1. Diagnosis and Management
ASTHMA IN CHILDREN:
Diagnosis and Management
Milagros S. Salvani-Bautista, MD
Pediatric Pulmonologist

2. OPERATIONAL DESCRIPTION:
“ Asthma is a chronic inflammatory disorder
of the airways in which many cells and cellular elements play a role. The chronic inflammation is associated with airway hyperresponsiveness that leads to recurrent episodes of wheezing, breathlessness, chest tightness, and coughing, particularly at night or in the early morning. These episodes are usually associated with widespread, but variable, airflow obstruction within the lung that is often reversible either spontaneously or with treatment”
GINA: 2002,2006,2007

3. What Is Asthma ?

4. What is known about Asthma?
increasing PREVALENCE especially in children
CHRONIC INFLAMMATORY DISORDER of the airways
chronically inflamed airways are HYPERRESPONSIVE
EPISODIC WHEEZING, BREATHLESSNESS, CHEST TIGHTNESS and COUGHING
can be CONTROLLED

5. PATTERNS OF RECURRENT WHEEZE IN PEDIATRIC PATIENTS
Transient wheezing
Non-atopic wheezing
Persistent asthma
Tucson Children’s Respiratory Study
JACI 2003; 111:
Severe, intermittent wheezing
Bacharier. JACI 2007; 119:

6. DETAILED HISTORY AND PE
PRESENTING FEATURES
Wheeze
Dry cough
Breathlessness
Noisy breathing
DETAILED HISTORY AND PE
Pattern of illness
Severity/control
Differential clues No
IS IT ASTHMA?
Follow relevant course of action
Seek specialist assistance
Probably
Possibly
INVESTIGATE OR SEEK
Causal factors
Exacerbating factors
Complications
Comorbidity
DIFFERENTIAL DIAGNOSTIC TESTS &/or TRIALS OF ASTHMA THERAPY
Asthma likely
Asthma unlikely
ASTHMA ACTION PLAN
DIAGNOSIS OF ASTHMA IN CHILDREN
Poor response
Good response

7. CLASSIFICATION OF ASTHMA SEVERITY
GINA 2002
Intermittent
Symptoms less than once a week
Brief exacerbations
Nocturnal symptoms not more than 2x/mo.
• FEV1 or PEF ≥ 80% predicted
• PEF or FEV1 variability < 20%
Mild Persistent
Symptoms more than once a week but less than once a day
Exacerbations may affect activity and sleep
Nocturnal symptoms more than 2x/mo.
• PEF or FEV1 variability < 20 – 30%
Moderate Persistent
Symptoms daily
Exacerbations may affect activity & sleep
Nocturnal symptoms more than once a wk.
Daily use of inhaled short-acting 2-agonist
• FEV1 or PEF 60-80% predicted
• PEF or FEV1 variability > 30%
Severe Persistent
Frequent exacerbations
Frequent nocturnal asthma symptoms
Limitation of physical activities
• FEV1 or PEF ≤ 60% predicted

8. Level of Asthma Control
Characteristic
Controlled (All of the ff)
Partly Controlled (Any measure present in any week)
Uncontrolled
Daytime symptoms
None (2x or </wk.)
More than 2x/wk
Three or more features of partly controlled asthma present in any week
Limitations of activities
None
Any
Nocturnal symptoms/ awakening
Need for reliever/rescue tx
None (2x or less/week)
More than 2x/ wk
Lung function (PEF or FEV1)+
Normal
<80% predicted or personal best (if known)
Exacerbations
One or more/ yr*
One in any wk╪
* Any exacerbation should prompt review of maintenance treatment to ensure that it is adequate By definition, an exacerbation in any week makes that an uncontrolled asthma week ╪ Lung function testing is not reliable for children 5 years and younger.
GINA 2006

9. ASTHMA MANAGEMENT: COMPONENTS OF THERAPY
Assess and monitor asthma severity and asthma control
Education for a partnership in care
Control of environmental factors and co-morbid conditions that affect asthma
Medications

10. Medicines in Childhood Asthma
GINA ASTHMA GUIDELINES 2002, 2006, 2007
Medicines in Childhood Asthma
Controllers
Inhaled and systemic corticosteroids
Leukotriene modifiers
Long-acting B2 agonist (LABA) with Inhaled Corticosteroid ICS
Sustained release theophyllines
Cromones
Relievers
Rapid-acting inhaled Beta (B)2 agonist
Inhaled anti-cholinergics
Short acting theophylline
Short acting B2 agonist
(SABA)
Classification of medication are the same.

