Asthma: Pathophysiology, Diagnosis, and Management
Pathophysiology
Asthma is a chronic inflammatory disorder of the airways characterized by three key features: variable airflow obstruction, airway hyperresponsiveness, and chronic airway inflammation 1, 2. The inflammatory response leads to structural changes in the airways that can develop early, even in preschool years, making timely diagnosis and treatment critical to prevent long-term morbidity 3.
Diagnostic Criteria
The diagnosis of asthma requires both characteristic symptoms AND objective demonstration of reversible airway obstruction using spirometry 1.
Clinical Presentation
Look for these specific features in the history 3, 4:
- Recurrent episodes of wheezing, breathlessness, chest tightness, or cough
- Variability of symptoms (worse at night, early morning, or with exercise)
- Symptoms triggered by viral infections, allergens, exercise, weather changes, or irritants
- Family history of asthma or atopic conditions
Objective Testing
Spirometry is mandatory in all patients ≥5 years of age at initial assessment 3:
- Measure FEV1 and FEV1/FVC ratio
- Demonstrate reversibility: ≥12% and ≥200 mL improvement in FEV1 after inhaled short-acting beta-agonist
- For children, FEV1/FVC is more sensitive than FEV1 alone 3
Peak expiratory flow (PEF) variability ≥20% confirms the diagnosis when spirometry shows normal baseline values 4. This can be demonstrated either during symptomatic periods or after bronchodilator/treatment response 4.
Bronchoprovocation testing (methacholine, histamine, cold air, or exercise challenge) is useful when asthma is suspected but spirometry is normal 3. A negative test is more helpful to rule out asthma than a positive test is to confirm it 3.
Diagnostic Pitfalls to Avoid
Do not rely solely on history and physical examination without objective testing 5. Common misdiagnoses include:
- Vocal cord dysfunction (VCD): Look for variable flattening of inspiratory flow loop on spirometry; diagnose by direct visualization during episodes 3
- COPD: Obtain diffusing capacity if there's smoking history or persistent obstruction 3
- Cardiac disease: Consider in older adults with dyspnea 3
- Cough variant asthma: Cough may be the only manifestation; confirm with positive response to asthma medications 3
In children 0-4 years, diagnosis is challenging without objective lung function. Avoid labels like "wheezy bronchitis" or "reactive airway disease" that delay appropriate treatment 3.
Classification of Asthma Severity
Initial Assessment (Before Treatment)
Classify severity using both impairment and risk domains 3:
Intermittent Asthma 3:
- Symptoms <2 days/week
- Nighttime awakenings <2×/month
- SABA use ≤2 days/week
- No interference with normal activity
- FEV1 >80% predicted, normal FEV1/FVC
- 0-1 exacerbations/year requiring oral corticosteroids
Mild Persistent 3:
- Symptoms >2 days/week but not daily
- Nighttime awakenings 3-4×/month
- SABA use >2 days/week but not daily
- Minor limitation of activity
- FEV1 >80% predicted, normal FEV1/FVC
- ≥2 exacerbations/year requiring oral corticosteroids
Moderate Persistent 3:
- Daily symptoms
- Nighttime awakenings >1×/week but not nightly
- Daily SABA use
- Some limitation of activity
- FEV1 60-80% predicted, reduced FEV1/FVC
- ≥2 exacerbations/year requiring oral corticosteroids
Severe Persistent 3:
- Symptoms throughout the day
- Nighttime awakenings often (≥7×/week)
- SABA use several times per day
- Extremely limited activity
- FEV1 <60% predicted, reduced FEV1/FVC >5%
- ≥2 exacerbations/year requiring oral corticosteroids
Assessment of Asthma Control (During Treatment)
Once treatment is initiated, shift focus from severity to control assessment 3. Assess at every visit using these criteria 3:
Well Controlled 3:
- Symptoms ≤2 days/week
- Nighttime awakenings ≤2×/month
- SABA use ≤2 days/week
- No interference with activity
- FEV1 or PEF >80% predicted/personal best
- 0-1 exacerbations/year requiring oral corticosteroids
Not Well Controlled 3:
- Symptoms >2 days/week
- Nighttime awakenings 1-3×/week
- SABA use >2 days/week
- Some limitation of activity
- FEV1 or PEF 60-80% predicted/personal best
Very Poorly Controlled 3:
- Symptoms throughout the day
- Nighttime awakenings ≥4×/week
- SABA use several times per day
- Extremely limited activity
- FEV1 or PEF <60% predicted/personal best
- ≥2 exacerbations/year requiring oral corticosteroids
Management
Stepwise Treatment Approach
Inhaled corticosteroids (ICS) are the most consistently effective anti-inflammatory therapy for persistent asthma at all steps of care 3.
