What is the step-up therapy for Chronic Obstructive Pulmonary Disease (COPD) using inhalers (puffer regimen)?

From the Guidelines

The most effective step-up therapy for COPD involves a single-inhaler triple therapy with LAMA/LABA/ICS for patients with persistent moderate to severe dyspnea and/or poor health status despite treatment with single-inhaler dual therapy with LAMA/LABA or ICS/LABA, as recommended by the 2023 Canadian Thoracic Society guideline 1.

Step-Up Therapy Approach

The step-up therapy for COPD typically follows a progressive approach based on symptom severity and exacerbation risk.

• Initially, patients should start with a short-acting bronchodilator like albuterol (salbutamol) or ipratropium as needed for symptom relief.
• As symptoms persist, the next step involves adding a long-acting bronchodilator, either a long-acting muscarinic antagonist (LAMA) such as tiotropium (Spiriva) 18mcg once daily, or a long-acting beta-agonist (LABA) like salmeterol (Serevent) 50mcg twice daily.
• For patients who remain symptomatic on a single long-acting bronchodilator, dual bronchodilation with both LAMA and LABA is recommended, such as umeclidinium/vilanterol (Anoro Ellipta) 62.5/25mcg once daily or tiotropium plus salmeterol.

Triple Therapy

If exacerbations continue despite dual bronchodilation, adding an inhaled corticosteroid (ICS) is appropriate, moving to triple therapy with LAMA/LABA/ICS, such as fluticasone/umeclidinium/vilanterol (Trelegy Ellipta) 100/62.5/25mcg once daily, which has been shown to reduce mortality in individuals with moderate-severe disease and a high risk of AECOPD 1.

Key Considerations

• Proper inhaler technique should be regularly assessed, and patients should be monitored for side effects such as oral thrush with ICS use, which can be minimized by rinsing the mouth after administration.
• The 2023 Canadian Thoracic Society guideline 1 provides the most recent and highest quality evidence for the management of stable COPD, and its recommendations should be prioritized in clinical practice.

From the FDA Drug Label

Formoterol Fumarate Inhalation Solution is indicated for the long-term, twice daily (morning and evening) administration in the maintenance treatment of bronchoconstriction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. If the recommended maintenance treatment regimen fails to provide the usual response, medical advice should be sought immediately, as this is often a sign of destabilization of COPD. Under these circumstances, the therapeutic regimen should be re-evaluated and additional therapeutic options should be considered

The puffer regimen for COPD step-up therapy may involve adding another medication to the current treatment.

• Step-up therapy options may include adding a different class of medication, such as an inhaled corticosteroid (ICS) or a phosphodiesterase-4 (PDE4) inhibitor, to the current long-acting beta2-adrenergic agonist (LABA) therapy, such as formoterol.
• Alternatively, adding a long-acting muscarinic antagonist (LAMA), such as aclidinium, to the current treatment regimen may be considered. However, the specific step-up therapy regimen should be determined on a case-by-case basis, taking into account the individual patient's response to treatment and medical history 2.

From the Research

Puffer Regimen for COPD Step-Up Therapy

The management of Chronic Obstructive Pulmonary Disease (COPD) often involves a step-up approach in therapy, particularly when patients experience persistent symptoms or frequent exacerbations. The following points outline the key considerations and options for a puffer regimen in COPD step-up therapy:

• Initial Treatment: For patients with mild COPD who do not have recurrent symptoms, regular medication may not be necessary. However, for those with symptoms, short-acting beta-2 agonists can be used as needed to improve dyspnea 3.
• Step-Up to Long-Acting Bronchodilators: Long-acting beta-2 agonists (LABAs) such as salmeterol and formoterol, and long-acting muscarinic antagonists (LAMAs) like tiotropium, are recommended for symptomatic patients. These medications can reduce breathlessness, acute exacerbations, and improve quality of life 3, 4.
• Combination Therapy: Combining an inhaled LABA with a LAMA or an inhaled corticosteroid (ICS) can provide additional benefits for patients with more severe symptoms or frequent exacerbations. For example, tiotropium/budesonide/formoterol has been shown to be effective in reducing exacerbations 5.
• Ultra-LABAs and LAMAs: Newer ultra-LABAs (e.g., indacaterol, olodaterol) and LAMAs (e.g., glycopyrronium, aclidinium) offer once-daily dosing regimens and may be considered for step-up therapy 6, 3.
• Safety and Efficacy Considerations: When selecting a puffer regimen, it's essential to consider the safety and efficacy profiles of different medications. For instance, ICS can increase the risk of pneumonia, while certain LAMAs may have a higher risk of cardiovascular effects 3, 5.
• Individualized Treatment: Treatment should be tailored to the patient's symptoms, frequency of exacerbations, and response to therapy. Subphenotyping patients with COPD may help identify those who are most likely to benefit from specific treatments, such as the addition of ICS to bronchodilating therapy 6.