A message was forwarded to me about a news broadcast from Chicago that highlighted a tool that can be used to help with asthma diagnosis and management. The FDA has recently approved this according to the message. This tool is the measurement of exhaled nitric oxide (eNO). In allergic asthma  airway inflammation involves numerous inflammatory cells especially eosinophils. These inflammatory cells have a marker for their involvement and activation called nitric oxide. We are able to measure this by-product of airway inflammation in the breath. I also received another link on this measure of airway inflammation. In this second newsbroadcast Dr. Wolfe, an allergist, does a nice job in explaining this test, this measure, and allergic asthma.

This is not a new procedure. At Riley Hospital our group has been using this measurement in the care of children with asthma. It is nice to see that the concept of eNO is catching on and its value is appreciated.

I feel that a measure of eNO offers a significant amount of information regarding the role of allergy and the level of control patients with asthma have. I use eNO measures frequently in my Allergy/Asthma practice.

FEL

The comment in question was posted to my October 15, 2009 entry titled Phadia Allergy Tests and Asthma .

The commenter disagrees with my interpretation feelings towards in-vitro testing. I am, in the commenter’s perspective, being self-serving by berating this type of allergy test in favor of high cost allergy skin tests that are “archaic”. The commenter also pointed out that it would be impossible for all 23 million patients with asthma to be seen by the 4,000 practicing allergists, and thus most asthmatics must be managed by the primary caretaker. The commenter points out that it is a disservice to disallow a patient to know the ‘root of their problem’–and in their practice, the immunocap is used daily to uncover the triggers that are causing symptoms. Mention is made of two studies in which allergists ‘…cannot guess sensitivities based on history or physical alone by more than 50%’. The comment ends with the commenter hoping that I and my allergy colleagues feel good about a futile and self-serving vendetta against in-vitro allergy testing. I was then challenged to talk about something called ‘allergy component’ testing.

There are quite a few issues here.

1. I use the Phadia Immunocap for IgE levels to specific foods. This is how we look for possible food allergy resolution. For many foods a specific concentration of specific IgE antibody is related to a risk of a reaction with exposure. We proceed with a food challenge based on the value of an in-vitro test. Without the in-vitro tests our practice would not have so many successes in outgrowing food allergies. IN-VITRO TESTS HAVE VALUE. I USE IN-VITRO TESTS.

2. I do have specific issues with in-vitro testing and that is the use of a PANEL. Too often the panel contains items that are not relevant (meaning there is no exposure to the allergen). The panel wraps a number of items and offers specific IgE at one price. Representatives from the ‘in-vitro testing industry’ recognize that this is an issue. However, by adding additional items a higher price can be justified.

      For example look at one Michigan hospital’s Phadia ImmunoCAP Food Allergy Panel - Clam, Egg White, Codfish, Corn, Milk, Peanut, Scallop, Shrimp, Soybean, Walnut, Wheat, and a total IgE. As individual in-vitro tests these can be $100 a piece. By the way, a skin prick test is about $10 per item. There clearly are a few foods on here that are not part of the usual diet- they are not clinically relevant. How many infants who have atopic dermatitis are eating scallops, shrimp, and clam? A food panel that contained egg white, wheat, soybean, codfish, peanut, and milk would be appropriate. A second panel with the shellfish and a third with the tree nuts would be very acceptable if used based on the food exposure history.

      A report by Anna Wetherbee in the journal Lab Medicine, November 2007 (Vol 38, no. 11 649-650)talks about the clinical appeal of in-vitro testing and the use of allergen panels. Interestingly, primary care physicians have been slow to embrace in-vitro testing partially due to a questionable total value proposition. The panel offers 15 or more specific allergens and billing for the panels is computed on a per allergen basis where the cost can be as much as $185 (Medicare fee schedule)

POINT- ORDER SPECIFIC ITEMS RELATED TO THE TIMING OF SYMPTOMS. AVOID PANELS.

