Pediatric Asthma

1. Pediatric Asthma Kimberly D. Watts MD, MS Pediatric Pulmonary Medicine

2. The Burden of Pediatric Asthma

3. The Scope of Asthma • Most common chronic disease of childhood • Affects more than 7 million children in the United States • Approximately 9% of all US children have asthma • This rate has increased more than 160% in children under 5 in the last 20 years

4. Healthcare Utilization

5. The Cost of Asthma • The annual economic cost of asthma is $19.7 billion • Direct costs such as medications and indirect costs such as loss of productivity • 13 million school days are missed each year

6. Rising Prevalence of Asthma • Increase in asthma prevalence from 1980 to 1996 of greater than 50 % • Largest increase in patients younger than 18 years old • Estimated current asthma prevalence in general increased between 2001-2009

7. Why the increasing numbers? • Improved hygiene • Less exposure to pathogens disrupting innate immunity • Increased indoor air pollution • Caused by increase in energy efficient building • Increased incidence of early onset viral infections • Increase in host susceptibility • Small lungs due to prematurity or maternal smoking • Increased recognition and awareness

8. Asthma death per 1,000 people with asthma ( 2007-09)

9. Pathophysiology

10. Definition of Asthma • Chronic inflammatory lung disease • Cough, wheezing, dyspnea and chest tightness • Airway narrowing that is partially or completely reversible • Increased airway responsiveness to stimuli

11. Asthma Pathophysiology Overview Inflammation Narrowed airways Constricted muscles Airway hyper-reactivity Remodeled airway

12. The wet dry asthma cough • Airways edema • Cellular infiltration • Eosinophils • Activated helper T cells • Mast cells • +/- neutrophils • Increased airway secretions • Secreted mucus • Desquamated lining cells • Intraluminal eosinophils

13. Inflammation • Chronic inflammation occurs even in the most mild of symptomatic patients • Bronchoalveolar lavage of asthmatics demonstrates • Neutrophils, eosinophils, lymphocytes and mast cells • Cytokines including leukotrienes • Alterations in innate lung immunity • Impaired glutathione homeostasis • Decreased capacity to reduce reactive oxygen species

14. Reversible Airflow Obstruction • Reduced expiratory airflow by spirometry • FEV1 < 80 % predicted and a reduced FEV1 / FVC ratio of < 0.80 • Significant reversibility is an increase of >12% in FEV1 from baseline

15. Airway Hyperresponsiveness • Degree to which airways narrow in response to stimuli • Methylcholine • Cold Air • Histamine • Viral upper respiratory infections • Allergens • Air pollutants

16. Normal vs. Asthma Airway

17. Evaluation and Diagnosis

18. Clinical Presentation • Most common cause of chronic cough in children older than 3 years old is asthma • Not always accompanied by wheezing • 80 % of children with asthma develop symptoms before 5 years of age • Breathlessness, chest tightness, chest pressure and chest pain • Poor school performance and fatigue

19. Cough • Cough lasting more than 3 weeks • Night time cough • Cough to specific exposures • Dry and hacking cough • Productive with clear / white sputum • Usually eosinophils • With activity

20. Wheezing • Polyphonic • Tends to be expiatory but can be inspiratory • Monophonic wheezes need further evaluation • Rings/slings • Malacia • When albuterol makes it worse

21. Symptom Patterns • Intermittent exacerbations on a asymptomatic baseline • Chronic symptoms with worsening on exacerbations • Morning “ dipping” • Worsening of symptoms in the morning corresponding to the physiologic dip in pulmonary function • September epidemics • Viral infections, mycoplasma pneumoniae or Chlamydia pneumoniae infection

22. Precipitating Factors and Risk Factors • Weather, second hand smoke, allergens and irritants • Wood fires, kerosene space heaters, room deodorizers • 30 % children with food allergy have asthma • Higher rate of intubation • Children of asthmatic parents odds ratio 2.6 ( 1 parents) and 5.2 ( 2 parents) • Sleep disordered breathing 3.6 fold increase risk for severe asthma • Higher BMI associated with greater asthma severity

23. Diagnosis - Spirometry • National Asthma Educations and Prevention Program recommends spirometry to be performed in patients older than 5 years old • FEV1 < 80% predicted • FEF 25-75% less than 65% correlated with reversible airflow obstruction in children with normal FEV1 • Before and after bronchodilator • Increase in 12 % ( maybe 9% in children) • Normal spirometry or the lack of reversibility does not exclude the diagnosis of asthma

24. Spirometry loops

25. Diagnosis – Peak Flow • More variable and effort dependent • Wide variability in published predicted peak expiratory flow reference values • Can alter brand to brand • Peak flows should not be used to diagnose asthma • More helpful to monitor a patient’s response over time for a subgroup of patients

26. Other Diagnostic Modalities • Impulse Oscillometry • Passive cooperation • Evaluates resistance pre and post bronchodilator • Bronchoprovocation Testing • Methylcholine, histamine , cold air , exercise • If patient fails empiric trial of asthma medsications • Chest x-ray • Congential malformations • Airspace disease • Signs of asthma

27. Other Diagnostic Modalities • Sweat Chloride • Barium Swallow • TEF, reflux, vascular anomolies • Negative study cannot exclude GER • Allergy testing • Limited to seasons and suspect exposures • Exhaled nitric oxide • Levels elevated in patients with asthma • Chornic exposere to passive smoking may falsely decrease the levels

28. Treatment

29. Acute management

30. Short Acting Beta Agonists • Relaxes smooth muscle • Overuse or regular use is associated with poor control • Theoretical concern regarding down regulation of beta receptors with chronic use • Can impact medication needed for urgent care

31. Short acting medications • Albuterol • MDI with spacer or nebulizer • No role for oral albuterol given side effects • Levalbuterol • R- enantiomer – active isomer only • Approved MDI > 4 years old and neb > 6years old • Hospitalization rate lower among childrens who received levoalbuterol in the ER vs. albuterol but studies are mixed • Comparable, no evidence for superiority

32. Ipratropium Bromide • Anti-cholinergic • Bronchodilator through smooth muscle relaxation • Adjuvant for albuterol in the ER • Reduce hospital admissions • Improve lung function in severe asthma • Also can use as an alternative agent to albuterol • Tracheomalacia • MDI not administered to soy or peanut allergy patients • Contains soy lecithin

33. Steroids • 2007 NAEPP expert panel no longer recommends doubling dose of inhaled steroids for quick relief during acute exacerbations • Not found effective in reducing severity or progression of exacerbation • Higher dose ( > 2 times the normal dose) may be an alternative to oral steroids in mild exacerbations if patient does not tolerate oral steroids • Short course of oral steroids in addition to short acting beta agonists for acute exacerbations

34. Chronic Management

36. Who should get controller therapy? • 0 to 4 years old • Greater than 4 episodes of wheezing • Parental history of asthma • Patient with atopic dermatitis or allergies • Food allergies with eosinophilia or wheezing without colds • Require albuterol more than two days per week • Experiences severe illness < 6 weeks apart • 2 rounds of steroids in 6 months • Intermittent disease with severe exacerbation

37. Controller therapy 5 years and older • For any persistent asthma • Any symptoms > 2 days a week • Night time symptoms greater than 2 times a month • Albuterol more than 2 days a week • Any interference with normal activity • Requires oral steroids more than once a year • Severity and interval of exacerbations

38. Intermittent - - - > Step 1 Mild - - -> Step 2 Moderate - - -> Step 3 Severe - - -> Step 3 or 4

39. Starting controller therapy • Two to six week interval is needed to assess response • Adherence with current regimen needs to be assessed before escalating therapy • Included assessment of barriers • When controlled for 2 to 6 months can begin reducing regimen

40. Inhaled Corticosteroids • Inhibiting steps in the inflammatory cascade • Associated with reduction in • Symptoms • Irreversible decline in lung function • Asthma exacerbations • Functional limitations • Side effects from other medications • Reduction in parameters better than with leukotriene antagonist • First line control therapy for persistent ( or step 2 or greater ) asthma

41. Inhaled Corticosteroids • Fraction of the dose than systemic steroids • Minimal side effects • Almost all the trivial amount of drug absorbed is deactivated after one pass through the liver • Differences in medications

42. Inhaled Corticosteroids • Minimize risk of adverse side effects • Step down treatment to lowest possible dose to maintain control • Optimize adherence to lowest dose possible • Optimize delivery • Evaluate for complicating factors • Avoid triggers

43. Inhaled Steroids and Disease Progression • Did not alter disease progression • Patients 2-3 years old with > 4 episodes of wheezing- - > fluticasone or placebo • Fluticasone fewer symptoms and exacerbations • At the last observational year no significant differences • Early , intermittent intervention had no effect on disease progression from episodic to persistent wheezing • 411 infants first thee years of life ICS or placebo • At 5 years of age no difference between lung function or symptoms or asthma medication use between placebo group or ICS group

44. Intermittent Use of ICS Con Pro Budesonide 1 mg BID for 7 days at first onset of symptoms as effective as budesonide 0.5 mg qhs for 12-53 month old patients Meta-analysis no difference in daily ICS vs. intermittent in need for oral steroids but daily ICS better control and more symptoms free days • Intermittent inhaled budesonide at 400 mcg BID x 7 days less effective than daily ICS in children 5-10 years old • No difference in placebo vs. high dosed ICS for 3 days at the first signs of a viral URI with wheezing

45. Leukotriene Receptor Agonists • Cysteinyl leukotrienes found in BAL in asthmatic patients • Inhibit production at various points in the cascade • Adjuvant therapy to ICS in patients > 1 year old • No evidence to support use as first line controller agent or as intermittent therapy • Can be used to step down therapy from ICS or in mild patient who cannot tolerate ICS

46. Montelukast VS. Placebo Vs. ICS Meta-analysis in mild to moderate persistent asthma children ICS had better pulmonary function and better asthma control ICS more cost effective • 2-5 years olds • Intermittent asthma associated with viral symptoms • Better than placebo with a reduced rate of exacerbations and decreased use of ICS

47. Response variability • Double cross over ( 6-17 years old) – Fluticasone and montelukast • 17 % responded to both medications • 23 % responded to fluticasone only • 5% to montelukast only • 55% to neither • Inhaled steroids as the first line controller agent • Intermittent use of moneltukast was associated with some improvement but not difference from placebo in hospitalizations, albuterol use or oral steroids use • More studies needed

48. Long Acting Beta Agonists • Used as an adjuvant to ICS • Should not be used for acute exacerbations • Once control is obtained, effort should be made to go to a single agent ICS • Reserved for patients who “ fail” medium dose ICS • Black box warning • May increase the chance of severe asthma episodes and asthma related deaths

49. Anti IgE ( Omalizumab) • Monoclonal anti IgE • Moderate to severe asthma • Not controlled on ICS • Elevated IgE levels • Approved if > 12 year old in US • IgE levels 30 -700 • Positive allergy testing

50. Chronic Oral Steroids • Severe persistent asthma • Long term effects • Adrenal suppression • Weight gain • Diabetes • Hypertension • Cataracts • Delayed growth • Immune suppression • Osteoporosis • Behavioral effects • Lowest possible dose, every other day administration, trying all other modalities is preferable