Taking Control of Asthma Through Proper Medication Selection and the Use of Asthma Action Plans Julie M. Koehler, Pharm.D., FCCP

Taking Control of Asthma Through Proper Medication Selection and the Use of Asthma Action Plans Julie M. Koehler, Pharm.D., FCCP Associate Dean for Clinical Education and External Affiliations & Professor of Pharmacy Practice, Butler University College of Pharmacy & Health Sciences & Ambulatory Care Clinical Pharmacist, Adult Ambulatory Care Center / Methodist Hospital, Indiana University Health

Objectives State the general recommendations for stepwise approach to asthma therapy as recommended by the 2007 NIH guidelines put forth by the NAEPP. Applying the 2007 NIH NAEPP guidelines, formulate a patient-specific therapeutic plan for both initial and ongoing medication therapy management of a patient with chronic asthma. Given the frequency of day and nighttime symptoms, classify a patient s asthma as either well controlled, not well controlled, or very poorly controlled, according to the 2007 NIH NAEPP guidelines.

Objectives Discuss the general process for providing asthma education: Explain what is meant by good asthma control; Explain how and when to take asthma medications; Explain how to monitor asthma symptoms and level of asthma control; and Develop a patient-provider partnership in asthma care through the use of the written Asthma Action Plan.

Asthma Statistics 7 million children and 18.7 million adults with asthma in the U.S. 1 in 13 children and 1 in 11 adults in Indiana >30,000 ED visits per year in Indiana related to asthma in 2010; 38% among children >8,000 asthma-related hospitalizations in 2010 Hospitalization (4x) and death (2.5x) more likely in African Americans 44.7% of school-age children with asthma missed school due to poor asthma control between 2006 and 2010 34.7% of adults with asthma in Indiana missed work or experienced limitations in activities due to poor asthma control in 2010 Only 47.7% of children and 28.6% of adults with asthma in Indiana had a written Asthma Action Plan during 2006-2010 www.chronicdisease.isdh.in.gov

Initial Classification of Asthma Severity Severity = Intrinsic intensity of the disease Must consider: Impairment (Present) Frequency and intensity of symptoms Impact on quality of life Risk (Future) Exacerbations Loss of pulmonary function Risk of ADRs Clinically, classification of severity is most useful for initiating controller therapy

Classification of Severity: 1997/2002 vs. 2007 NIH Recommendations 1997/2002 (EPR-2) Mild Intermittent 2007 (EPR-3) Intermittent Mild Persistent Mild Persistent Moderate Persistent Moderate Persistent Severe Persistent Severe Persistent

Perception of Risk of Death from Childhood Asthma is Underestimated Clinical Assessment of Asthma Severity in Children with Asthma Who Died 40 33 31 36 Deaths (%) 30 20 10 0 Mild Moderate Severe Robertson CF et al. Pediatr Pulmonol 1992; 13: 95-100.

Goals of Therapy: Decreasing Impairment Prevent symptoms No need for reliever medications (2x or less per week) No daytime symptoms (2x or less per week) No nighttime symptoms (2x or less per week) Maintain normal pulmonary function Maintain normal activity/lifestyle No limitations in daily activities No limitations in exercise Meet patients and families expectations EPR-3

Goals of Therapy: Decreasing Risk Prevent recurrent exacerbations Decrease ED visits and hospitalizations Prevent progressive loss of lung function Achieve maximal pharmacotherapeutic benefit with minimal side effects / ADRs EPR-3

1997 NIH Asthma Guidelines: Concepts Still Applicable Today NEW CONCEPTS INTRODUCED IN 1997 Major emphasis on: Meeting patients expectations Providing patient education Developing a written, long-term action plan Using peak flow meters Avoiding asthma triggers

1997 NIH Asthma Guidelines: Concepts Still Applicable Today NEW CONCEPTS INTRODUCED IN 1997 New classification of drugs: quick relief vs. bronchodilators long-term control vs. anti-inflammatories Quick relief drugs are for TREATMENT! Long-term control drugs are for PREVENTION!

Classification of Meds Quick Relief Short-Acting ß 2 - Agonists Anticholinergics Systemic Corticosteroids Long-Term Control Inhaled Corticosteroids Mast Cell Stabilizers Long-Acting ß 2 -Agonists Methylxanthines Leukotriene modifiers Immunomodulators

General Approach to Treatment: Focus on Long-Term Control Inflammation plays a primary role in the pathogenesis of asthma Prevention and suppression of underlying inflammation: reduction of bronchial hyperresponsiveness prevention of airway remodeling improvement in long-term control and outcomes

Effects of Inhaled Corticosteroids on Inflammation E = Epithelium BM = Basement Membrane Pre and post 3-month treatment with budesonide (BUD) 600 mcg b.i.d. Laitinen. J Allergy Clin Immunol.1992;90:32-42.

