Thirty eight asthmatic patients were studied on pulmonary diffusing capicity for carbon monoxide, history of bronchial asthma, chest X-ray and some of pulmonary function tests. Moreover, pulmonary diffusing capacity among normal subjects was measured and compared to that of asthmatic patients. D_LCO was measured by Forster's single breath method modified by Oglivie and CO-workers. Krough's “Permiability” (K_CO) was calculated from the same procedure as D_LCO.
1) Pulmonary diffusing capacity was found to decrease with advancing age and to increase with increasing either height or alveolar volume. Pulmonary diffusing capacity of asthmatic patients was almost equal to or higher than that of nomal subjects.
2) No significant correlation was found between pulmonary diffusing capacity and FEV 1.0/FVC.
3) Pulmonary diffusing capacity, especially K_CO, showed an tendency to decrease with increasing severity of asthma and with advancing emphysematous change in chest X-ray.
4) Asthmatic patients were divided into 2 groups; patients who had asthmatic symptoms since childhood, and patients who had the first experience of asthmatic attacks after adolescence. There was found no significant difference between pulmonary diffusing capacity of these 2 groups. From this result, an impression is given that long-standing bronchial asthma does not necessarily progress to diffuse obstructive emphysema.
5) The more the patients showed severe asthmatic symptoms, the more marked emphysematous changes were proved in chest X-ray of the majority.
6) Pulmonary diffusing capacity was measured among asthmatic patients with history similar to “Tokyo-Yokohama asthma”. No cases showed lowered pulmonary diffusing capacity. This result suggests that there is neither destructive changes as seen in the lung of chronic emphysema nor alveo-capillary block among these patients.

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The pathologic physiology of bronchial asthma has mainly been evaluated by the pulmonary ventilation function tests.
However, it is considered that these tests alone may be unable to demonstrate the real physiologic change of respiration because they are impossible to indicate exact alveolar function which takes up oxygen and eliminates carbon dioxide.
To clarify the pathologic physiology of bronchial asthma, the parameters of pulmonary gas exchange were measured by modified oxygen saturation method of Briscoes and compared with the data of other pulmonary function tests, such as spirogram, FRC, D_LCO, and so forth, before and after administration of bronchodilator using I. P. P. B..
At the calculation of alveolar ventilation volume, the existence of physiologic dead space was taken into consideration.
The results were as follows:
1) Normal space increased from 28 to 34 per cent whereas slow space decreased from 64 to 57 per cent, making no change in fast space.
2) Alveolar ventilation increased from 4.44 to 4.82 1., especially its distribution to slow space increased from 14 to 16 per cent.
3) Turn over rate of slow space elevated from 0.27 to 0.41. There was tendency to approach towards that of normal space.
4) The percentage of perfusion of fast-normal space increased from 52 to 57 whereas that of slow space decreased from 45 to 40. These results indicated that fast-normal space was over-perfused and slow space was underperfused. Besides, these uneven distributions of perfusion were also observed by syncigram using I¹³¹ M. A. A..
5) Ventilation-perfusion ratio of fast-normal space decreased from 1.35 to 1.18 whereas that of slow space increased 0.25 to 0.34, therefore, the improvement of gas exchange in the whole lung was observed.
6) Shunt like effect due to ventilation-perfusion unevenness, calculated A-aD_O2, and a-AD_CO2, were much reduced from 23.0 to 14.1 per cent, from 32.4 to 22.6mmHg, from 6.2 to 3.4mmHg, respectively.
7) The existence of about 1 to 4 per cent of perfusion passed through unventilated space was presumed from an anatomical shunt. Consequently, these observations apparently indicate that the rate of venous admixture in the whole lung is the most superior indicator to demonstrate unevenness of ventilation-perfusion relationships.
8) The fact that the rate of venous admixture maintained within 17 per cent even after administration of bronchodilators shows that some cases of bronchial asthma should be improved gas exchange following the elevation of oxygen tension in the arterial and mixed venous blood by inspiration of high concentrated oxygen with the aid of bronchodilators.
9) It is clear that these analyses of alveolar function used the present study are accurate because correlative relation was observed between calculated A-aD_O2, a-AD_CO2, and observed values of the same cases.
Based on these findings, it is evident that not only uneven distributions of alveolar ventilation but those of perfusion also exist in the patient with bronchial asthma even while mild attack or remission. In addition, it is reasonable to presume that when severe attack occurs, the perfusion of slow space may increase inspite of the decrease of its ventilation, so that the regulation mechanisms of ventilation-perfusion might be disturbed.