3. The value of any allergy test is only as good as the history that supports it. The test makes no one allergic, it only demonstrates the production of IgE antibody which may or may not be relevant. They cannot be used to predict alllergy and the clinician needs to assess the clinical relevance of the test. Individual in-vitro allergy tests can do this. A set panel may not be appropriate for the seasonality of the patient’s symptoms. A simple example- if wheezing occurs August 15 and continues until the second frost then ragweed would lead the list of usual suspects. Of what use is the value for tree pollen given this history? A panel may obligate an analysis of other allergens that have no relevance and would add to the cost.

4. In-vitro testing overcalls inhalant allergy. Please see the results of the NHANES study(earlier posting in the blog ). This study involved a health survey of 4000 children and was published in a reputable journal. In this study the in-vitro test declared that almost 50% of the study population was allergic whereas by the children’s (parents’) history, only about 20% had symptoms of an allergic condition. The in-vitro tests are used extensively with our food allergy children and they are not as effective for inhalant allergy.

5. Intra-dermal skin testing is rarely done in our practice. The literature and evidence suggests that this type of test in most instances does not further the diagnosis.

6. If immunotherapy is considered, testing should be performed with the materials that are to be used in the immunotherapy extracts.

7. There are specific recommendations regarding when to refer to an asthma specialist. These can be found in Section 3 Component 1 page 68 of the 2007 National Heart, Blood, and Lung Institutes, National Asthma Education and Prevention Program, Expert Panel Report 3. There is no intention that every patient with asthma be seen by an allergist and clearly not every patient needs allergy testing. The use of allergy testing is considered within the context of severity and control with their subcomponents of risk and impairment.

8. I love to review articles. My training as a PhD student in pharmacology helped me learn the knack of critical review. My recent training in Public Health has added epidemiologic skills and insight to biostatistics. When I quote something it is always referenced so the reader can go to the source.

      There are two articles that have the batting average of an allergist at 500 for identifying a specific allergen by history or physical examination. I wonder, what was the gold standard in these studies? Remember, the best test for a trigger is a challenge. The history of seasonality or perennial exposures, symptom free days, and symptomatic days helps me sort out what I think is going on. The allergy tests help verify my clinical impression. Would you have the laboratory result determine the clinical impression or the history? Allergy tests can be falsely positive and falsely negative.

      The sensitivity of a test is the ability of the test to identify correctly those who have the condition of interest.

      The specificity of a test is the ability to identify correctly those who do not have the condition of interest (M.Szklo and F. Nieto, Epidemiology, Beyond the basics, 2^nd edition).

      In many reviews of the in-vitro tests, the sensitivity is high and even up to 100% for some allergens (correctly identifying those who are allergic). However, the specificity can be as low as 50%, correctly identifying those who do not have the condition. The in-vitro test can identify who has sensitization, however there as a fair number identified as having allergy by the test, but do no have symptoms (false positive results). We have to careful on how the results are interpreted. 

9. The email address of the person who wrote these comments indicated an association with a particular health care organization. I wonder what their background is—a physician, a nurse or a nurse clinician, a researcher, or a laboratory worker? The health care group has at least two allergy practices within its coverage. I wonder what the credentials of the commenter are in this area.

10. I am not sure what allergy component testing is. I entered the term in a search engine and got no results. I would be most happy to talk about it if I knew what it was.

I use in-vitro testing, I use the Phadia system for IgE. It is an excellent test when used in the proper context. I do, however, have issues with the marketing of panels, including cost, confusion, interpretation, outcomes. The use of these panels has generated a good number of referrals. I have been significantly busier with children (parents) coming for explanations, apprehensions, and fears based on what a panel revealed.  In the long run, if I was asked to pick what the 4 most important allergens to evaluate they would be house dust mites (two species), cat (if the history supports), dog (if the history supports), and cockroach (also history dependent). The family could actually do something about these exposures.