Corticosteroids Inhaled Beclomethasone dipropionate (QVAR ) Budesonide (Pulmicort Flexhaler TM, Pulmicort Respules ) Ciclesonide (Alvesco ) Flunisolide (Aerobid, Aerospan ) Fluticasone (Flovent Diskus, Flovent HFA) Mometasone furoate (Asmanex ) Combination products containing steroid + LABA (Advair Diskus, Advair HFA, Symbicort, Dulera ) Systemic Methylprednisolone (Solu-Medrol, Medrol ) Prednisolone (Prelone, Orapred, Orapred ODT, Pediapred ) Prednisone (Deltasone )

Corticosteroid Indications Inhaled CS Long-term prevention of symptoms in mild, moderate, and severe persistent asthma Suppression, control, and reversal of inflammation Reduction of need for systemic CS Systemic CS Long-term prevention of symptoms in severe persistent asthma

Corticosteroid Mechanism of Action Anti-inflammatory Action: reduction in synthesis and release of proinflammatory cytokines reduction in inflammatory cell activation, recruitment, and infiltration reduction in vascular permeability Effect on Beta-receptors: increase in number of receptors improve receptor responsiveness to adrenergic stimulation

Growth Suppression with Inhaled Corticosteroids Precaution in PI of INH CS about possible growth suppression More likely with higher doses Is adult height affected? (i.e., does catchup growth occur?) Recommend use of lowest effective dose

Growth Suppression with Inhaled Corticosteroids 142 budesonide-treated children with asthma followed for average of nine years until adult height attained Compared to two control groups Significantly less growth noted during first two years of treatment with budesonide No overall differences in mean adult height noted Agertoft J, Pederson S. N Engl J Med 2000; 343: 1064-1069. 943 patients randomized to receive budesonide, nedocromil, or placebo x 4-6 yrs; followed for average of eight years until adult height attained (mean age 25 yrs) Significantly less growth noted during first two years of treatment with budesonide Mean adult height significantly lower (1.2cm) in budesonide group Kelly HW et al. N Engl J Med 2012 Sep 3; [Epub ahead of print].

Adverse Effects of CS Cough, dysphonia Oral thrush (candidiasis) Systemic effects (more likely to occur with high-dose corticosteroids) adrenal suppression/growth suppression osteoporosis skin thinning/easy bruising weight gain/fluid retention

Tips for CS Users Benefits of INH CS generally outweigh potential risks of adverse effects To reduce adverse effect potential: Administer INH CS with spacer (if using MDI)! Rinse mouth thoroughly following inhalation! Use lowest effective CS dose Consider adding a long-acting beta-agonist to low-tomed. dose of INH CS before maximizing INH CS dose Monitor growth in children Consider osteoporosis prophylaxis in adults

Available Product: cromolyn sodium (Intal ) Indications: Mast Cell Stabilizers Long-term prevention of symptoms Preventive treatment prior to exposure to exercise or known allergen Anti-inflammatory Mechanisms: stabilize mast cell membranes inhibit activation and release of inflammatory mediators from eosinophils block early and late reaction to allergen inhibit acute response to exercise, cold air, sulfur dioxide

Mast Cell Stabilizers Overall, extremely well-tolerated 15% to 20% of patients complained of unpleasant taste with nedocromil (removed from market due to low use) Overall, safety profile has been cited as the primary advantage of these agents...

Mast Cell Stabilizers Effective anti-inflammatory agents for mildpersistent asthma Have been used as alternatives to INH CS in patients where there is concern for toxicity (e.g., in pediatric patients) Can be used for exercise- or known allergeninduced bronchospasm Lack of recent evidence to suggest benefit over INH CS, or INH CS + other Tx; therefore, not preferred treatment (EPR-3)

Long-Acting Beta 2 -Agonists Products Approved for Asthma: Salmeterol (Serevent ) Formoterol (Foradil ) Albuterol Sustained-Release Tablets* Indications for Salmeterol & Formoterol: Long-term prevention of symptoms (especially nocturnal symptoms) IN ADDITION TO ANTI- INFLAMMATORY AGENTS Prevention of exercise-induced bronchospasm *Inhaled long-acting Beta 2 -Agonists are preferred over sustained-release tablets due to fewer side effects and longer duration of action.

Albuterol vs LABA s: Pharmacokinetics Albuterol Salmeterol Formoterol Onset 5 min 20 min 5 min? Duration 4-8 hrs 12 hrs 12 hrs LABA s should not be used to treat acute symptoms!

Salmeterol + Beclomethasone: Early Evidence of Benefit Salmeterol 50mcg bid + Beclomethasone 200mcg bid vs Beclomethasone 500mcg bid Similar asthma exacerbation frequency Greater improvement in salmeterol + beclomethasone group: Symptoms of asthma Symptoms requiring additional bronchodilators PEFR in am and pm nocturnal awakening Greening et al., Lancet 1994

Salmeterol + Beclomethasone Change in PEF (L/min) 35 30 25 20 15 10 5 0-5 -10 Change in PEF (am & pm) Over 6 Months 1 5 9 13 17 21 Sal/Bec AM Sal/Bec PM Bec AM Bec PM Weeks of Treatment Greening et al., Lancet 1994

Salmeterol + Beclomethasone: Defining the role of LABA s CONCLUSION Adding a long-acting ß 2 -adrenergic agonist to INH CS treatment may be more effective than increasing the dose of INH CS. Greening et al., Lancet 1994

Salmeterol + Fluticasone Propionate (FP) vs Increased-Dose FP Salmeterol 42 mcg b.i.d. + FP 88 mcg b.i.d. (n = 221) FP 88 mcg b.i.d. (n = 437) Follow-up 2-4 week run-in FP 220 mcg b.i.d. (n = 216) 6-month treatment period Condemi JJ, et al. Ann Allergy Asthma Immunol. 1999;82:383-389.