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The airway resistance during forced expiration was measured by our modified and simplified methods. The characteristic difference in driving pressure, airflow and airway resistance during forced expiration were observed by this method between three groups: normal subjects and patients with airway obstruction of mild degree or sever degree.
1) The airway resistance during forced expiration can be measured without laborious mathematical corrections for volume change due to temperature- and humidity-change between expired and inspired air such as those required in measuring the airway resistance during normal breathing.
2) In patients with airway obstruction of mild degree, the alveolar pressure during forced expiration was higher than that in normal subjects, while there was no significant difference in the airflow rate during forced expiration between normal subjects and patients with mild airway obstruction. In patients with mild airway obstruction, the flow is well maintained within normal rate by elevating alevolar pressure against incresed flow-resistance. As aiway resistance is more increased the point is reached where alveolar pressure can not be elevated and eventually any more the airflow begins to decrease despite of maximal effort.
3) Therefore, the measurement of airflow rate during forced expiration such as indirect tests (FEV_1.0, % FEV_1.0, MMF, MEFR and Peak Flow Rate) may not be sensitive enough to assess the airway obstruction of slight degree, because normal airflow is well maintained by increased driving pressure. The measurement of airflow rate during forced expiration can be of diagnostic value only when the airway obstruction advances moderately or severely and consequently the airflow rate decreases due to lack of the increase in the alveolar pressure even with maximal expiratory effort.
4) The airway resistance during forced expiration with maximal effort in normal subjects was found relatively constant with little scattering at upper two third of vital capacity. The significant difference in airway resistance during forced expiration at the middle of vital capacity was observed between normal subjects and patients with mild airway obstruction.

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The increase of resistance of the respiratory tract plays a leading part of the obstructive airway disease. The ratio of FEV₁ to VC of spirogram has been used as an indicator to know the patho-physiology of these diseases. However, the value of FEV₁ is influenced by the expiratory effort of a subject and the lung volume of starting period of expiration. Because of the independency, it was thought as appropriate to calculate the ratio of ΔV to V of spirogram.
The following results and conclusion were obtained.
1) The straight line relationship was obtained between V and V from resting expiratory level to maximal exiratory level. This ratio of ΔV th ΔV, namely (ΔV/ΔV)_FRC was independent either exiratory effort or lung volume of starting period of expiration. The values of (ΔV/ΔV)_FRC were 2.66±0.50 in healthy Subject, 0.58±0.38 in bronchial asthma, and 0.17±0.07 in chronic pulmonary enphysema.
2) (ΔV/ΔV)_FRC and FEV₁/VC obtained by same spirogram were exponentially correlated in all cases (ΔV/ΔV=e^{0.0493(FEV₁/VC)-3.326}), whereas, only the subjects showing less than 55 per cent of FEV₁/VC were straightly correlated ΔV/ΔV=0.0148(FEV₁/VC)-0.274 and its coefficient of correlation were 0.81.
It was improper to judge the obstructive disturbance of the respiratory tract by using the peak flow rate because of dependency on expiratory effort and lung volume of starting period of expiration.
4) When plotting V and V on the expiratory and inspiratory curve of maximum effort obtained by the spirogram which was drawn % VC on the ordinate and V on the abscissa, only the decrease of flow of expiration was observed in chronic pulmonary emphysema, however, either inspiration or expiration was disturved in the patient with bronchial asthma. Moreover, the improvements of peak flow rate, % VC, and (ΔV/ΔV) after treatment were observed on the curve in bronchial asthma. This fact was regarded to be valid on differential diagnosis of the obstructive airway disease.
Based on these findings, we made a diagram which scaled % VC on the ordinate with arthmetic scale and (ΔV/ΔV) on the abscissa with arithmetic or semilogarithmic scale. This diagram would indicate that % VC showed not only restrictive ventilatory impairment, but also existence of unventilated alveoli caused by the change of mucus secretion or alveolar surface tension etc. and (ΔV/ΔV) showed the degree of expiratory disturbance within functional residual capacity.
Therefore, our diagram is capable to make a diagnosis of the obstructive airway disease and a judgement of its reversibility as well, especially in bronchial asthma and other cases with light grad of obstructive impairment.

