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)