Advances in Asthma and Allergy Treatment: Q and A with Dr. Stephen Lockey

In 1819, Dr. John Bostock first accurately described hay fever as a disease that affected the upper respiratory tract .

Fifty years later, Charles Blakely performed the first skin test by applying pollen through a small break in the skin.

About forty years later, in 1911, Sir Henry Dale was the first to identify the role of the chemical histamine in the mechanism of allergies.

In 1937, Daniel Bovet synthesized the first antihistamine drug.

This was followed in 1948 by the introduction of corticosteroids by Philip Hench and Edward Kendall .

Those treatments opened the way for other advances which were to come much more quickly.

Dr. Stephen Lockey, of Allergy & Asthma Center is an allergist, amateur botanist, fly-fisherman and his son's lacrosse trainer, but not his coach. He's been in practice for 30 years and has seen great changes in asthma and allergy treatments.

Q: Let's talk about asthma medications and treatments first. There are so many asthma and allergy triggers; tree and grass pollen, dust, cigarette smoke, animal dander, molds, certain foods and medications, respiratory infections, and more. Is total avoidance of exposure to the trigger still the best?

Dr. Lockey : It's part of the solution, but it's almost impossible to avoid a specific allergen. Patients can take some steps to interfere with their exposure but they still have to engage in their normal lifestyle activities, such as being with their family, friends, doing their work around the house and outside their homes. So you can't relieve most of the allergens completely. There are some that you can do an excellent job with, for instance, dust mites. Environmental controls can reduce dust mite exposure significantly. For the most part those allergens, such as pollens and molds, are produced by Mother Nature outside the home, and it's pretty difficult to avoid them.

Q: So it's a nice idea but not really terribly realistic?

Dr. Lockey: Correct.

Asthma Medications

Q: Let's talk about groups of asthma medications and how they have grown and changed the treatment of asthma; for example, inhaled bronchodilators .

Dr. Lockey : These have evolved over the years. I can recall when I first went into practice people used to use inhaled epinephrine solutions. Epinephrine is a drug we still use to treat some allergic reactions and it's available in a racemic form.

Q: What's does that mean?

Dr. Lockey: It's available in an altered form in Primatine Mist which is sold over-the-counter. But it's not as specific in terms of this activity as the bronchodilators we have today.

Q: Am I correct, in saying that bronchodilators relax the muscles around the airways and that they are usually prescribed in aerosol form and taken with an inhaler, although they are available in other forms?

Dr. Lockey: That is correct. There are some powdered forms. Originally they were available only in a solution form and you would put the solution in a glass device with a bulb attached to it, which would allow you to pump air into the nebulizer. Then you would inhale the nebulizer solution through this device. Later, the solutions came out in an aerosol form, such as Bronchaid Mist and Isoprel. The ones we have available today allow the smooth muscles to relax around the airways.

Q: And open up the air spaces?

Dr. Lockey: And open the air spaces for better air movement. It is a temporary effect and it is certainly not something you would use exclusively as a form of treatment. In fact today we call most bronchodilators rescue medications and we use them on a when necessary basis, for example Proventil , Ventolin , Maxair and Alupent . The generic of those are albuterol, pirbuterol, and metaproterenol.. Newer forms are long-acting beta agonists drugs and these last up to 12 hours. They are used today in combination with other medications and are not rescue inhalers. They include Serevent Diskus (salmeterol), and Foradil (formoterol).

Q: How about non-steroidal inhalers?

Dr. Lockey: Well there are a number of non-steroidal inhalers available today , such as Intal and Tilade that weren't available 30 years ago. These drugs act to reduce the inflammation component of the asthmatic's problem. Airway inflammation is the target of all current therapy. Now we don't use them as frequently as we did back maybe 10 or 15 years ago because the inhaled corticosteroids are so much more effective and those drugs we use primarily to control airway inflammation.

Q: What about ones that aren't inhaled, such as oral corticosteroids?

