Childhood Asthma

Quick Reference

Critical Alerts

• Silent chest is ominous: Absence of wheeze may indicate severe airflow obstruction with minimal air movement
• Hypoxia is a late sign: Respiratory fatigue and hypercapnia typically precede significant oxygen desaturation
• Magnesium for severe asthma: 40 mg/kg IV (max 2g) over 20 minutes for refractory cases
• Continuous salbutamol for severe exacerbations: Back-to-back nebulisers, not PRN dosing
• Early corticosteroids reduce admissions: Administer within first hour of presentation
• Avoid intubation if possible: Associated with significant morbidity in status asthmaticus

Severity Assessment at Presentation

Emergency Treatment Protocol (BTS/SIGN)

---

Overview

Childhood asthma is a chronic inflammatory disorder of the airways characterised by variable airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation. It represents the most common chronic disease of childhood globally, affecting approximately 14% of children worldwide with significant geographic variation. [1] The condition manifests as recurrent episodes of wheeze, cough, breathlessness, and chest tightness that are typically reversible either spontaneously or with treatment.

The diagnosis of asthma in children, particularly those under 5 years of age, presents significant challenges due to the inability to perform objective lung function testing and the overlap with other wheezing phenotypes. Approximately 50% of preschool children will experience at least one wheezing episode before age 6, yet only a minority will develop persistent asthma. [2] Understanding wheeze phenotypes and their natural history is essential for appropriate diagnosis and management.

Management encompasses both acute exacerbation treatment and long-term controller therapy. Current guidelines from BTS/SIGN and GINA recommend a stepwise approach to chronic management, escalating therapy based on symptom control and exacerbation frequency. [3] Early recognition and aggressive treatment of acute exacerbations significantly reduces morbidity, hospitalisations, and mortality.

---

Epidemiology

Global Burden

Asthma affects an estimated 262 million people worldwide, with 14% of children globally experiencing asthma symptoms. [1] The prevalence varies substantially by region, with highest rates observed in high-income English-speaking countries.

Age and Sex Distribution

Asthma demonstrates distinct age-related patterns. In childhood, males are more commonly affected (male:female ratio approximately 1.5:1), though this reverses after puberty when females become more frequently affected. [4] Peak onset occurs in the first 5 years of life, with 80% of asthmatic children developing symptoms before age 6.

Healthcare Utilisation

Childhood asthma accounts for significant healthcare resource utilisation:

• 1.8 million emergency department visits annually in the United States (age less than 18 years)
• 130,000 hospitalisations per year
• Leading cause of school absenteeism, responsible for 13.8 million missed school days annually
• Estimated annual cost of $81.9 billion in the United States [5]

Mortality

Asthma deaths in children have declined significantly over the past two decades but remain a concern. The United Kingdom reports approximately 25 deaths annually in children under 18 years. [6] Risk factors for fatal asthma include:

---

Aetiology and Risk Factors

Genetic Factors

Asthma has a strong genetic component with heritability estimates of 35-95%. Multiple genes have been implicated in asthma susceptibility:

The 17q21 locus (ORMDL3/GSDMB) represents the most replicated genetic association with childhood asthma, with risk alleles increasing asthma risk approximately 1.5-fold. [7] This association is particularly strong for early-onset, rhinovirus-triggered wheeze.

Environmental Risk Factors

Prenatal and Early Life Exposures:

• Maternal smoking during pregnancy (OR 1.85)
• Prematurity and low birth weight
• Mode of delivery (caesarean section associated with 20% increased risk)
• Early antibiotic exposure
• Lack of breastfeeding

Allergen Sensitisation:

• House dust mite
• Pet dander (cat, dog)
• Cockroach allergen
• Mould (Alternaria, Aspergillus)
• Pollen

Environmental Exposures:

• Environmental tobacco smoke exposure
• Traffic-related air pollution (NO2, PM2.5)
• Indoor air quality (gas cooking, volatile organic compounds)

Protective Factors

The "hygiene hypothesis" and subsequent "microbiome hypothesis" suggest that early microbial exposures may protect against asthma development:

• Farm exposure in early life (OR 0.5-0.7) [8]
• Having older siblings
• Pet exposure in early infancy (controversial)
• Diverse gut microbiome in infancy
• Attendance at day care

---

Pathophysiology

Airway Inflammation

Asthma is characterised by chronic airway inflammation involving multiple cell types and inflammatory mediators. The inflammatory cascade results in:

