PEDBASE.org - The Pediatric Database - Detailed information of CHRONIC ASTHMA

CHRONIC ASTHMA

DEFINITION:

An inherited inflammatory disorder of the respiratory mucosa characterized by recurrent and prolonged cough, wheeze, and dyspnea.

EPIDEMIOLOGY:

incidence: 10-20% of children
age of onset:
- 80% by 5 years of age
risk factors:
- triggers
  - allergens, irritants - exercise
  - viruses, weather change
- family history - 30% risk if one parent has asthma
- M > F (smaller airways in males)

PATHOGENESIS:

1. Early Phase

rapid onset; test for by skin testing
begins almost immediately after the initial challenge and is characterized by airway hyperresponsiveness to a specific stimulus
characterized by smooth muscle bronchoconstriction
beta-2 agonists rapidly reverse
prevented by cromolyn but not steroids

2. Late Phase

gradual onset; test for by bronchoprovocation test
begins 6-8 hours after the initial challenge and is character-ized by non-specific airway hyperresponsiveness to a variety of stimuli lasting several days or weeks
characterized by airway inflammation with increased neutrophils and eosinophils
beta-2 agonists do not reverse
prevented by cromolyn and steroids

DIAGNOSIS:

1. Typical Symptoms

at least 3 episodes of cough, wheeze, dyspnea

2. Suggestive Risk Factors

family and/or past medical history of atopy and/or eczema

3. By Exclusion

of other causes of cough and/or wheeze

4. Obstructive Lung Disease on Pulmonary Function Testing

for patients older than 6 years of age

5. Positive Response to Therapy

CLINICAL FEATURES:

1. Respiratory Manifestations

1. Recurrent (at least 3 episodes) and Prolonged (>2 weeks):

1. Cough

nocturnal, morning, daytime
with feeds, laughing, crying, and/or activity
does coughing cause vomiting of phlegm
productive or non-productive (i.e., throat clearing)

2. Wheeze

with colds and/or activity

3. Dyspnea

with colds and/or activity

2. Triggers

allergies - viruses - exercise
irritants - weather change

3. Degree of Severity

1. Mild Chronic Asthma

morning cough, cough with activity
no or infrequent (<1/week) need for Ventolin
no recent emergency room (ER) visits

2. Moderate Chronic Asthma

nocturnal wheeze or cough
frequent (>1/week) need for Ventolin
recent ER visit or hospitalization

3. Severe Chronic Asthma

ascultory findings on chest exam

4. Timing

1. Seasonal

symptoms wax and wane with the seasons

2. Perennial

symptoms occur year round

3. Intermittent

occasional episodes with no symptoms in between

5. Associated Symptoms

do colds settle in the head or chest
recurrent otitis media

6. Physcial Exam

ENT
respiratory (with coughing, deep breathing, tickling)
cardiovascular

INVESTIGATIONS:

1. First Line

Chest X-Ray (+/- inspiratory/expiratory films)
Pulmonary Function Test (if >6 yrs of age)
Skin Testing (if indicated on history)

2. Second Line (where indicated)

1. Imaging Tests

Sinus X-Ray and/or CT - Barium Swallow
Chest CT - 2D Echo
Lateral Neck X-Ray

2. Serum

CBC
Immunoglobulins - IgA, IgM, IgG (plus subclasses)
serology for viruses, bacteria, and/or fungi

3. Others

sweat chloride test
nasal secretions for eosinophils
ECG
bronchoscopy/endoscopy

MANAGEMENT:

I. APPROACH

1. Diagnosis + Education
2. Goals of Therapy
3. Treatment Options
4.Avoidance of Triggers
5.Medical
1. Step-up Management

2. Step-down Management
6. Medications
1. Beta-2 Agonists
2. Non-Steroidal Antiinflammatory Drugs
- Sodium Cromoglycate (Intal)
- Ketotifen (Zaditen)
- Nedocromil Sodium (Tilade)
3. Steroids
- Inhaled
- Oral

1. Diagnosis + Education

1. What is Asthma

diagnosis based upon history, physical, investigations, etc
2 components - inflammation, bronchospasm

2. Identification of Triggers

viral, weather change, exercise
allergens, irritants

3. Management Plans For:

1. Asthma

interval asthma - period between exacerbations
acute exacerbation
when asthma is out of control

2. Medications

mechanism of action and side effects

3. Follow-up

to follow response to therapy (for diagnosis)
keep an asthma diary

also remember that controlling allergic rhinitis (+/-sinusitis will help to control the asthma

2. Goals of Therapy

absence of cough (nocturnal, morning, with crying or laughing, with exercise)
normal exercise tolerance
normal spirometry or peak flows
mild episodes during viral infections
infrequent or no bronchodilator use

3. Treatment Options

1. Prevention

Avoidance of Triggers

2. Conservative

Do nothing and reassure patient that will probably outgrow asthma with time if not atopic

