Allergy, Asthma and Immunotherapy Give Your Patients Back Their Lives S545v2

Facts & Figures Over 60 million people in the US suffer from allergies If you have allergies, you may have undiagnosed asthma or be at risk for developing it Asthma is diagnosed in 7% of the population and is on the rise 80% of patients with asthma have allergic symptoms More than 20% of children with allergic symptoms develop asthma Allergy and asthma are more common in industrialized nations Asthma is the 6 th most common primary care diagnosis

How Does Allergy Work? The type of antibody responsible for allergy is IgE. IgE is thought to have evolved to recognize parasitic infections, such as intestinal worms. Bacterial infections are recognized by another antibody, IgG, which has a different, non-allergic, response. So, to an allergic immune system, a harmless protiean is the same thing as a parasitic infection. This is referred to as a Type I Allergy (IgE-Antibody-Dependent) –There are other types of allergy (Type II, III, etc), but these have different mechanisms and are not relevant to our topic.

symptoms Type I Allergy Sensitization (Complex View) Initial immune exposure –Allergen encountered –T cells activated (Th2) –IgE produced towards allergen –Mast cells bind circulating IgE Subsequent exposure –Allergen binds IgE on mast cells –Mast cells release chemicals that cause immune response: Histamine Leukotrienes prostaglandins Organ-specific reaction (local) Peripheral reaction (systemic)

The Hygiene Hypothesis – The cause? Based on global population studies, rates of allergy are much lower in poor countries that lack advanced sanitation and have more parasitic infections. When advanced sanitation is developed, these infections decline. However, the body’s ability to recognize and respond to these infections does not disappear. Instead, IgE simply reacts to other proteins the body is exposed to (pollen, cat hair, etc). This leads to a widespread pattern of unnecessary immune responses (allergy) in societies that have advanced sanitation. Therefore, rates of allergy and asthma are much higher in modern, wealthy societies.

What is Asthma An inflammatory disease of the airways Triggered by many factors including allergens, environment, infections, and other irritants Most common symptoms: –Wheezing and dry cough –Increased mucus production –Bronchospasm and airway constriction Severity levels vary and can be measured by degree of decreased pulmonary function

Diagnosing Asthma Severity Mild intermittent asthma: Symptoms rarely occur and only after above normal levels of activity Mild persistent asthma: Symptoms occur <1/day and only exacerbated by activity Moderate persistent asthma: Daily symptoms and routine activities become difficult. Oral corticosteroids needed. Severe persistent asthma: Continual symptoms, must limit activity and many “attacks” occur. Additional daily treatments needed. Krouse, J, et al. OTO – Head & Neck Surgery 2007;136:S75-S106

Differential Diagnosis These conditions can be confused with asthma symptoms and should be considered during evaluation –COPD –Pulmonary fibrosis –Tumors –Infections –GERD

Between 1980 and 1998, reported cases of asthma doubled in the U.S. The prevalence of asthma is consistently higher in children. CDC, Forecasted state-specific estimates of self-reported asthma prevalence – United States, 1998; MMWR 1998;47(47):

The Cost of Asthma In 2007, the average annual medical cost for an asthmatic patient was ~ $1,300 and continues to rise. While only 10-20% of patients have severe asthma, this accounts for over 50% of all asthma costs. Annual medical costs are 46% higher in patients with associated asthma and allergic rhinitis. In any given 12-month period there are: –14 million lost school days –20 million missed work days –20 million outpatient visits –1.8 million ED visits –5,000 deaths Krouse, J, et al. OTO – Head & Neck Surgery 2007;136:S75-S106

Is Asthma Really Under Control? Relying on patient reports could overestimate the level of control. Patients often overestimate their pulmonary function when compared to peak flow results. This affects compliance with medication. Symptom management often misses underlying issues like allergies. Be Proactive. Don’t wait for symptoms to present themselves. Krouse, J, et al. OTO – Head & Neck Surgery 2007;136:S75-S106

Linking Allergies with Asthma Allergy is one of the main triggers of asthma and is often a precursor. There is a significant correlation between the severity of allergic rhinitis and the ability to control asthma. Exposure to allergens can cause rapid onset of bronchospasm. Doctors frequently overlook the allergic trigger in asthmatic patients or the asthmatic potential in allergic patients. Vinuya, R. Ann Allergy Asthma Immunol 2002;88(Suppl):8-15 Krouse, J, et al. OTO – Head & Neck Surgery 2007;136:S75-S106

