What are the key updates in the 2025 Global Initiative for Chronic Obstructive Lung Disease (GOLD) report regarding COPD diagnosis, classification, and pharmacologic and non‑pharmacologic management?

GOLD 2025 Updates in COPD

Major Diagnostic Changes: Pre- and Post-Bronchodilator Spirometry

The most significant 2025 update is the new two-step spirometry pathway: use pre-bronchodilator spirometry to rule out COPD, then confirm diagnosis with post-bronchodilator testing showing FEV₁/FVC < 0.70. 1, 2, 3

The New Diagnostic Algorithm

• Step 1: Perform pre-bronchodilator spirometry first. If FEV₁/FVC ≥ 0.70, COPD is ruled out in most cases. 1, 3
• Step 2: If pre-BD FEV₁/FVC < 0.70, proceed to post-bronchodilator testing (≥400 µg salbutamol or 80 µg ipratropium). 1, 2, 4
• Confirmation: Only diagnose COPD when post-BD FEV₁/FVC remains < 0.70 in a patient with chronic respiratory symptoms and relevant exposure history. 1, 2, 3

Critical Nuances: Flow vs. Volume Responders

• "Flow responders" (pre-BD < 0.70 → post-BD ≥ 0.70) should NOT be diagnosed with COPD but require close follow-up every 3–6 months, as nearly 50% develop persistent obstruction over time, especially if they continue smoking. 1, 3
• "Volume responders" (pre-BD ≥ 0.70 → post-BD < 0.70) represent true COPD cases that would be missed without post-BD testing; these patients have more severe gas trapping and disease characteristics. 1, 3
• When post-BD FEV₁/FVC falls between 0.60–0.80, repeat spirometry on a separate occasion (suggested 3–6 months) to confirm the diagnosis and account for biological variation. 1, 2

Why This Matters

This two-step approach reduces COPD overdiagnosis (estimated at 11–35% in smokers using pre-BD values alone) while ensuring volume responders with more severe disease are not missed. 1, 3 The change prioritizes post-BD values because they better predict long-term outcomes and minimize false-positive diagnoses. 1

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ABCD Classification: Symptoms and Exacerbations Only

Since 2017, GOLD ABCD groups are determined exclusively by symptom burden and exacerbation history—spirometric severity (GOLD 1–4) is assessed separately and does NOT determine the ABCD group. 1, 2

How to Assign ABCD Groups

• Symptom assessment: Use mMRC dyspnea scale (≥2 = high symptoms) or CAT score (>20 = high symptoms). 2
• Exacerbation history: Count moderate exacerbations (requiring antibiotics/oral steroids) and severe exacerbations (requiring hospitalization) in the past 12 months. 2
• Group A: Low symptoms (mMRC 0–1 or CAT ≤20) AND 0–1 moderate exacerbations (no hospitalizations). 2
• Group B: High symptoms (mMRC ≥2 or CAT >20) AND 0–1 moderate exacerbations (no hospitalizations). 2
• Group C: Low symptoms AND ≥2 moderate exacerbations OR ≥1 hospitalization. 2
• Group D: High symptoms AND ≥2 moderate exacerbations OR ≥1 hospitalization. 2

Common Pitfall

Do not use FEV₁ % predicted to assign ABCD groups. A patient with FEV₁ <30% (GOLD 4) but no exacerbations and low symptoms is Group B, not Group D. 1, 2 Spirometric severity informs prognosis and consideration of interventional therapies (lung volume reduction, transplant) but not initial pharmacologic choice. 1

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Pharmacologic Management: Escalation and De-escalation

Group A (Low Symptoms, Low Risk)

• Initial: Short-acting bronchodilator (SABA or SAMA) as needed. 1, 2
• Escalation: If symptoms persist, add a long-acting bronchodilator (LAMA or LABA monotherapy). 1, 2

Group B (High Symptoms, Low Risk)

• Initial: Long-acting bronchodilator monotherapy (LAMA or LABA). 1, 2, 3
• Escalation: If dyspnea persists, escalate to dual bronchodilation (LABA/LAMA combination). 1, 2
• For severe breathlessness, consider starting with LABA/LAMA directly. 1

Group C (Low Symptoms, High Risk)

• Initial: LAMA monotherapy is preferred. 2
• Escalation: If exacerbations continue, add a second long-acting bronchodilator (LABA/LAMA). 2

Group D (High Symptoms, High Risk)

• Initial: LABA/LAMA combination is the recommended starting point. 1, 2
• Escalation to triple therapy (LABA/LAMA/ICS): Add ICS only when ALL three criteria are met:
  1. Blood eosinophil count ≥300 cells/µL. 2
  2. High symptom burden (mMRC ≥2 or CAT >20). 2
  3. ≥2 moderate exacerbations per year OR any severe exacerbation despite optimal bronchodilation. 2
• Triple therapy reduces moderate-to-severe exacerbations (rate ratio 0.74; 95% CI 0.67–0.81) and improves quality of life (≥4-point SGRQ reduction). 2, 4
• Triple therapy is the only pharmacologic intervention shown to reduce mortality (RR 0.82; 95% CI 0.69–0.98). 4, 5

De-escalation Concept

GOLD 2017 introduced the concept of stepping down therapy when disease control is achieved, though specific algorithms remain under development. 1, 2 Consider ICS withdrawal in patients with no exacerbations for ≥12 months and eosinophils <100 cells/µL, but monitor closely for exacerbation recurrence. 1

