TORONTO-An expert panel containing three former American Academy of Otolaryngic Allergy presidents recently provided a look at the future of allergic rhinitis, as well as a refresher on how best to treat it.
During the course of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) annual meeting here, AAOA past presidents J. David Osguthorpe, MD; M. Jennifer Derebery, MD; Edwyn L. Boyd, MD; and moderator Berrylin J. Ferguson, MD, presented Allergic Rhinitis: What’s True About What’s New.
According to Dr. Osguthorpe, more than 50 million Americans suffer from allergic diseases. Allergy is said to be a causative factor in up to 50% of patients presenting at otolaryngology offices. Patients with perennial or seasonal nasal congestion and sneezing, or with chronic rhinosinusitis, as well as those in whom the role of allergy is not commonly considered, such as those with hoarseness, disordered sleep, and the sequelae of eustachian tube dysfunction, all fit within this description.
In his presentation, Dr. Osguthorpe covered what is currently available for the treatment of allergies, focusing on salient aspects that physicians should consider when selecting a therapy.
Asthma affects both physical and mental status-mostly it is a ‘presenteeism’ problem, he said. Allergic rhinitis, this IgE media phenomenon, sits in the middle of a number of diseases. Asthma, of course, has the same inflammatory type of underlying process, which is true for some of the others as well.
The most common treatments for allergic rhinitis have been avoidance or environmental modification, and pharmacotherapy.
Allergic rhinitis broadly affects how one feels about getting up in the morning, Dr. Osguthorpe said. It is worst at night…is bad in the early morning…and exacerbates sleep apnea.
If you look at people who are allergic, their productivity goes down as pollen count goes up. These people just aren’t up to speed.
Omalazumab and Zileuton
Dr. Ferguson followed Dr. Osguthorpe, talking about uses for and efficacy of omalazumab (Xolair) and zileuton (Zyflo).
Omalazumab is a human monoclonal antibody that has been designed to bind to the FC-Epsilon receptor of the immunoglobulin E molecule where IgE will bind to a receptor in a mast cell. The antigen-specific portion of the immunoglobulin is not touched at all by omalazumab, Dr. Ferguson said, so it prevents the binding of IgE to the affector cells. The dosage is based on the weight of the patient, as well as his or her IgE level.
Some IgE levels are so high it would cost too much to make this work effectively, she said. Of course you can give steroids to lessen those levels…and you would need to have them come in twice per month. Those with low levels can come in once per month.
Dr. Ferguson pointed out that there have been four randomized clinical trials in which omalazumab showed a benefit-reducing asthma symptoms and patients’ need for corticosteroids.
With regard to monitoring patients while on omalazumab, Dr. Ferguson suggested that everything be done on a clinical basis, because no commercial assay exists for looking at free IgE.
Remember that [omalazumab] is complexing with this IgE molecule, so when you assay [subjects’] serum with normal patients, IgE is going to be elevated because [the test] is going to be seeing this complex, she said. It won’t be able to distinguish whether it is free IGE or a complex that is there as a result of the [omalazumab].
Ninety percent of patients respond to the drug within 12 weeks and most within 16 weeks, Dr. Ferguson said. No studies have been done concerning the duration of the effect after discontinuation.
Zileuton is indicated for the treatment of asthma. According to Dr. Ferguson, the drug became nonprofitable for Abbott Laboratories, so the company discontinued its manufacture several years ago. Two years ago Clinical Therapeutics started marketing the drug again for a small subgroup of patients, and it has been successful.
This is a good drug, but you must monitor liver function, she said. Because you’re using it for asthma and upper airway, if it is not working within a month, I move on to something else.
Zileuton is an enzyme blocker that has undergone double-blind trials regarding its efficacy on asthma. Dr. Ferguson said one study done in her office showed great promise.
The drug had a clinical response in three of our seven patients, she said, one of whom had their polyps go from Stage IV to Stage II obstructing.
With better elucidation of the immunology underlying type 1 hypersensitivity disease, therapy is increasingly being directed at disease modulation rather than solely confined to symptom control. This involves not only traditional injection-based immunotherapy, but potentially more cost-effective and less morbid approaches, such as sublingual delivery of antigens.
Dr. Derebery detailed the pros and cons of sublingual immunotherapy, stressing that doctors must inform patients that it is an investigational technique.
Subcutaneous works, so the question is, why does it matter? Dr. Derebery said. Well, people don’t like taking shots.
The mechanism of action requires that there be antigen contact with oral mucosa long enough for the therapy to work. The antigen is subsequently captured by dendritic cells, matures, and migrates to the lymph nodes, where the nodes then produce IgG-blocking antibodies and immunosuppressor T-cells.
There is an immune deviation toward a T-reg cell response, she said. With the T-reg cell response we get the secretion of ILT and [transforming growth factor beta] and these two cytokines are quite important. They induce antigen-specific IgG4 production and IgA production, causing the suppression of the affector cells…while the cytokines cause decreased production of IgE antibodies as well. So that is the desired state we want.
T-reg cells control and establish the allergic response. They are important for the induction of the T-cell response to antigens or to self-tissue.
We know that in the animal model, sublingual immunotherapy does indeed induce mucosal tolerance, but does it stimulate these T-reg cells? Is there something different about this if we give it sublingually? Dr. Derebery said. Officially, we say it is not known yet, but the recent literature review I did for this presentation indicates it probably does.
One study recently showed that efficacy after sublingual immunotherapy continued five years after it had been stopped and no deaths have ever been reported form administering the drug this way. However, there are limitations.
The trials have always been conducted on mono- or duo-sensitized patients, she said. In English that means they’re being treated with one or two extracts, and many extracts are not biologically compatible. This is good for kids, but what about the adult who typically is polysensitized?
Host Response to Allergens
Dr. Boyd ended the session by talking about the host response to allergens via the TH2 lymphocyte pathway.
At birth, we all have an abundance of TH2 cells…so why are we becoming more and more allergic? he asked. One possible explanation is the hygiene hypothesis-if you are not raised around dust mites and dirt and other children, then your immune system is never going to be fully flipped over. The TH2 cells are not unlike unsupervised adolescents with too much time on their hands.
Dr. Boyd said that children who grow up on a farm or are in day care with other children are forcing the TH2 cells in their bodies to go to work fighting off invaders. For children raised in a spic-and-span environment, without any exposure to dust or other issues, the defenses never develop as well.
Kids in a day care situation, even though they are quite sick as infants, are less likely to get sick than children not raised in day care as they get older, he said.
©2006 The Triological Society