1. Mast cell activation: Allergen cross-linking of IgE on mast cells triggers degranulation, releasing histamine, prostaglandins, and leukotrienes
2. Eosinophilic infiltration: IL-5 driven eosinophil recruitment and activation, releasing major basic protein and eosinophil cationic protein
3. T-helper 2 (Th2) response: CD4+ T cells producing IL-4, IL-5, and IL-13, driving IgE production and eosinophilia
4. Epithelial dysfunction: Barrier disruption, alarmin release (IL-33, TSLP, IL-25), and goblet cell metaplasia

Exam Detail: Molecular Pathways in Asthma:

The type 2 inflammatory pathway is central to most childhood asthma:

1. Epithelial alarmins: Damaged epithelium releases IL-33, TSLP, and IL-25
2. ILC2 activation: Innate lymphoid cells type 2 produce IL-5 and IL-13 independent of adaptive immunity
3. Th2 polarisation: Dendritic cells present allergen to naive T cells, inducing Th2 differentiation
4. B cell class switching: IL-4 drives IgE production
5. Eosinophil recruitment: IL-5 promotes eosinophil maturation, release, and survival
6. Mucus hypersecretion: IL-13 induces goblet cell metaplasia and MUC5AC production
7. Smooth muscle hypertrophy: Chronic inflammation leads to airway remodelling

Non-type 2 asthma (less common in children) involves neutrophilic inflammation, IL-17 pathways, and is often associated with obesity and poorer corticosteroid response.

Airway Hyperresponsiveness

Bronchial hyperresponsiveness (BHR) is the exaggerated bronchoconstrictor response to stimuli that would not affect normal airways. Mechanisms include:

• Increased smooth muscle mass and contractility
• Enhanced cholinergic neural activity
• Reduced smooth muscle relaxation due to epithelial damage (loss of epithelium-derived relaxing factors)
• Geometric amplification from airway wall thickening

Airway Remodelling

Chronic inflammation leads to structural changes in the airway wall:

Acute Exacerbation Pathophysiology

Acute exacerbations involve rapid amplification of inflammation and bronchoconstriction:

1. Trigger exposure: Viral infection (most common), allergen, irritant
2. Epithelial injury: Viral cytopathic effect, alarmin release
3. Inflammatory cell influx: Neutrophils (early), eosinophils (late)
4. Bronchospasm: Smooth muscle contraction
5. Mucus plugging: Inspissated secretions obstruct small airways
6. Airway oedema: Vascular leakage
7. Air trapping: Incomplete expiration leads to dynamic hyperinflation
8. V/Q mismatch: Hypoxaemia
9. Respiratory muscle fatigue: Hypercapnia (late, ominous)

Clinical Significance of Silent Chest

A "silent chest" in acute severe asthma indicates minimal airflow, not improvement. With severe bronchospasm and mucus plugging, air movement is insufficient to generate wheeze. This is a pre-arrest state requiring immediate aggressive intervention.

---

Diagnosis in Children Under 5 Years

Challenges in Preschool Diagnosis

Diagnosing asthma in children under 5 years presents unique challenges:

1. Inability to perform spirometry: Objective confirmation not possible
2. Wheeze phenotype heterogeneity: Multiple phenotypes with different prognoses
3. High prevalence of viral wheeze: Most preschool wheeze is transient
4. Symptom overlap: Bronchiolitis, viral-induced wheeze, and asthma overlap clinically

Wheeze Phenotypes

Understanding preschool wheeze phenotypes is essential for prognostication and management decisions. [9]

Temporal Pattern Classification:

Trajectory-Based Classification (Birth Cohort Studies):

Clinical Features Suggesting Asthma

Features increasing probability of asthma:

• Wheeze on more than one occasion
• Chronic cough, especially at night or early morning
• Symptoms triggered by multiple factors (cold air, exercise, emotions)
• Personal history of atopy (eczema, allergic rhinitis)
• Family history of asthma or atopy in first-degree relatives
• Widespread wheeze on auscultation
• History of improvement with bronchodilator therapy
• Symptoms improve when on controller therapy

Red flags suggesting alternative diagnosis:

• Neonatal or very early symptom onset (less than 4 weeks)
• Continuous wheeze from birth
• Failure to thrive
• Focal or fixed lung signs
• Symptoms associated with feeding/vomiting
• Productive cough with purulent sputum
• Cardiac murmur
• No response to asthma therapy

Diagnostic Approach

Step 1: Structured Clinical Assessment

Detailed history focusing on:

• Pattern of symptoms (episodic vs persistent, triggers)
• Severity and frequency
• Night-time symptoms
• Response to previous treatment
• Atopic personal and family history
• Environmental exposures

Step 2: Trial of Therapy

BTS/SIGN and GINA recommend a structured trial of therapy: [3]

Trial of therapy protocol:

1. Initiate ICS (moderate dose) for 8-12 weeks
2. Assess symptom response, reliever use, and parent-reported control
3. If improved, attempt dose reduction or withdrawal
4. Monitor for symptom recurrence

Step 3: Objective Testing (When Possible)

Exam Detail: Predictive Indices for Asthma in Preschoolers:

Modified Asthma Predictive Index (mAPI): Predicts asthma at school age in children with ≥4 wheezing episodes in first 3 years

Major criteria (need 1):

• Parental asthma
• Physician-diagnosed atopic dermatitis
• Allergic sensitisation to ≥1 aeroallergen

Minor criteria (need 2):

• Allergic sensitisation to milk, egg, or peanut
• Wheezing unrelated to colds
• Blood eosinophilia ≥4%

Positive mAPI: 77% will have active asthma at age 6-13 years Negative mAPI: 91% will NOT have active asthma

This index is useful for counselling parents but should not determine treatment decisions, which should be based on symptom control.

Differential Diagnosis

---

Severity Classification and Stepwise Approach

Chronic Asthma Control Assessment

Asthma control should be assessed at every visit using validated tools:

GINA Assessment of Control (Children 6-11 years):

For children ≤5 years (GINA):

• Symptom frequency (days/week)
• Night waking (times/month)
• Activity limitation (any/none)
• Reliever need (days/week)

Validated Control Questionnaires

BTS/SIGN Stepwise Approach

The British Thoracic Society and Scottish Intercollegiate Guidelines Network provide a stepwise approach for chronic asthma management: [3]

Children Under 5 Years:

Children 5-12 Years:

Clinical Pearl: BTS/SIGN vs GINA Differences:

BTS/SIGN recommends LABA as first add-on therapy to ICS in children 5-12 years, while GINA suggests either LABA or LTRA based on phenotype. Both agree that ICS remains the cornerstone of therapy and that response to treatment should guide ongoing management.

GINA now recommends that adolescents (≥12 years) should receive ICS-formoterol as both reliever AND controller (MART/SMART) where appropriate, reducing exacerbation risk compared to SABA-only reliever.

ICS Dose Equivalents

Beclometasone dipropionate equivalent doses (mcg/day):

Treatment Goals

1. Minimal symptoms during day and night
2. No limitations on physical activity
3. Normal lung function (or personal best)
4. No exacerbations requiring oral corticosteroids, ED visits, or hospitalisation
5. Minimal reliever use (≤2 days per week)
6. Minimal medication side effects

---

Chronic Management: Pharmacotherapy

Inhaled Corticosteroids (ICS)

ICS remain the cornerstone of asthma controller therapy at all ages. They reduce airway inflammation, decrease bronchial hyperresponsiveness, reduce symptoms, improve lung function, and decrease exacerbations. [10]

Evidence Base:

• Meta-analyses demonstrate consistent reduction in exacerbations (RR 0.52-0.56) with regular ICS use
• Number needed to treat to prevent one exacerbation: 9 patients treated for 1 year
• Effects on airway inflammation persist only while taking medication

Practical Prescribing:

Safety Considerations:

• Minimal systemic effects at low-moderate doses
• High doses may affect growth velocity (1-2 cm reduction in first year, less subsequently) [11]
• Adrenal suppression possible at high doses - consider morning cortisol if on high-dose ICS > 6 months
• Local side effects: oral candidiasis, dysphonia (rinse mouth after use)

Long-Acting Beta-2 Agonists (LABA)

LABAs (salmeterol, formoterol) provide sustained bronchodilation and reduce exacerbations when added to ICS in children with inadequate control on ICS alone.

Key Points:

• NEVER use as monotherapy - must always be combined with ICS
• Licensed as add-on therapy from age 4-5 years (varies by product)
• Formoterol has rapid onset (suitable for MART regimens in adolescents)
• Salmeterol has slower onset (not suitable for relief)

Evidence Base:

• Addition of LABA to ICS improves FEV1 and symptom control [12]
• Reduces exacerbations compared to doubling ICS dose
• SMART/MART regimens (ICS-formoterol as both maintenance and reliever) reduce exacerbations in adolescents

Leukotriene Receptor Antagonists (LTRA)

Montelukast blocks cysteinyl leukotriene receptors, reducing inflammation and bronchoconstriction.