Fred Leickly

Evidence-based medicine (EBM) tries to provide a framework for treatment that is supported by the latest proven research. The article talks about this enhancing a medical practice. I think that patients and families should be aware of EBM. I can see value of EBM in the practice of allergy by board-certified allergists especially in an environment where the label of ‘allergy’ is given too loosely. In my practice I am seeing conditions labeled as allergy (apraxia, autism, sensory integration defects, ADHD to name a few) because tests for allergy return as positive. Many times the clinical condition and the test has nothing to do with allergy. IgG to food would be a prime example. I have seen significant amounts of money spent and hopes of families dashed by the use of tests and therapies that are not evidence-based.

The EBM approach first asks a very specific clinical question. The question could be about a test, a treatment, a diagnosis, or an outcome. Next the literature is searched for information on the topic. The information is then evaluated to see if it is valid, useful, and related to the question. The review of the literature looks critically at many different aspects of the scientific studies. The numbers, the methods, and the statistics are evaluated. The EBM may conclude that there exists type A evidence (great supportive studies in a large number of patients) that a treatment is effective.

Other support for diagnosing and treating can be found in ‘Guidelines’ . Many specialty organizations offer guidelines for common clinical conditions and the guidelines will incorporate EBM.

Resistance to EBM stems from concerns that it is a cookbook approach to medical practice. Another issue is how can a busy practitioner  integrate EBM into a practice. The article provides ideas and links for the practitioner.

Now the journal also had an excerpt from an article written by D. Isaacs and D. Fitzgerald that appeared in the British Medical Journal a few years ago (BMJ 1999;319:1618) that poked a little fun at EBM. What follows was the results of a poll that asked physicians what they would do if there was no solid evidence in the literature to help with a clinical decision. The article was titled, “Seven alternatives to evidence-based medicine”. This made me smile.

1. Eminence Based Medicine- The more senior the person, the less need for evidence. Experience outweighs evidence. Faith in clinical experience was defined as making the same mistake with increasing confidence over an impressive number of years.

2. Vehemence Based Medicine- Substituting volume for evidence as an effective technique for brow-beating a more timid colleague.

3. Eloquence Based Medicine- The perennial sun tan, carnation on the Armani suit, the silk tie accompany a tongue as equally smooth. Tailored eloquence and verbal eloquence are powerful substitutes for evidence.

4. Providence Based Medicine- If the caring practitioner has no clue what to do next, the decision may be best left in the hands of the Almighty.

5. Nervousness Based Medicine- The fear of litigation is a driving force for more tests and excessive treatments.

6. Confidence Based Medicine- Restricted to surgeons

Now I am puzzled- the quip in Physicians Practice said seven, I count only six. This second article ended and I could not find that seventh alternative. Finally, I found the original article at the Ruth Lilly Library on OVID. Here is number seven.

7. Diffidence Based Medicine- Some doctors see a problem and look for an answer. Others merely see a problem. The diffident doctor may do nothing from a sense of despair. This, of course, may be better than doing something merely because it hurts the doctor’s pride to do nothing (BMJ, 1999).

That was the original article on alternatives to EBM. Now it gets even better. Others have added to this list, we now have the following alternatives; Effervescence Based Medicine, Webidence Based Medicine, Profit Based Medicine, Annoyance Based Medicine, Propaganda Based Medicine, and Arrogance Based Medicine to name a few. We see a significant amount of Webidence Based Medicine. I urge caution with the internet. Look to sites sanctioned by well known organization- the American Academy of Pediatrics, the American Academy of Allergy, Asthma, and Immunology, the Food Allergy and Anaphylaxis Network, the National Institutes of Health, the National Heart, Lung, and Blood Institute to name a few. Profit Based Medicine – as a personal word of caution, ask about insurance coverage. Your insurance may not cover something because it is experimental or without EBM to support what is done. There is usually a reason why something is not covered by insurance. Ask about it.

I do my best to abide by evidence- based medicine. It makes sense to me. Evidence for my diagnosis, evidence for my selection of tests to help with that diagnosis, and evidence for the best treatment for the condition. Medicine is changing all the time. EBM helps evaluate what we have done and helps to consider what we need to do for the benefit of those we are taking care of.

Fred Leickly