At what stage of chronic obstructive pulmonary disease (COPD) should inhalers be initiated in patients?

When to Start Inhalers in COPD

Inhalers should be started as soon as patients with confirmed COPD (post-bronchodilator FEV1/FVC <0.70) develop respiratory symptoms, beginning with long-acting bronchodilator monotherapy (LAMA or LABA) rather than short-acting agents, even in mild disease with FEV1 ≥80% predicted. 1, 2

Symptom-Based Initiation Strategy

Patients with Low Symptom Burden (CAT <10, mMRC <2)

• Start with a single long-acting bronchodilator (LAMA or LABA) if FEV1 ≥80% predicted and symptoms are present 1, 2
• No significant difference exists between LAMA versus LABA as initial choice in this population 1
• Short-acting bronchodilators as needed are insufficient for maintenance therapy and should not be the primary approach 1, 2

Patients with Moderate-to-High Symptoms (CAT ≥10, mMRC ≥2)

• Initiate LAMA/LABA dual therapy immediately if FEV1 <80% predicted 1, 2
• This represents a change from older guidelines that recommended monotherapy escalation 1
• Dual therapy provides superior efficacy compared to monotherapy with similar safety profiles 1

Exacerbation History Determines Escalation

High-Risk Patients (≥2 Moderate or ≥1 Severe Exacerbation/Year)

• Start triple therapy (LAMA/LABA/ICS) immediately if CAT ≥10, mMRC ≥2, and FEV1 <80% predicted 1, 2
• Triple therapy reduces mortality with moderate certainty of evidence, making it the preferred initial choice over dual therapy in this population 1, 2
• Single-inhaler triple therapy (SITT) is preferred over multiple inhalers to reduce errors and improve adherence 1

Low-Risk Patients (0-1 Moderate Exacerbation/Year, No Severe)

• Start with LAMA/LABA dual therapy if symptomatic 1, 2
• Do not initiate ICS-containing regimens in low-risk patients without exacerbation history 2

Critical Timing Considerations

The earlier treatment is initiated, the greater the impact on disease progression. 3 Long-acting bronchodilators have been shown to slow lung function decline, reduce exacerbations and mortality, and improve health-related quality of life in patients with mild-to-moderate COPD 3. Delaying maintenance therapy until disease becomes severe misses the opportunity to modify disease trajectory 3.

Common Pitfalls to Avoid

• Never prescribe ICS monotherapy in stable COPD at any stage—it increases pneumonia risk without adequate bronchodilation 1, 2
• Do not wait for severe symptoms before starting long-acting bronchodilators; symptomatic patients with any degree of airflow limitation benefit from maintenance therapy 1, 2
• Avoid starting with short-acting bronchodilators alone as maintenance therapy in symptomatic patients—this is outdated practice 1, 2
• Do not prescribe ICS-containing regimens to patients without exacerbation history, as this increases pneumonia risk without clear benefit 2
• Beta-blocking agents (including eye drops) should be avoided in all COPD patients 1

Blood Eosinophil-Guided Decisions

When considering ICS-containing therapy:

• Eosinophils <100 cells/μL: Do not escalate to triple therapy; add oral therapies instead (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

Device Selection and Technique

• Inhaler technique must be demonstrated before prescribing and rechecked periodically 1, 4
• If patients cannot use metered-dose inhalers correctly, more expensive devices are justified 1, 4
• Poor inhaler technique compromises symptom relief in most patients using hand-held inhalers 5, 6
• Prescribing multiple devices with different inhalation techniques increases exacerbations and medication errors 2

Concomitant Asthma Exception

ICS/LABA combination therapy should be used in individuals with concomitant asthma, regardless of exacerbation history 1. However, LAMA/LABA dual therapy is preferred over ICS/LABA in pure COPD due to superior lung function improvements and lower pneumonia rates 1.