Dosing:

Indications:

• Add-on to ICS when control inadequate
• Exercise-induced bronchoconstriction
• Concomitant allergic rhinitis
• First-line in children where ICS not possible/desired (though less effective)

Efficacy:

• Less effective than ICS as monotherapy
• Modest benefit as add-on to ICS (less than LABA in most studies)
• May be particularly effective in viral-triggered wheeze and exercise-induced symptoms

Safety Considerations (FDA Boxed Warning 2020):

• Neuropsychiatric adverse events reported (sleep disturbance, behavioural changes, depression, suicidal ideation)
• Reported incidence low but parents should be counselled and symptoms monitored
• Benefits should be weighed against risks on individual basis

Long-Acting Muscarinic Antagonists (LAMA)

Tiotropium (Spiriva Respimat) is licensed as add-on therapy for children aged ≥6 years with severe asthma inadequately controlled on ICS-LABA.

Dosing:

• 2.5 mcg two puffs once daily via Respimat device

Evidence:

• Improves FEV1 and reduces exacerbations when added to ICS-LABA [13]
• Well tolerated in paediatric population
• Reserve for Step 4-5 therapy under specialist guidance

Biologic Therapies for Severe Asthma

Biologics are reserved for children with severe asthma uncontrolled on high-dose ICS-LABA with significant morbidity. Assessment in a specialist severe asthma centre is required.

Exam Detail: Selecting Biologics in Severe Paediatric Asthma:

Key biomarkers for selection:

• Blood eosinophils ≥150-300 cells/μL: Supports anti-IL-5 agents or dupilumab
• Elevated FeNO (> 25 ppb): Supports type 2 phenotype, dupilumab
• Elevated total IgE + sensitisation: Supports omalizumab
• Clinical phenotype: Allergic vs eosinophilic vs overlap guides choice

Response assessment at 4-6 months:

• Exacerbation frequency
• Oral corticosteroid requirement
• Symptom control scores
• Lung function
• Quality of life

Non-responders should have biologic switched or discontinued and diagnosis reconsidered.

Other Therapies

Theophylline:

• Rarely used in modern practice due to narrow therapeutic window
• May have anti-inflammatory properties at low doses
• Consider only in severe asthma unresponsive to other therapies
• Requires therapeutic drug monitoring

Oral Corticosteroids:

• Reserved for acute exacerbations and severe refractory asthma
• Long-term use associated with significant morbidity (growth suppression, osteoporosis, adrenal suppression)
• If required regularly, urgent specialist referral needed

Immunotherapy (Allergen-Specific Immunotherapy):

• Subcutaneous or sublingual immunotherapy for allergic asthma
• May reduce symptoms and medication requirements
• Consider in children with clearly identified allergen triggers and inadequate control on pharmacotherapy
• 3-5 year course recommended

---

Inhaler Device Selection and Technique

Device Selection by Age

Correct device selection is crucial for effective drug delivery. The best device is the one the child can and will use correctly. [16]

Spacer Devices

Types:

• Small volume (150-250 mL): Suitable for infants/toddlers (e.g., AeroChamber, Volumatic paediatric)
• Large volume (750 mL): For older children (e.g., Volumatic, Nebuhaler)

Key Points:

• Reduces oropharyngeal deposition
• Reduces need for coordination between actuation and inhalation
• Single puff technique (one actuation per 5 breaths) preferred over multiple puffs
• Wash monthly with detergent, air dry to reduce static

Dry Powder Inhalers (DPI)

Requirements:

• Adequate inspiratory flow (typically ≥30 L/min, device-dependent)
• Ability to follow multi-step instructions
• Not suitable for acute exacerbations (flow-dependent delivery)

Common Devices:

Technique Assessment

Inhaler technique should be assessed at EVERY consultation. Studies show 50-80% of patients use inhalers incorrectly. [17]

pMDI + Spacer Technique Checklist:

1. Remove cap, shake inhaler, insert into spacer
2. Place mouthpiece in mouth (or mask over nose and mouth for young children)
3. Breathe out gently
4. Press canister once
5. Breathe in slowly and deeply (tidal breathing with mask)
6. Hold breath 5-10 seconds (or 5-6 breaths with mask)
7. Wait 30 seconds before second dose if required
8. Rinse mouth after ICS

DPI Technique Checklist:

