Asthma
ABDULLAH M. AL-OLAYAN
MBBS, SBP, ABP.
ASSISTANT PROFESSOR OF PEDIATRICS.
PEDIATRIC PULMONOLOGIST.
Objectives
① Define asthma, and describe its pathogenesis,
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pathophysiology and the clinical manifestations.
Describe the risk factors and types of asthma.
List the differential diagnosis of a wheezy child.
Enumerate the types of drugs used in the treatment
of asthma (pharmacologic effects and side effects).
Define the status asthmaticus and recognize the
assessment parameters.
Discuss the principles of management and
subsequent treatment.
Definition
 Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation.
 It is defined by the history of respiratory
symptoms such as wheeze, shortness of breath,
chest tightness and cough that vary over time and in
intensity, together with variable expiratory
airflow limitation.
( GINA 2015 )
Pathophysiology
A. Inflammatory cells (mast cells, eosinophils,
T lymphocytes, neutrophils),
B. Chemical mediators (histamine, leukotrienes,
platelet activating factor, bradykinin).
C. Chemotactic factors (cytokines, eotaxin).
 Mediate the underlying inflammation found in
asthmatic airways.
 Inflammation contributes to air way
hyperresponsiveness.
Pathophysiology
 It also results in edema, increased mucus
production in the lungs, influx of inflammatory
cells into the airway, and epithelial cell
denudation.
 Chronic inflammation can lead to airway
remodeling, which results from a proliferation of
extracellular matrix proteins and vascular
hyperplasia and may lead to irreversible
structural changes and a progressive loss of
pulmonary function.
Epidemiology
 Childhood asthma is among the most common
causes of childhood emergency department visits,
hospitalizations, and missed school days.
 Boys are more likely than girls to have asthma.
Clinical Manifestations
 Children with asthma have symptoms of :
Coughing.
II. Wheezing.
III. Shortness of breath or rapid breathing.
IV. Chest tightness.
I.
Clinical Manifestations
 Exacerbating factors include :
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Viral infections.
Exposure to allergens and irritants (e.g., smoke,
strong odors, fumes).
Exercise.
Emotions.
Change in weather / humidity.
 Nighttime symptoms are common.
Clinical Manifestations
 Rhinosinusitis, gastroesophageal reflux, and
nonsteroidal anti-inflammatory drugs (especially
aspirin) can aggravate asthma.
 During acute episodes :
① Tachypnea.
② Tachycardia.
③ Cough.
④ Wheezing, and a prolonged expiratory phase.
Clinical Manifestations
 As the attack progresses :
1) Cyanosis.
2) Diminished air movement.
3) Retractions.
4) Agitation.
5) Inability to speak.
6) Tripod sitting position.
7) Diaphoresis.
8) Pulsus paradoxus (decrease in blood pressure of >15 mm Hg
with inspiration).
 Physical examination may show evidence of other atopic
diseases such as eczema or allergic rhinitis.
Types of Asthma
 1) Recurrent wheezing in early childhood,
primarily triggered by common respiratory viral
infections, usually resolves during the
preschool/lower school years.
 (2) Chronic asthma associated with allergy that
persists into later childhood and often adulthood.
Laboratory and Imaging Studies
 Objective measurements of pulmonary function
test (spirometry) help establish the diagnosis and
direct the treatment of asthma.
 Children older than 5 years of age can perform
spirometry maneuvers.
 Allergy skin testing should be included in the
evaluation of all children with persistent asthma but
not during an exacerbation of wheezing.
Laboratory and Imaging Studies
 Chest X Ray Indications :
① Focal examination findings (eg, crackles or
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decreased breath sounds).
Fever (>39ºC).
Severe disease.
To rule out pneumonia, atelectasis, and air leak
Uncertainty about the diagnosis.
Tachypnea, hypoxemia, or chest pain that are
present after initial therapy has been given.
Differential Diagnosis
Treatment
 3 main components :
① Environmental control.
② Pharmacologic therapy.
③ Patient education.
Pharmacologic Therapy
 Asthma medications can be divided into :
A. Quick-relief medications.
B. Long-term control medications.
Pharmacologic Therapy
 Quick-relief medications :
 Short-Acting β2-Agonists :
Short-acting β2-agonists, such as Salbutamol (Ventolin),
and levalbuterol.
Drugs of choice for acute asthma symptoms (“rescue”
medication).
MOA :
Bronchodilators by relaxing bronchial smooth muscle
within 5 to 10 minutes of administration.
They last for 4 to 6 hours.
Pharmacologic Therapy
 Quick-relief medications :
 Short-Acting β2-Agonists :
It is available in both MDI and nebulizer
formulations.
Side effects :
① Tremor.
② Tachycardia.
③ Irritability.
④ Hypokalemia.
Pharmacologic Therapy
Pharmacologic Therapy
 Quick-relief medications :
 Anticholinergic Agent :
Ipratropium bromide is an anticholinergic bronchodilator.
It seems to have an additive effect with β2-agonists when
used for acute asthma exacerbations.
MOA :
Binding acetylcholine at the muscarinic receptors found in
bronchial smooth muscle.
