Asthma

February, 1924

By E. H. Williams, M.B.

In the first place I must express my appreciation of the honour you have done me in asking me to open this discussion on asthma. Except that I have interested myself in this subject in its more recent conception, I can lay no claim to fitness for so important a position. If the date of this discussion were 1913 instead of 1923, our remarks would be in terms of Curschman’s spirals, Leyden’s crystals, or the perles of Lannec, and we would be repeating what we had learned as students. During the last ten years, however, much has been explained that was hardly guessed at before that time, and a most interesting or even fascinating study has centred round the symptom called asthma and some allied conditions. While my contribution to this discussion is almost entirely the result of my own personal experience in practice, and that chiefly among children, it will be necessary for me to mention a few scientific facts just so far as they have been helpful to me in explaining certain phenomena.

Of the more technical aspect Dr. Carmalt Jones will speak more fully and give us the results of special study in immunity and its relation to anaphylaxis. I wish it understood that in my remarks I refer to spasmodic asthma, excluding renal and cardiac dyspnoea, obstructive dyspnoea from tracheo-bronchial gland enlargement, abnormalities or infections of the nasopharynx, reflex causes, bacterial infection generally, primary lung condition such as bronchitis and emphysema preceding the asthmatic complication.

In Progressive Medicine, 1922, it says: “In the study of ex-service men the greatest difficulty has been experienced in distinguishing between chronic bronchitis with exacerbations and with the varied types of dyspnoea incident to this condition and true bronchial asthma with added bronchitis. Neither the clinical history and observation nor a complete physical examination will differentiate between them. Unless such conditions as I have just mentioned are first eliminated, treatment by desensitisation will be disappointing; and even when the asthma is primary to bronchitis and emphysema, in cases older than 40, though there may be great relief from treatment, disappointment follows.

I mentioned without any specific purpose the year 1913—merely because a decade has elapsed since then—but in Osler’s System of Medicine of that date, besides the terms referred to earlier—Leyden’s crystals, etc.—one finds certain observations set down which indicate that attention was being drawn in the right direction without the true explanation being forthcoming. Osler speaks of swelling of bronchial mucous membrane, spasms of peribronchial muscles, a viscid exudation in bronchioles as observed by Curschman, the association of angio-neurotic oedema with asthma, of asthma following upon an attack of whooping cough. He refers, as do other writers, to asthma arising from flowers and grasses and animal emanations: to the effects of certain diets or articles of food. He mentions the phenomenon of anaphylaxis in connection with fatal results following the injection of antitoxin in asthmatic subjects; he refers to the presence of eosinophilia in the blood of those recovering from an attack of asthma. Yet he concludes as follows: “Briefly stated, then, bronchial asthma is a neurotic affection characterised by hyperæmia and turgescence of the mucosa of smaller bronchial tubes and a peculiar exudate of mucin.

Most of Osler’s observations are explained in the light of our present knowledge, and, while it must be admitted that a medical hobby-horse is often ridden till it drops, the explanation of spasmodic asthma and hay asthma by anaphylaxis or allergy is almost entirely convincing.

In much more recent publications than Osler of 1913 one finds similar observations without what appears to be the correct explanation of asthmatic attacks. One must remember, however, that many writers compiled their articles before the war—that is, before recent experimental work helped to explain this subject—and have only recently succeeded in getting their articles published.

In the Synopsis of Medicine, 1922, H. Lethaby Tidy refers to (1) spasm of muscular coat of smaller bronchi as being the generally accepted factor. Stimulation of vagus causes constriction of bronchi, distension of lungs with air resulting. Drugs controlling this vagotonia are recommended, belladonna or atropine giving striking results in this direction. (2) Swelling of bronchial mucous membrane, the rapidity of onset being parallel to urticaria, the paroxysm being an urticaria of the mucous membrane. These observations are not in advance of Osler’s, and though asthma and urticaria are mentioned together, the importance of their relationship does not seem to be appreciated.

Dale and Auld, in the British Medical Journal during the last two years, have contributed several articles to the subject of specific sensitiveness and anaphylaxis, and without encroaching upon the technical aspect of their work, to which Dr. Carmalt Jones may wish to refer, I should like to pick out a few experimental and clinical facts mentioned in their articles which may have some significance:

1.       “When a guinea-pig dies suddenly from the intravenous introduction of a foreign protein to which it is sensitive, as a result of anaphylaxis there is a tense contraction of plain muscle surrounding the bronchioles, with the lungs in full inspiration and with right-side heart failure. Recovery, if it occurs, is associated with eosinophilia.”—This is strictly comparable to one variety of anaphylactic attack in man or to severe spasmodic asthma, as pointed out by Tidy, from whom I have just quoted.

2.       In speaking of passive anaphylaxis it is stated “that if a guinea-pig be sensitised to a foreign protein, the serum of this animal injected into another of the same species will cause a similar tendency.”—Somewhat analogous to this is the reported case of blood from a donor conveying horse asthma to the recipient, hitherto a stranger to it.

3.       The usual interval of eight to ten days that elapses before the appearance of a serum rash in man is the same interval of time noticed in a guinea-pig after the first injection, before the anaphylactic condition develops in that animal.

4.       Anaphylaxis produced in rabbits is more often associated with gastro-intestinal symptoms.—In children suffering from anaphylactic manifestations the attack may resemble the pulmonary condition seen in the guinea-pig or the intestinal symptoms found in the rabbit.

5.       Anti-anaphylaxis is taken to mean a period of freedom from sensitiveness following an attack. During this period the antigen will not act if injected, and such a person may eat egg, for instance, with impunity.—Though some writers are not in agreement with this statement, it is certainly inconclusive to depend upon the results of skin tests immediately following upon an attack of asthma.

Auld’s work is based upon the non-specific treatment by peptone, and his conclusions are supported by Dale, who says a dose of peptone not in itself large enough to produce any pronounced reaction will weaken the response of a sensitised guinea-pig to the sensitising antigen, so that after such a dose it is possible to desensitise without at any time producing any pronounced reaction. Auld believes that the character of anaphylaxis and peptone poisoning or shock are identical.

The work of Chandler Walker is well known to all of us. He is the American representative of the specific protein theory school. To arrive at the particular antigen concerned in asthmatic attacks in a patient, skin tests are performed and the local reaction noted. These tests may be few or very numerous, embracing in some cases most of the proteins known in the animal and vegetable kingdoms. He prefers the dermal to the intra dermal method, the latter being too sensitive. That valuable information can be gained from skin tests is indisputable, but the procedure is apt to be cumbersome and irksome, so that the non-specific treatment with peptone offers considerable advantages.

Herbert French in the Medical Annual, 1922, in supporting non-specific protein therapy, says: “It might seem illogical, after thirty years of satisfactory effort to perfect specific therapy, to study non-specific therapy, but if we analyse the subject we will see it is by no means true. Instead of trying to alter or modify the agent causing the disease, whether microbic or toxic, by specific treatment, we may alter the reaction of the body—that is, the inflammatory reaction to the offending agent.” During the war it was noted that gonococcal infections were benefitted by typhoid vaccines; in 1918, that numerous cases of arthritis and fibrositis answered to blunderbus injections or influenza and catarrhal vaccine, the effect being probably due to the protein content of those vaccines and serums.