The Action of Histamine on the Respiratory Tract in Normal and Asthmatic Subjects 1

Abstract

While investigating the systemic effects of histamine in man, Weiss and his co-workers (1, 2) observed that the intravenous injection of histamine frequently precipitated asthmatic-like attacks in patients with asthma. They also noted that it decreased the vital capacity of 'patients with bronchial or cardiac asthma, bronchitis or emphysema. The details of these disturbances were not reported. In view of the recent interest in antihiistaninie preparations, it appeared worth-while to study more thoroughly the effects of histamine oni the respiratory tract in man. METHODSHistamine was administered to 3 groups of subjects in whom the degree of bronchoconstriction. was assayed chiefly by recording the measurement of the vital capacity. The first group was comprised of 10 normal subjects. The second group included 10 patients who had a history of severe allergic disturbances, including in some a history of asthma, but who were asymptomatic at the time of observation. The third group was made up of 9 patients with varying degrees of chronic bronchitis, emphysema and asthma. An attempt was made to include in this group young, adult patients with uncomplicated conitinuous asthma, and to exclude patients who because of language or other difficulties could not perform the vital capacity tests without marked unaccountable variations.Because of seasonal and other variations known to occur in asthmatic patients, one patient, B. R., a 28-yearold, single female with chronic asthma, was studied several times during the course of a 10 month period. Through training, she became an extraordinarily reliable subject, and was used for the majority of the observations. We are grateful to her for her cooperation. The other subjects were helpful mainly in confirming and enlarging the information obtained from patient B. R. Although several methods (3 to 6) have been advocated for the study of respiratory function in asthma, the determination of the vital capacity was one of thlefirst, and is simple and fairly reliable. Since but a short period of time is required to perform the test, rapid variations in respiratory function can be detected. It was noted, however, that to do a series of vital capacity measurements in some asthmatic 1 This work was supported in part by a grant from the Upjohn Company, Kalamazoo, Michigan. patients was not an easy procedure. This was due not only to fatigue, but also to coughing spells precipitated by forced expiration, especially in patients with bronchitis.A Standard Benedict Roth Metabolism Apparatus was used for the vital capacity measurements, which were recorded on a smoked drum revolving at a speed of 34 cm. a minute with a signal magnet marking 1 second intervals. By this method the slope of the expiratory curve, as well as its volume, could be studied, and bronchoconstriction distinguished from failure to perform the test with a maximal effort. While theoretically the reduction in vital capacity could be due either to bronchospasm or to edema formation, the rapidity of the changes found in this st...

Allergen challenge of lung tissue from asthmatics elicits bronchial contraction that correlates with the release of leukotrienes C4, D4, and E4.

“…Asthmatics have been observed to be hyperreactive to inhalation of PGF2, (26) and histamine (27). However, the present finding that histamine, PGF2a, and LTC4 had the same absolute and relative contractile potency in bronchi from asthmatics as in bronchi from nonasthmatics (3) would seem to indicate that hyperreactivity is an in vivo phenomenon due to factors other than hypersensitivity of the bronchial smooth muscle to the agonists.…”

“…The major cyclooxygenase product, TXB2, had a specific radioactivity of [25][26][27][28][29][30][31][32][33][34][35] pCi/pmol, as compared with 56 pCi/pmol for the added exogenous substrate. The mono-HETEs showed a specific radioactivity of 4-10 pCi/pmol, indicating a lower, but still significant, incorporation of exogenous substrate into these lipoxygenase products.…”

The Effect of Antihistamine Substances and Other Drugs on Histamine Bronchoconstriction in Asthmatic Subjects 1

“…The methods used in this study were similar to those described in a previous 'communication (11). Bronchoconstriction wvas demonstrated by a decrease in the vital capacity.…”

“…Such tests have not been applied to normal human subjects because of failure to demonstrate significant amounts of bronchoconstriction after doses of histamine that may be safely administered. However, the occurrence of bronchoconstriction in many asthmatic patients following the administration of histamine has been confirmed (11). It was also discovered that this sensitivity to histamine varied from person to person and in the same individual with the severity of the asthmatic symptoms.…”

Antihistamines in Bronchial Asthma

“…It had been shown experimentally that they counteracted bronchial spasm induced by histamine in animals and man (Curry, 1946). Schiller and Lowell (1947) and Curry and Lowell (1948) It must be emphasized that the dosage of phenergan used in the induced attacks varied greatly-from 25 to 75 mg.-and that in one case I was not able to suppress a mild attack caused by acetyl-/-methylcholine chloride.…”