1. Diagnosing and Managing Asthma in Children LARRY S. POSNER M.D. Associate Clinical Professor of Pediatrics, UCSF Principal, North Bay Allergy and Asthma Associates

2. Asthma Is Prevalent: Significant Morbidity and Mortality Approximately 11 People Die From Asthma Each Day 22.2 Million People Are Currently Diagnosed With Asthma 12.2 Million People Suffer From Asthma Attacks Annually Approximately 4000 Asthma- Related Deaths Occur Annually 32.6 Million People Have Had an Asthma Diagnosis in Their Lifetime Available at: http://www.cdc.gov/nchs/products/pubs/pubd/hestats/asthma/asthma.htm. Accessed March 12, 2007.

3. 1.American Academy of Allergy, Asthma, and Immunology, Inc., 1999. 2.Mannino DM, et al. MMWR Morb Mortal Wkly Rep. March 29, 2002;51(SS01);1-13. Pediatric Asthma: Facts and Figures Asthma is the most common chronic disorder in children and adolescents 1 Asthma is the most common chronic disorder in children and adolescents 1 Asthma is a leading cause of school absences, resulting in 14 million missed school days a year 2 Asthma is a leading cause of school absences, resulting in 14 million missed school days a year 2

4. Child and Adult Asthma Prevalence United States, 1980-2007 12-Month Lifetime Child  Adult Source: National Health Interview Survey; CDC National Center for Health Statistics Current

5. Asthma Trends A child born a generation from now is twice as likely to develop asthma as one born today

6. Number of Deaths Among Children Aged 0-17 Years Due to Asthma Has Declined Since 1996 Beginning with data year 1999, cause-of-death statistics published by NCHS are classified according to the Tenth Revision of the International Classification of Diseases (ICD-10). CDC/NCHS, Mortality Component of the National Vital Statistics System. Asthma Deaths per 1 Million Children ICD Revision 1999 US Department of Health and Human Services. Centers for Disease Control and Prevention National Center for Health Statistics. Number 381, December 12, 2006.

7. Emergency Department Visits and Hospitalizations for Asthma Remain High Among Children Aged 0-17 Years US Department of Health and Human Services. Centers for Disease Control and Prevention National Center for Health Statistics. Number 381, December 12, 2006. Asthma ED visits represented about 3% of all ED visits among children 0-17 years of age in 2004. Asthma hospitalizations represented about 3% of all hospitalizations among children 0-17 years of age in 2004. CDC/NCHS, National Hospital Ambulatory Medical Care Survey Emergency Visits per 10,000 Children CDC/NCHS, National Hospital Discharge Survey Asthma Hospitalizations per 10,000 Children

8. Are Children With Asthma Achieving the NIH Goals of Therapy?

9. Guidelines for the Diagnosis and Management of Asthma—Update on Selected Topics 2002. NIH, NHLBI. May 2003 (reprint). NIH publication 02-5075. Where Should We Start NIH Goals of Asthma Therapy Minimal or no chronic symptoms day or night Minimal or no exacerbations No limitations on activities; no missed school/work Maintain (near) normal pulmonary function Minimal use of inhaled short-acting beta 2 - agonists Minimal or no adverse effects from medications

10. Children and Asthma in America Goals of Asthma Therapy Are Inadequately Met Children and Asthma in America  : A Landmark Survey. Executive Summary. SRBI; 2004. Symptoms in Past 4 Weeks Sudden Severe Episodes in Past Year % of Respondents 62% 54% 0 20 40 60 80 100 Activity Limitation Missed School in Past Year 67% 54%

11. Children and Asthma in America Parent-Child Gap in Perception of Asthma Symptoms in the Past 4 Weeks 44% 50% 27% 60% 68% 26% 0% 10% 20% 30% 40% 50% 60% 70% During DayDuring ExerciseDuring Night % of Respondents Parents Children (10-15) Children and Asthma in America  : A Landmark Survey. Executive Summary. SRBI; 2004.