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The effects of alloxan on pulmonary and bronchial vascular systems were studied in the anesthetized, thoracotomized dogs. Both bronchial arterial flow and cardiac output were measured with two electromagnetic flowmeters simultaneously. Pressures in the pulmonary artery, the bronchial artery and the left atrium were recorded continuously, using a electromanometer and recorder.
The increases of pulmonary arterial pressure and pulmonry vascular resistance were seen within 15 seconds of injection of alloxan in doses of 10 to 50 mg/kg into the pulmonary artery. These changes reached a maximum in 1 to 2 minutes after the injection, and returned to control values within 15 minutes.
The same results were observed in pulmonary arterial pressure and pulmonary vascular resistance after the injection of alloxan into bronchial artery, while the bronchial vascular resistance showed no marked changes.
These results suggested that the pulmonary hypertension produced by alloxan was due to the damage of pulmonary vascular bed rather than the pulmonary vasoconstriction.

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The pulmonary insufficiency is recieving more attention as the progress of study in the pulmonary diseases and pulmonary physiology. Acetazolamide has been reported to be effective in treatment of respiratory acidosis.
The purpose of the experiment reported here is to observe various responses of the pulmonary function in obstructive ventiratory disterbance following the administration of acetazolamide. Dogs weighing 8-13kg were ansthetized and studied.
The effects of the expiratory airway resistance used in this experiment were observed for 150min., and the decreases of MV, Pa_O2 and a tendency to respiratory acidosis were confirmed.
The effects of single intravenons administration of 50mg/kg acetazolamide observed for 120 min were the increases of MV (150% of the control level), Pa_O2, temporarily decresase of CO₂ output immediately after the administration and the decreases of Pa_CO2, the arterial blood pH to produce metabolic acidosis.
The effects of acetazolamide during obstructive ventilatory disterbance were observed giving 50mg/kg acetazolamide intravenously to the dogs in which the expiratory airway resistance had been interposed 40min in advance. Thus produced effects were as follows. MV was increased but only 116% of the control level at 120min. The decrease of CO₂ elimination was sharp. The drop of Pa_CO2 was rather sluggish. The arterial blood pH failed to 0.07 bellow the control level.
The decrease of CO₂ output immediately after the medication inspite of the increase of MV suggested an interference by 50mg/kg acetazolamide with the elimination of CO₂ at the lung. Correction of hypercapnea by acetazolamide was expected with increase of MV and brought with the decrease of arterial blood pH. Obstructive ventiratory disterbance experimentally made effected unfavorably to the lowering of Pa_CO2 by acetazolamide.

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It has been known that CO₂ transfer in vivo is achieved by catalytic action of carbonic anhydrase to the process of H₂O+CO₂_??_H₂CO₃, and Tomashefski has demonstrated the development of a-AD_CO2 as the result of interference with CO₂ transport in the lung following inhibition of carbonic anhydrase by acetazolamide.
In the work reported here, in vitro activity of acetazolamide on carbonic anhydrase was measured and carbonic anhydrase inhibition in the erythrocyte, the effects on the pulmonary function including a-AD_CO2 following acetazolamide administration were studied.
In vitro measurement of carbonic anhydrase activity was carried as described by Roughton and Booth. Acetazolamide of 0.08-0.3mg/cc, 1.25mg/cc in the blood of dog showed about 20%, 60% inhibition of enzyme activity respectively.
Pulmonary function under inhibition of carbonic anhydrase was studied in the anesthetized dogs giving acetazolamide intravenously in a single dose of 2 levels i. e. 10mg/kg: ordinary dose medically used and 100mg/kg: the dose inhibiting enzyme activity maximally without the influences of Na dissolved in acetazolamide solution.
The effects of 10mg/kg. Inhibition of enzyme activity was 19%. MV increased. Pa_CO2 and arterial blood pH falled. No change of a-AD_CO2 was observed.
The effects of 100mg/kg. Inhibition of enzyme activity was 48% MV increased. CO₂ output decreased sharply. Pa_CO2 was not decreased and arterial blood pH falled markedly to produce the mixed type of acidosis. A definite a-AD_CO2 of about 20mmHg developed.
Theoretical estimation indicated higher pH of the pulmonary capillary blood than the observed arterial blood pH under inhibition of carbonic anhydrase.
Although no indication of impaired CO₂ transfer in the lung was detected by administration of 10mg/kg acetazolamide, interference of CO₂ elimination at the lung after higher inhibiton of carbonic anhydrase was obvious from the marked changes such as a decrease of CO₂ output, low alveolar pCO₂, development of a-AD_CO2, following 100mg/kg acetaxolamide administration.

