What are the key aspects of asthma pathophysiology, diagnosis, and management?

Asthma Study Cheat Sheet for Viva Exam

Definition and Pathophysiology

Asthma is a chronic inflammatory disorder of the airways characterized by three distinct pathophysiologic responses: inflammation, bronchial hyperresponsiveness, and airway remodeling. 1, 2, 3

Key Pathophysiologic Features:

• Chronic airway inflammation involving multiple cell types: eosinophils, neutrophils, lymphocytes, mast cells, and plasma cells in bronchial tissues and secretions 3
• Bronchial hyperresponsiveness documented by decreased airflow after provocation with methacholine, histamine, cold air, exercise, viral infections, or allergens 3
• Variable airway obstruction that is at least partially reversible 4
• Airway remodeling from repeated inflammation-injury-repair cycles, producing long-term structural changes including smooth muscle hypertrophy, lamina reticularis thickening, mucosal edema, epithelial sloughing, and mucus gland hypersecretion 3

Immunologic Mechanisms:

• Th2 lymphocyte-mediated inflammation with cytokine secretion (IL-4, IL-5, IL-13) leading to mast cell stimulation, eosinophilia, and enhanced IgE production 3, 5
• IgE-mediated reactions: Cross-linkage of two IgE molecules by allergen causes mast cell degranulation, releasing histamine, leukotrienes, and inflammatory mediators 3
• Biphasic response to allergen: Early phase IgE-mediated bronchial obstruction followed by late-phase reaction with decreased airflow for 4-8 hours 3

Genetics and Environmental Interactions:

• Strong genetic component: 80% of children with two asthmatic parents develop asthma versus 40% with one parent and 10% with no asthmatic parents 6
• Gene-environment interactions are critical—genetics alone cannot explain the asthma epidemic; environmental exposures at crucial times in immune development are essential 6
• In utero exposures (maternal smoking) increase childhood asthma risk in dose-dependent pattern 6

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Diagnosis

Asthma is a clinical diagnosis requiring episodic symptoms of airflow obstruction PLUS demonstration of reversible airway obstruction using spirometry. 1, 4

Essential Diagnostic Criteria (All Three Required):

1. Episodic Symptoms of Airflow Obstruction 1:

• Difficulty breathing
• Chest tightness
• Cough (characteristically worse at night)
• Wheezing
• Symptoms occurring/worsening at night, awakening the patient
• Symptoms triggered by exercise, viral infections, weather changes, strong emotions, menses, or exposure to animals, dust mites, mold, smoke, pollen, chemicals

2. Airflow Obstruction at Least Partially Reversible 1:

• Spirometry showing obstruction: Reduced FEV₁ and FEV₁/FVC ratio
• Reversibility demonstrated by: ≥12% AND ≥200 mL increase in FEV₁ after bronchodilator use
• Diurnal PEF variation: >20% over 1-2 weeks
• Note: Patients with asthma can have normal lung function between exacerbations 1

3. Alternative Diagnoses Excluded 1:

In Children:

• Allergic rhinosinusitis
• Cystic fibrosis
• Foreign body aspiration
• Enlarged lymph nodes or tumor
• Heart disease
• Viral bronchiolitis
• Vocal cord dysfunction

In Adults:

• COPD (chronic bronchitis/emphysema)
• Congestive heart failure
• Pulmonary embolism
• Mechanical airway obstruction (benign/malignant tumors)
• Pulmonary infiltration with eosinophilia
• ACE inhibitor-induced cough
• Vocal cord dysfunction

Additional Diagnostic Testing:

• Spirometry is mandatory for initial assessment, evaluation of treatment response, and assessment every 1-2 years—not just PEF meters 1
• Bronchoprovocation testing (methacholine, histamine, cold air, exercise) useful when asthma suspected but spirometry normal; positive test confirms airway hyperresponsiveness but negative test more helpful to rule out asthma 1
• Chest x-ray may be needed to exclude other diagnoses 1
• Additional pulmonary function studies (diffusing capacity for COPD, lung volumes for restrictive defects, inspiratory flow-volume loops for vocal cord dysfunction) if diagnostic uncertainty 1

Common Diagnostic Challenges:

• Cough variant asthma: Cough is principal or only manifestation; diagnosis confirmed by positive response to asthma medications 1
• Vocal cord dysfunction (VCD): Can mimic or coexist with asthma; asthma medications provide little relief; variable flattening of inspiratory flow loop on spirometry is suggestive; diagnosis requires vocal cord visualization during episode; consider in difficult-to-treat, atypical asthma and elite athletes with exercise-related breathlessness unresponsive to medication 1
• Children ages 0-4 years: Diagnosis challenging due to difficulty obtaining objective lung function measurements; avoid labels like "wheezy bronchitis," "recurrent pneumonia," or "reactive airway disease" that delay appropriate treatment 1
• Comorbid conditions: GERD, obstructive sleep apnea, allergic bronchopulmonary aspergillosis may coexist and complicate diagnosis 1

