Allergy and Asthma: Improving Outcomes in Primary Care

Allergy and Asthma: Improving Outcomes in Primary Care
El Paso November, 2007 Welcome and thank you for joining us [today/this evening]. I’d like to discuss with you the management of allergies and allergy-like symptoms in children and adults. In particular, we’ll address the use of allergy testing in primary care to aid diagnosis and management. We’ll focus on three key disease groups regularly managed by primary care clinicians and the potential role of diagnostic tests in the management of these patients. I’ll also spend a bit of time discussing the changing pharmaceutical market and its effect on patient management. After that, I’ll provide an overview of CAP RAST Specific IgE blood testing, and share with you some examples of third-party support for such testing by primary care clinicians in the management of common childhood diseases and respiratory diseases. Len Fromer, M.D., FAAFP

The Etiology Challenge
Common symptoms and diseases have many possible etiologies IgE-mediated allergies trigger symptoms from infancy into adulthood Identification of true underlying cause is essential for effective management Every day, you and your primary care colleagues see patients with a variety of common symptoms and illnesses that may or may not have an allergic etiology. The key IgE-mediated diseases may be divided into what we call the “three triads.” The first group is childhood diseases, or CHDs, which include atopic dermatitis, GI distress, and recurrent otitis media. Upper respiratory diseases (URDs) with classic allergy-like symptoms include allergic rhinitis, non-allergic rhinitis, and sinusitis. And allergy can play a key role in lower respiratory diseases (LRDs), especially asthma. Estimates show that patient history and physical alone yield a correct diagnosis of allergy only 50% of the time.1 With each patient, identification of the true underlying cause offers an essential key to unlock effective management. Homburger HA. Arch Pathol Lab Med. 2004;128:

The Allergic Inflammatory Response
As we all learned long ago, the body produces a whole family of immunoglobulin antibodies—A, D, E, G, and M. IgE is the antibody responsible for allergic responses, and therefore, the one we will focus on today. Here is a basic scientific review of the IgE-mediated allergic inflammatory process. [Click] First, B lymphocytes are exposed to an allergen, which, as we know, can be anything from cat dander or food to a mold spore or pollen. [Click] The initial exposure triggers the production of IgE antibodies for that particular allergen. [Click] Those IgE antibodies then attach themselves to basophils and mast cells. [Click] During subsequent allergen exposures, the basophils and mast cells release histamines and other chemicals that trigger inflammation and cause symptoms.

Common Childhood Diseases
CHDs The illnesses of the Allergy March Atopic dermatitis (eczema) GI distress Recurrent otitis media Allergic rhinitis Allergic asthma The symptoms Inflammatory in nature Multiple etiologies Treated empirically Some of the symptoms we’re talking about aren’t necessarily ones that you’d equate with allergy, like colic, diarrhea, or an earache. For those children with a genetic predisposition to allergy, atopy may emerge early on in the form of common illnesses that manifest from low-level food and inhalant sensitivities. These illnesses may evolve over time in a progression known as the Allergy March. Generally, the first manifestation is atopic dermatitis, followed by a range of gastrointestinal conditions and symptoms (what we call GI distress). Otitis media can then occur and recur due to allergic inflammation. The March then progresses into the airways, causing allergic rhinitis, and ultimately asthma.1,2 Listed here we have the five key illnesses defining the Allergy March. For each of these conditions the symptoms are – inflammatory in nature – identical to those caused by non-atopic conditions (making the underlying etiology difficult to detect) – and generally treated empirically Ahlstedt S. ACI Intl. 1998;10(2):33-44. ETAC® Study Group. Pediatr Allegy Immunol. 1998;9: CHDs

The Allergy March: A Progression of Seemingly Unrelated Diseases
CHDs Food Sensitivity Time (~years) Genetic Predisposition Atopic Dermatitis GI Distress Recurrent Otitis Media Allergic Rhinitis Allergic Asthma Inhalant Sensitivity Here is a graphic representation of the Allergy March. Taken in isolation, each of these five conditions seems unrelated, but as the ovals and lines illustrate, they can be tied to allergic sensitivities and inflammation, beginning with foods and shifting to inhalants. Although these illnesses often follow the progression of the March, allergy sensitivities may emerge with symptoms of any one of the five conditions, and may involve more than one illness at a time. This progression can commence early. Family history can predispose a child to allergy, and atopy can emerge soon after birth—in fact, IgE may be detected in children as young as 3 months. And in some young patients, allergic asthma may emerge by the age of 3 or 4.1 That’s why it’s critical that we work to recognize and treat underlying atopy, which can alter or arrest the march toward pediatric asthma. Understanding the allergic sensitivities in these diseases allows us to provide solid, evidence-based avoidance and treatment plans to treat the cause as well as the symptoms. Now, let’s take a look at each of these conditions to get a sense of prevalence and the specific role atopy plays for each. ETAC® Study Group. Pediatr Allegy Immunol. 1998;9: CHDs

CHDs Allergy March 10 20 30 40 50 Age (years)
10 20 30 40 50 Age (years) Prevalence of Atopic Disease 1 3 5 17 Symptoms Gastrointestinal Respiratory Skin Prevalence (%) Much of the research on the Allergy March has been conducted in Europe, and the allergy community there has embraced early testing and promoted its use among primary care clinicians. This graph illustrates one of the foundation studies of Allergy March research. Investigators at Children’s Hospital in Helsinki examined healthy children at various intervals from birth up to age 17 to gauge the impact of breast-feeding on the development of allergy.1 They observed for illnesses and also tested for atopy. These researchers gained a vivid picture of allergic illnesses in children—and how these illnesses shift over time. As you can see from the blue line, skin symptoms were the most common in the youngest children, followed very closely by the emergence of GI symptoms, illustrated in red. Before age 3, these children began to demonstrate respiratory symptoms, indicated in green, which progressed steadily with age. The eczema and GI symptoms, meanwhile, dropped off. What’s the take-away here? Allergic illnesses begin early, shift over time, and evolve into respiratory disease. Saarinen UM, Kajosaari M. Lancet. 1995;346: Saarinen UM, Kajosaari M. Lancet. 1995;346: CHDs

Mean score (Phadebas RAST Class)
Allergy March CHDs Age (years) 1 2 3 IgE Antibody Level 4 - 9 0 - 3 n= 12 29 12 Mean score (Phadebas RAST Class) Egg white Birch pollen Peanut This slide provides a compelling picture of shifting atopic sensitivities. Investigators in Sweden followed 324 children from birth over a 15-year period.1 Study subjects were assessed for atopic disease and tested for specific IgE antibodies to a variety of foods and inhalants. If you look at the white line, egg white allergy is very pronounced in children under 3 years of age. Like cow’s milk, egg white is one of the key food allergens implicated in the Allergy March. Meanwhile, sensitivity to inhalants, such as birch pollen, illustrated by the red line, is minimal. The blue line in the center illustrates peanut allergy. This line is relatively level, indicating that, in those with this allergy, sensitivity remains fairly constant. As these children age, their egg white sensitivity falls off steadily, while the birch pollen sensitivity increases severely, so that by age 5, a shift has clearly occurred between food-borne and inhalant allergies. So right here, you see the atopic etiology of the shift in disease manifestations illustrated on the previous slide. [Click back] [On previous slide:] Moving out from age 5, the green line indicating respiratory disease goes up, as the food allergen-related GI and skin symptoms taper off. [Click ahead two slides] Sigurs N, et al. J Allergy Clin Immunol. 1994;94: Sigurs N, et al. J Allergy Clin Immunol. 1994;94: CHDs

CHDs Atopic dermatitis (AD)1 17%-20% prevalence in US, other western countries Not necessarily severe reaction (anaphylaxis) Driven by early exposure and sensitization 40% of AD caused by food sensitivity Empirical treatment: trials of topicals As you can see, atopic dermatitis occurs in up to 20% of children in the US and other westernized countries. AD is triggered to a large degree by food sensitivities, but these are low-level reactions. And this is an important point to make. When we talk about allergy in children, we often think first of severe reactions—even full-blown anaphylaxis. But low-level sensitivities are also very serious, if not for acute symptoms, then for long-term health. Most children with atopic dermatitis go on to develop allergic rhinitis or asthma, and currently AD is treated empirically with various topical agents. So you can see that by addressing the underlying cause through confirming or ruling out atopy and identifying allergens for avoidance, you will not only help treat or alleviate acute symptoms but may also aid these children down the line. The data presented here were compiled by Donald Leung, the head pediatric allergist at National Jewish Medical Center in Denver. This information comes from Dr. Leung’s chapter on AD in the textbook he edited along with Hugh Sampson and other experts entitled Pediatric Allergy: Principles and Practice.1 Leung DYM. In: Pediatric Allergy: Principles and Practice. St. Louis, Mo: Mosby-Year Book, Inc; 2003: Leung DYM. In: Pediatric Allergy: Principles and Practice. Mosby-Year Book, Inc; 2003: CHDs

