N₂ clearance curves obtained by a multiple breathing method were analysed on the basis of 50 multiple compartments by means of a mathematical technic using a computer, using the following theoretical function reported by Lewis.
C_j/Co=Σ^m_j=1Vi⋅(1/1+Si)^j i=1, 2, ...., 50
(C_j: end tidal N₂ concentration at jth breath, Co: initial N₂ concentration, Voi: volume of each compartment of lung at the FRC level, V_A: alveoral ventilation (V_A=V_T-V_D), V_D: dead space, Vi: fraction of ventiation of each compartment, Si: ventilation/volume. (Si=Vi⋅V_A/Voi))
The data recovered from subjects were analyzed on the basis of the following expression, with specified compartments equally spaced on a log scale of Si from 0.005 to 10.
minimize Σⁿ_j=1[Σ^m_j=1Vi⋅(1/1+Si)^j-Cj/Co]²
subject to Σ^m_j=1Vi=1
Vi≥0
i=1, 2, ...., m, j=1, 2, ...., n
In this paper, the above expression was considered as a nonlinear programing problem, and a new method for solving this problem was developed, starting from an initial feasible point, and locating new feasible points in an iterative manner by moving a direction conjugate in the previous direction of search. As such, it may be considered a new extension of the work of Rosen on problems involving linear constraints and the work of Hestenes and Siefel on unconstrained problems.
Using this technique, the recovery based on error-free data calculated from known distribution was studied. Distribution patterns in 10 normal subjects and 31 patients with chronic pulmonary diseases were discussed.
1) The intrapulmonary distribution of inspired gas could be shown visually and quantitatively, and the distribution patterns of both groups were distinctly different.
2) The recovery based on error-free data calculated from unimodal known Gaussian distribution almost completely fitted given data, and the recovery from bimodal or trimodal distribution bore a close resemblance to given data.
3) The stable distribution patterns were based on 1000 iterative calculations, and the sum of the squares was near 10^-5. The time requred for 1000 iterative calculation was about 8 minutes on an IBM 4341.
4) From 50 values of fraction of ventilation (Vi) to ventilation/volume (Si), the mean (Si-Mean) and standard deviation (Si-SD) of ventilation/volume were calculated. Si-Mean is a parameter of overall ventilation/volume ratio, and Si-SD is a parameter of unevenness of intrapulmonary distribution of inspired gas.
5) Si-SD correlate with FEV_1.0% (r=-0.672, p<0.01), %MVV (r=-0.698, p<0.01), RV/TLC% (r=0.568, p<0.01) and I.D.I. (r=0.485, p<0.05). This results suggested that the more severe the degree of obstruction and the greater the RV/TLC% ratio, the more uneven was the distribution. There was no correlation with PaO₂ and PaCO₂.
From these results, it was concluded that the analytical method reported in this paper is useful to evaluate the unevenness of intrapulmonary distribution of inspired gas.

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In order to know the relationship between the maximal expiratory flow rate response to low density gas breathing and conventional parameters to determine the site of airway obstruction, physiologic studies were performed in 23 asthmatics during the asymptomatic stage or during mild attack.
These subjects were divided into two groups; One group (SG-N group) consisted of 14 patients whose percent predicted specific airway conductance was 80% or more, and the other group (SG-A group) consisted of 9 patients whose percent predicted specific airway conductance was less than 80%.
In each group and also in all subjects, the correlations between the results of pulmonary function tests when breathing air and the percent increase of maximal expiratory flow at 50 percent of vital capacity when breathing a 80%-20% He-O₂ mixture as compared to air (ΔV₅₀ He-O₂/Air) were examined.
1. Significant correlations were seen between ΔV₅₀ He-O₂/Air and forced expiratory volume in one second in the SG-N group and all subjects, and between ΔV₅₀ He-O₂/Air and specific airway conductance in all subjects, but the correlation coefficients were relatively low. There was no significant correlation of ΔV₅₀ He-O₂/Air to peak flow rate in any group.
2. There were significant correlations of ΔV₅₀ He-O₂/Air to V₅₀, V₂₅ and maximal mid-expiratory flow in the SG-N group and in all subjects. A significant inverse correlation was seen between ΔV₅₀ He-O₂/Air and closing volume in the same groups. The relationships were more evident in the SG-N group than in all subjects. These correlation coefficients were higher than those in both specific airway conductance and forced expiratory volume in one second. There was no correlation between ΔV₅₀ He-O₂/Air and the above mentioned parameters in the SG-A group.
3. In 17 patients whose V₅₀ before breathing He-O₂ mixture was less than the lower limit of the predicted value, 13 cases showed ΔV₅₀ He-O₂/Air greater than 20%.
4. The patients medicated with corticosteroid showed lower ΔV₅₀ He-O₂/Air than patients without corticosteroid. The above results suggest that conventional paramenters to detect the peripheral airway obstruction, such as V₅₀, V₂₅ and closing volume, correlate with maximal expiratory flow response to low density gas breathing more closely than what are called parameters of large airways. Particularly when the specific airway conductances of the patients are within normal limits, these correlations become more evident. It also seems reasonable to suggest that the site of principal bronchoconstriction in asthmatics generally exists in large airways, although in some cases it may be in peripheral regions.