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Classification of Severity

Disease severity is determined by pulmonary function measurements, asthma symptoms, and need for rescue medication BEFORE starting treatment. 1

Classification Categories 7:

• Intermittent asthma
• Persistent asthma: Mild, moderate, or severe

Important Caveats About Classification:

• Classification is based on pre-treatment symptoms—once treatment begins, classification becomes difficult 1
• Asthma is variable—patients rarely remain in same category over time 1
• Patients underestimate symptoms, leading to incorrect classification 1
• Activity level not considered in current system—when included, 93% had persistent asthma and 77% had moderate-to-severe asthma 1
• Objective measures (PEF, FEV₁) don't always correlate with symptom severity or frequency; >25% with normal lung function had subsequent asthma attacks 1

Special Asthma Phenotypes 7:

• Allergic asthma (IgE-mediated)
• Nonallergic asthma (triggered by viral URIs or no apparent cause)
• Occupational asthma
• Aspirin-exacerbated respiratory disease
• Exercise-induced asthma
• Cough variant asthma (nonproductive cough responding to asthma treatment but not antibiotics, expectorants, mucolytics, antitussives, beta₂-agonists, or treatment for reflux/rhinosinusitis)

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Management Principles

Managing asthma long-term requires 4 components: assessment and monitoring, patient education for partnership in care, control of environmental factors and comorbid conditions, and medications using a stepwise approach. 1

Medication Framework:

Controller Medications (Daily Maintenance):

• Inhaled corticosteroids (ICS): Standard of care for persistent asthma; patients may benefit from earlier use, proven safe in usual dosages 1, 4
• Combination ICS + long-acting β₂-agonists (LABA): Effective when ICS alone insufficient 4
• Long-acting muscarinic antagonists (e.g., tiotropium) 4
• Biologic agents directed against proteins in asthma pathogenesis (e.g., omalizumab, mepolizumab, reslizumab) for moderate-to-severe asthma 4

Reliever Medications (Acute Symptoms):

• Inhaled short-acting β₂-agonists: Provide rapid relief of acute symptoms 4

Critical Safety Warnings:

NEVER use inhaled long-acting β₂-agonists alone—this is inappropriate and dangerous. 4

Strong CYP3A4 inhibitors (ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) should NOT be used with ICS/LABA combinations due to increased systemic corticosteroid effects and cardiovascular adverse effects. 8

Transitioning from Oral Corticosteroids:

When transferring patients from systemic corticosteroids to inhaled therapy 8:

• Reduce prednisone by 2.5 mg weekly during ICS therapy
• Monitor closely: FEV₁ or morning PEF, beta-agonist use, asthma symptoms
• Watch for adrenal insufficiency: Fatigue, lassitude, weakness, nausea, vomiting, hypotension
• Expect unmasking of allergic conditions previously suppressed (rhinitis, conjunctivitis, eczema, arthritis, eosinophilic conditions)
• Anticipate withdrawal symptoms: Joint/muscular pain, lassitude, depression despite maintained respiratory function

Monitoring and Follow-up:

• Spirometry for initial assessment, treatment response evaluation, and at least every 1-2 years 1
• Written action plans with or without PEF monitoring recommended by NAEPP, though evidence is inconclusive 1
• Identify clinically important allergen sensitivities 4
• Avoid aggravating environmental factors 4

Special Considerations:

Stress and psychological factors: Stress can amplify airway inflammatory responses to irritants, allergens, and infections; address both psychological stressors and physical triggers; consider additional education for self-management and coping skills in patients with stress-related exacerbations or depression 9

Severe asthma: Patients generally benefit from consultation with asthma specialist for consideration of additional treatment, including injectable biologic agents 4

Hypercorticism and adrenal suppression: ICS absorbed systemically at higher doses; titrate to lowest effective dose; observe for systemic corticosteroid effects, especially postoperatively or during stress 8

Paradoxical bronchospasm: Can occur with any inhaled medication; treat immediately with short-acting bronchodilator, discontinue offending agent, institute alternative therapy 8

Immediate hypersensitivity reactions: Anaphylaxis possible; patients with severe milk protein allergy should NOT use powder inhalers containing lactose 8

Cardiovascular effects: Beta-agonists can cause seizures, angina, hypertension/hypotension, tachycardia (up to 200 bpm), arrhythmias, ECG changes (T-wave flattening, QTc prolongation, ST depression); use with caution in cardiovascular disorders 8