3. Prednisone

4. Regular Medications

Ventolin, Non-Steroidal Antiinflammatory Drugs, Inhaled
Steroids

4. Avoidance of Triggers

1. Irritants

avoid first- and second-hand cigarette smoke in home or in car
avoid air pollutants

2. Allergens

see "CHRONIC ASTHMA"
dust mite and animal dander control
avoid foods causing allergies

3. Viral

remove from daycare

5. Medical

1. Step-up Management

1. Indications

mild asthma in those patients <3 years of age

2. Approach

initially use non-steroidal antiinflammatory drugs and if there is a failure to achieve sufficient control, step up to low-dose inhaled steroids

2. Step-down Management

1. Indications

moderate-severe asthma in those <3 years of age
all degrees of asthma in those older than 3 years of age

2. Approach

initially use inhaled steroids (+/- oral steroid) and then reduce the inhaled steroid to the minimum neces-sary for maintenance of a symptom-free state

3. Phases

1. Aggressive Control

to eliminate respiratory mucosal inflammation
use Ventolin on a prn basis

1. Inhaled Steroids

mild - 400 ug/d x 3-4 wks
moderate - 800-1000 ug/d x 3-4 wks
severe - 800-1000 ug/d x 3-4 wks + 1-2 mg/kg oral Prednisone x 5days

2. Reduction to Maintenance

begin once goals of therapy have been achieved
reduce dosage of inhaled steroid to the minimum necessary to keep the patient asymptomatic - reduce dosage over a 2-3 week period

3. Action Plan Therapy

with symptom recurrence or signs of an upper respiratory tract infection, double the dose of inhaled steroid and use bronchodilator on a prn basis
if bronchodilators needed more often than q4h or at the maximal dose of inhaled steroid add oral prednisone

6. Medications

1. Beta-2 Agonists

1. Salbutamol (Ventolin)

1. History

first report on the beta-adrenergic properties of salbutamol (Nature 219:863, 1968)

2. Mechanism of Action & Pathophysiologic Effects

beta-2 agonist - activates beta-2 receptors in the respiratory mucosa and thus causes broncho-dilation of the airways

3. Indications For Use

all types and degrees of acute and chronic asthma

4. Side Effects

irritability, hyperactivity, tachycardia

5. Delivery Systems

1. Formulations

oral - tablets - 2 & 4 mg/tablet
aerosol - inhaler (MDI) - 100 ug/puff
powder - rotacap - 200 & 400 ug/cap
diskhaler - 400 ug/disk
turbohaler - 500 ug/dose
nebulized - nebules - 2.5 & 5 mg/2.5cc

6. Management Considerations

use Ventolin as one would use tylenol for a headache, i.e., q4h prn
as rough guidelines - if taking:
- four puffs q4h - contact physician
- mask q3h - start Prednisone
- mask q2h - go to Emergency Department

2. Non-Steroidal Antiinflammatory Drugs (NSAID)

all 3 drugs can be used as a single prophylactic agent (mild chronic asthma, exercise-induced asthma) or as an adjunct to high-dose inhaled steroids

1. Sodium Cromoglycate (Intal)

1. History

available since 1967
derivative of chromone-2-carboxylic acid
lipid insoluble thus poorly absorbed (<1%) and that which is absorbed is rapidly eliminated (half life is 90 minutes)

2. Mechanism of Action & Pathophysiologic Effects

inhibits the early phase (mast cell stabilization, inhibits C-fibres or irritant receptors)
inhibits the late phase

3. Indications For Use

mild chronic asthma (in those <3 yrs of age)
allergen-induced asthma (pollen-sensitive)
exercise-induced asthma
irritant-induced asthma

4. Side Effects/Disadvantages

SE: local irritation & rash are extremely rare
time consumming to deliver nebulized medication

5. Delivery Systems

1. Formulations (for those >3 yrs of age)

aerosol - inhaler (MDI) - 1mg/puff
powder - spinhaler - 20 mg/cap

2. Nebulized (for those <3 yrs of age)

nebules - 20 mg/dose

6. Management Considerations

initially use 20 mg qid x 4-6 wks + Ventolin prn (can use 2 mg qid of the MDI)
after stabilization, stop Ventolin and decrease
Intal dosage to bid
if acute exacerbation, add back Ventolin and increase Intal dosage to 4-6x per day
75% respond to Intal and can be weaned to bid
25% require 3 or more treatments before response
continue use until trigger eliminated (i.e., al-lergen, irritant, cold season)

2. Ketotifen (Zaditen)

1. History

available since 1978 (1991 in Canada)
a benzocycloheptathiophene
rapidly absorbed from the GI tract with peak levels at 2-4 hours (half life is 21 hours)