1. Load dose according to device instructions
2. Breathe out away from device
3. Seal lips around mouthpiece
4. Breathe in quickly and deeply
5. Hold breath 5-10 seconds
6. Rinse mouth after ICS

Nebulisers

Indications:

• Acute severe exacerbations (though pMDI+spacer is equivalent or superior for bronchodilators)
• Infants unable to use spacer effectively
• Delivery of medications not available in other forms

Key Points:

• Oxygen-driven in acute asthma (6-8 L/min)
• Salbutamol nebuliser dose: 2.5 mg (less than 5 years), 5 mg (> 5 years)
• Takes longer than pMDI+spacer (10-15 min vs 1-2 min)
• Face mask or mouthpiece based on age

---

Acute Exacerbation Management

Definition and Severity Assessment

An acute asthma exacerbation is an acute or subacute deterioration in symptoms and lung function from the patient's usual status, sufficient to require a change in treatment. [3]

Severity Assessment (BTS/SIGN 2019):

Initial Management

Immediate Actions (First 60 Minutes):

1. Oxygen: Maintain SpO2 94-98%
2. Inhaled bronchodilators:
   • Salbutamol 2.5-5 mg nebulised OR 10 puffs via pMDI+spacer every 20 minutes for first hour
   • Add ipratropium 250-500 mcg nebulised for severe/life-threatening (first 3 doses only)
3. Systemic corticosteroids:
   • Prednisolone 1-2 mg/kg orally (max 40 mg)
   • Give within first hour - reduces admissions and relapse
4. Assess response at 30-60 minutes

Clinical Pearl: pMDI+Spacer vs Nebuliser:

Systematic reviews demonstrate that pMDI with spacer is at least as effective as nebuliser for bronchodilator delivery in acute asthma and may be superior, with shorter ED stay and fewer side effects (tachycardia). [18]

Use nebuliser when:

• Life-threatening asthma (oxygen-driven nebulisation)
• Unable to cooperate with spacer
• Continuous bronchodilation needed

Ongoing Management Based on Response

Good Response (SpO2 ≥94%, minimal distress, PEF > 50%):

• Space bronchodilators to 1-2 hourly
• Continue oral prednisolone 1-2 mg/kg daily for 3-5 days
• Consider discharge after 4 hours if sustained response

Poor Response or Severe Asthma:

• Continue high-dose bronchodilators
• Add ipratropium if not already given
• Consider IV magnesium sulfate 40 mg/kg (max 2g) over 20 minutes
• Involve senior clinician/PICU team

Life-Threatening Asthma:

• Nebulised salbutamol 5 mg continuously or every 15-20 minutes
• Nebulised ipratropium 500 mcg every 20 minutes x3
• IV hydrocortisone 4 mg/kg (max 100 mg) every 6 hours
• IV magnesium sulfate 40 mg/kg (max 2g) over 20 minutes
• IV salbutamol 15 mcg/kg bolus over 10 minutes, then infusion 1-5 mcg/kg/min
• Consider IV aminophylline (specialist/PICU only)
• PICU referral
• Prepare for possible intubation

Pharmacotherapy in Acute Exacerbation

Short-Acting Beta-2 Agonists (SABA):

Ipratropium Bromide:

Evidence:

• Adding ipratropium to salbutamol reduces hospital admission (NNT = 12) [19]
• Benefit limited to severe asthma and first 3 doses
• No benefit beyond initial treatment phase

Corticosteroids:

Evidence for Dexamethasone:

• Single dose of dexamethasone 0.6 mg/kg is equivalent to 5 days prednisolone [20]
• Two doses of dexamethasone may be superior for preventing relapse
• Better tolerated and may improve adherence

Magnesium Sulfate:

Evidence:

• Reduces hospitalisation in severe acute asthma (NNT = 4) [21]
• Most benefit in severe exacerbations not responding to initial bronchodilators
• Monitor blood pressure and reflexes
• Avoid in renal impairment and hypotension

Aminophylline:

Indications:

• Life-threatening or near-fatal asthma
• Failure to respond to maximal inhaled therapy and magnesium
• PICU/HDU setting only

Side Effects:

• Narrow therapeutic window
• Arrhythmias, seizures at toxic levels
• Nausea, vomiting, headache
• Drug interactions (macrolides, ciprofloxacin increase levels)

Non-Invasive and Invasive Ventilation

High-Flow Nasal Cannula (HFNC):

• May reduce work of breathing
• Flow rates: 2 L/kg/min (infant), 1 L/kg/min (child), max 50-70 L/min
• Provides PEEP effect and heated humidified oxygen
• Consider before escalating to NIV/intubation

