This document discusses goal directed therapies for treating asthma in children. It begins by describing asthma as an inflammatory airway disease, and outlines the pathophysiology involving bronchoconstriction, edema, and mucus formation. It then discusses various inflammatory mediators involved and how they lead to air trapping. The document outlines the initial presentation of wheezing in children of different ages and differentiates asthma from other causes of wheezing. It provides an overview of clinical presentation and the basic treatment principles involving bronchodilators, corticosteroids, and other agents. Finally, it discusses approaches for more severe asthma including heliox, magnesium, intravenous treatments, ventilation support, and ECMO.

1. Goal Directed Therapies
for Asthma
Ira M. Cheifetz, MD, FCCM, FAARC
Professor of Pediatrics
Chief, Pediatric Critical Care
Medical Director, PICU & Peds Resp Care
Duke Children’s Hospital

3. What is Asthma?
 Acute and chronic inflammatory disorder of
the airways and epithelium
 Most common respiratory disease of children
 Affects between 7-10% of the pediatric
population
 Asthma triad: smooth muscle spasm
(bronchoconstriction), airway edema
(inflammation), airway plugging (mucous
formation)

4. Pathophysiology:
The Asthma Triad

5. Inflammatory Mediators
♦ Cytokines are one category of mediators
that play a significant role in the chronic
inflammatory process in asthma
♦ The products are associated with WBCs,
mast cells, & other lung airway cells
♦ Mediators induce broncho-constriction,
edema and mucus secretion

6. Air Trapping
Inhalation
AIR

7. Air Trapping
Exhalation

8. Pathophysiology
♦ Hyperinflation
– obstructed small airways cause premature
airway closure
– air trapping and hyperinflation
♦ Hypoxemia
– inhomogeneous distribution of affected areas
results in V/Q mismatch

9. Initial Presentation of Wheezing
20% 30%
1-2 years <1 year
20%
2-3 years
30%
>3 years

10. Why do children wheeze?
 Increased airway resistance / airway narrowing
 Derived from Poiseuille’s equation, resistance is
proportional to 1/radius 44
 In small airways, very minor changes in airway
diameter significantly alter airflow
 The increased ‘turbulence’ in the narrowed
airways generates the high-pitched noise of
wheezing

12. All that wheezes is NOT asthma!
♦ Other causes of wheezing:
– bronchiolitis
– cystic fibrosis
– gastroesophageal reflux
– chronic lung disease of infancy (BPD)
– primary ciliary dyskinesia
– anatomic abnormalities
• tracheoesophageal fistula (TEF)
• vascular ring
• bronchomalacia

13. Clinical Presentation
 Cough
 Wheezing
 Increased work of breathing
 Anxiety
 Restlessness
 Oxygen desaturation

14. Basic Treatment Principles
 Standard therapy remains focused on
bronchodilators, anti-inflammatory agents,
and mucus thinning agents as needed
 Systemic or inhaled corticosteroids remain
the most effective agents for symptomatic
control of asthma
 Other agents include long-acting
bronchodilators, leukotriene-modifiers,
theophylline, heliox, magnesium, and inhaled
anesthetics

15. Basic Treatment Principles
 Children present difficulties in drug delivery:
– small airways and rapid respiratory rate
– nose breathers
– aversion to things on the face (masks)
– lack of cooperation/fussiness & crying
 With training and consistency, children adapt
and will cooperate with nebulized meds.

16. Treatment Hierarchy: Step 1
♦ Oxygen
♦ Inhaled short acting beta-agonists
- intermittent vs. continuous
- effective dosing is based on minute
ventilation – not mg/kg dosing
♦ Corticosteroids
- oral vs. parenteral
♦ Ipratropium?

17. Treatment Hierarchy: Step 2
♦ Continuous beta-agonist therapy
♦ IV corticosteroids
♦ Subcutaneous beta-agonists
♦ Heliox

18. Gas Densities
Relative density of He-O2 and N2-O2
2 2 2
mixtures compared with 100% O2. 2
Oppenheim-Eden, Chest, 2001.

19. Laminar Gas Flow
 Laminar gas flow is more efficient
than turbulent gas flow.
 Poiseuille’s Law:
Flow rate = P  r4
8l
 Independent of gas density.
 So, does heliox improve laminar gas
flow and, if so, how?

20. Reynold’s Number
 Re =
 VD

 Re > 4000 = turbulent flow

 Re < 2100 = laminar flow

 Densities:

O2 = 1.43, N2 = 1.25, He = 0.18
 Heliox is more likely to yield a lower

Reynold’s number and improved gas

21. Turbulent Gas Flow
 Occurs in constricted passages
 Flow rate = k P
 
  gas density yields  gas flow.
 Heliox improves turbulent gas flow.

22. Gas Flow
Forced
expiratory flow
rates in healthy
infants
Davis, J Appl Physiol, 1999.

23. Heliox P-V Loops

24. Asthma and Heliox in the
ED
 After 20 minutes of therapy
– Heliox group: PEF  58.4%
– N2-O2 group: PEF  10.1%
Kass, Chest, 1999.

25. Heliox and Asthma
* p < 0.001
*
Kudukis, J Pediatr, 1997.

26. Heliox and Asthma
* * p < 0.001
Kudukis, J Pediatr, 1997.

27. The ‘Spiral’ Effect
‘some’ improve gas
heliox exchange
increase decrease
heliox FiO2
concentration

28. The ‘Spiral’ Effect
improve gas
exchange
increase decrease
heliox FiO2
concentration

29. Treatment Hierarchy: Step 3
♦ Magnesium
♦ Intravenous beta-agonists
♦ IV aminophylline

30. Late-stage Asthma
♦ Impending respiratory failure
– altered level of consciousness
– inability to speak
– inability to protect airway
– absent breath sounds
– central cyanosis
– diaphoresis
– inability to lie down
– marked pulsus paradoxus

31. Avoid intubation, if possible….
♦ An ETT cannot stent open the smaller
airways, where the problem is.
♦ Positive pressure ventilation overdistends
airways and making air trapping worse
♦ Asthma is a disease of exhalation – not
inhalation!
♦ Intubate based on the patient’s clinical
appearance and indicators of pending
respiratory failure

32. Treatment Hierarchy: Step 4
♦ Mechanical ventilation
♦ Sedation / neuromuscular blockade
♦ Inhaled anesthetics
♦ Venovenous extracorporeal membrane
oxygenation (ECMO)

33. ECMO

34. Other Considerations
 Oxygen
– Asthma is primarily a disease of ventilation
– Significant oxygen requirement occurs with
severe asthma with resultant V/Q mismatch,
esp. if asthma is coupled with pneumonia
 Antibiotics
– Generally not indicated as most infectious
precipitants of asthma exacerbations are viral
– Consider coverage for mycoplasma
 SIADH: may be present in severe asthma

35. Natural History of Peds Asthma
Transient early Non-atopic IgE-associated
Wheezing Prevalence
wheezers wheezers wheeze/asthma
0 3 6 11
Age (Years)