CHDs GI distress1 Colic, diarrhea, vomiting, constipation, reflux Multiple etiologies: atopy, infection, intolerance, malabsorption, inflammatory bowel, anatomic defect 10%-42% of symptomatic patients are atopic2,3 50%-60% of infants with food sensitivities show GI symptoms (not necessarily full-blown food allergy) – Empirical treatment: trials of formulas As you can see, atopy has been found to play a role in a number of gastrointestinal symptoms and conditions.1 Of course, whether they have colic, diarrhea, vomiting, or one of these other symptoms, the challenge in managing these young patients is in discerning the true cause. In addition to atopy, these symptoms may be triggered by infection, intolerance, and other causes shown here.1 Depending on the issue, between 10% and 42% of symptomatic patients are atopic.2,3 And, inversely, at least half of all allergic kids demonstrate GI distress.1 Once again, these are low-level reactions triggering somewhat garden-variety symptoms— not full-blown anaphylaxis. GI distress is currently treated with empirical formula trials. Knowledge of specific food allergens could go a long way toward optimizing dietary modifications, but I need to stress that great care should be taken to prevent any changes that would needlessly cause malnourishment. Consultation or referral may be warranted. Høst A, Halken S. In: Pediatric Allergy: Principles and Practice. St. Louis, Mo: Mosby-Year Book, Inc; 2003: Australasian Society of Clinical Immunology and Allergy. Adverse reactions to food. Available at: Sicherer SH. Pediatrics. 2003;111: Høst A, Halken S. In: Pediatric Allergy: Principles and Practice. Mosby-Year Book, Inc; 2003: Australasian Society of Clinical Immunology and Allergy. Adverse reactions to food. Available at: Sicherer SH. Pediatrics. 2003;111: CHDs

CHDs Recurrent otitis media (OM) 26% prevalence in US1 Key risk factors include attendance in daycare, cigarette smoke exposure2 40%-50% involve atopy3,4 Common underlying cause = eustachian tube dysfunction Caused by inflammation related to allergy or infection Recurrence = not treating the underlying cause Empirical treatment: antibiotics, surgery Now I’d like to talk about otitis media that recurs, and the need to make sure there isn’t some underlying atopy causing this recurrence. Recurrent otitis media is generally defined as three or more episodes of acute otitis media in the last 6 months or four or more episodes in the last year.1 As you can see in the first statistic from Lanphear et al, somewhere around one-quarter of US school kids have recurrent otitis media.2 Risk factors for otitis media include attendance in daycare and exposure to cigarette smoke,3 but up to half of recurrent or chronic cases involve atopy.4,5 Of note, Fireman identified allergic rhinitis in up to 50% of kids older than 3 years with chronic OM.5 In children with atopic disease, atopy causes inflammation of the tissues lining the eustachian tubes. This inflammation hampers fluid drainage and helps create an ideal environment for bacteria, which leads to infection. Otitis media is generally treated empirically with antibiotics and/or insertion of tympanostomy tubes. In kids with recurrent otitis media, it really pays to know if atopy plays an underlying role in the precipitating inflammation and eustachian tube dysfunction. Through avoidance, this may reduce recurrence and prevent unnecessary use of antibiotics. And targeting allergy works: according to the AAAAI, control of allergic rhinitis in those with concomitant disease frequently results in the resolution of otitis media.3 Alho OP, et al. J Fam Pract. 1996;43: Lanphear BP, et al. Pediatrics. 1997;99:1-7. AAAAI. The Allergy Report. 2000;2: Data on file, Pharmacia Diagnostics. Fireman P. J Allergy Clin Immunol. 1997;99:S787-S797. Lanphear BP, et al. Pediatrics. 1997;99:1-7. AAAAI. The Allergy Report. 2000;2: Data on file, Pharmacia Diagnostics. Fireman P. J Allergy Clin Immunol. 1997;99:S787-S797 CHDs

Atopy’s Long-Term Consequences
CHDs Nearly 80% of children with AD go on to develop allergic rhinitis and/or asthma1 Children with early and long-lasting food sensitization: – 3x more likely to develop allergic rhinitis (AR) than those transiently sensitized2 – 5x more likely to develop asthma than those transiently sensitized2 Young wheezers with confirmed atopy are more likely to develop asthma3 1. Leung DYM. In: Pediatric Allergy: Principles and Practice. Mosby-Year Book, Inc; 2003: 2. Kulig M, et al. Pediatr Allergy Immunol. 1998;9:61-67. 3. Martinez FD, et al. J Allergy Clin Immunol 1999;104:S169-S174. The risks posed by allergic disease progression make it vital that we understand the underlying cause of common pediatric symptoms. Here are some specific data underlining the potential long-term impacts of early atopy. Nearly 80% of children with confirmed atopic dermatitis go on to develop allergic rhinitis or asthma.1 As discussed earlier, a good portion of those cases are driven by food sensitivities. The Multicenter Allergy Study group in Germany has shed more light on risks posed by food allergy, determining that Children with early and long-lasting food sensitization are 3 times more likely to develop allergic rhinitis, and 5 times more likely to develop asthma than those transiently sensitized2 And the final bullet point underscores the key role atopy plays in the development of lower respiratory symptoms and asthma.3 I’ll discuss wheezing and asthma in more detail a little later on in this presentation. Leung DYM. In: Pediatric Allergy: Principles and Practice. St. Louis, Mo: Mosby-Year Book, Inc; 2003: Kulig M, et al. Pediatr Allergy Immunol. 1998;9:61-67. Martinez FD, et al. J Allergy Clin Immunol. 1999;104:S169-S174. CHDs

Knowledge of Etiology Guides Treatment for Today and Tomorrow
CHDs Specific IgE testing in children can help the clinician: – Identify allergen sensitivities – Counsel for avoidance – Eliminate or reduce symptoms – Reduce medication use (including antibiotics) Targeting atopy can eliminate symptoms and interrupt the Allergy March1-5 – ETAC: Cetirizine and avoidance halved asthma risk in children with AD1 – PAT: Immunotherapy significantly reduced asthma risk in children with AR2 – CCAPPS: Multifaceted avoidance intervention reduced asthma prevalence 56% in high-risk children5 By using specific IgE testing, you can confirm the atopy and identify specific allergens, and then use that information to counsel for avoidance, and otherwise target the allergic disease process. This will reduce or eliminate symptoms, and can even help to reduce the use of some medications, especially antibiotics, whose overuse has proven so troubling in children. In fact, identification and treatment of atopy not only can help you eliminate symptoms, but also, as a growing body of evidence shows, may help to interrupt the progression of the Allergy March toward asthma The Early Treatment of the Atopic Child (ETAC) study group observed that children with atopic dermatitis who were managed with cetirizine and allergen avoidance were half as likely to develop asthma as those left untreated.1 And the Preventive Asthma Treatment (PAT) study also showed that targeting the allergic process, this time with immunotherapy for children with seasonal rhinoconjunctivitis, significantly reduced the risk of developing asthma.2 Most recently, the Canadian Childhood Asthma Primary Prevention Study5 (CCAPPS) demonstrated 56% reductions of asthma frequency by age 7 in high-risk children through an intervention program for the first year of their life that included avoidance of pets, secondhand smoke, and dust mites, and encouragement of breast-feeding. ETAC® Study Group. Pediatr Allergy Immunol. 1998;9: Möller C, et al. J Allergy Clin Immunol. 2002;109: Platts-Mills TAE. N Engl J Med. 2003;349: Sampson H. Ann Allergy Asthma Immunol. 2004;93: Chan-Yeung M, et al. J Allergy Clin Immunol. 2005;116:49-55. ETAC® Study Group. Pediatr Allergy Immunol. 1998;9: Möller C, et al. J Allergy Clin Immunol. 2002;109: Platts-Mills TAE. N Engl J Med. 2003;349: Sampson H. Ann Allergy Asthma Immunol. 2004;93: Chan-Yeung M, et al. J Allergy Clin Immunol. 2005;116:49-55. CHDs

URDs Etiology Is Elusive
Now we move on to Upper Respiratory Diseases, which affect patients young and old. What do we mean by Upper Respiratory Diseases (or URDs)? The three I’d like to focus on are allergic rhinitis, non-allergic rhinitis, and sinusitis. This group of diseases has similar symptom presentations, which can make it very difficult to differentiate between the common etiologies of viral or bacterial infection, allergy, hormone imbalance, anatomic defect, or some other pathology. URDs

URDs Overlapping Symptoms Allergic Rhinitis Non-allergic Rhinitis
Nasal congestion Rhinorrhea Increased secretions Sneezing Itchy, watery eyes Non-allergic Rhinitis Nasal congestion Rhinorrhea Increased secretions Postnasal drainage Chronic Sinusitis Nasal congestion Rhinorrhea Increased secretions Postnasal drainage Headache Facial pain This table compares the symptoms of the three URDs, and you can see the overlap of nasal congestion, rhinorrhea, and increased secretions. When the symptoms that fall outside this blue bar do not appear for a given condition, then the ones that you do see can be a bit more confounding than helpful. In other words, based on physical exam and patient history alone, these three conditions really start to look alike. URDs

Upper Respiratory Diseases
URDs Allergic rhinitis, non-allergic rhinitis, sinusitis Symptoms caused by inflammation Multiple etiologies, including: Allergic • Hormonal Anatomic • Vasomotor Infectious Usually treated empirically/symptomatically Depending upon etiology, treatment can/should be different The three upper respiratory diseases share inflammation as the key cause of the symptoms, but the etiology can vary. The congestion, rhinorrhea, and increased secretions may be triggered by allergies, hormone imbalances, some anatomic defects, a vasomotor reflex, or infection. Based on our training, we currently focus our treatment empirically on symptom relief. And, because none of the possible URDs really poses any grave threat to most adult patients, we don’t waste a lot of time evaluating them. We do what we can to make the patient feel better. Nevertheless, the treatment really should be tailored to the underlying cause. That way, we can provide truly effective disease management, and the patient is less likely to have lingering or recurrent disease. URDs

Productivity Loss $ per 1000 Employees
Not only are allergies a huge burden on the health care system they are also a huge burden on employees and employers. It is the number 1 reason for loss of productivity while on the job.

