Dr. Paul Ehrlich, co-founder of this website, says that in the olden days, dust for testing and immunotherapy was collected by paying church ladies to collect their household dust. The process is much more refined now, but there’s a movement afoot to ban the current method and replace it (at vast expense) with a laboratory-driven approach. Our friend Dr. Brian Schroer of Cleveland Clinic, has edited a special issue of JACI In Practice, an offshoot of the Journal of Allergy and Clinical Immunology (JACI), that tackles this subject, which is fraught with critical implications for the future of treating allergies, so we reached out to him to find out more about it, and to illuminate the process of editing a special issue, complete with continuing medical education (CME) credits. Dr. Schroer’s answers show us that advances in medical science and practice don’t travel on a straight line from laboratory to clinical trials to the clinician’s office. In this case it’s also a matter of committees, regulatory politics, and much more. Henry Ehrlich
AAC: The theme editorial by you and Rob Aalberse, PhD is very evocatively titled: Clinical Allergy at the Interface of Sticky Dust Particles and Crystal Clear Proteins. Could you explain the significance of this title? Also could you describe what you mean about extracts being the basic reagents of both diagnosis and treatment? And could you briefly explain how the current extracts are used by clinicians?
Brian: The title of this theme issue editorial was a play on the fact that we are at a point in allergy where the past may be meeting the future whether we like it or not. It alludes to the fact that most allergens float in the air stuck on small particles of dust mite allow the allergen such as dog or cat dander or dust mites to get into the nose, eyes and lungs of people with allergies and asthma. These allergens as you mention are currently collected, stored and used for two main purposes: diagnosis–skin testing and blood allergy testing– as well as therapy in the form of allergy shots and sublingual immunotherapy.
When it comes to diagnosis the allergens are sold in vials and we use them during skin prick testing to try and find the cause of allergy symptoms. Because many of these allergens are found all over the world, some such as cat, dust mites, northern grasses and ragweed are “standardized.” That is, they contain consistent amounts of allergens. This is because they have been widely studied. However, many allergens such as oak tree pollen, are regionally specific and are not standardized. They are used in specific regions where those plants live. Because of this we have greater diagnostic accuracy that can be tailored by allergists to the plants in their region. These lesser allergens are not as widely studied.
Naturally occurring allergens are not uniform when used as diagnostic and therapeutic tools and come with the potential for containing contaminants, which makes them imperfect for their current use. The future may hold a time where we can artificially produce specific proteins that represent the major allergens found in those dust particles. They would be crystal clear, unlike what we are now using for our diagnosis and treatment. The future, however, does not reflect our current reality. We do not have many of these artificially made proteins available and even if they become available, a lot of work needs to be done and money spent before they are known to be as useful as our current allergen products. And, because many of these allergens are not common, companies are not going to spend money to produce artificial forms of them. Until these new forms of allergens are available for diagnosis and treatment we are suggesting that allergists and our patients need to be able to continue to use the currently available allergens.
AAC: Ever since we’ve followed the subject (click here and here) of changing the way extracts are prepared and administered, I’ve been curious to ask, why now? What is the urgency of the United States Pharmacopeial Convention to replace the way extracts are formulated and utilized? It seems highly premature, and expensive.
Brian: It is expensive. And it will be premature. The situation though is standardization is the goal of regulatory agencies. These allergens for testing and therapy are “medical products” and therefore both US and European regulators have high standards for clinical. These allergens have been around for many, many years. When they were first available, they did not have to undergo the specific testing for efficacy and purity that many newer medical products are subject to. This is the threat to the current allergens. If the regulatory agencies require these allergens to go through this evaluation process and at the same time their use is restricted, then we will have fewer tools for diagnosis and treatment than we currently have.
AAC: What will the end game look like? How many allergens and in what pharmaceutically pure state? Will they be packaged in per-use doses? I know that occasionally the dilutions are computed wrongly before allergy shots, resulting in adverse reactions. Will these mistakes go away?