Non-Invasive Ventilation (BiPAP):

• Limited evidence in acute paediatric asthma
• May be useful bridge while awaiting therapy response
• Risk of air trapping - use with caution

Invasive Mechanical Ventilation:

Indications:

• Respiratory arrest or imminent arrest
• Deteriorating consciousness despite maximal therapy
• Severe hypoxia (SpO2 less than 85% on high-flow oxygen)
• Rising PaCO2 with acidosis despite treatment

Considerations:

• High-risk intubation (severe bronchospasm)
• Use ketamine for induction (bronchodilator properties)
• Accept permissive hypercapnia
• Low respiratory rate to allow expiration
• Risk of dynamic hyperinflation and barotrauma

---

Disposition

Discharge Criteria

• Sustained clinical improvement for ≥1 hour after last bronchodilator
• SpO2 ≥94% on room air
• Minimal or no wheeze
• No respiratory distress or accessory muscle use
• Tolerating oral intake and oral corticosteroids
• Adequate inhaler technique demonstrated
• Written asthma action plan provided
• Follow-up arranged within 2-7 days

Admission Criteria

• SpO2 less than 92% on room air
• Persistent respiratory distress after initial treatment
• Inadequate response to ED treatment
• Previous ICU admission or intubation (high-risk)
• Unable to tolerate oral medications
• Social concerns or inability to access follow-up
• Requirement for bronchodilators more frequently than 2-hourly

PICU/HDU Admission Criteria

• Life-threatening features at any point
• Severe asthma not responding to initial therapy
• Requirement for IV bronchodilators
• Requirement for magnesium or aminophylline
• SpO2 less than 92% despite supplemental oxygen
• Exhaustion or altered consciousness
• Rising PaCO2 or worsening blood gas

Discharge Medications and Education

Medications:

1. Complete oral corticosteroid course (3-5 days prednisolone or 1-2 doses dexamethasone)
2. Continue reliever SABA as needed (with spacer)
3. Resume or initiate controller therapy (ICS)

Education Checklist:

• Asthma action plan (written) reviewed and provided
• Inhaler technique demonstrated and checked
• Controller medication adherence emphasised
• Trigger avoidance discussed
• Recognition of warning signs for deterioration
• Clear instructions on when to seek emergency care
• Follow-up appointment confirmed

---

Prevention and Long-Term Outcomes

Primary Prevention

Interventions with Limited Evidence:

• Breastfeeding (may provide modest protection)
• Avoiding environmental tobacco smoke exposure
• Vitamin D supplementation during pregnancy (conflicting evidence)
• Probiotics (insufficient evidence)
• Delayed introduction of allergenic foods (not recommended - early introduction may be protective)

Secondary Prevention

Reducing Exacerbations:

• Optimal controller therapy adherence
• Inhaler technique optimisation
• Trigger avoidance (allergens, tobacco smoke)
• Influenza vaccination annually
• Treatment of comorbid conditions (allergic rhinitis, GORD)
• Written asthma action plan

Prognosis

Natural History:

• 30-50% of children with asthma will experience remission by adulthood [22]
• Risk factors for persistence: early-onset, severe disease, allergic sensitisation, reduced lung function, female sex
• Some children in apparent remission develop adult asthma later

Long-Term Lung Function:

• Early childhood asthma associated with reduced maximally attained lung function
• Airway remodelling may not be fully reversible
• Early effective treatment may prevent decline (hypothesis under investigation)

---

Special Populations

Infants (Under 12 Months)

• Diagnosis of asthma uncertain - "recurrent wheeze" or "suspected asthma" preferred
• Response to bronchodilators may be less predictable
• Lower threshold for hospital admission
• Consider alternative diagnoses carefully (bronchiolitis, tracheomalacia, cardiac disease)

Adolescents

• Adherence often poor - address barriers directly
• Assess for tobacco, vaping, cannabis use
• Mental health comorbidities common
• Sports participation and exercise-induced symptoms important
• Transition planning to adult services from age 14+
• SMART/MART regimens may improve adherence and outcomes

Exercise-Induced Bronchoconstriction

• Occurs in 40-90% of children with asthma
• Pre-exercise SABA effective for prevention
• Regular ICS reduces frequency
• Consider LTRA if frequent symptoms
• Adequate warm-up helpful
• Breathing through nose/face covering in cold weather

Allergic Asthma with Specific Triggers

• Allergen avoidance measures (dust mite covers - modest benefit)
• Consider immunotherapy for specific allergen-triggered asthma
• Assess for food allergies - coexistence increases anaphylaxis and fatal asthma risk
• Indoor air quality optimisation

---

Viva Points

Viva Point: Opening Statement: "Childhood asthma is a chronic inflammatory airway disease characterised by reversible airflow obstruction and bronchial hyperresponsiveness. It is the most common chronic disease of childhood, affecting approximately 10-15% of children in the UK. Diagnosis in children under 5 years is challenging due to inability to perform spirometry and overlap with transient wheeze phenotypes."

