Pulmonary · PANCE / PANRE

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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Question 1PulmonaryMedium
A 28-year-old woman with asthma reports symptoms every day and nighttime awakenings about three times per week. She uses her short-acting beta-agonist daily for relief, and her symptoms limit some normal activities. She is currently taking no controller medication. Spirometry shows an FEV1 of 72% predicted. Using the National Asthma Education and Prevention Program (NAEPP) framework, which of the following is the most appropriate initial treatment step?
  • AStep 2
  • BStep 3
  • CStep 1
  • DStep 4
Reveal answer & full explanation
Correct answer: B — Step 3
  • AStep 2
  • BStep 3
  • CStep 1
  • DStep 4

Why Step 3 is correct

  • Daily symptoms, nighttime awakenings more than once weekly, and an FEV1 of 60-80% predicted classify this as moderate persistent asthma
  • Per the NAEPP framework, moderate persistent asthma in an adolescent or adult is initiated at Step 3: low-dose inhaled corticosteroid (ICS) plus a long-acting beta-agonist (LABA), or low-dose ICS-formoterol used as both controller and reliever
  • Control is reassessed in a few weeks and therapy is stepped up if it is not achieved

Why the others are wrong

  • Step 1 — Step 1 is for intermittent asthma (symptoms two days per week or fewer, rare nighttime awakenings); daily symptoms exclude it (premature closure on the mildest category)
  • Step 2 — Step 2 corresponds to mild persistent asthma; daily symptoms and nighttime awakenings more than once weekly exceed mild criteria (buzzword-matching "persistent" without grading its severity)
  • Step 4 — Step 4 is reserved for severe persistent disease (symptoms throughout the day, awakenings often nightly, FEV1 under 60%); the FEV1 of 72% and three-nights-per-week awakenings defeat it (anchoring on the daily symptoms while ignoring the lung function)
Question 2PulmonaryEasy
A 32-year-old woman with a severe asthma exacerbation has SpO2 91% and peak flow 45% of predicted. After three back-to-back albuterol nebulizations she has only minimal improvement. Which of the following is the most appropriate next step?
  • AEndotracheal intubation
  • BAdd IV magnesium sulfate and systemic corticosteroids
  • CAdminister subcutaneous epinephrine
  • DContinue albuterol nebulization alone every 20 minutes
Reveal answer & full explanation
Correct answer: B — Add IV magnesium sulfate and systemic corticosteroids
  • AEndotracheal intubation
  • BAdd IV magnesium sulfate and systemic corticosteroids
  • CAdminister subcutaneous epinephrine
  • DContinue albuterol nebulization alone every 20 minutes

Why IV magnesium sulfate and systemic corticosteroids is correct

  • For a severe asthma exacerbation not responding to initial bronchodilator therapy, the next step is to add systemic corticosteroids and IV magnesium sulfate (a smooth muscle relaxant) and reassess every 30 minutes.

Why the others are wrong

  • Endotracheal intubation — Reserved for impending respiratory failure, indicated by a silent chest, exhaustion, altered mental status, or rising PaCO2, none of which are present here.
  • Administer subcutaneous epinephrine — Parenteral epinephrine is reserved for anaphylaxis or near-fatal asthma with poor aerosol delivery; this patient is still moving air and ventilating, so it adds systemic toxicity without outperforming inhaled beta-agonists plus corticosteroids and magnesium.
  • Continue albuterol nebulization alone every 20 minutes — Continuing bronchodilator therapy alone without escalating to corticosteroids and magnesium is insufficient for a severe exacerbation with poor initial response.
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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 StepPreferred ControllerReliever
1As-needed low-dose ICS-formoterolLow-dose ICS-formoterol PRN
2Daily low-dose ICS OR PRN ICS-formoterolLow-dose ICS-formoterol PRN
3Low-dose ICS-LABA (formoterol)Low-dose ICS-formoterol PRN (MART)
4Medium-dose ICS-LABALow-dose ICS-formoterol PRN (MART)
5High-dose ICS-LABA + add-on (LAMA, biologic)Low-dose ICS-formoterol PRN; refer specialist
GINA 2024 stepwise treatment for adults and adolescents (Track 1, ICS-formoterol-based).

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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