Dr. Lockey: Oral corticosteroids used to be one of the only ways we could control the asthmatic who was having an increase in his symptoms and sometimes the only way we could control the asthma on a day-to-day basis. It was the way we could deliver something that had a constant effect on the inflammation of the airways.

Q: Is this something you swallow?

Dr. Lockey: Oral steroids come usually in tablet form although they are used both intramuscularly and by intravenous injection. But most asthmatics were treated with it orally. Today some asthmatics require use of oral corticosteroids to control their problems but this is becoming less and less a mainstay form of treatment because of the newer products that are available. We don't seem to need to use them as frequently and as much as used in years past. The consequences, of course, of taking long-term oral corticosteroids are not very favorable. Long-term oral corticosteroid use does lead to early onset cataracts. It causes osteoporosis and thins the skin. It tends to sometimes, with long-term use, cause hair growth on the face as well as weight gain. There are other side effects too, and so we try our very best to see that most of our patients don't have to use oral corticosteroids on a continuing basis. We still use them when control of the patient's asthma is not possible by other means and on a more acute basis during exacerbations of their symptoms to regain control of their symptoms.

Q: What do you mean by "acute?"

Dr. Lockey: If their symptoms are deteriorating to the point where they are not getting the benefit from their medications that we expected, then oral corticosteroids are used for short periods of time, to regain control of the problem, The incidence of side effects is markedly less than they would be if you were using them on a regular basis.

Q: I've also heard of Mast cell stabilizers. What are they?

Dr. Lockey: The Mast cell is the primary location for the byproducts of inflammatory mechanisms which release active substances that cause airway damage. The Mast cells contain histamines but they also contain numerous other active substances . Mast cells are in everybody's airway but in the asthmatic airway they are activated by the inflammatory process to release histamines, and other substances of inflammation which result in the airway damage that occurs . Asthmatics may go to church, for example, and somebody has perfume on beside them and they have a response to that irritant. There might be some cleaning agent being used in a particular locality that causes their symptoms, or car fumes. They're not really allergic to those things, but they are sensitive to them because of their inflammation. If you control the airway inflammation, then their tendency to have problems when they get exposed to these things diminishes tremendously.

Q: Is this the main reason you have a notice hanging in your reception area that says not to wear perfumes or other highly scented products because they can affect the health of the other people who are waiting to see you?

Dr. Lockey: That's true, although in all frankness in our office we like to think of our asthmatics as being so well controlled they are not going to have this kind of problem. But every once in a while we have somebody who's having difficulty, and is waiting to see one of our physicians. Then somebody sits down beside them with an excessive amount of cologne or aftershave lotion. This can sometimes cause the patient considerable discomfort.

Q: I read an interesting story about the discovery of the Mast cell granule as the major source of histamine in the body. In 1953, two researchers depended on a valued partner and experimental subject named "Judy". This 10-year-old cocker spaniel earned a place in canine history, thanks to her Mast cell tumor which had the highest histamine contents ever recorded. Is animal testing common in the field of allergy and asthma?

Dr. Lockey: Veterinarians do skin test animals for allergies. Animals can have allergies just like human beings. The dog has been a model over the years for a number of investigative allergy studies. We have learned a great deal from these studies done on dogs which have benefitted them, as well as, ourselves.

Q: Tell me about the IgE antibody.

Dr. Lockey: It's the gammoglobulin that everybody has . But the allergic patient seems to have more of it and it is directed against allergens that are in their environment that are usually organic, such as feathers, dust mites, horse dander, cat or dog dander, or the pollens and molds. The antibody is connected to the Mast cell and in the presence of these allergens the MAST cell releases histamine. The secondary response then is what histamine and these other substances of inflammation cause, the inflammation of allergy. Practically speaking, the inflammation is manifested by sneezing, runny nose, nasal congestion, cough, chest congestion and wheezing.

Q: What about leukotriene modifiers or inhibitors? I have a note here that says leukotrienes are "potent chemicals that constrict airways and increase mucous production," but I've never heard of them.