Key Facts to Cite:

• BTS/SIGN stepwise approach - ICS is cornerstone of therapy
• Wheeze phenotypes: episodic viral wheeze vs multiple-trigger wheeze
• GINA 2023: ICS-formoterol SMART for adolescents reduces exacerbations
• Silent chest = life-threatening: minimal airflow, not improvement
• Magnesium 40 mg/kg IV for severe exacerbation not responding to initial therapy

Common Exam Questions

1. "Tell me about diagnosing asthma in a 3-year-old"

   • Emphasise clinical diagnosis based on pattern recognition
   • Wheeze phenotype classification
   • Trial of therapy approach
   • Modified Asthma Predictive Index

2. "How do you assess severity in acute asthma?"

   • Systematic approach: SpO2, speech, respiratory rate, heart rate, accessory muscles, consciousness
   • Moderate vs severe vs life-threatening
   • Warning signs (silent chest, exhaustion, altered consciousness)

3. "What is your management of severe acute asthma?"

   • Oxygen to maintain SpO2 94-98%
   • Salbutamol nebulised or pMDI+spacer every 20 minutes
   • Ipratropium for first 3 doses
   • Prednisolone 1-2 mg/kg within first hour
   • Magnesium 40 mg/kg IV if not responding
   • Consider IV salbutamol and PICU referral

4. "What biologics are available for severe paediatric asthma?"

   • Omalizumab (anti-IgE) from age 6 for allergic asthma
   • Mepolizumab (anti-IL-5) from age 6 for eosinophilic asthma
   • Dupilumab (anti-IL-4Rα) from age 6 for type 2 asthma
   • Selection based on phenotype and biomarkers

Common Mistakes

• Missing life-threatening features (silent chest, exhaustion, bradycardia)
• Delaying steroids beyond first hour
• Continuing ipratropium beyond first 3 doses (no additional benefit)
• Forgetting to check and teach inhaler technique
• Not providing written asthma action plan at discharge
• Diagnosing "asthma" definitively in a 2-year-old with first episode of wheeze

---

Quality Metrics

Performance Indicators

Documentation Requirements

• Baseline asthma control and medication history
• Severity assessment at presentation
• Trigger for exacerbation
• Response to treatment
• Peak flow if able to perform
• Inhaler technique assessment
• Discharge medications and education provided
• Follow-up arrangement documented

---

Key Clinical Pearls

Diagnostic Pearls

• Recurrent wheeze in a preschooler does not equal asthma - consider phenotype and trajectory
• Family history and atopy increase probability of true asthma
• Trial of therapy is diagnostic when objective testing not possible
• Asthma is unlikely if symptoms began at birth or in first 4 weeks of life

Management Pearls

• pMDI + spacer is at least as effective as nebuliser for bronchodilator delivery
• Dexamethasone single dose may be equivalent to 5-day prednisolone (better compliance)
• Ipratropium benefit limited to first 3 doses in acute setting
• Check inhaler technique at every visit - 50-80% use devices incorrectly
• Consider SMART regimen (ICS-formoterol) in adolescents for improved outcomes

Prognosis Pearls

• Early ICS reduces symptoms but does not modify natural history
• Severe early childhood asthma associated with reduced maximally attained lung function
• Up to 50% experience remission, but relapses in adulthood occur
• Persistent asthma phenotype more likely with atopy and early reduced lung function

---

References

1. Global Burden of Disease Study 2019. Global burden of chronic respiratory diseases and risk factors, 1990-2019. Lancet Respir Med. 2023;11(6):535-550. doi:10.1016/S2213-2600(23)00124-4

2. Martinez FD, Wright AL, Taussig LM, et al. Asthma and wheezing in the first six years of life. N Engl J Med. 1995;332(3):133-138. doi:10.1056/NEJM199501193320301

3. British Thoracic Society/Scottish Intercollegiate Guidelines Network. SIGN 158: British guideline on the management of asthma. 2019. https://www.brit-thoracic.org.uk/quality-improvement/guidelines/asthma/