AM Peak Expiratory Flow Salmeterol 42 mcg b.i.d. + FP 88 mcg b.i.d. FP 220 mcg b.i.d. 60 50 * * * * * 40 * 30 20 10 0 *P < 0.001 0 1-4 5-8 9-12 13-16 17-20 21-24 Condemi JJ, et al. Ann Allergy Asthma Immunol. 1999;82:383-389. Weeks of Treatment

Percent of Days Without Albuterol Days Without Albuterol (%) 70 60 50 40 30 Salmeterol 42 mcg b.i.d. + FP 88 mcg b.i.d. * * * * FP 220 mcg b.i.d. * * 20 10 *P < 0.001 0 1-4 5-8 9-12 13-16 17-20 21-24 Condemi JJ, et al. Ann Allergy Asthma Immunol. 1999;82:383-389. Weeks of Treatment

Change in Percent of Symptom-Free Days Salmeterol + FP 88 mcg b.i.d. FP 220 mcg b.i.d. 35 30 * * 25 20 15 * 10 *P 0.001 P < 0.014 5 0 1-4 5-8 9-12 13-16 17-20 21-24 Condemi JJ, et al. Ann Allergy Asthma Immunol. 1999;82:383-389. Weeks of Treatment

LABA Use in Children Salmeterol (Serevent Diskus ) FDA approved for prevention of bronchospasm and EIB in children as young as 4 years of age Dosage: one inhalation every 12 hours Formoterol (Foradil Aerolizer TM ) FDA approved for prevention of bronchospasm and EIB in children as young as 5 years of age Dose: one 12mcg capsule via inhalation every 12 hours

Current Controversy in Asthma Management: LABA Safety Profile Salmeterol Multi-center Asthma Research Trial (SMART) Compared the safety of salmeterol to placebo in patients with asthma over the course of 28 weeks RESULTS: Death-Rate Salmeterol-treated group: 13/13,176 patients Placebo-treated group: 3/13,179 patients Difference not significant Trial discontinued early CONCLUSION: Salmeterol may increase the risk of asthma-related death www.fda.gov/medwatch/safety/2003/serevent.htm

SMART Results: Important Considerations Differences in Ethnic Groups: 71% of the study population were Caucasian No significant difference in deaths between salmeterol vs. placebo 17% of the study population were African American Statistically significant greater number of events (including death) in salmeterol treated group vs. placebo More severe asthma at baseline in African American group www.fda.gov/medwatch/safety/2003/serevent.htm

SMART Results: Important Considerations Differences in Use of Inhaled Corticosteroids: 47% overall; 50% Caucasians; 38% African Americans No significant difference in deaths among those receiving inhaled corticosteroids Statistically significant difference (salmeterol > placebo) in those NOT receiving inhaled corticosteroids www.fda.gov/medwatch/safety/2003/serevent.htm

Current Controversy in Asthma Management: LABA Safety Profile The Black Box Warning: LABA s should ONLY be used as additional therapy for patients not adequately controlled on other asthmacontroller medications LABA s are NOT a substitute for inhaled corticosteroids LABA s should NOT be used to treat acute symptoms LABA s should NOT be initiated in patients with significantly worsening or acutely deteriorating asthma, which may be a life-threatening condition

Most Recent FDA Advisory on LABA Use Issued Feb. 18, 2010 The use of LABAs is contraindicated without the use of an asthma controller medication such as inhaled corticosteroid. Single-agent LABAs should only be used in combination with an asthma controller medication; they should not be used alone; LABAs should only be used long-term in patients whose asthma cannot be adequately controlled on asthma controller medications; LABAs should be used for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved. Patients should then be maintained on an asthma controller medication. Pediatric and adolescent patients who require a LABA in addition to an inhaled corticosteroid should use a combination product containing both an inhaled corticosteroid and a LABA to ensure compliance with both medications. http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm200931.htm

Post-EPR-3 Study on LABA Use in Children In a RDB triple-crossover trial, three step-up therapies evaluated in 165 children, ages 6 17 years who were poorly controlled on low-dose fluticasone (100mcg BID) alone: Step-up ICS to fluticasone 250mcg BID Low-dose ICS plus step-up with LABA 50mcg daily Low-dose ICS plus step-up with LTRA 5-10mg daily Primary Outcome = composite of change in FEV1, oral steroid use, and # of asthma-control days Results: 98% of children experienced improved asthma control; LABA best overall Tx response LABA vs. LTRA, 52% vs. 34% LABA vs. ICS, 54% vs. 32% Lemanske RF Jr et al. N Engl J Med. 2010;362:975.

Methylxanthines Available Products: Theophylline (sustained-release tablets and capsules) Indications: Long-term control and prevention of symptoms, especially nocturnal symptoms Mechanism: smooth muscle relaxation/bronchodilation via inhibition of phosphodiesterase

Potential Adverse Effects of Methylxanthines Effects associated with therapeutic doses: Insomnia GI upset/potentiation of gastroesophageal reflux possible hyperactivity in children Effects associated with toxic doses (dose-related): tachycardia, tachyarrhythmias nausea and vomiting CNS stimulation headache seizures hypokalemia

Methylxanthines: Place in Therapy Due to availability of better agents, theophylline is considered a third/last-line (adjunctive) drug Overall, relatively weak bronchodilating properties Lacks clinically important anti-inflammatory properties (?) Difficult to use: numerous potential drug interactions serum concentration monitoring mandatory (narrow therapeutic range: 5-15mcg/mL)

Leukotriene Modifiers Available Products: Zafirlukast (Accolate ) Zileuton (Zyflo, Zyflo CR TM ) Montelukast (Singulair ) Indication: Long-term control and prevention of symptoms in persistent asthma

Leukotriene Pathway 5-Lipoxygenase Zileuton (Zyflo, Zyflo CR TM ) Arachidonic Acid LTA 4 FLAP LTB 4 LTC 4 LTD 4 LTE 4 Chemotaxis Immunomodulation Zafirlukast (Accolate ) Montelukast (Singulair ) Bronchoconstriction Mucus secretion Edema Hyperresponsiveness Eosinophilia Holgate ST et al. J Allergy Clin Immunol 1996; 98: 1-13.