Dr. Lockey: Leukotrienes are substances which are part of the active materials released during any kind of an inflammatory response and especially an allergic inflammatory response. Just as the pharmacological industry has developed antihistaminic products which block what histamine does, there are drugs today that block the effects of leukotrienes. They are called anti-leukotrienes. Two of the drugs are Singulair and Accolate and they're both used today but they weren't even available ten years ago. There's one other one called Zyflo . Then there are the corticosteroids. They prevent the inflammatory process from occurring in the first place. We think they prevent the inflammatory cells from responding to being called to the tissue by the substances that are released from the MAST cells.

Q: What are systemic bronchodilator medications?

Dr.Lockey: You can take a bronchodilator by mouth but most patients are receiving their bronchodilators by inhalation such as the standard drugs used for rescue purposes: Proventil , Ventolin (albuterol), Alupent (metaproterenol) , and Maxair (pirbuterol).

Q: And how about systemic corticosteroid medications?

Dr. Lockey: We physicians refer to those as "oral corticosteroids" as opposed to inhaled corticosteroids. The oral corticosteroids obviously have to be taken by mouth. They have to be absorbed into your system. They have to go out into the areas that you want to treat, so they're actually becoming available not just to the tissue you are interested in treating but to all tissue. That's one of the disadvantages to using oral corticosteroids. You are treating every cell in your body, even cells that don't need to be treated, as opposed to inhaled corticosteroids where you are directing the medication to the tissue that is directly involved with the inflammation of allergy.

Other Asthma Treatments

Q: Are there treatments other than medications for asthma?

Dr. Lockey: We like to be proactive and try to prevent asthma. To prevent anything you have to know what you're preventing. So, if you think you're allergic to something, you have to undergo some kind of testing to define exactly what you're allergic to, unless that's very obvious. For instance, if you hold a cat, and your eyes start watering and your nose starts running, and you start sneezing, and you start coughing and wheezing, it doesn't take an allergist to tell you that you're allergic to your cat. It may take an allergist to tell you to give up your cat, and some of our patients don't like to hear that. For those patients that can't actually give up their animals we do have alternative recommendations which, for the most part, help. In very serious situations where patients' life styles are being compromised tremendously and they are subjecting themselves to unnecessary medications and treatment, we try to encourage them to not have the animal in the home.

Q: Anything else you want to say about current asthma treatments?

Dr. Lockey: Only that the consensus among physicians who treat asthma today is that it is a very, very treatable condition . It requires compliance by the patient. And today we are able to deliver medications to patients in a manner which actually allows them a greater degree of freedom, less cumbersome systems so that compliance becomes more and more perfect. Control today is so far superior than it was even ten years ago. It is almost astounding. And today we are able to deliver medications to patients which are long-acting, and compliance by the patient has become much more achievable. Control today is so far superior than it was ten years ago it is almost astounding if the patients take their medications regularly.

Q: What's on the horizon in asthma treatment?

Dr. Lockey: There are some new drugs coming along. There are new antihistamines that are going to be marketed probably in the next couple of years which may have longer duration of activity and be more effective than even some of the antihistamines which have been around for the last several years. There is also a new product which has come on the market recently which counteracts the effects of IgE antibodies and is appropriate in patients who have severe allergic type asthma and are not responding to standard other therapeutic measures.

Q: In the development of these new drugs, are many of them focusing on the inflammation of the airways before it causes an asthma attack rather than on relief?

Dr. Lockey: The drugs that are used on a regular basis that we ask our patients to inhale are directed towards controlling the inflammation and therefore reducing the episodic wheezing that the asthmatic has had over the years.

Advances in Allergy Medications

Q: Let's move on to allergy medications and treatments, and how they have changed. In addition to the allergens that cause asthma and hay fever, allergens can also cause allergic reactions to insect stings, latex and other substances.

Dr. Lockey: All the things you have mentioned are allergens, and there are patients who have developed sensitivity to those specific allergens. We are interested in their problems and try to reduce their exposure or their reaction and aid them also in dealing with their reaction if they have inadvertent exposure under circumstances that they have no control over.