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The results of clinical and pathological study on twelve cases with unstable, wandering infiltrates, which are considered to be characteristic roentgenographic features of pulmonary infiltration with eosinophilia (PIE) syndrome, were reported.
Histological findings of transbronchial lung biopsy specimens of five cases with migratory infiltrates and peripheral blood eosinophilia were consistent with the features of eosinophilic pneumonia. These five cases and on additional three cases whose lungs were not biopsied, were finally diagnosed as chronic eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, or drug-induced pneumonitis with PIE syndrome. On the other hand, the histology of four cases without peripheral blood eosinophilia revealed interstitial and intra-alveolar cell infiltrates except eosinophils, and a definitive diagnosis of these cases was not obtained.
Therefore, in the casess with clinical and roentgenological findings similar to PIE syndrome apart from eosinophilia, further etiologic or allergic mechanical investigations are important.

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A case of chronic non-traumatic fracture of the left first rib occurring in a 38-year-old housewife with neuropathy-like symptoms resembling whiplash injury was presented.
Onset occurred abruptly during ploughing, but fracture was not recognized until more than one year and four months later. The site of fracture was at anterior neighbouring the cartilage, and roentgenographic findings showed pseudoarthrosis enveloped by a bulbous callus at the first visit to our clinic three years and three months after the onset.
Her clinical course, after correct diagnosis and treatment with medication of minor tranquillizer and calcium lactate, was not eventful and complete bone union with disappearance of clinical distress were observed within a half year.
In order to compare the presented case with those previously reported in our country, 35 cases of non-traumatic fracture of the first rib were listed and reviewed, and the author concluded that though the majority of fractures, especially in those aged under twenty, are induced by muscular pull; the remainder, about 15% of reviewed cases, all of which were over thirty years and including the presented case, should be considered as the result of thoracic inlet insufficiency.

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Immunosuppressive acidic protein (IAP) and carcinoembryonic antigen (CEA) levels in sputum from patients with various respiratory diseases were measured by single radial immunodiffusion method and enzyme immunoassay, respectively. The sputa were effectively solubilized with 2% N-acetyl-L-cysteine prior to the analysis. The mean value±S.D. of IAP (μg/ml) in sputum from patients with lung cancer (n=23), chronic bronchitis (n=45), bronchial asthma (n=5), bronchiectasis (n=6), pneumonia (n=5), chronic pulmonary emphysema (n=9) and idiopathic pulmonary fibrosis (n=18) was 212±396, 121±131, 110±141, 101±53, 68±55, 62±23 and 60±32, respectively. The IAP level in sputum increased in proportion to purulence and the number of causative bacteria cultured, except for a patient with bronchiolo-alveolar carcinoma. There was a weak correlation between serum levels and sputum levels of IAP (r=0.39, p<0.05). The mean value±S.E. (μg/ml) of CEA in sputum was 2, 387±1, 095 in patients with lung cancer (n=14) and 444±102 in those with non malignant pulmonary diseases (n=30), with a significant difference between them (p<0.05). These results indicate that IAP in sputum reflects local inflammatory change and that measurement of CEA in sputum appears to be a useful simple test in the diagnosis of lung cancer.

