after inhalation of DSCG. In contrast, 5 guinea pigs to which a 2.5mg/ml DSCG solution or physiological saline was administered, developed asthma following i. v. injection of anti IgE. A 2-minute inhalation of DSCG did not cause a change in bronchial response to histamine in guinea pigs. This is the first report showing prophylactic effectiveness of DSCG in guinea pig asthma.
Thus, our system seems to be useful for examination of antiasthmatic agents.

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The purpose of this study was to clarify the relationship between fibrin deposits in the bronchial basement membrane (BBM) and the distribution of Fosfomycin (FOM) to bronchial secretions and bronchial lavage fluids (BLF). Fifteen patients with respiratory disorders received 4.0g of FOM intravenously, and 30 minutes later bronchial secretions and BLF were aspirated by bronchofiberscope to examine the distribution of FOM in those fluids. Additionally, bronchial biopsies were performed to study fibrin deposits in the BBM.
The following results were obtained:
1) Marked fibrin deposits in the BBM were detected in 6 of 15 patients.
2) There was no significant correlation between the amounts of bronchial secretion, the yield of BLF and fibrin deposits in the BBM.
3) In the fibrin-positive group, the FOM concentration in BLF was significantly lower than that in the fibrin-negative group.
4) In the fibrin-positive group, the penetration rate of FOM into BLF was significantly lower than that in the fibrin-negative group.
These results suggest that fibrin deposits in the BBM may reduce the transfer of antimicrobial agents from capillaries to the bronchial lumen through the BBM.

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Methods of treatment and corresponding prognoses were examined concerning 126 cases of spontaneous pneumothorax treated at the Department of Surgery, Tokyo Medical College, during the 5 year-period between 1980 and 1984.
Thoracic drainage using the Heimlich valve was attempted in the outpatient department for patients with a first episode of pneumothorax. Unsuccessfully treated cases were admitted for low pressure continuous drainage or thoracotomy. In the past 2 years about 50% of all cases were treated successfully in the outpatient department by the Heimlich valve, while in most admitted cases surgery was indicated. This suggests that treatment using the Heimlich valve is as effective as continuous drainage and is socially and economically advantageous for patients.
In thoracic drainage, including both low pressure continuous drainage and the Heimlich valve, the recurrence rate was 22.2% and all cases of recurrence occured on the same side.
In cases treated by thoracotomy, the recurrence rate on the same side was 4.41%, but contralateral occurence was 13.2%. This was considered to be rather high. The possibility that operation promotes contralateral pneumothorax was considered to be a problem requiring further discussion.

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A 63-year-old nonsmoking woman had a 6-year history of rheumatoid arthritis. She was frequently treated with aspirin in low doses. Because the arthritis was not adequately controlled, therapy with gold sodium thiomalate (Shiosol^®) was begun in June 1985. After 2 month of gold salt therapy, a skin rash, nonproductive cough, and progressive dyspnea developed. The gold therapy was stopped and she was subsequently hospitalized. The total dose of gold received was 140mg.
The admission chest X-ray film showed diffuse interstitial infiltrates with a predominance in both upper lobes. Arterial blood gases showed hypoxemia and pulmonary function studies showed a mixed ventilatory defect accompanied by an abnormal diffusing capacity. Bronchoalveolar lavage (BAL) was performed. Total cell count revealed 3.0×10⁷cells/ml, with 30% lymphocytes, 68% macrophages and 1%neutrophils. Lymphocyte subpopulations evaluated with Leu monoclonal antibodies showed 1% Leu-3a helper/inducer and 66% Leu-2a suppressor/cytotoxic lymphocytes and an inverted ratio of 0.01. (The normal BAL differential in our hospital, as mean percent±1 S. D. is: total cell count, 7±2×10⁶ cells; lymphocytes, 7±1%; macrophages, 85±4%; polymorphonuclers, 2±1%; Leu-3a, 49±7%; Leu-2a, 32±5%; Leu-3a/Leu-2a ratio, 1.6±0.6). We also confirmed the presence of lymphokines such as macrophage chemotactic factor (MCF), lymphocyte chemotactic factor (LCF) and migration inhitition factor (MIF) in BAL fluid. MCF and LCF were assayed by a modification of Boyden's method using polycarbonate filter (MCF assay) or cellulose nitrate filter (LCF assay), and blind-well chemotaxis chambers. MIF assay was carried out according to David et al., using guinea pig peritoneal exudate cells. Prednisone therapy (50mg daily) was initiated. After 1 month, clinical inprovement was marked, and 4 months later, the appearance on chest X-ray returned to normal along with the pulmonary function test results, while BAL data were as follows: total cell count, 1.0×10⁷ cells with 9% lymphocytes, 87% macrophages; Leu-3a, 55%; Leu-2a, 25%; Leu-3a/Leu-2a ratio, 2.2.
These findings suggest that a cell-mediated hypersensitivity reaction to a drug plays an important role in the etiology of gold-induced interstitial pneumonitis, and BAL analysis of cells, especially the number of lymphocytes and T-helper/T-suppressor cell ratio, may be of diagnostic, therapeutic, and investigative value in evaluating patients with gold-induced interstitial pneumonitis.