2. Mechanisms of Action & Pathophysiologic Effects

inhibits both the immediate and late phases by inhibiting the release of histamine (an antihis-tamine) and other inflammatory mediators

3. Indications for Use

mild chronic asthma (in those <3 yrs of age)
allergen-induced asthma
other allergic disorders (rhinitis, urticaria, eczema)

4. Side Effects/Disadvantages

transient sedation (8%), weight gain (5%)

5. Delivery Systems

oral preparations only
1 mg tablets; 1mg/5cc elixer

6. Management Considerations

initially use 1 mg po bid x 6-8 weeks + Ventolin prn
after stabilization, stop Ventolin and continue with Ketotifen as a single prophylactic agent - if acute exacerbation, add back Ventolin - atopic patients more likely to respond - 50-60% of patients do not respond

3. Nedocromil Sodium (Tilade)

1. History

new product approved for used in patients >12 yrs
5-10% of drug absorbed from lungs

2. Mechanism of Action & Pathophysiologic Effects

inhibits the release of inflammatory mediators
inhibits the reflex response triggered by neuronal pathways in the airways

3. Indications For Use

mild chronic asthma (in those <3 yrs of age)
exercise-induced asthma
allergen-induced asthma
irritant-induced asthma

4. Side Effects/Disadvantages

bad taste (13%), headaches (5%), nausea (4%)

5. Delivery Systems

aerosol - inhaler (MDI) - 2 mg/puff

6. Management Considerations

initially use 4 mg qid x 1-2 weeks + Ventolin prn
after stabilization, stop Ventolin and decrease Tilade dosage to 2mg bid slowly
if acute exacerbation, add back Ventolin and increase Tilade dose to 4 mg qid

3. Inhaled Steroids

1. History

represent one of the most significant advances in asthma therapy over the past few decades

2. Mechanism of Action & Pathophysiologic Effects

potent topical antiinflammatory effect on respiratory mucosa
decreases mucous secretion, decreases fluid leakage from cells and vasculature, suppresses PMN response - inhibits the early and late phases, the latter only after 1-2 weeks of therapy
only asthma medication which reverses pathology

3. Indications For Use

mild -> severe chronic asthma of all types
no role in management of acute asthma attacks

4. Side Effects/Disadvantages

evidence that low-dose inhaled steroids (<500 ug/day) is safe in children older than 5 but risks are unknown in those less than 5 years of age
there is no evidence that high-dose inhaled steroids (>500 ug/day) is safe in children of any age

1. Minor

cough/wheeze - oropharyngeal candidiasis
Cushingoid appearance - psychic side effects
dysphonia - skin thinning & purpura

2. Major

changes in bone metabolism (osteoporosis)
growth suppresion
Hypothalamus-Pituitary-Adrenal Axis suppression

3. Ways of Minimizing Side Effects

rinse mouth after inhalation
decrease frequency and amount of steroid given (<400 ug/day or 14 ug/kg/day considered safe)
use spacer device
do not use long term
add a NSAID and reduce steroid dosage
use Budesonide when higher doses are required

5. Delivery Systems

1. Formulations

aerosol - inhaler (MDI) +/- spacer
powdered - rotahaler, diskhaler, turbohaler
nebulized - nebules

6. Medications

1. Beclomethasone

1. Beclovent

1. MDI (aerosol)

50 ug/puff

2. Rotahaler (powder)

100 & 200 ug/cap

2. Becloforte MDI (aerosol)

250 ug/puff

3. Beclodisk (powder)

100 & 200 ug/cap

2. Budesonide

1. Pulmicort

1. MDI and Spacer (aerosol)

50 & 200 ug/puff

2. Turbuhaler (powder)

100, 200, & 400 ug/cap

3. Nebuamp (nebulized)

250 & 500 ug/dose

3. Flunisolide

1. Bronalide MDI (aerosol)

250 ug/puff

4. Triamcinolone Actetonide

1. Azmacort MDI (aerosol)

100 ug/puff

7. Management Considerations

initially use 400-2000 ug/day bid-qid + Ventolin prn
after stabilization, stop Ventolin and decrease steroid dosage to <400 ug/day bid
if acute exacerbation add back Ventolin and increase dosage to 400-2000 ug/day bid-qid x 1 week - low dose inhaled steroid: <400 ug/day
high " : >400 "
moniter height while on inhaled steroids

4. Oral Prednisone

1-2 mg po/pr od x 5 days

REFERENCES:

1. Hargreave et al., J. Allergy Clin. Immunol. 85:1098 (1990)
2. NAEP Expert Panal, " 88:425 (1991)
3. International Consensus Group, Arch. Dis. Childhood 67:240 (1992)
4. Zimmerman, Contemporary Pediatrics, Feb. 1994:11 (1994)

Pediatric Database - CHRONIC ASTHMA

Pediatric Organization - Pedbase [at] Gmail.com