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270 patients with sarcoidosis underwent transbronchial lung biopsy (TBLB) at 25 hospitals in Japan between 1973 and July, 1980.
The frequency of non-caseating epithelioid cell granulomas in the specimens obtained by the TBLB was correlated with the stages of chest radiographic changes, and was not correlated to the selected biopsy site among stage I patients, the presence or absence of a past history of corticosteroid treatment or of extrathoracic lesions, the strength of Mantoux reaction and the level of serum γ-globulin.
The epithelioid cell granulomas were recognized in the histological specimens obtained by TBLB: in one of 10 patients at stage 0(10%), in 42 of 101 patients at stage I (42%), in 88 of 119 patients at stage II (74%), and in 24 of 40 patients at stage III (60%).
The frequency of the epithelioid cell granulomas in specimens obtained by the TBLB from the stage I patients was maximal (65%) when three specimens were obtained. The frequency in specimens obtained by TBLB was comparable to the results of the scalene lymph node biopsy in stage II and III patients.
Complications due to the TBLB occured in 27 patients (10%): pneumothoraces in 13, bleeding in 13, and chest pain in one patient but most did not require treatment.
In consideration of the ease, safety and accuracy of histological examination results, TBLB would be the first diagnostic procedure of choice for histopathological diagnosis in most cases suspicious of sarcoidosis.

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Four hundred and ninety-six specimens obtained by transbronchial lung biopsy (TBLB) from 205 patients with sarcoidosis were examined microscopically. A histopathological classification of the findings of the specimens obtained by TBLB was submitted. Noncaseating epithelioid cell granulomas were classified into three types: hypertrophic, atrophic, and fibrous and/or hyalinous. The frequency of giant cells and the intensity of perigranulomatous lymphocytic cuffing were divided into three grades.
After lesions caused by the biopsy were excluded, thickening of alveolar septums (AST) were evaluated and classified into cellular or fibrous type when the alveolar area was broader than 400×400 microns. The diffuseness of AST was divided into three grades. Cellular type AST consisted of interstitial infiltration of lymphocytes, histiocytes or other inflammatory cells other than polymorphonuclear neutrophils. Fibrous type AST consisted of an increase in eosinophilic collagenous matrix and fibroblasts in the alveolar septum.
Lung specimens from 71 sarcoidosis patients without steroid treatment before TBLB were examined by five pathologists applying the above histopathological classification. Noncaseating epithelioid cell granulomas were present in 42 patients (59%) and AST was noted in 20 patients (28%).
Among the 42 patients with epithelioid cell granulomas in the specimens obtained by TBLB, AST was observed in 18 patients (43%: cellular type in 9 and fibrous type in 9), whereas only 2 patients (7%: one each cellular and fibrous type) were evaluated positive for AST among 29 patients with no definite epithelioid cell granulomas in those obtained by TBLB (p<0.01).
AST was noted in 9 of 15 patients (60%: cellular type in 5 and fibrous type in 4) when lymphocytic cuffing was around the epithelioid cell granulomas, whereas AST was noted in 9 of 27 patients (33%: cellular type in 4 and fibrous type in 5) when no definite lymphocytic cuffing was around the granulomas.
Eight of 9 patients (89%) with cellular type AST were associated with hypertrophic epithelioid cell granulomas, whereas 5 of 9 patients (56%) with fibrous type AST were associated with those granulomas.
All of the 9 patients with fibrous type AST were associated with atrophic, fibrous and/or hyalinous epithelioid cell granulomas, whereas only 5 of 9 patients (56%) with cellular type AST were associated with those types of granulomas (p<0.05).