Comparison of Quality-of-Life in Asthmatic & Chronic Rhinitis Patients
It is interesting to note that although many do not consider allergies as a serious disease, in a study conducted by Bousquet et al, it was determined that Quality of Life (QOL) of rhinitis patients is lower than for asthmatics! This is a very serious disease from the patient’s perspective.

Distribution of URD in US1-3
URDs 39% of total population (115M of 295M) have URD 40M 35M Sinusitis 30% Non-allergic Rhinitis 35% Allergic Rhinitis URDs are common, as these prevalence data show. Here we have estimates for the three conditions, weighed against the current US population. Allergic rhinitis and non-allergic rhinitis are thought to have roughly the same prevalence.1 According to the US Agency for Healthcare Research and Quality, that would be about 40 million people2 (35% of those with URDs). Sinusitis is not far behind, with 35 million people3 (or 30% of those with URDs). Spector SL, ed. Dialogues in Redefining Rhinitis. 1996;1(1,4):1-16. AHRQ. Management of allergic and nonallergic rhinitis. May AHRQ Pub. No. 02-E023. Allergy Statistics.AAAAI Web site. Available at: AHRQ. Management of allergic and nonallergic rhinitis. May 2002: AHRQ Pub. No. 02-E023. Spector SL, ed. Dialogues in Redefining Rhinitis. 1996;1(1,4):1-16. Allergy Statistics.AAAAI Web site. Available at: URDs

Actual Atopy and Antihistamine Use
URDs Identification of allergic disease among users of antihistamines1 Allergic rhinitis, non-allergic rhinitis, sinusitis Study of managed-care patients repeatedly prescribed oral antihistamines Convenience sample of 246 evaluated with in vitro allergy testing Results revealed non-atopic symptom etiology in 2/3 of patients 35% Atopic Etiology 65% Non-atopic Etiology Here are data from a study that looked at patients in a managed care plan, who were repeatedly prescribed non-sedating antihistamines (NSAs) for their allergy-like symptoms.1 A convenience sample cohort of 246 patients was evaluated using in vitro allergy testing (CAP RAST Specfic IgE blood testing). Of those tested, only 35% were atopic and would benefit from NSAs. That means that 2/3 of patients taking antihistamines were not allergic. Some of you may be puzzled by these data, thinking that a larger percentage of your URD patients seem to benefit from the use of NSAs. I’d like to remind you that some people without underlying atopy may experience a strong placebo effect from antihistamines. Furthermore, many of today’s “D” formulations have an added decongestant to provide direct symptom relief. So if a patient is taking one of those, it may appear to be relieving symptoms, even if there is no allergy causing the symptoms. As a result, in non-atopic patients the underlying cause of symptoms is not being addressed. Szeinbach SL, et al. J Manag Care Pharm. 2004;10(3): 1. Szeinbach SL, et al. J Manag Care Pharm. 2004;10(3): URDs

Non-allergic Rhinitis
URDs Wide array of types and etiologies1,2 Includes: infectious, vasomotor, hormonal, anatomic, occupational, drug-induced Not caused by IgE-mediated allergic inflammation Non-sedating antihistamines and other allergy-targeted therapies will not treat underlying cause So, in the two-thirds of rhinitis patients who aren’t atopic, what’s causing their symptoms? Well, there’s a wide array of possibilities that include infection, vasomotor reflex, hormone imbalance, an occupational exposure, or some type of drug-induced rhinitis.1,2 (Hidden slide available here.) The key is that the symptoms these patients experience are not caused by IgE-mediated inflammation—so antihistamines and other allergy-targeted therapies will not treat the underlying cause. AAAAI. The Allergy Report. 2000;2:1-31. Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81: AAAAI. The Allergy Report. 2000;2:1-31. Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81: URDs

Non-allergic Rhinitis: Many Possible Etiologies
URDs Return to previous slide How would you treat a non-allergic patient? First, you would need to identify the true cause—and there are many possible etiologies for non-allergic URD. I know this is a bit hard to read, but this graphic shows in rather dramatic fashion all the possible non-atopic causes of allergy-like upper respiratory symptoms (including sinusitis). In this decision tree, only the green portion at left denotes URDs with an atopic etiology. Those depicted in red, yellow, and blue are non-atopic. In all of these conditions listed to the right of the green portion, antihistamines will not treat the true cause of your patient’s symptoms. URDs

URDs Allergic Rhinitis Triggered by seasonal or perennial allergen(s)
Symptoms may include: nasal congestion, rhinorrhea, increased secretions, sneezing, itchy nose/eyes, watery eyes, coughing, postnasal drip1,2 Cumulative threshold disease3,4: Patients are rarely monosensitized Symptoms emerge after “allergic threshold” has been exceeded Now in those cases where atopy truly is the cause (for example, allergic rhinitis), the allergens may be seasonal or perennial. In addition, AR can demonstrate a number of other telltale symptoms beyond the “big three” of nasal congestion, rhinorrhea, and increased secretions. These are sneezing, itching in the eyes and nose, watery eyes, coughing, and the postnasal drip that often causes the cough.1,2 Allergy is a cumulative threshold disease.3,4 In other words, the patient who is sensitized to more than one allergen may only have mild sensitization to each allergen, but multiple exposures can combine to achieve a cumulative allergic load, which pushes the patient across the symptom threshold. AAAAI. The Allergy Report. 2000;2:1-31. Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81: Pharmacia & Upjohn Diagnostics. The Value of Allergen Identification Publication Wickman M. Allergy. 2005;60(suppl 79):14-18. AAAAI. The Allergy Report. 2000;2:1-31. Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81: Pharmacia & Upjohn Diagnostics. The Value of Allergen Identification Publication Wickman M. Allergy. 2005;60 (Suppl 79):14-18. URDs

Cumulative Threshold Disease1
URDs Symptoms Cat dander Dust mites Ragweed Situation A2 No avoidance measures Situation B3 No avoidance measures Third allergen Situation C3 Avoidance measures employed Third allergen Here’s an illustration of the cumulative threshold concept.1 The patient depicted here is sensitized to cat dander, dust mites, and ragweed. He or she may not have sufficient exposures to any one of these allergens to develop symptoms to that trigger alone. Situation A shows how with low exposure, the sensitized patient can “fly under the radar” of allergy symptoms,2 but when sensitivity to one or more reaches the right level (in this case the addition of ragweed in Situation B), then symptoms begin.3 It’s essential for clinicians to understand the underlying disease processes in order to provide avoidance measures, because if we limit these exposures, then we can reduce the patient’s total allergic load, and with it, their symptoms.3, 4 Situation C illustrates how, by reducing exposure to cat dander and dust mites, the patient is pulled back from the symptom threshold—the ragweed becomes less of an issue. And this can work with any of the three, so that by sufficiently reducing the patient’s exposure to ragweed or dust mites, the patient avoids developing symptoms—and therefore, if he or she is a cat lover, Fluffy needn’t be sent away to live with Aunt Martha. (Hidden “Avoidance” slide available here.) Pharmacia & Upjohn Diagnostics. The Value of Allergen Identification Publication Ciprandi G, et al. J Allergy Clin Immunol. 1995;96: Boner AL, et al. Clin Exp Allergy. 1993;23: Wickman M. Allergy. 2005;60(suppl 79):14-18. 1. Pharmacia & Upjohn Diagnostics. The Value of Allergen Identification Publication 2. Ciprandi G, et al. J Allergy Clin Immunol. 1995;96: 3. Boner AL, et al. Clin Exp Allergy. 1993;23: URDs

