Breath of Fresh Air: Feature Articles

Some of our patients have inquired about a news report describing a potential vaccine to protect against asthma. Developing a method to prevent the onset of asthma is one of the goals of modern asthma research. Is there a vaccine on the horizon?

The source of the news feature was a medical article reporting a laboratory experiment conducted by asthma researchers in New Zealand (Dr. Klaus Erb and colleagues, Journal of Experimental Medicine, volume 187, page 561, February 16, 1998). These scientists knew of earlier studies that suggested that children exposed to infection with the tuberculosis germ were less likely to develop asthma than children who had never been infected with or vaccinated against tuberculosis. This observation is consistent with the idea that our immune system — and in particular, one type of cell within the immune system, called the lymphocyte — can be stimulated to proceed down either of two major pathways. One pathway leads to lymphocytes with specialized ability to fight certain germs, including those that cause tuberculosis, measles, whooping cough, and other infections. The other pathway leads to lymphocytes better suited to fight worms and parasites and — in the absence of worms and parasites — very much involved with allergic inflammation throughout our bodies. The New Zealand researchers wondered whether they might be able to direct lymphocytes away from the allergic pathway by causing a harmless infection that would stimulate lymphocytes to become germ-fighting lymphocytes.

They conducted their experiments in mice. They delivered a harmless variant of the tuberulosis germ through the nose to the respiratory system of the mice. The germ-fighting lymphocytes were mobilized to fight this respiratory infection, and when the mice were then sensitized with something that usually provokes in them an allergic response, they made almost no allergic reaction to the allergen over the next several weeks. Their experiment worked. The lymphocytes of these mice were working as germ-fighting cells and not able to provoke much of an allergic response.

You can imagine that a great distance remains between this interesting observation in mice and the development of a safe, effective, and long-lasting vaccine against asthma in humans. No asthma vaccine is currently being prepared for even experimental use in humans. But better understanding of the detailed workings of the immune systems in laboratory animals and in humans is undoubtedly the right beginning in pursuit of an asthma vaccine. It does not at all seem far-fetched that we will someday be able to redirect our immune cells away from harmful allergic reactions without impairing their ability to defend successfully against all kinds of infections.

Thirty years ago scientists discovered a protein in the body that is crucial to allergic reactions, including asthma. This protein is an antibody, meaning that it has a special ability to recognize foreign substances, such as allergens. Once allergens bind to this antibody protein, the protein can signal cells in the body to begin the allergic response. The antibody protein important in allergic reactions is one of a family of similar proteins involved with protecting us from infections. These proteins as a group are called immunoglobulins. This particular protein involved in allergic responses is called immunoglobulin-E or IgE for short.

Modern biotechnology has the ability to isolate these IgE proteins, study their structure, and then create new, “designer” proteins capable of blocking the functioning of IgE antibodies. By infusing these blocking molecules intravenously, one might be able to head off the allergic process at its very start. In the news this Spring was a report of one of the first experiments with people using a specially designed IgE blocking medicine to treat severe asthma.

Research is still in very early stages testing whether the medication will be effective and safe. It is too early to know whether this will prove to be an important asthma and allergy therapy of the future. There is ample cause for optimism, however. As we refine our understanding of each of the steps involved in allergic reactions, molecule by molecule, we will increasingly find points in the process that can be blocked without harmful side effects. Major steps have already been taken down this road.

Inhaled corticosteroids are a mainstay in the preventative treatment of asthma. They reduce the allergic inflammation of the bronchial tubes, with several beneficial effects. Their regular use results in fewer symptoms of asthma, less need for "rescue" treatments with inhaled bronchodilator, improved lung function, fewer attacks of asthma, fewer severe attacks of asthma requiring hospitalization, and reduced risk of death from asthma. A potential benefit from their regular use is preservation of lung function over time, reducing the likelihood of developing scarring and permanent narrowing of the airways.

What about the effect of inhaled corticosteroids in emphysema and chronic bronchitis, the cigarette smoking-related obstructive lung diseases? Recently, medical reports described the results of two large, long-term studies investigating the effect of inhaled corticosteroids in persons with these chronic obstructive pulmonary diseases, referred to as COPD. The results were striking in their difference from asthma.