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To investigate the role of infection in acute exacerbations of emphysema, 33 patients with acute exacerbations of emphysema over a period of 22 years (1959-1980) were examined.
The following results were obtained:
1) Of the 56 exacerbations studied in 33 patients with emphysema, 67.8% were associated with respiratory infection: respiratory tract infection (41%) and pneumonia (26.8%). The respiratory infection was the most important cause, although there were many causes of acute exacerbation of emphysema. Seven (77.8%) out of 9 cases with a fatal outcome of exacerbations died from respiratory infection.
2) Twelve (31.6%) out of all 38 exacerbations were caused by microbial infections, 9 of them were associated with bacteria and 3 with viruses. The microbes were Staphylococcus aureus (2), Haemophilus influenzae (2), Pseudomonas aeruginosa (2). Streptococcus pneumoniae (1), both Streptococcus pneumoniae and Haemophilus influenzae (2). Influenza virus A (2) and Parainfluenza type 3 (1).
3) The monthly incidence of exacerbations was greatest in January, February, July and November.
4) The main symptoms in exacerbations were remarkable dyspnea, cyanosis in about half, and dehydration in association with sweating and tachypnea. It was worth mentioning that about 30% of infectious cases had no fever.
5) It was noted that test results were within normal limits in 42% in WBC, 52% in ESR and 26% in CRP in cases of respiratory infection. Laboratory findings showing WBC over 13, 000/mm³, ESR over 50mm/hr and CRP over (3+) in exacerbations were strongly suggestive of respiratory infection.
6) Blood gas findings showing PaO₂ below 40 Torr and PaCO₂ over 60 Torr in exacerbation indicated a poor prognosis.
7) FEV_1.0 and FEV_1.0% in cases of respiratory infection were significantly below those of non-infectious cases (p<0.01).

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The presence of angiotensin I converting enzyme (ACE) activity in lung is a relatively recent finding. It is well known that serum ACE activity increases markedly in patients with sarcoidosis. In this experiment serum ACE activity was determined in patients with pneumonia.
1) Mean values and standard deviation (SD) of serum ACE activity in acute and recovered phases were 27.9±10.6U and 34.8±13.1U, respectively. There were significant differences between these values.
2) Mean values and standard deviation of serum ACE activity in patients in the acute phase of bacterial and viral pneumonia were 23.8±9.2U and 27.1±9.4U, respectively. There were no significant differences between these values.
3) Mean values and standard deviation of serum ACE activity in patients with pneumonic infiltration area less than 10% and more than 10% were 29.9±6.3U and 20.5±8.4U, respectively. There were significant differences between these values.
The above results may suggest that the decrease of serum ACE activity in patients with pneumonia results from the decrease of pulmonary vascular beds.

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A 63-year-old male was diagnosed as having thymoma and hypogammaglobulinemia with 2.5% in total protein in 1974. Preoperative respiratory function tests revealed normal vital capacity and a slightly impaired one second forced expiratory volume, only 61% of vital capacity. After thymectomy, adjuvant of gammaglobulin therapy was continued, however hypogammaglobulinemia persisted. About two and a half year after thymectomy, he was re-admitted because of increasing cough. Sputum bacterial culture revealed H. Influenzae infection. Since then, he has suffered from aphtous stomatitis, uveitis and recurrent bronchopneumonia. He was admitted a sixth time in 1980 because of fever, cough and dyspnea.
His gammaglobulin levels were very low and the PPD skin test was negative. He died of pneumonia and respiratory failure. Macroscopic examination at autopsy revealed yellow micronodules on lung cut-surface coincident with bronchioles. Microscopic examination showed chronic inflammatory change in bronchioles with foamy cells. Generalized Herpes virus infection was demonstrated in liver, adrenal gland and the mucous membrane of the oro-pharynx and esophagus. Due to the negative PPD skin test and hypogammaglobulinemia of this patient, hyperfunction of suppressor T-cell was considered to have suppressed the function of B-cell and effector T-cell. The region of respiratory bronchioles is weak location in terms of lung defence mechanism. Viral or bacterial infection on bronchiole of this immunologically compromized patient seemed to produce diffuse panbronchiolitis.

