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Pulmonary Medicine›Condition·Updated Jul 11, 2026·v1

Asthma

Asthma is a heterogeneous inflammatory airway disease managed with a stepwise, biomarker-informed approach. The GINA framework prioritizes ICS-based therapy from step 1, with as-needed ICS-formoterol as the preferred reliever. For severe asthma, add-on biologics targeting type 2 inflammation reduce exacerbations by 50-60% and can induce clinical remission. Avoiding SABA overuse and achieving early remission are key to preserving lung function and reducing mortality.

High Evidence814 references·9,836 words·40 min read·v1
asthmapulmonary medicineairway inflammationbronchial hyperresponsivenessinhaled corticosteroidsbiologicsGINA guidelinesclinical remission

Quick Reference

RxDrug of choiceAs-needed low-dose budesonide-formoterol (200/6 μg) for mild asthma; maintenance budesonide-formoterol (160/4.5 μg BID) plus as needed for moderate-to-severe asthma.
AltAlternativesBiologics (omalizumab, mepolizumab, benralizumab, dupilumab, tezepelumab), azithromycin 500 mg three times weekly, LAMA (umeclidinium 62.5 μg daily).
⊘AvoidSABA monotherapy (GINA 2021), non-dihydropyridine CCBs, nonselective beta-blockers, NSAIDs in aspirin-exacerbated respiratory disease.
DxTest of choiceSpirometry with bronchodilator reversibility (≥12% and ≥200 mL increase in FEV1).
ScKey scoreGINA step classification, Asthma Control Questionnaire (ACQ-5), blood eosinophil count, FeNO.
→When to referSevere asthma (Step 4-5), poor control despite optimal therapy, need for biologic initiation, occupational asthma, diagnostic uncertainty, consideration of bronchial thermoplasty.
Asthma is a heterogeneous inflammatory airway disease managed with stepwise ICS-based therapy; biomarker-guided add-on biologics reduce exacerbations by 50-60%; avoid SABA overuse and aim for early clinical remission to preserve lung function.
Asthma is a chronic inflammatory airway disease affecting 260 million people worldwide, characterized by variable airflow obstruction and respiratory symptoms that fluctuate over time. The cornerstone of management is inhaled corticosteroid-based therapy, with as-needed low-dose ICS-formoterol replacing SABA monotherapy as the preferred reliever across all severity steps. Biomarker-guided add-on therapies, including biologics targeting IL-5, IL-4Rα, IgE, and TSLP, have transformed outcomes for severe asthma, reducing exacerbations by 50-60% and enabling clinical remission in a substantial minority. Avoiding SABA overuse (≥3 canisters/year) is critical, as it independently predicts increased exacerbation risk and mortality. This page provides a comprehensive overview of asthma diagnosis, classification, and evidence-based management, with emphasis on the stepwise GINA framework and treatable traits approach.

Overview and Recommendations

Background

  • •Asthma is a chronic inflammatory airway disease affecting 260 million people worldwide, characterized by variable airflow limitation, airway hyperresponsiveness, and episodic symptoms (wheeze, dyspnea, cough, chest tightness). It is a heterogeneous syndrome with multiple phenotypes, allergic, eosinophilic, exercise-induced, obesity-related, and aspirin-exacerbated, each driven by distinct molecular pathways.
  • •The T2-high endotype (eosinophilic, driven by IL-4, IL-5, IL-13) accounts for ~50% of asthma and responds well to inhaled corticosteroids. The T2-low endotype (neutrophilic or paucigranulocytic) is less corticosteroid-responsive and often associated with obesity, smoking, or IL-17-driven inflammation.
  • •Airway remodeling, subepithelial fibrosis, smooth muscle hypertrophy, goblet cell metaplasia, develops from both inflammation and mechanical forces of bronchoconstriction. This structural change accelerates lung function decline: each 100 cells/μL higher blood eosinophil count adds 1.0 mL/year FEV1 loss.
  • •Asthma mortality remains ~180,000 deaths annually. SABA overuse is a critical risk factor: ≥11 canisters/year increases mortality 2.35-fold; even 3-5 canisters/year carries 26% excess mortality. GINA 2021 eliminated SABA monotherapy, establishing as-needed low-dose ICS-formoterol as the preferred reliever.

Evaluation

  • •Suspect asthma in patients with episodic dyspnea, cough, wheeze, or chest tightness, worse at night, early morning, after exercise, or with allergen/irritant exposure. Nocturnal awakenings are a hallmark.
  • •Ask about triggers (allergens, viruses, exercise, occupational exposures, NSAIDs), atopic history (eczema, allergic rhinitis), and family history. Document smoking history and SABA use frequency.
  • •Examine for expiratory wheeze, prolonged expiration, hyperinflation. Between exacerbations, examination may be normal. In severe exacerbations, look for silent chest, pulsus paradoxus >10 mmHg, accessory muscle use, cyanosis.
  • •Order spirometry with bronchodilator testing: confirm asthma with ≥12% and ≥200 mL increase in FEV1 after albuterol 400 μg. If normal, consider methacholine, exercise, or mannitol challenge.
  • •Measure biomarkers: blood eosinophil count (≥150 cells/μL suggests T2-high), FeNO (≥25 ppb indicates eosinophilic inflammation), and serum IgE. These predict exacerbation risk and guide therapy.
  • •Consider chest CT if atypical features: fixed obstruction, hemoptysis, suspicion of bronchiectasis, ABPA, or asthma-COPD overlap. Mucus plug burden on CT is an emerging prognostic marker.
  • •Assess control with ACQ-5 or ACT: well-controlled = daytime symptoms ≤2 days/week, no nocturnal awakenings, no activity limitation, SABA use ≤2 days/week.
  • •Evaluate for comorbidities: vocal cord dysfunction, GERD, obesity, sleep apnea, chronic rhinosinusitis with nasal polyps, ABPA.
  • •In children unable to perform spirometry, use impulse oscillometry. Consider alternative diagnoses: primary ciliary dyskinesia, bronchopulmonary dysplasia, foreign body aspiration.
  • •Red flags for severe exacerbation: inability to speak in full sentences, accessory muscle use, pulsus paradoxus >20 mmHg, silent chest, cyanosis, somnolence, PEF <50% personal best.