Key Caveat: ICS and Pneumonia Risk

ICS increase pneumonia risk; therefore, LABA/LAMA is preferred over LABA/ICS for Group A patients with persistent exacerbations. 1 Reserve ICS for patients meeting the triple-therapy criteria above. 2

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Non-Pharmacologic Management

Smoking Cessation: The Single Most Effective Intervention

• Smoking cessation slows COPD progression and reduces mortality more than any medication. 1, 2
• Offer counseling plus pharmacologic aids (nicotine replacement, varenicline, or bupropion) at every visit. 1, 2
• Long-term quit rates of up to 25% are achievable with dedicated resources and combination therapy (counseling + pharmacotherapy). 1
• E-cigarettes as cessation aids remain controversial; efficacy is uncertain. 1

Vaccinations

• Annual influenza vaccination reduces serious illness, death, ischemic heart disease risk, and total exacerbations. 1, 2
• Pneumococcal vaccination (PCV13 and PPSV23) is recommended for all patients ≥65 years. 1, 2

Pulmonary Rehabilitation

• Improves health status, dyspnea, and exercise capacity in symptomatic patients, particularly those with FEV₁ <60% predicted or notable functional limitation. 1, 2, 4
• Should be offered to all patients with persistent symptoms despite optimal pharmacotherapy. 1

Long-Term Oxygen Therapy (LTOT)

• LTOT reduces mortality (RR 0.61; 95% CI 0.46–0.82) in patients with chronic hypoxemia. 2, 4
• Indicated for resting PaO₂ ≤55 mmHg or SpO₂ ≤88%. 1, 2
• Do NOT prescribe LTOT routinely for stable COPD with resting or exercise-induced moderate desaturation; individual factors should guide decisions. 1

Noninvasive Ventilation (NIV)

• In patients with severe chronic hypercapnia and history of hospitalization for acute respiratory failure, long-term NIV may decrease mortality and prevent rehospitalization. 1

Interventional Therapies

• In select patients with advanced emphysema refractory to optimized medical care, surgical (lung volume reduction surgery, lung transplantation, bullectomy) or bronchoscopic interventions may be beneficial. 1
• Consider these options in GOLD 4 patients with low exacerbation rates (e.g., Group B). 1

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Acute Exacerbation Management

• Increased short-acting bronchodilator use (SABA ± SAMA). 2
• Systemic corticosteroids: Prednisone 40 mg daily for 5 days. 2
• Antibiotics: When sputum purulence or other signs of bacterial infection are present. 2
• Supplemental oxygen: Titrate to maintain SpO₂ 88–92%. 2
• Hospital admission: For severe exacerbations, poor response to outpatient therapy, or significant comorbidities. 2

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Follow-Up and Monitoring

Early Follow-Up (4–6 Weeks)

• Re-evaluate after initiating or changing therapy to assess treatment response, inhaler technique, symptom control, and need for adjustment. 2, 3
• Inhaler technique must be assessed regularly—poor technique is a common cause of treatment failure. 1, 2

Annual Review

• Perform annual spirometry, symptom assessment (mMRC or CAT), review exacerbation history, and screen for comorbidities (cardiovascular disease, osteoporosis, anxiety/depression, lung cancer). 2, 3

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Comorbidity Management

• Most COPD deaths are due to comorbidities (cardiovascular disease, lung cancer), not COPD itself. 2
• Manage comorbidities according to their respective standard guidelines, recognizing shared risk factors like smoking. 2
• Screen for overlap syndrome (COPD + obstructive sleep apnea), which worsens nocturnal hypoxemia and raises pulmonary hypertension risk; overnight oximetry can identify sleep-disordered breathing. 2
• Co-existing bronchiectasis is frequently under-diagnosed and associated with longer exacerbations and higher mortality. 2

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Screening Recommendations

• Routine screening spirometry in asymptomatic adults without respiratory symptoms is NOT recommended; the USPSTF finds no net benefit. 2, 4
• Only perform spirometry in individuals ≥40 years with chronic respiratory symptoms (dyspnea, cough, sputum, wheeze) and relevant exposure history (tobacco, biomass fuels, occupational dusts). 1, 2

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Emerging Concepts: Pre-COPD and PRISm

GOLD 2025 recognizes earlier-stage conditions like "pre-COPD" (chronic respiratory symptoms or structural lung changes without spirometric obstruction) and "PRISm" (preserved ratio impaired spirometry: FEV₁ <80% predicted with FEV₁/FVC ≥0.70). 6 These categories mark a shift toward early detection and personalized management, though specific treatment algorithms for these populations are still under development. 6 Patients with PRISm or pre-COPD warrant longitudinal monitoring and aggressive risk-factor modification. 6

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Key Takeaways for Clinical Practice

• Use the two-step spirometry pathway (pre-BD to rule out, post-BD to confirm) to reduce overdiagnosis while capturing volume responders. 1, 2, 3
• Assign ABCD groups based solely on symptoms and exacerbations—ignore spirometric severity for this purpose. 1, 2
• Start Group D patients on LABA/LAMA; escalate to triple therapy only when eosinophils ≥300, high symptoms, and ≥2 exacerbations/year. 1, 2
• Smoking cessation is the single most effective intervention—offer it at every visit. 1, 2
• Triple therapy is the only pharmacologic treatment proven to reduce mortality. 2, 4, 5
• Assess inhaler technique at every visit—it is a common, correctable cause of treatment failure. 1, 2