Drug Inter actions General Comparison of Leukotriene Modifiers Consideration Zafirlukast Zileuton Montelukast (Accolate ) (Zyflo, Zyflo CR TM ) (Singulair ) Age > 5 years > 12 years > 1 year Usual Dose 20mg bid (adults and children > 12 yrs); 10 mg bid (children 5-11 yrs) 600 mg qid (immed. release) 1200 mg bid (controlled release) 10mg qhs(adults) 5mg chewable qpm (kids 6-14 yrs); 4mg chewable or granules qpm (kids 1-5 yrs) None Warnings? Churg-Strauss Increased LFTs? LFTs (monitoring req d) Metabolism P450: 3A4, 2C9 P450: 1A2, 3A4, 2C9 P450: 3A4, 2C9 Dosing Considerations Empty stomach (food abs 40%) Within 1 hr of meals (CR) None

Low-Dose Fluticasone vs. Oral Montelukast for First-Line Treatment of Persistent Asthma Fluticasone 44 mcg b.i.d. (MDI) Run-in (n = 271) Pts remaining symptomatic while taking short-acting betaagonists Montelukast 10 mg daily (n = 262) 8-14 days Busse W, et al. J Allergy Clin Immunol 2001;107:461-8. 24 weeks

Low-Dose Fluticasone vs. Oral Montelukast for First-Line Treatment of Persistent Asthma 25 20 Fluticasone Montelukast * * * * * * * 15 10 5 0 Baseline 8 16 24 Treatment Week Busse W, et al. J Allergy Clin Immunol 2001;107:461-8. *P < 0.001

Salmeterol vs Oral Montelukast in Patients Using ICS ICS therapy for > 30 days prior to randomization Run-in Salmeterol 50 mcg b.i.d. (powder) + ICS n = 236 Montelukast 10 mg daily + ICS n = 231 2-Weeks 12 Weeks Fish J, et al. Am J Respir Crit Care Med 2000;161-163:A203.

AM PEFR Change From Baseline (L/min) 50 45 40 35 30 25 20 15 10 5 * * * * * * * * Salmeterol * * Montelukast 0 *P < 0.05 0 1 2 3 4 5 6 7 8 9 10 11 12 Weeks Fish J, et al. Am J Respir Crit Care Med. 2000;161-163:A203. * *

Leukotriene Modifiers: Place in Therapy Possible initial therapy in mild persistent asthma as an alternative to INH CS or cromolyn Not superior to INH CS alone Possible adjunctive therapy in addition to INH CS at any level of asthma severity Not superior to LABA when combined with INH CS May be useful in children or adults with poor inhaler technique, or in younger children in whom LABA are not indicated

Immunomodulator Therapy: Omalizumab (Xolair ) First humanized antibody for treatment of asthma; approved by the FDA in June 2003 Indicated for adults and adolescents (12 years of age or older) with moderate-to-severe persistent asthma who: have had a positive skin test to a perennial aeroallergen, and have symptoms that are inadequately controlled with inhaled corticosteroids

Omalizumab (Xolair ): Mechanism of Action A recombinant DNA-derived humanized monoclonal antibody that selectively binds to human immunoglobulin E (IgE) Inhibits binding of IgE to high-affinity IgE receptors on the surface of mast cells and basophils, resulting in a decrease in the release of allergic response mediators May also reduce the number of high-affinity IgE receptors present on basophils

Omalizumab (Xolair ): Dosing and Administration 150 to 375mg subcutaneously every 2 to 4 weeks Dose and frequency determined by the serum total IgE level (IU/mL), measured before the start of treatment, and body weight (kg)

Omalizumab (Xolair ): Adverse Effects Malignancy (0.5% vs. 0.2% control) most patients observed for less than one year impact of long-term administration in higher risk patients unknown Anaphylaxis (<0.1%; 3 patients in pre-marketing clinical trials) Several post-marketing case reports Black Box Warning w/in 2 hrs of first or subsequent administration observation following injection required Other: injection site reaction (5-20%)

Omalizumab (Xolair ): Evidence-Based Medicine Pooled analysis of 3 multicenter, RDBCT (phase III) Adults/ adolescents: n=1071; Children, ages 6-12 (n=334) Inclusion: moderate-to-severe allergic asthma of at least one year duration total serum IgE level between 30 and 700 IU/mL (adolescents/adults), or 30 and 1300 IU/mL (children) positive skin prick test to dustmite, cockroach, dog, or cat J Allergy Clin Immunol 2003;111:87-90.

Omalizumab (Xolair ): Evidence-Based Medicine Intervention: Randomization: Omalizumab or placebo injections (subq) every 2-4 weeks Steroid-Stable Phase: Dosages of inhaled beclomethasone dipropionate (INH BDP) kept stable over first 16 weeks Steroid-Reduction Phase: INH BDP dosages reduced x 25% every two weeks over an eight week period, with the lowest effective dose maintained over for a further four weeks J Allergy Clin Immunol 2003;111:87-90.

Steroid-Stable Phase Exacerbations (% patients) 40 30 20 10 0 P =.009 P <.001 P =.095 P <.001 Study 008 Study 009 Study 010 All studies Omalizumab Placebo J Allergy Clin Immunol 2003;111:87-90.

Steroid-Reduction Phase Exacerbations ( % patients ) 40 30 20 10 0 P =.004 P <.001 P <.001 P <.001 Study 008 Study 009 Study 010 All studies Omalizumab Placebo J Allergy Clin Immunol 2003;111:87-90.