Q: Antihistamines have been here a long time. But now you don't necessarily have to get prescriptions for them and they don't necessarily make you as sleepy as they used to.

Dr. Lockey: Correct, there are at least three antihistamines on the market now which do not cause any drowsiness and one that causes minimal drowsiness. All of them are 24-hour duration medication. So patients take them once a day and they get a fairly nice response from them.

For example, there are Allegra , and Claritin , which is now available over-the-counter, and the third is Clarinex . Then there is a fourth, Zyrtec . Some patients notice a little drowsiness from this one.

Q: What's the primary purpose of antihistamines?

Dr. Lockey: To block the affects of the histamine release during the allergic inflammatory response.

Q: In terms of specific symptoms, sneezing?

Dr. Lockey: Yes, they are excellent in reducing symptoms of sneezing, watery nasal discharge, itchiness of the nose, itchiness of the throat and itchiness of the eyes to some extent.

Q: Then there is immunotherapy, an area that you've been involved in all your medical life.

Dr. Lockey: Correct.

Q: What is it and what's happening right now?

Dr. Lockey: It's also evolving. The extracts are becoming more and more standardized; that is they're the same batch to batch as opposed to years ago when they weren't standardized.

Q: We're talking about shots.

Dr. Lockey: Right, we're talking about the allergy injections or "shots". The standardization of the extracts makes it easier for doctors to interchange information as to what the patients are receiving. The system, however, hasn't changed for many, many years. The idea is that you are trying to create a response of the immunological system of the patient to block the response that they're currently having with exposure to allergens. And specifically to aeroallergens, allergens that are in the air as opposed to other types of allergens.

Q: These injections, if I'm correct, come as a result of the testing that starts with a lot of needle sticks, dabbed in all kinds of things that you may be allergic to. The ones that end up looking like mosquito bites are the ones are that you are allergic to and need to be treated for.

Dr. Lockey: To some extent. What we like to do is correlate the skin test result with the clinical picture. If you tell me you are having problems during certain times of the year, for instance March, April and early May, and have no problems any other time of the year, clinically you are allergic to tree pollen because that is the time of the year tree pollens are out. We may do skin tests on you and discover that you have some positivity to some tree pollens as well as, perhaps, the grass or maybe mold or your cat. But if the only time you have symptoms is during the tree season that is all we would treat you for as for as far as your allergy injections because the rest of the year you are not clinically showing any symptoms . So there would be no point in desensitizing you to those other allergens. What we like to do is administer what is termed specific allergy desensitization, that is, to those allergies we think are clinically important to your problem. Allergy injections do three things. They stabilize the Mast cell membrane and prevent it from releasing as much histamine as it did before. Then they create what are called blocking antibodies. The blocking antibody has a greater affinity for the protein that you're allergic to and in a sense, gets to it before your IgE antibody does and prevents the IgE antibody from connecting to the protein. Therefore there is no release of histamine. The third thing allergy injections do is reduce the IgE antibody you have to that specific allergen.

Q: Do these injections work for everyone?

Dr. Lockey: Not everybody responds to allergy injections and generally speaking we like to place a person on injections for a two year trial. If there's no significant improvement after two years we will readdress the situation and either go in another direction in forms of therapy or perhaps upgrade their extract formula. But two years is generally enough time for a patient to decide whether or not there is significant improvement. If there is improvement then we continue the injections for a period of two years beyond the point that they are not having symptoms or they have reached a plateau in their improvement. If they've gone so far and they don't seem to go any farther; then we'll stop their injections and see how they do. Some of them will have no recurrence of their symptoms. Some of them will have only minimal recurrence and are satisfied using just the medications, and some of them have recurrence of their symptoms to the point where they may want to go back on their injections again.

Q: Another one of the treatments I've read about for allergies and asthma is air cleaners or filters such as HEPA filters in the home.