Support for Avoidance in the Management of Allergies and Asthma
URDs URDs …It has become clear that early intervention may modulate the natural course of atopic disease…the reduction in exposure of high-risk infants to food and house-dust mite allergens substantially lowers the frequency of allergic manifestations in infancy.”1 – Halmerbauer, et al. “Extensive experience suggests that both drug treatment and immunotherapy are more effective if patients also decrease exposure. The approach is to identify the allergen source (or sources) to which the patient is allergic and to educate patients extensively.”2 – Platts-Mills, et al. The NIH, AAAAI, and AAFP urge trigger avoidance as a cornerstone of asthma management3-5 There is solid evidence that avoidance is a highly effective tool in the management of allergic disease, especially when used as part of a multifaceted treatment program. In fact, two of the studies cited today, ETAC®1 and the Canadian Childhood Asthma Primary Prevention Study,2 have demonstrated the major role avoidance plays in helping to reduce asthma incidence in high-risk children. Here we have further support for avoidance. The first statement, from Gerhard Halmerbauer and colleagues with the Study on the Prevention of Allergy in Children in Europe (SPACE), reinforces the role avoidance can play in interrupting the childhood Allergy March.3 In the second statement, Thomas Platts-Mills, a highly respected allergist at the University of Virginia, speaks to avoidance as it is integrated into the management of respiratory disease.4 Finally, I’d like to point out that guidelines published by the National Institutes of Health, the American Academy of Allergy, Asthma & Immunology, and the American Academy of Family Physicians, all urge trigger avoidance as a cornerstone of effective asthma management.5-7 ETAC® Study Group. Pediatr Allergy Immunol. 1998;9: Chan-Yeung M, et al. J Allergy Clin Immunol. 2005;116:49-55. Halmerbauer G, et al. Pediatr Allergy Immunol. 2003;14:10-17. Platts-Mills TAE, et al. J Allergy Clin Immunol. 2000;106(5): NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication AAAAI. The Allergy Report. 2000;2: AAFP. Asthma & Allergy Resource Guide. 2004:11-13. 1. Halmerbauer G, et al Pediatr Allergy Immunol. 2003;14:10-17. 2. Platts-Mills TAE, et al. J Allergy Clin Immunol. 2000;106(5) NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication 4. AAAAI. The Allergy Report. 2000;2: 5. AAFP. Asthma & Allergy Resource Guide. 2004:11-13 Return to >> Cumulative Threshold

URDs Sinusitis Multiple etiologies Common comorbidity–often with atopy
Caused by inflammation from infection, allergy, structural abnormalities, other causes1 ENT experts use term “rhinosinusitis” due to epithelial continuum of sinus/nasal passages1,2 Common comorbidity–often with atopy Rarely occurs without concurrent rhinitis2 >50% of moderate to severe asthmatics have chronic rhinosinusitis3 Sinusitis is the third URD, and although allergy is generally not directly involved, the inflammation it causes is considered a key precipitating factor.1 Our ENT colleagues now refer to sinusitis as “rhinosinusitis,” due to anatomic proximity and coincidence of symptoms between the sinuses and nasal passages.1,2 When the telltale symptoms of headache, facial pain, and thick yellow-green mucus are present, a diagnosis can be fairly straightforward, but as the bottom half of the slide shows, sinusitis often coexists with rhinitis and even asthma.3 So, it stands to reason that allergy testing may serve as a useful tool in a sinusitis work-up. Whether you want to rule out atopy in suspected sinusitis or investigate possible allergy in comorbid disease, a clear picture of the patient’s atopic status could be a highly valuable disease-management tool. Brook I, et al. Ann Otol Rhinol Laryngol. 2000;109:2-20. AAO-HNS. Fact sheet. ENT Link Web site. Available at: AAAAI. The Allergy Report. 2000;2:7, Brook I, et al. Ann Otol Rhinol Laryngol. 2000;109:2-20. AAO-HNS. Fact sheet. ENT Link Web site. Available at: AAAAI. The Allergy Report. 2000;2:7, URDs

URDs Why Should You Test?
History and physical alone yield a correct diagnosis only 50% of the time1 Different etiologies demand different treatment approaches Testing for specific IgE levels can rule in/out atopy If atopic: – NSAs probably drug of choice – Testing can help clinician pinpoint offending allergens If non-atopic: – Results will allow you to focus on other etiologies – Drugs of choice may include decongestants/steroids – Patient can avoid unnecessary/ineffective treatment Non-allergic rhinitis, sinusitis, and allergic rhinitis present with similar symptoms. A definitive diagnosis of URD is difficult without objective evidence. In fact, studies show that primary care physicians correctly diagnose allergies only 50% of the time using history and physical (H&P) alone.1 The most persuasive reason for testing? Diagnostic test results may affect how you manage your patient. Treatment options for atopic and non-atopic patients are different, and you can’t select an effective treatment without a definitive diagnosis. Right now, you may be prescribing antihistamines, but they won’t work if the patient is not allergic. Specific IgE testing will definitively rule in or rule out atopy (allergy) as a cause of nasal symptoms. If your patient is allergic, testing can identify the specific offending allergens so you can counsel for avoidance and prescribe antihistamines with the confidence that they will truly target the underlying etiology. If there is no atopy, you will then be able to focus your evaluation on other possibile non-allergic etiologies and select appropriate, effective treatments. Homburger HA. Arch Pathol Lab Med. 2004;128: 1. Homburger HA. Arch Pathol Lab Med. 2004;128:

URD Management Options
URDs Specific IgE-Positive/Abnormal Atopic Etiology Specific Allergen Avoidance Adequate Response Allergy-Targeted Pharmacotherapy (eg, NSAs, LTRAs) Stop Inadequate Response Referral? Specific IgE-Negative/Normal Non-Atopic Etiology Adequate Response Pharmacotherapy (allergy-targeted Rx not helpful) Stop Inadequate Response Referral? Let’s talk about how specific IgE test results can guide your clinical management of URDs. If the test comes up positive, you can counsel for avoidance of the offending allergens. Sometimes that’s all it takes to relieve the patient’s symptoms. If not, then you can try allergy medications, such as antihistamines and leukotriene antagonists. If medications don’t work, you may want to consider referral to an allergist or ENT. If the allergy testing is negative or normal, your treatment options include antibiotics for an infection, intranasal steroids to reduce inflammation, and decongestants for direct symptom relief. Again, with an inadequate response from these options, you’ll need to consider referral.

The Experts on Differential Diagnosis of Rhinitis
URDs “A positive diagnosis (or diagnoses) should be made before formulating management.”1 A number of experts recommend the need for a confirmed diagnosis before treatment of allergy-like symptoms. As you’ll see, some of these experts also support the use of allergy testing by primary care clinicians to aid that diagnosis. This quotation from Middleton’s text, Allergy: Principles & Practice is very straightforward: “A positive diagnosis (or diagnoses) should be made before formulating management.”1 1. Middleton E, et al, eds. Allergy: Principles & Practice. Vol II, 5th ed. St. Louis, Mo: Mosby-Year Book, Inc; 1998:1007. Middleton E, et al, eds. Allergy: Principles & Practice. Vol II, 5th ed. St. Louis, Mo: Mosley-Year Book, Inc; 1998:1007. URDs

URDs An expert panel in the area of allergy diagnosis recommended selective use of in vitro allergy testing by primary care physicians. According to these experts, in vitro tests1: Offer a well standardized alternative to skin testing Are easily used by generalist physicians Are effective in the diagnosis of allergy Here we have support expressed by a group of experts from a workshop in clinical allergy and immunology, as well as experts in in vitro allergy testing. This panel, co-chaired by John Selner and Timothy Sullivan, included such experts asThomas Platts-Mills and Brock Williams. This group directly recommended selective use of in vitro allergy testing by primary care physicians.1 They point out that in vitro tests offer a well standardized alternative to skin testing, are easily used by generalist physicians, and are effective in the diagnosis of allergy. Selner JC, et al. Ann Allergy Asthma Immunol. 1999;82: 1. Selner JC, et al. Ann Allergy Asthma Immunol. 1999;82:

URDs The Experts on Differential Diagnosis of Rhinitis “Allergy [IgE] testing should be considered in all patients with a suspected diagnosis of allergic rhinitis.”1 And here’s another expert statement; this one from Bierman’s Allergy, Asthma, and Immunology From Infancy to Adulthood allergy textbook1: “Allergy [IgE] testing should be considered in all patients with a suspected diagnosis of allergic rhinitis.”1 Bierman CW, et al, eds. Allergy, Asthma, and Immunology From Infancy to Adulthood. 3rd ed. Philadelphia, Pa: WB Sanders Company; 1995: Bierman CW, et al, eds. Allergy, Asthma, and Immunology From Infancy to Adulthood. 3rd ed. Philadelphia, Pa: WB Sanders Company; 1995: URDs

Etiology Linked to Triggers
LRDs Now we move on to Lower Respiratory Diseases. The three conditions we will focus on are allergic asthma, non-allergic asthma, and bronchitis. You’ll see here that bronchitis is listed in quotation marks, which is meant to signify the somewhat vague use of this diagnosis outside the bounds of clear diagnostic criteria. I’ll discuss this in more detail in a moment. LRDs

LRDs Overlapping Symptoms “All that wheezes is not asthma.”
– Chevalier Jackson [ ] Allergic Asthma Wheezing Cough Dyspnea Chest tightness Rhinitis Conjunctivitis Non-allergic Asthma Wheezing Cough Dyspnea Chest tightness “Bronchitis” Wheezing Cough Dyspnea As with URDs, the clinician may be faced with overlapping allergy-like symptoms when trying to diagnose LRDs. At the top, you’ll see the quotation from the laryngologist and “father of American bronchoscopy,” Chevalier Jackson, who told us, “All that wheezes is not asthma.”1 Indeed, the diagnosis of asthma requires fulfillment of distinct criteria, but symptom overlap between allergic asthma, non-allergic asthma, and bronchitis may obscure the clinical picture. You’ll see that among these three symptom lists, wheezing is joined by cough and dyspnea as symptoms common to all three conditions. Under Allergic Asthma you’ll also see rhinitis and conjunctivitis, two common presentations of allergic disease. Krieger B. Postgrad Med. 2002;112(2): LRDs