Results: Omalizumab (Xolair ): Evidence-Based Medicine Rate of unscheduled, asthma-related outpatient visits lower for omalizumab (rate ratio [95% CI], 0.60 [0.44,0.81];P < 0.01) Rate of asthma-related ED visits lower for omalizumab (rate ratio [95% CI], 0.47 [0.24,1.01];P = 0.05) Hospitalizations reduced in omalizumab group (rate ratio [95% CI], 0.08 [0.00,0.25];P < 0.01) J Allergy Clin Immunol 2003;111:87-90.

Comparison of Omalizumab to Standard of Care Double-blind, parallel group, multi-center study 419 patients inadequately controlled despite therapy with high-dose INH CS + LABA Randomized to receive omalizumab vs. placebo injections subq RESULTS: Omalizumab significantly reduced the rate of asthma exacerbations and ED visits vs. placebo Humbert M, et al. Allergy 2005;60:309-16.

Omalizumab (Xolair ): An Emerging Treatment Option? Only for patients with known allergy-induced asthma (documented positive skin test) who are poorly controlled on inhaled corticosteroids Benefit of reduced steroid dosage relative to total cost of therapy unclear Estimated cost: $5000 - $10,000 per year! Risk of anaphylaxis must be considered Role of omalizumab better defined in new NIH asthma guidelines: After treatment has been maximized with high-dose INH CS + LABA

NAEPP Expert Panel Report Guidelines (EPR-3): Where are we today? 1997 2002 2007 National Asthma Education and Prevention Program. Executive summary of the NAEPP expert panel report (EPR-3): Guidelines for the diagnosis and management of asthma. Bethesda, MD: U.S. Department of Health and Human Services, Public Health Service, National Institutes of Health, National Heart, Lung, and Blood Institute, Full Report 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/index.htm

STEPWISE APPROACH FOR MANAGING ASTHMA IN YOUTHS > 12 YEARS AND ADULTS Intermittent Asthma Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 or higher care is required Consider consultation at step 3 Quick-Relief Medication for All Patients SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of systemic oral corticosteroids may be needed. Use of beta 2 -agonist >2 days a week for symptom control (not prevention of EIB) indicates inadequate control and the need to step up treatment. Step 1 Preferred: SABA prn Step 2 Preferred: Low-dose ICS Alternative: LTRA Cromolyn Theophylline Step 3 Preferred: Med-dose ICS OR Low-dose ICS+ either LABA, LTRA, Theophylline Or Zileutin Step 4 Preferred: Medium-dose ICS+LABA Alternative: Medium-dose ICS+either LTRA, Theophylline Or Zileutin Step 5 Preferred: High dose ICS + LABA AND Consider Omalizumab for patients with allergies Step 6 Preferred: High-dose ICS + LABA + oral Corticosteroid AND Consider Omalizumab for patients with allergies Step up if needed (check adherence, environmental control and comorbidities) Assess Control Step down if possible (if asthma well controlled for 3 months) Patient Education and Environmental Control at Each Step EPR-3

STEPWISE APPROACH FOR MANAGING ASTHMA IN CHILDREN 5-11 YEARS OF AGE Intermittent Asthma Persistent Asthma: Daily Medication Consult with asthma specialist if step 4 or higher care is required Consider consultation at step 3 Quick-Relief Medication for All Patients SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of systemic oral corticosteroids may be needed. Use of beta 2 -agonist >2 days a week for symptom control (not prevention of EIB) indicates inadequate control and the need to step up treatment. Step 1 Preferred: SABA prn Step 2 Preferred: Low-dose ICS Alternative: LTRA Cromolyn Theophylline Step 3 Preferred : Low-dose ICS + either LABA, LTRA, or Theophylline OR Medium-dose ICS Step 4 Preferred: Medium-dose ICS+LABA Alternative: Medium-dose ICS+either LTRA, or Theophylline Step 5 Preferred: High dose ICS + LABA Alternative: High-dose ICS+ either LTRA or Theophylline Step 6 Preferred: High-dose ICS + LABA + oral Corticosteroid Alternative: High-dose ICS +either LTRA or Theophylline + oral corticosteroid Step up if needed (check adherence, environmental control and comorbidities) Assess Control Step down if possible (if asthma well controlled for 3 months) Patient Education and Environmental Control at Each Step EPR-3

STEPWISE APPROACH FOR MANAGING ASTHMA IN CHILDREN 0-4 YEARS OF AGE Intermittent Asthma Persistent Asthma: Daily Medication Consult with asthma specialist if step 3 or higher care is required Consider consultation at step 2 Quick-Relief Medication for All Patients SABA as needed for symptoms. Intensity of treatment depends on severity of symptoms: up to 3 treatments at 20-minute intervals as needed. Short course of systemic oral corticosteroids may be needed. Use of beta 2 -agonist >2 days a week for symptom control (not prevention of EIB) indicates inadequate control and the need to step up treatment. Step 1 Preferred: SABA prn Step 2 Preferred: Low-dose ICS Alternative: LTRA Cromolyn Step 3 Preferred: Medium-dose ICS Step 4 Preferred: Medium-dose ICS AND either LTRA OR LABA Step 5 Preferred: High dose ICS AND either LTRA OR LABA Step 6 Preferred: High dose ICS AND either LTRA OR LABA AND Oral Corticosteroid Step up if needed (check adherence, environmental control ) Assess Control Step down if possible (if asthma well controlled for 3 months) Patient Education and Environmental Control at Each Step EPR-3

ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN CHILDREN 0-4 YEARS OF AGE EPR-3 IMPAIRMENT Components of Control Symptoms Nighttime awakenings Interference with normal activity SABA use Classification of Asthma Control Well Controlled Not Well Controlled Very Poorly Controlled < 2 days/week > 2 days/week Throughout the day < 1/month > 2 x/month >2x/week none Some limitation Extremely limited < 2 days/week > 2 days/week Several times/day RISK Exacerbations requiring oral steroids Treatment-related adverse effects 0-1 per year 2-3 per year > 3 per year Medication-related sides effects can vary from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk. Recommended Action For Treatment Maintain current step REGULAR FOLLOW UP EVERY 3-6 MONTHS Consider step down if well controlled at least 3 months Step up 1 step Reevaluate in 2-6 weeks If no clear benefit in 4-6 wks, consider alt. dx or adjust therapy Consider oral steroids Step up (1-2 steps) and reevaluate in 2 weeks If no clear benefit in 4-6 wks, consider alt. dx or adjust therapy

ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN CHILDREN 5-11 YEARS OF AGE EPR-3 Components of Control IMPAIRMENT Symptoms Classification of Asthma Control Well Controlled < 2 days/wk, <1/day Not Well Controlled >2 days/wk or multiple times on < 2 days/wk Very Poorly Controlled Throughout the day Nighttime awakenings Interference with normal activity SABA use < 1/month none < 2 days/week > 2 x/month Some limitation > 2 days/week >2x/week Extremely limited Several times/day FEV 1 or peak flow > 80% predicted/ 60-80% predicted/ <60% predicted/ personal best personal best personal best FEV 1 /FVC > 80% predicted 75-80% predicted <75% predicted RISK Exacerbations lung growth Treatment-related adverse effects Recommended Action For Treatment 0-1/ year > 2 / year (Consider severity and interval) Evaluation requires long-term follow up care Medication-related sides effects can vary from none to to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk. Maintain current step; consider step down if well controlled x 3mos Step up 1 step Reevaluate in 2-6 weeks Consider oral steroids Step up 1-2 steps & reevaluate in 2 wks

ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN YOUTHS > 12 YEARS OF AGE AND ADULTS EPR-3 Components of Control Symptoms Nighttime awakenings Classification of Asthma Control Well Controlled Not Well Very Poorly Controlled Controlled < 2 days/week > 2 days/week Throughout the day < 2/month 1-3/week > 4/week IMPAIRMENT RISK Interference with normal activity SABA use FEV 1 or peak flow Validated questionnaires ATAQ/ACT Exacerbations Progressive lung function Treatment-related adverse effects none Some limitation Extremely limited < 2 days/week > 2 days/week Several times/day > 80% predicted/ personal best 60-80% predicted/ personal best <60% predicted/ personal best 0/> 20 1-2/16-19 3-4/< 15 0-1 per year >2 per year Evaluation requires long-term follow up care Medication-related sides effects can vary from none to to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk. Recommended Action For Treatment Maintain current step Consider step down if well controlled x 3 mos Step up 1 step Reevaluate in 2-6 weeks Consider oral steroids Step up 1-2 steps and reevaluate in 2 weeks

The 4 Components of Asthma Management Measures of Asthma Assessment and Monitoring Medications Control of Environmental Factors and Comorbid Conditions That Affect Asthma Education for a Partnership in Asthma Care EPR-3

Involving Patients in Their Own Asthma Care Dear Patient, The most important ingredient in your asthma care is YOU. It is important for you to understand your disease, know how to recognize your symptoms, and know how and when to take your medicine. Take control of your asthma. Don t let your asthma take control of you. I am here to help you learn how YOU can take control. Sincerely, Your Respiratory Therapist

Education for a Partnership in Asthma Care No matter how much WE as health care providers know about asthma, effective treatment of patients can only occur if the patients also comprehend and are willing to participate in their own care. Providing asthma education and encouraging self-management is crucial. A partnership between the patient and the clinician(s) should be established to promote effective asthma management.

The Role of the Respiratory Care Provider as a Partner in Asthma Care Promote open communication Good communication between patient and clinician helps identify patient concerns, makes patient teaching more effective and promotes patient self-confidence to follow the treatment plan Ensure patients have a basic and ACCURATE foundation of knowledge about asthma Ensure patients understand the treatment approach Ensure patients have the self-management skills necessary to monitor the disease objectively and take medications effectively Be a sympathetic coach

Health Care Team Approach at Multiple Points of Care The Primary Clinician(s) Introduce(s) key educational messages and negotiate(s) agreements with patients (goals of treatment, medications, actions to take to promote asthma control, etc.) The Health Care Team Includes ALL HEALTH CARE PROFESSIONALS who encounter asthma patients through multiple points of care Should reinforce key educational messages at every opportunity Points of Care Clinic visits, ED visits, pharmacy visits, telephone calls, in community centers, in schools

Key Educational Messages Basic Facts About Asthma What is asthma? What is meant by good asthma control? Role of Medications Patient Skills Ability to take medications properly Ability to monitor and recognize symptoms of worsening asthma Ability to understand and utilize Written Asthma Action Plan

Education: What is Good Asthma CONTROL? Few daytime symptoms 2x or less per week No nighttime awakenings 2x or less per month Limited need for quick-relief medications 2x or less per week Able to engage in normal activities No limitations in daily activities No limitations in exercise **Be sure to ask about the patients and families goals and expectations!

