Asthma
Chronic reversible airway inflammation with episodic bronchoconstriction.
Also known as: asthma, reactive airway disease, bronchial asthma, RAD, wheezing
Overview
Heterogeneous chronic inflammatory airway disease characterized by reversible airflow obstruction, bronchial hyperresponsiveness, and variable respiratory symptoms (wheezing, dyspnea, chest tightness, cough).
Epidemiology
~8% of US adults, ~7% of children. Higher prevalence in non-Hispanic Black and Puerto Rican populations. Most childhood-onset cases are atopic (Th2-high); adult-onset is more often non-atopic.
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Risk factors
- Atopy (eczema, allergic rhinitis, food allergy) — the 'atopic march'
- Family history of asthma or atopic disease
- Environmental allergens: dust mites, cockroach, mold, pet dander, pollen
- Tobacco smoke exposure (prenatal and postnatal)
- Respiratory viral infections in infancy (especially RSV, rhinovirus)
- Obesity, GERD
- Occupational exposures (isocyanates, flour, animal proteins)
Pathophysiology
Th2-driven inflammation with eosinophils, mast cells, IgE, and cytokines (IL-4, IL-5, IL-13) → airway smooth muscle constriction, mucosal edema, mucus hypersecretion, and over time, airway remodeling (subepithelial fibrosis, smooth muscle hypertrophy). Triggers (allergens, exercise, cold air, viruses, NSAIDs in aspirin-exacerbated respiratory disease) provoke acute bronchoconstriction.
Clinical presentation
Symptoms
- Episodic wheeze, cough (often nocturnal), chest tightness, dyspnea
- Triggered by allergens, exercise, cold air, viral URIs, NSAIDs, beta-blockers, emotional stress
- Diurnal variation: worse at night and early morning
Signs / physical exam
- Expiratory wheeze on auscultation, prolonged expiratory phase
- Use of accessory muscles, tachypnea, tachycardia in acute exacerbation
- Pulsus paradoxus >10 mmHg in severe exacerbation
- Silent chest (no wheeze) = ominous sign of severe airflow obstruction
Classic findings
Wheezing that improves with short-acting beta-agonist; nocturnal cough; symptom relief between episodes.
Differential diagnosis
- COPD — Older smoker, persistent (not reversible) airflow obstruction on PFTs, FEV1/FVC <0.7 post-bronchodilator that does not normalize
- Vocal cord dysfunction — Inspiratory stridor (not expiratory wheeze), throat tightness, normal PFTs between episodes, flattened inspiratory flow-volume loop; diagnosed by laryngoscopy during episode
- Heart failure ('cardiac asthma') — Orthopnea, PND, elevated BNP, cardiomegaly and pulmonary edema on CXR, S3 gallop
- Bronchiectasis — Chronic productive cough with copious purulent sputum, recurrent infections, tram-track opacities on HRCT
- Foreign body aspiration — Sudden onset in toddler or after choking event, unilateral wheeze, focal hyperinflation on expiratory CXR
- Pulmonary embolism — Acute dyspnea, pleuritic pain, hypoxia, tachycardia; risk factors for VTE
- ABPA (allergic bronchopulmonary aspergillosis) — Poorly controlled asthma + central bronchiectasis + elevated total IgE (>1000) and Aspergillus-specific IgE
- Eosinophilic granulomatosis with polyangiitis (EGPA) — Asthma + peripheral eosinophilia + sinusitis + neuropathy or pulmonary infiltrates
Diagnostic workup
Diagnostic criteria
GINA: history of variable respiratory symptoms + confirmed variable expiratory airflow limitation (bronchodilator reversibility, methacholine positivity, or PEF variability).
