What is asthma, its pathophysiology, triggers, and recommended management?

What is Asthma?

Asthma is a chronic inflammatory disorder of the airways characterized by variable and reversible airflow obstruction, bronchial hyperresponsiveness, and underlying inflammation involving mast cells, eosinophils, neutrophils, T lymphocytes, macrophages, and epithelial cells 1.

Pathophysiology

The disease manifests through three interconnected mechanisms that determine clinical severity and treatment response:

Airway Inflammation

• Cellular infiltration: Mast cells, eosinophils (or neutrophils in sudden-onset fatal exacerbations, occupational asthma, and smokers), T lymphocytes, macrophages, and epithelial cells drive the inflammatory process 1
• Inflammatory mediators: These cells release substances causing recurrent episodes of coughing (particularly nocturnal or early morning), wheezing, breathlessness, and chest tightness 1

Airflow Limitation Mechanisms

Three distinct processes narrow the airways:

• Bronchoconstriction: Bronchial smooth muscle contracts rapidly in response to allergens or irritants 1
• Airway hyperresponsiveness: Exaggerated bronchoconstrictor response to various stimuli 1
• Airway edema: Progressive inflammation leads to edema, mucus hypersecretion, and inspissated mucus plugs that further limit airflow 1

Airway Remodeling

Persistent structural changes occur over time, including:

• Sub-basement fibrosis
• Mucus hypersecretion
• Epithelial cell injury
• Smooth muscle hypertrophy
• Angiogenesis

Critical caveat: Reversibility of airflow limitation may be incomplete in some patients despite treatment 1.

Clinical Presentation

Cardinal Symptoms

The hallmark features are symptoms that are variable, intermittent, worse at night, and provoked by triggers 2:

• Wheeze
• Shortness of breath
• Chest tightness
• Cough (particularly nocturnal or early morning)

When cough predominates without wheeze, this represents "cough variant asthma" 2.

Physical Examination

• During exacerbations: Diffuse, polyphonic, bilateral wheeze (especially expiratory); reduced peak flow or obstructive spirometry pattern 2
• Between episodes: May have no objective signs; chronic asthma may show hyperinflation with or without wheeze 2

Triggers and Risk Factors

Environmental Triggers

Environmental tobacco smoke and indoor allergens (house dust mite, cockroach, cat and dog) worsen asthma in sensitized individuals 3. Other triggers include:

• Allergens (pollens, dust, feathered/furry animals)
• Viral respiratory infections
• Exercise
• Chemical irritants
• Cold air

Host Factors

• Genetics: Strong family history of asthma or atopy 1
• Atopic conditions: Personal history of eczema or allergic rhinitis 2

Medication Triggers

• Aspirin/NSAIDs
• Beta-blockers 2

Diagnosis

Diagnosis requires characteristic symptoms PLUS demonstration of reversible airflow obstruction using spirometry 4. The diagnosis is clinical—there is no confirmatory blood test, radiograph, or histopathological investigation 2.

Objective Testing

• Spirometry or peak expiratory flow (PEF): Shows decreased FEV1 and/or PEF
• Variability: Spontaneous variation over time or response to therapy is characteristic 2
• Between episodes: Lung function may be completely normal; if repeatedly normal with symptoms, the diagnosis is in doubt 2

Additional Diagnostic Tools

• Fractional exhaled nitric oxide (FeNO): Conditionally recommended to assist in diagnosis and monitoring, but not alone 5, 6
• Allergy testing: Recommended for perennial indoor allergens in patients with persistent asthma on daily medications 3

Management Approach

Stepwise Treatment Algorithm (Ages 12+ Years)

The 2020 guidelines fundamentally changed asthma management: SABA-only therapy is no longer recommended—all patients should receive ICS-containing medication 5, 6, 7.

Step 1 (Intermittent Asthma)

• Preferred: PRN SABA (though 2024 GINA advises against SABA alone) 5
• Alternative: Consider as-needed low-dose ICS-formoterol 7

Step 2 (Mild Persistent Asthma)

• Preferred: Daily low-dose ICS + PRN SABA 5
• Alternative: As-needed concomitant ICS and SABA therapy 6

Step 3 (Moderate Persistent Asthma)

• Preferred: Daily and PRN low-dose ICS-formoterol (single maintenance and reliever therapy—SMART) 5, 6
• Alternative: Daily low-dose ICS-LABA + PRN SABA 5

Step 4 (Moderate-Severe Persistent Asthma)