Relieves bronchoconstriction.
Decreases mucus hypersecretion.
Pharmacologic Therapy
 Quick-relief medications :
Oral Corticosteroids :
 Steroids decrease inflammation by:
① Alter transcription of certain target genes resulting in
inhibition of the translation of the genes for many
cytokines.
② Increase the breakdown of some cytokines and
inhibit the synthesis of their receptors thus decrease
the inflammation.
③ Inhibit cellular immune response.
④ Increase 2 adrenergic receptors.
⑤ Inhibit mucous secretion into the airways.
Pharmacologic Therapy
 Quick-relief medications :
Oral Corticosteroids :
Short course of oral corticosteroids (3 to 5 days) are
administered to children with acute exacerbations.
Prednisone 1 to 2 mg/kg/day 3 to 5 days.
Pharmacologic Therapy
 Quick-relief medications :
Oral Corticosteroids :
Side effects :
① Hypothalamic-pituitary-adrenal suppression.
② Cushingoid features.
③ Weight gain.
④ Hypertension.
⑤ Diabetes.
⑥ Cataracts.
⑦ Glaucoma.
⑧ Osteoporosis.
⑨ Growth suppression.
Pharmacologic Therapy
 Long-term control medications :
Inhaled Corticosteroids :
 Inhaled corticosteroids are the most effective
anti-inflammatory medications for the
treatment of chronic, persistent asthma.
 Early intervention with inhaled corticosteroids
reduces morbidity but does not alter the natural
history of asthma.
Pharmacologic Therapy
 Long-term control medications :
 Inhaled Corticosteroids :
Side effects :
① Reduction in growth velocity.
② Dysphonia.
③ Candidiasis.
Rinsing the mouth after inhalation and using spacers
help lessen the local adverse effects of dysphonia and
candidiasis.
Pharmacologic Therapy
Pharmacologic Therapy
 Long-term control medications :
 Leukotriene Modifiers :
Leukotrienes, are potent mediators of inflammation
and smooth muscle bronchoconstriction.
Leukotriene modifiers are oral, daily-use
medications that inhibit these biologic effects in the
airway.
Pharmacologic Therapy
 Long-term control medications :
 Leukotriene Modifiers :
 Two classes of leukotriene modifiers include :
① Cysteinyl leukotriene receptor antagonists
(zafirlukast and montelukast).
② Leukotriene synthesis inhibitors (zileuton).
Pharmacologic Therapy
 Long-term control medications :
Leukotriene Modifiers :
o Used for exercise-induced bronchoconstriction.
o May be helpful as steroid-sparing agents in patients.
Pharmacologic Therapy
 Long-term control medications :
Long-Acting β2-Agonists :
 Long-acting β2-agonists, formoterol and salmeterol.
 Relax airway smooth muscle for 12 hours.
 Formoterol is approved for children older than 5 years for
maintenance therapy and for prevention of exercise-induced
asthma. It has a rapid onset of action (15 minutes).
 Salmeterol is approved for children 4 years of age or older and
has an onset of 30 minutes.
o Adding a long-acting bronchodilator to inhaled
corticosteroid therapy is more beneficial than doubling the
dose of inhaled corticosteroids.
Pharmacologic Therapy
Pharmacologic Therapy
 Long-term control medications :
Theophylline :
o Theophylline was more widely used previously, but,
because current management is aimed at inflammatory
control, its popularity has declined.
o It is mildly to moderately effective as a bronchodilator.
Pharmacologic Therapy
 Long-term control medications :
Omalizumab :
o Omalizumab (Xolair) is a humanized anti-IgE monoclonal
antibody that prevents binding of IgE to high-affinity
receptors on basophils and mast cells.
o It is approved for moderate to severe allergic asthma in
children 12 years of age and older.
o Xolair is delivered by subcutaneous injection every 2 to 4
weeks, depending on body weight and pretreatment serum
IgE level.
Approach to Therapy
 A step- wise approach is used for management of infants
and young children 0 to 4 years, children 5 to 11 years,
youths 12 years or older, and adults.
 Medication type, amount, and scheduling are
determined by the level of asthma severity or asthma
control.
 Therapy is then increased (stepped up) as necessary and
decreased (stepped down) when possible.
Status Asthmaticus
 Acute exacerbation of asthma that does not
respond adequately to therapeutic measures and
may require hospitalization.
 Status Asthmaticus is the condition of a patient in
progressive respiratory failure due to asthma.
Initial Therapies:
*** If intubated, utilize this side
of pathway for escalation.
