Pharmacological management

pharmacological treatment

Medications commonly used to treat COPD include:

Bronchodilators

Inhaled bronchodilators are the main agents used for management of symptoms and are commonly given on a regular basis to prevent or reduce symptoms (1)

• beta2-agonists
  • short-acting beta2-agonists (SABA)
    • effects usually wears off in about 4-6 hours
    • regular and as-needed use improve FEV1 and symptoms
    • for single dose, as-needed use in COPD, there appears to be no advantage in routinely using levalbuterol over conventional bronchodilators
      
  • long-acting beta2-agonists (LABA)
    • duration of action is 12 hours or more
    • do not preclude additional benefits from as-needed SABAs
    • formoterol and salmeterol
      • are twice daily preparations
      • significantly improve FEV1 and lung volumes, dyspnoea, health status, exacerbation rates
      • has no effect on mortality or rate of decline of lung function
    • indacaterol is a once daily LABA that improves breathlessness, health status and exacerbation rate. Some patients experience cough following the inhalation of indacaterol
    • oladaterol and vilanterol are additional once daily LABAs that improve lung function and symptom
      
• antimuscarinic drugs
  • can be
    • short acting antimuscarinic (SAMAs) - ipratropium, oxitropium
      • regular and as-needed use improve FEV1 and symptoms
      • a systemic review of RCTs reported that ipratropium alone provided small benefits over SABAs in terms of lung function health status and requirement for oral steroids
    • long acting antimuscarinic (LAMAs) - tiotropium, aclidinium
      • significantly improve FEV1 and lung volumes, dyspnoea, health status, exacerbation rates
      • clinical trials have shown a greater effect on exacerbation rates and decrease hospitalisation for LAMA treatment (tiotropium) versus LABA treatment
        
• methylxanthines
  • exacts effects of xanthine derivatives remains controversial
  • theophylline is the most commonly used methylxanthine
  • theophylline added to salmeterol produces a greater improvement in FEV1 and breathlessness than salmeterol alone
  • is limited and contradictory evidence regarding the effect of low-dose theophylline on exacerbation rates
    
• combination bronchodilator therapy
  • combinations of SABAs and SAMAs are superior compared to either medication alone in improving FEV1 and symptoms
  • combinations of LABAs and LAMA when compared to monotherapy
    • increase FEV1 and reduces symptoms
    • reduces exacerbations

Anti-inflammatory therapy

• inhaled corticosteroids (ICS)
  • evidence that ICS+LABA is more effective than monotherapy in improving lung function and health status and reducing exacerbations in patients with exacerbations and moderate to severe COPD
  • regular treatment with ICS increases the risk of pneumonia especially in those with severe disease
  • there is a continuous relationship between blood eosinophil counts and ICS effects; no and/or small effects are observed at lower eosinophil counts, with incrementally increasing effects observed at higher eosinophil counts
    • data modelling indicates that ICS containing regimens have little or no effect at a blood eosinophil count < 100 cells/muL
    • threshold of a blood eosinophil count > 300 cells/muL identifies the top of the continuous relationship between eosinophils and ICS, and can be used to identify patients with the greatest likelihood of treatment benefit with ICS. These thresholds of < 100 cells/muL and > 300 cells/muL should be regarded as estimates
      
• oral glucocorticoids
  • systemic glucocorticoids in acute exacerbations (in hospitalised or emergency department visits) have shown to reduce the treatment failure, the rate of relapse and improve lung function and breathlessness
  • due to lack of benefit balanced against side effects, it has no use in long term treatment
    
• phosphodiesterase-4 (PDE4) inhibitors
  • principal action of PDE4 inhibitors is to reduce inflammation by inhibiting the breakdown of intracellular cyclic AMP
  • roflumilast is a once daily oral medication with no direct bronchodilator activity
    • reduces moderate and severe exacerbations treated with systemic corticosteroids in patients with chronic bronchitis, severe to very severe COPD, and a history of exacerbations
    • effects on lung function are also seen when roflumilast is added to long-acting bronchodilators, and in patients who are not controlled on fixed-dose LABA/ICS combinations
      
• antibiotics
  • long term azithromycin and erythromycin reduces exacerbations over one year
    
• mucolytic/antioxidants
  • regular use of NAC and carbocysteine reduces the risk of exacerbations in select populations

Each treatment regimens should be individualised since severity of symptoms, airflow limitation and severity of exacerbation may vary from patient to patient (1).

It is important to educate and train patients on proper inhalation techniques when prescribing an inhaler device

• determinants of poor inhaler techniques include: older age, use of multiple devices, and lack of previous education on inhaler technique
• recheck at each visit that patients continue to use their inhaler correctly
• inhaler technique and adherence to therapy should be assessed before concluding that the current therapy is insufficient
• following implementation of therapy, patients should be reassessed for attainment of treatment goals and identification of any barriers for successful treatment. Following review of the patient response to treatment initiation, adjustments in pharmacological treatment may be needed
• study evidence has has demonstrated that initial COPD treatment with an LABA/ICS is more effective than treatment with a LAMA in patients with previous exacerbations and high blood eosinophils > 300 cells/muL

Initial pharmacological management explanation (1):

Rescue short-acting bronchodilators should be prescribed to all patients for immediate symptom relief.

• Group A:
  • all Group A patients should be offered bronchodilator treatment based on its effect on breathlessness. This can be either a short- or a long-acting bronchodilator
  • this should be continued if benefit is documented
    
• Group B:
  • treatment should be initiated with LABA+LAMA combination
  • if a LABA+LAMA combination is not considered appropriate, there is no evidence to recommend one class of long-acting bronchodilator over another (LABA or LAMA) for initial relief of symptoms in this group of patients. In the individual patient, the choice should depend on the patient's perception of symptom relief
  • Group B patients are likely to have comorbidities that may add to their symptomatology and impact their prognosis, and these possibilities should be investigated
    
• Group E:
  • use of LABA+ICS in COPD is not encouraged; if there is an indication for ICS, then LABA+LAMA+ICS has been shown to be superior LABA+ICS and is therefore the preferred choice
  • Consider LABA+LAMA+ICS in group E if blood eosinophil counts >=300 cells/µl (practical recommendation)
  • If patients with COPD have concomitant asthma, they should be treated like patients with asthma. Hence, the use of ICS is mandatory.

Initiation of pharmacologic management of COPD according to the individualized assessment of symptoms and exacerbation risk following ABE scheme, and also accounting for blood eosinophil count, is shown in Figure 3.7, which can be found in GOLD 2024

Reference:

1. Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2024. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease