1. Wheeze and Asthma Mark Minor, M.D. Section of Pulmonary Medicine
Dayton Children’s Hospital

2. Conflicts of Interest / Disclaimers
None

3. Question 1
What is the timeframe for onset of action of systemic prednisone (orapred)?
A. 30 minutes
B. 1-2 hours
C. 4-6 hours
D. 12 hours

4. Question 2
Which 2 year old child has a positive asthma predictive index?
3 episodes of wheezing/year and allergic rhinitis
3 episodes of wheezing/year and 7% blood eosinophils
3 episodes of wheezing/year and eczema
3 episodes of wheezing/year and wheezing outside of colds

5. Objectives Overview of causes of wheezing
Define natural course of wheezing in infants
Review risk factors for asthma
Review step method for asthma treatment
Review alternatives for uncontrolled persistent asthma

6. Case 9 year old with recurrent wheeze and persistent dry cough
Cough present for about two years, day and night
Multiple visits to PCP, ED, Urgent Care with complaint of cough
Documentation of wheeze and use of Albuterol and/or systemic steroids on separate occasions
Multiple courses of systemic steroids for wheeze / cough with subjective improvement
Usually accompanied with URI symptoms
Minimal improvement with use of Albuterol
On exam: Dry cough, mild inspiratory and expiratory wheeze

7. Causes of wheezing Asthma Vascular rings or slings
Tracheomalacia, Bronchomalacia
Viruses
Chronic aspiration
Cystic Fibrosis
Foreign body
Mediastinal or airway mass

8. Wheezing in infancy Common problem
Approximately 1/3 of infants (Kuehni et al. Eur Resp Journal; (1):81-5)
Recurrent wheeze in about 1:5 infants (Alvarez et al. Aller Immun; 2018, )
Kuehni et al. Eur Resp Journal, 2000

9. Risk factors for recurrent wheeze
Viral respiratory tract infections (RSV, rhinovirus etc.)
Atopic sensitization
Family history of asthma
Pre-natal and Post-natal exposure to maternal smoking
Gastroesophageal reflux/Aspiration
Exposure to environmental pollution
Prematurity (BPD), Male gender
Structural airway anomalies
< 24 months of age

10. Foreign body aspiration
Toddlers at special risk
Peanuts, hotdogs, hard candies, toys
Can result in:
Complete airway obstruction
Stridor
Wheeze
Persistent pneumonia
Hemoptysis

11. Foreign body aspiration
Persistent cough, asymmetric wheeze refractory to treatment
Dx: X-ray, Bronchoscopy
Hyperinflation, ball valve obstruction

12. Peanut in Right Mainstem Bronchus

13. Virus induced wheezing
Strong association between viral bronchiolitis and recurrent wheezing during infancy
Infants in daycare have more wheezing episodes than infants who are not in daycare due to increased exposure to viruses

14. Virus induced wheezing
20% of all children have at least one episode of lower respiratory illness associated with wheezing in the first year of life
Rhino Virus infection leading to hospitalization during infancy is an early predictor of the subsequent development of asthma
Kotaneimi-syrjanen A. et al. JACI 2003, 111: 66
Risk of asthma after viral bronchiolitis is increased in the presence of allergic sensitization in early life and if the infection is more severe

15. Childhood asthma

16. Epidemiology of Childhood Asthma
Most important chronic respiratory disorder in childhood
Affects approximately 5-15% of all children
Boys > Girls in young children
Girls > Boys in adolescents
Adverse outcomes significantly determined by race and ethnicity
Akinbami L. Centers for Disease Control 2006; 381:1

18. Evaluation and Treatment of Atopy in Childhood Asthma
Atopy is present in > 75% of children with persistent asthma
Role in exacerbations based on age:
< 3 years: viral respiratory infections
> 3 years: viral infections + allergen exposure
Sensitization pattern based on age:
< 1 year: eczema/milk, soy, egg, wheat, peanut
> 3 years: dust mite, molds, pollen, ragweed
Heymann et al, J Allergy Clin Immunol 2004; 114:239
Atopy refers to the genetic tendency to develop allergic diseases such as allergic rhinitis, asthma and atopic dermatitis (eczema). Atopy is typically associated with heightened immune responses to common allergens, especially inhaled allergens and food allergens.

