Asthma in Children: Managing the Uncertainty Principle

1. Asthma in Children:Managing the Uncertainty Principle Olatunji W. Williams, M.D. Pediatric Pulmonologist Peyton Manning Children’s Hospital

2. Asthma Impact in the U.S. • Affects more than 22 million Americans • Including more than six million children • Total health care costs in billions

3. Asthma Prevalence is Highest in Pediatrics Rate/1,000 Persons 80 Age (years) 70 <18 18-44 45-64 65+ Total (All Ages) 60 50 40 Asthma Prevalence by Age U.S., 1985-1996 30 20 95 96 85 86 87 88 89 90 91 92 93 94 Year Global Initiative For Asthma – Statistical Report 2005

4. Hospitalization Rates for Asthma by Age, U.S., 1974 - 2000 Rate/100,000 Persons 40 <15 15-44 45-64 65+ 35 30 25 20 15 10 5 0 74 76 78 80 82 84 86 88 90 92 94 96 98 00 Year Global Initiative For Asthma – Statistical Report 2005

5. What is Asthma ? • Molecular Diagnosis • “ chronic inflammatory disorder of the airways in which many cells and cellular elements play a role: in particular, mast cells, eosinophils, neutrophils…” • Clinical Diagnosis • “ a disease characterized by hyper-responsiveness of the airways to various stimuli, resulting in airway obstruction that is reversible to a significant degree “ NHLBI 2007 Asthma Guidelines M Weinberger, Pediatric Health 2008

6. Bronchoconstriction Airway Edema & Hypersecretion Airway Inflammation Asthma Pathophysiology

7. What Causes Asthma ? • Innate ( hygeine hypothesis ) • Involves the balance between Th1-type ( bacterial ) and Th2-type (allergic immune response) • Exposure to other children  Th1 promoting • Less frequent antibiotic use  Th1 promoting • Country living  Th1 promoting • Genetic • Inheritable component but not fully understood • Environmental • Airborne allergens ( alternaria and dust mites ) • Viral infections

8. Diagnosing Asthma Recurrent episodes of airflow obstruction Airflow obstruction that is reversible Alternative diagnoses are excluded

9. Recurrent Airflow Obstruction • Recurrent episodes of wheezing • Troublesome cough at night • Cough or wheeze after exercise • Cough, wheeze or chest tightness after exposure to airborne allergens or pollutants • Colds “go to the chest” or take more than 10 days to clear

10. Reversible Airflow Obstruction Clinical history of response to conventional asthma therapy Spirometry Objective confirmation of airflow obstruction and also whether airflow obstruction in reversible

11. Alternative Diagnoses are Reasonably Excluded History and Physical critical Top six alternatives in children Allergic rhinitis Recurrent viral infections Dysphagia with aspiration Vascular sling Congenital airway anomaly Cystic Fibrosis

12. Goals of AsthmaTherapy Symptom Control Prevent chronic troublesome symptoms Decrease need for albuterol ( < 2 /week ) Maintain near normal pulmonary function Reduce Risk Recurrent asthma attacks, ED visits and hospitalization Prevent loss of lung function

13. Asthma Care:Four Component Approach Medications Assessing and monitoring asthma severity and control Education for partnership in care Control of environmental factors and co-morbid conditions that effects asthma

14. Asthma Care:Four Component Approach Medications Assessing and monitoring asthma severity and control Education for partnership in care Control of environmental factors and co-morbid conditions that effects asthma

15. Class Warfare • Albuterol, Levalbuterol (SABA) • Inhaled Corticosteroids (ICS) • Blecomethasone, budesonide, fluticasone • Leukotriene Antagonists (LTRA) • Montelukast • Combination therapy (ICS/LABA) • Fluticasone /salmeterol, blecomethasone/formoterol • Immunotherapy • Omalizumab

16. Inhaled Corticosteroids • Are the most potent and consistently effective long-term control medication for asthma • Improved symptom control • Fewer ED visits / hospitalizations • Decreased need for oral steroids • Majority of patients improve on low (100mcg/day) and medium (200 – 400 mcg/day) dosing

17. ICS Safety • Local Adverse Effects (oral candidiasis, dysphonia, cough) • Dose dependent ( decreased at low dose ) • Decreased with valved holding chamber use • Systemic effects (bone density, cataracts, HPA depression) • Rare on low to medium dose ICS. Increased with high dose ICS use • Approximately 1 cm in linear height loss, but typically catch up growth occurs in puberty

18. LABA • Is not recommended as monotherapy, but works very effectively in combination with ICS • Approved for children > 5 y.o. • Can be considered as an option in step-up instead of increasing ICS dose

19. LABA – Safety Concerns • Daily treatment with salmeterol (LABA) vs. placebo  salmeterol group exhibited: • Increased risk of asthma related deaths ( 13 vs. 3 ) • Monotherapy with Formoterol resulted in increased number of severe asthma exacerbations • Together this has earned LABAs the infamous Black Box warning • Step down to ICS monotherapy is recommended once symptom control is achieved (stability over 4 – 6 months) Nelson et al 2006 Mann et al 2003

20. Assessing and Monitoring Asthma Severity and Control

21. Assessing and Monitoring Asthma Severity and Control

22. Assessing and Monitoring Asthma Severity and Control

23. Assessing and Monitoring Asthma Severity and Control

24. When Symptoms Aren’t Enough Blunted response to increased respiratory load in asthma Takashima et al, N Engl J of Med1994

