Pediatric Annals

A Pediatrician's View

Milton I Levine, MD

Abstract

All of us, I'm sure, have marveled at the workings of the human body. There seem to be so many intricate mechanisms at work to build up and nourish, to rid the body of waste products, to protect it against irritation and infection.

In the respiratory system the protective mechanism works beautifully to a degree - but in my estimation, only to a degree. Let me explain.

First, there is the cough reflex to remove irritating foreign particles. Then there is mucus formation, which entraps irritating substances. This mucus is brought up by coughing and also by the action of the cilia lining the inner surface of the bronchial tree. Furthermore, in normal respiration, the bronchial tree expands on inspiration and narrows on expiration. This narrowing on expiration causes the mass of expired air to go through the tubes faster and with greater pressure than during inhalation - a further mechanism to remove small particles. So far so good.

But then, one day, some cat dander is inhaled and some of its protein enters the mucosa - acts on the plasma cells just within the lining and causes them to form IgE molecules (reagins). These, in turn, leave the plasma cells and attach themselves to the surface membrane of mast cells or circulating basophils. Now that person is sensitized to cat dander, and the next time he or she is in contact with cats, the sensitized mast cells or basophils release histamine and the person gets an asthmatic attack. The body is trying to protect itself against this irritating animal protein, but it overdoes itself in its efforts. The histamine causes the bronchial tree to contract and the mucosa to swell, narrowing the passageway so that the expired air goes through it faster in an effort to remove the irritant. But, in addition, excessive mucus, thick and tenacious, is produced - also in an effort to rid the passageway of the noxious substance.

And so it has always seemed to me that the body overacts to protect itself and causes the sensitized person to have great difficulty breathing, especially on expiration when the tube may be extremely narrowed.

Being highly allergic myself and having treated numerous children with asthma, I have closely followed the scientific advances that have been made in the field of allergy during the past 50 years. Diagnostic measures have advanced very little - the general procedures still being scratch tests or intradermal tests for various allergens. In the area of treatment, however, there has been steady improvement in the past 30 to 40 years. Before that time treatment of asthma was largely confined to elimination of the allergen if possible or graded injections of the allergen protein extract to build up the body's toleration. For an asthmatic attack epinephrine by injection was the standard therapy. Ephedrine was also given by mouth, but its effect was slow and minimal. Then came the use of aminophylline - and later theophylline - by mouth and rectum. They proved to be very effective, and are still today among our most valuable therapeutic agents. Next, as 1 recall, came the discovery that nebulized epinephrine 1:100 or isoproterenol 1:200 inhaled from a special glass nebulizer was efficacious in relieving the early symptoms of asthma. Some years later, these were supplanted by metal nebulizers by which the epinephrine was propelled by an inert gas.

Then came the discovery that oral steroids were effective and the results were so remarkable that many of us felt that the problem of asthma had been finally solved. But the steroids were soon found to have serious side…

All of us, I'm sure, have marveled at the workings of the human body. There seem to be so many intricate mechanisms at work to build up and nourish, to rid the body of waste products, to protect it against irritation and infection.

In the respiratory system the protective mechanism works beautifully to a degree - but in my estimation, only to a degree. Let me explain.

First, there is the cough reflex to remove irritating foreign particles. Then there is mucus formation, which entraps irritating substances. This mucus is brought up by coughing and also by the action of the cilia lining the inner surface of the bronchial tree. Furthermore, in normal respiration, the bronchial tree expands on inspiration and narrows on expiration. This narrowing on expiration causes the mass of expired air to go through the tubes faster and with greater pressure than during inhalation - a further mechanism to remove small particles. So far so good.

But then, one day, some cat dander is inhaled and some of its protein enters the mucosa - acts on the plasma cells just within the lining and causes them to form IgE molecules (reagins). These, in turn, leave the plasma cells and attach themselves to the surface membrane of mast cells or circulating basophils. Now that person is sensitized to cat dander, and the next time he or she is in contact with cats, the sensitized mast cells or basophils release histamine and the person gets an asthmatic attack. The body is trying to protect itself against this irritating animal protein, but it overdoes itself in its efforts. The histamine causes the bronchial tree to contract and the mucosa to swell, narrowing the passageway so that the expired air goes through it faster in an effort to remove the irritant. But, in addition, excessive mucus, thick and tenacious, is produced - also in an effort to rid the passageway of the noxious substance.

And so it has always seemed to me that the body overacts to protect itself and causes the sensitized person to have great difficulty breathing, especially on expiration when the tube may be extremely narrowed.

Being highly allergic myself and having treated numerous children with asthma, I have closely followed the scientific advances that have been made in the field of allergy during the past 50 years. Diagnostic measures have advanced very little - the general procedures still being scratch tests or intradermal tests for various allergens. In the area of treatment, however, there has been steady improvement in the past 30 to 40 years. Before that time treatment of asthma was largely confined to elimination of the allergen if possible or graded injections of the allergen protein extract to build up the body's toleration. For an asthmatic attack epinephrine by injection was the standard therapy. Ephedrine was also given by mouth, but its effect was slow and minimal. Then came the use of aminophylline - and later theophylline - by mouth and rectum. They proved to be very effective, and are still today among our most valuable therapeutic agents. Next, as 1 recall, came the discovery that nebulized epinephrine 1:100 or isoproterenol 1:200 inhaled from a special glass nebulizer was efficacious in relieving the early symptoms of asthma. Some years later, these were supplanted by metal nebulizers by which the epinephrine was propelled by an inert gas.

