1. Tips for Caring for Patients with Reactive Airways Jason E. Knuffman, MD Allergy October 27, 2004

2. Objectives for CME Review the goals of asthma care Review the fundamental therapeutic options for asthmatics Recognize allergic asthmatic patients who would potentially benefit from referral to a specialist This talk has not been sponsored by any organization

3. Outline Impact of Asthma Goals of Therapy Conventional Treatment of Asthma Allergic Asthma Referral Indications

4. Impact of Asthma 15 million persons with asthma in U.S. 4.8 million children – most common chronic disease of childhood 478,000 hospitalizations and 4,400 deaths per year –A disproportionate rate among African American and Hispanic populations Middleton

5. Goals Identify asthma triggers Correct inhaler or device technique Focus on long-term control of symptoms Maintaining normal daily activities, including exercise Minimize ER or urgent care visits No medication side effects Recognize signs of impending exacerbation and execute action plan Education Middleton

6. Conventional therapy Environmental control –Need to identify what patient is allergic to by skin or serum testing –Identify respiratory irritants (cigarette smoke, pollutants, perfumes etc.) –Aspirin sensitivity –Vigorous attempts at smoking cessation are considered first-line therapy equivalent!!! Middleton

7. Environmental Control cont… House dust mite (HDM) measures –Removal of carpet, upholstered furniture –Mattress and pillow encasements (~$100) –Routine hot-water washing of bedding –Humidity <50% –Less useful options are HEPA filters and other air filters (not recommended) For pets, avoidance is key –Periodic exposure exception Middleton

8. Pharmacotherapy Two key goals of therapy: –Reduce airway inflammation –Improve symptom control

9. NAEPP

11. Controller Medications Daily usage: –Inhaled Corticosteroids –Long acting ß-2 agonists –Methylxanthines –Mast Cell Stabilizers –Leukotriene Modifiers

12. Pharmacotherapy Inhaled Corticosteroids (ICS) –Drugs of choice for management of persistent asthma –Strong data from randomized, double-blinded, placebo controlled trials in children and adults supports their efficacy –Compared to short-acting ß2 agonists¹ alone without a controller med Improvements in pre-bronchodilator FEV1 Reduced airway responsiveness Reduced symptom scores and frequency Fewer courses of oral corticosteroids (OCS) Lower hospitalization rates ¹ Childhood Asthma Management Program trial et al from 2002 update

13. Comparing ICS to other controllers Long acting ß agonists vs. ICS –¹Those using salmeterol as monotherapy had deterioration in FEV1 over time Theophylline vs. ICS –²ICS reduced symtoms,supplemental bronchodilators, OCS needs, bronchial hyperresponsiveness and eosinophilia –No outcomes were improved with theophylline –May get small steroid-sparing effect ¹Verberne et al.1997; ²Reed et al 1998

14. Comparing ICS to other Controllers Nedocromil –¹CAMP trial found no difference between nedocromil and placebo in: Lung function Symptom scores –Nedocromil DID reduce use of OCS and reduced number of urgent care visits over placebo –Results strongly favored ICS over nedocromil when they were compared on all endpoints ¹CAMP data

15. Pharmacotherapy Leukotriene Modifiers –5-lipoxygenase inhibitors (zileuton-discontinued) –Leukotriene receptor antagonists (zafirlukast and montelukast) –Add-on therapy to ICS –If used as monotherapy, there has been shown to be modest improvement in lung function in adults and children compared to placebo –Again, ¹ICS significantly and clearly favored over LTRA’s in persistent asthma ¹Busse et al, 2001

16. Pharmacotherapy Mast Cell Stabilizers –Nedocromil and cromolyn –Used for preventative purposes only –Could be considered for treatment of persistent asthma –NOT preferred, though

17. Pharmacotherapy Long Acting ß agonists –¹164 patients ages 12-65 with well controlled asthma on ICS Randomized to continued ICS vs. LABA 16 week study LABA group had more treatment failures (24% vs. 6%) LABA group with more exacerbations (20% vs 7%) –Evidence supports steroid-sparing effect –Can be useful for exercise-induced bronchospasm ¹Lazarus et al 2001