Dr. Lockey: There are a lot of devices that are being advertised as being effective in helping people with allergies but the manufacturers themselves are not putting the devices to the test scientifically . When these devices are put to scientific tests, they don't seem to come out as well as we would like. I tell my patients if there was a mechanical answer to make some kind of a device that created an environment where my patients would be fine we would buy the stock or close the doors to the office. It is not that easy and there is no simple answer to this problem when you have multiple allergens. One allergen, for instance, dust mites, you can do a lot within your home environment to prevent that particular allergen from being in your life. Perhaps there is a place for a HEPA filter and an electrostatic air filter in the corner of your room if you have a radiant heating system. Electrostatic air filters or electronic air filters and media type air filters can help in homes which have forced air heating systems.

Q: How about the side effects of some of these treatments. antihistamines, decongestants, immunotherapy?

Dr. Lockey: There isn't any form of treatment that does not have some side effects but fortunately today the side effects are fairly minimal for the standard allergic patient and that is a wonderful thing, especially when you think how things were 40 to 50 years ago for the allergic and asthmatic patient. I can recall when I went into practice with my father.

Q: Who, by the way, was a world famous allergist.

Dr. Lockey: Well, he was an innovator and a leader in his field at a time when allergy was felt to be some sort of alternative medicine, frankly. And, in terms of the medical community it was not well accepted. But, that is the way all the allergists were looked at 50 years ago. The specialty and treatments have come a long way. I think back to what tools he had to take care of his patients and the lifestyle he had to live because of the suffering he had to deal with, with minimal tools, The devotion and unbelievable amount of time he had to spend with these patients just to get them through their crises as opposed to today was incredible. There are crises in caring for the allergic patient and there are sometimes outcomes we would not like to have but the facts are that the conditions are much more treatable and the patients have a much better lifestyle than they had 50 years ago.

Q: What do you see coming in new allergy treatments?

Dr. Lockey: As far as conditions like hay fever and allergic conjunctivitis and manifestations of allergy, what is happening is we are getting long acting medications . We are getting medications which are probably more effective. There are some people who are doing research studies with altered allergens and there is a possibility we might see a patient being desensitized with four or five injections instead of four or five years of injections. That type of thing is out there but all these things have to go through extensive studies. They have to be put through scientific tests and then they have to go before boards and decisions have to be made as to whether or not they may be influencing other immunological responses. Therefore one can't really give you a good idea as to whether or not that is really going to be just around the corner or it is going to be 10 or 15 years from now or even longer . Allergic disease is genetically determined and it is very hard to cure diseases that are genetically defined. If it were a pathogen, like a bacteria, we might be able to give you a pill and get rid of it, but we don't think it is a pathogen. The idea that something is going to come out that is going to take care of everyone's problems with one single swoop doesn't seem to be very likely in the immediate future.

Q: You have come a long way since 1819 when Dr. John Bostock first accurately described hay fever as a disease that affected the upper respiratory tract.

Dr. Lockey: Our knowledge has expanded tremendously and, as the mechanisms of the allergic inflammatory condition are becoming more and more clear, therapeutic interventions are becoming greater and more effective.

Q: So what is the best advice you can give to people who have allergy and asthma now?

Dr. Lockey: I would like to remind people to do something about allergic disease early . If you had a sore foot for three months out of the year and couldn't conduct your lifestyle each year for those three months I am sure you would go and see an orthopedic surgeon or a podiatrist very quickly. The allergic individual often delays seeking help because it is something that is "in the family" and is simply accepted as such.

Q: It sounds like you are saying that people need to learn to take charge of their asthma or allergy and not let it take charge of them. They need to know what all these new drugs are, know what they do and how to use them. Since they are reading this interview on a computer, they can use the computer to find out more of this new information and, once found, discuss it with their allergist. Right?

Dr. Lockey: Right. There is every reason for them to want to interfere with their symptoms because it will free their lifestyle up and improve their ability to function at work, at home, and on a social level. One of the big mysteries for the allergist is why patients are putting up with these symptoms for so long and not doing anything about them.

Q: You are here to do something about them.

Dr. Lockey: That we are.

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