12. Children and Asthma in America Many children with asthma are not achieving the NIH goals of therapy Poorly controlled asthma has a significant impact on daily lives of children and their families The survey highlights the need for improved asthma management Better assessment and treatment Proper patient and family education Improved dialogue between the child, parents, and their clinician

13. Diagnosing Asthma: Spirometry Testing of lung function is one means of diagnosing asthma.

14. Challenges in Treating Childhood Asthma May be difficult to make a “definitive” diagnosis in very young children Lack of objective measurement Lack of subjective awareness of symptoms Underdiagnosis of asthma is a frequent problem in children

15. Diagnosing Asthma: Medical History Symptoms Coughing Wheezing Shortness of breath Chest tightness Patterns to Symptoms Family History Response to medication

16. Onset of Symptoms in Children With Asthma McNicol and Williams. BMJ 1973;4:7-11. Wainwright et al. Med J Aust 1997;167:218-222. 30% 20% 30% 20% 1-2 years >3 years <1 year 2-3 years

17. Asthma is a Spectrum of Disease Mild intermittent asthma Severe persistent asthma Cough/wheeze only with colds or exercise Daily symptoms at rest

18. Precipitating / Aggravating Factors “Asthma triggers” Viral upper respiratory infections Allergen exposure Exercise Irritants (especially smoke) Weather Strong emotion Gastroesophageal reflux

19. Approaches to Treatment AVOIDANCE  Environmental control PHARMACOLOGIC THERAPY  Step therapy per NHLBI guidelines ALLERGY IMMUNOTHERAPY

20. Avoidance Influenza vaccination Tobacco smoke Fireplace smoke Air “fresheners” Allergens

21. Reducing Indoor Allergens Essential: Encase mattress/box-spring in an allergen- impermeable cover Encase pillow in an allergen-impermeable cover or wash weekly Wash sheets and blankets in hot water weekly (>130 o F is necessary for killing mites) Remove other reservoirs from the bedroom Carpet treatments unclear House-Dust Mites

22. Cat Allergen Major cat allergen Fel d1 found in saliva and dander In homes with indoor cats, 35% of allergen reservoir is continually airborne. Dander accumulates in carpet upholstered furniture and bedding Cat dander is an almost ubiquitous indoor allergen

23. Teach Patients To Reduce Exposure to Inhalant Allergens Teach Patients To Reduce Exposure to Inhalant Allergens Remove pet from house (ideal) Keep animal out of patient’s bedroom (at a minimum) Mattress/pillow encasements Wipe down surfaces with a damp cloth Portable HEPA air filtration Keep window closed Seal or put a filter on air ducts that lead to bedroom ANIMAL DANDER

24. Pharmacotherapy

25. Stepwise Approach to Therapy for Adults and Children: Maintaining Control STEP 1 Quick-relief medication: PRN STEP 2 1 Long-term-control medication: anti-inflammatory (Preferred low-dose ICS) STEP 3 > 1 Long-term-control meds (Preferred low dose ICS+LABA) STEP 4 Multiple long- term-control medications, including prednisone STEP 1 Mild Intermittent STEP 2 Mild Persistent STEP 3 Moderate Persistent STEP 4 Severe Persistent Step Up Step Down

26. 2007 NIH Asthma Guidelines: Patients 5-11 Years of Age (For patients newly diagnosed or on SABA alone) and consider short course of systemic oral corticosteroids In 2–6 weeks, evaluate level of asthma control achieved; adjust therapy accordingly Step 3, medium- dose ICS option, or step 4 Step 3, medium-dose ICS option Step 2Step 1 Recommended step for initiating therapy Relative annual risk of exacerbations may be related to FEV 1 Consider severity and interval since last exacerbation. Frequency and severity may fluctuate over time for patients in any severity category. ≥2/year0–1/year Exacerbations requiring oral systemic corticosteroids Risk FEV 1 < 60% predicted FEV 1 /FVC <75% FEV 1 = 60%– 80% predicted FEV 1 /FVC = 75%–80% FEV 1 = >80% predicted FEV 1 /FVC >80% Normal FEV 1 between exacerbations FEV 1 >80% predicted FEV 1 /FVC >85% Lung function Extremely limitedSome limitationMinor limitationNone Interference with normal activity Several times per day Daily >2 days/week but not daily ≤2 days/week Short-acting beta 2 - agonist use for symptom control (not prevention of EIB) Often 7x/week > 1x/week but not nightly 3–4x/month≤2x/monthNighttime awakenings Throughout the dayDaily >2 days/week but not daily ≤2 days/weekSymptoms Impairment SevereModerateMild PERSISTENT NTERMITTENT Classification of Asthma Severity: 5–11 Years of Age COMPOMENTS OF SEVERITY NIH, National Heart, Lung and Blood Institute. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma (EPR–3 2007). NIH Item No. 08–4051. Available at: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm. Accessed December 19, 2008.`