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A 40 year-old female was admitted on January 31, 1981, with fever, dyspnea, productive cough and jaundice. On admission, severe anemia and acrocyanosis were observed. Chest X-ray film showed bilateral diffuse infiltrative shadow in the midlower lung fields. The ESR was 172mm/hr. hemoglobin 5.9g/100ml. WBC 34800mm³ with 73% neutrophils. The reticulocyte count was 164%, the indirect serum bilirubin 1.3mg/100ml and the serum LDH 1096 with especially elevated LDH₁. The sternal marrow showed marked erythroid hyperplasia. The direct Coombs' test was positive and antibodies on the erythrocytes were found to be IgM and C₃d. Cold agglutinin titer was 1 to 16384, CF titer for Mycoplasma pneumoniae was 1 to 1024. From these data the diagnosis of autoimmune hemolytic anemia associated with Mycoplasma pneumonia was made. Following institution of antibiotic therapy and steroid therapy the patient made a rapid recovery, and the chest X-ray showed remarkable improvement. After 10 weeks of hospitalization the patient was discharged, the direct Coombs' test was negative, the cold agglutinin titer was 1 to 1024, the CF titer for Mycoplasma pneumoniae was 1 to 128.

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A 59-year-old female case of chronic pulmonary sarcoidosis with multiple bronchostenosis was reported. X-ray examination in June, 1974, showed diffuse granular—nodular shadows in the lung and sarcoidosis was confirmed by open lung biopsy. After 2.5 year steroid treatment, the shadow disappeared almost completely in June, 1977. She complained of exertional dyspnea in September, 1979. X-ray examination showed a peri-hilar fibrous lung shadow. Pulmonary function tests, revealed obstructive impairment, abnormal pulmonary diffusing capacity and hypoxemia. Marked bronchostenosis of RML and RUL bronchi was noticed by bronchoscopy and the bronchial biopsy showed submucosal epitheloid cell granuloma. Steroid treatment was started again in April 1980. Exertional dyspnea, bronchial lesions and abnormal pulmonary function had improved one year later.
Pulmonary function was studied in five patients with chronic fibrotic pulmonary sarcoidosis. A decrease in FEV_1.0% was present in only one patient. In two patients without restrictive impairment, one showed decrease in % MMF and Vmax, and the other showed decrease in Vmax and abnormal Visov. These results suggest that airway dysfunction is not uncommon in chronic fibrotic pulmonary sarcoidosis.

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A case of multiple pulmonary arterio-venous (A-V) fistulas associated with liver cirrhosis was presented. The patient, a 54 year-old male, who had been suffering from dyspnea with cyanosis for 3 years was admitted to Yokohama City University Hospital, and a moderate degree of cyanosis, digital clubbing and multiple teleangiectasia was noted.
Laboratory findings and liver scintigraphy suggested liver cirrhosis. The arterial blood gas data showed hypoxemia. Cardiac catheterization and cardio-angiography ruled out congenital heart disease, but the multiple pulmonary A-V fistulas were suspected and the A-V shunt ratio was shown to be 26.4%. Pulmonary scintigraphy by ^99mTc-MAA ruled out massive blood flow defect and the A-V shunt ratio was calculated to be a 26.7%. According to these data, the case was clinically diagnosed as hypoxemia due to multiple A-V fistulas with liver cirrhosis. About one year later, he had hematemesis about 500ml. Five days later, he was dead.
Autopsy showed Miyake's type B cirrhosis. The lower esophagus and upper stomach showed many varices and two varices in the upper stomach were ruptured. When silicone rubber was injected from the pulmonary artery subpleural vessels because filled with the silicone rubber. Microscopically, many enlarged subpleural vessels were shown, hemangiomatous lesions were present and the silicone rubber was present in many vessels categorized in the pulmonary vein. These findings suggested that multiple A-V fistulas existed in subpleural and intra-pulmonary regions.
From these findings, we recognized that this case suggested multiple pulmonary A-V fistulas in liver cirrhosis clinically and pathologically. To our knowledge, this is the first autopsy case of multiple pulmonary A-V fistulas in liver cirrhosis in Japan.

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A 38-year-old female was shown to have an abnormal lung shadow when she was admitted for the appendectomy.
9 months later, the same shadow was identified when she was readmitted for the resection of uterus myoma. When she was transfered to our ward, she had a 5×6cm localized tumor shadow adjacent to the left thoracic wall on the chest roentgenographic examination. Tomography, bronchography and CT-scan of the chest were carried out. In July, 1981, thoracotomy was performed.
A round tumor with smooth surface and adherent to the left lower lobe was resected. The size of a tumor was 6×4×2cm and was well encapsulated. From the histological examination, it was comfirmed that to be fibroma.

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