11. ACUTE ASTHMA EXACERBATION

12. Severity of Asthma Exacerbations…..
GINA 2002, 2006, 2007
Severity of Asthma Exacerbations…..
MILD MODERATE SEVERE RESPIRATORY
ARREST
IMMINENT
Breathless Walking Talking At rest
Infants – softer Infants- Stops
shorter cry feeding
Can lie flat Prefers sitting *Hunched forward
Talks in Sentences Phrases Words
Alertness May be agitated Usually agitated Usually agitated
Respiratory Rate Increased Increased *Often >30/min Bradypnea
GUIDE TO RATES OF BREATHING ASSOCIATED WITH
RESPIRATORY DISTRESS IN AWAKE CHILDREN
AGE NORMAL RATE
> 2 months < 60/min
2-12 months < 50/min
1-5 years < 40/min
6-8 years < 30/min
The 2002 ,2006 and the 2007 GINA GUIDELINES are in agreement regarding the severity classification of asthma exacerbations

13. Severity of Asthma Exacerbations…..
GINA 2002, 2006, 2007
Severity of Asthma Exacerbations…..
MILD MODERATE SEVERE RESPIRATORY
ARREST IMMINENT
Accessory None Present Present Present
Muscles & Thoraco-abdominal
Suprasternal Movement
Retraction
Wheeze Audible with Audible with Audible w/o Absence of wheeze
stethoscope stethoscope stethoscope with decreased to
absent breathe sounds
Pulses/min < > Bradycardia
GUIDE TO LIMITS OF NORMAL PULSE RATE IN CHILDREN
Age Normal Limits
Infants months <160/min
Preschool 1-2 years <120/min
School Age 2-6 years <110/min

14. Severity of Asthma Exacerbations
GINA 2002,2006,2007
Severity of Asthma Exacerbations
MILD MODERATE SEVERE RESPIRATORY
ARREST
IMMINENT
Pulses Paradoxus Absent May be present Often present Absence suggests
<10mm Hg 10—20mm Hg 20-40mm Hg respiratory muscle
fatigue
PEF  80% % <60%
%predicted Or
%personal best
PaO2 RA Normal 60mm Hg <60mmHg
test NOT usually Possible Cyanosis
necessary
PaCO2 45 mm Hg 45 mm Hg >45 mm Hg possible
respiratory failure
SaO2 RA 95% % <90%
Hypercapnea (hypoventilation) develops more rapidly in young children

15. GINA ASTHMA GUIDELINES: (2002, 2006,2007)
Management of Asthma Exacerbation in Acute Care S1
Initial Assessment
History, Physical Examination(auscultation, use of accessory muscles,
HR, RR, PEF or FEV1, O2 saturation, ABG’s if patient in extremis)
Initial Treatment
Oxygen to achieve O2 saturation ≥90% (95% in children)
Inhaled rapid β2-agonist continuously for one hour
Systemic GCS, if no immediate response, or if patient recently took
Oral GCS, of if episode is severe
SEDATION is CONTRAINDICATED in the treatment of an exacerbation
Reassess after 1 hour : PE, PEF, O2 saturation & other tests as needed
Criteria for MODERATE Episode:
PEF 60-80% predicted/personal best
Physical exam: moderate symptoms,
Accessory muscle use
Treatment:
O2,
Inhaled β2 agonist + anticholinergic every 60 min
Oral GCS
Continue treatment for 1-3 hours,provided
There is improvement
Criteria for SEVERE Episode:
History of risk factors for near fatal asthma
PEF < 60% predicted/personal best
PE: severe symptoms at rest, chest retraction
NO improvement after initial treatment
Treatment:
O2,
Inhaled β2 agonist + anticholinergic
Systemic GCS
IV Magnesium
Continuation next slide