Labs
- CBC (eosinophilia supports allergic phenotype)
- Total IgE and allergen-specific IgE if considering biologics or ABPA
- FeNO (fractional exhaled nitric oxide) — elevated in Th2-high asthma
Imaging
- CXR — usually normal or hyperinflation; obtain to exclude alternative diagnoses or complications (pneumothorax, pneumonia)
- HRCT if bronchiectasis or alternative diagnosis suspected
Other studies
- Spirometry with bronchodilator response — first-line: obstructive pattern (FEV1/FVC reduced) with ≥12% AND ≥200 mL improvement in FEV1 post-bronchodilator confirms reversibility
- Methacholine challenge if spirometry normal but high clinical suspicion — PC20 ≤8 mg/mL is positive
- Peak expiratory flow monitoring for home tracking; diurnal variability >10% supports diagnosis
Diagnostic algorithm
| GINA Step | Preferred Controller | Reliever |
|---|---|---|
| 1 | As-needed low-dose ICS-formoterol | Low-dose ICS-formoterol PRN |
| 2 | Daily low-dose ICS OR PRN ICS-formoterol | Low-dose ICS-formoterol PRN |
| 3 | Low-dose ICS-LABA (formoterol) | Low-dose ICS-formoterol PRN (MART) |
| 4 | Medium-dose ICS-LABA | Low-dose ICS-formoterol PRN (MART) |
| 5 | High-dose ICS-LABA + add-on (LAMA, biologic) | Low-dose ICS-formoterol PRN; refer specialist |
Treatment
First-line
- GINA 2024 has eliminated SABA-only treatment; all adults and adolescents should receive ICS-containing therapy
- Step 1-2 (mild): low-dose ICS-formoterol PRN (preferred 'MART' approach) — budesonide-formoterol or beclomethasone-formoterol
- Step 3 (moderate): low-dose ICS-LABA daily + ICS-formoterol PRN as reliever
- Step 4: medium-dose ICS-LABA + ICS-formoterol PRN
- Step 5: high-dose ICS-LABA, refer for biologic/specialist
- Inhaled corticosteroid (ICS) options: fluticasone, budesonide, mometasone, beclomethasone, ciclesonide
- Long-acting beta-agonist (LABA): formoterol, salmeterol, vilanterol (NEVER as monotherapy in asthma)
Second-line / adjunct
- Long-acting muscarinic antagonist (LAMA) add-on: tiotropium, umeclidinium
- Leukotriene receptor antagonist: montelukast (FDA black-box warning for neuropsychiatric effects), zafirlukast
- Biologics for severe uncontrolled asthma: omalizumab (anti-IgE), mepolizumab/reslizumab/benralizumab (anti-IL-5/IL-5R), dupilumab (anti-IL-4Rα), tezepelumab (anti-TSLP)
- Oral corticosteroid burst for exacerbation: prednisone 40-60 mg daily × 5-7 days (no taper needed for short courses)
- Acute exacerbation: nebulized albuterol + ipratropium, systemic corticosteroids, oxygen to SpO2 ≥92% (≥94% in pregnancy), magnesium sulfate 2 g IV for severe
Complications
- Status asthmaticus, respiratory failure requiring intubation
- Pneumothorax, pneumomediastinum from barotrauma
- Airway remodeling with fixed obstruction (asthma-COPD overlap)
- ICS side effects: oral candidiasis, dysphonia, decreased growth velocity in children (small, reversible)
- Aspirin-exacerbated respiratory disease (AERD/Samter triad): asthma + nasal polyps + NSAID sensitivity
PANCE pearls
- GINA 2024 emphasizes anti-inflammatory reliever (ICS-formoterol) over SABA-only — SABA monotherapy is no longer recommended at any step.
- Silent chest, exhaustion, drowsiness, paradoxical thoracoabdominal motion, or pCO2 normalization (after initial hyperventilation) signal impending respiratory failure.
- Exercise-induced bronchoconstriction: pretreat with SABA 15 min before exercise; if frequent, daily ICS.
- Pregnancy: budesonide is the preferred ICS (most safety data). Uncontrolled asthma is more dangerous than medication.
- Beta-blockers and NSAIDs can trigger severe exacerbations in susceptible patients — verify tolerance before use.
References
- GINA 2024 — Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2024 Update (ginasthma.org)
- NAEPP 2020 — 2020 Focused Updates to the Asthma Management Guidelines (Cloutier et al., J Allergy Clin Immunol 2020)
- SYGMA Trials — As-Needed Budesonide-Formoterol vs Maintenance Budesonide in Mild Asthma (O'Byrne et al., NEJM 2018)
- ATS/ERS — ATS/ERS Standards for Diagnosis of Asthma in Adults and Children (Louis et al., Eur Respir J 2022)
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