27. Prevent chronic and troublesome symptoms Require infrequent use of inhaled SABA (≤2 days/week) Maintain (near) “normal” pulmonary function Maintain normal activity levels Meet patients’ expectations of, and satisfaction with, asthma care Reduce Risk Prevent recurrent exacerbations Minimize need for emergency department visits or hospitalizations Prevent progressive loss of lung function Provide optimal pharmacotherapy, with minimal or no adverse effects Goal of Asthma Therapy: ACHIEVE CONTROL Reduce Impairment NAEPP = National Asthma Education and Prevention Program; SABA = short-acting β 2 -agonists.

29. Stepwise Approach for Managing Asthma in Children Aged 5 to 11 Years: NAEPP Guidelines LTRA = leukotriene receptor antagonist. Step 1 Preferred: SABA prn Step 2 Preferred: Low-Dose ICS (A) Alternative: LTRA (B), Cromolyn (B), Nedocromil (B), or Theophylline (B) Step 3 Preferred: Medium-Dose ICS (B) or Low-Dose ICS and either LABA (B), LTRA (B), or Theophylline (B) Step 5 Preferred: High-Dose ICS + LABA (B) Alternative: High-Dose ICS and either LTRA (B) or Theophylline (B) ------------- Step 4 Preferred: Medium-Dose ICS + LABA (B) Alternative: Medium-Dose ICS and either LTRA (B) or Theophylline (B) Step 6 Preferred: High-Dose ICS + LABA + Oral Corticosteroid (D) Alternative: High-Dose ICS and either LTRA or Theophylline and Oral Corticosteroid (D) ----------------

30. Stepwise Approach for Managing Asthma in Children Aged 0 to 4 Years: NAEPP Guidelines ICS = inhaled corticosteroid; LABA = long-acting β 2 -agonist; SABA = short-acting β 2 -agonist. Step 1 Preferred: SABA prn Step 2 Preferred: Low-Dose ICS (A) Alternative: Montelukast (A) or Cromolyn (B) Step 3 Preferred: Medium-Dose ICS (D) Step 5 Preferred: High-Dose ICS and either Montelukast or LABA (D) Step 4 Preferred: Medium-Dose ICS and either Montelukast or LABA (D) Step 6 Preferred: High-Dose ICS and either Montelukast or LABA and Oral Corticosteroids (D) Moderate to Severe Persistent Mild Persistent Intermittent

31. Immunotherapy for Asthma Meta-analyses: Abramson et al AJRCCM 1995;151:969-974 Allergy 1999;54:1022-41 Ross et al Clinical Therapeutics 2000;22:329-341

32. What’s the Evidence? 0 5 10 15 20 25 30 Total No. of studies Meta-analysis of clinical studies 962 asthmatics with documented allergy Immunotherapy clinically effective in 71% of studies Studies with children Effective with children107 24 Source: Ross RN, Nelson HS, Finegold I. Clin Ther 2000 Number of studies

33. Prevention of asthma in patients with Seasonal Allergic rhinitis 0 10 20 30 40 50 60 70 80 ImmunotherapyControl No asthma Asthma Odds ratio 2.52 Percentage of patients Moller et al. J Allergy Clin Immunol. 2002 Feb;109(2):251-6.

34. Prevention of New Sensitivities After Treatment of 3 Years None 0 2 4 6 8 10 12 14 Control CatDogAlternaria Grass Source:Roches et al. JACI. New sensitivities

35. Prevention of New Sensitivities After Treatment of 3 Years None 0 2 4 6 8 10 12 14 ControlActive CatDogAlternaria Grass Source:Roches et al. JACI. New sensitivities

36. Summary Asthma in children is increasing in prevalence While mortality from asthma has improved in recent years, morbidity has not The diagnosis of asthma in young children is challenging Asthma is children is generally not adequately controlled. Management of asthma includes reduction of triggers, pharmacotherapy and immunotherapy NHLBI guidelines for asthma management emphasizes: assessing control at each visit Stepping up or down therapy