Management

  • •For mild asthma (Steps 1-2), prescribe as-needed low-dose budesonide-formoterol (200/6 μg, 1 inhalation as needed), reduces severe exacerbations by 64% vs SABA alone with lower ICS exposure.
  • •For moderate asthma (Step 3), use MART: budesonide-formoterol 160/4.5 μg, 2 inhalations BID plus as needed. Reduces exacerbations 40-50% vs fixed-dose ICS/LABA plus SABA.
  • •For severe asthma (Steps 4-5), escalate to high-dose ICS/LABA (e.g., fluticasone furoate/vilanterol 200/25 μg daily) and add LAMA (umeclidinium 62.5 μg daily), azithromycin 500 mg three times weekly, or biologic therapy based on biomarkers.
  • •Select biologic by phenotype: omalizumab (75-600 mg SC q2-4wk) for allergic asthma; mepolizumab (100 mg SC q4wk) or benralizumab (30 mg SC q4wk×3 then q8wk) for eosinophilic; dupilumab (200-300 mg SC q2wk) for T2-high; tezepelumab (210 mg SC q4wk) for all severe asthma regardless of eosinophils.
  • •For acute exacerbations, give albuterol 4-8 puffs via MDI with spacer or 5 mg nebulized every 20 min for first hour. Add ipratropium 0.5 mg nebulized every 20 min for three doses in severe cases.
  • •Start systemic corticosteroids: prednisolone 40-50 mg orally daily (or IV methylprednisolone 80 mg/day) for 5-7 days. Oral and IV are equally effective.
  • •Titrate oxygen to SpO2 94-98%. Consider NIV for respiratory failure (pH <7.35, PaCO2 >45 mmHg), may reduce intubation (RR 0.55). Do not delay intubation if deteriorating.
  • •Monitor PEF (target >60% predicted), SpO2, respiratory rate, accessory muscle use, pulsus paradoxus. ICU criteria: refractory hypoxemia, altered mental status, exhaustion, rising PaCO2, failed NIV.
  • •Avoid SABA overuse: ≥3 canisters/year increases exacerbation risk (HR 1.26) and mortality (HR 1.26-2.35). Use as-needed ICS-formoterol as reliever.
  • •Avoid non-dihydropyridine CCBs, nonselective beta-blockers, and NSAIDs in N-ERD.
  • •Aim for clinical remission: zero exacerbations, no OCS, ACQ-5 ≤1.5, FEV1 ≥80% predicted. Remission within 1 year of ICS initiation slows FEV1 decline by 31.6 mL/year.
  • •Step-down after ≥3 months of control: reduce OCS first, then consider biologic taper if remission >12 months, then reduce ICS to lowest effective dose. Do not stop biologic abruptly, COMET trial showed loss of control (HR 1.61) after stopping mepolizumab.

Board Review — High Yield

  • •T2-high vs T2-low endotype, T2-high asthma (eosinophilic, elevated FeNO, IgE) responds to ICS and biologics; T2-low (neutrophilic, paucigranulocytic) is less corticosteroid-responsive and often associated with obesity or smoking.
  • •GINA stepwise approach, GINA 2021 eliminated SABA monotherapy; as-needed low-dose ICS-formoterol is the preferred reliever for all severities, reducing severe exacerbations by 64% in mild asthma.
  • •SMART/MART therapy, Maintenance-and-reliever therapy with budesonide-formoterol reduces exacerbations by 40-50% compared to fixed-dose ICS/LABA plus SABA, with lower total ICS exposure.
  • •SABA overuse mortality, Collecting ≥11 SABA canisters per year increases mortality risk 2.35-fold; even 3-5 canisters carries 26% excess mortality.
  • •Clinical remission, A composite endpoint (zero exacerbations, no OCS, ACQ-5 ≤1.5, FEV1 ≥80% predicted) is achievable with biologics in 20-38% of severe asthma patients; early remission predicts slower lung function decline.
  • •Biologics for severe asthma, Six biologics are approved: omalizumab (anti-IgE), mepolizumab/benralizumab (anti-IL-5/5R), dupilumab (anti-IL-4Rα), tezepelumab (anti-TSLP), and depemokimab (ultra-long-acting anti-IL-5). Tezepelumab is effective regardless of eosinophil count.
  • •Airway remodeling, Bronchoconstriction alone can induce remodeling via mechanical forces; achieving airway patency may be as important as suppressing inflammation for long-term outcomes.
  • •FeNO and eosinophils as predictors, Per 10-fold increase in blood eosinophils, exacerbation rate ratio is 1.48; per 10-fold increase in FeNO, 1.44. These biomarkers guide biologic selection and predict future attack risk.
  • •Azithromycin for remission, Azithromycin 500 mg three times weekly induced clinical remission in 50.6% of patients vs 38.9% with placebo in the AMAZES trial, particularly in noneosinophilic asthma.
  • •Occupational asthma, At least 16% of adult-onset asthma is attributable to occupational exposures; systematic inquiry and serial PEF monitoring are essential for diagnosis.

Deep Dive — Evidence Details

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