16. GINA ASTHMA GUIDELINES: (2002, 2006,2007)
Cont. (S2)
Management of Asthma Exacerbation in Acute Care
Reassess after 1 – 2 hours
Good Response within 1-2 hours:
Response sustained 60 minutes
after last treatment
PE normal: no distress
PEF > 70%
O2 saturation > 90% (95% in children)
Incomplete Response within 1-2 hours:
Risk Factors for near fatal asthma
PE : mild to moderate signs
PEF < 60%
O2 saturation: NOT IMPROVING
Poor Response within 1-2 hours:
Risk factors fro near fatal asthma
PE : symptoms severe, drowsiness,
confusion
PEF : < 30%
PCO2 : > 45mmHg
PO2: < 60mmHg
ADMIT to ACUTE CARE Setting
Oxygen
Inhaled β2-agonist ± anticholinergic
Systemic GCS
Intravenous Magnesium
Monitor PEF, O2 saturation, Pulse
ADMIT to INTENSIVE Care
Oxygen
Inhaled β2-agonist+anticholinergic
IV GCS
Consider IV β2 agonist
Consider IV theophylline
Possible intubation
mechanical ventilation
Improved: Criteria for Discharging Home
PEF > 60% predicted / personal best
Sustained on oral/inhaled medications
HOME TREATMENT:
Continue inhaled β2 agonist
Consider in most cases, oral GCS
Consider adding a combination inhaler
Patient education: take medicine correctly
review action plan
close medical check up
Reassess at Intervals
Poor Response:
Admit to intensive Care
Incomplete response in 6-12 hours
Consider admission to Intensive Care
If No improvement within hours
Improved

17. Inhaled β2-agonists are the mainstay of therapy in acute asthma.

18. However, once response to the initial β2-agonists is minimal, incomplete or poor …
COMBINATION of INHALED β2-AGONIST and INHALED ANTICHOLINERGIC is RECOMMENDED
This is for moderate to severe attacks.

19. GINA ASTHMA GUIDELINES:
2002
Recommended Medications by Level of Severity: Children
All Steps: In addition to daily controller therapy, rapid-acting inhaled β2 agonist* should be taken as needed to relieve symptoms, but should not be taken more than 3 to 4 times a day.
INTERMITTENT
PERSISTENT
MILD MODERATE SEVERE
Daily Controller
Medications
Other Treatment
Options
None
necessary
IGCS µg BUD
IGCS< 800µg BUD
PLUS
Sustained released
theophylline OR
IGCS <800µg BUD
PLUS LABA OR
IGCS >800µg OR
IGCS <800mcg PLUS
Leukotriene modifier
IGCS >800µg BUD
PLUS one or more
of the following:
Sustained-
release theophylline
Long Acting Inhaled
β-2 agonist
Leukotriene modifier
Oral glucocortico
steroid
IGCS
mcg
BUD
Sustained-
release
Theophylline, OR
Cromone,
Leukotriene
modifier
In all steps: Once control of asthma is achieved and maintained for at least 3months, a gradual reduction of the maintenance therapy should be tried in order to identify the minimum therapy required to maintain control

20. 1 2 3 4 5 LEVEL OF CONTROL TREATMENT OF ACTION TREATMENT STEPS REDUCE
controlled
partly controlled
uncontrolled
exacerbation
LEVEL OF CONTROL
maintain and find lowest controlling step
consider stepping up to gain control
step up until controlled
treat as exacerbation
TREATMENT OF ACTION
INCREASE
GINA Guidelines 2006
TREATMENT STEPS
REDUCE
INCREASE
STEP 1 2 3 4 5