Education: What is the Role of Medications? Appropriate asthma management requires the proper use of long term control and quick relief medications. Terminology (quick relief vs. long-term control) and technique (MDI vs. DPI) are important! Patients need to understand the importance of taking daily long-term control medications. Inhaled corticosteroids are the most potent and consistently effective long-term control medications for persistent asthma.

Education: Self-Monitoring Skills How to recognize intensity and frequency of asthma symptoms How to use peak flow meter (if prescribed) Monitor for early S/Sx of worsening asthma: Nighttime or early morning awakening Increased medication use Decreased activity tolerance

Proper Monitoring: Symptoms vs. PEF Measurements Depends on patient and clinician preference PEF-based plans may be particularly useful for patients who have difficulty perceiving signs of worsening asthma Whether peak flow monitoring, symptom monitoring, or a combination of approaches is used, self-monitoring is important to the effective self-management of asthma (Evidence A). NHLBI. NAEPP EPR-3: Guidelines for the Diagnosis and Management of Asthma, 2007. Available at http://www,nhlbi.nih.gov/guidelines/asthma/index.htm.

Interpretation of Asthma Symptoms Green Zone Yellow Zone Red Zone PEF > 80% personal best 50% 79% personal best < 50% personal best Symptoms No coughing Coughing, OR Very SOB, OR & Activity No wheezing No chest tightness No SOB (day or night) Can do usual activities Wheezing, OR Chest tightness, OR SOB (day or night), OR Limitations in usual activities No relief from quickrelief medication, OR Cannot do usual activities, OR Symptoms are same or worse after 24 hours in Yellow Zone Interpretation Doing Well Asthma Is Getting Worse Medical Alert!!

Key Elements of a Written Asthma Action Plan 1. Daily (Chronic) Management What medicine to take daily (include specific names, both brand and generic), how much to take, and when to take it What actions to take to control environmental factors that worsen asthma 2. Acute Management: How to Recognize and Manage Worsening Asthma What signs, symptoms, and PEF measurements indicated worsening asthma What symptoms and PEF measurements indicate the need for urgent medical attention Emergency contact information for MD, ED, and person/service to transport patient rapidly for medical care

Who Should Have a Written Asthma Action Plan? Patients with moderate or severe persistent asthma..? Patients with a history of severe asthma exacerbations..? Patients with poorly controlled asthma.? ALL patients* who have asthma should have a written Asthma Action Plan! *Only 47.7% of children and 28.6% of adults with asthma in Indiana had a written Asthma Action Plan during 2006-2010 NAEPP Guidelines Implementation Report, December 2008

Case Studies in Asthma Management

According to the 2007 NIH asthma guidelines, which of the following medications is the preferred first-line controller medication for long-term control of asthma symptoms in a TWO YEAR OLD patient with MILD-PERSISTENT asthma? a. budesonide (low-dose) b. formoterol c. cromolyn d. theophylline e. montelukast

For a 21 year old patient who is receiving only a MEDIUM-DOSE inhaled corticosteroid and whose asthma is not well controlled, which of following approaches is preferred, according to the 2007 NIH guidelines: a. Increase the dose of the inhaled corticosteroid b. Add a long-acting beta agonist c. Add a mast cell stabilizer d. Add a leukotriene modifier e. Add theophylline

JB is a 44 yof with asthma for which she takes daily fluticasone and has an albuterol inhaler for prn use. She presents to the clinic in no acute distress for a routine follow-up visit to assess her level of asthma control. During her visit she reports having to use her albuterol for symptom relief approximately 3 to 4 times per week during the daytime. She reports no limitations in her activities and no nighttime symptoms due to her asthma. She states that as far as she knows, her PEF s have been running at or above 80% of her personal best. Based on the information provided by JB about the frequency of her asthma symptoms, how would you classify the level of control of her asthma, according to NIH guidelines? a. Well Controlled b. Not Well Controlled c. Very Poorly Controlled d. Out of Control e. Intermittently Controlled

JB is a 33 yof with asthma for which she takes daily fluticasone and has an albuterol inhaler for prn use. She presents to the clinic in no acute distress for a routine follow-up visit to assess her level of asthma control. During her visit she reports having to use her albuterol for symptom relief approximately 3 to 4 times per week during the daytime. She reports no limitations in her activities and no nighttime symptoms due to her asthma. She states that as far as she knows, her PEF s have been running at or above 80% of her personal best. Based on the information provided by JB about the frequency of her asthma symptoms, how would you classify the level of control of her asthma, according to NIH guidelines? a. Well Controlled b. Not Well Controlled c. Very Poorly Controlled d. Out of Control e. Intermittently Controlled

AB, a SIX year old patient who was initially diagnosed with mild persistent asthma and prescribed a low-dose inhaled corticosteroid and an albuterol MDI for prn use, returns to your clinic for follow-up and assessment of asthma control. The patient s mother indicates that AB needs to use her albuterol approximately three times per week to control her symptoms (cough and shortness of breath) during the day. The patient s mother also reports that AB is awakened a few (approximately 3) times per month due to a cough. When reviewing KB s peak flow records, you note that her peak flows have been averaging approximately 75 80% of her personal best. According to the 2007 NIH guidelines, which of the following is the most appropriate assessment of AB s asthma control and recommended action at this time? a. AB s asthma is well controlled ; maintain current therapy and reassess in 3 months b. AB s asthma is well controlled ; consider stepping down therapy at this time c. AB s asthma is not well controlled ; step up therapy and reevaluate in 3 months d. AB s asthma is not well controlled ; step up therapy and reevaluate in 2 to 6 weeks e. AB s asthma is very poorly controlled ; step up therapy, add oral methylprednisolone, and reassess in 2 weeks