Albuterol 10 mg/hr or 25 mg/hr continuous neb
Atrovent 0.5 mg q6h neb x 24hrs
Methylprednisolone IV 1 mg/kg q6 (max 60 mg q6h)
Continued Respiratory Distress
***
Minimal Wheeze, fair/good air entry
Marked wheezing, poor air entry
Hemodynamically Stable
If FiO2 < 50%
Hemodynamically
Unstable
If FiO2 >50%
Heliox + Albuterol
Magnesium*
BiPap
Tachycardic or
unstable hemodynamics
Not Tachycardic
Terbutaline*
BiPap
If no improvement
after 1-2 hours
Aggressively treat
hemodynamics
Severely
Tachycardic
Terbutaline*
Need for escalation despite BiPap, albuterol,
and multiple bronchodilators
Consider Aminophylline * for wheeze,
poor air entry or long exhalation
Additional Standard
Medications/Monitoring
•IV Fluids containing potassium at 1.5X
maintenance
•GI prophylaxis with H2 blocker or PPI
•Serial electrolytes q12h (at least K)
while on continuous -agonist
•May use IM epinephrine as rescue
therapy
Escalation if marked wheeze,
Or poor air entry
Not Tachycardic
BiPap
Medication requires
special ongoing monitoring
BiPap
Magnesium*
Aggressively treat
hemodynamics
*
BiPap
Escalation w/ minimal wheeze,
Ongoing respiratory distress and fair air entry
Intubation with mechanical ventilation
Hemodynamic Parameters
Inhalational
Anesthetics
ECMO
•Severe Tachycardia:>180 if <5yo; >150 bpm if >5yo.
•Unstable: Hypotensive for age, diastolic hypotension, cap refill
>4 seconds or <1 second, abnormal pulses, lactic acidosis,
evidence of CV ischemia.
•Hemodynamic interventions should include aggressive fluid
resuscitation and possible vasopressors.
Asthma Treatment Guide
Medications
Magnesium
•Given as magnesium sulfate either as bolus or infusion
•Dosage is bolus of 50-75 mg/kg over 20 minutes (max dose 2g)
•Effect seen immediately; decreased wheeze or improved air
entry right after dose complete.
•Maintenance dose is a drip at 15-20 mg/kg/hr (adjusted for
levels) or 50-75 mg/kg q4h if can’t use a drip.
•Monitoring: Check serum magnesium level every 4 hours while
on magnesium. Target level of 4-5.
•WATCH for hypotension or severe weakness as sign of toxicity.
Terbutaline
•Given as a bolus dose followed by infusion.
•Initial bolus dose of 10 mcg/kg over 10 minutes.
•Initial drip rate of 0.5-1 mcg/kg/min.
•May titrate drip q30 min with 5 mcg/kg bolus and increase of 0.5
mcg/kg/min increments
•Should consider alternate therapy when infusion >3 mcg/kg/min.
•Monitoring: Requires continuous EKG monitoring and serial
serum potassium (and troponin levels if age >12y).
•DO NOT USE if evidence of cardiac injury or ischemia.
•WATCH for hypokalemia, hypotension, or severe tachycardia.
Aminophylline
•May consider earlier in treatment if patient smokes.
•Given as a bolus dose followed by infusion
•Initial bolus of 6 mg/kg over 20-30 minutes.
•Initial drip rate is age dependant.
<6 months old: 0.5 mg/kg/hr
6-12 months old: 0.7 mg/kg/hr
1-9 years old: 1 mg/kg/hr
>9 years old (nonsmoker):0.5 mg/kg/hr
>9 years old (smoker):0.8 mg/kg/hr
•Monitoring: Requires q12h serum theophylline levels on infusion
plus level 30 minutes after loading dose.
•Goal Level: 10-20 mcg/mL
•May repeat load for low serum level. Load of 1 mg/kg will
increase level ~ 2 mcg/mL.
BiPap Management
Settings
•Should start with EPAP of 4-6 and IPAP of 10-12
•Titrate IPAP based on pt comfort, work of breathing, and
improved air entry.
•Use caution with IPAP over 20 or if unable to wean FiO2 below
60%.
•Use caution in patients with emesis or decreased level of
consciousness.
Sedation
•Many patients may require some sedation to tolerate BiPap.
•Consider low-dose ketamine or dexmedetomidine.
•Ketamine drip: 0.5-1 mg/kg/hr
•Dexmedetomidine: 0.3-1 mcg/kg/hr
Heliox
•May use heliox with non-invasive vent but only using Avea with
patients who are developmentally able to remove mask
De-escalation
•Decreases in care should occur in stepwise fashion.
•De-escalation should begin with therapies with highest toxicity.
•Recommended order as follows:
•Discontinue ECMO or Inhalational Anesthetic
•Wean and discontinue ventilation via ETT.
•Discontinue aminophylline (if applicable).
•Wean and discontinue terbutaline. Wean in same way
as escalation (e.g. by 0.2-0.5 mcg/kg/hr) every 30-60
minutes.
•Discontinue magnesium.
•Wean and discontinue BiPap
•Space albuterol treatments
• Note: May alter order of weaning aminophylline, terbutaline,
magnesium, albuterol and BiPap, depending on patient needs
such as wheezing vs. work of breathing.
Prevention
 Education plays an important role in helping
patients and their families adhere to the prescribed
therapy and needs to begin at the time of diagnosis.
① Teaching basic asthma facts.
② Explaining the role of medications.
③ Teaching environmental control measures.
④ Improving patient skills in the use of spacer devices.
• Families should have an asthma management plan for
daily care and for exacerbations.
Reference