25. Increased ED Visits, Hospitalizations, Near-Fatal Asthma, and Deaths Associated with Perception of Dyspnea POD = Perception of dyspnea Magdle et al, Chest 2002

26. Utilizing Spirometry in Asthma Should be consistent with ATS standards with regards to repeatability, technique and machine calibration recommendations Allows objective measurement of pulmonary function Allows stratification of risk for future asthma attacks

27. Obstructive Ventilatory Defect • Disproportionate reduction in maximal airflow in relation to the maximal volume • Implies airway narrowing during exhalation • Earliest signs of obstructive defect are observed in the small airways

28. FEV1 FVC Flow - Volume Loop : Normal Expiration Flow TLC RV Inspiration Volume

29. FEV1 Flow - Volume Loop : Normal Obstructive defect Expiration Flow TLC RV FEV1 Inspiration Volume

30. Obstructive Pattern FVC FEV1 FEV1 / FVC Due to diseases leading to mucus plugging, bronchospasm, inflammation, or loss of elastic support of the airways (asthma, CF)

31. Spirometry in Asthma Management • FEV1 < 60% is associated with a decrease in symptom free days and increase in asthma related events J Allergy Clin Immunol 2001 • FEV1 < 60% is an independent risk factor for future attacks Pediatrics 2006

32. Asthma Care:Four Component Approach Medications Assessing and Monitoring Asthma severity and control Education for partnership in care Control of environmental factors and co-morbid conditions that effects asthma

33. Education for Partnership in Care Asthma – Basic Facts What is asthma ? What is an asthma attack ? What is airway inflammation ? Asthma Medications Different types How they work ( control vs. rescue ) Potential side effects Patient / Family skills Inhaler technique ( VHC ) Awareness of symptoms Avoiding triggers Utilization of asthma action plan

34. Factors Associated with Non-Compliance in Asthma Care • Patient/Physician • Misunderstanding/lack of information • Underestimation of severity • Attitudes toward ill health • Cultural factors • Poor communication Medication Usage • Difficulties associated with inhalers • Complicated regimens • Fears about, or actual side effects • Cost

35. Asthma Care:Four Component Approach Assessing and Monitoring Asthma severity and control Medications Education for partnership in care Control of environmental factors and co-morbid conditions that effects asthma

36. Control of Environmental Factors and Co-morbid Conditions that Effects Asthma Environmental Factors Inhaled allergens most important Identified by skin testing or in vitro studies Dehumidifiers best to minimize dust mite and mold levels Smoke exposure HEPA filters not a magic bullet Consideration of immunotherapy

37. Control of Environmental Factors and Co-morbid Conditions that Effects Asthma Co-Morbid Conditions Poorly controlled allergic rhinitis Obesity Obstructed Sleep Apnea Vocal Cord Dysfunction Stress / Depression GERD

38. The Problem with Toddlers…. Young children are often mislabeled (chronic or wheezy bronchitis, RAD, recurrent pneumonia or GERD ) Not all wheeze or cough are caused by asthma Lack of objective data However…… 50 - 80% of asthmatics present before their 5th birthday

39. I can’t tell the future but….. Asthma Predictive Index: Major Criteria ( Any 1 ) - Parental history of asthma - Diagnosis of atopic dermatitis - Evidence of sensitization to aeroallergen Minor ( Any 2 ) - Evidence of sensitization to foods - > 4 percent peripheral blood eosinophilia - Wheezing apart from colds

40. Indications for Daily Asthma Therapy in Infants and Toddlers • Positive Asthma Index plus: • Symptoms more twice a week for more than four consecutive weeks (or) • Four or more episodes of wheezing in one year (or) • Two or more episodes requiring oral steroids in six months • Daily therapy during high risk time period can be considered (i.e. winter / viral season) with subsequent weaning of therapy

41. Infants and Toddlers: What to Use and Why • Inhaled Corticosteroids (ICS) are still preferred • Either by nebulization or valved holding chamber with mask • Budesonide FDA approved to 1 y.o. and older • Montelukast (leukotriene antagonist) approved to 2 y.o. and older Off label use occurs frequently but should be guided by asthma specialist

42. Unproven Interventions • Chronic macrolide antibiotic therapy • Methotrexate, Monoclonal IL-5, Cyclosporin A and IVIG • Acupuncture • Chiropractic therapy • Yoga

43. When to Refer • Confirmation of diagnosis • Poor symptom control after 4 – 6 weeks of therapy • Toddlers on long term medium – high dose ICS or combination therapy • Any patient requiring hospitalization • For intensive asthma education

44. Resource Material • NHLBI Guidelines for the Diagnosis and Management of Asthma(http://www.nhlbi.nih.gov/guidelines/asthma/) • Global Initiative for Asthma - GINA(http://www.ginasthma.org) • A clinical index to define risk of asthma in young children with recurrent wheezing.American Journal Respiratory Crit Care Med.2000 • Inhaled corticosteroids should be used in infants and preschoolers with recurrent wheezing.Pediatric Allergy, Imunology, and Pulmonology2011 • Step-up therapy for children with uncontrolled asthma receiving inhaled corticosteroids. New England Journal of Medicine 2010