What are the key recommendations for COPD management in the 2025 update to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines?

GOLD 2025 COPD Management Update

The 2025 GOLD guidelines introduce "pre-COPD" and "PRISm" (preserved ratio impaired spirometry) as new diagnostic categories, enabling earlier detection and intervention before traditional COPD criteria are met. 1

Key Diagnostic Innovations

Expanded Diagnostic Framework

• Pre-COPD recognition: The guidelines now identify patients with early symptoms or structural lung changes who don't yet meet traditional spirometric COPD criteria, allowing for preventive interventions before irreversible damage occurs 1
• PRISm category: Patients with preserved FEV1/FVC ratio but impaired spirometry are now formally recognized, capturing a previously overlooked population at risk for disease progression 1
• Advanced diagnostic tools: The framework emphasizes comprehensive assessment using imaging and biomarkers alongside spirometry to identify diverse pathophysiological profiles 1

Pharmacological Management Algorithm

Group A (Low Symptoms, Low Exacerbation Risk)

• Initial therapy: Start with long-acting bronchodilator monotherapy (LABA or LAMA) rather than short-acting agents for symptomatic patients with confirmed spirometry 2
• FEV1 ≥80% with mMRC 1: Long-acting bronchodilator preferred over short-acting options, with no significant difference between LAMA or LABA choice 2

Group B (High Symptoms, Low Exacerbation Risk)

• Initial approach: LAMA/LABA dual therapy is now the strong recommendation for patients with mMRC ≥2 and FEV1 <80% predicted, representing a change from 2019 guidelines 2
• Persistent breathlessness: Escalate from monotherapy to dual bronchodilator therapy (LABA/LAMA) 2, 3
• Severe breathlessness: Consider initiating dual bronchodilators upfront rather than starting with monotherapy 2

Group D (High Symptoms, High Exacerbation Risk)

• First-line therapy: Single-inhaler triple therapy (LAMA/LABA/ICS) is strongly recommended for patients with CAT ≥10, mMRC ≥2, FEV1 <80% predicted, and ≥2 moderate or ≥1 severe exacerbation in the past year 2
• Mortality benefit: Triple therapy reduces mortality with moderate certainty of evidence in this high-risk population, making it the preferred choice over LABA/LAMA dual therapy 2
• LABA/LAMA as alternative: If single bronchodilator chosen initially, LAMA is preferred over LABA for exacerbation prevention 2

Blood Eosinophil-Guided Therapy

ICS Escalation Decisions

• Eosinophils <100 cells/μL: Do NOT escalate from LABA/LAMA to triple therapy; instead add oral therapies (azithromycin or N-acetylcysteine) 2
• Eosinophils ≥300 cells/μL: Do NOT withdraw ICS in patients with moderate-high symptom burden and high exacerbation risk 2
• Continuum interpretation: Blood eosinophil count functions as a continuum to predict ICS response, not an absolute threshold 4

ICS Withdrawal Considerations

When to Consider Stopping ICS

• Adverse effects: Withdraw if significant side effects occur, particularly recurrent pneumonia 2
• Stable disease: ICS can be rationally discontinued in patients with stable disease without unfavorable effects on lung function or exacerbation risk 5
• Low eosinophils: Patients with eosinophils <100 cells/μL are less likely to benefit from ICS continuation 2

When NOT to Withdraw ICS

• High exacerbation risk: Do not withdraw in patients with moderate-high symptom burden and high risk of exacerbations 2
• Elevated eosinophils: Avoid withdrawal when blood eosinophils ≥300 cells/μL 2

Additional Pharmacological Options

For Persistent Exacerbations on Triple Therapy

• Roflumilast: Add for patients with FEV1 <50% predicted, chronic bronchitis phenotype, and ≥1 hospitalization for exacerbation in the previous year 2, 3
• Macrolide therapy: Consider in former smokers with recurrent exacerbations, weighing risk of resistant organisms 2
• Oral adjuncts: N-acetylcysteine or azithromycin can be added to triple therapy in appropriate patients 2

Critical Safety Warnings

Pneumonia Risk

• ICS-associated pneumonia: All ICS formulations increase pneumonia risk as a class effect, but this is outweighed by benefits in high-risk exacerbators 2, 4
• Risk stratification: Carefully assess individual risk-benefit profile before initiating or continuing ICS therapy 4, 5
• Never use ICS monotherapy: ICS should only be used in combination with long-acting bronchodilators 3

Single-Inhaler Preference

• Superior outcomes: Single-inhaler triple therapy demonstrates better health status and lung function improvements compared to multiple-inhaler regimens 2
• Reduced errors: Multiple devices with similar inhalation techniques show lower exacerbation rates than devices requiring different techniques 2
• Study evidence: Most guideline evidence is based on single-inhaler combinations; efficacy cannot be extrapolated to multiple-inhaler approaches 2

Non-Pharmacological Interventions

Essential Components

• Smoking cessation: Remains the single most important intervention, with varenicline, bupropion, and nicotine replacement increasing long-term quit rates to 25% 2, 3
• Pulmonary rehabilitation: Strongly recommended for all symptomatic patients (Groups B, C, D), considering individual characteristics and comorbidities 2, 3
• Oxygen therapy: Indicated for resting hypoxemia (PaO2 ≤55 mmHg or SaO2 ≤88%) to improve survival 2, 3

Advanced Interventions

• Alpha-1 antitrypsin augmentation: For patients with severe hereditary deficiency and established emphysema 2, 3
• Low-dose opioids: Consider for dyspnea management in severe disease refractory to other treatments 2, 3
• Surgical options: Lung volume reduction or transplantation for select patients with GOLD grade 4, low exacerbation burden, and refractory symptoms 2

Common Pitfalls to Avoid

• Overuse of ICS: Do not prescribe ICS-containing regimens to low-risk patients without exacerbation history 2
• Ignoring eosinophils: Blood eosinophil counts should guide ICS decisions, particularly at extremes (<100 or ≥300 cells/μL) 2
• Multiple-inhaler confusion: Prescribing multiple devices with different inhalation techniques increases exacerbations and medication errors 2
• Delayed triple therapy: In high-risk exacerbators, starting with dual therapy and waiting for further exacerbations delays mortality benefit 2
• Environmental impact: Consider carbon footprint when selecting between equivalent inhaler options, particularly for short-acting beta-agonists which constitute 71% of Canadian inhaler use 2