21. GINA 2006

22. Asthma Medications As needed: RELIEVER BRONCHODILATORS
Short acting β2-Agonists
Anticholinergics (inhaled)
Short acting Theophyllines
Daily: CONTROLLER
ANTI-INFLAMMATORY
Corticosteroids (inhaled and systemic)
Leukotriene modifier
Long acting β2 agonists
Sustained release theophyllines
GINA 2006

23. Inhaled Corticosteroids
Most effective long-term control for persistent asthma
Small risk for adverse events at recommended dosage
Benefits of daily use
Reduction of
asthma symptoms
frequency of exacerbations
airway inflammation
airway responsiveness
asthma mortality
Improvement of
lung function
quality of life

24. Estimated Equipotent Doses of Inhaled Glucocorticosteroids for Children
Drug
Low Daily Dose (µg)
Medium Daily Dose (µg)
High Daily Dose (µg)
Beclomethasone dipropionate
>
>400
Budesonide*
Budesonide-Neb Inhalation Susp.
>
>1000
Ciclesonide*
80-160
>
>320
Flunisolide
>
>1250
Fluticasone
>
>500
Mometasone furoate*
Triamcinolone acetonide
>
>1200
GINA 2006

25. COMPARISON OF PHARMACOKINETICS & PHARMACODYNAMIC PARAMETERS OF ICS
BDP/BMP
BUD FP
LIPOPHILICITY
Mod/high
Low
High
PROTEIN BINDING:FREE FRACTION
87:13
88:12
90:10
T1/2, hr
0.5/2.7
2.8
7.8
Vd, Li
20/424
183
318
Clearance, L/h
15/120 84 69

26. TECHNIQUES FOR BALANCING SAFETY AND EFFICACY OF ICS
Selection and use of ICS
Select safest ICS drug
Use minimum effective dose
Dose in AM when once daily dosing
If control is poor, add another controller rather than double dose of ICS
To maximize ICS delivery to lung, consider:
CFC vs HFA propellant formulation
pMDI vs DPI formulation
Use of spacer device
Patient technique
Rinse mouth of ICS and discard

27. TECHNIQUES FOR BALANCING SAFETY AND EFFICACY OF ICS
Use of ICS – sparing strategies
Reduce allergens and smoke
Inoculate with influenza vaccine
Diagnose and treat rhinosinusitis or GERD
Use add-on therapies
Monitor growth at all ICS doses
Monitor eyes and bone mineral density when using > 1600 ug/day ICS
Consider first line alternatives to ICS for mild persistent asthma

28. SYSTEMIC SIDE EFFECTS OF ICS THERAPY IN CHILDREN
EVIDENCE GRADE
EFFECT ON
CONCLUSION
A, B, C
GROWTH
Potential to decrease growth velocity. Effects are small, non-progressive, reversible A
BONE MINERAL DENSITY
No serious adverse effects
A, C
CATARACTS
GLAUCOMA
No significant effects on incidence of subcapsular cataracts or glaucoma
HPA AXIS FUNCTION
Rare individuals may be susceptible to ICS effects on HPA axis even on conventional doses

29. LEUKOTRIENE MODIFIERS
Mechanisms
5-LO inhibitors (zileuton)
CysLT 1 receptor antagonists (montelukast, pranlukast, zafirlukast)
Indications
Alternative treatment in mild persistent asthma
Aspirin-sensitive asthma
Add-on therapy, but less effective than LABA
Concomitant asthma with allergic rhinitis 29

30. LEUKOTRIENE MODIFIERS
CHILDREN OLDER THAN 5 YRS.
Clinical benefit at all levels of severity, but, generally less that that of low-dose ICS
Partial protection against EIA
As add-on treatment
CHILDREN 5 YRS. AND YOUNGER
In addition to above, it reduces viral-induced asthma exacerbation in children 2-5 yrs with a history of intermittent asthma.
GINA 2006