19. Diagnosing asthma in infancy
Infants and toddlers who present with frequent early wheeze is a challenge
Almost 80% of asthma starts before 5 years of age

20. Diagnosing asthma in infancy
Asthma Predictive Index
> 3 episodes of wheeze in one year, AND
1 Major Criteria
Diagnosis of asthma in parent, maternal > paternal
Diagnosis of eczema in infant
Allergic sensitization to aeroallergen OR
2 Minor Criteria
Peripheral eosinophilia (4%)
Wheezing episodes not associated with URI
Diagnosis of allergic rhinitis
Positive Index: 65% chance of asthma by age 6
Castro-Rodriguez JA, et al. J Allergy Clin Immunol. 2016:
Aeroallergen: House dust mite, cockroach, dog, cat, mold, grass, tree, and weed.

21. Other predictors increasing risk of asthma
Maternal overweight or obesity during pregnancy
Prenatal maternal smoking
Postnatal maternal smoking, < 5 years of age
Other household smoking
Preterm birth and low birth weight
RSV infection
Household mold
BMI > 95th %
Maternal obesity 1.21 x increase odds of current asthma or wheeze
Prenatal smoking x increase
Postnatal smoking x
Preterm, 1.46

22. Approach to acute asthma exacerbation, or status asthmaticus
Administer treatment of inhaled SABA, repeat times three, and promptly give oral corticosteroids if needed
Addition of Ipratropium Bromide (Atrovent) is effective
Prednisone 2 mg/kg/day up to mg for 3-7 days, or
Dexamethasone 0.6 mg/kg (maximum 12 mg), repeat x1 in 24 hours
Prednisone has onset of action: 4 to 6 hours
IV Fluids if dehydrated, watch for SIADH, hypokalemia
Keep Oxygen saturation > 95%

23. Approach to acute asthma exacerbation, or status asthmaticus
Chest xray?
Severe respiratory distress
Unilateral wheeze
Focally diminished breath sounds
No antibiotics unless reasonable evidence of an acute bacterial infection

24. Beta-Agonists Can Worsen Hypoxemia in Acute Asthma

25. Nebulizer vs MDI with Spacer

27. Changes/Updated in 2018 to GINA Guidelines
Step 1
It is explained that the reason ICS should be considered for patients with mild asthma (rather than prescribing SABA alone) is to reduce their risk of serious exacerbations (Pauwels, Lancet 2003; O’Byrne AJRCCM 2001; Reddel Lancet 2017)
Steps 3-4
From the large FDA LABA safety studies: adding LABA to ICS in a combination inhaler reduces risk of exacerbations and improves symptoms and lung function, compared with the same dose of ICS alone, but with only a small reduction in reliever use (Stempel NEJM 2016, Peters NEJM 2016)
Step 5 management of severe asthma
Subcutaneous benralizumab (monoclonal anti-IL5 receptor α antibody) is another add-on treatment for patients aged ≥12 years with severe eosinophilic asthma

28. Uncontrolled asthma Co-morbidities (GERD, rhinitis, etc)
Poor adherence
Ineffective delivery of treatment, ie poor inhaler technique
Severe therapy-resistant disease
Ongoing exacerbating triggers (smoke, allergens, pollutants)
Misdiagnosis
Inadequate treatment

29. Persistent asthma
Consider Biologic Therapy (injection therapy) if appropriate
Xolair
Nucala
Dupixent – newest for certain types

30. Biologic targeting IgE
Omalizumab (Xolair)
Binds to free IgE
Approved for above age 6 years
Shown to decrease: symptoms, exacerbations, ICS dose
Shown to increase: FEV1, quality of life

31. Biologic targeting eosinophils
Mepolizumab (Nucala)
IL-5 binding to eosinophils
Approved for age 12 years and above
Decreases exacerbations, symptoms, ICS dose
Increases FEV1 and quality of life

32. Biologic targeting IL-4 and IL-13
Dupilumab (Dupixent)
Recently approved for asthma control
For treatment of atopic dermatitis, eczema, and persistent asthma
Approved for ages 12 years and above

33. Summary of key points
Asthma is a complex disease with significant phenotypic heterogeneity
Control of exacerbating factors can improve symptoms
Treatment of asthma is based on severity-based guidelines
New therapies are available to treat severe/uncontrolled asthma

34. Case continued

35. Case continued
9 year old with recurrent wheeze and persistent dry cough

36. Case continued
Spirometry

37. Case continued
Normal chest x-ray
Lateral neck x-ray

38. Case continued
Lateral neck x-ray

39. Case continued

40. Case continued Granular cell tumor
Required removal and tracheal reconstruction

41. Thank You! Mark Minor, MD Section of Pulmonary Medicine
Dayton Children’s Hospital