18. Rescue Medications As-needed usage: –Short acting ß agonists –Oral corticosteroids

19. Pharmacotherapy Short-acting bronchodilators –Numerous tradenames Albuterol, pirbuterol –Drug of choice for “rescue”purposes –NOT for scheduled usage –Usage reflects control –Can be used as monotherapy in exercise- induced asthma

20. Pharmacotherapy Oral Glucocorticoids –The most potent treatment for asthma symptoms Decrease inflammatory cell function and activation Stabilize vascular leakage Decrease mucus production Increase B-adrenergic response –Work by binding intracellular glucocorticoid receptors and inhibiting transcription of target genes Middleton

21. Oral Glucocorticoids, cont… Can be used as a ‘short burst’ to win back control of asthma symptoms –ie, prednisone 10mg bid-tid for 5-7 days, then stop – warn of usual SE’s (increased appetite, sporadic glucose readings, psychiatric etc…) Consider methylprednisolone usage if psychiatric SE’s are a concern –Keep prednisone ‘burst supply’ at home – a good idea with compliant patients

22. NAEPP

23. Miscellaneous Topics Exercise-induced bronchospasm Severe, life-threatening asthma PREGNANCY…

24. Asthma in Pregnancy New guidelines are forthcoming – November 2004 nhlbiinfo@nhlbi.nih.gov http://www.nhlbi.nih.gov/about/naepp/ National Asthma Education and Prevention Program

25. Allergic Asthma Allergen immunotherapy Anti-IgE therapy

26. Allergen IT Immunotherapy for allergic rhinitis has clearly proven useful IT for asthma demands more carefully selected candidates, and in correct setting is also very effective IT is a long-term commitment for the patient –Weekly buildup, initially –Monthly maintenance thereafter –Usually continue shots for 3-5 years Middleton

27. Allergen IT ¹No new randomized, controlled trials for IT literature in adult asthmatics over last 5 years ²Cochrane Airways Group selected RC trials using allergen-specific IT to treat asthma –75 trials, 3,506 participants –Various antigens used –There was observed an overall significant reduction in asthma symptoms and medication usage as well as improvement in bronchial hyperreactivity with IT NNT=4 to prevent 1 patient with worsening symptoms NNT=5 to prevent 1 patient from requiring increased meds ¹Norman 2004 ²Abramson 2003

28. ²Abramson 2003Abramson 2003

30. Anti IgE Omalizumab

31. Busse and Lemanske 2003

32. Anti-IgE Therapy Omalizumab (Xolair) –Approved in 2003 for moderate to severe asthma –Monoclonal antibody, binds IgE –Shown to reduce asthma exacerbations –Reduces need for oral CSs and reduces dose of ICSs Rambasek et al 2004

33. Omalizumab, cont… Indications: –Perennial allergic asthma (positive skin testing perennial allergens such as dust mites, cats, dogs, cockroaches) –IgE level between 30 and 700 IU/ml. –12 yo and older Rambasek et al 2004

34. Omalizumab cont… Busse et al, RPCDB trial –525 patients with severe allergic asthma, poorly controlled, requiring daily ICS –placebo or omalizumab –kept constant dose of ICS for 16 weeks, then 12 week taper –primary outcome: # of asthma exacerbations –secondary outcome: mean reduction of ICS dose Busse et al. JACI 2001; 108: 184-90.

35. Busse et al

38. Omalizumab, cont… Administration: –Dosed by formula incorporating body weight and IgE level –Subcutaneously, every 2-4 weeks depending on the dose –Need to monitor in office for urticaria (2-3%) or anaphylaxis (0.01-0.1%) –Average cost between $5,000 and $25,000 per year Rambasek et al 2004

39. Referral Indications Is it asthma? Allergic component Significant morbidity, altered lifestyle Steroid-dependent Overuse of beta agonists Education

40. Conclusion Impact of Asthma Goals of Therapy Conventional Treatment of Asthma Allergic Asthma Referral Indications

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