Step 1 (Intermittent Asthma) 3:
- SABA as needed only
- No daily controller medication
Step 2 (Mild Persistent) 3:
- Preferred: Low-dose ICS
- Alternative: Leukotriene receptor antagonist (LTRA), cromolyn, or theophylline
- SABA as needed
Step 3 (Moderate Persistent) 3:
- Preferred: Low-to-medium dose ICS + long-acting beta-agonist (LABA)
- Alternative: Medium-dose ICS alone, or low-dose ICS + LTRA or theophylline
- SABA as needed
Step 4 (Moderate-Severe Persistent) 3:
- Preferred: Medium-dose ICS + LABA
- Alternative: Medium-dose ICS + LTRA or theophylline
- SABA as needed
Step 5 (Severe Persistent) 3:
- Preferred: High-dose ICS + LABA
- Consider omalizumab for allergic asthma
- SABA as needed
Step 6 (Severe Persistent) 3:
- High-dose ICS + LABA + oral corticosteroids
- Consider omalizumab for allergic asthma
- SABA as needed
Critical Management Principles
Never use LABA as monotherapy 6, 1. LABAs must always be combined with ICS due to increased risk of serious asthma-related events 6.
Do not combine fluticasone/salmeterol with additional LABA-containing medications due to overdose risk 6.
Doubling ICS doses during exacerbations is not effective 3. Use oral corticosteroids instead 3.
Monitoring Schedule
Schedule follow-up visits based on control status 3:
- Every 2-6 weeks when initiating therapy or stepping up treatment 3
- Every 1-6 months once control is achieved 3
- Every 3 months if considering step-down therapy 3
Perform spirometry 3:
- At initial assessment
- After treatment initiation when symptoms and PEF stabilize
- During periods of progressive loss of control
- At least every 1-2 years (more frequently if not well controlled)
At every visit, assess 3:
- Asthma control using validated questionnaires (ACT, ACQ, ATAQ) 3
- Medication technique (inhaler, spacer use)
- Written asthma action plan adherence
- Environmental triggers and comorbidities
Comorbidity Management
Identify and treat conditions that impede asthma control 3:
- Allergic rhinitis and sinusitis
- Gastroesophageal reflux disease (GERD)
- Obstructive sleep apnea (OSA)
- Obesity
- Depression and stress
Perform allergy testing for perennial indoor allergens in patients with persistent asthma requiring daily medications 3. Implement allergen avoidance strategies once sensitivities are identified 3.
Administer annual influenza vaccination to all patients with persistent asthma 3.
Referral to Specialist
Refer to an asthma specialist when 3:
- Difficulty achieving or maintaining control
- Patient required >2 bursts of oral corticosteroids in 1 year
- Any hospitalization for asthma exacerbation
- Step 4 or higher care required (Step 3 or higher for children 0-4 years)
- Considering immunotherapy or omalizumab
- Life-threatening exacerbation occurred
- Atypical presentation or diagnostic uncertainty 3
Patient Education
Provide written asthma action plan to all patients 3 with instructions for:
- Daily management (controller medications, environmental control)
- Recognizing worsening asthma
- When to increase treatment
- When to seek emergency care
Teach proper inhaler technique and verify at every visit 3.
Instruct patients on self-monitoring using either symptoms or peak flow 3. Peak flow monitoring is particularly important for patients with moderate-severe asthma, history of severe exacerbations, or poor symptom perception 3.