• Preferred: Daily and PRN medium-dose ICS-formoterol 5
• Alternative: Daily medium-dose ICS-LABA + PRN SABA 5

Step 5 (Severe Persistent Asthma)

• Preferred: Daily medium-high dose ICS-LABA + PRN SABA 5
• Add-on: Long-acting muscarinic antagonist (LAMA) if not controlled on ICS-formoterol 5, 6

Step 6 (Very Severe Persistent Asthma)

• Daily high-dose ICS-LABA or oral systemic corticosteroids 5
• Consider asthma biologics (anti-IgE, anti-IL5, anti-IL5R, anti-IL4/IL13) 5
• Bronchial thermoplasty is NOT recommended as standard care 5, 6

Key Management Principles

Inhaled corticosteroids are the mainstay of preventive treatment, combining effectiveness with relative freedom from side effects 8. Use the lowest dose providing acceptable symptom control 8.

Critical Medication Rules

• Never use long-acting β2-agonists (LABAs) alone—always combined with ICS 4
• Short-term increases in ICS dose alone for worsening symptoms are NOT recommended 6
• Formoterol-containing ICS combinations allow single-inhaler maintenance and reliever therapy 5

Environmental Control

Allergen mitigation is recommended ONLY in individuals with documented exposure and relevant sensitivity or symptoms 5, 6. When used:

• Must be allergen-specific
• Include multiple allergen-specific mitigation strategies
• Acaricides have shown little clinical benefit 8

Immunotherapy

• Subcutaneous immunotherapy: Conditionally recommended as adjunct to standard pharmacotherapy in controlled asthma 5, 6
• Sublingual immunotherapy: NOT specifically recommended for asthma 6

Self-Management Components

Every patient must have a written asthma action plan 1, 8, 7. The three essential elements are:

1. Monitoring: Symptoms, peak flow, and drug usage
2. Prearranged action: Patient-initiated treatment adjustments
3. Written guidance: Clear instructions on when to escalate therapy

Key actions in the plan:

• Recognize early warning signs
• Increase SABA use
• Initiate or increase inhaled corticosteroids
• Self-administer oral corticosteroids when PEF falls below agreed level or <60% predicted 8
• Seek urgent medical attention when treatment fails 8

Exacerbation Management

Home Management

• Increase SABA (up to 3 treatments at 20-minute intervals) 1
• Add oral systemic corticosteroids in some cases 1
• Remove environmental triggers 1

Emergency Department Management

• Assess severity: Lung function measures, symptom assessment 1
• Treat: Supplemental oxygen, repetitive/continuous SABA, oral systemic corticosteroids 1
• Severe exacerbations (FEV1 or PEF <40% predicted): Consider magnesium sulfate or heliox if unresponsive to initial treatment 1
• Discharge: Oral systemic corticosteroids, consider initiating ICS, SABA, follow-up referral, discharge plan, review inhaler technique 1

Monitoring and Follow-Up

Schedule routine visits every 1-6 months depending on severity and control 3. At each visit:

• Assess adherence and inhaler technique
• Review medication use and management plan
• Evaluate environmental control measures
• Perform spirometry at initial assessment and every 1-2 years after stabilization 3

Step up therapy if needed; reassess in 2-6 weeks. Step down if asthma is well controlled for at least 3 consecutive months 5.

Specialist Referral Indications

Consult respiratory specialist for 8, 3:

• Diagnostic uncertainty
• Life-threatening exacerbation
• Continuing symptoms despite high-dose inhaled steroids
• Step 4 or higher therapy required (consider at Step 3)
• Possible occupational asthma
• Pregnant women with worsening asthma
• Recent hospital discharge
• Consideration for nebulized bronchodilators or biologics

Special Populations

Children (0-2 years)

Particular challenges 8:

• Recurrent wheeze often viral-related without atopy
• Diagnosis relies on symptoms, not objective testing
• Variable bronchodilator response in first year (but still try)
• Rule out mimics: gastroesophageal reflux, cystic fibrosis, chronic lung disease of prematurity

Children (Growth Concerns)

Inhaled steroids at doses >400 µg/day show short-term reductions in tibial growth rate, but these cannot be extrapolated to long-term effects 8. Asthma itself delays growth and puberty, with eventual catch-up growth 8.

Comorbid Conditions

Evaluate and treat when symptoms persist despite medication adjustments 3:

• Allergic rhinitis
• Sinusitis
• Gastroesophageal reflux
• Medication sensitivities

Annual influenza vaccination is recommended for all patients with persistent asthma 3.