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Relationships between output from the central respiratory center and principal variables of breathing patterns were analyzed by a program, designated as MAP (multi-analysis program) using a microcomputer. Written in BASIC with 370 program steps, MAP processes raw data into eleven linear and nonlinear regression lines and displays the graphs on a CRT screen within 70 to 100 seconds. Twenty healthy normal men and women participated as subjects in this study.
Ventilatory and occlusion pressure (p_0.1) response to CO₂ were 1.92±1.13L/mmHg, and 0.57±43cmH₂O/mmHg respectively. These data were in accordance with the normal values reported elsewhere.
Three basic types of patterns pertaining to the changes of V_T, T₁ and T_E in response to progressive hypercapnia were demonstrated on the newly devised V_T, T₁ and T_E diagrams. Four subject showed no significant changes in T₁ and T_E (A type). Six subjects demonstrated remarkable shortening of T_E (B type). Both T₁ and T_E were shortened in ten subjects (C type). P_0.1 (CIA) related well with mean inspiratory flow V_T/T₁ in all types. A significant linear correlation between P_0.1 and 1/T₁ (r=0.968±0.023) were noted in ten subjects in type C. These breathing patterns were not related to anthropometric data nor pulmonary mechanics of the subjects in this study.
Inspiratory duty cycle T₁/T_TOT changed significantly only in type B. While ventilation was increasing, tidal volume increased up to 50% of FEV_1.0, and thereafter shortening of T₁ resulted in an increase in mean inspiratory flow V_T/T₁. Effective compliance was 184.0±78.9ml/cmH₂O when tidal volume increased from resting level to 50% of FEV_1.0. Effective impedance was 7.24±3.02cmH₂O/L/sec.
The results of this new analysis of breathing patterns were considered to be valuable in studying breathing control.

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A 42 year-old female was admitted to our hospital for further examination of left unilateral hyperlucency on chest X-ray. She was diagnosed as Swyer-James syndrome by bronchography, pulmonary arteriography, pulmonary perfusion scan and ventilation scan. Bronchial arteriography and mesurements of P_O2 in pulmonary arteries demonstrated no evidence of bronchial arteries-pumonary arteries shunt. After administration of sublingual nifedipine, there was a marked decrease in pulmonary artery resistance and a moderate decrease in Pa_O2. It was considered that the vessels of the affected side could be dilated by this drug. Aerosol inhalation scintigraphy revealed that mucociliary transport mechanism was not impaired in the central respiratory tract of the affected side.

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A case of organizing pneumonia (with bronchiolitis obliterans) which was proved by open lung biopsy is reported. Multiple round shadows were found on a chest mass survey in an asymptomatic 53 year-old female.
Her physical findings were unremarkable except for low grade fever. Laboratory data showed mild lymphcytosis and mild elevation of erythrocyte sedimentation rate. Serological examination was negative, including CRP, RA, cold agglutination test, and antibodies to mycoplasm. Metastatic lung tumor was clinically suspected because of the presence of multiple round shadows and lack of symptoms.
Various examinations to detect primary tumor turned out to be negative, and open lung biopsy was carried out to obtain a definitive pathological diagnosis.
In pathological examination of the biopsied lung, mononuclear cell infiltration in the membranous portion of the bronchioles and respiratory bronchioles, as well as obstruction of the respiratory bronchioles by organizing inflmmatory exudate, which was also noted in the alveolar ducts, sacs, and occasionally in the alveoli, were seen. There were cellular interstitial pneumonia and secondary lipid pneumonia in the affected areas. A diagnosis of idiopathic organizing pneumonia (with bronchiolitis obliterans) was made. Abnormal pulmonary shadows disappeared gradually during antibiotic treatment.
The pathological diagnosis of “bronchiolitis obliterans organizing pneumonia” has appeared in the literature very recently, but nearly the same category has been reported in terms of “cryptogenic organizing pneumonia”, and those cases were sensitive to steroid therapy. Previous interpretations of this pathological condition considered it to be residuae of bacterial pneumonia, however it may be a disease of another etiological background.

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A 34 year-old man was admitted complaining of fever and exertional dyspnea. He had allergic factors in his family and past history. On admission, his chest X-ray showed no abnormal findings but fine creakles were auscultated. ⁶⁷Ga scintigram showed strong diffuse accumlation in both lungs, and the results of TBLB and BAL suggested granulomatous hypersensitivity pneumonitis. From these findings, the relation of his symptoms to the use of a humidifier in his house, and the results of a provocation test, we suspected humidifier lung. Because the provocation test was positive, a diagnosis of humildifier lung was made.

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