ASSESSING ASTHMA CONTROL AND ADJUSTING THERAPY IN CHILDREN 5-11 YEARS OF AGE Components of Control IMPAIRMENT Symptoms Nighttime awakenings Interference with normal activity Classification of Asthma Control Well Controlled < 2 days/wk, <1/day Not Well Controlled >2 days/wk or multiple times on < 2 days/wk EPR-3 Very Poorly Controlled Throughout the day < 1/month > 2 x/month >2x/week none Some limitation Extremely limited SABA use < 2 days/week > 2 days/week Several times/day FEV 1 or peak flow > 80% predicted/ 60-80% predicted/ <60% predicted/ personal best personal best personal best FEV 1 /FVC > 80% predicted 75-80% predicted <75% predicted RISK Exacerbations lung growth Treatment-related adverse effects Recommended Action For Treatment 0-1/ year > 2 / year (Consider severity and interval) Evaluation requires long-term follow up care Medication-related sides effects can vary from none to to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk. Maintain current step; consider step down if well controlled x 3mos Step up 1 step Reevaluate in 2-6 weeks Consider oral steroids Step up 1-2 steps & reevaluate in 2 wks

KB, a SIX year old patient who was initially diagnosed with mild persistent asthma and prescribed a low-dose inhaled corticosteroid and an albuterol MDI for prn use, returns to your clinic for follow-up and assessment of asthma control. The patient s mother indicates that KB needs to use her albuterol approximately three times per week to control her symptoms (cough and shortness of breath) during the day. The patient s mother also reports that KB is awakened a few (approximately 3) times per month due to a cough. When reviewing KB s peak flow records, you note that her peak flows have been averaging approximately 75 80% of her personal best. According to the 2007 NIH guidelines, which of the following is the most appropriate assessment of KB s asthma control and recommended action at this time? a. KB s asthma is well controlled ; maintain current therapy and reassess in 3 months b. KB s asthma is well controlled ; consider stepping down therapy at this time c. KB s asthma is not well controlled ; step up therapy and reevaluate in 3 months d. KB s asthma is not well controlled ; step up therapy and reevaluate in 2 to 6 weeks e. KB s asthma is very poorly controlled ; step up therapy, add oral methylprednisolone, and reassess in 2 weeks

KM is a 45 year old female with moderate persistent asthma. She was hospitalized two days ago for treatment of an acute asthma exacerbation. She is being discharged today with prescriptions for the following medications: albuterol HFA, 2 puffs Q 6 h prn SOB Advair Diskus 250/50, 1 inhalation BID prednisone, 40 mg daily x 4 more days She has a peak flow meter at home. She is in need of a written Asthma Action Plan.

SAMPLE LONG-TERM TREATMENT PLAN FOR A 45 YEAR OLD ADULT WITH MODERATE PERSISTENT ASTHMA CLINICAL CONDITION Baseline Plan & When asthma is under control At FIRST sign of a cold or mild asthma symptoms At FIRST sign of a mild asthma attack For rapidly worsening asthma (severe attack) When there is no cough or wheeze for 3 months For cough or wheeze with exercise PEAK FLOW (% predicted) FEV 1 /FVC Above 80% 75 to 80% 50 to 75% Below 50% Over 80% for 3 months MEDICATION Reliever: Inhaled short-acting beta 2 -agonist 2 puffs as needed Albuterol HFA Controller: Inhaled med dose corticosteroid + LABA 1 puff 2x/day Advair 250/50 Corticosteroid Tablet or Syrup 0 Immunizations: Influenza annually, pneumococcal vaccine x 1

SAMPLE LONG-TERM TREATMENT PLAN FOR A 45 YEAR OLD ADULT WITH MODERATE PERSISTENT ASTHMA CLINICAL CONDITION PEAK FLOW (% predicted) FEV 1 /FVC Baseline Plan & When asthma is under control At FIRST sign of a cold or mild asthma symptoms At FIRST sign of a mild asthma attack For rapidly worsening asthma (severe attack) Above 80% 75 to 80% 50 to 75% Below 50% When there is no cough or wheeze for 3 months Over 80% for 3 months For cough or wheeze with exercise MEDICATION Reliever: Inhaled short-acting beta 2 -agonist Albuterol HFA Controller: Inhaled med dose corticosteroid + LABA Advair 250/50 Corticosteroid Tablet or Syrup 2 puffs as needed 1 puff 2x/day 0 2 puffs every 4 hr 1 puff 2x/day 0 4 puffs every 20 min x 3 doses, then 2-4 puffs every 4 hr 1 puff 2x/day Begin with 1-2 mg/kg/day 4-6 puffs every 20 min x 3 doses 1 puff 2x/day Prednisone 60 mg now 2 puffs as needed Consider step-down to Advair 100/50 2 puffs 5-10 minutes before exercise NOTIFY MD CALL 911 Immunizations: Influenza annually (last dose 11/10/11); pneumococcal vaccine complete (given 11/10/11) 0

Summary of Key Points Baseline assessment of asthma severity can help define initial asthma pharmacotherapy Ongoing assessment and management should focus on CONTROL, and therapy should be stepped up or stepped down accordingly INH CS are the preferred first-line agents for long-term control regardless of the age of the patient Current NIH guidelines provide for the option of titrating to a medium dose of INH CS before adding LABA Role of therapies for allergy-related asthma continue to be defined When asthma is well-controlled for a period of 3 months, consideration can be given to stepping down therapy. Education is essential all patients should have an individualized, written Asthma Action Plan!

Thank you for your attention! Questions?