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Chronic Pulmonary diseases, especially in chronic pulmonary emphysema, are increasing in population and are becoming more important problems to be resoluted by the physician. Chronic respiratory disease recognized mostly common among the pupulation of male over 50 years in age, is rash to become a serious problem in a view of public health.
The diagnosis of the respiratory disease is easy as usual, but might be exceedingly difficult to recognize at early stage.
Because the electrocardiographic findings in pulmonary emphysema are not resemble to showed in acqired or congenital heart disease, right ventricular hypertrophy in patients with pulmonary emphysema is particularly difficult to detect electrocardiographically. Chronic pulmonaly emphysema may affect the electrocardiogram directly or indirectly in the following ways: 1) The emphysematous lung contains far more air than the normal lung. Because the lung tissue interposed between the heart and body surface contains more air than normally and air is an extremely poor conductor, the electrical forces arising in the heart are poorly transmitted to the surface electrodes of the electrocardiography. In this event, the electrocardiogram displays low-voltage deflections in all leads. 2) Emphysema is accompanied by lowering of the diaphragm, and this in turn causes “dropped heart” which showed a more vertical position, and a clockwise direction around its longitudinal axis. The clockwise rotation lets the left ventricle to be posterioly and the right venticle to be a more anterior position. 3) The indirect hemodynamic effect of emphysema can lead to pulmonary hypertension, right ventricular overloading, right ventricular hypertrophy and dilatation.
In fact, many investigators could not observed typical electrocardiographic findings of right ventricular hypertrophy in patients with chronic pulmonary emphysema.
Therefore, this study attempt to establish definitive electrocardiogram for diagnosis of chronic pulmonary emphysema, the author analyze a series of electrocardiogram of 100 patients with chronic pulmonary diseases, 40 with chronic pulmonary emphysema, 38 with chronic bronchial asthma and 22 with other chronic respiratory diseases.
The result of this study is as follows: 1. The effect that emphysema exerts in masking the diagnostic electrocardiographic findings of chronic pulmonary disease has been noted. 2. The electrocardiographic criteria for the diagnosis of emphysema must be separated from the criteria for the diagnosis of right ventricular hypertrophy in the presence of emphysema. 3. Electrocardiographic manifestations of chronic pulmonary emphysema; (1) Tendency to right axis deviation of the mean electrical axis of the QRS complex. (2) Clockwise rotation in the precordial leads (leftward shift of the transitional zone). (3) S patterns in lead left precordial leads. (4) Increased amplitude and or tented P waves in leads II, III and aV_F. Inverted P wave in lead aV_L. P axis +60 to +90 degrees is the frontal plane but especially greater than +70 degrees. 4. Above mentioned criteria based on these changes are proposed to diagnose chronic pulmonary emphysma with and without right ventricular hypertrophy.