31. LONG-ACTING INHALED B2-AGONISTS
Monotherapy should be avoided
Most effective when combined with ICS, preferably in a fixed combination inhaler
May be used to prevent exercise-induced bronchospasm
Regular use of rapid acting B2-agonists, in both short and long acting forms, may lead to relative refractoriness to B2-agonists
Asthma related deaths and deteriorations with long term use of salmeterol among asthmatics with unusual geotype for beta receptors (with substitution of arginine for glucine at position B-16) whether or not administeredwith ICS

32. THEOPHYLLINES
Effective as monotherapy and as add-on treatment to ICS or oral steroids, but efficacy is less than that of low-dose ICS
Anti-inflammatory function noted at low dose of less than 10 mkd
As add-on therapy, theophylline is less effective than LABA
Side effects: GI, arrhythmias, seizures, drug interactions

33. CROMONES: Na CROMOGLYCATE AND NEDOCROMIL Na
Limited role in long term treatment of asthma in children
Can attenuate bronchospasm induced by exercise or cold air
Side effect: Uncommon, cough and sore throat

34. ANTI-IgE TREATMENT
(Omalizumab)
Addition to other controller medications has been shown to improve control of allergic asthma (Evidence A)

35. Do not underestimate the severity of an attack
Manage Exacerbations
Do not underestimate the severity of an attack
Patient should seek medical help if:
The attack is severe
The response to the initial bronchodilator treatment is not prompt
There is no improvement within 2-6 hours
There is further deterioration

36. Asthma Attack requires prompt treatment:
Manage Exacerbations
Asthma Attack requires prompt treatment:
Inhaled rapid acting B2-agonists
Oral glucocorticosteroids
Oxygen (to achieve SaO2 of 95%)
Combination B2-agonist/anticholinergic therapy
Therapies not recommended:
Sedatives
Mucolytics
Chest physical therapy

37. Do not underestimate the severity of an attack
Manage Exacerbations
Do not underestimate the severity of an attack
Patient should seek medical help if:
The attack is severe
The response to the initial bronchodilator treatment is not prompt
There is no improvement within 2-6 hours
There is further deterioration

38. Bronchodilators : Mechanism of Action

39. RAPID ACTING INHALED B2-AGONISTS
RELIEVER MEDICATIONS
RAPID ACTING INHALED B2-AGONISTS
Most effective bronchodilator
Preferred treatment for acute asthma
Inhaled route is preferred
Protection against exercise-induced bronchoconstriction
Oral therapy is rarely needed and reserved for young children who cannot use inhaled therapy

40. RELIEVER MEDICATIONS ANTICHOLINERGICS
Inhaled anticholinergics are not recommended for long term management of asthma inchildren

41. Comparative Pharmacokinetics of Nebulized Salbutamol and Ipratropium
Parameters
Salbutamol
Ipratropium
Onset of bronchodilation
within 5 mins.
within minutes
Peak effect
1-2 hours
Duration of effect
3-4 hours
5-7 hours
Onset of bronchodilation is faster with salbutamol. The duration of effect however is longer for ipratropium. These 2 distinct characteristics makes it ideal to combine the 2 drugs. 41

42. REFERRAL to an Asthma Specialist (NAEP EPR 3 Report)
Difficulties achieving or maintaining control of asthma
Patient required > 2 bursts of oral steroids in 1 year or has an exacerbation requiring hospitalization
Step 4 care or higher is required (Step 3 care or higher for 0-4 years)
If immunotherapy or omalizumab is considered or if additional testing is indicated

43. SUMMARY
Asthma is a serious chronic inflammatory disease of the airways
Controller medication – primarily inhaled corticosteroids – is the cornerstone of asthma management
Essential components of successful asthma management include
Pharmacotherapy
Allergen avoidance
Patient education
Use of a standardized diagnostic questionnaire, use of an asthma control test

44. SUMMARY
ALLERGEN AVOIDANCE is recommended when there is sensitization and a clear association between allergen exposure and symptoms.
ALLERGY TESTING (at all ages) to confirm the possible contribution of allergens to asthma exacerbation
EXERCISE SHOULD NOT BE AVOIDED:
Asthmatic children should be encouraged to participate in sports, with efficient control of asthma inflammation and symptoms.

45. Thank You