Summary
Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19–40% FEV1 fall) in all thirteen, additional definite late asthmatic responses (17–29% FEV1 fall) in four, and equivocal late asthmatic responses (5–11% FEV1 fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.

Allergen‐induced increase in non‐allergic bronchial reactivity

Allergen-specific immunotherapy can ameliorate the symptoms of allergic diseases and has shown long-lasting benefits. Recent work discussed in this Review indicates that the beneficial effects result from immunomodulation, including a switch to IgG responses and induction of regulatory T cells. Allergen-specific immunotherapy has been carried out for almost a century and remains one of the few antigen-specific treatments for inflammatory diseases. The mechanisms by which allergen-specific immunotherapy exerts its effects include the modulation of both T-cell and B-cell responses to allergen. There is a strong rationale for improving the efficacy of allergen-specific immunotherapy by reducing the incidence and severity of adverse reactions mediated by IgE. Approaches to address this problem include the use of modified allergens, novel adjuvants and alternative routes of administration. This article reviews the development of allergen-specific immunotherapy, our current understanding of its mechanisms of action and its future prospects.

Immunological mechanisms of allergen-specific immunotherapy

,8-IMINAZOLYLETHYLAMINE is the amine which is produced when carbon dioxide is split off from histidine. It was first prepared synthetically by Windaus and Vogt'. Recently Ackermann2 obtained a large yield of the base by submitting histidine to the action of putrefactive organisms. It has been shown that several of the amines thus related to amino-acids possess marked physiological activity. The activity of j8-iminazolylethylamine was discovered in the course of the investigation of ergot and its extracts by G. Barger and one of us3, who attributed this structure to a base which they obtained, and which in minute doses produced tonic contraction of the uterus. The synthetic substance, and the base produced by splitting off carbon dioxide from histidine by bacterial action or by chemical means, were found to have an identical action. Meanwhile Kutscher4 had simultaneously and independently described the isolation from ergot of a base having this action and presumably identical with that obtained by Barger and Dale. By its chemical properties this first ergot base of Kutscher was not distinguishable from 8-iminazolylethylamine; but certain apparent differences in the physiological action of the two bases, observed by Ackermann and Kutscber-5, led them to the conclusion that the ergot base, though closely related to 8-iminazolylethylamine, is not identical with it. The alleged difference in action, on the existence and cause of which our experiments throw light, was as follows: the

The physiological action of β-iminazolylethylamine

Experiments with chickens, pidgeons, mice, rats, guinea-pigs, cats, dogs, squirrel-monkeys and chimpanzees show that stereotyped activity can be produced by amphetamine in doses of 1–20 mg/kg in all these species ranging from birds to primates. In man amphetamine in similar dose, i.e. higher than the therapeutic doses, can produce a psychosis, which so closely resembles schizophrenia, that misdiagnoses have been made. All the known symptoms of schizophrenia are reported, including stereotyped activity.

Stereotyped activities produced by amphetamine in several animal species and man.

Anaphylaxis

Histamine antagonists: III. The effect of oral and local use of β-dimethylaminoethyl benzhydryl ether hydrochloride† on the whealing due to histamine, antigen-antibody reactions, and other whealing mechanisms. Therapeutic results in allergic manifestations

https://www.jacionline.org/article/0021-8707(56)90103-4/pdf

Asthma and rhinitis from insect allergens. I. Clinical importance.

Acth and cortisone in allergic manifestations: Therapeutic results and studies on immunological and tissue reactivity

One of the penalties of progress in therapy is the accompanying toxic and allergic reactions that frequently accompany some of the new therapeutic products. Penicillin is an outstanding example in this field. It can be credited with the saving of tens of thousands of lives and with reduction of morbidity and complications from infections in millions. Nevertheless, its use causes numerous allergic reactions. With more than 300 tons of penicillin manufactured annually in the United States, constituting 150 million courses of 3 million units each, 1 it is apparent that the drug is widely used. Allergic reactions are quite common and are on the increase. Indeed, penicillin has become the primary problem in drug allergy. There are a variety of types of allergic reactions to penicillin. Cutaneous manifestations include urticaria, rashes, exfoliative dermatitis, contact dermatitis, and erythema nodosum and multiforme. Purpura has been noted. Increasing numbers of instances of periarteritis

Samuel M. Feinberg

Papers

Histamine antagonists: III. The effect of oral and local use of β-dimethylaminoethyl benzhydryl ether hydrochloride† on the whealing due to histamine, antigen-antibody reactions, and other whealing mechanisms. Therapeutic results in allergic manifestations

Asthma and rhinitis from insect allergens. I. Clinical importance.

Acth and cortisone in allergic manifestations: Therapeutic results and studies on immunological and tissue reactivity

Allergy to penicillin: guest editorial

Atopy to simple chemical compounds—Sulfonechloramides