Chronic Asthma

• A chronic respiratory disease affecting 1-18% of the population, characterized by symptoms of wheeze, dyspnoea, chest tightness and cough with variable airflow limitation.
• Airflow limitations are as a consequence of acute on chronic airway inflammation
• Airways are often hyperresponsive to direct or indirect stimuli which may cause episodic exacerbation

Phenotypes of asthma

• Allergic asthma: starts in childhood, often with a family history of allergic diseases e.g. eczema, allergic rhinitis and/or food and medication allergies. Sputum often eosinophilic. Respond well to inhaled corticosteroids (ICS)
• Non-allergic asthma: Sputum may be neutrophilic, eosinophilic or paucigranulocytic. Less short-term response to ICS
• Adult-onset asthma: often non-allergic, less responsive to ICS. Must rule out occupational asthma (asthma due to exposure to allergen(s) at work)
• Asthma with persistent airflow limitation: asthma associated with irreversible airway obstruction, possibly due to remodelling.
• Asthma with obesity: often non-allergic (little eosinophilic airway inflammation)

Investigation

• Physical exam: often normal if not in acute exacerbation, may have prolonged expiration + wheeze
• Assess for the likelihood of symptoms
  • Symptoms supportive of the diagnosis: wheeze, shortness of breath, chest tightness and cough
  • More than one of the above (i.e., isolated cough unlikely to be due to asthma)
  • Symptoms occur variably over time and vary in intensity
  • Symptoms are often worse at night or on waking
  • Symptoms are often triggered by exercise, laughter, allergens, cold air
  • Symptoms often appear or worsen with viral infections
• Documented expiratory airflow limitation: at a time when FEV1 is reduced, confirm that FEV1/FVC is reduced compared with the lower limit of normal (lower limit of normal: 0.75 – 0.80 in adult, 0.9 in children) AND
• Documented excessive variability in lung function:
  • Positive bronchodilator responsiveness: FEV1 increase of > 12% and > 200 mL in adults (10-15 minutes after 200-400 mcg salbutamol)
  • Excessive variability in twice-daily PEF over 2 weeks: average daily diurnal PEF variability > 10%
  • Significant increase in lung function after 4 weeks of anti-inflammatory treatment: same criteria as bronchodilator response
  • Positive exercise challenge test: fall in FEV1 of > 10% and > 200 mL from baseline
  • Positive bronchial challenge test (methacholine): fall of FEV1 by > 20% from baseline
  • Excessive variation in lung function between clinic visits: FEV1 variability > 12% and 200 mL

NB: This diagnostic protocol applies to patients uninitiated on controller therapy. If they are on controller therapy and still meet the criteria above, then asthma is diagnosed.

Patients already on controller therapy

• Variable respiratory symptoms but no variable airflow limitation → repeat spirometry after withholding bronchodilators or when having symptoms
• Few variable respiratory symptoms but no variable airflow limitation → repeat spirometry after withholding treatment or during symptoms (as above), may also consider stepping down treatment.
• Persistent shortness of breath and persistent airflow limitation → stepping up controller treatment for 3 months then reassess lung function.

Management

• Track 1 (preferred)
  • Step 1&2: low-dose ICS-formoterol as required
  • Step 3: step 1&2 + low-dose maintenance ICS-formoterol
  • Step 4: step 1&2 + medium-dose maintenance ICS-formoterol
  • Step 5: step 4 + long-acting muscarinic antagonist (LAMA) + consider switch to high-dose maintenance ICS-formoterol + consider anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP + consider assessment of phenotype
• Track 2 (alternative)
  • Step 1: Short-acting beta2-agonist (SABA) + ICS as required
  • Step 2: step 1 + low-dose maintenance ICS
  • Step 3: step 1 + low-dose maintenance ICS + LABA
  • Step 4: step 1 + medium/high-dose maintenance ICS + LABA
  • Step 5: step 4 + LAMA + consider high-dose maintenance ICS-formoterol + consider anti-IgE, anti-IL5/5R, anti-IL4R, anti-TSLP + consider assessment of phenotype
• Additional treatments (applicable to both track 1 and 2)
  • Step 2: add low-dose ICS whenever SABA taken or daily LTRA or HDM SLIT (house dust mite sublingual immunotherapy)
  • Step 3: add medium-dose ICS or daily LTRA or add HDM SLIT
  • Step 4: add daily LAMA or LTRA or switch to high-dose ICS
  • Step 5: add azithromycin or LTRA or oral corticosteroids (last resort)

Reference: GINA Guideline 2022