Tips for Caring for Patients with Reactive Airways

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

10. 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 2003 Abramson 2003

29. Abramson 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

36. Busse et al Busse et al

37. 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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