What is the basis of treatment for Chronic Obstructive Pulmonary Disease (COPD) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria?

GOLD Criteria and Treatment Basis for COPD

The basis of COPD treatment according to GOLD criteria is a stepwise approach using long-acting bronchodilators (LAMA and/or LABA) as the foundation, with treatment selection determined by symptom burden (measured by CAT or mMRC scores) and exacerbation history, not spirometric severity alone. 1, 2

GOLD Classification System

The GOLD framework stratifies patients into groups based on two key parameters 2:

• Symptom assessment: CAT score or mMRC dyspnea scale to quantify symptom burden
• Exacerbation history: Frequency and severity of past exacerbations (≥2 moderate or ≥1 requiring hospitalization defines high risk)
• FEV1 measurement: Used for diagnosis and monitoring, but no longer the primary driver of treatment decisions 1, 2

This represents a fundamental shift from older spirometry-based staging to a more clinically relevant symptom-and-risk-based approach. 1

Treatment Algorithm by GOLD Group

Group A (Low Symptoms, Low Risk)

• Start with short-acting bronchodilator (SABA or SAMA) as needed for intermittent symptoms 1, 2, 3
• If symptoms persist, escalate to a long-acting bronchodilator (LABA or LAMA) 1, 3
• Continue only if symptomatic benefit is demonstrated 1

Group B (High Symptoms, Low Risk)

• Initiate with a single long-acting bronchodilator (LABA or LAMA) as first-line therapy 1, 2, 3
• No evidence favors one class over another for initial symptom relief; choice depends on individual response 1
• For persistent breathlessness on monotherapy, escalate to dual bronchodilator therapy (LABA/LAMA) 1, 2, 3
• For severe breathlessness at presentation, consider starting directly with LABA/LAMA combination 1

Group C (Low Symptoms, High Risk)

• LAMA is preferred over LABA for exacerbation prevention when choosing monotherapy 1, 2
• LABA/LAMA combination is an alternative for this group 1

Group D (High Symptoms, High Risk)

• Initiate with LABA/LAMA combination as first-line therapy 1, 2, 3
• This recommendation is based on three critical advantages 1:
  • Superior patient-reported outcomes versus single bronchodilator
  • Superior exacerbation prevention versus LABA/ICS combination
  • Lower pneumonia risk compared to ICS-containing regimens

Treatment Escalation Pathways for Persistent Exacerbations

For Patients on LABA/LAMA with Ongoing Exacerbations

Two alternative pathways exist 1, 2:

1. Escalate to triple therapy (LABA/LAMA/ICS) if:

   • Blood eosinophil count ≥300 cells/µL 2
   • History of hospitalizations for exacerbations 2
   • ≥2 moderate exacerbations per year despite appropriate bronchodilator therapy 2

2. Switch to LABA/ICS, then add LAMA if no improvement 1

LABA/ICS may be considered as initial therapy in patients with asthma-COPD overlap (ACO) or high blood eosinophil counts 1

For Patients on Triple Therapy with Persistent Exacerbations

Add roflumilast if 1, 2:

• FEV1 <50% predicted
• Chronic bronchitis phenotype present
• At least one hospitalization for exacerbation in the previous year

Add macrolide therapy in former smokers 1, 2:

• Consider the risk of developing resistant organisms in decision-making
• Not recommended for current smokers

Consider stopping ICS if no benefit, given elevated pneumonia risk 1

Critical Safety Considerations

What NOT to Do

• Never use ICS as monotherapy in COPD (Evidence A) 1, 3
• Never use long-term oral corticosteroids (Evidence A) 1
• Do not prescribe statins for exacerbation prevention (Evidence A) 1
• Avoid drugs approved for primary pulmonary hypertension in COPD-related pulmonary hypertension (Evidence B) 1

ICS-Related Risks

ICS increase pneumonia risk, particularly in 1, 2:

• Older patients
• Those with severe disease
• Group D patients at baseline higher risk

This is why LABA/LAMA is preferred over LABA/ICS for initial therapy in Group D patients, despite both being effective. 1

Non-Pharmacologic Management

Essential Components

• Smoking cessation is the single most important intervention and should be continuously encouraged 1, 3
• Pulmonary rehabilitation for all symptomatic patients (Groups B, C, D), especially those with exercise limitation 1, 2, 3
• Programs should combine constant/interval training with strength training 2
• Education and personalized self-management tailored to individual needs and goals 1, 2

Vaccinations and Oxygen

• Annual influenza vaccination and pneumococcal vaccination (PCV13 and PPSV23) for all COPD patients 2
• Oxygen therapy for resting hypoxemia (PaO2 ≤55 mmHg or SaO2 ≤88%) 2, 3

Special Therapies for Specific Situations

• Alpha-1 antitrypsin augmentation therapy for patients with severe hereditary deficiency and established emphysema (Evidence B) 1, 3
• Low-dose long-acting opioids may be considered for dyspnea in severe disease (Evidence B) 1, 3
• Antioxidant mucolytics recommended only in selected patients (Evidence A) 1
• Antitussives cannot be recommended (Evidence C) 1

Common Pitfalls to Avoid

ICS overuse remains a major problem in clinical practice 4, 5, 6:

• Real-world data show clinicians frequently prescribe ICS inappropriately
• The incorrect assumption that adding ICS is the logical next step after LABA/LAMA fails drives this overuse
• Adhere strictly to eosinophil and exacerbation criteria before adding ICS 2, 5

Treatment goals should focus on 1:

• Reducing current symptom severity
• Preventing future exacerbations
• Slowing disease progression
• Improving quality of life and exercise capacity
• Reducing mortality risk