Lower Respiratory Diseases
LRDs Course and severity affected by inflammation (often caused by allergy) Underlying atopy shown to increase symptoms and precipitate exacerbations A wide range of possible triggers include: Allergy Occupational exposures Infection GERD Tobacco smoke Emotional stress Exercise Cold weather As with URDs, LRDs are inflammatory in nature. Allergy is often the cause of that inflammation, and is shown to increase symptoms and precipitate exacerbations. In LRDs, the key to management is identification of symptom triggers, and you can see quite a range of possible triggers here. As you will learn, the key distinguishing factor in identifying symptom triggers is determining the presence or absence of atopy. LRDs

LRDs Asthma Widespread Allergic vs. non-allergic asthma
7% prevalence (>20 million1) and rising 73% managed by PCPs2 Allergic vs. non-allergic asthma 60% of asthmatics have allergic asthma3 90% of children with asthma also have allergies4 As we all know, asthma is widespread and growing. According to data from the National Center for Health Statistics, more than 20 million Americans have asthma,1 and the vast majority—almost 3/4—are managed by primary care clinicians.2 Asthma can generally be classified as allergic or non-allergic. Overall, more than half of asthmatics have allergic asthma,3 but statistics show that most children with asthma will also have allergies.4 NCHS. Asthma prevalence, health care use and mortality Available at: NCHS. Ambulatory care visits 1999–2000. Available at: Milgrom H. Understanding allergic asthma [AAAAI News Release]. June 18, 2003. Høst A, Halken S. Allergy. 2000;55: NCHS. Asthma prevalence, health care use and mortality Available at: NCHS. Ambulatory care visits 1999–2000. Available at: Milgrom H. Understanding allergic asthma [AAAAI News Release]. June 18, 2003. HØst A, Halken S. Allergy. 2000;55: LRDs

The “One Airway” Concept
LRDs Common inflammatory process links upper and lower airways1 Asthma and allergic rhinitis commonly co-exist2,3 In concomitant disease, experts recommend evaluation and treatment of one condition to aid management of the other4 Asthma management guidelines from ARIA,4 the NIH,5 AAFP,6 and AAAAI7 encourage treatment of AR (and other URDs) to help control asthma More and more, experts support the one-airway concept, which holds that, due to shared inflammatory processes, the upper and lower airways may be linked, and that symptoms in one will have an effect on the other.1 Supporting this concept is the very strong evidence that asthma and allergic rhinitis commonly co-exist.2,3 As a result of these findings, experts now urge that patients with asthma be evaluated for allergic rhinitis and vice versa, because it has been shown that treating one condition will aid management of the other.4 Allergic Rhinitis and its Impact on Asthma (ARIA), an international non-governmental organization sponsored by the World Health Organization, has really led the way on this. Its expert panel members have conducted a lot of research into this area, and have gone to great lengths to promote the management of concomitant AR and asthma. In addition to ARIA’s recommendations, asthma guidelines from the NIH, AAFP, and AAAAI all encourage direct treatment of concomitant AR—as well as non-allergic rhinitis and sinusitis—to help reduce asthma symptoms and severity.4-7 Bachert C, et al. Immunol Allergy Clin N Am. 2004;24:19-43. Nayak AS. Allergy Asthma Proc. 2003;24: Halpern MT, et al. J Asthma. 2004;41: Bousquet J, et al. Allergic Rhinitis and its Impact on Asthma (ARIA). Allergy. 2002;57: NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication AAFP. Asthma & Allergy Resource Guide. 2004:18. AAAAI. The Allergy Report. 2000;2:33,54. Bachert C, et al. Immunol Allergy Clin N Am. 2004;24:19-43. Nayak AS. Allergy Asthma Proc. 2003;24: Halpern MT, et al. J Asthma. 2004;41: Bousquet J, et al. Allergic Rhinitis and its Impact on Asthma (ARIA). Allergy. 2002;57: NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication AAFP. Asthma & Allergy Resource Guide. 2004:18. AAAAI. The Allergy Report. 2000;2:33,54.

LRDs NIH Asthma Guidelines1
Trigger identification/control is primary management step “For at least those patients with persistent asthma on daily medications, the clinician should: Identify allergen exposures Use the patient’s history to assess sensitivity to seasonal allergens Use skin testing or in vitro [blood] testing to assess sensitivity to perennial indoor allergens Assess the significance of positive tests in context of the patient’s medical history” In the management of asthma, trigger identification and control is the primary management step. The key guidelines for the management of asthma come from the National Institutes of Health’s National Asthma Education and Prevention Program,1 and in those guidelines, trigger identification is put front and center. For at least those patients with persistent asthma on daily medications, the clinician should: Identify allergen exposures Use the patient’s history to assess sensitivity to seasonal allergens Use skin testing or in vitro (blood) testing to assess sensitivity to perennial indoor allergens Assess the significance of positive tests in context of the patient’s medical history NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication LRDs

NIH Asthma Guidelines1 (cont’d)
LRDs “Use skin testing or in vitro testing to determine the presence of specific IgE antibodies to the indoor allergens to which the patient is exposed year round.” Allergy testing is the only reliable way to determine sensitivity to perennial indoor allergens.” For selected patients with asthma at any level of severity, detection of specific IgE sensitivity to seasonal or perennial allergens may be indicated as a basis for avoidance, or immunotherapy, or to characterize the patient’s atopic status.” Return to >> Third-party Perspectives The NIH NAEPP Guidelines go on to say1: “Use skin testing or in vitro (CAP RAST®) testing to determine the presence of specific IgE antibodies to the indoor allergens to which the patient is exposed year round.” Allergy testing is the only reliable way to determine sensitivity to perennial indoor allergens.” For selected patients with asthma at any level of severity, detection of specific IgE sensitivity to seasonal or perennial allergens may be indicated as a basis for avoidance, or immunotherapy, or to characterize the patient’s atopic status.” NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication NIH. Guidelines for the Diagnosis and Management of Asthma NIH publication LRDs

Knowledge of Symptom Triggers Guides Management
LRDs Allergy testing may be conducted along with pulmonary function tests and other diagnostic evaluations1 In allergic asthma: Confirm atopy and identify specific allergic triggers for avoidance counseling, symptom reduction, and control of severity and comorbid AR In non-allergic asthma: Rule out atopy to focus on possible non-allergic triggers Prevent needless control measures This slide summarizes the clinical utility of allergy testing in the management of asthma. In general, it makes sense to conduct this testing during the diagnostic process at the same time as PFTs and other evaluations.1 Then, if the test comes back positive, you can confirm that you are dealing with allergic asthma and use the report to identify specific allergens to help you in counseling for avoidance. I want to stress that this is widely considered a vital step, both to control asthma and to help manage comorbid allergic rhinitis. A negative (or normal) result is equally valuable because it will allow you to focus your evaluation on other possible, non-atopic triggers while preventing needless control measures for suspected allergens. NIH. Practical Guide for the Diagnosis and Management of Asthma NIH publication NIH. Practical Guide for the Diagnosis and Management of Asthma NIH publication LRDs

Asthma Management Options
LRDs Specific IgE-Positive/Abnormal Atopic Etiology Specific Allergen Avoidance Adequate Response Pharmacotherapy Treat AR (eg, NSAs) LTRAs Controller(s) Rescue Rx Stop Inadequate Response Referral? Specific IgE-Negative/Normal Non-Atopic Etiology Referral? Inadequate Response Adequate Response Pharmacotherapy Allergy Rx not helpful Controller(s) Rescue Rx Stop Focus on Non-allergic Triggers Let’s talk about how specific IgE test results can guide your clinical management of asthma. If the test demonstrates significant specific IgE levels, you can use the report to identify symptom triggers and counsel for avoidance of the offending allergens. Sometimes that’s all it takes to relieve the patient’s symptoms. If not, then you can try medications. Non-sedating antihistamines can be used to target comorbid allergic rhinitis (AR), which will help relieve asthma symptoms. The direct asthma pharmacotherapy includes leukotriene antagonists, controllers, and rescue medication. If, after trial of all these medications, your patient still has symptoms, then you may want to consider referral to a pulmonologist. If the allergy testing is negative or normal, you can focus your evaluation to identify non-atopic triggers. If trigger control alone doesn’t reduce symptoms, treatment options include controllers and rescue medications. It’s important to remember that, in non-allergic asthma, allergy medications are not considered helpful. Again, with an inadequate response from medications, you’ll need to consider referral.

