Clinical examinations were performed in asthmatics with the crude extracts prepared by 10 KC sonic disruption from the microorganisms in the respiratory tract and the fractions obtained from the crude extracts. Results obtained were as follows: Asthmatic attack was induced in 3 of 10 asthmatics in the inhalation test with the crude microbial extracts (auto), which were respectively prepared from isolated microorganisms in the sputa of each asthmatics. One of them was positive in the inhalation test with the crude extracts of both Candida and Klebsiella, and was suggested to have an antibody which might be common to both bacteria. In the investigations using agar gel diffusion, the antibodies to Candida and Klebsiella existed in the serum of the patients, and the crude extracts of both Candida and Klebsiella were related each other. Four of 20 asthmatics showing a positive immediate intradermal test with the crude extract of Candida (hetero) were positive in the inhalation test and reacted positively to PK reaction. However, these 4 patients were negative in the immediate intradermal test, PK reaction and the inhalation test with the crude extract of Klebsiella (hetero). In the correlation of the immediate intradermal and inhalation test with the crude extract of Candida (hetero), 3 of 4 asthmatics showing a positive inhalation test were positive in the immediate intradermal test with the crude extract of the concentration of 0.01 μg protein per milliliter, while, none of 17 asthmatics showing a negative inhalation test were positive in the immediate intradermal test with the crude extract of the same protein concentration. An active fraction of the crude extract of Candida was obtained in the supernatant of the extract saturated with ammonium sulfate, and that of Klebsiella was precipitate at 50% saturation of ammonium sulfate. The investigation using gel filtration of Sephadex G-75 revealed that active fraction of the crude extracts of Candida and Klebsiella were eluted in the void volume. In 3 asthmatics showing a positive immediate intradermal test, PK reaction and inhalation test with the crude extracts (auto or hetero) hyposensitization therapy with the corresponding extracts were highly effective.

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A study was attempted to clarify the pituitary adrenocortical function in the patients with bronchial asthma. Several clinical tests were taken to investigate the pituitary adrenocortical function in 193 asthmatics according to severity or type of bronchial asthma. The following results were obtained. 1) A decrease of urinary 17-OHCS excretion was observed in severe or chronic asthmatics. 2) Adrenocortical reserve, using urinary 17-OHCS excretion following the administration of ACTH, was more decreased in severe asthmatics than those in mild and moderate cases, but no significant difference was observed between paroxysmal and chronic type of bronchial asthma. 3) By means of determining plasma cortisol in rapid ACTH test, adrenocortical reserve was decreased in severe or chronic asthmatics. 4) In diurnal variation of plasma cortisol levels during symptom free period, pituitary adrenocortical hypofunction was suggested in severe or chronic asthmatics on the basis of no increase of plasma cortisol levels at 8.00 a.m.. 5) In asthmatics administered a large dosage of steroids, no increase of plasma cortisol levels in the early morning was observed. 6) No increase of plasma cortisol levels in the early morning was observed in asthmatics of a long suffering duration even without steroid therapy. 7) In metopirone test, pituitary reserve was more decreased in severe asthmatics than those in the two other groups. It was presumed from the facts mentioned above that recurrence of the severe respiratory distress of asthmatic attack and administration of a large dosage of steroids in long term may cause exhaution of the pituitary and adrenal cortex.

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For the purpose of clarifying the etiological factor of pituitary adrenocortical hypofunction in asthmatics, plasma cortisol levels were measured in 109 male guinea pigs treated with inhalation of histamine solution and/or administration of dexamethasone for 1, 4 and 7 months. The experiments gave the following results. 1) In the three groups with experimentaly induced asthma provoked by inhalation of histamine solution every day for 1, 4 and 7 months, no differences of cortisol levels in the plasma were observed. 2) In the three groups treated with inhalation of histamine solution once a week for 1, 4 and 7 months, no differences of cortisol levels in the plasma were observed. 3) In the three groups treated with the subcutaneous administration of dexamethasone every day for 1, 4 and 7 months, a significant decrease of cortisol levels in the plasma was observed in the group treated for 1 month, but cortisol levels of the other two groups were within normal range. 4) In the groups treated with both inhalation of histamine solution and subcutaneous administration of dexamethasone every day for 1 and 4 months, plasma cortisol levels were within normal range, but a significant decrease of plasma cortisol levels was observed in cases with treatment for 7 months. From these results, it seemed that pituitary adrenocortical function in asthmatics was suppressed due to cumulative actions of both recurrence of the respiratory distress of asthmatic attack and administration of a small dosage of steroids during a long suffering time.

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