Both studies found that the lung function of cigarette smokers with mild-to-moderate COPD continued to deteriorate at an abnormally fast rate whether they used regular inhaled corticosteroids or placebo. Inhaled steroids neither prevented the decline in lung function nor decreased the frequency of exacerbations that was found in the placebo-treated group.

These studies confirm an important difference between asthma and cigarette smoking-induced lung diseases. The former is associated with allergic-type inflammation of the bronchial tubes; the latter involves a different type of inflammation, one that is less steroid-responsive. With continued cigarette smoking, in COPD lung function predictably worsens over time. The best treatment is smoking cessation. In persons with asthma, with good preventative care lung function can be maintained normal.

Up until recently, laboratory confirmation of a diagnosis of the flu (respiratory infection caused by the influenza virus) required a minimum of several days for the virus to grow in culture and sometimes longer, if one waited the two weeks for antibodies against the influenza virus to appear in the blood. Symptoms of the flu might resolve by the time a diagnosis was confirmed.

Now, modern immunologic techniques have made possible the diagnosis of influenza infection within 10-20 minutes. Samples of sputum or swabs of the nasal or oral cavities can be tested for characteristic influenza proteins. The commercial names for these tests, each of which uses a different technique to identify the influenza proteins, are Flu OIA, QuickVue, and ZstatFlu. The test results, if positive for influenza, are more than 95% reliable in indicating that you have the flu. A negative test result is not definitive, however. These tests find influenza proteins in only about three-quarters of the cases when an influenza infection is present. The cost of the test about $15-20 each.

The best protection against the flu is the influenza vaccine. As Benjamin Franklin was quoted as saying, "An ounce of prevention is worth a pound of cure."

This year, two new prescription medications have become available to treat influenza infections once they have started. Both interfere with the ability of the influenza virus to reproduce itself within our bodies. They are anti-virals, in the way that antibotics are drugs used to treat bacterial infections. They block a viral protein of the influenza germ called neuraminidase, so this specific type of medicine is known as a neuraminidase inhibitor.

One, called zanamivir (Relenza®), is taken by inhalation twice daily for 5 days. The other, called oseltamivir (Tamiflu®), is a tablet taken by mouth twice daily for 5 days. They appear to be free of side effects or interactions with other medications.

In experiments conducted in this country and around the world, these medicines shortened the duration of "the flu" by 1-2 days. Treatment was begun within 48 hours of the onset of symptoms. The cost of 5 days of treatment is approximately $45-50.

The first published report describing the therapeutic effect of a new immune therapy for persons with asthma appeared in the medical literature in December. The results appear encouraging. Intravenous infusions of this treatment, given every two weeks, improved symptoms, allowed reduction in steroid dosage, and reduced the requirement for quick-relief bronchodilators compared to placebo.

The treatment is a genetically engineered molecule that blocks immunoglobulin E (IgE), a crucial protein involved in allergic diseases. Information about this new treatment (called anti-IgE antibody) appears in a previous News about Asthma article in this Chapter. In brief, treatment with anti-IgE antibody interrupts the pathway by which allergens that we inhale stimulate allergic reactions. By blocking the IgE molecule, it interferes with allergic responses regardless of the particular allergic trigger. It may also prove effective in allergic rhinitis ("hay fever") and allergic dermatitis (eczema), but the report in the New England Journal of Medicine (December 23, 1999) described the results in persons specifically with allergic asthma.

Patients in this study had moderate-to-severe persistent asthma. Half were able to reduce their inhaled steroid dose by at least 50% with this treatment (compared to 38% in the placebo group). Approximately 20% of patients treated with anti-IgE antibody stopped their inhaled steroids altogether, compared to 12% in the placebo group. Also, treatment with this immune therapy reduced the number of asthmatic attacks requiring treatment with a course of prednisone from 28% (placebo group) to approximately 15% (treatment group). The only side effect was the development of hives in a small number of patients.

Anti-IgE antibody has not been approved by the Food and Drug Administration and is not yet available at pharmacies. More studies will be done to see whether it can be given by injection rather than intravenous infusion and whether treatment intervals greater than every 2 weeks will still be effective. Nonetheless, the new millenium will begin brightly with the prospect of new "designer molecules" specially engineered to counteract harmful allergic reactions in persons with asthma and related diseases.