LRDs “Bronchitis” Generally acute or chronic
The catchall diagnosis when symptom etiology is unclear1 Chronic cough: a key symptom associated with2,3: Postnasal drip (due to rhinitis, allergic rhinitis, or sinusitis) GERD Cough-variant asthma (documented as leading cause in children4) In children: atopy is the most important risk factor for wheezing, diminished lung function, and asthma5 Empirical treatment: antibiotics, bronchodilators Sometimes “bronchitis” can be the catchall diagnosis,1 even though there are some very clear diagnostic criteria for both acute and chronic bronchitis. Again, symptom overlap may be the confounding factor, and the symptom of chronic cough has proven vexing. In addition to asthma and bronchitis, chronic cough has also been implicated in postnasal drip (due to rhinitis, allergic rhinitis, or sinusitis) and gastroesophageal reflux disease.2,3 In children, the most common cause of chronic cough is a rare form of asthma known as cough-variant asthma4 (in which cough is the sole symptom). Research indicates that atopy may play a role in this form of asthma.5 Whatever the cause, chronic cough is best managed by specific therapy to treat the underlying disease.2-4 Another confounding symptom in children is wheezing. Some wheezers resolve their disease while others go on to develop more serious disease. Atopy is the key risk factor for wheezing that may persist and develop into asthma.6 (Hidden slide available here.) Bronchitis is generally treated empirically with antibiotics and bronchodilators, but as you can see, an allergy evaluation may be needed to identify and manage those catchall cases of bronchitis. Hueston WJ, Mainous AG. Am Fam Physician. 1998;57: Lawler WR. Am Fam Physician. 1998;58(9): Irwin RS, Madison JM. Am J Respir Crit Care Med. 2002;165: Holinger LD, Sanders AD. Laryngoscope. 1991;101: Zeidler MR, et al. Advance for Managers of Respiratory Care [online edition]. March 9, 2004. Martinez FD, Godfrey SG. Wheezing Disorders in the Preschool Child. New York, NY: Martin Dunitz; 2003. Hueston WJ, Mainous AG. Am Fam Physician. 1998;57: Lawler WR. Am Fam Physician. 1998;58(9): Irwin RS, Madison JM. Am J Respir Crit Care Med. 2002;165: Holinger LD, Sanders AD. Laryngoscope. 1991;101: Martinez FD, Godfrey S. Wheezing Disorders in the Preschool Child. Martin Dunitz; 2003:2-35. LRDs

Wheezing, Atopy, and Asthma
LRDs LRDs Return to previous slide Age (years) Prevalence of Childhood Wheezing1 6 3 Wheezing Prevalence 11 IgE-associated wheeze/asthma Non-atopic wheezers Transient early wheezers It’s important to remember that as Jackson said, “All that wheezes is not asthma.” In children, atopy is the most important risk factor for wheezing, as well as for diminished lung function and asthma.1 This graph, based on data by Martinez and colleagues,2 shows different types of wheezers, the general duration of wheezing, and the role atopy plays. Most infants who wheeze have no increased risk of asthma or allergies later in life. However, for a minority of infants, early wheezing episodes may be related to future asthma. These children have elevated IgE levels during the first months of life and have lung function deficits by 6 years of age. Martinez FD, Godfrey SG. Wheezing Disorders in the Preschool Child. New York, NY: Martin Dunitz; 2003. Martinez FD, et al. J Allergy Clin Immunol. 1999;104:S169-S174. Martinez FD, et al. J Allergy Clin Immunol 1999;104:S169-S174.

What Is Happening to Treatment?
Mechanism of disease is better understood Means that treatments are nearer the root cause Therapeutic specificity is increasing Diseases are different and differentiation is key The mechanism of action of drugs is more specific than ever Diagnostic precision by PCP is necessary New diagnostic technology must be employed The case for allergy testing in primary care is derived not just from the challenge of diagnosing and managing allergies, but also from the nature of the medications now used. The mechanisms of these diseases are now better understood, so the treatments are being honed to target the root cause. As a result, therapeutic specificity is increasing. Now, we need not rely merely on the resolution of common symptoms of varying etiologies—our medications can target those different etiologies with specific mechanisms of action. (Hidden slide available here.) Due to this therapeutic specificity, our diagnosis now needs to be more precise, and the best means for precision is the use of next-generation diagnostic testing. Treatment

Market Review: The Role of Diagnostics in Pharmacotherapy
Treatment Medications for Respiratory Allergy Cost Therapeutic Approach Treatment Results Mode(s) of Action Treatment Progression $ Broad (shotgun) Non-specific resolution of symptoms regardless of etiology Antihistamine effect + Anticholinergic effect 1st Generation Antihistamines (1970s) $$ Introduction of “D” formula creates less specific treatment More specific resolution of symptoms primarily due to atopic etiology — necessitates more specific diagnosis Antihistamine effect with very little anticholinergic effect Non-sedating Antihistamines (1990s) $$$ Very specific to atopy — necessitates even more accurate diagnosis (Doctors report marginal response for AR with Singulair — could be 65% are not allergic) Specific resolution of symptoms of atopy by blocking another mediator pathway Leukotriene antagonist Montelukast (2002) $$$$$$ Highly specific treatment Highly specific resolution of symptoms due to IgE response only — necessitates perfect diagnosis Binds to IgE; Suppression of IgE response Anti-IgE Vaccine (2003) This table illustrates the progression of medications used for respiratory allergies. As we move from left to right and top to bottom you will see an increasing therapeutic specificity with an associated increased cost. [Click] The first column represents the first-generation antihistamines. These had a very strong anticholinergic or drying effect, so they tended to resolve symptoms regardless of the etiology, which led us to believe that antihistamines always worked on the symptoms, no matter the underlying cause. [Click] In the 1990s we saw the emergence of non-sedating antihistamines developed to offset the drowsiness caused by the first-generation products. Well, it turns out that sedation and the anticholinergic effect are linked, so that by removing the drowsiness you also lose the broader drying effect. As a result, because these NSAs target histamine release in the allergic process, they truly are only effective in patients with atopy. Now, of course, the NSA manufacturers have developed “D” formulations that have an added decongestant for additional symptom relief, but this has broadened the drugs’ effects to permit that old “shotgun” approach. As a result, people on prescription “D” formulations are paying $85 or $90 for about $5 worth of Sudafed. [Click] Next came the leukotriene antagonists, which offer very specific resolution by targeting leukotrienes, another inflammatory and allergic mediator.[Click] Finally, there’s Xolair, the anti-IgE vaccine that’s highly specific and requires a diagnosis of IgE-mediated allergy confirmed by either a skin prick test or in vitro allergy test. This specificity comes with a high price tag. Treatment Treatment

? Disease Paradigms Diabetes Mellitus Type 2 Hypercholesterolemia
Treatment Hx & PE lab tests diet & exercise pharmacotherapy Diabetes Mellitus Type 2 lipid profile Hypercholesterolemia CHDs, URDs, LRDs ? IgE profile avoidance Blood testing is already common in primary care. In fact, some assays (such as CBC or lipid profile) are used routinely. For allergies, lab tests are rarely used and behavior modification or avoidance in this case is seldom discussed with objective evidence. As you can see in this diagram, specific IgE testing is a logical addition to your testing array, because it fits into the work-up in the same manner as the assays you regularly order for managing diabetes or hypercholesterolemia. For diabetes and hypercholesterolemia, a very consistent model is followed. You start with a thorough history and physical, order lab tests to aid management, commence primary therapy in the form of lifestyle modification, and then begin pharmacotherapy. And the same can go for allergies. Along with the history and physical, you can order a specific IgE blood profile. If positive, you can use the information contained in the report to guide lifestyle modification (in the form of allergen avoidance), and, if necessary move on to pharmacotherapy. Treatment

CAP RAST: Gain Knowledge to Guide Treatment
FDA-cleared quantitative measure of specific IgE Only a single blood draw required Covered under most insurance plans Accuracy superior to RASTTM*1 Next-generation assay offers consistently improved sensitivity,2 De facto standard, documented in >2,700 peer-reviewed publications3 In vitro blood testing and skin prick testing (SPT) viewed as interchangeable4 CAP RAST is available throughout the nation from all major reference and clinical laboratories, including Quest Diagnostics, NS-LIJ & BioReference CAP RAST offers primary care clinicians an exceedingly valuable and relatively convenient tool for use in your daily management of common illnesses and allergy-like symptoms. It’s an FDA-cleared quantitative measure of specific IgE. Unlike skin prick testing, CAP RAST requires only a single blood draw. CAP RAST is covered under most insurance plans. It offers accuracy superior to RASTTM1, which is very important: despite what you’ve been told about previous in vitro allergy test modalities and their shortcomings, CAP RAST is NOT RAST, but several generations beyond. Its enhanced accuracy and sensitivity is consistently reproducible lab to lab,2 and evidence presented in more than 2,000 peer-reviewed scientific publications has established CAP RAST as the de facto standard for in vitro allergy testing.3 In fact, in vitro blood testing and skin prick testing (SPT) are now viewed as interchangeable.4 (Hidden slide available here.) CAP RAST is available throughout the nation from clinical laboratories including Quest Diagnostics. Williams PB, et al. J Allergy Clin Immunol. 2000;105: Szeinbach SL, et al. Ann Allergy Asthma Immunol. 2001;86: Johansson SGO. Expert Rev Mol Diagn. 2004;4: Hamilton RG. In: Pediatric Allergy: Principles and Practice. Mosby-Year Book, Inc; 2003: * RAST is a trademark of Pharmacia Diagnostics. Williams PB, et al. J Allergy Clin Immunol. 2000;105: Szeinbach SL, et al. Ann Allergy Asthma Immunol. 2001;86: 3. Johansson SGO. Expert Rev Mol Diagn. 2004;4: 4. Hamilton RG. In: Pediatric Allergy: Principles and Practice. Mosby-Year Book, Inc; 2003: CAP RAST®