Brian: The goal of the editorial we wrote was to argue for what should be done: allow continued use of older allergens, while the work is being performed to identify which pure proteins or mixtures of pure proteins will be equally efficacious than the current options or even more so. Honestly, no one knows what will happen. We do know that restricting the availability of these allergen extracts will limit our diagnostic and therapeutic options now and for years.
AAC: Now for some process questions. First I’d like to know how this issue came about. Were you and your co-editor, Dr. Aalberse. approached with this theme, or did you go to the editors of In Practice with the theme in mind?
Brian: The editorial board of JACI In Practice meets once per year at the AAAAI annual meeting and votes on the various themes we want to cover in the year ahead. Some themes such as food allergy are done every year because there is so much new information all the time. Allergens and allergen products had not been done since the journal was first published. When we vote on the themes we are permitted to put our names in as potential theme coordinators. I was fortunate enough to be chosen for this theme issue with Dr. Aalberse.
AAC: How did you choose the very intriguing format of asking and answering both patient and clinician questions, some of which are more or less different versions of the same thing, sort of like the four questions on Passover? Do you think doctors need to hear about how the other side thinks?
Brian: I chose this format to help frame the types of questions I wanted to answer when it came to writing the outlines of the different papers for the theme issue. I wanted these papers to answer two types of questions. One is, “What do clinicians need to know about these allergens and extracts to help them be the best physicians they can be?” And two is, “What questions do the patients have so we can give them answers?” This type of thinking may come from my own relationship-centered style. Taking care of patients requires a relationship between the physician and the patient. It should not be doctor centered or exclusively patient centered. In order for the relationship to work well, both need to respect the wealth of experience the other brings to the relationship. The doctor has knowledge and the ability to explain symptoms or reassure. The patient has expert knowledge of what symptoms have been occurring, what they think is going on, and what they think may be helpful or not work to make them feel better. I wanted the theme issue and the editorial to reflect that way of thinking.
AAC: Once you arrived at your theme, how did you go about acquiring pertinent articles? Did you read lots of stuff or did you solicit particular authors? Were they friends, or people whose reputations you knew?
Brian: The individual articles solicited were ideas that both Rob Aalberse and I wanted to cover. That included writing a specific outline of questions for each review article. Once we had these ideas written down, I looked at who has published on these issues before and created a list of possible authors. Some of these authors were experts whom we had previous relationships with, and some I just searched the literature and found the best authors for the job.
AAC: Several articles have CME (continuing medical education) exams attached to them. Why were some of the articles considered CME material and not others? And what is the process of creating this component? Who writes the exams, how are they graded, and how is credit granted?
Brian: The CME articles are usually picked by the head editors from the journal, though we were able to make suggestions. CME credit really could have been given with any of the articles. The CME process is long and bureaucratic. It requires that the learner reading the article answer questions about the article to ensure they took away knowledge, attitudes or ideas about skills to help make their practice better. The exams for JACI In Practice and JACI are often written by allergy fellows. I did that a few times when I was a fellow 8 years ago. The credit is awarded through the CME committee on the AAAAI. It is part self-regulated and part paperwork to ensure the CME process is followed.
AAC: Thanks for your time.
Brian: You are welcome. Thank you for taking interest in the nuts and bolts of coordinating these theme editorials.
Brian Schroer, MD is a staff physician at Cleveland Clinic Children’s Hospital. He sees both kids and adults in clinical practice. He trained in allergy at Cleveland Clinic and internal medicine and pediatrics training at The Ohio State University and Nationwide Children’s hospital. He attended medical school at the University of South Florida College of Medicine and did his undergraduate studies at Duke University. His clinical focus is on children and adults with food allergies as well as other general allergic conditions. He teaches medicine to allergy fellows, pediatrics residents and medical students in the allergy clinic. Outside of clinic he teaches communication skills to medical students during their first and second years and to staff at all levels of experience. Finally, he is a member of the Editorial Board for JACI In Practice and reviews articles for that journal.
Pollen photo from Wikipedia Commons