Questions and Answers
Are oral corticosteroids not effective enough in treating asthma?
The problem is not the effectiveness of corticosteroids. Patients respond to corticosteroids, but because of the toxic effects of the drug, we’re always looking for what we call a corticosteroid-sparing effect. We want to reduce the use of steroids through alternative medication, but it’s not a question of one drug being better than the other.
Are you concerned about dependency on corticosteroids, or about other side effects?
Corticosteroids are not like cocaine, which creates a physical dependency. We’re much more concerned about toxicity, particularly in children. Steroids stunt growth, can cause cataracts, high blood pressure, hair all over your body, and can induce a diabetic-like state. But the major concerns are that it stunts growth and weakens bones. Some patients can fracture their ankle just stepping off a curb.
What is IgE and why do some people have more of it than others?
Immunoglobulin E or IgE is the allergic antibody, discovered in Denver in the 50s. Clearly, it’s one of the major causes of allergy-induced problems, whether it’s rhinitis (people who have ragweed allergy or hay fever), skin disease such as eczema, or in some cases, asthma. A high percentage of asthmatics manifest this allergic reaction, particularly children. In most cases of asthma it’s the allergy to whatever is in the environment that triggers the allergic response, which in this case targets the airways.
Is asthma caused by IgE reactions to allergens harder or easier to treat than non-allergic asthma?
It depends. Some people have what’s called exercise-induced asthma, and they can take a bronchodilator just before they exercise and they’ll be fine. Others have aspirin-sensitive asthma, and as long as they avoid anything containing aspirin, they’ll be fine. It’s not that one is easier or harder to treat. It’s just that one has to identify and then target different mediators and causes with different drugs in the various types of asthma.
What is inflammation?
Let’s say that you’re allergic to dogs. Your family has a history of allergy, because there’s a big genetic component to it. You encounter a dog, and inadvertently inhale some of the dog dander. What happens is: the IgE binds to mast cells, which are a type of cell that is present throughout the body’s airways. The allergen also binds to the IgE. The mast cells then degranulate and release a lot of mediators. Other cells, such as lymphocytes (white blood cells), also get activated. This activation process calls in a lot of inflammatory cells.
In the case of asthma and other allergic reactions, a major cell that’s called in is the eosinophil. The eosinophils accumulate around the airway, probably releasing their own mediators that break down the epithelium (lining) of the airways. That leads to altered control of some of the nervous functions of the airways. You get smooth muscle hypertrophy (swelling), and contraction and constriction of the airways.
Are immune globulin injections as effective in treating asthma as corticosteroids?
One has to think of the therapy of asthma. There are controllers of asthma and there are relievers of asthma. The relievers of asthma are those drugs that go straight to the airway such as beta-agonists — ventolin, for example — where they act to relieve bronchoconstriction. You take the inhaler, and within seconds you get relief. But if you’re looking for a more prolonged effect to keep inflammation down, you need something that’s going to work to keep those inflammatory cells from coming in. The first line therapy is drugs such as cromolyn and nedocromil, which are weak drugs.
They may be okay, however, taken as a prophylactic by people with mild asthma. The really effective anti-inflammatory that is available today is corticosteroid; nothing can beat it. But if you take these drugs by mouth, the toxicity is great, particularly if you take it on a continuing basis. Hence the big push to taking steroids by inhalation. The next step after cromolyn or nedocromil is now inhaled corticosteroids. The toxicity is clearly much lower than when taken by mouth, because they act locally with as little systemic absorption as you can get away with. But some patients continue to have inflammatory changes and asthmatic symptoms, so they need oral corticosteroids.
And once you’re on oral corticosteroids as a requirement for control, you start to look at experimental therapies for inflammatory control, because you just want to get the patient off the steroids if you can. A lot of what has been tried has followed from the rheumatoid arthritis literature. Arthritis is also an inflammatory disease, and it’s been treated using things like methotrexate, gold and chloroquin. All of these anti-inflammatory drugs have been tried with asthma, without any great success. Also, some of these drugs are themselves quite toxic: methotrexate, for example, is an anti-cancer drug. We were looking for something that had an anti-inflammatory effect without the toxicity, and we were pleasantly surprised to find that gamma globulin (IgG) has that effect. We were able to significantly reduce the need for steroids without losing control of the disease.
This is an experimental therapy. Double-blind, placebo-controlled studies need to be done to determine the efficacy of gamma globulin, and pilot studies have already been done which have supported its efficacy. It’s also a very costly therapy, and that fact is likely to limit its use. But we’re talking about using this therapy in the very small subset of asthmatic patients whose asthma cannot be controlled using conventional methods. Probably no more than one in 100 to one in 500 asthmatics really have severe steroid-dependent asthma. Of course, when you consider that there are 16 million asthmatics in the United States, that’s still a pretty large number of people who stand to benefit.