4. Almqvist C, Worm M, Leynaert B. Impact of gender on asthma in childhood and adolescence: a GA2LEN review. Allergy. 2008;63(1):47-57. doi:10.1111/j.1398-9995.2007.01524.x

5. Nurmagambetov T, Kuwahara R, Garbe P. The economic burden of asthma in the United States, 2008-2013. Ann Am Thorac Soc. 2018;15(3):348-356. doi:10.1513/AnnalsATS.201703-259OC

6. Royal College of Physicians. Why asthma still kills: The National Review of Asthma Deaths (NRAD). 2014. https://www.rcplondon.ac.uk/projects/national-review-asthma-deaths

7. Moffatt MF, Gut IG, Demenais F, et al. A large-scale, consortium-based genomewide association study of asthma. N Engl J Med. 2010;363(13):1211-1221. doi:10.1056/NEJMoa0906312

8. Von Mutius E, Vercelli D. Farm living: effects on childhood asthma and allergy. Nat Rev Immunol. 2010;10(12):861-868. doi:10.1038/nri2871

9. Henderson J, Granell R, Heron J, et al. Associations of wheezing phenotypes in the first 6 years of life with atopy, lung function and airway responsiveness in mid-childhood. Thorax. 2008;63(11):974-980. doi:10.1136/thx.2007.093187

10. Adams NP, Bestall JC, Lasserson TJ, Jones P, Cates CJ. Fluticasone versus placebo for chronic asthma in adults and children. Cochrane Database Syst Rev. 2008;(4):CD003135. doi:10.1002/14651858.CD003135.pub4

11. Zhang L, Prietsch SO, Ducharme FM. Inhaled corticosteroids in children with persistent asthma: effects on growth. Cochrane Database Syst Rev. 2014;(7):CD009471. doi:10.1002/14651858.CD009471.pub2

12. Ducharme FM, Ni Chroinin M, Greenstone I, Lasserson TJ. Addition of long-acting beta2-agonists to inhaled steroids versus higher dose inhaled steroids in adults and children with persistent asthma. Cochrane Database Syst Rev. 2010;(4):CD005533. doi:10.1002/14651858.CD005533.pub2

13. Vogelberg C, Engel M, Laki I, et al. Tiotropium add-on therapy improves lung function in children with symptomatic moderate asthma. J Allergy Clin Immunol Pract. 2018;6(6):2160-2162. doi:10.1016/j.jaip.2018.04.032

14. Milgrom H, Berger W, Nayak A, et al. Treatment of childhood asthma with anti-immunoglobulin E antibody (omalizumab). Pediatrics. 2001;108(2):e36. doi:10.1542/peds.108.2.e36

15. Bacharier LB, Maspero JF, Katelaris CH, et al. Dupilumab in children with uncontrolled moderate-to-severe asthma. N Engl J Med. 2021;385(24):2230-2240. doi:10.1056/NEJMoa2106567

16. Laube BL, Janssens HM, de Jongh FH, et al. What the pulmonary specialist should know about the new inhalation therapies. Eur Respir J. 2011;37(6):1308-1331. doi:10.1183/09031936.00166410

17. Sanchis J, Gich I, Pedersen S; Aerosol Drug Management Improvement Team. Systematic review of errors in inhaler use: has patient technique improved over time? Chest. 2016;150(2):394-406. doi:10.1016/j.chest.2016.03.041

18. Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;(9):CD000052. doi:10.1002/14651858.CD000052.pub3

19. Plotnick LH, Ducharme FM. Combined inhaled anticholinergics and short-acting beta2-agonists for initial treatment of acute asthma in children. Cochrane Database Syst Rev. 2000;(2):CD000060. doi:10.1002/14651858.CD000060

20. Keeney GE, Gray MP, Morrison AK, et al. Dexamethasone for acute asthma exacerbations in children: a meta-analysis. Pediatrics. 2014;133(3):493-499. doi:10.1542/peds.2013-2273

21. Griffiths B, Kew KM. Intravenous magnesium sulfate for treating children with acute asthma in the emergency department. Cochrane Database Syst Rev. 2016;4(4):CD011050. doi:10.1002/14651858.CD011050.pub2

22. Sears MR, Greene JM, Willan AR, et al. A longitudinal, population-based, cohort study of childhood asthma followed to adulthood. N Engl J Med. 2003;349(15):1414-1422. doi:10.1056/NEJMoa022363