Then came the discovery that oral steroids were effective and the results were so remarkable that many of us felt that the problem of asthma had been finally solved. But the steroids were soon found to have serious side effects, so that their use had to be confined to children with chronic severe refractive cases of asthma.

Next, cromolyn was discovered in England, and, although it was not used or even helpful in the treatment of acute asthma, it was found to be very effective when given by inhalation in preventing asthma. Its benefits were especially marked in children.

In the past 10 years, newer preparations have been devised that act like epinephrine on the bronchial tree but minimize the effect on the heart. Among these are isoetharine (Bronkosol) given by nebulizer, metaproterenol (Alupent) given by liquid or nebulizer, and terbutaline (Brethine), given as a tablet. These three drugs have been used more and more in the treatment of asthma.

The most recent preparation in use is beclomethasone (Vanceril), a steroid, given by inhalation. Like that of cromolyn, its action is for prophylaxis rather than treatment. Given in this manner, the steroid is only very slightly absorbed into the system, but, because of the slight absorption, it is only used in resistant cases.

So, through the years the prophylaxis and treatment of asthma have become more and more effective, and research has given us a much greater understanding of the biochemical reactions responsible for this condition. This present issue of Pediatric Annals is devoted to the modern therapy of allergic conditions in children and once again is under the guest editorship of Dr. William A. Howard, chief of the Division of Allergy and Immunology of the Children's Hospital National Medical Center in Washington, D.C.

An excellent article, on allergic dermatologie conditions and their treatment, by Dr. Andrew M. Margileth, appeared as the last paper on allergic therapy in the previous issue of this magazine. The first article in this present symposium is on allergic rhinitis and was written by Dr. Howard. At the outset the author refers to the frequent difficulty in differential diagnosis but provides clarification with a table presenting the various nasal problems of infants and children. Then, concentrating on the allergic conditions, he dwells individually on seasonal allergic rhinitis, perennial nasal allergy, and recurrent upperrespiratory involvement of allergic origin. Treatment is advised for each specific type.

Next, Dr. Howard presents a helpful discussion of the criteria used to read skin tests, with a discussion of both prick test and intradermal test reactions, and what they should suggest to the pediatrician treating an allergic child.

The following paper covers the management of asthma and is contributed by Dr. R. Michael Sly, also of the Children's Hospital National Medical Center, Washington, D.C, where he is director of allergy and immunology. This article is a superb review of the whole subject. Starting with suggestions for avoidance of offender allergens, Dr. Sly includes lists of foods associated with milk, egg, or wheat allergies. (I had forgotten - or never knew - that root beer and some meat loaf contained eggs.) He continues with a review of immunotherapy and modern pharmacologic therapy. The most important section for the practicing pediatrician is on status asthmaticus. Since this condition is rarely seen and may be very dangerous when present, Dr. Sly describes clearly and in detail the steps to be taken if such a situation occurs. This whole article should be carefully read by all pediatricians and kept for ready reference.

The fourth article, "Drugs Other Than Corticosteroids for the Treatment of Asthma," has been prepared by Dr. Jorge Abarzua, staff physician, Division of Allergy and Clinical Immunology, and Dr. John A. Anderson, Head of the Division of Allergy and Clinical Immunology of the Henry Ford Hospital, Detroit. This and the next article, "Corticosteroids for Allergic Disorders in Children," by Dr. Sheldon C. Siegel, Codirector of the Pediatric Allergy Training Program, UCLA School of Medicine, Los Angeles, give an excellent and clear description of the newer drugs, their action, and possible side effects.

Drs. Abarzua and Anderson start their article with a brief review of biologic mechanisms and forces of the sympathetic and parasympathetic nervous systems. This is followed by a study of theophylline and the drugs that act on the sympathetic system to relax bronchospasm and reduce mucus formation - epinephrine, isoproterenol, isoetharine, metaproterenol and terbutaline. Then cromolyn sulfate and its prophylactic action are considered. Next, the authors comment on the anticholinergic drugs used in asthma - specifically atropine and a new preparation, ipratropium bromide, which is not yet available in the United States.

Dr. Siegel's article deals with the modern concepts in the use of corticosteroids for allergy in children. This is an interesting and important paper; most pediatricians recognize the rapid response of allergic conditions under steroid therapy, but we are also aware of the potential dangers associated with its absorption into the system. The author first discusses the general action of the steroids on the body systems and then considers their anti-inflammatory and antiallergic effects. Next he presents the various corticosteroid preparations - oral, parenteral, and topical - and gives advice on their proper usage and on potential dangers of overtreatment. It is emphasized that the dose of corticosteroids must always be individualized according to the severity of the condition and the size of the patient. After noting the complications related to corticosteroid therapy, Dr. Siegel discusses methods available to minimize such complications. He emphasizes the use of corticosteroid-sparing agents, such as the ß-adrenergic and xanthine products, certain antibiotics, and cromolyn sodium. The use of beclomethasone by aerosol inhalation is discussed. The author's studies with this last-named preparation have not only confirmed its effectiveness but have failed to show any evidence of pituitary-adrenal gland suppression or other serious adverse effects.

10.3928/0090-4481-19790901-03

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