Solid-phase Protein Binding Capacity Comparison
CAP RAST cellulose polymer binds almost 150 times more protein than a passively coated tube, well or bead, and about 250 percent more protein than a paper disc. Compared with other materials used for solid phase immunoassays, CAP RAST has a much higher capacity to bind allergen and therefore also IgE antibodies. Solid Phase H. Drevin, 1989 A. Kober, 2004

Accuracy of Immunoassays for Specific IgE
CAP RAST® Line represents minimum acceptable R2 performance values Alastat/ 3gAllergyTM** RAST/ Modified RAST Newest generation: CAP RAST Ideal Test (Correlation Coefficient) 1.0 .82 .65 In clinical tests, CAP RAST technology has been demonstrated to be close to an ideal lab determination. In a recent study (Williams, et al., J Allergy Clin Immunol, 2000;105; ) illustrated in this slide, laboratories evaluated more than 12,000 blinded serum samples containing various levels of specific IgE, using a number of lab tests in order to compare accuracy and precision. This summary slide reflects the average standardized slope coefficients; the ideal would be The results in the study ranged from 0.65 to 0.98. The CAP RAST technology produced the best assessments ( ), performing almost as well as the ideal standard. RAST tests ranged from 0.65 to As the researchers concluded, “The Pharmacia CAP system performed well when compared with the standard of an ideal assay, although other assays often did not perform up to this standard.” *The authors noted that regression values below 0.80 reflect poor performance in the ability to correctly detect levels of specific IgE antibodies. ONLY CAP RAST had consistently acceptable regression values. **Alastat was recently replaced by 3gAllergy. Studies show 93% agreement between both methods. Williams PB, et al. J Allergy Clin Immunol. 2000;105: CAP RAST®

Poor Performance For Tests With R2 Below 0.80
“Given the dilution range used in this study, values of R-Square below approximately 0.80 generally reflect poor performance in the ability to correctly detect levels of specific IgE antibodies. Only CAP RAST had consistently acceptable R-Square values, suggesting good performance in their ability to correctly detect the concentrations of specific IgE antibodies across the different samples and allergens.” Source: Williams PB, Barnes JH, Szeinbach SL, Sullivan T. Analytical precision and accuracy of commercial immunoassays for specific IgE: establishing a standard. J Allergy Clin Immunol. 2000;105(6):

Predictive Value vs. Skin Prick Testing (SPT)*
CAP RAST Return to previous slide Performance parameters In vitro† SPT Sensitivity (%) 87.2 93.8 Specificity (%) 90.5 80.1 PPV (%) 91.1 90.1 NPV (%) 86.4 87.1 Clinical Efficiency (%) 88.8 89.2 Besides an assessment of clinical history and physical examination, the diagnosis of allergy often rests in part upon the results of skin prick tests or in vitro specific IgE blood assays. While some clinicians may have a preference for skin prick tests (in use for years before commercial in vitro allergy tests were introduced in the early 1970s), studies have shown that test results from these two methods are highly correlated.1,2 In one study, Wood et al examined the usefulness of these test methods in making the diagnosis of cat allergy.3 Reviewing test results from 120 patients, investigators assessed the sensitivity, specificity, positive and negative predictive values, and clinical efficiency of skin prick tests and in vitro allergy testing, using CAP RAST technology. As shown here, results were similar between these assays. Poon A, et al. Am J Manag Care. 1998;4: Ceska M, Lundkvist U. Immunochemistry. 1972;9: Wood RA, et al. J Allergy Clin Immunol. 1999;103: Authors concluded that CAP RAST Specific IgE blood test and SPT values both exhibited excellent efficiency1 *Adapted from Reference 1. †CAP RAST Specific IgE blood test was used in this study. 1. Wood RA, et al. J Allergy Clin Immunol. 1999;103: CAP RAST®

Profiles Carefully Designed
CAP RAST Profiles engineered to detect >95% of patients with allergy1-3 Regional respiratory profiles include key indoor/outdoor allergens selected according to: Geographic pollen patterns Regional disease prevalence Cross reactivity to other allergens in each inhalant class Allergy March profiles include key food/inhalant allergens Six foods account for 90% of food allergy reactions in children4 Inhalants include common/cross-reactive indoor and outdoor allergens Generally recommended for children ≤6 years of age, based on symptoms To aid in the process of choosing allergens for testing, Pharmacia Diagnostics has developed allergen profiles. These may include up to 20 allergens, all pre-selected based on typical patient allergy patterns and designed to provide allergy detection more than 95 percent of the time.1-4 Frequently, profiles are based on the prevalence of indoor and outdoor allergens common to particular regions: for example, pollens specific to certain geographic areas or related to diseases prevalent in isolated areas. These and other types of profiles often include inhalant allergens characterized by high cross-reactivity—that is, allergens that elicit patient sensitivity similar to certain other allergens within the same class.5 Likewise, Allergy March profiles include key food and inhalant allergens selected to reflect common allergen sensitivities in children. It is generally recommended that clinicians order the Allergy March profile for children 6 years and younger, depending on symptoms. In children older than 6 with respiratory symptoms, the URD or asthma profiles are recommended. Sampson HA, Ho DG. J Allergy Clin Immunol. 1997;100: Yunginger JW, et al. J Allergy Clin Immunol. 2000;105: Poon AW, et al. Am J Manag Care. 1998;4: AAAAI. The Allergy Report. 2000;3:69. Yman L. Botanical Relations and Immunological Cross-reactions in Pollen Allergy. 2nd ed. Uppsala, Sweden: Pharmacia Diagnostics AB; 1982:2-9. Sampson HA, Ho DG. J Allergy Clin Immunol. 1997;100: Yunginger JW, et al. J Allergy Clin Immunol. 2000;105: Poon AW, et al. Am J Man Care. 1998;4: AAAAI. The Allergy Report. 2000;3:69. CAP RAST®

Understanding Total IgE1
CAP RAST Total IgE often of little practical value when considered alone Levels rarely high when specific IgE titers are not Lacks sensitivity as a rule-out screen: Specific IgE levels may be significantly high when total IgE is low/normal Extremely high total IgE may be seen in some very rare non-atopic conditions2: Certain immunodeficiency diseases (including HIV) IgE myeloma Drug-induced interstitial nephritis Graft-versus-host disease Parasitic diseases Skin diseases in addition to eczema Hyper-IgE syndrome (dermatitis, recurrent pyogenic infection) In talking about the clinical value of specific IgE testing, it’s important to differentiate it from total IgE testing. Now, many of you have either employed total IgE testing or have heard about it. Total IgE is often of little practical value when considered alone1 because the levels are rarely high when specific IgE titers are not, and it lacks sensitivity as a rule-out screen. In other words, specific IgE levels may be significantly high when total IgE is low (or normal). [Hidden slide available here.] In addition, extremely high total IgE may be seen in some very rare non-atopic conditions,2 and you can see some of them here, including certain immunodeficiency diseases (including HIV), IgE myeloma, parasitic diseases, and some skin diseases in addition to eczema. What’s the take-away? IgE has clinical value, but it is not the only tool. Just as you would look beyond a patient’s total cholesterol (and review HDL and LDL) to ascertain his or her lipid status, it’s important to reviewspecific IgE levels to gain the whole atopy picture. Fromer LM. J Fam Pract. 2004;suppl:S4-S14. AAAAI. The Allergy Report. 2000;1:35. Fromer LM. J Fam Pract. 2004;suppl:S4-S14. AAAAI. The Allergy Report. 2000;1:35. CAP RAST®

Understanding Total IgE
CAP RAST Interpretation of Total IgE* Results Negative (Normal) Positive (Abnormal, Elevated) Non-allergic Patient Scenario A Rare1 Scenario B Allergic Scenario C Scenario D Specific IgE Reading Total IgE Reading Return to previous slide This table illustrates the key parameters for interpreting a Total IgE result. Scenario A When both specific IgE and total IgE results are negative, the patient has a very high probability of being non-allergic. When specific IgE and total IgE are normal, other causes need to be investigated as atopy can be virtually ruled out. Scenario B There are instances where total IgE is elevated and specific IgE is normal. There are several possibilities: 1) Other disease processes increase total IgE, such as in parasitic infections. 2) The profile has a very high predictive value, but is not designed to identify specific IgE to venoms, foods, or occupational allergens. It is possible that these other exposures are elevating the total IgE. Consider additional history/testing, or referral to a specialist. Scenario C, D Specific IgE is the most accurate marker for the atopic condition. In both these scenarios, we know that the patient is atopic, but what class and type of allergen is he or she sensitized to? If, for example, there is an elevated specific IgE to a weed pollen, there may well be other weed pollens that the patient is also sensitive to. Either way, we know that weeds are the culprit, so avoidance and treatment with an anti-histamine or anti-leukotriene is warranted at or prior to the onset of weed pollen in your area. *Includes URDs (Upper Respiratory Diseases), CHDs (Childhood Diseases), and LRDs (Lower Respiratory Diseases) 1. AAAAI. The Allergy Report. 2000;1:35. CAP RAST®

