Asthma

Differential Diagnosis

• Bronchopulmonary dysplasia
• Cystic fibrosis and other causes of bronchiectasis
• Eosinophilic granulomatosis with polyangiitis (eGPA): asthma, eosinophilia, and granulomatous vasculitis
• Vocal cord dysfunction: recurrent or severe 'asthma' with normal PFTs, needs laryngoscopy for diagnosis
• Allergic bronchopulmonary Aspergillosis (ABPA)
• Reactive airway dysfunction syndrome (RADS): irritant-induced asthma following a single high-intensity exposure
  • Treat like asthma exacerbation, usually resolves over 3 months

Risk Factors

• Parental asthma (RR=2)

Clinical Manifestations

• Trigger-induced wheeze, dyspnea, cough, or chest tightness
  • Trigger can include exercise, cold, seasonal allergies
• Chronic cough

Diagnosis

• Requires both of:
  • Variable respiratory symptoms: wheeze, dyspnea, chest tightness, or cough that vary over time
  • Variable expiratory airflow limitations: documentation by PFTs with either bronchodilator response or methacholine challenge, or possibly peak flows and exercise

Variable expiratory airflow limitations

• Document FEV1/FVC below the lower limit of normal at least once to document airflow limitation
• PFTs may be normal at time of initial assessment

Bronchodilator reversibility

• Improvement of FEV1 by 12% and 200 mL 10-15 minutes after 200-400 mcg salbutamol
• Better as a rule-out test than a rule-in test

Methacholine challenge

• Minimum concentration of methacholine required to produce a 20% decrease in FEV1 (PC20)
• Asthma diagnosed with PC20 <4 mg/mL
• Asthma excluded with PC20 >16 mg/mL

Exercise challenge

• Decrease in FEV1 of >10% and 200 mL from baseline following exercise

Peak expiratory flow (PEF)

• Twice daily peak flows over 2 weeks that have average daily diurnal variability >10%

Response to empiric treatment

• Improvement in FEV1 by >12% and 200 mL (or peak flow by >20%) after 4 weeks of empiric treatment

Repeated PFTs

• Excessive variation in FEV1 between visits >12% and 200 mL

Classification

Uncontrolled Asthma

• Poor symptom control, or
• 2+ exacerbations requiring oral steroid in the past year, or
• One serious exacerbation requiring hospitalization in the past year, or
• Sustained FEV1 <80% of personal best

Severe Asthma

• Asthma requiring high-dose ICS with another puffer for the past year, or
• Oral steroids needed for 50% of the past year, or
• Uncontrolled asthma despite these therapies

Investigations

• Pulmonary function tests, methacholine challenge
  • Reversible airway obstruction: used for its NPV rather than PPV for asthma
• Peak expiratory flow

Severe Asthma

• Total IgE
• CBC for peripheral eosinophils
• Sputum eosinophils and FeNO, where available

Management

Non-pharmacologic

• Confirm diagnosis
  • Don't forget to rule out ABPA (allergic bronchopulmonary aspergillosis) if they have difficult-to-control asthma
• Environmental control and education
  • Including inhaler technique, adherence, trigger avoidance, and management of comorbidities
  • Asthma Action Plan
• Weight loss and exercise
• Allergen/trigger avoidance and consider allergen immunotherapy
• Smoking cessation
• Vaccinations
• Avoid NSAIDs (and also non-selective beta blocker if possible)
• Manage comorbidities such as GERD, PND, and obesity

Pharmacologic

• Step-up management
  1. SABA prn, or ICS/LABA prn if age >12
  2. Add inhaled corticosteroid (ICS)
  3. Add LABA if age >12
  4. Add leukotriene receptor antagonist (LTRA)
• Before stepping up therapy, confirm inhaler technique and adherence!
• If they have had symptom control for 2 months and are at low risk of exacerbation, consider stepping down therapy
• If severe asthma, refer to Respirology

Specific Inhalers

• ICS decreases exacerbations, hospitalizations, and symptoms, and increases quality of life and lung function
  • Decreases asthma-related mortality
• LTRA: only appropriate for first-line if they cannot tolerate ICS or has allergic rhinitis
• For step-up from low-dose ICS, ICS-LABA better than ICS-LTRA

Specific Populations

• Seasonal allergic asthma: start ICS as soon as symptoms begin, and continue until four weeks after the relevant pollen season ends
• Exercise-induced: salbutamol pre-exercise, then LTRA pre-exercise, then scheduled ICS
• Pregnancy:
  • 1/3 improve, 1/3 stable, 1/3 worsen
  • Exacerbations more common in second trimester
  • Most evidence for budesonide, but treat as you would anyone else
• Aspirin-induced respiratory disease (Samter's triad): avoid ASA/NSAIDs, and treat as normal but often responds well to LTRA. Can try desensitizing to ASA.

Severe Asthma

• Should be referred on to Respirology
• Needs total IgE levels, CBC for eosinophils, and sputum eosinophils or FeNO (where available)
• Step-up therapies, in order of evidence (I believe):
  • Can add tiotropium (LAMA) mist inhaler to ICS/LABA
  • Can add chronic azithromycin to ICS/LABA
  • Can add low-dose oral steroid
• Can add biologic
  • Anti-IgE (omalizumab): for severe allergic asthma with IgE 30-700
  • Anti-IL5 (mepolizumab, reilzumab, benralizumab): severe eosinophilic asthma (eos >300)
  • Anti-IL4/IL13 (dupulimumab): severe eosinophilic asthma

Asthma Control

• Having asthma control is defined as having all of the following:
  • Daytime symptoms <4 days/week
  • Nighttime symptoms <1 night/week
  • Physical activity is normal
  • Mild and infrequent exacerbations
  • No abscence from work or school due to asthma
  • <4 doses/week of rescue inhaler are needed
  • FEV1 or PEF ≥90% of personal best
  • PEF diurnal variation <10-15%
  • <2-3% sputum eosinophils
• If all of the above conditions are not met, the patient does not have asthma control and medication should be titrated up
• If all of the above conditions are met and they are stable for several months, consider titrating down their medication

Further Reading

• Lougheed MD, et al. Canadian Thoracic Society 2012 Guideline Update: Diagnosis and Management of Asthma in Preschoolers, Children and Adults: Executive Summary. Can Resp J. 2012;19(6):e81-e88.