The Unified Airway - Linking Allergies and Asthma Inflammation in the upper respiratory tract Inflammation in the lower respiratory tract Isolated irritants in one part of the respiratory system have been shown to cause inflammation in distant parts, suggesting a common inflammatory pathway. Vinuya, R. Ann Allergy Asthma Immunol 2002;88(Suppl):8-15 Ricca, V, et al. J Allergy Clin Immunol 1999;104:54-57 Serrano, C, et al. Arch Bronconeumol 2005;41(10):

Allergens Causing Asthma? Chronic allergens can drastically increase the risk of developing asthma in vulnerable patients: –Dust Mites –Molds –Pets (Hair & Dander) –Cockroaches Allergic responses to these allergens can also be interpreted as uncontrolled asthma, which masks the underlying cause and delays adequate treatment. Vinuya, R. Ann Allergy Asthma Immunol 2002;88(Suppl):8-15 Gaffin, J, & Phipatanakul, W. Curr Opin Allergy Clin Immunol 2009;9(2):

Important Tests for Potential Immunotherapy Patients Allergy –The patient’s allergic response must be diagnosed as Type I hypersensitivity (IgE antibody mediated) through skin or in-vitro testing. –Skin test results can be used as an immediate educational tool to illustrate the impact of different allergens to the patient. Respiratory –An objective evaluation of patient lung function establishes a baseline for monitoring disease progression –Commonly done with Peak Flow and Spirometry –Requires patient and staff training to implement effectively

Controlling the Allergy Trigger Avoidance –Can be effective if used in combination with treatment –However, many allergens are essentially unavoidable Symptomatic treatment (e.g. Antihistamines) –Provides immediate relief –However, doesn’t change the underlying cause of the symptoms. –Relief only lasts as long as the patient is compliant. Immunotherapy –Changes the underlying immune response to the allergen –Provides long-term relief –May see a positive impact within 3-6 months Serrano, C, et al. Arch Bronconeumol 2005;41(10):

Immunotherapy and Asthma Allergy Immunotherapy (IT) has been shown to –Reduce allergic rhinitis thus improving asthmatic symptoms –Reduce the need for asthma medications –Reduce general inflammation in the airways over time –Drastically slow or halt the progression of asthmatic disease In numerous clinical studies, subjects reported significantly fewer asthma symptoms and required less asthma medication than the placebo group. Experts found that IT was effective in treating allergic asthma in 71% of patients. Passalacqua, G, & Durham, S. J Allergy Clin Immunol 2007;119: Abramson, M, et al. Allergy 1999;54: Ross, R, et al. Clin Ther 2000;22: Jacobsen, L, et al. Allergy 2007;62:

“Immunotherapy is the only treatment that influences the basic course of allergic disease” World Health Organization (WHO) Position Paper, 1998

Recommendations of the Allergic Rhinitis and Its Impact on Asthma (ARIA) Workshop Group Patients with persistent rhinitis should be assessed for the presence of asthma. Patients with persistent asthma should be assessed for the presence of rhinitis. An appropriate therapeutic strategy should combine safe and effective management of the upper and lower airways. RHINITIS ASTHMA Nasal Corticosteroids Antihistamines Inhaled Corticosteroids Education and Measures to Avoid Exposure to Allergens Immunotherapy Adapted from: Serrano, C, et al. Arch Bronconeumol 2005;41(10):

Refer to An Allergist National Asthma Education and Prevention Program guidelines recommend that patients who require daily asthma medication be considered for allergy testing. If a patient’s allergies can not be controlled, and they are a candidate for immunotherapy, they should be referred to an Allergist. Platts-Mills, T, et al. Am Fam Physician 2007;76:

Asthma Candidates for Immunotherapy The patient’s allergic response is a major component of his/her asthma symptoms There is clear evidence that the patient is exposed to, and symptomatic towards, unavoidable allergens Symptoms are chronic and persistent Patient requires daily asthma medications Patient is interested in treatment options besides medication Platts-Mills, T, et al. Am Fam Physician 2007;76:

Immunotherapy Precautions IT does not provide immediate improvement IT can be dangerous, resulting in anaphylaxis in some patients Patients with uncontrolled asthma should NOT be given IT since they are more likely to have severe adverse reactions

Summary Asthma is a complex disease, influenced by many factors Since asthma shares a common inflammatory pathway as allergic rhinitis, with significant comorbidity, both conditions should be addressed simultaneously. In some asthma patients, immunotherapy may be an effective treatment option.