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In order to clarify the epidemiological features of pneumoconiosis due to diatmaceous earth, the author carried out an epidemiological survey, which included a X-ray examination of chest and nose, a pulmonary function test, a tuberculin test and an environmental investigation, for all the employees of a diatomaceous earth factory in Wakura area of Ishikawa Prefecture.
The results thus obtained are summarized as follows:
1. Pneumoconiosis was found present in 25% of all the examinees and in 37% of the workers in a dusty environment. These rates were higher than those of the workers in dusty factories of other industries.
2. The prevalence rate of pneumoconiosis tended to increase with age of workers and length of work at a dusty job, and pneumoconiosis among the workers aged 40 and over who worked at a dusty job over 5 years was found apt to be worsened.
3. The prevalence rate of tuberculosis was particularly high among the workers with pneumoconiosis aged 40-49 and tuberculosis in this group tended to become progressive.
4. Significant differences were not seen in the percentage of tuberculin reactors by sex and working conditions. It was, however, observed that the reaction of the cases with pneumoconiosis or pulmonary tuberculosis tested with tuberculin prepared from unclassified mycobacteria, particularly from the photochromogen strain, exceeded that from tubercle bacilli more frequently than occurred in other healthy persons.
5. Observations of the environmental factors disclosed that there were no significant differences between cases with pneumoconiosis and healthy persons as to dietary habits and working conditions, although the former group included a greater number of inhabitants in rural districts than the latter group did.
6. Rhinological examination revealed that the condition of the passage of the nasal meatus was closely related to the occurance of pneumoconiosis.
Other examinations failed to show the difference between the pneumoconiosis group and the healthy group.

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With the view of obtaining the patho-physiological analysis of chronic pulmonary diseases, the respiratory variations in intra-abdominal and intra-thoracic pressures and their interrelations were studied in 30 patients with chronic pulmonary diseases and in 10 normal subjects.
Intra-abdominal and intra-thoracic pressures were measured with an air-filled flaccid latex balloon in the stomach and esophagus, respectively. The respiratory variations in intra-abdominal and intra-thoracic pressures were recorded simultaneously.
1) The mean value of the respiratory variations in intra-abdominal pressure at rest, in sitting position, was 5.1cm H₂O in 30 patients which was not significantly different from that in normal subjects (Fig. 3).
2) In the most cases of pulmonary patients, the patterns of intra-abdominal pressure revealed no parallel relation with those of ventilatory volume, this being different from the result in normal subjects.
3) The respiratory variations of the intra-abdominal and intra-thracic pressures, at rest and during voluntary hyperventilation, were analysed from the stand points of the magnitude, the direction and the time lag, and the following four groups were noticed (Fig. 7):
Group I: The respiratory movement of intra-abdominal pressure was inverse in direction to that of intra-thoracic pressure, while the time lag and the magnitude difference between these two pressures were small. This interrelation mainly noticed in normal subjects.
Group II: The respiratory movement of intra-abdominal pressure was inverse in direction to that of intra-thoracic pressure, while the time lag and the magnitude difference between these pressures were large.
Group III: The respiratory movement of intra-abdominal pressure was double peaked in contour. The interrelation between the two pressures tended to be more similar in time lag & magnitude difference to Group IV than to Group II.
Group IV: The respiratory movement of intra-abdominal and intra-thoracic pressures was in the same direction. The magnitude of the former was smaller than the latter and the time lag of the respiratory movement between these two pressures was small.
Ventilatory function, mechanics of breathing, pulmonary circulation, hepatic circulation and blood gases were compared among these four groups.
(a) Most of the patients of Group I had normal ventilatory function, while all patients of Group IV had moderate or severe combined ventilatory impairment (Fig. 8).
(b) These four groups had a close correlation with the viscous resistance and viscous work of the lung increased in order of the group number, i. e., these were the minimum in Group I and the maximum in Group IV (Fig. 12 and 13).
During voluntary hyperventilation and when the airway resistance is artificially increased, the patients of Group I, Group III tended to show the pattern of Group IV, as pulmonary viscous resistance had increased (Fig. 14 and 16).
Consequently, it is considered that the interrelations between intra-abdominal and intra-thoracic pressures are mainly influenced by pulmonary viscous resistance, and that the pattern of respiratory movement of intra-abdominal pressure becomes similar to that of intra-thoracic pressure when pulmonary viscous resistance is significantly increased.
(c) The pulmonary arterial mean pressure was less than 15mmHg in all patients of Group I, while it was more than 15mmHg in all patients of Group III and Group IV (Fig. 18).
(d) The interrelations of the respiratory movement of the right atrial pressure and the wedged hepatic veinous pressure could also be classified into four groups, which were the same as the interrelations between the intra-thoracic and intra-abdominal pressures (Fig. 20).
(e) The arterial oxygen saturation was normal or slightly decreased in Group I, while all patients of Group III and IV had arterial hypoxemia (Fig. 22).

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