Third-party Perspectives
Childhood diseases EAACI AAP Upper respiratory diseases JCAAI (guidelines for chronic rhinitis) AAAAI – The Allergy Report AHRQ (Agency for Healthcare Research and Quality) Multiple textbooks Lower respiratory diseases NIH (asthma guidelines) AAFP (asthma guidelines) FDA (Xolair® indications) This slide summarizes the third-party support for specific IgE testing in primary care and for CAP RAST. As you can see, the key specialty societies and government agencies are represented here and they are arranged according to the three disease groups. (Note: the support statements listed here may only be viewed by clicking upon these links. They are not otherwise visible.) Now let’s take a look at what these experts have to say. Perspectives

From the European Academy of Allergy and Clinical Immunology1
Perspectives From the European Academy of Allergy and Clinical Immunology1 “Generally, all individuals with severe, persisting or recurrent possible ‘allergic symptoms’ and individuals with need for continuous prophylactic treatment should be tested for specific allergy regardless of the age of the child.” Return to >> Third-party Perspectives As we’ve discussed earlier, the European allergy community performed much of the early research into the Allergy March, and has long promoted early allergy testing in children. To step up the timing of such evaluations, the European Academy of Allergy and Clinical Immunology (EAACI) has mounted a campaign to encourage allergy testing by generalist pediatricians prior to or in lieu of referral to an allergist. The EAACI’s basic recommendation is spelled out here: “Generally, all individuals with severe, persisting or recurrent possible ‘allergic symptoms’ and individuals with need for continuous prophylactic treatment should be tested for specific allergy regardless of the age of the child.”1 Høst A, et al. Allergy. 2003;58: Høst A, et al. Allergy. 2003;58: Perspectives

From the American Academy of Pediatrics1
Perspectives Panel Discussion: Recent Advances in Allergy Hugh A. Sampson, MD: “The pediatrician could certainly order the blood test initially to see whether or not there were significant levels of antibody to milk, egg, or peanut in these children with atopic dermatitis….” Laurie J. Smith, MD: “It’s important to specify, however, that the only in vitro test with which such diagnostic assumptions can be made is with the CAP RAST and no other in vitro test that is available.” Return to >> Third-party Perspectives A group of experts took part in the AAP’s 2001 panel discussion, Recent Advances in Allergy.1 Hugh A. Sampson, MD: “The pediatrician could certainly order the blood test initially to see whether or not there were significant levels of antibody to milk, egg, or peanut in these children with atopic dermatitis….” Laurie J. Smith, MD: “It’s important to specify, however, that the only in vitro test with which such diagnostic assumptions can be made is with the CAP RAST and no other in vitro test that is available.” Now, in order to avoid confusion, I’d like to point out that many physicians commonly use the term RAST for many specific IgE blood tests, despite the fact that most newer-generation assays use completely different technologies. The test that Dr. Smith refers to here as “CAP RAST” is CAP RAST. AAP Pediatric Update. 2001;22:1-8. AAP Pediatric Update. 2001;22:1-8. Perspectives

From the Joint Council of Allergy, Asthma, and Immunology1
Perspectives Rhinitis should be classified by etiology as allergic or non-allergic Since approximately 50% of patients with rhinitis do not have allergic rhinitis, other potential causes must be ruled out Return to >> Third-party Perspectives The Joint Council of Allergy, Asthma, and Immunology is a combined advisory body of the American Academy of Allergy, Asthma & Immunology and the American College of Allergy, Asthma & Immunology. This combined group’s Joint Task Force on Practice Parameters in Allergy, Asthma, and Immunology issued guidelines on the diagnosis and management of rhinitis.1 These allergy experts state very straightforwardly: Rhinitis should be classified by etiology as allergic or non-allergic — Since approximately 50% of patients with rhinitis do not have allergic rhinitis, other potential causes must be ruled out Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81: Dykewicz MS, et al. Ann Allergy Asthma Immunol. 1998;81: Perspectives

From the American Academy of Allergy, Asthma & Immunology1
Perspectives “Diagnostic evaluation, including specific testing, is necessary to: Confirm the allergic diagnosis Differentiate allergic disorders from other diseases Uncover previously unsuspected allergens Guide treatment” Return to >> Third-party Perspectives In its extensive management guidelines, The Allergy Report,1 the American Academy of Allergy, Asthma & Immunology (AAAAI) has this to say about diagnostic allergy testing: “Diagnostic evaluation, including specific testing, is necessary to: – Confirm the allergic diagnosis – Differentiate allergic disorders from other diseases – Uncover previously unsuspected allergens – Guide treatment” AAAAI. The Allergy Report. 2000;1:31. AAAAI. The Allergy Report. 2000;1:31. Perspectives

From the Agency for Healthcare Research and Quality1
Perspectives From the Agency for Healthcare Research and Quality1 “Given the absence of studies to differentiate nonallergic rhinitis, diagnostic testing rather than symptoms or signs is necessary to differentiate isolated vasomotor or nonallergic rhinitis from allergic rhinitis.” Return to >> Third-party Perspectives This quotation comes from the Agency for Healthcare Research and Quality, and its evidence report, Management of Allergic and Nonallergic Rhinitis: “Given the absence of studies to differentiate nonallergic rhinitis, diagnostic testing rather than symptoms or signs is necessary to differentiate isolated vasomotor or nonallergic rhinitis from allergic rhinitis.”1 AHRQ. Management of allergic and nonallergic rhinitis. May AHRQ Pub. No. 02-E023. AHRQ. Management of allergic and nonallergic rhinitis. May AHRQ Pub. No. 02-E023. Perspectives

From the American Academy of Family Physicians1
Perspectives “Determining whether and how allergies play a role in a patient’s asthma is an important part of the clinical picture.” “Family physicians are in an ideal position to consider the full spectrum of potential allergic and non-allergic triggers in their evaluation of patients who have asthma.” “The CAP RAST serum specific immunoglobulin E (IgE) assay may also be appropriate for patients in whom skin testing is not an option….Quantitative testing…may be more useful because it identifies a patient’s specific causative allergens. CAP RAST testing is often less expensive than RAST and is a fairly simple way for family physicians to screen patients before referral to an allergist.” Return to >> Third-party Perspectives The American Academy of Family Physicians published its own asthma management guidelines in As quoted here, these guidelines are especially illuminating because they urge allergy testing in the management of asthma, encourage testing by primary care clinicians, and support CAP RAST, by name, as a diagnostic tool for the management of asthma in primary care. Here are selected portions of the guidelines: “Determining whether and how allergies play a role in a patient’s asthma is an important part of the clinical picture.” “Family physicians are in an ideal position to consider the full spectrum of potential allergic and non-allergic triggers in their evaluation of patients who have asthma.” “The CAP RAST serum specific immunoglobulin E (IgE) assay may also be appropriate for patients in whom skin testing is not an option…. Quantitative testing…may be more useful because it identifies a patient’s specific causative allergens. CAP RAST testing is often less expensive than RAST and is a fairly simple way for family physicians to screen patients before referral to an allergist.” AAFP. Asthma & Allergy Resource Guide. 2004:11-13. AAFP. Asthma & Allergy Resource Guide. 2004:11-13. Perspectives

From the U.S. Food and Drug Administration1
Perspectives Indication fo omalizumab “Omalizumab is indicated for adults and adolescents (12 years of age and above) with moderate to severe asthma who have a positive skin test or in vitro reactivity to a perennial allergen and whose symptoms are inadequately controlled with inhaled corticosteroids.” Return to >> Third-party Perspectives The Xolair anti-IgE vaccine targets the allergic process. For a prescription, the FDA requires proof of IgE-mediated allergy. Shown here is the FDA-approved indication for this medication, straight from the Xolair prescribing information1: “Xolair (omalizumab) is indicated for adults and adolescents (12 years of age and above) with moderate to severe asthma who have a positive skin test or in vitro reactivity to a perennial allergen and whose symptoms are inadequately controlled with inhaled corticosteroids.” 1. Xolair (omalizumab) Prescribing Information. * Xolair is a registered trademark of Genentech, Inc. and Novartis Pharmaceuticals Corporation. 1. Xolair (omalizumab) Prescribing Information. Perspectives

Summary Diagnostic precision leads to evidence-based medical care
Improves patient care Creates better patient satisfaction Provides more appropriate referrals CAP RAST Specific IgE blood test is an accurate test to differentiate atopic from non-atopic patients Experts, specialty organizations, and government agencies support allergy testing in primary care In conclusion, we’ve explored the full range of allergic diseases commonly managed by primary care clinicians. In managing these cases, diagnostic precision leads to evidence-based medical care. As a result, we can improve patient care, create better patient satisfaction, and provide more appropriate referrals. The CAP RAST® Specific IgE blood test is an accurate assay for differentiating atopic from non-atopic disease, and is, therefore, an excellent tool for evidence-based primary care. Finally, I’d like to stress that allergy experts, specialty organizations, and government agencies all support allergy testing in primary care. Now I’d be happy to answer any questions before we open up the discussion. Thanks for listening. Summary

URD Inhalant Panel Interpretation Of Results

Allergy and Asthma: Improving Outcomes in Primary Care

Similar presentations

Presentation on theme: "Allergy and Asthma: Improving Outcomes in Primary Care"— Presentation transcript:

Similar presentations

About project

Feedback

Log in

Auth with social network:

Allergy and Asthma: Improving Outcomes in Primary Care

Similar presentations

Presentation on theme: "Allergy and Asthma: Improving Outcomes in Primary Care"— Presentation transcript:

Similar presentations

About project

Feedback